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The Driwan’s  Cybermuseum

















the end @ copyright dr Iwan suwnady 2001


The Haemophilia Disease Informations










The Driwan’s  Cybermuseum


clotting factor VIII (haemophilia A) and 

factor IX deficiency(haemophilia B)

Classification and external resources

Deficiency in coagulation factor VIII is the most common cause of haemophilia.
ICD10 D66D68
ICD9 286
OMIM 306700 306900 264900
DiseasesDB 5555 5561 29376
MedlinePlus 000537
eMedicine med/3528
MeSH D025861

Haemophilia (English pronunciation: /hiːməˈfɪliə/; also spelled hemophilia in North America, from the Greek haima αἷμα ‘blood’ and philia φιλος ‘love’[1]) is a group of hereditary genetic disorders that impair the body’s ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken. Haemophilia A (clotting factor VIII deficiency) is the most common form of the disorder, present in about 1 in 5,000–10,000 male births.[2] Haemophilia B (factor IX deficiency) occurs in around 1 in about 20,000–34,000 male births.

Like most recessive sex-linked, X chromosome disorders, haemophilia is more likely to occur in males than females. This is because females have two X chromosomes while males have only one, so the defective gene is guaranteed to manifest in any male who carries it. Because females have two X chromosomes and haemophilia is rare, the chance of a female having two defective copies of the gene is very low, so females are almost exclusively asymptomatic carriers of the disorder. Female carriers can inherit the defective gene from either their mother or father, or it may be a new mutation. Although it is not impossible for a female to have haemophilia, it is unusual: a female with Haemophilia A or B would have to be the daughter of both a male haemophiliac and a female carrier, while the non-sex-linked Haemophilia C, which can affect either sex, is extremely rare.

Haemophilia lowers blood plasma clotting factor levels of the coagulation factors needed for a normal clotting process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent fibrin formation, which is necessary to maintain the blood clot. A haemophiliac does not bleed more intensely than a person without it, but can bleed for a much longer time. In severe haemophiliacs even a minor injury can result in blood loss lasting days or weeks, or even never healing completely. In areas such as the brain or inside joints, this can be fatal or permanently debilitating.


 Signs and symptoms

Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called “bleeds”.[3][4] Patients with more severe haemophilia suffer more severe and more frequent bleeds, while patients with mild haemophilia typically suffer more minor symptoms except after surgery or serious trauma. Moderate haemophiliacs have variable symptoms which manifest along a spectrum between severe and mild forms.

Prolonged bleeding and re-bleeding are the diagnostic symptoms of haemophilia. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces.[5] This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement.[5] Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment.

Children with mild to moderate haemophilia may not have any signs or symptoms at birth especially if they do not undergo circumcision. Their first symptoms are often frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs.


Severe complications are much more common in severe and moderate haemophiliacs. Complications may be both directly from the disease or from its treatment:[6]

  • Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb.
  • Joint damage from haemarthrosis, potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis.
  • Transfusion transmitted infection from blood transfusions that are given as treatment.
  • Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective.
  • Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death.

 Life expectancy

Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who don’t receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years.[5] By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years.[5] Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.[7]

Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products.[5] The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of patients with haemophilia. Two other major causes of death include: hepatitis infections causing cirrhosis and, obstruction of air or blood flow due to soft tissue haemorrhage.[5]


  • Haemophilia A is a recessive X-linked genetic disorder involving a lack of functional clotting Factor VIII and represents 80% of haemophilia cases.
  • Haemophilia B is a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. It comprises approximately 20% of haemophilia cases.[8]
  • Haemophilia C is an autosomal genetic disorder (i.e. not X-linked) involving a lack of functional clotting Factor XI. Haemophilia C is not completely recessive: heterozygous individuals also show increased bleeding.[9]


X-linked recessive inheritance

Females possess two X-chromosomes, males have one X and one Y-chromosome. Since the mutations causing the disease are X-linked, a woman carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent allele on her other chromosome should express itself to produce the necessary clotting factors, due to X inactivation. However, the Y-chromosome in men has no gene for factors VIII or IX. If the genes responsible for production of factor VIII or factor IX present on a male’s X-chromosome are deficient there is no equivalent on the Y-chromosome to cancel it out, so the deficient gene is not masked and he will develop the illness.

Since a male receives his single X-chromosome from his mother, the son of a healthy female silently carrying the deficient gene will have a 50% chance of inheriting that gene from her and with it the disease; and if his mother is affected with haemophilia, he will have a 100% chance of being a haemophiliac. In contrast, for a female to inherit the disease, she must receive two deficient X-chromosomes, one from her mother and the other from her father (who must therefore be a haemophiliac himself). Hence haemophilia is far more common among males than females. However, it is possible for female carriers to become mild haemophiliacs due to lyonisation (inactivation) of the X-chromosomes. Haemophiliac daughters are more common than they once were, as improved treatments for the disease have allowed more haemophiliac males to survive to adulthood and become parents. Adult females may experience menorrhagia (heavy periods) due to the bleeding tendency. The pattern of inheritance is criss-cross type. This type of pattern is also seen in colour blindness.

A mother who is a carrier has a 50% chance of passing the faulty X-chromosome to her daughter, while an affected father will always pass on the affected gene to his daughters. A son cannot inherit the defective gene from his father.

Genetic testing and genetic counselling is recommended for families with haemophilia. Prenatal testing, such as amniocentesis, is available to pregnant women who may be carriers of the condition.

As with all genetic disorders, it is of course also possible for a human to acquire it spontaneously through mutation, rather than inheriting it, because of a new mutation in one of their parents’ gametes. Spontaneous mutations account for about 33% of all cases of haemophilia A. About 30% of cases of haemophilia B are the result of a spontaneous gene mutation.

If a female gives birth to a haemophiliac child, either the female is a carrier for the disease or the haemophilia was the result of a spontaneous mutation. Until modern direct DNA testing, however, it was impossible to determine if a female with only healthy children was a carrier or not. Generally, the more healthy sons she bore, the higher the probability that she was not a carrier.

If a male is afflicted with the disease and has children with a female who is not even a carrier, his daughters will be carriers of haemophilia. His sons, however, will not be affected with the disease. The disease is X-linked and the father cannot pass haemophilia through the Y-chromosome. Males with the disorder are then no more likely to pass on the gene to their children than carrier females, though all daughters they sire will be carriers and all sons they father will not have haemophilia (unless the mother is a carrier).


There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, patients with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1-5% active factor have moderate haemophilia, and those with mild haemophilia have between 5-40% of normal levels of active clotting factor.[5]


Haemophilia A can be mimicked by von Willebrand disease.

von Willebrand Disease

  • von Willebrand Disease could significantly affect as many as 1 in 10,000 people.[10]
  • von Willebrand Disease type 2A, where decreased levels of von Willebrand Factor can lead to premature proteolysis of Factor VIII. In contrast to haemophilia, vWD type 2A is inherited in an autosomal dominant fashion.
  • von Willebrand Disease type 2N, where von Willebrand Factor cannot bind Factor VIII, autosomal recessive inheritance. (i.e.; both parents need to give the child a copy of the gene).
  • von Willebrand Disease type 3, where lack of von Willebrand Factor causes premature proteolysis of Factor VIII. In contrast to haemophilia, vWD type 3 is inherited in an autosomal recessive fashion.

Additionally, severe cases of vitamin K deficiency can present similar symptoms to haemophilia. This is because vitamin K is necessary for the human body to produce several protein clotting factors. This vitamin deficiency is rare in adults and older children but is common in newborns. Infants are born with naturally low levels of vitamin K and do not yet have the symbiotic gut flora to properly synthesise their own vitamin K. Bleeding issues due to vitamin K deficiency in infants is known as “haemorrhagic disease of the newborn“, to avoid this complication newborns are routinely injected with vitamin K supplements.

Condition Prothrombin time Partial thromboplastin time Bleeding time Platelet count
Vitamin K deficiency or warfarin prolonged prolonged unaffected unaffected
Disseminated intravascular coagulation prolonged prolonged prolonged decreased
von Willebrand disease unaffected prolonged prolonged unaffected
Haemophilia unaffected prolonged unaffected unaffected
Aspirin unaffected unaffected prolonged unaffected
Thrombocytopenia unaffected unaffected prolonged decreased
Early Liver failure prolonged unaffected unaffected unaffected
End-stage Liver failure prolonged prolonged prolonged decreased
Uremia unaffected unaffected prolonged unaffected
Congenital afibrinogenemia prolonged prolonged prolonged unaffected
Factor V deficiency prolonged prolonged unaffected unaffected
Factor X deficiency as seen in amyloid purpura prolonged prolonged unaffected unaffected
Glanzmann’s thrombasthenia unaffected unaffected prolonged unaffected
Bernard-Soulier syndrome unaffected unaffected prolonged unaffected [11]


Commercially produced factor concentrates such as “Advate”, a recombinant Factor VIII produced by Baxter International, come as a white powder in a vial which must be mixed with sterile water prior to intravenous injection.

Though there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in haemophilia A or factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some haemophiliacs develop antibodies (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.

If a patient becomes refractory to replacement coagulation factor as a result of circulating inhibitors, this may be partially overcome with recombinant human factor VII (NovoSeven), which is registered for this indication in many countries.

In early 2008, the US Food and Drug Administration (FDA) approved Xyntha (Wyeth) anti-haemophilic factor, genetically engineered from the genes of Chinese hamster ovary cells. Since 1993 (Dr. Mary Nugent) recombinant factor products (which are typically cultured in Chinese hamster ovary (CHO) tissue culture cells and involve little, if any human plasma products) have been available and have been widely used in wealthier western countries. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of any sort are difficult to obtain in developing countries.

In Western countries, common standards of care fall into one of two categories: prophylaxis or on-demand. Prophylaxis involves the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. On-demand treatment involves treating bleeding episodes once they arise. In 2007, a clinical trial was published in the New England Journal of Medicine comparing on-demand treatment of boys (< 30 months) with haemophilia A with prophylactic treatment (infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI.[12] Prophylactic treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the NEJM supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin.[13] This study resulted in the first (October 2008) FDA approval to label any Factor VIII product to be used prophylactically.[14] As a result, the factor product used in the study (Bayer’s Kognate) is now labelled for use to prevent bleeds, making it more likely that insurance carriers in the US will reimburse consumers who are prescribed and use this product prophylactically. Despite Kognate only recently being “approved” for this use in the US, it and other factor products have been well studied and are often prescribed to treat Haemophilia prophylactically to prevent bleeds, especially joint bleeds.[15]

Preventive exercises

It is recommended that people affected with haemophilia do specific exercises to strengthen the joints, particularly the elbows, knees, and ankles.[16] Exercises include elements which increase flexibility, tone, and strength of muscles, increasing their ability to protect joints from damaging bleeds. These exercises are recommended after an internal bleed occurs and on a daily basis to strengthen the muscles and joints to prevent new bleeding problems. Many recommended exercises include standard sports warm-up and training exercises such as stretching of the calves, ankle circles, elbow flexions, and quadriceps sets.

Alternative medicine

While not a replacement for traditional treatments, preliminary scientific studies indicate that hypnosis and self-hypnosis may be effective at reducing bleeds and the severity of bleeds and thus the frequency of factor treatment.[17][18][19][20] Herbs which strengthen blood vessels and act as astringents may benefit patients with haemophilia, however there are no peer reviewed scientific studies to support these claims.[17]


Anticoagulants such as Heparin and Warfarin are contraindicated for people with haemophilia as these can aggravate clotting difficulties. Also contraindicated are those drugs which have “blood thinning” side effects. For instance, medications which contain aspirin, ibuprofen, or naproxen sodium should not be taken because they are well known to have the side effect of prolonged bleeding.[21]

Also contraindicated are activities with a high likelihood of trauma, such as motorcycling and skateboarding. Popular sports with very high rates of physical contact and injuries such as American football, hockey, boxing, wrestling, and rugby should be avoided by people with haemophilia.[21][22] Other active sports like soccer, baseball, and basketball also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a doctor.[21]


Haemophilia is rare, with only about 1 instance in every 10,000 births (or 1 in 5,000 male births) for haemophilia A and 1 in 50,000 births for haemophilia B.[23] About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually occurs in males and less often in females.[24] It is estimated that about 2500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B.[25]


“About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. (…) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.”

John C. Otto, 1803[26]

 Scientific discovery

The first written account of haemophilia occurred in the 2nd century in the Babylonian Talmud. In it Rabbi Judah haNasi, redactor of the Mishneh, wrote: “If she circumcised her first child and he died, and a second one also died, she must not circumcise her third child.” This passage refers to both the prolonged bleeding caused by circumcision and to the maternal inheritance of the disease.[27] The first medical professional to describe a disease was Albucasis. In the tenth century he described families whose males died of bleeding after only minor traumas.[28][dead link] While many other such descriptive and practical references to the disease appear throughout historical writings, scientific analysis did not begin until the start of the nineteenth century.

In 1803, Dr. John Conrad Otto, a Philadelphian physician, wrote an account about “a hemorrhagic disposition existing in certain families” in which he called the affected males “bleeders.”[29] He recognised that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of colour blindness by John Dalton who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John Hay published an account in The New England Journal of Medicine.[30][31]

A Finnish Doctor in 1924 discovered a heredity bleeding disorder similar to Haemophilia localised in a group of islands (called the “Aland Islands”) which are located to the southwest of Finland. This bleeding disorder is called “Von Willebrand Disease”.

The term “haemophilia” is derived from the term “haemorrhaphilia” which was used in a description of the condition written by Friedrich Hopff in 1828, while he was a student at the University of Zurich.[29][32] In 1937, Patek and Taylor, two doctors from Harvard, discovered anti-haemophilic globulin.[27] In 1947, Pavlosky, a doctor from Buenos Aires, found haemophilia A and haemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one haemophiliac to another haemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of haemophilia.

 European royalty

Queen Victoria passed haemophilia on to some of her descendants.

Haemophilia has featured prominently in European royalty and thus is sometimes known as “the royal disease”. Queen Victoria passed the mutation for Haemophilia B[33][34] to her son Leopold and, through some of her daughters, to various royals across the continent, including the royal families of Spain, Germany, and Russia. In Russia, Tsarevich Alexei Nikolaevich, son of Nicholas II, was a descendant of Queen Victoria through his mother Empress Alexandra and suffered from haemophilia.


It was claimed that Rasputin was successful at treating the Tsarevich‘s haemophilia.

Rasputin The Mad Monk
Russia’s greatest love machine!

Rasputin (1869-1916) was a Russian mystic and preacher. Born of illiterate peasant parents, he arrived in Saint Petersburg in the early 20th century, where he had some success in treating Tsarevich Alexei, who suffered from haemophilia. He managed to turn this, and the fascination in upper-class Russian circles with religious mysticism, healing, and sex, into becoming a close associate of the Tsar family and an important figure in pre-revolution Russia. 

Due to his many affairs and drunkenness (his personal faith required sin, in his case alcohol and sex, followed by repentance), he became a target of anti-Romanov and anti-Tsarist groups in Russia. He was murdered in 1916. The accounts from the murderers, primarily Felix Yusupov, were widely published, but also very exaggerated and were changed frequently. According to popular myth, he was first poisoned, then beaten, then shot, and finally drowned before he died. In reality, the poison evaporated while baked, and he died of the gunshot wounds before he was thrown in the river. 


Trope Namer for Rasputinian Death. The frequent myths and interesting history around him has made him a frequent target for a Historical Villain Upgrade or Beethoven Was an Alien Spy, as well as a figure in a Conspiracy Theory


  • Alan Rickman did a sympathetic portrayal of the man in Rasputin. It is notable his portrayal argued Rasputin may actually have been a saint with legitimate supernatural powers derived from God and at the very least didn’t deserve the crap piled on his memory.
  • In the Don Bluth film Anastasia, Rasputin was an undead sorcerer. Nevermind the other historical inaccuracies.
    • The Nostalgia Chick review included a call-in from the historical Rasputin, who argued he was a holy man who didn’t deserve this.
  • A Team Fortress 2 achievement for the Heavy references Rasputin. The Heavy needs to suffer several types of damage in a single life.
  • Showed up as a Big Bad (though not THE Big Bad, since he basically shows up in the middle of the game) in Shadow Hearts 2: Covenant. Turns out, he’s secretly a demon. Fortunately, you’ve got the help of a camera-wielding Princess Anastasia, and her magical, flying Farberge Egg!
  • He shows up as a Camp Gay fighter in the World Heroes series.
  • He gets a mention in Assassin’s Creed 2, as an agent of the Templars who stole the Staff of Eden from Czar Nicholas and thus precipitated the revolution that would follow. The Assassin order were the ones who killed him, though naturally, it took a while.
  • A robot from the future made in the image of Rasputin shows up as an antagonistic Devil Summoner in Raidou Kuzunoha vs. The Soulless Army (set years after his supposed death and in Japan no less).
  • Razputin is the psychic prodigy star of Psychonauts, with no other real connection to his namesake.
  • He is an antagonist (in service of an Eldritch Abomination ) in Hellboy.
  • He is also an ancestor of Colossus in X-Men. An ancestor that is very eager to be reincarnated in one of his blood.
  • Appeared in about a dozen books in the old World of Darkness… and each of them told a different story with him as another type of supernatural. They are all true, Rasputin became a Wraith after death and possessed all the supernaturals he was featured as.
  • The Doctor Who Past Doctor Adventures novel Wages of Sinis set in pre-Revolution Russia and has Rasputin as a character. It’s a historically-straight portrayal mostly, although his famous hard-to-kill-ness does turn out to be due to a time traveller trying to keep him alive.
    • He gets far more hilarious in Faction Paradox. To start with, the Faction recruited him a few days before his death, took him to the Eleven-Day Empire, and replaced him with an exact duplicate. Then the Celestis came along, didn’t realise the Faction had made the switch, and offered him their standard deal that includes resurrection. The duplicate had been briefed not to argue with any War-era powers it met, and so accepted the deal. By the time of the assassination attempt, the Great Houses noticed something was going on, assumed the Faction would try to take him to the Empire at the point of death, and so implanted a device that would replace the Faction duplicate with a Great House duplicate. House constructs are by default immune to poisoning. As such, when the poison failed, he was shot. Then the Celesti protocols resurrected him, producing a creature whose mind was struggling between Great Houses, Celesti, and Faction protocols which had to be shot repeatedly and beaten to death simply to get it to lie down long enough to be thrown ino the river, where it finally froze to death. As a result, none of the three powers involved like to talk about it and everyone in the War agreed to leave celebrities well alone. The real Rasputin, meanwhile, persuaded Anastasia (who was also a Faction recruit) to set up a rival state, then went mad and died under mysterious circumstances. Anastasia’s Thirteen-Day Republic was shortly afterwards annihilated.
  • He was the subject of an episode of the TV version of The Crow.
  • In an Animaniacs short, Rasputin has the ability to hypnotize others instantly into doing his will…until he meets the Warners.
  • Wizardry has Rattkin NPC named Ratsputin. Though he’s a ninja, not monk — name is due to mice- and rat- related puns Theme Naming.
  • Tom Baker played a darkly charismatic Rasputin in the historical biopic Nicholas and Alexandra before taking up the scarf.
  • Alan Rickman played him in the HBO original movie.
  • And Leonard Nimoy played a Rasputin-like character in “The Choice”, an episode of Mission: Impossible, indestructibility and all.
  • One Dilbert comic had the Pointy-Haired Boss hiring Rasputin, saying he had “charisma”. He then proceeded to suffocate Asok with a Death Glare. After that, he tried to do the same to Wally, but his powerful anti-charisma caused him to choke instead.
  • A Cahill from the Tomas branch in The 39 Clues.
  • The band Boney Mhas a song about him. The chorus refers to Rasputin as “Russia’s greatest love machine.”
  • When Karl Kesel homaged elements of Kamandi in Superboy he introduced a Ratsputin as the Evil Chancellor of Great Caesar.
  • Rasputin shows up among the army of wax droids in an episode of Red Dwarf, serving mainly as Caligula’s lackey.
  • Rasputin is the final boss of Lime-iro Senkitan. He’s presented as a monk, at least. He’s also presented as a villain mastermind with his own henchmen and an intent to take over Russia (and then, presumably, the world.)
  • Rasputin (in one of his coolest appearances) is the main villain of the Dungeons and Dragons game the main characters of The Word Weary play.
  • Rasputin was the Big Bad for both the comic series and film, Hell Boy.
  • Makes an appearance as a literal Disc One Final Boss in Shadow Hearts: Covenant. Actually plays pretty close to what history claims about him – with the sorcery and demonic influences taken Up to Eleven.
  • Hammer did a movie about him called Rasputin the Mad Monk, with Christopher Lee in the title role.

 At the time, a common treatment administered by professional doctors was to use aspirin, which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Alexei.

In Spain, Queen Victoria’s youngest daughter, Princess Beatrice, had a daughter Victoria Eugenie of Battenberg, who later became Queen of Spain. Two of her sons were haemophiliacs and both died from minor car accidents: Her eldest son, Prince Alfonso of Spain, Prince of Asturias, died at the age of 31 from internal bleeding after his car hit a telephone booth. Her youngest son, Infante Gonzalo, died at age 19 from abdominal bleeding following a minor car accident where he and his sister hit a wall while avoiding a cyclist. Neither appeared injured or sought immediate medical care and Gonzalo died two days later from internal bleeding.

Blood contamination issues

Ryan White was an American haemophiliac who became infected with HIV/AIDS through contaminated blood products.

Prior to 1985, there were no laws enacted within the U.S. to screen blood. As a result, many haemophilia patients who received untested and unscreened clotting factor prior to 1992 were at an extreme risk for contracting HIV and hepatitis C via these blood products. It is estimated that more than 50% of the haemophilia population, over 10,000 people, contracted HIV from the tainted blood supply in the United States alone.[35]

As a direct result of the contamination of the blood supply in the late 1970s and early/mid 1980s with viruses such as hepatitis and HIV, new methods were developed in the production of clotting factor products. The initial response was to heat-treat (pasteurise) plasma-derived factor concentrate, followed by the development of monoclonal factor concentrates, which use a combination of heat treatment and affinity chromatography to inactivate any viral agents in the pooled plasma from which the factor concentrate is derived. The Lindsay Tribunal in Ireland investigated, among other things, the slow adoption of the new methods

the end @ copyright Dr Iwan suwandy 2011

The GuillaIn Barre Syndrome Informations



Georges Guillain.
Georges Guillain
Jean-Alexandre Barré.
Jean-Alexandre Barré










The Driwan’s  Cybermuseum

Guillain–Barré syndrom


Andy Griffith

Andy Griffith

Andy Griffith receiving the Presidential Medal of Freedom.
Born Andy Samuel Griffith
June 1, 1926 (1926-06-01) (age 85)
Mount Airy, North Carolina, United States
Nationality American
Education Mount Airy High School
Alma mater University of North Carolina at Chapel Hill
Occupation Actor, comedian, director, producer, singer (country, bluegrass & southern gospel), writer
Years active 1954–present
Notable works The Andy Griffith Show
Political party Democrat
Spouse Barbara Bray Edwards (m. 1949–72) (divorced)
Solica Cassuto (m. 1975–81) (divorced)
Cindi Knight (1983–present)American actor Andy Griffith developed Guillain-Barré syndrome in 1983

Andy Samuel Griffith (born June 1, 1926) is an American actor, director, producer, Grammy Award-winning Southern-gospel singer, and writer.[1] He gained prominence in the starring role in director Elia Kazan‘s epic film A Face in the Crowd (1957) before he became better known for his television roles, playing the lead characters in the 1960–68 situation comedy, The Andy Griffith Show, and in the 1986–95 legal drama, Matlock. Griffith was awarded the Presidential Medal of Freedom by US President George W. Bush on November 9, 2005.

Guillain-Barré syndrome
Classification and external resources
ICD10 G61.0
ICD9 357.0
OMIM 139393
DiseasesDB 5465
MedlinePlus 000684
eMedicine emerg/222 neuro/7 pmr/48 neuro/598
MeSH D020275

Guillain–Barré syndrome (GBS) (French pronunciation: [ɡiˈlɛ̃ baˈʁe], English pronunciation: /ˈɡlænˈbɑr/), sometimes called Landry’s paralysis, is an acute inflammatory demyelinating polyneuropathy (AIDP), a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom. It can cause life-threatening complications, particularly if the breathing muscles are affected or if there is dysfunction of the autonomic nervous system. The disease is usually triggered by an acute infection. Guillain–Barré syndrome is a form of peripheral neuropathy.

