Creutzfeldt-Jakob disease

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Classification according to ICD-10
A81.- Atypical viral infections of the central nervous system
A81.0 Creutzfeldt-Jakob disease
F02.1 * Dementia in Creutzfeldt-Jakob disease
ICD-10 online (WHO version 2019)

The Creutzfeldt-Jakob disease (CJD) (English Creutzfeldt Jakob Disease , CJD) is a human very infrequent, fatal and atypical proteins (called prions ) marked on transmissible spongiform (with sponge-like resolution of brain tissue associated) encephalopathy . This neurodegenerative disease occurs in humans as a transmitted, genetic, or sporadic form. It is characteristic of the disease that the abnormally folded prion proteins, especially in the brain, force their changed structure on the normally present “cousins” with a healthy structure and thus trigger a disastrous biochemical process there, which ultimately leads to degeneration of the brain . The abnormally folded proteins are deposited in nerve cells and form clumps. The function of the nerve cells is increasingly disturbed, leading to programmed cell death ( apoptosis ). As the disease progresses, the affected brain takes on a sponge-like, perforated structure with thread-like, protein-containing deposits. However, only very small amounts of the infectious prions are present in the blood of a sick person .

The disease was named at the beginning of the 1920s after its first description, the neurologists Creutzfeldt (in Breslau ) and (independently) Jakob (in Hamburg ).

The Robert Koch Institute for Germany reported 77 cases in 2017, and 78 cases in 2018.

Initial description

Spongiform (spongiform) dissolution of brain tissue in sheep suffering from scrapie was documented in Great Britain in 1732.

During a further training stay, the future Kiel neurologist Hans Gerhard Creutzfeldt treated a young woman with speech disorders , confusion and muscle twitching at the Breslau University Neurological Clinic under the direction of Alois Alzheimer , who died a short time later. During the First World War he was only able to publish this “strange, focal disease of the central nervous system” in 1920, shortly before the Hamburg neurologist Alfons Maria Jakob .

The eponym goes back to the German neuropathologist Walther Spielmeyer, who suggested the name Creutzfeldt-Jakob disease in 1922.


This condition is the most common transmissible spongiform encephalopathy (TSE) found in humans . Classic CJD is divided into three previously known forms:

Sporadic prion disease (sCJD)

The sporadic form of Creutzfeldt-Jakob disease is the most common form of disease occurring in humans worldwide. The triggering factors are likely prions .


The disease occurs with a similar frequency of around 1 case per million population worldwide, but is often misdiagnosed initially , most commonly as viral encephalitis , cerebellar paraneoplastic atrophy , depression , vertigo, or Alzheimer's disease . In Germany the gender ratio of women to men is 2: 1. The risk of disease increases with age, and the peak of the disease is around the age of 70. At this age, the annual probability of illness is about 1: 125,000. After that, the risk drops again. Occasionally younger people also get sick. In Germany, around 7 people who are younger than 50 years old develop sporadic CJD every year. Even adolescents can become ill, although so far only a handful of such cases have been described worldwide. The probability of falling ill before the age of 30 is around 1 in 3,000,000.

Course of the disease / symptoms

The disease begins insidiously at first, but a sick person loses his mental and motor skills inexorably and rapidly. The following symptoms can be observed: nervousness, motor disorders ( myoclonus , ataxia ), memory disorders, disorders of perception ( hallucinations ) and vigilance , visual disorders and personality changes, vegetative disorders and confusion up to dementia . The late stage of the disease is characterized by akinetic mutism . The disease usually leads to death within a few months. The duration of the illness can range from 3–6 weeks to more than 2 years. The mean duration of the illness is 4–6 months.

In the Brownell-Oppenheimer form, which is also known as the cerebellar ( cerebellar ) variant, only signs of a cerebellar disorder without cognitive limitations appear in the first month of the disease . Around 20% of sporadic diseases belong to this form. With a mean age of onset of 63 years, gait unsteadiness , dizziness and coordination disorders usually occur , but after a mean three months the progressive full form including cognitive disturbances also develops. Nevertheless, even with the cerebellar form in magnetic resonance imaging in the diffusion-weighted and T2-weighted FLAIR sequences, there are usually no hyperintensities in the cerebellum, but in the basal ganglia and in the thalamus .

Genetic prion disease

A whole group of familial hereditary diseases is summarized in this form. In all of these forms, a specific mutation is inherited, which leads to a faulty prion protein . This group of diseases is very uneven ( heterogeneous ) and it is characterized by very variable clinical symptoms. The peak of the disease is around the age of 50 and thus earlier than in the sporadic form. The duration of the illness is also often longer. These forms of disease include familial / genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). The familial form of Creutzfeldt-Jakob disease was already described in 1930 by Friedrich Meggendorfer .

Transferred forms

Direct transmission of the pathogen from person to person has so far only been proven by iatrogenic means (caused by doctors) via contact with infectious tissue. This happened particularly earlier with meningeal and corneal transplants and with insufficiently sterilized neurosurgical instruments. In addition, a direct transmission of growth hormones or gonadotropins extracted from cadaver pituitary was observed. There are a total of 132 known cases of growth hormone supplement infection worldwide, with most of these cases reported in France and the UK. So far, no case has been reported in Germany, although there, too, small patients were treated with growth hormones.

Most of the cases associated with meningeal transplants have occurred in Japan. These diseases are almost exclusively attributed to the German product Lyodura from B. Braun Melsungen AG . Due to inadequate controls of the meninges donors and the manufacturing process, in which meninges were insufficiently disinfected and stacked in stacks, which continued to lead to cross-contamination of healthy meninges with prions, this product was considered particularly dangerous. Lyodura was used as a kind of "plaster" not only for the reconstruction of the meninges, but also in a variety of non-neurosurgical operations, especially as it was characterized by low rejection reactions. Lyodura had to be withdrawn from circulation in 1996.

New variant of Creutzfeldt-Jakob disease

In the UK, on ​​March 20, 1996, it was announced that several young people had died of a new variant of CJD (nvCJD).


So-called. Florid plaque in the cerebral cortex (autopsy specimen) of a patient with the new variant of Creutzfeldt-Jakob disease (nvCJD)

According to current knowledge, there is a 99% probability that this variant (known today as nvCJD, nv = new variant = new variant) is caused by the consumption of BSE- contaminated beef. Presumably, however, a majority of the population is resistant to infection from food contaminated with BSE, because all previous nvCJD sufferers had a genetic predisposition that is found in just under 40 percent of the European population. At a critical point in the gene that codes for the prion protein, they only ever provided instructions for incorporating the amino acid methionine . The majority of the population, however, is mixed-breed and also has a gene that causes the incorporation of valine at this point. It can be concluded that human prions can be more easily refolded by BSE prions if they contain the amino acid methionine at the designated point.

Tonsil biopsy of a patient with nvCJD. The brown structures are follicular-dendritic cells that contain the abnormal prion protein (immunohistochemical staining with antibody ICSM35 against prion protein)


In contrast to the sporadic disease (sCJD), which originates in the brain itself and is essentially restricted to the central nervous system (small amounts of the abnormal prion protein have also been detected in nerves and muscles), the new variant CJD (nvCJD) also relates to the so-called lymphoreticular system (Lymph nodes, spleen, tonsils (tonsils)). A tonsil biopsy (surgical sampling of the tonsils) can therefore be used to diagnose nvCJD. The tonsils are always positive in nvCJD, while they are always negative in sporadic CJD (sCJD), in iatrogenic CJD (human-to-human transmission through dura transplants or pituitary extract) and in the hereditary forms .

There is also evidence that, in principle, people can also be infected with the new variant of Creutzfeldt-Jakob disease (nvCJD) via blood transfusions. In Great Britain there are a few noticeable individual cases in which it seems very plausible that the disease was transmitted in this way. Also, animal studies suggest this possibility to a high probability. However, this transmission path could not yet be proven with 100% certainty. From the possibility of infection via blood transfusions (and thus blood or blood components per se), it is assumed that a chain of unfortunate circumstances and coincidences in the past in Great Britain could in rare individual cases lead to infections during operations. In addition to blood transfusions, surgical instruments were also suspected to be the cause of these unlikely cases of infection. This is justified by the fact that disinfection techniques were sometimes used in the past, in which it cannot be ruled out with certainty that prions outlived the procedure and subsequent storage of the devices. However, so far not a single case is known in which there was a concrete suspicion of this transmission route; it is a pure assumption regarding a conceivable transmission route. Whether there will ever be such a case cannot be predicted.

New research results at the University of Zurich allow the conclusion that transmission via aerosols in the air is possible. In practice, however, this form of infection should only play a role when working with the carcasses of sick animals in slaughterhouses and laboratories.


In August 2005, the neurologist Claudio Soto and his colleagues from the University of Texas (USA) announced that the bovine disease BSE and the new variant of Creutzfeldt-Jakob disease can now be diagnosed with a blood test. The researchers took advantage of the ability of abnormally modified infectious prions to impose their structure on other healthy prions to multiply the infectious prions in the blood of sick people by a factor of ten million and thus make them easily detectable. In test series with hamsters, the infectious prions could be detected with a reliability of 89% and without false alarms. Work is being carried out on the applicability also for diagnosis in humans and the control of blood donations.

The misfolded protein is resistant to cleavage by proteases , but not the normal form of PrP. In diagnostics, normal proteins can be “digested”; and if there are residues then it must be the pathogenic form of the protein.

Apart from that, nvCJD prions can also be detected in tonsil, spleen or appendix tissue long before they attack the brain. An almond biopsy can therefore be performed to confirm suspicion of nvCJD.

Magnetic resonance imaging

For diagnosis, magnetic resonance imaging is the imaging study of choice for clinically suspected nvCJD. In over 90% of the neuropathologically confirmed nvCJD cases, the so-called pulvinar sign was already evident in the thalamus in the early stages of the disease (2 to 10 months after the onset of symptoms) . In most cases, this enables diagnosis without the need for further examinations.


