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0DAMAGE TO THE NERVOUS SYSTEM DUE TO HIV
Zokirov Muzaffar
FERGANA MEDICAL INSTITUTE OF PUBLIC HEALTH Dadabaeva Shirin FERGANA STATE UNIVERSITY
ARTICLE INFO
ABSTRACT
Received: 11th July 2024 Accepted: 16th July 2024 Online: 17th July 2024
Overview of literature on problems of nervous manifestations of HIV-infection is presented. Issues of pathogenesis, classification, diagnostics of nervous system affection are reflected. Characteristics of illness proceeding in children are considered. Key words: HIV-infection, nervous system, diagnostics, children.
KEY WORDS
HIV infection, Highly active antiretroviral therapy, cognitive
impairment, dementia, inflammatory diseases.
Introduction. HIV infection is a disease caused by a retrovirus that infects cells of the immune, nervous, and other systems of the human body [1, 2]. Damage to the nervous system, primarily the brain, is one of the most important problems associated with HIV and infection. Neurological lesions in HIV infection are observed in 50-80% of patients and are clinically pronounced in more than 10% of them [3, 4]. Damage to the nervous system is primary in 7.2% of patients [5, 6]. NeuroAIDS is the leading clinical syndrome in 30% of patients [6]. There are several hypotheses for HIV penetration into the CNS: HIV penetration through the blood-brain barrier with infected lymphocytes and microphages; penetration of HIV into the central nervous system along nerve fibers; penetration through the gaps between the endothelial cells of the capillaries. Causative factors of neurological disorders in HIV infection: direct action of HIV, mediated damage to brain tissue by cytokines, exposure to pathogens of secondary infections, neoplasms, vascular complications. Psychogenic and iatrogenic factors can also acquire pathogenic significance [4, 5, 7].
Main part. In 70-90% of patients who died from AIDS, brain tissue changes were found [4]. Pathological changes are represented by inflammatory perivascular infiltration, proliferation of vascular wall cells, oligodendroglia and microglia, reactive gliosis, degenerative changes in white matter, and focal demyelination [5, 6, 8].
Topical classification identifies the following neurological manifestations of HIV infection:
- brain and meninges: HIV - meningoencephalitis, opportunistic infections of the central nervous system, neoplastic processes, acute disorders of cerebral circulation, convulsive syndrome;
- spinal cord: HIV-mediated vacuolar myelopathy, acute myelopathy in opportunistic infections;
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- peripheral nervous system: distal symmetric polyneuropathy, polyneuropathy in opportunistic infections, neuropathy of the facial nerve, neural amyotrophy, multiple mononeuritis, lumbosacral polyradiculopathy, demyelinating polyradiculo-neuropathy [6].
Aseptic meningitis occurs during seroconversion, both acutely and chronically. A subclinical course of meningitis is possible [4]. There are no specific clinical signs. In the cerebrospinal fluid (CSF), mononuclear pleocytosis up to 20 or more cells. HIV can be determined in the cerebrospinal fluid. The course is favorable, but relapses are likely [4, 5-7].
Acute encephalitis often occurs in the first three months of the disease development, it is clinically characterized by fever, general malaise, mood changes, epileptic seizures, and changes in the level of consciousness [3, 4]. Full recovery of functions occurs within 2-4 weeks. Acute meningoencephalitis occurs in 5-10% of cases and is often accompanied by lesions of the V, VII, and VIII pairs of cranial nerves [4, 7]. Subacute encephalitis (AIDS - dementia complex, AIDS-DC) is observed in 6-21% of adult patients [4]. In most cases, AIDS-DC develops against a background of profound immunodeficiency. However, it may be the first clinical manifestation of HIV infection.
For AIDS-DC is characterized by a triad: cognitive impairment, movement disorders and altered behavior [5]. Dementia is predominantly fronto-subcortical type [4]. Severe impairments in the cognitive sphere, difficulties in concentrating attention and memory impairment are noted [3, 5]. Often there are sleep disorders, akinetic-rigid syndrome, tremor, cerebellar ataxia. Perhaps the appearance of symptoms of oral automatism, oculomotor disorders [4, 5]. In the neurological status, muscle hypotension is also detected in combination with a high reflex background [6]. In the later stages of AIDS, dementia, paresis and paralysis develop, generalized convulsions are possible. In the terminal stage, patients approach a vegetative state. The course of the disease is progressive over several months and even years; long-term remission is possible [4]. The most severe lesions of the central nervous system are determined when the content in the peripheral blood is less than 0.2 x 109/l of CD4-lymphocytes and with a viral load of more than 10,000 copies/ml. In the natural course of the disease, the terminal phase in more than 80% of cases occurs within 4-8 years [5].
Among the laboratory parameters, the most characteristic is the high content of protein in the CSF (up to 1.0 g/l). lymphocytic cytosis is often small, about 200 cells / pi, a decrease in glucose concentration is possible, but there may be no changes [4-6]. