Creutzfeldt-Jakob disease is a rare degenerative brain disease associated with the accumulation of pathological prion protein in neurons. Clinically, disease is manifested by dementia, pyramidal and extrapyramidal disorders, myoclonia, symptoms of cerebellar damage and visual impairment. The diagnosis is based on a combination of clinical symptoms, EEG data, analysis of cerebrospinal fluid, MRI and PET of the brain, as well as morphological examination of a sample of brain tissue obtained as a result of biopsy or postmortem. An effective treatment has not yet been found. The disease has a 100% fatal outcome.
A81.0 Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease is a very rare disease. Earlier in the literature it was indicated that the frequency of its occurrence is about 1 case per 1 million people of the population. However, in the 90s of the last century, cases of the so-called new variant of Creutzfeldt-Jakob disease, associated with infection from cattle and called “mad cow disease”, began to be noted. In England alone, 86 people have died from this disease in 5 years. Creutzfeldt-Jakob disease is most common among people aged 65-70 years and older. However, in the new variant, disease often affects young people. A relatively high incidence rate is observed in England, Israel, Chile and Slovakia.
It has been established that Creutzfeldt-Jakob disease has an infectious character. Infection can occur during transplantation of tissues infected with prions, through a neurosurgical instrument and blood preparations, with the introduction of certain hormonal drugs (human gonadotropin for the treatment of infertility and somatotropin for the treatment of hypopituitarism). Creutzfeldt-Jakob disease of a new form can develop after eating the meat of diseased animals (cows) or carriers of infection (sheep and goats).
As a result of a number of studies, it became known that Creutzfeldt-Jakob disease is associated with the penetration of an infectious prion protein into the body. Normally, human brain cells contain a healthy prion with a slightly different structure. An infectious prion entering the human body is not destroyed, but with the blood flow enters the brain and is deposited on the surface of neurons. Its interaction with normal brain cell prions leads to the fact that they change their structure, gradually transforming into a pathogenic, infectious prion-like form. Pathogenic prions form plaques and lead to neuron death.
Creutzfeldt-Jakob disease has a rather long incubation period associated with the time required for the penetration of infectious prions into brain tissue and pathogenic transformation of healthy prions. The duration of the incubation period directly depends on the method of infection. When brain tissue is infected with an infected surgical instrument, Creutzfeldt-Jakob disease develops after 15-20 months. In case of infection through tissues implanted in the parabdinal structures (for example, the dura mater, cornea of the eye), the incubation period can last up to 5.5 years. With intramuscular administration of infected drugs (for example, gonadotropin, somatotropin, bovine thrombin-containing hemostatics), Creutzfeldt-Jakob disease begins to manifest itself after 12.5 years.
Hereditary forms of Creutzfeldt-Jakob disease associated with genetic disorders leading to the formation of pathological prions are also noted.
Practical neurology classifies Creutzfeldt-Jakob disease according to its clinical form. In accordance with this, there are: subacute spongiform encephalopathy, characterized by a rapid course and diffuse lesion of the cerebral cortex; the classical (dyskinetic) form, which is a combination of pyramidal and extrapyramidal symptoms with dementia; an intermediate form of Creutzfeldt—Jakob disease, characterized by a predominance of cerebellar and subcortical disorders; amyotrophic form, motor and speech disorders in which resemble the clinic of amyotrophic lateral sclerosis.
There is also a previously observed sporadic form of the disease and a new variant of Creutzfeldt-Jakob disease (“mad cow disease”).
In most cases, Creutzfeldt-Jakob disease is characterized by gradual development, but a subacute or acute onset is possible. In about 30% of cases, Creutzfeldt-Jakob disease begins with prodromal symptoms: irritability, absent-mindedness, headache, sleep disorders, dizziness, memory impairment, decreased vision, lack of initiative, decreased libido, changes in behavioral reactions. There may be an episodic occurrence of euphoria and / or causeless fear, abrupt delusional or hallucinatory experiences. Neurological disorders in the prodromal period include: unsteadiness during walking, paresthesia, disorder of the higher functions of the cerebral cortex (alexia, acalculia, etc.). Several cases have been described when Creutzfeldt-Jakob disease debuted with the appearance of cortical blindness.