The diagnosis is usually made by nerve conduction studies. With prompt treatment by intravenous immunoglobulins or plasmapheresis, together with supportive care, the majority will recover completely. Guillain–Barré syndrome is rare, at 1–2 cases per 100,000 people annually, but is one of the leading causes of acute non-trauma-related paralysis in the world. The syndrome is named after the French physicians Georges Guillain and Jean Alexandre Barré, who described it in 1916.

Guillain Barré Syndrome Support Group Trust

Welcome to the website of the Guillain Barré (pronounced gee-lane bah-ray) Syndrome Support Group New Zealand Trust.

Georges Guillain.
Georges Guillain
Jean-Alexandre Barré.
Jean-Alexandre Barré

Guillain Barré syndrome was discovered by the French physicians Jean-Alexandre Barré, Georges Guillain and Andre Strohl in the early 1900s following tests on soldiers returning from World War 1. Many cases of an identical condition had been described over the preceding 80 years but these neurologists identified one of the characterising features of the disease – the increased concentration of protein in the spinal fluid without evidence of inflammation.

GBS is a polyneuritis (an inflammation of many nerves) that affects the peripheral nerves connecting the skin and muscles to the central nervous system and leads to progressive weakness in the arms and legs. It is caused by the body’s own immune system turning on itself and attacking the nerves by mistake


Guillain-Barré syndrome (GBS) (pengucapan Prancis: [ɡilɛ baʁe], pengucapan bahasa Inggris: / ɡi lænbɑreɪ ː /), kadang-kadang disebut kelumpuhan Landry, adalah suatu polineuropati demielinasi inflamasi akut (AIDP), gangguan yang mempengaruhi sistem saraf perifer. Ascending kelumpuhan, kelemahan awal pada kaki dan tangan dan bermigrasi ke bagasi, adalah gejala paling khas. Hal ini dapat menyebabkan komplikasi yang mengancam jiwa, terutama jika otot-otot pernapasan dipengaruhi atau jika ada disfungsi dari sistem saraf otonom. Penyakit ini biasanya dipicu oleh infeksi akut. Guillain-Barré syndrome adalah bentuk neuropati perifer.

Diagnosis biasanya dibuat dengan studi konduksi saraf. Dengan pengobatan prompt dengan imunoglobulin intravena atau plasmapheresis, bersama-sama dengan perawatan suportif, mayoritas akan sembuh sepenuhnya. Sindrom Guillain-Barré jarang, pada 1-2 kasus per 100.000 orang per tahun, namun merupakan salah satu penyebab utama akut non-trauma yang berhubungan dengan kelumpuhan di dunia.


Georges Guillain.
Georges Guillain
Jean-Alexandre Barré.
Jean-Alexandre Barré

Sindrom ini dinamai setelah Georges Guillain dan Jean dokter Alexandre Barre dari Perancis , yang digambarkan pada tahun 1916

contoh kasus di Indonesia

Askes Tanggung Biaya Pengobatan Penderita GBS


M. Azka Arriziq, (4), penderita penyakit langka Guillain Barre Syndrome (GBS) yang tengah menjalani perawatan di RSUP Cipto Mangungkusumo. (ist/doc)  � PT Askes (Persero) akhirnya menjamin seluruh biaya pengobatan M. Azka Arriziq, (4), penderita penyakit langka Guillain Barre Syndrome (GBS) yang tengah menjalani perawatan di RSUP Cipto Mangungkusumo.

Seperti diketahui, sebelum dirawat di RSCM, Azka yang merupakan anak satu-satunya dari pasangan Anto Ariyanto, (42), dan Rina, (38), sudah dirawat sejak 21 Juli 2011 diruang Perinatal Intensive Care Unit, RS Azra, Bogor. Namun, sejak Selasa (2/8) lalu, Azka dipindahkan perawatannya ke RSCM Jakarta.

Direktur Utama PT Askes (Persero), I Gede Subawa usai mengunjugi Azka di RSUP Cipto Manungunkusumo, kepada waratwan mengatakan  saat ini Askes sudah menjamin seluruh kebutuhan medis Azka, sampai hari ke-6 per 8 Agustus 2011. Gede, juga menekankan bahwa penyakit GBS, termasuk dalam kategori penyakit katastropik.

Gede menambahkan, sejak dirawat di RS Azra Bogor, biaya pengobatan Azka mencapai Rp87.557.000. Meski RS tersebut tidak bekerja sama dengan Askes, namun Gede mengatakan akan memberikan penggantian penuh atas biaya perawatannya.

�Kita sudah bayar biaya sebesar Rp32 juta dari total Rp87.557.000. Sisanya, akan dibayarkan secara bertahap. Dan ked epannya, Azka akan dijamin biaya kesehatannya tanpa ada batasan biaya dan hari rawat sesuai sistem yang dianut oleh PT. Askes sesuai prosedur dan aturan berlaku,� jelasnya.

Di tempat yang sama, Anto Ariyanto mengaku lega karena PT Askes mau menanggung seluruh biaya medis yang dibutuhkan Azka termasuk hutang di RS Azra Bogor. �Kami berterima kasih kepada Askes karena menanggulangi seluruh biaya pengobatan Aska secara utuh. Sebelumnya saya sempat stress karena biaya yang dibutuhkan untuk mengobatan Azka rata-rata Rp10 juta per hari,� ucapnya.

Guillain Barre Syndrome (GBS) merupakan penyakit langka dan menyerang satu dari 100.000 ribu orang per tahun. Hingga kini, belum diketahui penyebab dan bagaimana awal munculnya penyakit GBS ini. Berdasarkan catatan medis, GBS disebabkan oleh auto imun yang menghasilkan antibodi berlebih saat menghadapi virus atau bakteri juga menyerang syaraf tepi.

Sebelumnya, gerakan kepedulian seribu rupiah bagi penderita penyakit langka Guillain-Barre Syndrome (GBS) yang menimpa Muhammad Azka Arriziq dan Shafa dimulai Minggu (7/8) lalu. Aksi sosial tersebut dilakukan setelah kedua bocah malang berusia 4 tahun itu tidak sanggup membayar biaya pengobatan yang mencapai ratusan juta rupiah.

�Gerakan ini untuk menghimpun dana kemanusiaan masyarakat luas untuk meringankan biaya pengobatan dan perawatan Shafa dan Azka,” ungkap Ketua Gerakan Rp1.000, Silvia Wahyuni, di Jakarta belum lama ini



Six different subtypes of Guillain–Barré syndrome exist:[citation needed]

  • Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form of GBS, and the term is often used synonymously with GBS. It is caused by an auto-immune response directed against Schwann cell membranes.
  • Miller Fisher syndrome (MFS) is a rare variant of GBS and manifests as a descending paralysis, proceeding in the reverse order of the more common form of GBS. It usually affects the eye muscles first and presents with the triad of ophthalmoplegia, ataxia, and areflexia. Anti-GQ1b antibodies are present in 90% of cases.
  • Acute motor axonal neuropathy (AMAN),[1] also known as Chinese paralytic syndrome, attacks motor nodes of Ranvier and is prevalent in China and Mexico. It is probably due to an auto-immune response directed against the axoplasm of peripheral nerves. The disease may be seasonal and recovery can be rapid. Anti-GD1a antibodies[2] are present. Anti-GD3 antibodies are found more frequently in AMAN.
  • Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN but also affects sensory nerves with severe axonal damage. Like AMAN, it is probably due to an auto-immune response directed against the axoplasm of peripheral nerves. Recovery is slow and often incomplete.[3]
  • Acute panautonomic neuropathy is the most rare variant of GBS, sometimes accompanied by encephalopathy. It is associated with a high mortality rate, owing to cardiovascular involvement, and associated dysrhythmias. Impaired sweating, lack of tear formation, photophobia, dryness of nasal and oral mucosa, itching and peeling of skin, nausea, dysphagia, constipation unrelieved by laxatives or alternating with diarrhea occur frequently in this patient group. Initial nonspecific symptoms of lethargy, fatigue, headache, and decreased initiative are followed by autonomic symptoms including orthostatic lightheadedness, blurring of vision, abdominal pain, diarrhea, dryness of eyes, and disturbed micturition. The most common symptoms at onset are related to orthostatic intolerance, as well as gastrointestinal and sudomotor dysfunction (Suarez et al. 1994). Parasympathetic impairment (abdominal pain, vomiting, constipation, ileus, urinary retention, dilated unreactive pupils, loss of accommodation) may also be observed.
  • Bickerstaff’s brainstem encephalitis (BBE), is a further variant of Guillain–Barré syndrome. It is characterized by acute onset of ophthalmoplegia, ataxia, disturbance of consciousness, hyperreflexia or Babinski’s sign. The course of the disease can be monophasic or remitting-relapsing. Large, irregular hyperintense lesions located mainly in the brainstem, especially in the pons, midbrain and medulla are described in the literature. BBE despite severe initial presentation usually has a good prognosis. Magnetic resonance imaging (MRI) plays a critical role in the diagnosis of BBE. A considerable number of BBE patients have associated axonal Guillain–Barré syndrome, indicative that the two disorders are closely related and form a continuous spectrum.

 Signs and symptoms

The disorder is characterized by symmetrical weakness which usually affects the lower limbs first, and rapidly progresses in an ascending fashion. Patients generally notice weakness in their legs, manifesting as “rubbery legs” or legs that tend to buckle, with or without dysesthesias (numbness or tingling). As the weakness progresses upward, usually over periods of hours to days, the arms and facial muscles also become affected. Frequently, the lower cranial nerves may be affected, leading to bulbar weakness, oropharyngeal dysphagia (drooling, or difficulty swallowing and/or maintaining an open airway) and respiratory difficulties. Most patients require hospitalization and about 30% require ventilatory assistance for treatment of Type II respiratory failure.[4] [5] Facial weakness is also commonly a feature, but eye movement abnormalities are not commonly seen in ascending GBS, but are a prominent feature in the Miller-Fisher variant (see below.) Sensory loss, if present, usually takes the form of loss of proprioception (position sense) and areflexia (complete loss of deep tendon reflexes), an important feature of GBS. Loss of pain and temperature sensation is usually mild. In fact, pain is a common symptom in GBS, presenting as deep aching pain, usually in the weakened muscles, which patients compare to the pain from overexercising. These pains are self-limited and should be treated with standard analgesics. Bladder dysfunction may occur in severe cases but should be transient. If severe, spinal cord disorder should be suspected.

Fever should not be present, and if it is, another cause should be suspected.

In severe cases of GBS, loss of autonomic function is common, manifesting as wide fluctuations in blood pressure, orthostatic hypotension, and cardiac arrhythmias.

Acute paralysis in Guillain–Barré syndrome may be related to sodium channel blocking factor in the cerebrospinal fluid (CSF). Significant issues involving intravenous salt and water administration may occur unpredictably in this patient group, resulting in SIADH. SIADH is one of the causes of hyponatremia and can be accompanied with various conditions such as malignancies, infections and nervous system diseases. Symptoms of Guillain-Barré syndrome such as general weakness, decreased consciousness, and seizure are similar to those of hyponatremia

The symptoms of Guillain–Barré syndrome are also similar to those for progressive inflammatory neuropathy.[6]

indonesia version

Tanda dan gejala
Kelainan ini ditandai oleh kelemahan simetris yang biasanya mempengaruhi tungkai bawah pertama, dan dengan cepat berkembang dalam mode menaik. Pasien umumnya menyadari kelemahan di kaki mereka, mewujudkan sebagai “kaki karet” atau kaki yang cenderung gesper, dengan atau tanpa dysesthesias (mati rasa atau kesemutan). Sebagai kelemahan berlangsung ke atas, biasanya selama periode jam untuk hari, lengan dan otot-otot wajah juga menjadi terpengaruh. Sering, saraf kranial yang lebih rendah mungkin akan terpengaruh, menyebabkan kelemahan bulbar, disfagia orofaringeal (air liur, atau kesulitan menelan dan / atau mempertahankan jalan napas terbuka) dan kesulitan pernafasan. Kebanyakan pasien memerlukan rawat inap dan sekitar 30% memerlukan bantuan ventilasi untuk pengobatan kegagalan pernafasan Tipe II [4] [5]. Kelemahan wajah juga sering fitur, tapi mata kelainan gerakan yang tidak biasa terlihat dalam ascending GBS, tetapi fitur yang menonjol di varian Miller-Fisher (lihat di bawah.) kehilangan sensorik, jika ada, biasanya mengambil bentuk hilangnya proprioception (rasa posisi) dan areflexia (hilangnya lengkap refleks tendon dalam), sebuah fitur penting dari GBS. Hilangnya sensasi nyeri dan suhu biasanya ringan. Bahkan, nyeri adalah gejala yang umum di GBS, menyajikan sebagai nyeri yang dalam, biasanya pada otot melemah, yang pasien dibandingkan dengan rasa sakit dari overexercising. Rasa sakit adalah diri terbatas dan harus diobati dengan analgesik standar. Disfungsi kandung kemih dapat terjadi pada kasus yang berat tetapi harus sementara. Jika parah, gangguan sumsum tulang belakang harus dicurigai.

Demam tidak harus hadir, dan jika itu, penyebab lain harus dicurigai.

Dalam kasus yang parah GBS, hilangnya fungsi otonom adalah umum, mewujudkan sebagai fluktuasi luas dalam tekanan darah, hipotensi ortostatik, dan aritmia jantung.

Kelumpuhan akut pada sindrom Guillain-Barré mungkin berkaitan dengan saluran natrium memblokir faktor dalam cairan cerebrospinal (CSF). Isu-isu signifikan yang melibatkan garam intravena dan administrasi air dapat terjadi tak terduga pada kelompok pasien ini, sehingga SIADH. SIADH adalah salah satu penyebab hiponatremia dan dapat disertai dengan berbagai kondisi seperti keganasan, infeksi dan penyakit sistem saraf. Gejala sindrom Guillain-Barré seperti kelemahan umum, penurunan kesadaran, dan kejang yang mirip dengan hiponatremia

Gejala-gejala sindrom Guillain-Barré juga mirip dengan yang untuk neuropati inflamasi progresif


Structure of a typical neuron

All forms of Guillain–Barré syndrome are due to an immune response to foreign antigens (such as infectious agents) that is mistargeted at host nerve tissues instead. The targets of such immune attack are thought to be gangliosides, compounds naturally present in large quantities in human nerve tissues. The most common antecedent infection is the bacterium Campylobacter jejuni.[7][8] However, 60% of cases do not have a known cause. One study suggests that a minority of cases may be triggered by the influenza virus, or by an immune reaction to the influenza virus.[9]

The end result of such autoimmune attack on the peripheral nerves is damage to the myelin, the fatty insulating layer of the nerve, and a nerve conduction block, leading to a muscle paralysis that may be accompanied by sensory or autonomic disturbances.

However, in mild cases, nerve axon (the long slender conducting portion of a nerve) function remains intact and recovery can be rapid if remyelination occurs. In severe cases, axonal damage occurs, and recovery depends on the regeneration of this important tissue. Recent studies on the disorder have demonstrated that approximately 80% of the patients have myelin loss, whereas, in the remaining 20%, the pathologic hallmark of the disorder is indeed axon loss.

Guillain-Barré, unlike disorders such as multiple sclerosis (MS) and Lou Gehrig’s disease (ALS), is a peripheral nerve disorder and does not generally cause nerve damage to the brain or spinal cord.


Becoming infected with influenza increases both the risk of developing GBS and the risk of death (up to 1 in 10,000 who get influenza will die from it). While influenza vaccines have sometimes been suspected to raise the incidence of GBS, the evidence is equivocal, as shown below. Moreover, the highest level of suspected risks from the influenza vaccine is less than one-tenth the risk from the influenza disease itself, as discussed in more detail in the next section.[10][11][12]

Influenza vaccine

GBS may be a rare side-effect of influenza vaccines; a study of the Vaccine Adverse Event Reporting System (VAERS) indicates that it is reported as an adverse event potentially associated with the vaccine at a rate of 1 per million vaccines (over the normal risk).[13] There were reports of GBS affecting 10 per million who had received swine flu immunizations in the 1976 U.S. outbreak of swine flu—25 of which resulted in death from severe pulmonary complications, leading the United States Center of Disease Control to end that immunization campaign within the United States. (By comparison, the average flu season kills around 30,000 people in the United States).[14] However, the role of the vaccine even in those 25 cases in 1976 has remained unclear, partly because GBS had an unknown but very low incidence rate in the general population making it difficult to assess whether the vaccine was really increasing the risk for GBS. Later research has pointed to the absence of, or only a very small increase in, the GBS risk due to the 1976 swine flu vaccine.[15] Furthermore, the GBS may not have been directly due to the vaccine but to a bacterial contamination of the 1976 vaccine.[16]

Since 1976, no other influenza vaccines have been linked to GBS, though as a precautionary principle, caution is advised for certain individuals, particularly those with a history of GBS.[17][18]

From October 6 to November 24, 2009, the U.S. CDC, through the VAERS reporting system, received ten reports of Guillain-Barré syndrome cases associated with the H1N1 vaccine and identified two additional probable cases from VAERS reports (46.2 million doses were distributed within the U.S. during this time). Only four cases, however, meet the Brighton Collaboration case criteria for Guillain–Barré syndrome, while four do not meet the criteria and four remain under review.[19] A preliminary report by the CDC‘s Emerging Infections Programs (EIP) calculates the rate of GBS observed in patients who previously received the 2009 H1N1 influenza vaccination is an excess of 0.8 per million cases, which is on par with the rate seen with the seasonal trivalent influenza vaccine.[20]

Although one review gives an incidence of about one case per million vaccinations,[21] a large study in China, reported in the NEJM covering close to 100 million doses of vaccine against the 2009 H1N1 “swine” flu found only eleven cases of Guillain-Barré syndrome (0.1%) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects; “The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination.”[22]


The diagnosis of GBS usually depends on findings such as rapid development of muscle paralysis, areflexia, absence of fever, and a likely inciting event. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and electrodiagnostic tests of nerves and muscles (such as nerve conduction studies) are common tests ordered in the diagnosis of GBS.

Typical CSF findings include albumino-cytological dissociation. As opposed to infectious causes, this is an elevated protein level (100–1000 mg/dL), without an accompanying increased cell count pleocytosis. A sustained increased white blood cell count may indicate an alternative diagnosis such as infection.
  • Electrodiagnostics
Electromyography (EMG) and nerve conduction study (NCS) may show prolonged distal latencies, conduction slowing, conduction block, and temporal dispersion of compound action potential in demyelinating cases. In primary axonal damage, the findings include reduced amplitude of the action potentials without conduction slowing.

Diagnostic criteria

Required:[citation needed]

  • Progressive, relatively symmetrical weakness of two or more limbs due to neuropathy
  • Areflexia
  • Disorder course < 4 weeks
  • Exclusion of other causes (see below)

Supportive:[citation needed]

  • relatively symmetric weakness accompanied by numbness and/or tingling
  • mild sensory involvement
  • facial nerve or other cranial nerve involvement
  • absence of fever
  • typical CSF findings obtained from lumbar puncture
  • electrophysiologic evidence of demyelination from electromyogram

Differential diagnosis:[citation needed]


Supportive care with monitoring of all vital functions is the cornerstone of successful management in the acute patient. Of greatest concern is respiratory failure due to paralysis of the diaphragm. Early intubation should be considered in any patient with a vital capacity (VC) <20 ml/kg, a negative inspiratory force (NIF) that is less negative (i.e., closer to zero) than -25 cmH2O, more than 30% decrease in either VC or NIF within 24 hours, rapid progression of disorder, or autonomic instability.

Once the patient is stabilized, treatment of the underlying condition should be initiated as soon as possible. Either high-dose intravenous immunoglobulins (IVIg) at 400 mg/kg for 5 days or plasmapheresis can be administered,[23][24] as they are equally effective and a combination of the two is not significantly better than either alone. Therapy is no longer effective two weeks after the first motor symptoms appear, so treatment should be instituted as soon as possible. IVIg is usually used first because of its ease of administration and safety profile, with a total of five daily infusions for a total dose of 2 g/kg body weight (400 mg/kg each day). The use of intravenous immunoglobulins is not without risk, occasionally causing hepatitis, or in rare cases, renal failure if used for longer than five days. Glucocorticoids have not been found to be effective in GBS. If plasmapheresis is chosen, a dose of 40-50 mL/kg plasma exchange (PE) can be administered four times over a week.

Following the acute phase, the patient may also need rehabilitation to regain lost functions. This treatment will focus on improving ADL (activities of daily living) functions such as brushing teeth, washing, and getting dressed. Depending on the local structuring on health care, a team of different therapists and nurses will be established according to patient needs. An occupational therapist can offer equipment (such as wheelchair and special cutlery) to help the patient achieve ADL independence. A physiotherapist would plan a progressive training program and guide the patient to correct functional movement, avoiding harmful compensations which might have a negative effect in the long run. There is also some evidence supporting physiotherapy in helping patients with Guillain–Barré syndrome regain strength, endurance, and gait quality,[25] as well as helping them prevent contractures, bedsores, and cardiopulmonary difficulties.[26] A speech and language therapist would be essential in the patient regaining speaking and swallowing ability if they were intubated and received a tracheostomy. The speech and language therapist would also offer advice to the medical team regarding the swallowing abilities of the patient and would help the patient regain their communication ability pre-dysarthria. There would also be a doctor, nurse and other team members involved, depending on the needs of the patient. This team contribute their knowledge to guide the patient towards his or her goals, and it is important that all goals set by the separate team members are relevant for the patient’s own priorities. After rehabilitation the patient should be able to function in his or her own home and attend necessary training as needed.


Most of the time recovery starts after the fourth week from the onset of the disorder. Approximately 80% of patients have a complete recovery within a few months to a year, although minor findings may persist, such as areflexia. About 5–10% recover with severe disability, with most of such cases involving severe proximal motor and sensory axonal damage with inability of axonal regeneration. However, this is a grave disorder and despite all improvements in treatment and supportive care, the death rate among patients with this disorder is still about 2–3% even in the best intensive care units. Worldwide, the death rate runs slightly higher (4%), mostly from a lack of availability of life support equipment during the lengthy plateau lasting four to six weeks, and in some cases up to one year, when a ventilator is needed in the worst cases. About 5–10% of patients have one or more late relapses, in which case they are then classified as having chronic inflammatory demyelinating polyneuropathy (CIDP).

Poor prognostic factors include: 1) age, over 40 years, 2) history of preceding diarrheal illness, 3) requiring ventilator support, 4) high anti-GM1 titre and 5) poor upper limb muscle strength.


The incidence of GBS during pregnancy is 1.7 cases per 100,000 of the population.[27] The mother will generally improve with treatment but death of the fetus is a risk. The risk of Guillain–Barré syndrome increases after delivery, particularly during the first two weeks postpartum. There is evidence of Campylobacter jejuni as an antecedent infection in approximately 26% of disease cases, requiring special care in the preparation and handling of food. Congenital and neonatal Guillain–Barré syndrome have also been reported.[28]


The disorder was first described by the French physician Jean Landry in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and discovered the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count.[29]

GBS is also known as acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French polio, Landry’s ascending paralysis and Landry Guillain Barré syndrome.

Canadian neurologist C. Miller Fisher described the variant that bears his name in 1956.[30]

Notable cases

American actor Andy Griffith developed Guillain-Barré syndrome in 1983. Griffith is seen here receiving an award at the White House in 2005

Case Report From Indonesia (Lois)

In 1982 my younger sister suddenly paralyzed after a few days before experiencing pain colds / flu-like. The beginning of a limp leg and quickly loose all over his body, but does not affect the face, the power of memory and can speak normally. The doctor said the pain is GBS as contained in this post. Time was already seeing where where in Indonesia and also to China, but my sister still remains paralyzed from the waist down.

While my brother was not able to walk and uses a wheelchair, he can run the business legacy of our parents’ shop. Hopefully those who also suffer from GBS disease now can get the treatment that is more up to date …. until the paralysis is not permanent

Indonesia version

Laporan Kasus Dari indonesia(Lois)

Tahun 1982 adik perempuan saya tiba tiba lumpuh setelah beberapa hari sebelumnya mengalami sakit masuk angin/seperti flu. Permulaan kaki yang lemas dan dengan cepat lemas sekujur badan, tapi tidak mempengaruhi wajah, daya ingatan dan bisa berbicara normal. Kata dokter sakitnya adalah GBS seperti yang termuat dalam posting ini. Waktu itu udah berobat kemana mana di Indonesia dan juga sampai ke China, tapi adik saya sampai sekarang masih tetap lumpuh dari pinggang kebawah.

