Subacute sclerosing panencephalitis is a slow infection caused by the measles virus. The latency period is up to 8 years. Subacute measles panencephalitis debuts with personality and behavior disorders, then progressive musculotonic, motor, visual, cognitive disorders, paroxysmal states appear. The main diagnostic methods are electroencephalography, CT / MRI of the brain, analysis of cerebrospinal fluid, detection of antibodies to measles in the blood, cerebrospinal fluid. Etiotropic therapy is carried out with antiviral pharmaceuticals, symptomatic treatment is carried out with antiepileptic drugs.
ICD 10
A81.1 Subacute sclerosing panencephalitis
General information
Subacute sclerosing panencephalitis (SSP) was first described in 1933 by the American pathologist J. Dawson called “encephalitis with inclusions”. In 1945, in Belgium, neurologist Van Bogart supplemented the available information about the disease, pointed to the processes of demyelination with a predominant lesion of the white cerebral substance and proposed a new term — “subacute sclerosing leukoencephalitis”. In honor of the mentioned researchers in the modern American literature on neurology, SSP is referred to under the names “Dawson encephalitis”, “Van Bogart leukoencephalitis”. Subacute sclerosing panencephalitis occurs with a frequency of 1 case per 1 million population, 85% of the cases belong to the age category of 5-15 years, boys get sick 3 times more often. There are individual cases of the disease in young children and in adults over 30 years old.
Causes
Pathology is a classic slow infection of the central nervous system. The infectious agent is the measles virus, which persists in the body in a persistent state after a natural measles infection. In most cases, SSP is observed in children who have had measles at the age of two years. The latent period lasts 6-8 years, after which rapidly progressive measles panencephalitis develops. The factors causing viral persistence remain unknown. Some authors suggest that the basis is an altered immunological reactivity of the body, causing incomplete elimination of the virus.
Pathogenesis
Etiopathogenetic mechanisms have not been studied, triggers causing virus activation have not been identified. After a long-term latent period, measles viruses persisting in cerebral cells begin active replication, which causes total inflammatory changes in brain tissues — subacute panencephalitis. The white matter, subcortical ganglia, cortex, and meninges are involved in the inflammatory process. The lesions are distributed unevenly, neurons die in them, glial tissue grows compensatorily. In the later stages, sclerosing panencephalitis is characterized by diffuse demyelination in combination with gliosis. Microscopically, specific inclusions are detected in the affected neurons. A study using labeled antibodies reveals the presence of measles virus antigens in them.
Classification
The clinical symptoms of SSP are very variable, however, a stage course is observed in all patients. Understanding the phase of the disease has clinical and prognostic significance, and therefore subacute sclerosing panencephalitis is classified into 4 main stages:
- Stage I (initial, psychotic) is characterized by increasing changes in the character, behavior, and intellectual abilities of the patient. Before the appearance of musculotonic disorders, it is often misdiagnosed as a psychiatric pathology. Lasts 2-12 months.
- Stage II begins with the appearance of motor disorders (hyperkinesis), paroxysmal episodes (convulsive seizures, absences, atonic falls). In the future, various neurological symptoms are added. The stage lasts 6-12 months.
- Stage III proceeds with a rapid progression of dementia, an increase in muscle rigidity, and a weakening of the convulsive syndrome. Lasts for several months.
- Stage IV (terminal, comatose) — complete breakdown of mental functions, decerebration rigidity, cachexia. Patients fall into a coma with a subsequent fatal outcome.
Symptoms
Subacute sclerosing panencephalitis debuts with gradually worsening deviations in behavior: the patient becomes sloppy, stubborn, aggressive, irritable, indifferent to others. Primitive qualities begin to prevail: greed, selfishness. Psychopathic reactions, sleep disorders appear, schoolchildren have difficulties in learning. By the end of the initial period, progressive mnestic disorders, intellectual decline, speech disorders (dysarthria, aphasia) are observed.
Then extrapyramidal symptoms are added: involuntary movements in the form of athetosis, tremor, torsion dystonia, hemiballism, myoclonia, mixed disorders of muscle tone. Generalized convulsive seizures, episodes of “disconnection” of consciousness (absences), atonic paroxysms are observed. Against the background of the expanded clinic, pyramidal disorders (paresis, pathological reflexes), cerebellar ataxia occur. Cognitive dysfunction is progressing, characterized by apraxia, amnesia, agraphia, alexia, agnosia. In half of the cases, visual disturbances are detected due to the development of cortical chorioretinitis, damage to the optic nerve, the cortex of the occipital lobe.
