Adenovirus encephalitis is an inflammation of brain tissue caused by pathogens from the Adenovirus family. The risk of developing the disease increases with impaired immune status, at an early age, in patients after transplantation. The disease manifests itself with typical respiratory symptoms of adenovirus infection in combination with focal neurological signs, headache, impaired consciousness. Diagnosis of pathology requires instrumental (MRI, CT, EEG), laboratory research methods (PCR, serological reactions). Treatment is mainly pathogenetic — the fight against cerebral edema, neuroprotection, neurometabolic therapy.
85.1 Adenovirus encephalitis
Adenovirus infection accounts for one third of all respiratory viral infections, especially common in children aged 6 months to 7 years. It is widespread everywhere, outbreaks in organized collectives are possible. The share of adenoviruses in the infectious morbidity is 10%. Encephalitis refers to rare complications of the infectious process, there are no statistics on its prevalence. However, the problem does not lose its relevance due to the risk of severe consequences, residual neurological deficit.
The disease is associated with infection of the patient with DNA-containing viruses of the Adenoviridae family of the genus Mastadenovirus. A total of 49 human pathogenic serotypes are known, which are grouped into 7 groups according to antigenic structure and pathogenicity factors. Manifest forms of the disease are most often caused by viruses of groups B and E (serotypes 3, 4, 7, 14, 21). The probability of developing an adenovirus infection with the transition to encephalitis increases if the following risk factors are present:
- Seasonality. The largest number of infections occurs in winter and spring, which is due to the peculiarities of the pathogenesis of viral infection, increased susceptibility of the population.
- Increased virulence. In some types of adenoviruses, more aggressive pathogenicity factors are detected, which is why they more often lead to generalized forms of the disease.
- Age. Adenovirus encephalitis is characteristic of infants of the first year of life, whose immune defenses are not yet sufficiently formed, and brain tissues are more prone to hydrophilicity, necrotic processes.
- Decreased immunity. This includes both a temporary decrease in protective forces (under stress, after a prolonged illness), and primary, secondary forms of immunodeficiency.
- Transplantation. Severe adenovirus infection is attributed to one of the causes of transplant-associated mortality in children after hematopoietic stem cell transplantation.
Infection with adenoviruses occurs through the respiratory mucosa by airborne droplets, less often through the intestinal epithelium by fecal-oral mechanism. First, local inflammation develops in the pharynx, tonsils, conjunctiva, after which viruses enter the blood by lymphogenic means. Viremia lasts up to 10 days — at this time, with a combination of unfavorable factors and high pathogenicity of adenoviruses, their penetration into the cerebral tissue is possible.
Pathogenesis of nerve tissue damage involves pathogens themselves that have a direct cytotoxic effect, and inflammatory cytokines: gamma interferon, tumor necrosis factor, some types of interleukins. Against the background of inflammation, microcirculation disorders, dysregulation of vascular tone, damage to the endothelium of cerebral vessels are noted. This provokes brain hypoxia, local or diffuse interstitial edema.
Adenovirus encephalitis is characterized by damage to the cerebellar tissue, the temporal lobe of the cortex is in second place in terms of the frequency of involvement in the process. The intensity ranges from transient edema to irreversible degeneration of the nervous tissue, which, taking into account the volume of the lesion, determines the severity of the condition, the number of complications. Diffuse spread of inflammatory changes, tendency to necrosis, formation of cerebral cysts are more typical for newborns.
The development of encephalitis is preceded by catarrhal manifestations specific to adenovirus infection. Worried about the symptoms of rhinitis, pharyngitis, wet cough. Examination of the throat reveals hyperemia and swelling of the posterior pharyngeal wall, hyperplasia of lymphoid follicles. Eye damage is typical: lacrimation, photophobia, puffiness of the eyelid skin. One or more groups of peripheral lymph nodes are often enlarged.
Encephalitis manifests with febrile fever, accompanied by intense headaches, and sick young children often have nausea, vomiting, and stool disorders. Patients lose their appetite, experience severe weakness, drowsiness. Meningeal signs are poorly expressed: slight rigidity of the muscles of the occiput, hypersensitivity to bright light and loud sounds, questionable symptoms of Kernig, Brudzinsky.
Focal signs of adenovirus encephalitis depend on the location of the lesion. When inflammation spreads to the cerebellum, there is an uncertain staggering gait, impaired coordination of movements, inability to control fine motor skills. Muscle tone decreases, tremors occur when trying to maintain a pose or performing purposeful movements.