Walau adik saya itu tidak bisa jalan dan menggunakan kursi roda, dia bisa menjalankan usaha toko peninggalan orang tua kami. Semoga mereka yang juga menderita penyakit GBS sekarang ini bisa mendapatkan pengobatan yang lebih up to date…. hingga kelumpuhan tidak bersifat permanen



The M S Disease Informations(Penyakit Pelawak Pepeng)











The Driwan’s  Cybermuseum

special for Mas and his friend in order to open the diesease mystery

Khusu buat Mas pepeng,family and teman-temannya serta para pengemarnya untuk mengungkap misteri penyakit yang dideritanya

Saya salut atas semangat Mas pepeng yang tetap kreatif walaupun menderita penyakit MS

Multiple sclerosis

Multiple sclerosis
Classification and external resources

Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100
ICD10 G35
ICD9 340
OMIM 126200
DiseasesDB 8412
MedlinePlus 000737
eMedicine neuro/228 oph/179 emerg/321 pmr/82 radio/461
MeSH D009103
GeneReviews Multiple Sclerosis Overview

Multiple sclerosis (abbreviated MS, known as disseminated sclerosis or encephalomyelitis disseminata) is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms.[1] Disease onset usually occurs in young adults, and it is more common in women.[1] It has a prevalence that ranges between 2 and 150 per 100,000.[2] MS was first described in 1868 by Jean-Martin Charcot.[3]

MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body’s own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals.[4] The name multiple sclerosis refers to scars (scleroses—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.[3] Although much is known about the mechanisms involved in the disease process, the cause remains unknown. Theories include genetics or infections. Different environmental risk factors have also been found.[4][5]

Almost any neurological symptom can appear with the disease, and often progresses to physical and cognitive disability.[4] MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms).[6] Between attacks, symptoms may go away completely, but permanent neurological problems often occur, especially as the disease advances.[6]

There is no known cure for multiple sclerosis. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability.[4] MS medications can have adverse effects or be poorly tolerated, and many patients pursue alternative treatments, despite the lack of supporting scientific study. The prognosis is difficult to predict; it depends on the subtype of the disease, the individual patient’s disease characteristics, the initial symptoms and the degree of disability the person experiences as time advances.[7] Life expectancy of people with MS is 5 to 10 years lower than that of the unaffected population.[1]

indonesia version

Multiple sclerosis (disingkat MS, yang dikenal sebagai disebarluaskan sclerosis atau encephalomyelitis disseminata) adalah penyakit inflamasi di mana selubung mielin di sekitar akson lemak otak dan sumsum tulang belakang yang rusak, menyebabkan demielinasi dan jaringan parut serta spektrum yang luas dari tanda-tanda dan gejala [1]. Onset penyakit biasanya terjadi pada dewasa muda, dan lebih umum pada perempuan. [1] Ia memiliki prevalensi yang berkisar antara 2 dan 150 per 100.000. [2] MS pertama kali dijelaskan pada 1868 oleh Jean-Martin Charcot [3].

MS mempengaruhi kemampuan sel-sel saraf di otak dan sumsum tulang belakang untuk berkomunikasi satu sama lain secara efektif. Sel saraf berkomunikasi dengan mengirimkan sinyal-sinyal listrik yang disebut potensial aksi turun serat panjang yang disebut akson, yang terkandung dalam zat isolator yang disebut mielin. Pada MS, serangan tubuh sendiri sistem kekebalan tubuh dan kerusakan myelin. Ketika myelin hilang, akson tidak bisa lagi efektif melakukan sinyal. [4] nama multiple sclerosis mengacu pada bekas luka (scleroses-lebih dikenal sebagai plak atau lesi) khususnya dalam masalah putih otak dan sumsum tulang belakang, yang terutama terdiri mielin [3]. Meskipun banyak yang diketahui tentang mekanisme yang terlibat dalam proses penyakit, penyebabnya masih belum diketahui. Teori termasuk genetika atau infeksi. Berbagai faktor risiko lingkungan juga telah ditemukan [4] [5].

Hampir semua gejala neurologis dapat muncul dengan penyakit ini, dan sering berkembang menjadi cacat fisik dan kognitif [4]. MS mengambil beberapa bentuk, dengan gejala baru yang terjadi baik dalam serangan diskrit (kambuh bentuk) atau perlahan-lahan terakumulasi dari waktu ke waktu (bentuk progresif). [ 6] Antara serangan, gejala bisa hilang sepenuhnya, tapi masalah neurologis permanen sering terjadi, terutama karena kemajuan penyakit. [6]

Tidak ada obat dikenal untuk multiple sclerosis. Perawatan upaya untuk kembali berfungsi setelah serangan, mencegah serangan baru, dan mencegah kecacatan [4] MS obat dapat memiliki efek samping atau buruk ditoleransi, dan banyak pasien mengejar pengobatan alternatif,. Meskipun kurangnya mendukung studi ilmiah. Prognosis sulit untuk memprediksi;. Itu tergantung pada subtipe penyakit, karakteristik penyakit pasien individu, gejala awal dan tingkat kecacatan orang mengalami seiring kemajuan zaman [7] Harapan hidup orang dengan MS adalah 5 sampai 10 tahun lebih rendah dari populasi tidak terpengaruh [1].




Progression of MS subtypes

Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized four subtype definitions:[6]

  1. relapsing remitting,
  2. secondary progressive,
  3. primary progressive, and
  4. progressive relapsing.

The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during attacks may either resolve or leave sequelae, the latter being more common as a function of time.[1] This describes the initial course of 80% of individuals with MS.[1] When deficits always resolve between attacks, this is sometimes referred to as benign MS,[8] although patients will still accrue some degree of disability in the long term.[1] The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a patient has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis.[1][9] However only 30 to 70% of persons experiencing CIS later develop MS..

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Perkembangan subtipe MS

Beberapa subtipe, atau pola perkembangan, telah dijelaskan. Subtipe menggunakan saja masa lalu penyakit dalam upaya untuk memprediksi masa depan saja. Mereka penting tidak hanya untuk prognosis tetapi juga untuk keputusan terapeutik. Pada tahun 1996 Amerika Serikat National Multiple Sclerosis Masyarakat standar empat subtipe definisi: [6]

timbul kambuh,
sekunder progresif,
primer progresif, dan
kambuh progresif.
Subtipe hilang-timbul kambuh ditandai dengan tidak terduga diikuti oleh periode bulan untuk tahun relatif tenang (remisi) dengan tidak ada tanda-tanda aktivitas penyakit baru. Defisit menderita selama serangan baik dapat mengatasi atau meninggalkan gejala sisa, yang terakhir menjadi lebih umum sebagai fungsi waktu [1]. Ini menjelaskan program awal 80% dari individu dengan MS. [1] Ketika defisit selalu menyelesaikan antara serangan, ini kadang-kadang disebut sebagai MS jinak, [8] walaupun pasien masih akan bertambah beberapa derajat kecacatan dalam jangka panjang [1]. subtipe hilang-timbul biasanya dimulai dengan suatu sindrom klinis terisolasi (CIS). Dalam CIS, pasien memiliki serangan sugestif dari demielinasi, tetapi tidak memenuhi kriteria untuk multiple sclerosis. [1] [9] Namun hanya 30 sampai 70% dari orang mengalami CIS kemudian mengembangkan MS


Nerve axon with myelin sheath

Secondary progressive MS

Secondary progressive MS (sometimes called “galloping MS”) describes around 65% of those with an initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission.[1][6] Occasional relapses and minor remissions may appear.[6] The median time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.[10] The primary progressive subtype describes the approximately 10–15% of individuals who never have remission after their initial MS symptoms.[11] It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.[6] The age of onset for the primary progressive subtype is later than for the relapsing-remitting, but similar to mean age of progression between the relapsing-remitting and the secondary progressive. In both cases it is around 40 years of age.[1]

Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also suffer clear superimposed attacks. This is the least common of all subtypes.[6]

Atypical variants of MS with non-standard behavior have been described; these include Devic’s disease, Balo concentric sclerosis, Schilder’s diffuse sclerosis and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases.[12] Multiple sclerosis also behaves differently in children, taking more time to reach the progressive stage.[1] Nevertheless they still reach it at a lower mean age than adults.[1]

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Sekunder progresif MS

Sekunder progresif MS (kadang-kadang disebut “berderap MS”) menjelaskan sekitar 65% dari mereka dengan hilang-timbul MS awal, yang kemudian mulai memiliki penurunan neurologis progresif antara serangan akut tanpa periode tertentu remisi [1] [6]. Sesekali kambuh dan remisi kecil mungkin muncul [6] median waktu antara onset penyakit dan konversi dari hilang-timbul ke MS progresif sekunder adalah 19 tahun.. [10] subtipe progresif primer menjelaskan sekitar 10-15% individu yang tidak pernah memiliki pengampunan setelah gejala awal mereka MS [11]. Hal ini ditandai dengan perkembangan cacat dari awal, tanpa, atau hanya sesekali dan ringan, remisi dan perbaikan. [6] usia onset untuk subtipe progresif primer ini kemudian dibandingkan untuk kambuh -timbul, tetapi mirip dengan usia rata-rata perkembangan antara hilang-timbul dan progresif sekunder. Dalam kedua kasus itu adalah sekitar 40 tahun. [1]

MS kambuh Progresif menggambarkan orang-orang yang, dari awal, mengalami penurunan neurologis stabil tapi juga menderita serangan ditumpangkan jelas. Ini adalah yang paling umum dari semua subtipe. [6]

Atipikal varian dari MS dengan non-standar perilaku telah dijelaskan, ini termasuk penyakit Devic itu, Balo konsentris sclerosis, sklerosis menyebar Schilder dan sclerosis multiple Marburg. Ada perdebatan tentang apakah mereka MS varian atau penyakit yang berbeda [12] Multiple sclerosis juga berperilaku berbeda pada anak-anak, mengambil lebih banyak waktu untuk mencapai tahap progresif.. [1] Meskipun demikian mereka masih mencapainya pada usia rata-rata lebih rendah daripada orang dewasa

Signs and symptoms

Main symptoms of multiple sclerosis

A person with MS can suffer almost any neurological symptom or sign, including changes in sensation such as loss of sensitivity or tingling, pricking or numbness (hypoesthesia and paresthesia), muscle weakness, clonus, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis including phosphenes,[13][14] or diplopia), fatigue, acute or chronic pain, and bladder and bowel difficulties.[1] Cognitive impairment of varying degrees and emotional symptoms of depression or unstable mood are also common.[1] Uhthoff’s phenomenon, an exacerbation of extant symptoms due to an exposure to higher than usual ambient temperatures, and Lhermitte’s sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS although not specific.[1] The main clinical measure of disability progression and symptom severity is the Expanded Disability Status Scale or EDSS.[15]

Symptoms of MS usually appear in episodic acute periods of worsening (called relapses, exacerbations, bouts, attacks, or “flare-ups”), in a gradually progressive deterioration of neurologic function, or in a combination of both.[6] Multiple sclerosis relapses are often unpredictable, occurring without warning and without obvious inciting factors with a rate rarely above one and a half per year.[1] Some attacks, however, are preceded by common triggers. Relapses occur more frequently during spring and summer.[16] Viral infections such as the common cold, influenza, or gastroenteritis increase the risk of relapse.[1] Stress may also trigger an attack.[17] Pregnancy affects the susceptibility to relapse, with a lower relapse rate at each trimester of gestation. During the first few months after delivery, however, the risk of relapse is increased.[1] Overall, pregnancy does not seem to influence long-term disability. Many potential triggers have been examined and found not to influence MS relapse rates. There is no evidence that vaccination and breast feeding,[1] physical trauma,[18] or Uhthoff’s phenomenon[16] are relapse triggers.


Most likely MS occurs as a result of some combination of genetic, environmental and infectious factors,[1] and possibly other factors like vascular problems.[19] Epidemiological studies of MS have provided hints on possible causes for the disease. Theories try to combine the known data into plausible explanations, but none has proved definitive.

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Gejala Utama multiple sclerosis

Seseorang dengan MS dapat mengalami gejala neurologis hampir semua atau tanda, termasuk perubahan sensasi seperti kehilangan sensitivitas atau kesemutan, menusuk atau mati rasa (hypoesthesia dan paresthesia), kelemahan otot, clonus, kejang otot, atau kesulitan dalam bergerak; kesulitan dengan koordinasi dan keseimbangan (ataksia); masalah dalam pidato (disartria) atau menelan (disfagia), masalah visual (nystagmus, neuritis optik termasuk phosphenes, [13] [14] atau diplopia), nyeri kelelahan, akut atau kronis, dan kandung kemih dan usus kesulitan [1]. gangguan kognitif dari berbagai derajat dan gejala emosional dari depresi atau mood yang tidak stabil juga umum. [1] Uhthoff itu fenomena, eksaserbasi gejala yang masih ada karena eksposur lebih tinggi dari suhu lingkungan biasa, dan menandatangani Lhermitte, sebuah sensasi listrik yang berjalan di belakang ketika menekuk leher, terutama karakteristik dari MS meskipun tidak tertentu [1]. Ukuran klinis utama dari perkembangan dan keparahan gejala kecacatan adalah Skala Cacat Status Expanded atau EDSS. [15]

Gejala biasanya muncul MS dalam periode akut episodik yang memburuk (disebut kambuh, eksaserbasi, pertarungan, serangan, atau “flare-up”), dalam penurunan secara bertahap progresif fungsi neurologis, atau kombinasi keduanya sclerosis [6]. Beberapa kambuh sering tidak terduga, terjadi tanpa peringatan dan tanpa faktor menghasut yang jelas dengan tingkat jarang di atas satu setengah per tahun [1]. Beberapa serangan, bagaimanapun, adalah didahului oleh pemicu umum. Relaps terjadi lebih sering selama musim semi dan musim panas [16]. Infeksi virus seperti pilek, influenza, atau gastroenteritis meningkatkan risiko kambuh [1] Stres juga dapat memicu serangan [17]. Kehamilan mempengaruhi kerentanan terhadap kambuh,. dengan tingkat kekambuhan lebih rendah pada setiap trimester kehamilan. Selama beberapa bulan pertama setelah melahirkan, bagaimanapun, risiko kekambuhan meningkat. [1] Secara keseluruhan, kehamilan tampaknya tidak mempengaruhi kecacatan jangka panjang. Memicu banyak potensi telah diperiksa dan ditemukan tidak mempengaruhi tingkat MS kambuh. Tidak ada bukti bahwa vaksinasi dan menyusui, [1] trauma fisik, [18] atau fenomena Uhthoff itu [16] adalah pemicu kambuh.

MS paling mungkin terjadi sebagai hasil dari beberapa kombinasi dari faktor genetik, lingkungan dan menular, [1] dan mungkin faktor-faktor lain seperti masalah vaskuler [19]. Studi epidemiologis dari MS telah memberikan petunjuk tentang kemungkinan penyebab penyakit. Teori mencoba untuk menggabungkan data yang dikenal dalam penjelasan yang masuk akal, tetapi tidak ada yang terbukti definitif


HLA region of Chromosome 6. Changes in this area increase the probability of suffering MS.

MS is not considered a hereditary disease. However, a number of genetic variations have been shown to increase the risk of developing the disease.[20]

The risk of acquiring MS is higher in relatives of a person with the disease than in the general population, especially in the case of siblings, parents, and children.[4] The disease has an overall familial recurrence rate of 20%.[1] In the case of monozygotic twins, concordance occurs only in about 35% of cases, while it goes down to around 5% in the case of siblings and even lower in half-siblings. This indicates susceptibility is partly polygenically driven.[1][4]

It seems to be more common in some ethnic groups than others.[21]

Apart from familial studies, specific genes have been linked with MS. Differences in the human leukocyte antigen (HLA) system—a group of genes in chromosome 6 that serves as the major histocompatibility complex (MHC) in humans—increase the probability of suffering MS.[1] The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6.[1] Other loci have shown a protective effect, such as HLA-C554 and HLA-DRB1*11.[1]

Environmental factors

Different environmental factors, both of infectious and non infectious origin have been proposed as risk factors for MS. Although some are partly modifiable, only further research—especially clinical trials—will reveal whether their elimination can help prevent MS.[22]

MS is more common in people who live farther from the equator, although many exceptions exist.[1] Decreased sunlight exposure has been linked with a higher risk of MS.[22] Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun.[22][23][24]

Severe stress may also be a risk factor although evidence is weak.[22] Smoking has also been shown to be an independent risk factor for developing MS.[23] Association with occupational exposures and toxins—mainly solvents—has been evaluated, but no clear conclusions have been reached.[22]Vaccinations were also considered as causal factors for the disease; however, most studies show no association between MS and vaccines.[22] Several other possible risk factors, such as diet[25] and hormone intake, have been investigated; however, evidence on their relation with the disease is “sparse and unpersuasive”.[23]

Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in MS patients as compared to normal individuals. This led to the theory that uric acid protects against MS, although its exact importance remains unknown.[26]


Many microbes have been proposed as potential infectious triggers of MS, but none have been substantiated.[4]

Genetic susceptibility can explain some of the geographic and epidemiological variations in MS incidence, like the high incidence of the disease among some families or the risk decline with genetic distance, but does not account for other phenomena, such as the changes in risk that occur with migration at an early age.[5] An explanation for this epidemiological finding could be that some kind of infection, produced by a widespread microbe rather than a rare pathogen, is the origin of the disease.[5] Different hypotheses have elaborated on the mechanism by which this may occur. The hygiene hypothesis proposes that exposure to several infectious agents early in life is protective against MS, the disease being a response to a later encounter with such agents.[1] The prevalence hypothesis proposes that the disease is due to a pathogen more common in regions of high MS prevalence. This pathogen is very common, causing in most individuals an asymptomatic persistent infection. Only in a few cases, and after many years since the original infection, does it cause demyelination.[5][27] The hygiene hypothesis has received more support than the prevalence hypothesis.[5]

Evidence for viruses as a cause includes the presence of oligoclonal bands in the brain and cerebrospinal fluid of most patients, the association of several viruses with human demyelination encephalomyelitis, and induction of demyelination in animals through viral infection.[28] Human herpes viruses are a candidate group of viruses linked to MS. Individuals who have never been infected by the Epstein-Barr virus have a reduced risk of having the disease, and those infected as young adults have a greater risk than those who had it at a younger age.[1][5] Although some consider that this goes against the hygiene hypothesis, since the non-infected have probably experienced a more hygienic upbringing,[5] others believe that there is no contradiction since it is a first encounter at a later moment with the causative virus that is the trigger for the disease.[1] Other diseases that have also been related with MS are measles, mumps and rubella.[1]


 Blood-brain barrier breakdown

Demyelination in MS. On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).

The blood–brain barrier is a capillary system that should prevent entrance of T cells into the nervous system.[4] The blood–brain barrier is normally not permeable to these types of cells, unless triggered by infection or a virus, which decreases the integrity of the tight junctions forming the barrier.[4] When the blood–brain barrier regains its integrity, usually after infection or virus has cleared, the T cells are trapped inside the brain.[4]


MS is currently believed to be an immune-mediated disorder mediated by a complex interaction of the individual’s genetics and as yet unidentified environmental insults.[4] Damage is believed to be caused by the patient’s own immune system. The immune system attacks the nervous system, possibly as a result of exposure to a molecule with a similar structure to one of its own.[4]


The name multiple sclerosis refers to the scars (scleroses – better known as plaques or lesions) that form in the nervous system. MS lesions most commonly involve white matter areas close to the ventricles of the cerebellum, brain stem, basal ganglia and spinal cord; and the optic nerve. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.[4]

More specifically, MS destroys oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals.[4] MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron’s extensions or axons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.[4] A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cell’s myelin sheath.[29] Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons.[29] Different lesion patterns have been described.[30]


Apart from demyelination, the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by T cells, a kind of lymphocyte. Lymphocytes are cells that play an important role in the body’s defenses.[4] In MS, T cells gain entry into the brain via the previously described blood–brain barrier. Evidence from animal models also point to a role of B cells in addition to T cells in development of the disease.[31]

The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood–brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.[4]


T1-weighted MRI scans (post-contrast) of the same brain slice at monthly intervals. Bright spots indicate active lesions.

Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to other medical problems.[1][32] Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process especially in the first stages of the disease.[1] Historically, the Schumacher and Poser criteria were both popular.[33]

Currently, the McDonald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space for non-invasive MS diagnosis, though some have stated that the only proved diagnosis of MS is autopsy, or occasionally biopsy, where lesions typical of MS can be detected through histopathological techniques.[1][34][35]

Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate episodes of neurologic symptoms characteristic of MS.[34] Since some people seek medical attention after only one attack, other testing may hasten and ease the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.[34][36] Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.[34][37] The nervous system of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.[38]


Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some patients, despite the shortage of supporting, comparable, replicated scientific study.

Acute attacks

During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses.[1] Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[39] Oral and intravenous administration seem to have similar efficacy.[40] Consequences of severe attacks which do not respond to corticosteroids might be treated by plasmapheresis.[1]

Disease-modifying treatments

Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 1–3 month intervals.

Fingolimod (trade name Gilenya) was approved for MS by the FDA in 2010, and in Europe in 2011. As of 2011[update], after this approval, there are six disease-modifying treatments for MS approved by regulatory agencies of various countries, being the other five: Interferon beta-1a (trade names Avonex, CinnoVex, ReciGen and Rebif) and interferon beta-1b (U.S. trade name Betaseron, in Europe and Japan Betaferon). A third medication is glatiramer acetate (Copaxone), a non-interferon, non-steroidal immunomodulator. The fourth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy. The fifth is a humanized monoclonal antibody immunomodualtor, natalizumab (marketed as Tysabri).[1] The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.

All six kinds of medications are modestly effective at decreasing the number of attacks in relapsing-remitting MS (RRMS) while the capacity of interferons and glatiramer acetate is more controversial. Studies of their long-term effects are still lacking.[1][41] Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, both in terms of relapse rate reduction and halting disability progression.[42] Mitoxantrone may be the most effective of them all; however, it is generally not considered as a long-term therapy, as its use is limited by severe secondary effects.[1][41] The earliest clinical presentation of RRMS is the clinically isolated syndrome (CIS). Treatment with interferons during an initial attack can decrease the chance that a patient will develop clinical MS.[1]

Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in patients with secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in patients in short-term follow-up.[43] No treatment has been proven to modify the course of primary progressive MS.[44]

As with many medical treatments, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferon treatments. Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons produce symptoms similar to influenza;[45] some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes.[46] More dangerous but much less common are liver damage from interferons,[47] severe cardiotoxicity, infertility, and acute myeloid leukemia of mitoxantrone,[1][41] and the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy.[1]

Management of the effects of MS

Disease-modifying treatments reduce the progression rate of the disease, but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and disability. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, though neither influences disease progression.[1][48] Some symptoms have a good response to medication, such as unstable bladder and spasticity, while management of many others is much more complicated.[1] As for any patient with neurologic deficits, a multidisciplinary approach is key to improving quality of life; however, there are particular difficulties in specifying a ‘core team’ because people with MS may need help from almost any health profession or service at some point.[1] Multidisciplinary rehabilitation programs increase activity and participation of patients but do not influence impairment level.[49]

Historically, individuals suffering from MS were advised against participation in physical activity due to worsening symptoms.[50] However, under the direction of a physiotherapist, participation in physical activity can be safe and has been proven beneficial for patients with MS.[51] Research has supported the rehabilitative role of physical activity in improving muscle power,[52] mobility,[52] mood,[53] bowel health,[54] general conditioning and quality of life.[52] However, it is important to be cautious about not overworking or overheating the patient during the course of exercise. Physiotherapists have the expertise needed to adequately prescribe exercise programs that are suitable for the individual. The FITT equation (frequency of exercise, intensity of exercise, type of exercise and time/duration of exercise) is typically used to prescribe exercises.[51] Depending on the patient, activities may include resistance training,[55] walking, swimming, yoga, tai chi, and others.[54] Determining an appropriate and safe exercise program is challenging and must be carefully individualized to each patient being sure to account for all contraindications and precautions.[51]

 Alternative treatments

As with most chronic diseases, alternative treatments for multiple sclerosis, which are unsupported by clinical or scientific evidence, are pursued by some patients.[56] Examples are a dietary regimen,[57] herbal medicine (including the use of medical cannabis),[58] hyperbaric oxygenation[59] and self-infection with hookworm (known generally as helminthic therapy).[60]


Disability-adjusted life yearfor multiple sclerosis per 100,000 inhabitants in 2004

  no data
  less than 13
  more than 43

The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual’s sex, age, and initial symptoms; and the degree of disability the person experiences.[7] The disease evolves and advances over decades, 30 being the mean years to death since onset.[1]

Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.[7][61]

The life expectancy of people with MS is 5 to 10 years lower than that of unaffected people.[1] Almost 40% of patients reach the seventh decade of life.[61] Nevertheless, two-thirds of the deaths in people with MS are directly related to the consequences of the disease.[1] Suicide also has a higher prevalence than in the healthy population, while infections and complications are especially hazardous for the more disabled ones.[1]

Although most patients lose the ability to walk prior to death, 90% are still capable of independent walking at 10 years from onset, and 75% at 15 years.[61][62]


Ethnic groups such as the Sami have a lower incidence of MS, possibly due to genetic factors.

Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at a given time. Prevalence is known to depend not only on incidence, but also on survival rate and migrations of affected people. MS has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population.[2] Studies on populational and geographical patterns of epidemiological measures have been very common in MS,[27] and have led to the proposal of different etiological (causal) theories.[5][22][23][27]

MS usually appears in adults in their thirties but it can also appear in children.[1] The primary progressive subtype is more common in people in their fifties.[11] As with many autoimmune disorders, the disease is more common in women, and the trend may be increasing.[1][63] In children, the sex ratio difference is higher,[1] while in people over fifty, MS affects males and females almost equally.[11]

There is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator.[1][63] Climate, sunlight and intake of vitamin D have been investigated as possible causes of the disease that could explain this latitude gradient.[23] However, there are important exceptions to the north–south pattern and changes in prevalence rates over time;[1] in general, this trend might be disappearing.[63] This indicates that other factors such as environment or genetics have to be taken into account to explain the origin of MS.[1] MS is also more common in regions with northern Europe populations.[1] But even in regions where MS is common, some ethnic groups are at low risk of developing the disease, including the Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori.[64]

Environmental factors during childhood may play an important role in the development of MS later in life. Several studies of migrants show that if migration occurs before the age of 15, the migrant acquires the new region’s susceptibility to MS. If migration takes place after age 15, the migrant retains the susceptibility of his home country.[1][22] However, the age–geographical risk for developing multiple sclerosis may span a larger timescale.[1] A relationship between season of birth and MS has also been found which lends support to an association with sunlight and vitamin D. For example fewer people with MS are born in November as compared to May.[65]


Medical discovery

Detail of drawing from Carswell book depicting MS lesions in the brain stem and spinal cord (1838)

The French neurologist Jean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.[66] Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot’s triad 1 are nystagmus, intention tremor, and telegraphic speech, though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a “marked enfeeblement of the memory” and “conceptions that formed slowly”.[3]

Prior to Charcot, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease’s clinical details, but did not identify it as a separate disease.[66] Specifically, Carswell described the injuries he found as “a remarkable lesion of the spinal cord accompanied with atrophy”.[1] Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.[67][68]

After Charcot’s description, Eugène Devic (1858–1930), Jozsef Balo (1895–1979), Paul Ferdinand Schilder (1886–1940), and Otto Marburg (1874–1948) described special cases of the disease. During all the 20th century there was an important development on the theories about the cause and pathogenesis of MS while efficacious treatments began to appear in 1990.[1]

 Historical cases

There are several historical accounts of people who lived before or shortly after the disease was described by Charcot and probably had MS.


A young woman called Halldora, who lived in iceland around 1200, suddenly lost her vision and mobility, but after praying to the saints, recovered them seven days after.

Saint Lidwina of Schiedam (1380–1433),

 a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of 16 until her death at 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS.[69] Both cases have led to the proposal of a ‘Viking gene’ hypothesis for the dissemination of the disease.[70]

3.Augustus Frederick d’Este (1794–1848),

son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George III of the United Kingdom, almost certainly suffered from MS. D’Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) after the funeral of a friend. During the course of his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.[71][72]

4.WNP Barbelion

Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle with MS.[72] His diary was published in 1919 as The Journal of a Disappointed Man.[73]

5.Indonesian Artist Pepeng


Stay in the Hospital Comforts Pepeng

– Ferrasta Soebardi alias Pepeng did not give up.
His passion to entertain, work, and science menutuntut never extinguished, although the disease Multiple gnawing Scleorosis since March 2005.
The house is located dipertemuan Pepeng two watershed, precisely at the very back corner of the Earth Heritage Complex Cinere, Depok, a lot changed. Not only that, his hobby of hanging out in pengkolan also never again dilakoninya. Now dive into the life he learned from the bed where he lay suffering from the disease. “Many consider me sick because of the location of this house. I do not believe it. I am more afraid of thieves than a ghost, “joke.
The proof, every day something came to my house Pepeng. Not to put a sense of pity, but instead draw from the life sciences Pepeng.
It has been over five years Pepeng friends with Scleorosis Multiple disease (MS). Rare disease that makes the sufferer paralyzed. Even at a specific stage of the autonomic nervous taxable, the brain can go wrong command.
However, the disease which attacked him did not make Pepeng stop ‘ngebanyol’. Although the actions that had to do with his group, Sergeant Geronimo ‘, currently only done while lying in bed. Pepeng obstinacy, in addition to fighting the disease, also encouraged a love that never faded from his beloved wife, Siti Aishah Mariam Utami. “Love it makes my life as it is now,” said Pepeng when met recently.
Not just trying to make a living, in the midst of the struggle against diseases, remains persistent Pepeng studying to reach his goal earned a Bachelor Two (S2) in Post Graduate, Faculty of Psychology, University of Indonesia. Master’s degree in the field of Social Psychology Interventions achieved with the predicate ‘cum laude’ in 2006.
Not quite just that, Pepeng also berancana continuing education to a doctorate (S3). Pepeng spirit is once again showing and proving that the conditions of her condition at this time does not become an obstacle to academic achievement. “Hopefully I can reach S3,” said Pepeng vigorously.

Got a ‘wife’ New

Pepeng first glance seemed helpless because the condition can only lie in bed and wheelchair. However, the same conditions which made him even more excited to have a ‘wife’ new. Thus, his days are never quiet from a busy work ‘wife’ a new form of a laptop which he uses to develop his new business, sell the domain.
Even according to his wife, Utami, new activities Pepeng with his laptop had become like his own wife. “Wake up he immediately held a ‘wife’ new and can take hours. If I only ‘wife’ second. His new wife, yes the laptop, “explains Utami. With the same tool Pepeng working on a book about his life that was nearly completed, he added.
Indeed Pepeng illness, can no longer make a career in the performing and entertainment presenter. However, he would still be a man who is fortunate to have a pious wife. So Pepeng remains strong and able to meet the needs of families by performing a number of activities such as Moslem received stitches in his home.
In diseased condition, Pepeng also able to send their children to college broadcast in the neighbor country, Malaysia. “Honestly, almost Mamas education is hampered due to lack of fees. However, before the tuition payment deadline, some colleagues came to see her deliver the fees and others. With the money, eventually Mamas could continue his studies again. All this because God intervened, “he said.

Want Not Lost Meaning of Life

Pepeng also revealed exposures of MS disease-fighting spirit that attacked since last five years. “I can only pray and most importantly, the spirit should not be extinguished. I maker crowd. My prayer when the first pain is not to lonely because of my behavior. I know, all diseases are created at once with the medicine. Hopefully I still miss the cure, “jokes the father of Mamas, Mio, Lalo, and Izra it.
Once convicted of MS disease, Pepeng space is very limited. His days were spent more in the bedroom. From the bedroom, too, Pepeng work. Every Tuesday from morning until evening, Pepeng shooting for the show program ‘Meet Pepeng’ from her bedroom.
In the bedroom newly renovated it, Pepeng also receive his guests. He never refused to those who want to visit. An acquaintance of the Facebook social networking account, for example, comes with 100 colleagues sekantornya invites. There was absolutely no privacy in the home space Pepeng and he only comes once limited to 30 guests still have some breathing room in a room measuring 6 x 7 meters.
Madura typical joke has always been a fresh distraction while talking with the guests. However, every speech, Pepeng bombarded true pain. Because the jokes fresh and warm greeting, the other person often forget that Pepeng was ill. Pepeng actually able to spread the spirit of life and the laptop remains the flagship for a relationship with the outside world. O ato

Birth name: Ferrasta Soebardi
Date of Birth: 23 September 1954)
Place of Birth: Sumenep, Madura, Indonesia
Wife: Siti Aishah Mariam Utami
Children: Mamas, Mio, Lalo, and Izra
Occupation: Presenter, actor, writer
Years active: 1978 – present
Education: Graduate School of Psychology, University of Indonesia, majoring in Psychology of Social Intervention, passed August 4, 2006 with a very satisfactory value (A).
Which movie Starring: Rojali and Juleha (1979), Win-Delicious (1986), and his goods You (1986).
Work Experience: Employee Bank Pinaesaan (1988) and Bakrie Brothers (1989)

Ferrasta “Pepeng” Soebardi: “I’m Just Waiting for God’s Promise”
Rarely found who are grateful when wracked exam. Ferrasta Soebardi or better known as Pepeng is the one who bit it. In the middle of exams in the form of chronic pain that he could still smile and prejudice either to God.

Pepeng bersama istri tercinta

As is known, since five years ago, convicted Pepeng rare disease Multiple Sclerosis (MS), which is a disease that attacks the central nervous system and bring the process of inflammation (inflammation) of the spine. This disease will interfere with the delivery of “messages” between the brain and other body parts.

MS disease who suffered a former presenter of this famous cause paralysis and every moment felt incredible pain from waist to toe. How sakitkah? “As diketok mallet finger. But pain is not the time diketok, but after diketok. Carried away, carried away, carried away, “said Pepeng.

Pepeng sure there is wisdom behind a disease that God gives. He did not want depression and dissolve by this ordeal. This he proved by staying productive activity, although lived in the bed.

Pepeng admitted it when he gets sick a lot. Earned a master psychologist, for example. Even more closely interwoven friendship and wide when he was sick. Pepeng house almost every day on Earth Heritage Cinere guests visited Depok West Java, whether known or not. Not infrequently, many guests are enlightened after visiting the house Pepeng.

Middle of last month, Ahmad Damanik, Dadang Kusmayadi, Ibn Intercession, Saiful Hamiwanto, and Surya Fachrizal of Sound Hidayatullah visit to the residence Pepeng. This visit is solely for the interview, but also in the framework of friendship.

In the rooms there are many patches of paper testimonials from the guests, told the magazine Pepeng share stories of perseverance to face the disease

original info

Dalam Sakit Pepeng Tetap Menghibur

Ferrasta Soebardi alias Pepeng tak menyerah.
Semangatnya untuk menghibur, berkarya, dan menutuntut ilmu tak pernah padam, walau penyakit Multiple Scleorosis menggerogotinya sejak Maret 2005.Rumah Pepeng yang terletak dipertemuan dua aliran sungai, persisnya di pojok paling belakang Kompleks Bumi Pusaka Cinere, Depok, banyak berubah. Tidak hanya itu, hobinya nongkrong di pengkolan juga tak pernah lagi dilakoninya. Kini dia belajar menyelami kehidupan dari atas ranjang tempatnya terbaring sejak menderita penyakit. “Banyak yang menganggap saya sakit karena lokasi rumah ini. Saya nggak percaya. Saya lebih takut maling daripada hantu,” kelakarnya.
Buktinya, setiap hari selalu ada saja yang datang ke rumah Pepeng. Bukan untuk menaruh rasa iba, tapi justru menimba ilmu hidup dari Pepeng.
Sudah lebih lima tahun Pepeng berteman akrab dengan penyakit Multiple Scleorosis (MS). Penyakit langka itu membuat penderitanya lumpuh. Bahkan pada stadium tertentu syaraf otonom kena, otak bisa salah perintah.
Namun, penyakit yang menyerangnya tak membuat Pepeng berhenti ‘ngebanyol’. Meskipun aksi-aksi yang dulu dilakukannya bersama grupnya, Sersan Prambors’, saat ini hanya dilakukannya sambil berbaring di tempat tidur. Ketegaran Pepeng, selain untuk melawan penyakitnya, juga didorong cinta kasih yang tak pupus dari istri tercintanya, Utami Mariam Siti Aisyah. “Cinta itu membuat saya hidup seperti sekarang,” kata Pepeng saat ditemui baru-baru ini. 
Tidak hanya berusaha mencari nafkah, di tengah perjuangan melawan penyakit, Pepeng tetap gigih menuntut ilmu untuk mewujudkan cita-citanya meraih gelar Strata Dua (S2) di  Pasca Sarjana, Fakultas Psikologi, Universitas Indonesia. Gelar master  dibidang Psikologi Intervensi Sosial diraihnya dengan predikat ‘cumlaude’ pada 2006 silam.
Tidak cukup hanya itu, Pepeng juga berancana melanjutkan pendidikan hingga meraih gelar doktor (S3). Semangat Pepeng ini sekaligus menunjukkan dan membuktikan bahwa kondisi yang kondisi yang dialaminya saat ini tidak menjadi kendala untuk mengukir prestasi akademik. “Mudah-mudahan saya mampu meraih S3,” ungkap Pepeng penuh semangat.Punya ‘Istri’ BaruSepintas Pepeng tampak tak berdaya karena kondisinya yang hanya bisa terbaring di tempat tidur dan kursi roda. Namun, kondisi itu pula yang membuatnya semakin bersemangat hingga memiliki ‘istri’ baru. Sehingga, hari-harinya tak pernah sepi dari kesibukan mengerjakan ‘istri’ baru berupa laptop yang digunakannya untuk mengembangkannya bisnis barunya, menjual domain.
Bahkan menurut istrinya, Utami, kegiatan baru Pepeng bersama laptopnya sudah dijadikan layaknya istri sendiri. “Bangun tidur dia langsung megang ‘istri’ barunya dan bisa berjam-jam. Kalau saya cuma ‘istri’ kedua. Istri barunya, ya laptop,” jelas Utami. Dengan alat itu pula Pepeng menggarap buku tentang kehidupannya yang sudah hampir rampung, tambahnya.
Memang penyakit yang diderita Pepeng, membuatnya tak bisa lagi tampil berkarir di dunia presenter dan entertainment. Namun, dia tetap masih menjadi seorang pria yang beruntung karena memiliki istri yang soleh. Sehingga Pepeng tetap tegar dan mampu memenuhi kebutuhan keluarga dengan melakukan sejumlah  kegiatan seperti menerima jahitan busana muslim di rumahnya.
Dalam kondisi sakit, Pepeng juga mampu menyekolahkan anaknya kuliah broadcast di negeri Jiran, Malaysia. “Jujur saja, pendidikan Mamas nyaris terhambat karena ketiadaan biaya. Namun, sebelum batas waktu pembayaran kuliah, beberapa rekan datang menjenguk sambil mengantarkan honor dan lain-lainnya. Dengan uang itu, akhirnya Mamas bisa melanjutkan kuliahnya kembali. Semua ini karena turut campur tangan Allah,” ungkapnya.Tak Mau Kehilangan Makna HidupPepeng juga mengungkapkan, ikhwal semangatnya melawan penyakit MS yang menyerangnya sejak lima tahun terakhir. “Saya hanya bisa berdoa dan yang paling penting, semangat tidak boleh padam. Saya pembuat keramaian. Doa saya ketika pertama sakit adalah jangan sampai kesepian karena perilaku saya.  Saya tahu, semua penyakit diciptakan sekaligus dengan obatnya. Mudah-mudahan saya masih kebagian obatnya,” kelakar ayah dari Mamas, Mio, Lalo, dan Izra itu.
Setelah divonis penyakit MS, ruang gerak Pepeng memang sangat terbatas. Hari-harinya lebih banyak dihabiskan di kamar tidur. Dari kamar tidur itu pula, Pepeng bekerja. Tiap Selasa sejak pagi hingga petang, Pepeng melakukan pengambilan gambar untuk program acara ‘Ketemu Pepeng’ dari ruang tidurnya.
Di kamar tidur yang baru direnovasi itu, Pepeng juga menerima tamu-tamunya. Dia tak pernah menolak orang-orang yang ingin bertandang. Seorang kenalan dari akun jejaring sosial Facebook, misalnya, datang dengan mengajak 100 rekan sekantornya. Sama sekali tak ada ruang privasi di rumah Pepeng dan dia hanya membatasi 30 tamu sekali datang agar tetap punya ruang bernapas di kamar berukuran 6 x 7 meter itu.
Guyonan khas Madura selalu menjadi selingan segar ketika berbincang dengan para tamu. Tetapi, setiap berbicara, Pepeng sejatinya dihujani rasa sakit. Karena guyonan segar dan sapaan hangatnya, lawan bicara sering lupa bahwa Pepeng sedang sakit. Pepeng justru mampu menebar semangat hidup dan laptop tetap menjadi andalannya untuk menjalin hubungan dengan dunia luar. O atoBIODATA PEPENG
Nama lahir        : Ferrasta Soebardi
Tanggal Lahir    : 23 September 1954)
Tempat Lahir    : Sumenep, Madura, Indonesia
Istri                : Utami Mariam Siti Aisyah
Anak            : Mamas, Mio, Lalo, dan Izra
Pekerjaan         : Presenter, aktor, penulis
Tahun aktif         : 1978 – sekarang
Pendidikan        : Pasca Sarjana Fakultas Psikologi Universitas Indonesia, jurusan Psikologi Intervensi Sosial, lulus 4 Agustus 2006 dengan nilai sangat memuaskan (A).
Film Yang Dibintangi: Rojali dan Juleha (1979), Sama-Sama Enak (1986), dan Anunya Kamu (1986).
Pengalaman Kerja:  Pegawai Bank Pinaesaan (1988) dan Bakrie Brothers (1989)


Ferrasta “Pepeng” Soebardi:“Saya Tinggal Menunggu Janji Allah” 

Jarang sekali ditemukan orang yang bersyukur ketika didera ujian. Ferrasta Soebardi atau lebih dikenal dengan Pepeng adalah orang yang sedikit itu. Di tengah ujian berupa sakit yang menahun ia masih bisa tersenyum dan berprasangka baik kepada Allah.

Pepeng bersama istri tercinta 

Seperti diketahui,  sejak lima tahun silam, Pepeng divonis penyakit langka  Multiple Sclerosis (MS-red), yakni sebuah penyakit yang menyerang sistem saraf pusat dan memunculkan terjadinya proses inflamasi(peradangan) pada tulang belakang. Penyakit ini akan mengganggu penyampaian “pesan” antara otak dan bagian-bagian tubuh lainnya.


Penyakit MS yang dideritanya menyebabkan mantan presenter kondang ini mengalami kelumpuhan dan setiap saat merasakan nyeri yang luar biasa dari pinggang hingga ujung kaki. Seberapa sakitkah? “Seperti jari diketok palu. Tapi nyerinya bukan saat diketok, tapi setelah diketok. Nyut, nyut,nyut,” kata Pepeng.

Pepeng yakin ada hikmah di balik penyakit yang Allah berikan. Ia tak ingin depresi dan larut oleh penderitaan yang dialaminya ini. Ini ia buktikan dengan tetap melakukan aktivitas yang produktif, meski dijalani di atas tempat tidur.

Pepeng mengaku justru saat sakit ia mendapatkan banyak hal. Memperoleh gelar master psikolog, misalnya. Jalinan pertemanannya pun semakin erat dan luas saat ia sakit. Hampir setiap harinya rumah Pepeng di Bumi Pusaka Cinere Depok Jawa Barat dikunjungi tamu, baik yang dikenal maupun yang tidak. Tak jarang banyak tamu yang tercerahkan setelah berkunjung ke rumah Pepeng.

Pertengahan bulan lalu, Ahmad Damanik, Dadang Kusmayadi, Ibnu Syafaat, Saiful Hamiwanto, dan Surya Fachrizal dari Suara Hidayatullah berkunjung ke kediaman Pepeng. Kunjungan kali ini tidak semata-mata untuk wawancara, tapi juga dalam rangka silaturahim.

Di dalam kamarnya yang terdapat banyak tempelan kertas testimoni dari para tamu itu, kepada majalah ini Pepeng berbagi kisah tentang ketabahannya menghadapi penyakit.

Research directions



Chemical structure of alemtuzumab

Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments.[74] A number of treatments that may curtail attacks or improve function are under investigation. Emerging agents for RRMS that have shown promise in phase 2 trials include alemtuzumab (trade name Campath), daclizumab (trade name Zenapax), rituximab, dirucotide, BHT-3009, cladribine, dimethyl fumarate, estriol, fingolimod, laquinimod, minocycline, statins, temsirolimus and teriflunomide.[74]

In 2010, an FDA committee recommended approving fingolimod for the treatment of MS attacks,[75] and on September 22, 2010, fingolimod (trade name Gilenya) became the first oral drug approved by the Food and Drug Administration to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis.[76] Clinical trials of fingolimod have demonstrated side effects in treated patients, including cardiovascular conditions, macular edema, infections, liver toxicity and malignancies.[77][78]

Much interest has been focused on the prospect of utilizing vitamin D analogs in the prevention and management of CIS and MS, especially given its possible role in the pathogenesis of the disease. While there is anecdotal evidence of benefit for low dose naltrexone,[79] only results from a pilot study in primary progressive MS have been published.[80]

Disease biomarkers

The variable clinical presentation of MS and the lack of diagnostic laboratory tests lead to delays in diagnosis and the impossibility of predicting diagnosis. New diagnostic methods are being investigated. These include work with anti-myelin antibodies, analysis of microarray gene expression and studies with serum and cerebrospinal fluid but none of them has yielded reliable positive results.[81]

Currently there are no clinically established laboratory investigations available that can predict prognosis. However, several promising approaches have been proposed. Investigations on the prediction of evolution have centered on monitoring disease activity. Disease activation biomarkers include interleukin-6, nitric oxide and nitric oxide synthase, osteopontin, and fetuin-A.[81] On the other hand since disease progression is the result of neurodegeneration the roles of proteins indicative of neuronal, axonal, and glial loss such as neurofilaments, tau and N-acetylaspartate are under investigation.[81]

A final investigative field is work with biomarkers that distinguish between medication responders and nonresponders.[81]

Chronic cerebrospinal venous insufficiency

In 2008, Italian vascular surgeon Paolo Zamboni reported research suggesting that MS involves a vascular disease process he referred to as chronic cerebrospinal venous insufficiency (CCSVI, CCVI), in which veins from the brain are constricted. He found CCSVI in the majority of MS patients, performed a surgical procedure to correct it and claimed that 73% of patients improved.[82] Concern has been raised with Zamboni’s research as it was neither blinded nor controlled[83] and further studies have had variable results.[84] This has raised serious objections to the hypothesis of CCSVI originating multiple sclerosis.[85] The neurology community currently recommends not to use the proposed treatment until its effectiveness is confirmed by controlled studies, the need for which has been recognized by the scientific bodies engaged in MS research

the end @ copyright Dr iwan suwandy 2011

The Lou Gehrig ALS Disease Informations











The Driwan’s  Cybermuseum

Lou Gehrig Disease

amyotrophic lateral sclerosis (ALS),

“The Iron Horse” f

Lou Gehrig
First baseman
Born: June 19, 1903(1903-06-19)
Yorkville, New York City, New York
Died: June 2, 1941(1941-06-02) (aged 37)
Riverdale, New York City, New York
Batted: Left Threw: Left 
MLB debut
June 15, 1923 for the New York Yankees
Last MLB appearance
April 30, 1939 for the New York Yankees
Career statistics
Batting average     .340
Home runs     493
Hits     2,721
Runs batted in     1,995
Career highlights and awards
Member of the National
Empty Star.svg Empty Star.svg Empty Star.svg Baseball Hall of Fame Empty Star.svg Empty Star.svg Empty Star.svg
Induction     1939
Vote     Special Election (results unknown)

Henry LouisLouGehrig (June 19, 1903 – June 2, 1941), nicknamed “The Iron Horse” for his durability, was an American Major League Baseball first baseman. He played his entire 17-year baseball career for the New York Yankees (1923–1939). Gehrig set several major league records.[1] He holds the record for most career grand slams (23).[2] Gehrig is chiefly remembered for his prowess as a hitter, his consecutive games-played record and its subsequent longevity, and the pathos of his farewell from baseball at age 36, when he was stricken with amyotrophic lateral sclerosis.

Gehrig was elected to the Baseball Hall of Fame in 1939. In 1969 he was voted the greatest first baseman of all time by the Baseball Writers’ Association,[3] and was the leading vote-getter on the Major League Baseball All-Century Team, chosen by fans in 1999.[4]

A native of New York City, he played for the New York Yankees until his career was cut short by amyotrophic lateral sclerosis (ALS), now commonly known in the United States and Canada as Lou Gehrig’s disease.[5] Over a 15-season span from 1925 through 1939, he played in 2,130 consecutive games, the streak ending only when Gehrig became disabled by the fatal neuromuscular disease that claimed his life two years later. His streak, long considered one of baseball’s few unbreakable records,[6] stood for 56 years, until finally broken by Cal Ripken, Jr., of the Baltimore Orioles on September 6, 1995.