At the stage of advanced clinical manifestations, Creutzfeldt-Jakob disease is characterized by progressive spastic paralysis (paraplegia or hemiplegia), ataxia, and epileptic seizures. Extrapyramidal disorders occur: muscle rigidity, athetosis, tremor. Almost all patients have myoclonia — rapid irregular contractions of individual muscles. Most often, myoclonus of the lip and eyelid is noted. Secondary generalized myoclonic seizures are observed. Pronounced dementia appears and increases, accompanied by speech disorders up to its complete disintegration. The new variant of Creutzfeldt-Jakob disease is characterized by a predominance of psychiatric symptoms and sensitivity disorders. In 100% of cases, it is accompanied by cerebellar disorders, while with sporadic Creutzfeldt-Jakob disease, disorders of cerebellar function are observed only in 40% of cases.
In the terminal stage, Creutzfeldt-Jakob disease is characterized by deep dementia. Patients are not in contact, are in a state of prostration, lost control over the function of the pelvic organs. Hyperkinesis, pronounced muscular atrophy, swallowing disorders, bedsores are observed. Hyperthermia and epileptic seizures are possible. Death occurs in a comatose state against the background of decerebration rigidity and pronounced cachexia.
The clinical diagnosis of the disease is based on a combination of dementia progressing over 2 years, pyramidal and extrapyramidal disorders, myoclonia, cerebellar disorders and visual disturbances. To clarify the diagnosis, the neurologist prescribes instrumental examination methods: electroencephalography (EEG), PET and MRI of the brain, lumbar puncture. In doubtful cases, a stereotactic biopsy of the brain is performed to establish the diagnosis of Creutzfeldt-Jakob disease.
On the EEG, against the background of reduced bioelectric activity, periodic or pseudoperiodic acute waves are observed in most patients. Bilateral, focal or generalized myoclonic activity is noted, which is determined in the initial stage in half of patients, and in the terminal stage is detected in 100% of cases of sporadic Creutzfeldt-Jakob disease. A new variant of the disease often proceeds without significant changes in the EEG pattern.
When conducting an MRI of the brain in T2 mode, the so-called “honeycomb symptom” is determined – areas of increased signal emanating from the subcortical ganglia and thalamus. Often there are signs of atrophic changes in the cerebellum and cerebral cortex, expansion of the ventricles and lateral cisterns of the brain. PET diagnoses areas of reduced metabolism localized in the subcortical nuclei, hemispheres of the cerebellum and the cerebral cortex.
Lumbar puncture is mandatory for patients with suspected Creutzfeldt-Jakob disease. It allows you to assess the pressure of the cerebrospinal fluid and perform a study of the cerebrospinal fluid. The absence of pathological changes in the cerebrospinal fluid makes it possible to differentiate Creutzfeldt-Jakob disease from many other diseases of the central nervous system.
The most reliable diagnostic method is morphological examination of brain tissue samples, which can be obtained in vivo by biopsy or autopsy after the patient’s death. The use of the immunocytochemical method makes it possible to detect deposits of a pathological prion protein in the studied material.
Differential diagnosis of Creutzfeldt-Jakob disease should be carried out with frontotemporal dementia, herpevirus encephalitis, Alzheimer’s disease, multiinfarction dementia (dementia developing after repeated ischemic and hemorrhagic strokes), chronic meningitis, arachnoiditis, normotensive hydrocephalus, Hashimoto’s encephalopathy accompanying some cases of autoimmune thyroiditis, etc.
In modern medicine, approaches to the treatment of Creutzfeldt-Jakob disease are under active development. Conventional antiviral drugs, as well as passive immunization and vaccination of humans and animals were found to be ineffective. It is noted that Brefeldin A has a blocking effect on the synthesis of pathological prions in infected neurons, and calcium channel blockers prolong the life of infected cells. Usually, patients with Creutzfeldt-Jakob disease receive symptomatic treatment. It is aimed at the relief of myoclonic seizures and extrapyramidal disorders, in connection with which antiepileptic and antiparkinsonian drugs are used.
Creutzfeldt-Jakob disease is a fatal disease. The life expectancy of most patients does not exceed 1 year from the beginning of clinical manifestations; and the average duration is 8 months. Only 5-10% of cases live for 2 or more years. Hereditary Creutzfeldt-Jakob disease lasts on average about 26 months.