Slow CNS infections are lesions of the central nervous system by viral virions or infectious prions that occur after a long latent (incubation) period. Clinically characterized by paresis, hyperkinesis, disorder of cerebellar functions, mental disorders, cognitive decline to deep dementia. Diagnosis is carried out with the help of neurological examination, cerebral tomography, analysis of cerebrospinal fluid, determination of antiviral antibodies in the blood. Treatment is carried out by symptomatic means.
General information
The concept of slow CNS infections includes a number of neurological diseases caused by virions (viral particles) and prions (virus-like proteins). The first data were published in 1954 in Iceland by a scientist who had long observed previously undescribed diseases of sheep affecting the central nervous system. The author gave them the name slow infections. In 1957, a description of a new disease appeared — kuru, common among the inhabitants of New Guinea. The disease fully met the criteria for slow infections and opened a list of similar pathologies in humans, which continues to be replenished. Slow CNS infections are a rare group of nosologies, accurate data on the incidence have not been collected. Some forms are ubiquitous, others are endemic.
Causes
The study of the properties of pathogens allowed us to establish the viral nature of infections. Previously, it was mistakenly assumed that specific viral agents act as pathogens. Subsequently, it was possible to determine two etiological factors of the pathology: viruses and prions.
- Viruses. Currently, the theory of specific etiology has been refuted, the role of common viruses has been confirmed: polyomavirus, flavivirus, cytomegalovirus, measles, rubella, herpes simplex viruses. Slow infectious processes in the central nervous system develop due to the persistence of the virus in the body for many years after the typical form of the disease. Infection can occur by airborne, alimentary, parenteral, transplacental route.
- Prions. They are proteins that have some properties of viruses, unlike the latter do not have DNA or RNA. Infectious prions cause the development of the disease by transforming similar normal nerve cell proteins into pathological ones. Infection occurs when eating insufficiently heat-treated meat of infected animals, transplantation of tissues containing pathogenic prions, hemotransfusions, and neurosurgical interventions.
It is not known for certain what causes the long-term persistence of viruses that remain in the body of patients who have had a common infection. Possible causes are considered to be the defective structure of virions, insufficiency of the immune system, accompanied by reduced production of antibodies, activation of proliferative processes inside cells affected by viruses.
Pathogenesis
A common pathogenetic characteristic that unites various slow infections is the long-term latent development of pathology, accompanied by the accumulation of the pathogen in the cerebral tissues. After a viral disease (more often in utero or in early childhood), pathogens remain in the brain cells in an inactive form. The causes and mechanisms of their activation have not been established. Having entered the active phase, pathogens cause the gradual development of inflammatory changes in the central nervous system.
A prion trapped in a cell interacts with a gene inside it, which leads to the synthesis of similar prions instead of normal cellular proteins. The long latent period is due to the time required for prions to enter the brain, a long process of intracellular accumulation of synthesized pathological proteins. The result of abnormal protein synthesis is metabolic changes that lead to the death of a neuron.
The morphological picture of slow infections is quite variable. Most often, the formation of foci of gliosis, demyelinating areas, is observed in the tissues of the central nervous system. With a truly viral etiology of the process, the formation of perivascular lymphocytic infiltrates, foci of astrocytosis is typical. Morphological changes affect various areas of the brain, and are often widespread.
Classification
Slow CNS infections have a different clinical picture, however, there are individual features of the course of diseases associated with their viral or prion genesis. Taking into account this circumstance , in neurology , diseases are divided according to the etiological principle into:
- Virionic — caused by typical viruses. Accompanied by the production of specific antiviral antibodies. The most common are subacute sclerosing panencephalitis, progressive multifocal leukoencephalopathy, rubella panencephalitis.
- Prion — caused by prion proteins. The close similarity of infectious prions with intracellular proteins of the body causes an almost complete absence of an immune response when they are introduced. The majority of cases are Creutzfeldt-Jakob disease. Prion infections also include fatal familial insomnia, kuru, Gerstman syndrome.
Symptoms
A common feature of diseases of this group is a slow, imperceptible onset without a temperature reaction. The prodromal period is characteristic, in which irritability, emotional imbalance, absent-mindedness of the patient, mild coordination disorders, shakiness during walking are noted. The period of clinical manifestation is characterized by a gradual increase in symptoms, lasting 1-3 weeks. Typical are extrapyramidal and pyramidal disorders, ataxia, mental disorders, cognitive decline.