Gehrig accumulated 1,995 runs batted in (RBI) in 17 seasons, with a career batting average of .340, on-base percentage of .447, and slugging percentage of .632. Three of the top six RBI seasons in baseball history belong to Gehrig. He was selected to each of the first seven All-Star games (though he did not play in the 1939 game, as he retired one week before it was held),[7] and he won the American League‘s Most Valuable Player award in 1927 and 1936. He was also a Triple Crown winner in 1934, leading the American League in batting average, home runs, and RBIs.[8]


 Early life

Gehrig was born in the Yorkville section of Manhattan, weighing almost 14 pounds (6.4 kg) at birth, the second child out of four to German immigrants.[9] His father Heinrich was a sheet metal worker by trade, but frequently unemployed due to alcoholism, and his mother Christina was a maid, the main breadwinner and disciplinarian in the family.[10] His two sisters died from whooping cough and measles at an early age.[11] Young Gehrig helped his mother with her work, doing tasks such as folding laundry and picking up supplies from the local stores.[12] In 1910, Gehrig lived with his parents at 2266 Amsterdam Avenue in Manhattan.[13] In 1920 the family resided at 2079 8th Avenue in Manhattan [14]

Gehrig first garnered national attention for his baseball ability while playing in a game at Cubs Park (now Wrigley Field) on June 26, 1920. Gehrig’s New York School of Commerce team was playing a team from Chicago’s Lane Tech High School, in front of a crowd of more than 10,000 spectators.[15] With his team winning 8–6 in the top of the ninth inning, Gehrig hit a grand slam completely out of the major league park, an unheard-of feat for a 17-year old.[15][16]

Gehrig on the Columbia University baseball team

Lou Gehrig attended PS 132 in the Washington Heights section of Manhattan, then to Commerce High School, graduating in 1921.[17][18] Gehrig then studied at Columbia University for two years, although he did not graduate.[19] While attending Columbia, he was a member of Phi Delta Theta fraternity.[20] Initially, Gehrig could not play intercollegiate baseball for the Columbia Lions because he had played baseball for the minor-league Hartford Senators of the eastern League in the summer before his freshman year.[20] At the time, he was unaware that doing so jeopardized his eligibility to play any collegiate sport. However, Gehrig was ruled eligible to play on the Lions‘ football team and was a standout fullback. Later, he gained baseball eligibility and played on the Lions team.

On April 18, 1923, the same day that Yankee Stadium opened for the first time and Babe Ruth inaugurated the new stadium with a home run, Columbia pitcher Gehrig struck out seventeen Williams College batters to set a team record; however, Columbia lost the game. Only a handful of collegians were at South Field that day, but more significant was the presence of Yankee scout Paul Krichell, who had been trailing Gehrig for some time. It was not Gehrig’s pitching that particularly impressed him; rather, it was Gehrig’s powerful left-handed hitting. During the time Krichell had been observing the young Columbia ballplayer, Gehrig had hit some of the longest home runs ever seen on various Eastern campuses, including a 450-foot (137 m) home run on April 28 at Columbia’s South Field which landed at 116th Street and Broadway.[21] Within two months, Gehrig had signed a Yankee contract.[20] Gehrig returned to minor-league Hartford to play parts of two seasons, 1923 and 1924, batting .344 and crashing 61 home runs in 193 games. (It was the only time Lou ever played any level of ball — sandlot, high school, collegiate or pro — for a non-New York City-based team.)

 Major League career

Gehrig joined the New York Yankees midway through the 1923 season and made his debut on June 15, 1923, as a pinch hitter. In his first two seasons, he saw limited playing time, mostly as a pinch hitter — he played in only 23 games and was not on the Yankees’ 1923 World Series roster. In 1925, he batted .295, with 20 home runs and 68 runs batted in (RBIs).[22]

Babe Ruth and Lou Gehrig in exhibition game at West Point, New York (May 6, 1927)

The 23-year-old Yankee first baseman’s breakout season came in 1926, when he batted .313 with 47 doubles, an American League-leading 20 triples, 16 home runs, and 112 RBIs.[22] In the 1926 World Series against the St. Louis Cardinals, Gehrig hit .348 with two doubles and 4 RBIs. The Cardinals won a seven-game series four games to three.[23]

In 1927, Gehrig put up one of the greatest seasons by any batter in history, hitting .373, with 218 hits: 52 doubles, 18 triples, 47 home runs, a then-record 175 runs batted in (surpassing teammate Babe Ruth’s 171 six years earlier), and a .765 slugging percentage.[22] His 117 extra-base hits that season are second all-time to Babe Ruth’s 119 extra-base hits in 1921[22] and his 447 total bases are third all-time, after Babe Ruth’s 457 total bases in 1921 and Rogers Hornsby‘s 450 in 1922.[22] Gehrig’s production helped the 1927 Yankees to a 110–44 record, the AL pennant, and a four-game sweep of the Pittsburgh Pirates in the 1927 World Series. Although the AL recognized his season by naming him league MVP, it was overshadowed by Babe Ruth’s 60 home run season and the overall dominance of the 1927 Yankees, a team often cited as having the greatest lineup of all time — the famed Murderers’ Row.[24]

Despite playing in the shadow of the larger-than-life Ruth for two-thirds of his career, Gehrig was one of the highest run producers in baseball history: he had 509 RBIs during a three-season stretch (1930–32). Only two other players, Jimmie Foxx with 507 and Hank Greenberg with 503, have surpassed 500 RBIs in any three seasons; their totals were non-consecutive. (Babe Ruth had 498.)[25] Playing 14 complete seasons, Gehrig had 13 consecutive seasons with 100 or more RBIs (a major league record shared with Foxx until eclipsed in 2010 by Alex Rodriguez). Gehrig had six seasons where he batted .350 or better (with a high of .379 in 1930), plus a seventh season at .349. He had seven seasons with 150 or more RBIs, 11 seasons with over 100 walks, eight seasons with 200 or more hits, and five seasons with more than 40 home runs.[26] Gehrig led the American League in runs scored four times, home runs three times, and RBIs five times. His 184 RBIs in 1931 remain the American League record as of 2010 and rank second all-time to Hack Wilson‘s 191 RBIs in 1930. On the single-season RBI list, Gehrig ranks second, fifth (175), and sixth (174), with four additional seasons over 150 RBI. He also holds the baseball record for most seasons with 400 total bases or more, accomplishing this feat five times in his career.[26] He batted fourth in the lineup to Ruth’s third in the order, making it impractical to give up an intentional walk to Ruth.

During the 10 seasons (1925–1934) in which Gehrig and Ruth were both Yankees and played a majority of the games, Gehrig had more home runs than Ruth only once, in 1934, when he hit 49 compared to Ruth’s 22 (Ruth played 125 games that year). They tied at 46 in 1931. Ruth had 424 home runs compared to Gehrig’s 347. However, Gehrig outpaced Ruth in RBI, 1,436 to 1,316. Gehrig had a .343 batting average, compared to .338 for Ruth.[27]

Gehrig 1933 Goudey baseball card.

In 1932, Gehrig became the first player of the 20th century to hit four home runs in a game, accomplishing the feat on June 3 against the Philadelphia Athletics.[28] He narrowly missed getting a fifth home run in the game when Athletics center fielder Al Simmons made a leaping catch of another fly ball at the center field fence. After the game, manager Joe McCarthy told him, “Well, Lou, nobody can take today away from you.” On the same day, however, John McGraw announced his retirement after thirty years of managing the New York Giants. McGraw, not Gehrig, got the main headlines in the sports sections the next day.[29] The following year, in September 1933, Gehrig married Eleanor Twitchell, the daughter of Chicago Parks Commissioner Frank Twitchell.[22]

In a 1936 World Series cover story about Lou Gehrig and Carl Hubbell, Time proclaimed Gehrig “the game’s No. 1 batsman”, who “takes boyish pride in banging a baseball as far, and running around the bases as quickly, as possible”.[30]

] 2,130 consecutive games

Seven of the American League’s 1937 All-Star players, from left to right Lou Gehrig, Joe Cronin, Bill Dickey, Joe DiMaggio, Charlie Gehringer, Jimmie Foxx, and Hank Greenberg. All seven would eventually be elected to the Hall of Fame.

On June 1, 1925, Gehrig entered the game as a pinch hitter, substituting for shortstop Paul “Pee Wee” Wanninger. The next day, June 2, Yankee manager Miller Huggins started Gehrig in place of regular first baseman Wally Pipp. Pipp was in a slump, as were the Yankees as a team, so Huggins made several lineup changes to boost their performance. Fourteen years later, Gehrig had played 2,130 consecutive games. In a few instances, Gehrig managed to keep the streak intact through pinch hitting appearances and fortuitous timing; in others, the streak continued despite injuries. For example:

  • On April 23, 1933, an errant pitch by Washington Senators hurler, Earl Whitehill, struck Gehrig in the head. Although almost knocked unconscious, Gehrig recovered and remained in the game.
  • On June 14, 1933, Gehrig was ejected from a game, along with manager Joe McCarthy, but he had already been at bat, so he got credit for playing the game.
  • On July 13, 1934, Gehrig suffered a “lumbago attack” and had to be assisted off the field. In the next day’s away game, he was listed in the lineup as “shortstop”, batting lead-off. In his first and only plate appearance, he singled and was promptly replaced by a pinch runner to rest his throbbing back, never taking the field. A&E‘s Biography speculated that this illness, which he also described as “a cold in his back”, might have been the first symptom of his debilitating disease.[31]

In addition, X-rays taken late in his life disclosed that Gehrig had sustained several fractures during his playing career, although he remained in the lineup despite those previously undisclosed injuries.[32] On the other hand, the streak was helped when Yankees general manager Ed Barrow postponed a game as a rainout on a day when Gehrig was sick with the flu—even though it was not raining.[33]

Gehrig’s record of 2,130 consecutive games played stood until September 6, 1995, when Baltimore Orioles shortstop Cal Ripken, Jr. broke it.[34]


Plaque in St. Petersburg, Fla., where Gehrig collapsed in 1939 during spring training

Although his performance in the second half of the 1938 season was slightly better than in the first half, Gehrig reported physical changes at the midway point. At the end of that season, he said, “I tired mid-season. I don’t know why, but I just couldn’t get going again.” Although his final 1938 statistics were above average (.295 batting average, 114 RBI, 170 hits, .523 slugging percentage, 689 plate appearances with only 75 strikeouts, and 29 home runs), they were significantly down from his 1937 season, in which he batted .351 and slugged .643. In the 1938 World Series, he had four hits in 14 at-bats, all singles.[35]

When the Yankees began their 1939 spring training in St. Petersburg, Florida, it was clear that Gehrig no longer possessed his once-formidable power. Even Gehrig’s base running was affected, and at one point he collapsed at Al Lang Field, then the Yankees’ spring training park.[36] By the end of spring training, Gehrig had not hit a home run.[37] Throughout his career, Gehrig was considered an excellent baserunner, but as the 1939 season got under way, his coordination and speed had deteriorated significantly.[38]

By the end of April, his statistics were the worst of his career, with one RBI and a .143 batting average. Fans and the press openly speculated on Gehrig’s abrupt decline. James Kahn, a reporter who wrote often about Gehrig, said in one article:

I think there is something wrong with him. Physically wrong, I mean. I don’t know what it is, but I am satisfied that it goes far beyond his ball-playing. I have seen ballplayers ‘go’ overnight, as Gehrig seems to have done. But they were simply washed up as ballplayers. It’s something deeper than that in this case, though. I have watched him very closely and this is what I have seen: I have seen him time a ball perfectly, swing on it as hard as he can, meet it squarely — and drive a soft, looping fly over the infield. In other words, for some reason that I do not know, his old power isn’t there… He is meeting the ball, time after time, and it isn’t going anywhere.[39]

He was indeed meeting the ball, with only one strikeout in 28 at-bats; however, Joe McCarthy found himself resisting pressure from Yankee management to switch Gehrig to a part-time role. Things came to a head when Gehrig had to struggle to make a routine put-out at first base. The pitcher, Johnny Murphy, had to wait for Gehrig to drag himself over to the bag so he could field the throw. Murphy said, “Nice play, Lou.”[39]

On April 30, Gehrig went hitless against the Washington Senators. Gehrig had just played his 2,130th consecutive major league game.[27]

On May 2, the next game after a day off, Gehrig approached McCarthy before the game in Detroit against the Tigers and said, “I’m benching myself, Joe,” telling the Yankees’ skipper that he was doing so “for the good of the team.”[40] McCarthy acquiesced, putting Ellsworth “Babe” Dahlgren in at first base, and also said that whenever Gehrig wanted to play again, the position was his. Gehrig himself took the lineup card out to the shocked umpires before the game, ending the fourteen-year streak. Before the game began, the Briggs Stadium announcer told the fans, “Ladies and gentlemen, this is the first time Lou Gehrig’s name will not appear on the Yankee lineup in 2,130 consecutive games.” The Detroit Tigers’ fans gave Gehrig a standing ovation while he sat on the bench with tears in his eyes.[35] A wire service photograph of Gehrig reclining against the dugout steps with a stoic expression appeared the next day in the nation’s newspapers. Other than his retirement ceremony, it is the most-reproduced and best-remembered visual image of Gehrig.

Gehrig stayed with the Yankees as team captain for the rest of the season, but never played in a major league game again.[35]


As Lou Gehrig’s debilitation became steadily worse (he stumbled over curbs, fumbled with the baseball, and even slipped and fell while running bases), his wife Eleanor called the famed Mayo Clinic in Rochester, Minnesota. Her call was transferred to Charles William Mayo, who had been following Gehrig’s career and his mysterious loss of strength. Mayo told Eleanor to bring Gehrig as soon as possible.[35]

Eleanor and Gehrig flew to Rochester from Chicago, where the Yankees were playing at the time, arriving at the Mayo Clinic on June 13, 1939. After six days of extensive testing at Mayo Clinic, the diagnosis of amyotrophic lateral sclerosis (ALS) was confirmed on June 19, Gehrig’s 36th birthday.[9] The prognosis was grim: rapidly increasing paralysis, difficulty in swallowing and speaking, and a life expectancy of less than three years, although there would be no impairment of mental functions. Eleanor Gehrig was told that the cause of ALS was unknown but it was painless, non-contagious and cruel — the motor function of the central nervous system is destroyed but the mind remains fully aware to the end.[41][42]

At Eleanor’s request, the Mayo doctors intentionally withheld his grim prognosis from Gehrig. He often wrote letters to Eleanor, and in one such note written shortly afterwards, said (in part):

The bad news is lateral sclerosis, in our language chronic infantile paralysis. There isn’t any cure… there are very few of these cases. It is probably caused by some germ…Never heard of transmitting it to mates… There is a 50–50 chance of keeping me as I am. I may need a cane in 10 or 15 years. Playing is out of the question…[43]

Following Gehrig’s visit to the Mayo Clinic, he briefly rejoined the Yankees in Washington, D.C. As his train pulled into Union Station, he was greeted by a group of Boy Scouts, happily waving and wishing him luck. Gehrig waved back, but he leaned forward to his companion, a reporter, and said, “They’re wishing me luck — and I’m dying.”[9]

other famous persons with Lou Gehrig ALS Disease

1.Stephen Hawking To Highlight Lou Gehrig’s Disease


Stephen%20Hawking.jpgIsrALS, an Israeli association dedicated to finding a cure for amyotrophic lateral sclerosis (Lou Gehrig’s Disease), has announcedthat world renowned paralyzed British cosmologist, Stephen Hawking, who is in a wheelchair and speaks with the aid of a computer and voice synthesizer – will appear in a commercial to promote world awareness of muscle-wasting motor neuron disease:

[…] It will mark the first time in the 40 years since he was diagnosed with the paralysing disease that Hawking will participate in such a campaign, said IsrALS, which is 

Hawking, 65, will appear in two short clips to be filmed at Cambridge University, where he is Lucasian Professor of Mathematics – a post once held by Sir Isaac Newton.

“The move marks the recognition of British scientist, Professor Stephen Hawking, a well known sufferer of ALS disease, of a real opportunity for a scientific breakthrough in the research of the disease,” IsrALS said.

[…] “A hundred and fifty people die in Israel every year from ALS and many more in Britain. But nevertheless the disease is largely neglected by pharmaceutical companies and the scientific community,” IsrALS head Nir Tirosh said.

“We will hand over for free the clip to every ALS association in the world, every TV channel in the world that will be willing to use it,” he said.

There is presently no cure for ALS, and no treatment has been shown to significantly alter the course of the disease. However, much can be done to help maintain quality of life and to retain functional ability even in the face of progressive weakness which is one of the hallmarks of the disease

“The Luckiest Man on the Face of the Earth”

Lou Gehrig’s number 4 was retired by the New York Yankees in 1940.

The Yankee duo reunited – Lou Gehrig and Babe Ruth at Yankee Stadium on July 4, 1939. Within a decade a similar testimonial would be held for Ruth, who died from cancer 7 years after Gehrig’s death.

On June 21, the New York Yankees announced Gehrig’s retirement and proclaimed July 4, 1939, “Lou Gehrig Appreciation Day” at Yankee Stadium. Between games of the Independence Day doubleheader against the Washington Senators, the poignant ceremonies were held on the diamond. In its coverage the following day, The New York Times said it was “perhaps as colorful and dramatic a pageant as ever was enacted on a baseball field [as] 61,808 fans thundered a hail and farewell.”[44] Dignitaries extolled the dying slugger and the members of the 1927 Yankees World Championship team, known as “Murderer’s Row”, attended the ceremonies. New York Mayor Fiorello La Guardia called Gehrig “the greatest prototype of good sportsmanship and citizenship” and Postmaster General James Farley concluded his speech by predicting, “For generations to come, boys who play baseball will point with pride to your record.”[44]

Yankees Manager Joe McCarthy, struggling to control his emotions, then spoke of Lou Gehrig, with whom there was a close, almost father and son-like bond. After describing Gehrig as “the finest example of a ballplayer, sportsman, and citizen that baseball has ever known”, McCarthy could stand it no longer. Turning tearfully to Gehrig, the manager said, “Lou, what else can I say except that it was a sad day in the life of everybody who knew you when you came into my hotel room that day in Detroit and told me you were quitting as a ballplayer because you felt yourself a hindrance to the team. My God, man, you were never that.”[45]

The Yankees retired Gehrig’s uniform number “4”, making him the first player in Major League Baseball history to be accorded that honor.[46] Gehrig was given many gifts, commemorative plaques, and trophies. Some came from VIPs; others came from the stadium’s groundskeepers and janitorial staff. Footage of the ceremonies shows Gehrig being handed various gifts, and immediately setting them down on the ground, because he no longer had the arm strength to hold them.[9] The Yankees gave him a silver trophy with their signatures engraved on it. Inscribed on the front was a special poem written by The New York Times writer John Kieran.[47] The trophy cost only about $5, but it became one of Gehrig’s most prized possessions.[48] It is currently on display at the National Baseball Hall of Fame and Museum.

After the presentations and remarks by Babe Ruth, Gehrig addressed the crowd:

Fans, for the past two weeks you have been reading about the bad break I got. Yet today I consider myself the luckiest man on the face of the earth. I have been in ballparks for seventeen years and have never received anything but kindness and encouragement from you fans.

Look at these grand men. Which of you wouldn’t consider it the highlight of his career just to associate with them for even one day? Sure, I’m lucky. Who wouldn’t consider it an honor to have known Jacob Ruppert? Also, the builder of baseball’s greatest empire, Ed Barrow? To have spent six years with that wonderful little fellow, Miller Huggins? Then to have spent the next nine years with that outstanding leader, that smart student of psychology, the best manager in baseball today, Joe McCarthy? Sure, I’m lucky.

When the New York Giants, a team you would give your right arm to beat, and vice versa, sends you a gift — that’s something. When everybody down to the groundskeepers and those boys in white coats remember you with trophies — that’s something. When you have a wonderful mother-in-law who takes sides with you in squabbles with her own daughter — that’s something. When you have a father and a mother who work all their lives so that you can have an education and build your body — it’s a blessing. When you have a wife who has been a tower of strength and shown more courage than you dreamed existed — that’s the finest I know.

So I close in saying that I might have been given a bad break, but I’ve got an awful lot to live for. Thank you.

 — Lou Gehrig at Yankee Stadium, July 4, 1939[49]

The crowd stood and applauded for almost two minutes. Gehrig was visibly shaken as he stepped away from the microphone, and wiped the tears away from his face with his handkerchief.[48] Babe Ruth came over and hugged him as a band played “I Love You Truly” and the crowd chanted “We love you, Lou.” The New York Times account the following day called it “one of the most touching scenes ever witnessed on a ball field”, that made even hard-boiled reporters “swallow hard.”[44]

In December 1939, Lou Gehrig was elected to the National Baseball Hall of Fame and Museum in a special election by the Baseball Writers Association.[50] At age 36, he was the second youngest player to be so honored (behind Sandy Koufax).[51]

 Final years

“Don’t think I am depressed or pessimistic about my condition at present,” Lou Gehrig wrote following his retirement from baseball. Struggling against his ever-worsening physical condition, he added, “I intend to hold on as long as possible and then if the inevitable comes, I will accept it philosophically and hope for the best. That’s all we can do.”[9]

Lou Gehrig Way in New Rochelle, NY

In October 1939, he accepted Mayor LaGuardia‘s appointment to a ten-year term as a New York City Parole Commissioner and was sworn into office on January 2, 1940.[50] The Parole Commission commended the ex-ballplayer for his “firm belief in parole, properly administered”, stating that Gehrig “indicated he accepted the parole post because it represented an opportunity for public service. He had rejected other job offers – including lucrative speaking and guest appearance opportunities – worth far more financially than the $5,700 a year commissionership.” Gehrig visited New York City’s correctional facilities, but insisted that the visits not be covered by news media.[52] Gehrig, as always, quietly and efficiently performed his duties. He was often helped by his wife Eleanor, who would guide his hand when he had to sign official documents. About a month before his death, when Gehrig reached the point where his deteriorating physical condition made it impossible for him to continue in the job, he quietly resigned.[53]

On June 2, 1941, at 10:10 p.m., sixteen years to the day after he replaced Wally Pipp at first base and two years after his retirement from baseball, Lou Gehrig died at his home in the Riverdale section of the Bronx, New York.[54][55]

Upon hearing the news, Babe Ruth and his wife Claire went to the Gehrig house to console Eleanor. Mayor LaGuardia ordered flags in New York to be flown at half-staff, and Major League ballparks around the nation did likewise.[56]

Following the funeral at Christ Episcopal Church of Riverdale, Gehrig’s remains were cremated and interred on June 4 at Kensico Cemetery in Valhalla, New York. Lou Gehrig and Ed Barrow are both interred in the same section of Kensico Cemetery, which is next door to Gate of Heaven Cemetery, where the graves of Babe Ruth and Billy Martin are located.[57]

Lou Gehrig’s headstone in Kensico Cemetery (the year of his birth was inscribed erroneously as 1905)

Eleanor Gehrig never remarried following her husband’s death, dedicating the rest of her life to supporting ALS research.[16] She died on March 6, 1984, on her 80th birthday. They had no children.

The Yankees dedicated a monument to Gehrig in center field at Yankee Stadium on July 6, 1941, the shrine lauding him as, “A man, a gentleman and a great ballplayer whose amazing record of 2,130 consecutive games should stand for all time.” Gehrig’s monument joined the one placed there in 1932 to Miller Huggins, which would eventually be followed by Babe Ruth’s in 1949.[27]

Gehrig’s birthplace in Manhattan, at 1994 Second Avenue (near E. 103rd Street), is memorialized with a plaque marking the site, as is another early residence on E. 94th Street (near Second Avenue). The Gehrigs’ white house at 5204 Delafield Avenue in the Riverdale section of the Bronx, where Lou Gehrig died, still stands today on the east side of the Henry Hudson Parkway and is likewise marked by a plaque.[22]

 Records, awards, and accomplishments

Sixty years after his farewell to baseball, Gehrig received the most votes of any baseball player on the Major League Baseball All-Century Team, chosen by fan balloting in 1999.[4]


Gehrig sliding into home plate in 1925.