Gradually, hyperkinesis is replaced by symptoms of parkinsonism, mixed changes in tone turn into total rigidity. Extrapyramidal disorders are combined with vegetative symptoms: increased greasiness of the skin, hyperhidrosis, lability of pressure, hypersalivation. The increasing decerebration rigidity leads to the gradual disappearance of convulsive paroxysms. There is a complete disintegration of personality, violent laughter / crying, hyperthermic crises, swallowing and breathing disorders. In the terminal stage, the patient’s limbs are bent, there are flexion contractures, there is no productive contact, depression of consciousness reaches the stage of coma, trophic tissue changes occur.
Complications
The progression of visual disturbances leads to amaurosis. The supine position of the patient in the last stages of SSP can cause the formation of bedsores. Infection of the latter leads to local inflammatory changes, infection in the bloodstream leads to sepsis. Immobility of the patient, respiratory disorders of central genesis contribute to the occurrence of congestive pneumonia. Dysphagia is dangerous if food enters the respiratory tract with the development of aspiration pneumonia. The listed infectious complications are the most common causes of death of patients.
Diagnostics
Polymorphism, nonspecific symptoms, isolated psychotic manifestations of the initial period, rare occurrence cause late diagnosis of the disease. During the diagnosis, the neurologist relies on anamnestic information about measles suffered in childhood, changes in neurological status, EEG and neuroimaging data, and the results of studies on measles antibodies. A brain biopsy is not indicative, since the mosaicism of the cerebral lesion makes it possible to take material from an unchanged area of brain tissue. The list of necessary additional examinations includes:
- Electroencephalography. A typical pattern of increased slow-wave activity occurs at intervals of 6-8 seconds and alternating with periods of reduced bioelectric activity. The registered complexes are bilateral, symmetrical, synchronous.
- Neuroimaging. It is carried out by methods of computer or magnetic resonance imaging. MRI, CT of the brain diagnose diffuse multiple lesions of cerebral tissues, atrophic changes in the cortex, in some cases — hydrocephalus. Changes in the white matter are observed 4 months after the debut of the SSP. In 50% of cases, lesions of the basal ganglia are determined already at the 2nd stage.
- Examination of cerebrospinal fluid. Liquor for analysis is obtained by lumbar puncture. The study reveals a moderate increase in protein concentration with a significant increase in the relative content of gamma globulins, the presence of specific oligoclonal IgG. A sharp increase in the titer of anti-measles antibodies indicates a measles etiology of the lesion.
- Blood test for measles antibodies. Determines the increase of antibodies in serum to 1:4 — 1:128. Normally, the titer is 1:200 – 1:500. The detection of an increased titer in the blood and cerebrospinal fluid is the most important diagnostic sign.
Isolation of the measles virus from the affected brain tissues is rarely used in clinical practice due to the complexity of the implementation. In the initial stage, subacute sclerosing panencephalitis must be differentiated from mental disorders: neurasthenia, schizophrenia, hysteria. Subsequently, diffdiagnosis is carried out with a brain tumor, progressive rubella panencephalitis, tick-borne encephalitis, Creutzfeldt-Jakob disease.
Treatment
Specific therapy has not been developed. Proper patient care and prevention of infectious complications are of great importance. Etiotropic treatment with antiviral agents (ribavirin, inosine pranobex), interferon preparations is carried out, but it is ineffective. Anticonvulsants effective against myoclonia (diazepam, valproic acid derivatives) are prescribed as symptomatic therapy. Muscle relaxants (tolperizone, baclofen) are used to relieve spastic hypertension. Respiratory disorders in the final stages of the disease are an indication for the transfer of patients to a ventilator. Careful care and symptomatic treatment can prolong the patient’s life.
Prognosis and prevention
In 80% of cases, subacute sclerosing panencephalitis has a duration of 1-3 years and leads to a fatal outcome. In 10% of patients, a lightning-fast course is observed. In 10% of cases, it is possible to increase the patient’s life expectancy, sometimes up to 10 years. The best preventive measures to prevent the occurrence of SSP are measures to prevent measles. Specific prevention is carried out by routine vaccination against measles in children aged 12 months.