Creutzfeldt-Jakob disease: causes, symptoms, diagnosis, treatment

Creutzfeldt-Jakob disease is a sporadic or familial prion disease. Bovine spongiform encephalopathy (mad cow disease) is considered a variant of CJD.

Creutzfeldt-Jakob disease is characterized by the development of dementia, myoclonic seizures, and other neurological disorders; death occurs within 1 to 2 years. Infection can be prevented by taking precautions when working with infected tissue and using bleach to clean contaminated instruments. Treatment is symptomatic.

Creutzfeldt-Jakob disease usually affects people over 40 years of age (mean age 60 years). The disease occurs worldwide; incidence is higher in North African Jews. Most cases are sporadic, but 5% to 15% are inherited in an autosomal dominant manner. In the inherited form of CJD, the disease begins earlier and has a longer duration. Creutzfeldt-Jakob disease can be transmitted iatrogenically (eg, after cadaveric corneal or dura mater transplantation, by using stereotactic intracerebral electrodes, or by using growth hormone prepared from human pituitary glands).

New variant Creutzfeldt-Jakob disease (nvCJD) has become most prevalent in the UK. In the early 1980s, lax regulations allowed processed animal waste infected with (scrapie, a prion disease of sheep) to be fed to cattle. Thousands of animals became infected with bovine spongiform encephalopathy (BSE), also known as mad cow disease. People who ate the infected cattle developed Creutzfeldt-Jakob disease.

Because of the long incubation period of nvCJD, the link between the disease and contaminated meat was not established until nvCJD had developed into an epidemic, which was subsequently eradicated by mass culling. In the UK, the number of newly reported cases of nvCJD varied from 17 to 28 per year from 2000 to 2002. Whether the incidence is decreasing remains unclear. Although nvCJD has been confined to the UK and Europe, bovine spongiform encephalopathy has now been detected in North American cattle.

ICD-10 code

A81.0. Creutzfeldt-Jakob disease.

Epidemiology of Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease includes isolated, scattered cases of Creutzfeldt-Jakob disease that are not epidemiologically associated with either an established common source or a specific single route or factor of transmission of the pathogen. Sporadic Creutzfeldt-Jakob disease is common throughout the world. The annual incidence is 0.3-1 case per 1 million inhabitants. Creutzfeldt-Jakob disease is usually registered in the older age group, its peak is at 60-65 years. Patients with this form of the disease can be a source of iatrogenic Creutzfeldt-Jakob disease.

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What causes Creutzfeldt-Jakob disease?

The familial form of the disease, caused by mutations in the PRNP gene, is observed in 10-15% of families where Creutzfeldt-Jakob disease was previously diagnosed. Patients with this form are also likely sources of the iatrogenic form of the disease. Iatrogenic Creutzfeldt-Jakob disease can be considered a hospital-acquired infection. It has now been proven that this variant of Creutzfeldt-Jakob disease is caused by the implementation of an artificial (artificial) mechanism for transmitting the pathogen. This form includes cases of Creutzfeldt-Jakob disease if the patient's epidemiological history indicates any medical intervention associated with the source - a possible carrier of infectious prion proteins. Recipients of the dura mater, spinal cord, cornea, and donor blood are at serious risk. In epidemiological terms, it is considered dangerous to administer human pituitary gland extract (growth hormone and gonadotropin) to a patient, as well as medications prepared from the brain and other organs of animals. In total, 174 cases of iatrogenic Creutzfeldt-Jakob disease are known, registered in the world by 1998. In the new variant of the disease, the source of the pathogen is animals. This variant of the disease appeared following the epizootic of bovine spongiform encephalopathy in England. The genetic closeness of prions from cows that died from spongiform encephalopathy and prions obtained from patients with the new variant of Creutzfeldt-Jakob disease has been proven.

Symptoms of Creutzfeldt-Jakob disease

Prodromal symptoms of Creutzfeldt-Jakob disease are observed in 1/3 of patients several weeks or months before the appearance of the cardinal sign of Creutzfeldt-Jakob disease - progressive dementia. In the prodromal period, patients complain of weakness, sleep and appetite disturbances, loss of libido. The first symptoms of Creutzfeldt-Jakob disease are expressed in the form of visual disturbances, sometimes the disease debuts with cerebellar ataxia. Behavioral disturbances and mental disorders are characteristic: apathy, paranoia, depersonalization, emotional lability.