The electroencephalography shows diffuse slowdowns in most cases, but may be up to the occurrence of psychiatric or neurological symptoms inconspicuous.

Cerebrospinal fluid

The CSF examination is inconspicuous in the standard parameters, there is a normal number of cells, total protein and glucose, only rarely a slight to moderate barrier disorder.Detection of the protein 14-3-3 in the CSF has proven to be a reliable and sensitive marker for the sporadic Creutzfeldt- Jakob disease (sCJD) has been shown. In nvCJD, however, this is only 50% positive. However, it was found that an increased concentration of CSF-tau is a sensitive marker for nvCJD. A negative 14-3-3 has a negative predictive value of 63% and a negative tau has a negative predictive value of 81%. If both tests are negative, the negative predictive value for vCJD increases to 84%

Course of the disease / symptoms

The mean age at the beginning is 26 years (range 12-74 years). The duration of the illness is 14 months (6-39), unusually longer than in the sporadic form. Most patients were first examined by a psychiatrist in the course of the disease. The early stages of the Creutzfeldt-Jakob variant are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and occur from onset in 22% of cases in combination with psychiatric symptoms. Common early psychiatric features included dysphoria , anergy , loss of interest, insomnia , anxiety, and withdrawal , which in many cases led to a diagnosis of depression, but a minority of cases also developed psychotic features such as auditory or visual hallucinations and paranoid behavior or delusions. Many patients became agitated or aggressive, sometimes leading to management difficulties, but thoughts of suicide were rare (9% of cases) and there was no record of intentional self-harm. Fleeting delusions have been described as an uncommon psychiatric trait in previous reports, and although clearly a trait in some cases, they were relatively rare compared to the incidence of other more overt psychiatric symptoms. The possibility of an underlying neurological disorder has in many cases been increased by the development of cognitive impairment, including poor memory, difficulty concentrating, disorientation, or, in a minority, overt confusion. These features developed a median of 4 to 7.5 months from clinical onset, although in a small minority of cases they were already present in the earliest stages. The most common early neurological feature was pain that was not associated with sensory symptoms. This was stubborn and uncomfortable, and often affected the limbs , trunk, or face . Between a median of four and six months, common neurologic features included gait disorders, often in the form of a minor discontinuity, and dysarthria . Paresthesia and numbness in a similar distribution to pain often occurred in a median of 4 to 6 months and affected almost half of the patients. The combination of a psychiatric disorder with affective or psychotic features and persistent pain, dysarthria, gait ataxia, or sensory symptoms should at least arouse suspicion of a variant of Creutzfeldt-Jakob disease, especially if this is associated with evidence of cognitive impairment. Some of the neurological features, such as sensory symptoms, gait fluctuations, and dysarthria, may occur with psychiatric illness or as side effects of psychotropic drugs, but persistence of these symptoms and the development of additional neurological symptoms may indicate the Creutzfeldt-Jakob variant.

Suggestive neurological features of the Creutzfeldt-Jakob variant such as cerebellar signs , involuntary movements ( myoclonus , chorea, or dystonia ), signs of the upper motor neuron, and visual symptoms are very common but occur relatively late in the course of the disease. Psychiatric symptoms that suggest the likelihood of an organic etiology , e.g. B. Disorientation, hallucinations, and impaired self-sufficiency also occur late.

In the final stage, the patients of the disease no longer have the opportunity to make contact with their environment or to react to it. This is why end-stage nvCJD sufferers are often referred to as "The Living Dead." Sometimes a complete spastic paralysis of the body, the so-called dehiral rigidity , occurs. The patients remain in this final state of the disease (terminal state) for a long time until they die either from pneumonia or from respiratory paralysis .


As of February 2015, 177 people had died of nvCJD in the UK and an additional 52 people outside the UK, half of them in France. The number of diseases is decreasing, so the danger is considered averted. As recently as 2005 it was suspected that by 2015 a massive epidemic of "human mad cow disease" would hit Great Britain and possibly many thousands of people will succumb to the disease. This suspicion was also confirmed by a study in which it was established through examinations of removed tonsil and appendix tissue that several thousand British people must carry the nvCJD pathogen.

The BBC reported on January 12, 2005 findings from a group of scientists that a major epidemic is unlikely. This is supported by the fact that the number of deaths in the UK fell from 28 in 2000 to nine in 2004.

Reporting requirement

In Switzerland, the clinical suspicion of a form of Creutzfeldt-Jakob disease (CJD) , the death of a patient and the confirmation of the disease by autopsy must be reported according to the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Appendix 1 or Annex 2 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .

Transmissible spongiform encephalopathies are in Austria in accordance with § 1 para. 1, point 1 Epidemics Act 1950 on suspicion, illness and death notifiable . Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Germany, human spongiform encephalopathy (except for familial hereditary forms) is subject to notification by name in the event of suspicion, illness and death by the doctor etc. in accordance with Section 6 of the Infection Protection Act (IfSG) . The group of reporting persons is based on § 8 IfSG, what has to be reported according to § 9 IfSG.


Web links

Individual evidence

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