MLB Records
Accomplishment Record Refs
Most grand slams 23 [58]
Most consecutive seasons with 120+ RBIs 8 (1927–1934) [58]
Most runs batted in (RBI) by a first baseman 1,995 [58]
Most runs scored by a first baseman 1,888 [58]
Highest on-base percentage by a first baseman .447 [58]
Most walks by a first baseman 1,508 [58]
Highest slugging percentage by a first baseman .632 [58]
Most extra base hits by a first baseman 1,190 [58]
Most runs batted-in by a first baseman 184 (1931) [58]
Most runs scored by a first baseman 167 (1936) [58]
Highest slugging percentage by a first baseman .765 (1927) [58]
Extra-base hits by a first baseman 117 (1927) [58]
Most total bases by a first baseman 447 (1927) [58]
Most home runs[a] 4 [58]
  1. ^ The record is held with 14 other players

Awards and honors

Award/Honor # of Times Dates Refs
American League All-Star 7 1933–1939 [58]
American League MVP 2 1927, 1936 [58][59]
The Lou Gehrig Memorial Award[60] 1955–present [58]
Named starting first baseman on the Major League Baseball All-Century Team 1999 [4]
Inducted into National Baseball Hall of Fame and Museum 1939 [58]
World Series champion 6 1927, 1928, 1932, 1936, 1937, 1938  

Other accomplishments

Accomplishment Year
Other distinctions[58]
Triple Crown (.363 BA, 49 HR, 165 RBI) 1934
Only player in history to collect 400 total bases in five seasons 1927, 1930, 1931, 1934, 1936
With Stan Musial, one of two players to collect at least 500 doubles, 150 triples, and 400 home runs in a career
One of only six players (Babe Ruth, Jimmie Foxx, Joe DiMaggio, Stan Musial, and Ted Williams were the others) to end their career with a minimum .320 batting average, 350 home runs, and 1,500 RBI
With Albert Pujols, one of two players to hit 40 doubles and 40 home runs in the same season three separate times 1927, 1930, 1934
Scored game-winning run in 8 World Series games
First athlete ever to appear on a box of Wheaties
First baseball player to have his uniform number retired (January 6, 1940); his July 4, 1939, farewell speech was voted by fans as the fifth-greatest moment in Major League Baseball history in 2002 July 4, 1939
A Lou Gehrig 25-cent postage stamp was issued by the U.S. Postal Service on the 50th anniversary of his retirement from baseball, depicting him both in profile and at bat (Scott number 2417) 1989
On the 70th anniversary of his farewell address in Yankee Stadium, MLB dedicated a day of remembrance to him and to the awareness of ALS amyotrophic lateral sclerosis July 4, 2009
Gehrig was mentioned in the poem “Line-Up for Yesterday” by Ogden Nash:
“Line-Up for Yesterday”

G is for Gehrig,
The Pride of the Stadium;
His record pure gold,
His courage, pure radium.

 — Ogden Nash, SPORT (January 1949)[61]

 Film and other media

Lou Gehrig starred in the 1938 20th Century Fox movie Rawhide playing himself in his only feature film appearance.[62] In 2006, researchers presented a paper to the American Academy of Neurology, reporting on an analysis of Rawhide and photographs of Lou Gehrig from the 1937–1939 period, to ascertain when Gehrig began to show visible symptoms of amyotrophic lateral sclerosis. They concluded that while atrophy of hand muscles could be detected in 1939 photographs of Gehrig, no such abnormality was visible at the time Rawhide was made in January 1938. “Examination of Rawhide showed that Gehrig functioned normally in January 1938″, the report concluded.[63]

In 1942, the life of Lou Gehrig was portrayed in the movie The Pride of the Yankees, starring Gary Cooper as Gehrig and Teresa Wright as his wife Eleanor. It received 11 Academy Award nominations and won in one category, Film Editing. Real-life Yankees Babe Ruth, Bob Meusel, Mark Koenig and Bill Dickey (then still an active player) played themselves, as did sportscaster Bill Stern.

Later, in 1978, a TV movie, A Love Affair: The Eleanor and Lou Gehrig Story was released, starring Blythe Danner and Edward Herrmann as Eleanor and Lou Gehrig, respectively. It was based on the 1976 autobiography My Luke and I, written by Eleanor Gehrig and Joseph Durso.

In an episode of the PBS series Jean Shepherd’s America, the Chicago-born Shepherd told of how he and his father (Jean Shepherd, Sr.) would watch Chicago White Sox games from the right field upper deck at Comiskey Park in the 1930s. On one occasion, the Sox were playing the Yankees, and Shepherd Sr. had been taunting Gehrig, yelling at him all day. In the top of the ninth, with Sox icon Ted Lyons holding a slim lead, Gehrig came up with a man on base, and the senior Shepherd yelled in a voice that echoed around the ballpark, “Hit one up here, ya bum! I dare ya!” Gehrig did exactly that, hitting a screaming liner, practically into the heckler’s lap, for the eventual game-winning home run. Shepherd’s father was booed mercilessly, and he never again took junior Jean to a game. He apparently told this story originally when Gehrig’s widow was in the audience at a speaking engagement].

the end @ copyright Dr Iwan suwandy 2011

The Dawn Syndrome Informations










The Driwan’s  Cybermuseum

Down syndrome

Down syndrome
Classification and external resources

Boy with Down syndrome assembling a bookcase
ICD10 Q90
ICD9 758.0
OMIM 190685
DiseasesDB 3898
MedlinePlus 000997
eMedicine ped/615
MeSH D004314

Down syndrome, or Down’s syndrome (primarily in the United Kingdom),[1][2] trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th century by Jean Etienne Dominique Esquirol in 1838 and Edouard Seguin in 1844.[3] Down syndrome was identified as a chromosome 21 trisomy by Dr. Jérôme Lejeune in 1959. Down syndrome in a fetus can be identified through chorionic villus sampling or amniocentesis during pregnancy, or in a baby at birth.

Down syndrome is a chromosomal condition characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations). The effects and extent of the extra copy vary greatly among people, depending on genetic history, and pure chance. The incidence of Down syndrome is estimated at 1 per 733 births, although it is statistically more common with older parents (both mothers and fathers) due to increased mutagenic exposures upon some older parents’ reproductive cells. Other factors may also play a role. Down syndrome occurs in all human populations, and analogous effects have been found in other species such as chimpanzees[4] and mice.

Often Down syndrome is associated with some impairment of cognitive ability and physical growth, and a particular set of facial characteristics. Individuals with Down syndrome tend to have a lower-than-average cognitive ability, often ranging from mild to moderate disabilities. Many children with Down syndrome who have received family support, enrichment therapies, and tutoring have been known to graduate from high school and college, and enjoy employment in the work force. The average IQ of children with Down syndrome is around 50, compared to normal children with an IQ of 100.[5] A small number have a severe to high degree of intellectual disability.

Individuals with Down syndrome may have some or all of the following physical characteristics: microgenia (an abnormally small chin),[6] an unusually round face, macroglossia[7] (protruding or oversized tongue), an almond shape to the eyes caused by an epicanthic fold of the eyelid, upslanting palpebral fissures (the separation between the upper and lower eyelids), shorter limbs, a single transverse palmar crease (a single instead of a double crease across one or both palms), poor muscle tone, and a larger than normal space between the big and second toes. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastroesophageal reflux disease, recurrent ear infections that may lead to hearing loss, obstructive sleep apnea, thyroid dysfunctions, and obesity.

Early childhood intervention, screening for common problems, medical treatment where indicated, a conducive family environment, and vocational training can improve the overall development of children with Down syndrome. Education and proper care will improve quality of life significantly, despite genetic limitations.[8]



English physician John Langdon Down first characterized Down syndrome as a distinct form of mental disability in 1862, and in a more widely published report in 1866.[9] Due to his perception that children with Down syndrome shared physical facial similarities (epicanthal folds) with those of Blumenbach’s Mongolian race, Down used the term mongoloid, derived from prevailing ethnic theory.[10]




 by Catherine Slater, M.A. Cantab
A History of Mental Handicap/Learning Difficulties from 1000AD to 2000AD-

This BOOK  is about the history of people who have been described over the years as fools and intellectually impaired, mentally retarded and developmentally delayed, mentally handicapped and learning disabled, They have faced oppression and prejudice in the past but now are beginning to be recognised as individuals who should be included , respected and valued who have equal civil rights and who are unique indivuduals who can offer a great deal and live rich fulfilled lives just like anyone else.

To paraphrase Eliza Doolittle, ” it is not so much what a person is called but how s/he is treated which is important.

This page will link you to a biography of John Langdon Down and A History of People with a learning disability from ancient times to 2000AD entitled”IDIOTS,IMBECILES AND INTELLECTUAL IMPAIRMENT”.The author has a daughter with Downs Syndrome and a Master’s degree in History.from the University of Cambridge

It will also link you to other History of Disability Sites on the World Wide Web


Introduction From Ancient times to 1200AD|
Back to Disability History Home Page
Chapter Two .the mediaeval period 1200-1450|
Chapter Three Renaissance, Reformation and Beyond1450-1800|
Chapter Four Incarceration, Segregation and Eugenics 1800-1945|
Chapter Five Inclusion Civil Rights and a Better Life?1945-2000|
A biography of John Langdon Down

Gordon Slater’s response to the case of a doctor who was acquitted of murdering a baby with Downs Syndrome in 1981.

Here are some excellent sites..
A very good history of disability site

 We Support the World Association of Persons with Disabilities

A little more about Dr Down and a better photo

A fascinating page of paintings from the Renaisance and later
The theories of Dr Down |
A cornucopia of sites on the history of disability 

Dawn syndrome were the most recognizable form of Mental disability.

By the 20th century, Down syndrome had become the most recognizable form of mental disability. Most individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics movement, 33 of the (then) 48 U.S. states and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. “Action T4” in Nazi Germany made public policy of a program of systematic murder. Court challenges, scientific advances and public revulsion led to discontinuation or repeal of such sterilization programs during the decades after World War II.


Until the middle of the 20th century, the cause of Down syndrome remained unknown. However, the presence in all races, the association with older maternal age, and the rarity of recurrence had been noticed. Standard medical texts assumed it was caused by a combination of inheritable factors that had not been identified. Other theories focused on injuries sustained during birth.[11]

With the discovery of karyotype techniques in the 1950s, it became possible to identify abnormalities of chromosomal number or shape.

 In 1959, Jérôme Lejeune discovered that Down syndrome resulted from an extra chromosome.[12][13] The extra chromosome was subsequently labeled as the 21st, and the condition as trisomy 21.

In 1961, 18 geneticists wrote to the editor of The Lancet suggesting that Mongolian idiocy had “misleading connotations,” had become “an embarrassing term,” and should be changed.[14] The Lancet supported Down’s Syndrome. The World Health Organization (WHO) officially dropped references to mongolism in 1965 after a request by the Mongolian delegate.[15] However, almost 40 years later, the term ‘mongolism’ still appears in leading medical texts such as General and Systematic Pathology, 4th Edition, 2004, edited by Professor Sir James Underwood. Advocacy groups adapted and parents groups welcomed the elimination of the Mongoloid label that had been a burden to their children. The first parents group in the United States, the Mongoloid Development Council, changed its name to the National Association for Down Syndrome in 1972.[16]

In 1975, the United States National Institutes of Health convened a conference to standardize the nomenclature of malformations. They recommended eliminating the possessive form: “The possessive use of an eponym should be discontinued, since the author neither had nor owned the condition.”[17] Although both the possessive and non-possessive forms are used in the general population, Down syndrome is the accepted term among professionals in the U.S., Canada and other countries; Down’s syndrome is still used in the UK and other areas.[18]

Signs and symptoms


Main article: neoteny

The signs and symptoms Down syndrome are characterized by the neotenization of the brain and body to the fetal state.[19] Down syndrome is characterized by decelerated maturation (neoteny), incomplete morphogenesis (vestigia) and atavisms.[20] Dr. Weihs considers Down syndrome to be a condition of “neoteny” that makes people “like a baby.”[21]

Down syndrome can result from several different genetic mechanisms. This results in a wide variability in individual due to complex gene and environment interactions. Prior to birth, it is not possible to predict the symptoms that an individual with Down syndrome will develop.

Physical characteristics

Individuals with Down syndrome may have some or all of the following physical characteristics: microgenia (abnormally small chin),[6] oblique eye fissures with epicanthic skin folds on the inner corner of the eyes (formerly known as a mongoloid fold),[21][7] muscle hypotonia (poor muscle tone), a flat nasal bridge, a single palmar fold, a protruding tongue (due to small oral cavity, and an enlarged tongue near the tonsils) or macroglossia,[7][21] “face is flat and broad”,[10] a short neck, white spots on the iris known as Brushfield spots,[22] excessive joint laxity including atlanto-axial instability, excessive space between large toe and second toe, a single flexion furrow of the fifth finger, a higher number of ulnar loop dermatoglyphs and short fingers.[21]

Growth parameters such as height, weight, and head circumference are smaller in children with DS than with typical individuals of the same age. Adults with DS tend to have short stature and bowed legs[21]—the average height for men is 5 feet 1 inch (154 cm) and for women is 4 feet 9 inches (144 cm).[23] Individuals with DS are also at increased risk for obesity as they age[24] and tend to be “round in shape”.[21]

Characteristics Percentage[25] Characteristics Percentage[25]
mental retardation 100% small teeth 60%
stunted growth 100% flattened nose 60%
atypical fingerprints 90% clinodactyly 52%
separation of the abdominal muscles 80% umbilical hernia 51%
flexible ligaments 80% short neck 50%
hypotonia 80% shortened hands 50%
brachycephaly 75% congenital heart disease 45%
smaller genitalia 75% single transverse palmar crease 45%
eyelid crease 75% Macroglossia (larger tongue) 43%
shortened extremities 70% epicanthal fold 42%
oval palate 69% Strabismus 40%
low-set and rounded ear 60% Brushfield spots (iris) 35%

Mental characteristics

Most individuals with Down syndrome have intellectual disability in the mild (IQ 50–70) to moderate (IQ 35–50) range,[26] with individuals having Mosaic Down syndrome typically 10–30 points higher.[27]

Dr. Weihs notes the mental qualities of people with Down syndrome to be “unsexual,” “playful,” “affectionate,” “mischievous” and “imitative”.[21]

Language skills show a difference between understanding speech and expressing speech, and commonly individuals with Down syndrome have a speech delay.[28] Fine motor skills are delayed[29] and often lag behind gross motor skills and can interfere with cognitive development. Effects of the condition on the development of gross motor skills are quite variable. Some children will begin walking at around 2 years of age, while others will not walk until age 4. Physical therapy, and/or participation in a program of adapted physical education (APE), may promote enhanced development of gross motor skills in Down syndrome children.[30]

Criticism of IQ tests for people with Down syndrome

Chris Borthwick claims parents and educators have low expectations for people with Down syndrome which depresses tested IQ of people with Down syndrome.[31] Also, he claims that IQ tests do not take into account the hearing impairment 62% of people with Down syndrome face or the vision impairment 77% of people with Down syndrome face.[31] These physical disabilities would slow the test-taking performance of a person with Down syndrome, resulting in a lower IQ score.[31]


Karyotype for trisomy Down syndrome. Notice the three copies of chromosome 21

Recently, researchers have created transgenic mice with most of human chromosome 21 (in addition to the normal mouse chromosomes).[32] The extra chromosomal material can come about in several distinct ways. A typical human karyotype is designated as 46,XX or 46,XY, indicating 46 chromosomes with an XX arrangement typical of females and 46 chromosomes with an XY arrangement typical of males.[33]

Trisomy 21

Trisomy 21 (47,XX,+21) is caused by a meiotic nondisjunction event. With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 21; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the embryo now has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 95% of observed Down syndromes, with 88% coming from nondisjunction in the maternal gamete and 8% coming from nondisjunction in the paternal gamete.[34] The actual Down syndrome “critical region” encompasses chromosome bands 21q22.1-q22.3.[35]


Trisomy 21 is usually caused by nondisjunction in the gametes prior to conception, and all cells in the body are affected. However, when some of the cells in the body are normal and other cells have trisomy 21, it is called mosaic Down syndrome (46,XX/47,XX,+21).[36][37] This can occur in one of two ways: a nondisjunction event during an early cell division in a normal embryo leads to a fraction of the cells with trisomy 21; or a Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and among tissues. This is the cause of 1–2% of the observed Down syndromes.[34]

Robertsonian translocation

The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian translocation in the karyotype of one of the parents. In this case, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 [45,XX,der(14;21)(q10;q10)]. A person with such a translocation is phenotypically normal. During reproduction, normal disjunctions leading to gametes have a significant chance of creating a gamete with an extra chromosome 21, producing a child with Down syndrome. Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of 2–3% of observed cases of Down syndrome.[34] It does not show the maternal age effect, and is just as likely to have come from fathers as mothers.

Duplication of a portion of chromosome 21

Rarely, a region of chromosome 21 will undergo a duplication event. This will lead to extra copies of some, but not all, of the genes on chromosome 21 (46,XX, dup(21q)).[38] If the duplicated region has genes that are responsible for Down syndrome physical and mental characteristics, such individuals will show those characteristics. This cause is rare and no rate estimates are available.


Graph showing probability of Down syndrome as a function of maternal age.

The incidence of Down syndrome is estimated at one per 800 to one per 1000 births.[39] In 2006, the Centers for Disease Control and Prevention estimated the rate as one per 733 live births in the United States (5429 new cases per year).[40] Approximately 95% of these are trisomy 21. Down syndrome occurs in all ethnic groups and among all economic classes.

Maternal age influences the chances of conceiving a baby with Down syndrome. At maternal age 20 to 24, the probability is one in 1562; at age 35 to 39 the probability is one in 214, and above age 45 the probability is one in 19.[41] Although the probability increases with maternal age, 80% of children with Down syndrome are born to women under the age of 35,[42] reflecting the overall fertility of that age group. Recent data also suggest that paternal age, especially beyond 42,[43] also increases the risk of Down syndrome manifesting.[44]

Current research (as of 2008) has shown that Down syndrome is due to a random event during the formation of sex cells or pregnancy. There has been no evidence that it is due to parental behavior (other than age) or environmental factors.


Ultrasound of fetus with Down syndrome and megacystis

Pregnant women can be screened for various complications during pregnancy. Many standard prenatal screens can discover Down syndrome. Genetic counseling along with genetic testing, such as amniocentesis, chorionic villus sampling (CVS), or percutaneous umbilical cord blood sampling (PUBS) are usually offered to families who may have an increased chance of having a child with Down syndrome, or where normal prenatal exams indicate possible problems. In the United States, ACOG guidelines recommend that non-invasive screening and invasive testing be offered to all women, regardless of their age, and most likely all physicians currently follow these guidelines. However, some insurance plans will only reimburse invasive testing if a woman is >34 years old or if she has received a high-risk score from a non-invasive screening test.

Amniocentesis and CVS are considered invasive procedures, in that they involve inserting instruments into the uterus, and therefore carry a small risk of causing fetal injury or miscarriage. The risks of miscarriage for CVS and amniocentesis are often quoted as 1% and 0.5% respectively. There are several common non-invasive screens that can indicate a fetus with Down syndrome. These are normally performed in the late first trimester or early second trimester. Due to the nature of screens, each has a significant chance of a false positive, suggesting a fetus with Down syndrome when, in fact, the fetus does not have this genetic condition. Screen positives must be verified before a Down syndrome diagnosis is made. Common screening procedures for Down syndrome are given in Table 1.

Table 1: First and second trimester Down syndrome screens
Screen When performed (weeks gestation) Detection rate False positive rate Description
Quad screen 15–20 81%[45] 5% This test measures the maternal serum alpha feto protein (a fetal liver protein), estriol (a pregnancy hormone), human chorionic gonadotropin (hCG, a pregnancy hormone), and inhibin-Alpha (INHA).[46]
Nuchal translucency/free beta/PAPPA screen (aka “1st Trimester Combined Test”) 10–13.5 85%[47] 5% Uses ultrasound to measure Nuchal Translucency in addition to the freeBeta hCG and PAPPA (pregnancy-associated plasma protein A). NIH has confirmed that this first trimester test is more accurate than second trimester screening methods.[48] Performing an NT ultrasound requires considerable skill; a Combined test may be less accurate if there is operator error, resulting in a lower-than-advertised sensitivity and higher false-positive rate, possibly in the 5–10% range.
Integrated test 10-13.5 and 15–20 95%[49] 5% The integrated test uses measurements from both the 1st trimester combined test and the 2nd trimester quad test to yield a more accurate screening result. Because all of these tests are dependent on accurate calculation of the gestational age of the fetus, the real-world false-positive rate is >5% and may be closer to 7.5%.

Even with the best non-invasive screens, the detection rate is 90–95% and the rate of false positive is 2–5%. Inaccuracies can be caused by undetected multiple fetuses (very rare with the ultrasound tests), incorrect date of pregnancy, or normal variation in the proteins.

Confirmation of screen positive is normally accomplished with amniocentesis or chorionic villus sampling (CVS). Amniocentesis is an invasive procedure and involves taking amniotic fluid from the amniotic sac and identifying fetal cells. The lab work can take several weeks but will detect over 99.8% of all numerical chromosomal problems with a very low false positive rate.[50]

A non-invasive prenatal test, MaterniT21, detected Down syndrome based on fetal DNA in a sample of the mother’s blood in 209 of 212 cases (98.6%).[51][52] The International Society for Prenatal Diagnosis finds that this is an advanced screening test which may be of use, in conjunction with genetic counseling, in high-risk cases based upon existing screening strategies. While effective in the diagnosis of Down syndrome, it cannot assess other conditions which can be detected by invasive testing..[53]

Abortion rates

A 2002 literature review of elective abortion rates found that 91–93% of pregnancies in the United Kingdom and Europe with a diagnosis of Down syndrome were terminated.[54] Data from the National Down Syndrome Cytogenetic Register in the United Kingdom indicates that from 1989 to 2006 the proportion of women choosing to terminate a pregnancy following prenatal diagnosis of Down syndrome has remained constant at around 92%.[55][56]

In the United States a number of studies have examined the abortion rate of fetuses with Down syndrome. Three studies estimated the termination rates at 95%, 98%, and 87% respectively.[54]

Ethical issues

Medical ethicist Ronald Green argues that parents have an obligation to avoid ‘genetic harm’ to their offspring,[57] and Claire Rayner, then a patron of the Down’s Syndrome Association, defended testing and abortion saying “The hard facts are that it is costly in terms of human effort, compassion, energy, and finite resources such as money, to care for individuals with handicaps… People who are not yet parents should ask themselves if they have the right to inflict such burdens on others, however willing they are themselves to take their share of the burden in the beginning.”[58]

Some physicians and ethicists are concerned about the ethical ramifications of the high abortion rate for this condition.[59] Conservative commentator George Will called it “eugenics by abortion”.[60] British peer Lord Rix stated that “alas, the birth of a child with Down’s syndrome is still considered by many to be an utter tragedy” and that the “ghost of the biologist Sir Francis Galton, who founded the eugenics movement in 1885, still stalks the corridors of many a teaching hospital“.[61] Doctor David Mortimer has argued in Ethics & Medicine that “Down’s syndrome infants have long been disparaged by some doctors and government bean counters.”[62] Some members of the disability rights movement “believe that public support for prenatal diagnosis and abortion based on disability contravenes the movement’s basic philosophy and goals.”[63] Peter Singer argued that “neither haemophilia nor Down’s syndrome is so crippling as to make life not worth living from the inner perspective of the person with the condition. To abort a fetus with one of these disabilities, intending to have another child who will not be disabled, is to treat fetuses as interchangeable or replaceable. If the mother has previously decided to have a certain number of children, say two, then what she is doing, in effect, is rejecting one potential child in favour of another. She could, in defence of her actions, say: the loss of life of the aborted fetus is outweighed by the gain of a better life for the normal child who will be conceived only if the disabled one dies.”[64]


Individuals with Down syndrome have a higher risk for many conditions. The medical consequences of the extra genetic material in Down syndrome are highly variable and may affect the function of any organ system or bodily process. Some problems are present at birth, such as certain heart malformations. Others become apparent over time, such as epilepsy.

Congenital heart disease

The incidence of congenital heart disease in children with Down syndrome is up to 50%.[65] An atrioventricular septal defect also known as endocardial cushion defect is the most common form with up to 40% of patients affected. This is closely followed by ventricular septal defect that affects approximately 30% of patients.