Along with the typical form of Creutzfeldt-Jakob disease, its atypical variants are identified with a disease duration of more than 2 years. Also considered atypical are forms of the disease that manifest themselves in cerebellar disorders to a greater extent than mental ones (ataxic form). Variants of Creutzfeldt-Jakob disease have been described, where symptoms of cortical blindness due to damage to the occipital lobes predominate. The panencephalitic type of Creutzfeldt-Jakob disease includes cases with degeneration of the white matter of the brain and spongy vacuolization of the gray matter. In the case of severe muscle ataxia in the early stages of the disease, the amyotrophic variant of Creutzfeldt-Jakob disease is diagnosed.

The new variant of Creutzfeldt-Jakob disease differs clinically from the classic one in that the disease debuts with mental disorders in the form of anxiety, depression, behavioral changes, and sometimes dysesthesia of the face and limbs is recorded. After several weeks or months, neurological disorders join in, mainly cerebellar. In the late period of the disease, typical symptoms of Creutzfeldt-Jakob disease are noted: memory impairment, dementia, myoclonus or chorea, pyramidal symptoms. The EEG usually does not show changes characteristic of Creutzfeldt-Jakob disease. Patients die within the first six months, rarely survive to a year, even more rarely to 2 years. Such galloping cases have been described when the disease proceeds as acute encephalitis, and the patient dies within a few weeks.

Dementia in Creutzfeldt-Jakob disease

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ICD-10 code

F02.1. Dementia in Creutzfeldt-Jakob disease (A81.01).

Creutzfeldt-Jakob dementia is a progressive acquired dementia with extensive neurological symptoms.

Specific changes in the nervous system (subacute spongiform encephalopathy) are presumably genetically determined.

The disease usually begins in old age or senile age, although it can also develop in adulthood.

The clinical picture of the disease is characterized by the following triad:

1. rapidly progressive, devastating dementia:
2. severe pyramidal and extrapyramidal disorders with myoclonus;
3. characteristic three-phase EEG.

The disease manifests itself as progressive spastic paralysis of the limbs, tremor, rigidity, characteristic movements: in some cases ataxia, decreased vision, muscle fibrillation, atrophy of the upper motor neuron.

For diagnostics, including differential diagnosis, the following specific signs are important:

• rapid (within months or 1-2 years) progression;
• extensive neurological symptoms that may precede dementia;
• early onset of motor disorders.

Treatment of mental disorders that complicate the clinical picture of the disease is carried out according to the standards of treatment of the corresponding syndromes, taking into account the age and somatoneurological condition of the patient. It is also necessary to work with the patient's family members, psychological support for people caring for the patient.

The prognosis is unfavorable.

Diagnosis of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease should be considered in rapidly progressing dementia in the elderly, especially in the presence of myoclonic seizures and ataxia. In them, Creutzfeldt-Jakob disease should be differentiated from cerebral vasculitis, hyperthyroidism and bismuth intoxication. In young people, Creutzfeldt-Jakob disease is possible with the consumption of beef imported from the UK, but Wilson-Konovalov disease must be excluded.

The diagnosis of Creutzfeldt-Jakob disease is based on the identification of the classic symptom of Creutzfeldt-Jakob disease - progressive dementia (intellectual and behavioral disorders that rapidly increase) combined with myoclonus. Typical periodic complexes are detected on the EEG, and pathology is not detected in the cerebrospinal fluid. Modern diagnosis of Creutzfeldt-Jakob disease is based on the fact that cases of progressive dementia combined with the following syndromes (2 or more): myoclonus, cortical blindness, pyramidal, extrapyramidal or cerebellar insufficiency, typical EEG changes (biphasic or triphasic sharp waves with a frequency of 1-2 per second) almost always turn out to be cases of Creutzfeldt-Jakob disease during pathomorphological examination. Diagnosis may present certain difficulties. MRI reveals brain atrophy, diffusion-weighted MRI - pathological changes in the basal ganglia and cortex. CSF is usually unchanged, but the characteristic protein 1433 is often determined. Brain biopsy is usually not required.

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Treatment of Creutzfeldt-Jakob disease

There is no treatment for Creutzfeldt-Jakob disease. The average life expectancy from the onset of symptoms is 8 months, 90% of patients die within the first year of illness.

Personnel who come into contact with biological fluids and tissues of patients with suspected Creutzfeldt-Jakob disease should wear gloves and avoid contact of contaminated material with mucous membranes. If contaminated material comes into contact with the skin, first disinfect it with a 4% sodium hydroxide solution for 5-10 minutes, then rinse under running water. Autoclaving at 132° C for 1 hour or sterilization in a 4% sodium hydroxide solution or 10% sodium hypochlorite solution for 1 hour is recommended for disinfecting materials and instruments. Standard sterilization methods (e.g., formalin treatment) are ineffective.