Extrapyramidal symptoms include hyperkinesis (athetosis, tremor, dystonic syndromes), sometimes bradykinesia, parkinsonian stiffness. Pyramidal motor disorders occur in the form of progressive hemi- and tetraparesis. Cranial nerves may be affected, manifested by paresis of the facial muscles, hearing loss, visual impairment, difficulty swallowing, etc. Mental abnormalities are characterized by episodes of euphoria, phobias, delirium, confused consciousness, fragmentary hallucinations. All slow infections are accompanied by a gradual disintegration of intellectual functions (memory, thinking, attention) with an outcome in deep dementia. Speech disorders are caused simultaneously by sensorimotor aphasia and cognitive deficits. In the terminal stage, mutism is observed — speech is completely absent.
The symptoms of each individual infection have their own characteristics. For Creutzfeldt-Jakob disease, rubella panencephalitis, cerebellar ataxia is characteristic. A distinctive clinical manifestation of fatal insomnia is insomnia, which leads patients to mental and physical exhaustion. The basic symptom of Kuru’s disease is tremor, a typical violent smile. Gerstmann-Straussler-Scheinker syndrome occurs with muscle hypotension and inhibition of tendon reflexes.
The characteristic “slow” refers to a long incubation period and the gradual manifestation of infections. Further development of symptoms occurs fairly quickly and within 8-12 months (less often 2-4 years) leads the patient to the terminal stage. At this stage, there is almost complete immobility, deep dementia, mutism, disorders of consciousness (sopor, coma). The fatal outcome is noted in 100% of cases.
Diagnostics
Since slow infections are rare diseases, it is not easy to diagnose them. Nonspecific clinical symptoms, difficulties in isolating the pathogen virus, infectious prion complicate diagnosis. Diagnostic search is carried out within the framework of the following studies:
- Anamnesis collection. It is of great importance to ask about past (possibly intrauterine) infections, operations with tissue transplantation. The survey includes the identification of prodromal symptoms, features of the onset of pathological manifestations.
- Assessment of neurological status. Neurologists investigate motor, sensory, reflex, cognitive spheres, coordination. Based on the data obtained, a picture of a multi-focal lesion is formed, indicating the diffuse nature of pathological changes in cerebral tissues.
- Neuroimaging. It is carried out using MRI, CT of the brain. Tomography determines multifocal brain damage in the form of demyelination, degeneration, atrophy. There is an expansion of the ventricles, indicating the presence of hydrocephalus.
- Examination of cerebrospinal fluid. The material is obtained by lumbar puncture. The absence of inflammatory changes in the cerebrospinal fluid makes it possible to exclude typical neuroinfections. PCR studies are being conducted to identify DNA of probable pathogens, analysis for the presence of antiviral antibodies. In the case of virionic genesis of infection, these techniques make it possible to verify the pathogen in 70-90% of patients.
- Blood test for antibodies. Informative in the case of viral etiology. It is carried out with the determination of anti-acne, anti-redness antibodies. Repeated studies demonstrating an increase in titer during the activation of the virus are diagnostically significant.
- Brain biopsy. Performed when absolutely necessary. Examination of biopsies reveals intraneuronal clusters of prions. However, during the biopsy, there is a possibility of sampling an area of unchanged tissues.
If there are indications, consultations of related specialists are held: an ophthalmologist, a psychiatrist, an infectious disease specialist, a geneticist. Differential diagnosis with subacute encephalitis, vascular dementia, chronic encephalopathy, Alzheimer’s disease is necessary.
Treatment
Effective therapy has not been developed. The proposed treatment regimens with antiviral pharmaceuticals were unsuccessful. Symptomatic therapy is prescribed, which makes it possible to alleviate the condition of patients, but cannot slow down the progression of the pathological process. It includes decongestants, neuroprotective, vitamin, psychotropic, anticonvulsants. The search for effective treatment methods continues.
Prognosis and prevention
Slow CNS infections remain deadly diseases. The death of patients due to total brain damage occurs on average within 1-2 years from the moment of development of clinical symptoms. The longest life expectancy is observed in patients with Gerstman syndrome — 3-5 years. Preventive measures are reduced to preventing the spread of viral infections, maintaining a proper level of immunity. With regard to measles and rubella, specific prevention is possible, which is carried out by mandatory vaccination of children with appropriate vaccines. Methods for the prevention of prion diseases have not been found, since there are no methods for determining prions in transplanted tissues, blood preparations.