Hematologic malignancies such as leukemia are more common in children with DS. In particular, the risk for acute lymphoblastic leukemia is at least 10 times more common in DS and for the megakaryoblastic form of acute myelogenous leukemia is at least 50 times more common in DS. Transient leukemia is a form of leukemia that is rare in individuals without DS but affects up to 20 percent of newborns with DS. This form of leukemia is typically benign and resolves on its own over several months, though it can lead to other serious illnesses.[66] In contrast to hematologic malignancies, solid tumor malignancies are less common in DS, possibly due to increased numbers of tumor suppressor genes contained in the extra genetic material.[67]

Decreased incidence of many cancer types

Health benefits of Down syndrome include greatly reduced incidence of many common malignancies except leukemia and testicular cancer[68]—although it is, as yet, unclear whether the reduced incidence of various fatal cancers among people with Down syndrome is as a direct result of tumor-suppressor genes on chromosome 21,[69] because of reduced exposure to environmental factors that contribute to cancer risk, or some other as-yet unspecified factor. In addition to a reduced risk of most kinds of cancer, people with Down syndrome also have a much lower risk of hardening of the arteries and diabetic retinopathy.[45]

Thyroid disorders

Individuals with DS are at increased risk for dysfunction of the thyroid gland, an organ that helps control metabolism. Low thyroid (hypothyroidism) is most common, occurring in almost a third of those with DS. This can be due to absence of the thyroid at birth (congenital hypothyroidism) or due to attack on the thyroid by the immune system.[70]


Down syndrome increases the risk of Hirschsprung’s disease, in which the nerve cells that control the function of parts of the colon are not present.[71] This results in severe constipation. Other congenital anomalies occurring more frequently in DS include duodenal atresia, annular pancreas, and imperforate anus. Gastroesophageal reflux disease and celiac disease are also more common among people with DS.[72]


There is infertility among both males and females with Down syndrome; males are usually unable to father children, while females demonstrate significantly lower rates of conception relative to unaffected individuals.[citation needed] Women with DS are less fertile and often have difficulties with miscarriage, premature birth, and difficult labor. Without preimplantation genetic diagnosis, approximately half of the offspring of someone with Down syndrome also have the syndrome themselves.[73] Men with DS are almost uniformly infertile, exhibiting defects in spermatogenesis.[74] There have been only three recorded instances of males with Down syndrome fathering children.[75][76]


Children and adults with DS are at increased risk for developing epilepsy.[77][78] The risk for Alzheimer’s disease is increased in individuals with DS, with 10–25% of individuals with DS showing signs of AD before age 50, up to 50% with clinical symptoms in the sixth decade, and up to 75% in the 7th decade. This sharp increase in the incidence and prevalence of dementia may be one of the factors driving the decreased life expectancy of persons with Down syndrome.

Ophthalmology and otolaryngology

Eye disorders are more common in people with DS. Almost half have strabismus, in which the two eyes do not move in tandem. Refractive errors requiring glasses or contacts are also common. Cataracts (opacity of the lens), keratoconus (thin, cone-shaped corneas), and glaucoma (increased eye pressures) are also more common in DS.[79] Brushfield spots (small white or grayish/brown spots on the periphery of the iris) may be present.

Hearing loss

In the past, prior to current treatment, there was a 38–78% incidence of hearing loss in children with Down syndrome. Fortunately, with aggressive, meticulous and compulsive diagnosis and treatment of chronic ear disease (e.g. otitis media, also known as Glue-ear) in children with Down syndrome, approximately 98% of the children have normal hearing levels.[80]

However, more recent studies show that hearing impairment and otological problems are still found in 38-90% of children with Down syndrome compared to 2.5% for normal children.[81][82][83]

The elevated occurrence of hearing loss for individuals with Down is not surprising. Every component in the auditory system is potentially adversely affected by Down syndrome.[83] Problems may include:

  • stenosis of the ear canal
  • malformation of the malleus, incus, and stapes
  • shortened or narrow cochlea
  • neural transmission rates that are accelerated (at the level or brainstem) or delayed (at the level of the cortex)
  • weak immune system leading to increased middle ear pathology

Otitis media with effusion is the most common cause of hearing loss in Down children,[82] the infections start at birth and continue throughout the children’s lives.[84] The ear infections are mainly associated with Eustachian tube dysfunction due to alterations in the skull base. However, excessive accumulation of wax can also cause obstruction of the outer ear canal as it is often narrowed in children with Down syndrome.[85] Middle ear problems account for 83% of hearing loss in children with Down syndrome.[85] The degree of hearing loss varies but even a mild degree can have major consequences on speech perception, language acquisition, development and academic achievement[84] if not detected in time and corrected.[82]

Early intervention to treat the hearing loss and adapted education is useful to facilitate the development of children with Down syndrome, especially during the preschool period. For adults, social independence depends largely on the ability to complete tasks without assistance, the willingness to separate emotionally from parents and access to personal recreational activities.[81] Given this background it is always important to rule out hearing loss as a contributing factor in social and mental deterioration.[83]

Other complications

Instability of the atlanto-axial joint occurs in approximately 15% of people with DS, probably due to ligamental laxity. It may lead to the neurologic symptoms of spinal cord compression.[86] Periodic screening, with cervical x-rays, is recommended to identify this condition.

Other serious illnesses include immune deficiencies.


The above factors can contribute to a shorter life expectancy for people with Down syndrome. One study, carried out in the United States in 2002, showed an average lifespan of 49 years, with considerable variations between different ethnic and socio-economic groups.[87] However, in recent decades, the life expectancy among persons with Down syndrome has increased significantly up from 25 years in 1980. The causes of death have also changed, with chronic neurodegenerative diseases becoming more common as the population ages. Most people with Down syndrome who live into their 40s and 50s begin to suffer from an Alzheimer’s disease-like dementia.[88]


Treatment of individuals with Down syndrome depends on the particular manifestations of the condition. For instance, individuals with congenital heart disease may need to undergo major corrective surgery soon after birth. Other individuals may have relatively minor health problems requiring no therapy.

Examination at birth

Initial examination of newborns with DS should pay particular attention to certain physical signs that are more commonly found in DS. Evaluation of the red reflex can help identify congenital cataracts. Movement of the eyes should be observed to identify strabismus. Constipation should raise concerns for Hirschsprung’s disease and feeding problems should prompt intense education to ensure adequate input and nutrition.

At birth, an ultrasound of the heart (echocardiogram) should be done immediately in order to identify congenital heart disease (this should be carried out by someone with experience in pediatric cardiology). A complete blood count should be done in order to identify pre-existing leukemia. A hearing test using brainstem auditory evoked responses (BAERS) testing should be performed and any hearing deficits further characterized. The thyroid function should also be tested. Early Childhood Intervention should be involved from birth to help coordinate and plan effective strategies for learning and development.

The American Academy of Pediatrics, among other health organizations, has issued a series of recommendations for screening individuals with Down syndrome for particular diseases.[89] These guidelines enable health care providers to identify and prevent important aspects of DS. All other typical newborn, childhood, and adult screening and vaccination programs should also be performed.

Plastic surgery

Plastic surgery has sometimes been advocated and performed on children with Down syndrome, based on the assumption that surgery can reduce the facial features associated with Down syndrome, therefore decreasing social stigma, and leading to a better quality of life.[90] Plastic surgery on children with Down syndrome is uncommon,[91] and continues to be controversial. Researchers have found that for facial reconstruction, “…although most patients reported improvements in their child’s speech and appearance, independent raters could not readily discern improvement….”[92] For partial glossectomy (tongue reduction), one researcher found that 1 out of 3 patients “achieved oral competence,” with 2 out of 3 showing speech improvement.[93] Len Leshin, physician and author of the ds-health website, has stated, “Despite being in use for over twenty years, there is still not a lot of solid evidence in favor of the use of plastic surgery in children with Down syndrome.”[94] The U.S. National Down Syndrome Society has issued a “Position Statement on Cosmetic Surgery for Children with Down Syndrome”,[95] which states “The goal of inclusion and acceptance is mutual respect based on who we are as individuals, not how we look.”

Cognitive development

The identification of the best methods of teaching each particular child ideally begins soon after birth through early intervention programs.[96] Cognitive development in children with Down syndrome is quite variable. It is not currently possible at birth to predict the capabilities of any individual reliably, nor are the number or appearance of physical features predictive of future ability. Since children with Down syndrome have a wide range of abilities, success at school can vary greatly, which underlines the importance of evaluating children individually. The cognitive problems that are found among children with Down syndrome can also be found among other children. Therefore, parents can use general programs that are offered through the schools or other means.

Individuals with Down syndrome differ considerably in their language and communication skills. It is routine to screen for middle ear problems and hearing loss; low gain hearing aids or other amplification devices can be useful for language learning. Early communication intervention fosters linguistic skills. Language assessments can help profile strengths and weaknesses; for example, it is common for receptive language skills to exceed expressive skills. Individualized speech therapy can target specific speech errors, increase speech intelligibility, and in some cases encourage advanced language and literacy. Augmentative and alternative communication (AAC) methods, such as pointing, body language, objects, or graphics are often used to aid communication. Relatively little research has focused on the effectiveness of communications intervention strategies.[97]

In education, mainstreaming of children with Down syndrome is becoming less controversial in many countries. For example, there is a presumption of mainstream in many parts of the UK. Mainstreaming is the process whereby students of differing abilities are placed in classes with their chronological peers. Children with Down syndrome may not age emotionally/socially and intellectually at the same rates as children without Down syndrome, so over time the intellectual and emotional gap between children with and without Down syndrome may widen. Complex thinking as required in sciences but also in history, the arts, and other subjects can often be beyond the abilities of some, or achieved much later than in other children. Therefore, children with Down syndrome may benefit from mainstreaming provided that some adjustments are made to the curriculum.[98]

Some European countries such as Germany and Denmark advise a two-teacher system, whereby the second teacher takes over a group of children with disabilities within the class. A popular alternative is cooperation between special schools and mainstream schools. In cooperation, the core subjects are taught in separate classes, which neither slows down the typical students nor neglects the students with disabilities. Social activities, outings, and many sports and arts activities are performed together, as are all breaks and meals.[99]

Speech delay may require speech therapy to improve expressive language.[28]

Childhood and adulthood follow-up

As children with DS grow, their progress should be plotted on a growth chart in order to detect deviations from expected growth. Special growth charts are available so that children with DS can be compared with other children with DS. Thyroid function testing should be performed at 6 months and 12 months of age as well as yearly thereafter. Evaluation of the ears for infection as well as objective hearing tests should be performed at every visit. Formal evaluation for refractive errors requiring glasses should be performed at least every two years with subjective vision assessments with each visit. After the age of three, an x-ray of the neck should be obtained to screen for atlanto-axial instability. As the child ages, yearly symptom screening for obstructive sleep apnea should be performed.[89]

Alternative treatment

The Institutes for the Achievement of Human Potential is a nonprofit organization that treats children who have, as the IAHP terms it, “some form of brain injury,” including children with Down syndrome. The approach of “Psychomotor Patterning” is not proven,[100] and is considered alternative medicine.

Some experimental work with memantine – a NMDA-dampener usually used for Alzheimer’s – is being conducted by Alberto Costa, a physician and neuroscientist at University of Colorado. Dan Hurley (2011-07-29). “A Drug for Down Syndrome”. The New York Times. Retrieved 2011-07-30. 


Down syndrome is “a developmental condition characterized by trisomy of human chromosome 21” (Nelson 619). The extra copy of chromosome-21 leads to an over expression of certain genes located on chromosome-21.

Research by Arron et al. shows that some of the phenotypes associated with Down syndrome can be related to the disregulation of transcription factors (596), and in particular, NFAT. NFAT is controlled in part by two proteins, DSCR1 and DYRK1A; these genes are located on chromosome-21 (Epstein 582). In people with Down syndrome, these proteins have 1.5 times greater concentration than normal (Arron et al. 597). The elevated levels of DSCR1 and DYRK1A keep NFAT primarily located in the cytoplasm rather than in the nucleus, preventing NFATc from activating the transcription of target genes and thus the production of certain proteins (Epstein 583).

This disregulation was discovered by testing in transgenic mice that had segments of their chromosomes duplicated to simulate a human chromosome-21 trisomy (Arron et al. 597). A test involving grip strength showed that the genetically modified mice had a significantly weaker grip, much like the characteristically poor muscle tone of an individual with Down syndrome (Arron et al. 596). The mice squeezed a probe with a paw and displayed a .2 newton weaker grip (Arron et al. 596). Down syndrome is also characterized by increased socialization. When modified and unmodified mice were observed for social interaction, the modified mice showed as much as 25% more interactions as compared to the unmodified mice (Arron et al. 596).

The genes that may be responsible for the phenotypes associated may be located proximal to 21q22.3. Testing by Olson and others in transgenic mice show the duplicated genes presumed to cause the phenotypes are not enough to cause the exact features. While the mice had sections of multiple genes duplicated to approximate a human chromosome-21 triplication, they only showed slight craniofacial abnormalities (688–90). The transgenic mice were compared to mice that had no gene duplication by measuring distances on various points on their skeletal structure and comparing them to the normal mice (Olson et al. 687). The exact characteristics of Down syndrome were not observed, so more genes involved for Down syndrome phenotypes have to be located elsewhere.

Reeves et al., using 250 clones of chromosome-21 and specific gene markers, were able to map the gene in mutated bacteria. The testing had 99.7% coverage of the gene with 99.9995% accuracy due to multiple redundancies in the mapping techniques. In the study 225 genes were identified (311–13).

The search for major genes that may be involved in Down syndrome symptoms is normally in the region 21q21–21q22.3. However, studies by Reeves et al. show that 41% of the genes on chromosome-21 have no functional purpose, and only 54% of functional genes have a known protein sequence. Functionality of genes was determined by a computer using exon prediction analysis (312). Exon sequence was obtained by the same procedures of the chromosome-21 mapping.

Research has led to an understanding that two genes located on chromosome-21, that code for proteins that control gene regulators, DSCR1 and DYRK1A can be responsible for some of the phenotypes associated with Down syndrome. DSCR1 and DYRK1A cannot be blamed outright for the symptoms; there are a lot of genes that have no known purpose. Much more research would be needed to produce any appropriate or ethically acceptable treatment options.

Recent use of transgenic mice to study specific genes in the Down syndrome critical region has yielded some results. APP[101] is an Amyloid beta A4 precursor protein. It is suspected to have a major role in cognitive difficulties.[102] Another gene, ETS2[103] is Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have “demonstrated that over-expression of ETS2 results in apoptosis. Transgenic mice over-expressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome.”[103]

Human chromosome 21 contains five microRNA genes: miR-99a, let-7c, miR-125b-2, miR-155,and miR-802. MiR-155 and miR-802 regulate the expression of the methyl-CpG-binding protein (MeCP2). It has been suggested that the underexpression of MeCP2, secondary to trisomic overexpression of Human chromosome 21 derived miRNAs, may result in aberrant expression of the transcription factors of CREB1 and MEF2C . This in turn may lead to abnormal brain development through anomalous neuronal gene expression during the critical period of synaptic maturation by alterating neurogenesis, neuronal differentiation, myelination, and synaptogenesis.[104]


Advocates for people with Down syndrome point to various factors, such as additional educational support and parental support groups to improve parenting knowledge and skills. There are also strides being made in education, housing, and social settings to create environments that are accessible and supportive to people with Down syndrome. In most developed countries, since the early 20th century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, since the early 1960s parents and their organizations, educators and other professionals have generally advocated a policy of inclusion,[105] bringing people with any form of mental or physical disability into general society as much as possible. Such organizations included the National Association for Down Syndrome, the first known organization advocating for Down syndrome individuals in the United States founded by Kathryn McGee in 1960;[106] MENCAP advocating for all with mental disabilities, which was founded in the UK in 1946 by Judy Fryd;[107] and the National Down Syndrome Congress, the first truly national organization in the U.S. advocating for Down syndrome families, founded in 1973 by Kathryn McGee and others.[108] In many countries, people with Down syndrome are educated in the normal school system; there are increasingly higher-quality opportunities to move from special (segregated) education to regular education settings.

Despite these changes, the additional support needs of people with Down syndrome can still pose a challenge to parents and families. Although living with family is preferable to institutionalization, people with Down syndrome often encounter patronizing attitudes and discrimination in the wider community.

The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by European Down Syndrome Association during their European congress in Palma de Mallorca (febr. 2005). In the United States, the National Down Syndrome Society observes Down Syndrome Month every October as “a forum for dispelling stereotypes, providing accurate information, and raising awareness of the potential of individuals with Down syndrome.”[109] In South Africa, Down Syndrome Awareness Day is held every October 20.[110] Organizations such as Special Olympics Hawaii provide year-round sports training for individuals with intellectual disabilities such as Down syndrome.

Notable individuals

Scottish award-winning film and TV actress Paula Sage receives her BAFTA award with Brian Cox.

The Alzheimer Disease Informations










The Driwan’s  Cybermuseum

Alzheimer’s disease

Alzheimer’s disease
Classification and external resources

Comparison of a normal aged brain (left) and the brain of a person with Alzheimer’s (right). Differential characteristics are pointed out.
ICD10 G30, F00
ICD9 331.0, 290.1
OMIM 104300
DiseasesDB 490
MedlinePlus 000760
eMedicine neuro/13
MeSH D000544
GeneReviews [1]

Alzheimer’s disease (AD), also called Alzheimer disease, senile dementia of the Alzheimer type, primary degenerative dementia of the Alzheimer’s type, simply Alzheimer’s (as a stand-alone attributive adjective noun), and folk-etymological names such as “old-timers’ disease”, is the most common form of dementia. There is no cure for the disease, which becomes worse as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.[1] Most often, it is diagnosed in people over 65 years of age,[2] although the less-prevalent early-onset Alzheimer’s can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer’s is predicted to affect 1 in 85 people globally by 2050.[3]

Although Alzheimer’s disease develops differently for every individual, there are many common symptoms.[4] Early symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress.[5] In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behaviour and thinking abilities, often followed by a brain scan if available.[6]

As the disease advances, symptoms can include confusion, irritability and aggression, mood swings, trouble with language, and long-term memory loss. As the sufferer declines they often withdraw from family and society.[5][7] Gradually, bodily functions are lost, ultimately leading to death.[8] Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years.[9] Fewer than three percent of individuals live more than fourteen years after diagnosis.[10]

The cause and progression of Alzheimer’s disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain.[11] Current treatments only help with the symptoms of the disease. There are no available treatments that stop or reverse the progression of the disease. As of 2008[update], more than 500 clinical trials have been conducted to find ways to treat the disease, but it is unknown if any of the tested treatments will work.[12] Mental stimulation, exercise, and a balanced diet have suggested as possible ways to delay symptoms in healthy older individuals, but they have not been been proven as effective.[13]

Because AD cannot be cured and is degenerative, the sufferer relies on others for assistance. The role of the main caregiver is often taken by the spouse or a close relative.[14] Alzheimer’s disease is known for placing a great burden on caregivers; the pressures can be wide-ranging, involving social, psychological, physical, and economic elements of the caregiver’s life.[15][16][17] In developed countries, AD is one of the most costly diseases to society.[18][19]



The disease course is divided into four stages, with progressive patterns of cognitive and functional impairments.


The first symptoms are often mistakenly attributed to aging or stress.[5] Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria for diagnosis of AD.[20] These early symptoms can affect the most complex daily living activities.[21]

The most noticeable deficit is memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.[20][22]

Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of AD.[20]

Apathy can be observed at this stage, and remains the most persistent neuropsychiatric symptom throughout the course of the disease.[23] The preclinical stage of the disease has also been termed mild cognitive impairment,[22] but whether this term corresponds to a different diagnostic stage or identifies the first step of AD is a matter of dispute.[24]

Early Alzheimer

In people with AD the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small portion of them, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems.[25] AD does not affect all memory capacities equally. Older memories of the person’s life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat) are affected to a lesser degree than new facts or memories.[26][27]

Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, which lead to a general impoverishment of oral and written language.[25][28] In this stage, the person with Alzheimer’s is usually capable of adequately communicating basic ideas.[25][28][29] While performing fine motor tasks such as writing, drawing or dressing, certain movement coordination and planning difficulties (apraxia) may be present but they are commonly unnoticed.[25] As the disease progresses, people with AD can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.[25]

Moderate Alzheimer

Progressive deterioration eventually hinders independence; with subjects being unable to perform most common activities of daily living.[25] Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost.[25][29] Complex motor sequences become less coordinated as time passes and AD progresses, so the risk of falling increases.[25] During this phase, memory problems worsen, and the person may fail to recognise close relatives.[25] Long-term memory, which was previously intact, becomes impaired.[25]

Behavioural and neuropsychiatric changes become more prevalent. Common manifestations are wandering, irritability and labile affect, leading to crying, outbursts of unpremeditated aggression, or resistance to caregiving.[25] Sundowning can also appear.[30] Approximately 30% of people with AD develop illusionary misidentifications and other delusional symptoms.[25] Subjects also lose insight of their disease process and limitations (anosognosia).[25] Urinary incontinence can develop.[25] These symptoms create stress for relatives and caretakers, which can be reduced by moving the person from home care to other long-term care facilities.[25][31]

Advanced Alzheimer

During this last stage of AD, the person is completely dependent upon caregivers.[25] Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech.[25][29] Despite the loss of verbal language abilities, people can often understand and return emotional signals.[25] Although aggressiveness can still be present, extreme apathy and exhaustion are much more common results.[25] People with AD will ultimately not be able to perform even the simplest tasks without assistance.[25] Muscle mass and mobility deteriorate to the point where they are bedridden, and they lose the ability to feed themselves.[25] AD is a terminal illness, with the cause of death typically being an external factor, such as infection of pressure ulcers or pneumonia, not the disease itself.[25]


Microscopy image of a neurofibrillary tangle, conformed by hyperphosphorylated tau protein

1.The Cholinergic Hypothesis

The cause for most Alzheimer’s cases is still essentially unknown[32][33] (except for 1% to 5% of cases where genetic differences have been identified). Several competing hypotheses exist trying to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis,[34] which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine.

The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,[35] leading to generalised neuroinflammation.[36]

2.The amyloid Hypothesis

In 1991, the amyloid hypothesis postulated that amyloid beta (Aβ) deposits are the fundamental cause of the disease.[37][38] Support for this postulate comes from the location of the gene for the amyloid beta precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who have an extra gene copy almost universally exhibit AD by 40 years of age.[39][40] Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.[41] Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.[42]

An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia.[43] Researchers have been led to suspect non-plaque Aβ oligomers (aggregates of many monomers) as the primary pathogenic form of Aβ. These toxic oligomers, also referred to as amyloid-derived diffusible ligands (ADDLs), bind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication.[44] One receptor for Aβ oligomers may be the prion protein, the same protein that has been linked to mad cow disease and the related human condition, Creutzfeldt-Jakob disease, thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer’s disease.[45]

In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by aging-related processes in later life to cause the neuronal withering of Alzheimer’s disease.[46] N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21).[46] DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the aging brain to cause damage. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.

3.The Tau Hypothesis

A 2004 study found that deposition of amyloid plaques does not correlate well with neuron loss.[47] This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade.[38] In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.[48] When this occurs, the microtubules disintegrate, collapsing the neuron’s transport system.[49] This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.[50]

3.The Herpes Simplex Hypothesis

Herpes simplex virus type 1 has also been proposed to play a causative role in people carrying the susceptible versions of the apoE gene.[51]

4.Another Hypothesis

Another hypothesis asserts that the disease may be caused by age-related myelin breakdown in the brain. Demyelination leads to axonal transport disruptions, leading to loss of neurons that become stale[clarification needed]. Iron released during myelin breakdown is hypothesized to cause further damage. Homeostatic myelin repair processes contribute to the development of proteinaceous deposits such as amyloid-beta and tau.[52][53][54]

Oxidative stress and dys-homeostasis of biometal (biology) metabolism may be significant in the formation of the pathology.[55][56]

AD individuals show 70% loss of locus coeruleus cells that provide norepinephrine (in addition to its neurotransmitter role) that locally diffuses from “varicosities” as an endogenous antiinflammatory agent in the microenvironment around the neurons, glial cells, and blood vessels in the neocortex and hippocampus.[57] It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokines and their phagocytosis of Aβ.[57] This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains.[57]


Histopathologic image of senile plaques seen in the cerebral cortex of a person with Alzheimer’s disease of presenile onset. Silver impregnation.


Alzheimer’s disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.[36] Studies using MRI and PET have documented reductions in the size of specific brain regions in people with AD as they progressed from mild cognitive impairment to Alzheimer’s disease, and in comparison with similar images from healthy older adults.[58]

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.[11] Plaques are dense, mostly insoluble deposits of amyloid-beta peptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe.[59] Lewy bodies are not rare in the brains of people with AD.[60]


Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of senile plaques in AD.