Speech disorders are less common: vagueness of pronunciation of words, incorrect construction of phrases, difficulty in pronunciation at the beginning of a word or syllable. Nystagmus is possible — rapid involuntary fluctuations of the eyeballs. Sometimes auditory hallucinations appear in the form of monotonous noise, the inability to recognize speech while maintaining the ability to speak, vestibular disorders.
The most dangerous consequence of the acute period of encephalitis is edema-swelling of the brain, which, in the absence of timely dehydration, results in dislocation syndrome. When the brain is wedged into the large occipital foramen, there is a high probability of death from a violation of vital functions. The viral process is especially severe in immunocompromised patients – mortality reaches 70%.
In 30% of cases, inflammation spreads with the development of encephalomyelitis, meningoencephalitis, encephalomyelopolyradiculoneuritis. Other complications of the acute stage include multiple organ failure, cerebral hemorrhages. Long-term consequences of adenovirus encephalitis include muscle tone disorders, motor disorders, cognitive deficits. Occasionally, hydrocephalus, epilepsy is formed after the disease.
The examination of the patient by a neurologist begins with the collection of anamnesis, finding out cases of contact with those suffering from adenovirus infection. During the examination, attention is drawn to focal neurological symptoms, which helps to make a topical diagnosis, as well as an assessment of the condition of the skin, the work of the cardiovascular and respiratory systems. To confirm the diagnosis, specialized research methods are prescribed:
- MRI of the brain. Standard imaging, the use of contrast MR angiography and MR venography are the most informative diagnostic methods that show up to 90% of focal brain changes in encephalitis. As an alternative, a CT scan of the brain can be performed.
- Neurosonography. Ultrasound of the brain is recommended mainly up to the age of 5 as a safe and sufficiently informative way of daily monitoring of the patient’s condition. To exclude possible thrombotic complications, duplex scanning of cerebral vessels is performed.
- Additional visualization methods. With an unclear diagnosis and to predict outcomes, MRI with functional tests, MR spectroscopy are performed. Positron emission tomography is informative for assessing the functional state of the cerebral cortex.
- Neurophysiological examination. According to the prevailing clinical symptoms, electroencephalography, multimodal evoked brain potentials, transcranial magnetic stimulation are used. To detect peripheral lesions, ENMG and needle myography are performed.
- CSF research. With diagnostic lumbar puncture, mixed pleiocytosis is determined, which after 10-14 days acquires a lymphocytic character. The protein level is within the age norm or increased to 1.5-2 g / l, the indicators of chlorides and glucose without deviations.
- Identification of the pathogen. PCR of blood and cerebrospinal fluid is used to detect adenoviruses. Informative serological studies: ELISA for antibodies to adenovirus infection. In rare cases, they resort to isolation of the virus on tissue culture.
If viral encephalitis is suspected, starting therapy with drugs from the group of nucleotides and nucleosides is prescribed until the etiological factor is clarified. After verification of the adenoviral nature of the disease, this drug is canceled, antiviral amide derivatives of D-ribose are recommended as etiotropic treatment.
The basis of medical care for inflammation of cerebral tissues is a complex pathogenetic therapy, individually selected by the attending physician. Its main directions are:
- Dehydration. With cerebral edema, glucocorticosteroids are administered in age-related doses, osmodiuretics in combination with saluretics. The volume of infusion therapy is reduced to 75% of the physiological need.
- Neuroprotection. In an extremely severe course of the disease, a barbituric coma is used to prevent the spread of the lesion to other parts of the brain. From the first day of the illness, energy correctors are prescribed.
- Immunocorrection. To improve immunity, recombinant interferon preparations, intravenous immunoglobulins are indicated, plasmapheresis is performed in severe cases.
- Nootropic therapy. Medications are used to accelerate the recovery of neurological functions, increase the resistance of cerebral tissue to hypoxia, and improve metabolic processes in neurons.
After the relief of acute manifestations of adenovirus encephalitis, a residual neurological deficit is possible. Kinesiotherapy, mechanotherapy, and special massage complexes are prescribed for its correction. Cognitive disorders require speech therapy, neuroacoustic, defectological programs. Dispensary follow-up after encephalitis lasts 3-5 years, includes regular instrumental examinations.
Prognosis and prevention
For patients with normal immune status, the prognosis is favorable, up to 99% of cases end in recovery, regression of focal neurological symptoms. The prognosis is less optimistic for children under one year old, immunocompromised patients and people who have undergone transplantation. They more often have generalized forms of pathology, there is a risk of multiple organ failure, death.
To prevent infection with adenoviruses, it is necessary to isolate the sick, separate children in schools and kindergartens for the period of the outbreak of infection, carry out current and final disinfection. When in contact with patients, personal protective equipment should be used. Personal hygiene plays an important role: thorough washing of hands, treating them with antiseptics if necessary.