Alzheimer’s disease has been identified as a protein misfolding disease (proteopathy), caused by accumulation of abnormally folded A-beta and tau proteins in the brain.[61] Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron’s membrane. APP is critical to neuron growth, survival and post-injury repair.[62][63] In Alzheimer’s disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis.[64] One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.[11][65]

In Alzheimer’s disease, changes in tau protein lead to the disintegration of microtubules in brain cells.

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilizes the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron’s transport system.[66]

Disease mechanism

Exactly how disturbances of production and aggregation of the beta amyloid peptide gives rise to the pathology of AD is not known.[67] The amyloid hypothesis traditionally points to the accumulation of beta amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis).[68] It is also known that Aβ selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.[69]

Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer’s disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response.[70]

Alterations in the distribution of different neurotrophic factors and in the expression of their receptors such as the brain derived neurotrophic factor (BDNF) have been described in AD.[71][72]


The vast majority of cases of Alzheimer’s disease are sporadic, meaning that they are not genetically inherited although some genes may act as risk factors. On the other hand, around 0.1% of the cases are familial forms of autosomal dominant (not sex-linked) inheritance, which usually have an onset before age 65.[73] This form of the disease is known as Early onset familial Alzheimer’s disease.

Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: amyloid precursor protein (APP) and presenilins 1 and 2.[74] Most mutations in the APP and presenilin genes increase the production of a small protein called 42, which is the main component of senile plaques.[75] Some of the mutations merely alter the ratio between Aβ42 and the other major forms—e.g., Aβ40—without increasing Aβ42 levels.[75][76] This suggests that presenilin mutations can cause disease even if they lower the total amount of Aβ produced and may point to other roles of presenilin or a role for alterations in the function of APP and/or its fragments other than Aβ.

Most cases of Alzheimer’s disease do not exhibit autosomal-dominant inheritance and are termed sporadic AD. Nevertheless genetic differences may act as risk factors. The best known genetic risk factor is the inheritance of the ε4 allele of the apolipoprotein E (APOE).[77][78] Between 40 and 80% of people with AD possess at least one apoE4 allele.[78] The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes.[73] However, it must be noted that this “genetic” effect is not necessarily purely genetic. For example, certain Nigerian populations have no relationship between presence or dose of APOEε4 and incidence or age-of-onset for Alzheimer’s disease.[79] [80] Geneticists agree that numerous other genes also act as risk factors or have protective effects that influence the development of late onset Alzheimer’s disease,[74] but results such as the Nigerian studies and the incomplete penetrance for all genetic risk factors associated with sporadic Alzheimers indicate a strong role for environmental effects. Over 400 genes have been tested for association with late-onset sporadic AD,[74] most with null results.[73]


PET scan of the brain of a person with AD showing a loss of function in the temporal lobe

Alzheimer’s disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions.[81][82] Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computed tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.[83] Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer’s disease.[84]

Assessment of intellectual functioning including memory testing can further characterise the state of the disease.[5] Medical organisations have created diagnostic criteria to ease and standardise the diagnostic process for practicing physicians. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.[85]


The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA, now known as the Alzheimer’s Association) established the most commonly used NINCDS-ADRDA Alzheimer’s Criteria for diagnosis in 1984,[85] extensively updated in 2007.[86] These criteria require that the presence of cognitive impairment, and a suspected dementia syndrome, be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD. A histopathologic confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Good statistical reliability and validity have been shown between the diagnostic criteria and definitive histopathological confirmation.[87] Eight cognitive domains are most commonly impaired in AD—memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities. These domains are equivalent to the NINCDS-ADRDA Alzheimer’s Criteria as listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) published by the American Psychiatric Association.[88][89]


Neuropsychological screening tests can help in the diagnosis of AD. In them people have to copy drawings similar to the one shown in the picture, remember words, read, and subtract serial numbers.

Neuropsychological tests such as the mini-mental state examination (MMSE), are widely used to evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease.[90][91] Neurological examination in early AD will usually provide normal results, except for obvious cognitive impairment, which may not differ from that resulting from other diseases processes, including other causes of dementia.

Further neurological examinations are crucial in the differential diagnosis of AD and other diseases.[5] Interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease, over time, of the person’s mental function.[84] A caregiver’s viewpoint is particularly important, since a person with AD is commonly unaware of his own deficits.[92] Many times, families also have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.[93]

Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins,[94] both total tau protein and phosphorylated tau181P protein concentrations.[95] Searching for these proteins using a spinal tap can predict the onset of Alzheimer’s with a sensitivity of between 94% and 100%.[95] When used in conjunction with existing neuroimaging techniques, doctors can identify people with significant memory loss who are already developing the disease.[95] Spinal fluid tests are commercially available, unlike the latest neuroimaging technology.[96] Alzheimer’s was diagnosed in one-third of the people who did not have any symptoms in a 2010 study, meaning that disease progression occurs well before symptoms occur.[97]

Supplemental testing provides extra information on some features of the disease or is used to rule out other diagnoses. Blood tests can identify other causes for dementia than AD[5]—causes which may, in rare cases, be reversible.[98] It is common to perform thyroid function tests, assess B12, rule out syphilis, rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g. lead, mercury) and anemia. (See differential diagnosis for Dementia). (It is also necessary to rule out delirium).

Psychological tests for depression are employed, since depression can either be concurrent with AD (see Depression of Alzheimer disease), an early sign of cognitive impairment,[99] or even the cause.[100][101]


When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging are used to confirm a diagnosis of Alzheimer’s in conjunction with evaluations involving mental status examination.[102] In a person already having dementia, SPECT appears to be superior in differentiating Alzheimer’s disease from other possible causes, compared with the usual attempts employing mental testing and medical history analysis.[103] Advances have led to the proposal of new diagnostic criteria.[5][86]

A new technique known as PiB PET has been developed for directly and clearly imaging beta-amyloid deposits in vivo using a tracer that binds selectively to the A-beta deposits.[104] The PiB-PET compound uses carbon-11 PET scanning. Recent studies suggest that PiB-PET is 86% accurate in predicting which people with mild cognitive impairment will develop Alzheimer’s disease within two years, and 92% accurate in ruling out the likelihood of developing Alzheimer’s.[105]

A similar PET scanning radiopharmaceutical compound called (E)-4-(2-(6-(2-(2-(2-([18F]-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine, or 18F AV-45, or florbetapir-fluorine-18, or simply florbetapir, contains the longer-lasting radionuclide fluorine-18, has recently been created, and tested as a possible diagnostic tool in Alzheimer’s disease.[106][107][108][109] Florbetapir, like PiB, binds to beta-amyloid, but due to its use of fluorine-18 has a half-life of 110 minutes, in contrast to PiB’s radioactive half life of 20 minutes. Wong et al. found that the longer life allowed the tracer to accumulate significantly more in the brains of people with AD, particularly in the regions known to be associated with beta-amyloid deposits.[109]

One review predicted that amyloid imaging is likely to be used in conjunction with other markers rather than as an alternative.[110]

Volumetric MRI can detect changes in the size of brain regions. Measuring those regions that atrophy during the progress of Alzheimer’s disease is showing promise as a diagnostic indicator. It may prove less expensive than other imaging methods currently under study.[111]

Non-Imaging biomarkers

Recent studies have shown that people with AD had decreased glutamate (Glu) as well as decreased Glu/creatine (Cr), Glu/myo-inositol (mI), Glu/N-acetylaspartate (NAA), and NAA/Cr ratios compared to normal people. Both decreased NAA/Cr and decreased hippocampal glutamate may be an early indicator of AD.[112]

Early research in mouse models may have identified markers for AD. The applicability of these markers is unknown.[113]

A small human study in 2011 found that monitoring blood dehydroepiandrosterone (DHEA) variations in response to an oxidative stress could be a useful proxy test: the subjects with MCI did not have a DHEA variation, while the healthy controls did.[114]


Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.

At present, there is no definitive evidence to support that any particular measure is effective in preventing AD.[115] Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results. However, epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population’s likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.[116]

Although cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD,[117][118] statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease.[119][120] The components of a Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together reduce the risk and course of Alzheimer’s disease.[121] Its beneficial cardiovascular effect has been proposed as the mechanism of action.[121] There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of AD.[122]

Reviews on the use of vitamins have not found enough evidence of efficacy to recommend vitamin C,[123] E,[123][124] or folic acid with or without vitamin B12,[125] as preventive or treatment agents in AD. Additionally vitamin E is associated with important health risks.[123] Trials examining folic acid (B9) and other B vitamins failed to show any significant association with cognitive decline.[126] Docosahexaenoic acid, an Omega 3 fatty acid, has not been found to slow decline.[127]

Long-term usage of non-steroidal anti-inflammatory drug (NSAIDs) is associated with a reduced likelihood of developing AD.[128] Human postmortem studies, in animal models, or in vitro investigations also support the notion that NSAIDs can reduce inflammation related to amyloid plaques.[128] However trials investigating their use as palliative treatment have failed to show positive results while no prevention trial has been completed.[128] Curcumin from the curry spice turmeric has shown some effectiveness in preventing brain damage in mouse models due to its anti-inflammatory properties.[129][130] Hormone replacement therapy, although previously used, is no longer thought to prevent dementia and in some cases may even be related to it.[131][132] There is inconsistent and unconvincing evidence that ginkgo has any positive effect on cognitive impairment and dementia,[133] and a recent study concludes that it has no effect in reducing the rate of AD incidence.[134] A 21-year study found that coffee drinkers of 3–5 cups per day at midlife had a 65% reduction in risk of dementia in late-life.[135]

People who engage in intellectual activities such as reading, playing board games, completing crossword puzzles, playing musical instruments, or regular social interaction show a reduced risk for Alzheimer’s disease.[136] This is compatible with the cognitive reserve theory, which states that some life experiences result in more efficient neural functioning providing the individual a cognitive reserve that delays the onset of dementia manifestations.[136] Education delays the onset of AD syndrome, but is not related to earlier death after diagnosis.[137] Learning a second language even later in life seems to delay getting Alzheimer disease.[138] Physical activity is also associated with a reduced risk of AD.[137]

Medical marijuana appears to be effective in delaying Alzheimer’s Disease. The active ingredient in marijuana, THC, prevents the formation of deposits in the brain associated with Alzheimer’s disease. THC was found to inhibit acetylcholinesterase more effectively than commercially marketed drugs. THC was also found to delay amylogenesis.[139][140]

Some studies have shown an increased risk of developing AD with environmental factors such the intake of metals, particularly aluminium,[141][142] or exposure to solvents.[143] The quality of some of these studies has been criticised,[144] and other studies have concluded that there is no relationship between these environmental factors and the development of AD.[145][146][147][148]

While some studies suggest that extremely low frequency electromagnetic fields may increase the risk for Alzheimer’s disease, reviewers found that further epidemiological and laboratory investigations of this hypothesis are needed.[149] Smoking is a significant AD risk factor.[150] Systemic markers of the innate immune system are risk factors for late-onset AD.[151]


There is no cure for Alzheimer’s disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.


Three-dimensional molecular model of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD symptoms

Molecular structure of memantine, a medication approved for advanced AD symptoms

Four medications are currently approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat the cognitive manifestations of AD: three are acetylcholinesterase inhibitors and the other is memantine, an NMDA receptor antagonist. No drug has an indication for delaying or halting the progression of the disease.

Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer’s disease.[152] Acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down, thereby increasing the concentration of ACh in the brain and combating the loss of ACh caused by the death of cholinergic neurons.[153] As of 2008[update], the cholinesterase inhibitors approved for the management of AD symptoms are donepezil (brand name Aricept),[154] galantamine (Razadyne),[155] and rivastigmine (branded as Exelon[156] and Exelon Patch[157]). There is evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease,[158][159] and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of advanced AD dementia.[160] The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD.[161] The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately 10–20% of users and are mild to moderate in severity. Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.[162]

Glutamate is a useful excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Excitotoxicity occurs not only in Alzheimer’s disease, but also in other neurological diseases such as Parkinson’s disease and multiple sclerosis.[163] Memantine (brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda),[164] is a noncompetitive NMDA receptor antagonist first used as an anti-influenza agent. It acts on the glutamatergic system by blocking NMDA receptors and inhibiting their overstimulation by glutamate.[163] Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer’s disease. Its effects in the initial stages of AD are unknown.[165] Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue.[166] The combination of memantine and donepezil has been shown to be “of statistically significant but clinically marginal effectiveness”.[167]

Antipsychotic drugs are modestly useful in reducing aggression and psychosis in Alzheimer’s disease with behavioural problems, but are associated with serious adverse effects, such as cerebrovascular events, movement difficulties or cognitive decline, that do not permit their routine use.[168][169] When used in the long-term, they have been shown to associate with increased mortality.[169]

People with Alzheimer’s disease who have taken Huperzine A may have improved general cognitive function, global clinical status, functional performance and reduced behavioural disturbance compared to people taking placebos, according to a Cochrane Review, however, the poor methodological quality of the small trials, including problems with blinding and randomization, led reviewers to conclude “There is currently insufficient evidence of the effects of Huperzine A for Alzheimer’s disease (AD).”[170]

Psychosocial intervention

A specifically designed room for sensory integration therapy, also called snoezelen; an emotion-oriented psychosocial intervention for people with dementia

Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behaviour-, emotion-, cognition- or stimulation-oriented approaches. Research on efficacy is unavailable and rarely specific to AD, focusing instead on dementia in general.[171]

Behavioural interventions attempt to identify and reduce the antecedents and consequences of problem behaviours. This approach has not shown success in improving overall functioning,[172] but can help to reduce some specific problem behaviours, such as incontinence.[173] There is a lack of high quality data on the effectiveness of these techniques in other behaviour problems such as wandering.[174][175]

Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration, also called snoezelen, and simulated presence therapy. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired people adjust to their illness.[171] Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT, it may be beneficial for cognition and mood.[176] Simulated presence therapy (SPT) is based on attachment theories and involves playing a recording with voices of the closest relatives of the person with Alzheimer’s disease. There is partial evidence indicating that SPT may reduce challenging behaviours.[177] Finally, validation therapy is based on acceptance of the reality and personal truth of another’s experience, while sensory integration is based on exercises aimed to stimulate senses. There is little evidence to support the usefulness of these therapies.[178][179]

The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining, is the reduction of cognitive deficits. Reality orientation consists in the presentation of information about time, place or person in order to ease the understanding of the person about its surroundings and his or her place in them. On the other hand cognitive retraining tries to improve impaired capacities by exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities,[180][181] although in some studies these effects were transient and negative effects, such as frustration, have also been reported.[171]

Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities. Stimulation has modest support for improving behaviour, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the change in the person’s routine.[171]


Further information: Caregiving and dementia

Since Alzheimer’s has no cure and it gradually renders people incapable of tending for their own needs, caregiving essentially is the treatment and must be carefully managed over the course of the disease.

During the early and moderate stages, modifications to the living environment and lifestyle can increase patient safety and reduce caretaker burden.[182][183] Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labelling of household items to cue the person with the disease or the use of modified daily life objects.[171][184][185] The patient may also become incapable of feeding themselves, so they require food in smaller pieces or pureed.[186] When swallowing difficulties arise, the use of feeding tubes may be required. In such cases, the medical efficacy and ethics of continuing feeding is an important consideration of the caregivers and family members.[187][188] The use of physical restraints is rarely indicated in any stage of the disease, although there are situations when they are necessary to prevent harm to the person with AD or their caregivers.[171]

As the disease progresses, different medical issues can appear, such as oral and dental disease, pressure ulcers, malnutrition, hygiene problems, or respiratory, skin, or eye infections. Careful management can prevent them, while professional treatment is needed when they do arise.[189][190] During the final stages of the disease, treatment is centred on relieving discomfort until death.[191]

A small recent study in the US concluded that people whose caregivers had a realistic understanding of the prognosis and clinical complications of late dementia were less likely to receive aggressive treatment near the end of life. [192]

Feeding tubes

There is strong evidence that feeding tubes do not help people with advanced Alzheimer’s dementia gain weight, regain strength or function, prevent aspiration pneumonias, or improve quality of life.[193][194][195][196]


Disability-adjusted life yearfor Alzheimer and other dementias per 100,000 inhabitants in 2004.

  no data
  ≤ 50
  ≥ 250

The early stages of Alzheimer’s disease are difficult to diagnose. A definitive diagnosis is usually made once cognitive impairment compromises daily living activities, although the person may still be living independently. The symptoms will progress from mild cognitive problems, such as memory loss through increasing stages of cognitive and non-cognitive disturbances, eliminating any possibility of independent living.[25]

Life expectancy of the population with the disease is reduced.[9][197][198] The mean life expectancy following diagnosis is approximately seven years.[9] Fewer than 3% of people live more than fourteen years.[10] Disease features significantly associated with reduced survival are an increased severity of cognitive impairment, decreased functional level, history of falls, and disturbances in the neurological examination. Other coincident diseases such as heart problems, diabetes or history of alcohol abuse are also related with shortened survival.[197][199][200] While the earlier the age at onset the higher the total survival years, life expectancy is particularly reduced when compared to the healthy population among those who are younger.[198] Men have a less favourable survival prognosis than women.[10][201]

The disease is the underlying cause of death in 70% of all cases.[9] Pneumonia and dehydration are the most frequent immediate causes of death, while cancer is a less frequent cause of death than in the general population.[9][201]



Incidence rates
after age 65[202]
Age New affected
per thousand
65–69  3
70–74  6
75–79  9
80–84 23
85–89 40
90–     69

Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at any given time.

Regarding incidence, cohort longitudinal studies (studies where a disease-free population is followed over the years) provide rates between 10 and 15 per thousand person–years for all dementias and 5–8 for AD,[202][203] which means that half of new dementia cases each year are AD. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every five years after the age of 65, the risk of acquiring the disease approximately doubles, increasing from 3 to as much as 69 per thousand person years.[202][203] There are also sex differences in the incidence rates, women having a higher risk of developing AD particularly in the population older than 85.[203][204]

Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group.[205] Prevalence rates in less developed regions are lower.[206] The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030.[207] Other studies have reached similar conclusions.[206] Another study estimated that in 2006, 0.40% of the world population (range 0.17–0.89%; absolute number 26.6 million, range 11.4–59.4 million) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050.[3]


Alois Alzheimer’s patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer’s disease.

The ancient Greek and Roman philosophers and physicians associated old age with increasing dementia.[1] It was not until 1901 that German psychiatrist Alois Alzheimer identified the first case of what became known as Alzheimer’s disease in a fifty-year-old woman he called Auguste D. Alzheimer followed her until she died in 1906, when he first reported the case publicly.[208] During the next five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer’s disease.[1] The disease was first described as a distinctive disease by Emil Kraepelin after suppressing some of the clinical (delusions and hallucinations) and pathological features (arteriosclerotic changes) contained in the original report of Auguste D.[209] He included Alzheimer’s disease, also named presenile dementia by Kraepelin, as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published on July 15, 1910.[210]

For most of the 20th century, the diagnosis of Alzheimer’s disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference on AD concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility that they had different causes.[211] This eventually led to the diagnosis of Alzheimer’s disease independently of age.[212] The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer’s disease being used for those younger. Eventually, the term Alzheimer’s disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.[213]

Society and culture

Social costs

Dementia, and specifically Alzheimer’s disease, may be among the most costly diseases for society in Europe and the United States,[18][19] while their cost in other countries such as Argentina,[214] or South Korea,[215] is also high and rising. These costs will probably increase with the ageing of society, becoming an important social problem. AD-associated costs include direct medical costs such as nursing home care, direct nonmedical costs such as in-home day care, and indirect costs such as lost productivity of both patient and caregiver.[19] Numbers vary between studies but dementia costs worldwide have been calculated around $160 billion,[216] while costs of Alzheimer in the United States may be $100 billion each year.[19]

The greatest origin of costs for society is the long-term care by health care professionals and particularly institutionalisation, which corresponds to 2/3 of the total costs for society.[18] The cost of living at home is also very high,[18] especially when informal costs for the family, such as caregiving time and caregiver’s lost earnings, are taken into account.[217]

Costs increase with dementia severity and the presence of behavioural disturbances,[218] and are related to the increased caregiving time required for the provision of physical care.[217] Therefore any treatment that slows cognitive decline, delays institutionalisation or reduces caregivers’ hours will have economic benefits. Economic evaluations of current treatments have shown positive results.[19]

Caregiving burden

Further information: Caregiving and dementia

The role of the main caregiver is often taken by the spouse or a close relative.[14] Alzheimer’s disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects.[15][16][17] Home care is usually preferred by people with AD and their families.[219] This option also delays or eliminates the need for more professional and costly levels of care.[219][220] Nevertheless two-thirds of nursing home residents have dementias.[171]

Dementia caregivers are subject to high rates of physical and mental disorders.[221] Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviours of the cared person such as depression, behavioural disturbances, hallucinations, sleep problems or walking disruptions and social isolation.[222][223] Regarding economic problems, family caregivers often give up time from work to spend 47 hours per week on average with the person with AD, while the costs of caring for them are high. Direct and indirect costs of caring for an Alzheimer’s patient average between $18,000 and $77,500 per year in the United States, depending on the study.[14][217]

Cognitive behavioural therapy and the teaching of coping strategies either individually or in group have demonstrated their efficacy in improving caregivers’ psychological health.[15][224]

Notable cases

Further information: Alzheimer’s in the media

Charlton Heston and Ronald Reagan at a meeting in the White House. Both of them would later develop Alzheimer’s disease.

As Alzheimer’s disease is highly prevalent, many notable people have developed it. Well-known examples are former United States President Ronald Reagan and Irish writer Iris Murdoch, both of whom were the subjects of scientific articles examining how their cognitive capacities deteriorated with the disease.[225][226][227] Other cases include the retired footballer Ferenc Puskas,[228] the former Prime Ministers Harold Wilson (United Kingdom) and Adolfo Suárez (Spain),[229][230] the actress Rita Hayworth,[231] the actor Charlton Heston,[232] the novelist Terry Pratchett,[233] Indian politician George Fernandes,[234] and the 2009 Nobel Prize in Physics recipient Charles K. Kao.[235]

AD has also been portrayed in films such as: Iris (2001),[236] based on John Bayley‘s memoir of his wife Iris Murdoch;[237] The Notebook (2004),[238] based on Nicholas Sparks‘ 1996 novel of the same name;[239] A Moment to Remember (2004);Thanmathra (2005);[240] Memories of Tomorrow (Ashita no Kioku) (2006),[241] based on Hiroshi Ogiwara’s novel of the same name;[242] Away from Her (2006), based on Alice Munro‘s short storyThe Bear Came over the Mountain“.[243] Documentaries on Alzheimer’s disease include Malcolm and Barbara: A Love Story (1999) and Malcolm and Barbara: Love’s Farewell (2007), both featuring Malcolm Pointon.[244]

Research directions

As of 2010[update], the safety and efficacy of more than 400 pharmaceutical treatments had been or were being investigated in 858 clinical trials worldwide, and approximately a quarter of these compounds are in Phase III trials; the last step prior to review by regulatory agencies.[245]

One area of clinical research is focused on treating the underlying disease pathology. Reduction of amyloid beta levels is a common target of compounds[246] (such as apomorphine) under investigation. Immunotherapy or vaccination for the amyloid protein is one treatment modality under study.[247] Unlike preventative vaccination, the putative therapy would be used to treat people already diagnosed. It is based upon the concept of training the immune system to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease.[248] An example of such a vaccine under investigation was ACC-001,[249][250] although the trials were suspended in 2008.[251] Another similar agent is bapineuzumab, an antibody designed as identical to the naturally induced anti-amyloid antibody.[252] Other approaches are neuroprotective agents, such as AL-108,[253] and metal-protein interaction attenuation agents, such as PBT2.[254] A TNFα receptor fusion protein, etanercept has showed encouraging results.[255]

In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with methylthioninium chloride (trade name rember), a drug that inhibits tau aggregation,[256][257] and dimebon, an antihistamine.[258] The consecutive Phase-III trial of Dimebon failed to show positive effects in the primary and secondary endpoints.[259]

The possibility that AD could be treated with antiviral medication is suggested by a study showing colocation of herpes simplex virus with amyloid plaques.[260]

Preliminary research on the effects of meditation on retrieving memory and cognitive functions have been encouraging. Limitations of this research can be addressed in future studies with more detailed analyses.[261]

An FDA panel voted unanimously to recommend approval of florbetapir (tradename: Amyvid), which is currently used in an investigational study. The agent can detect Alzheimer’s brain plaques, but will require additional clinical research before it can be made available commercially.

the end @ copyright dr Iwan suwandy 2011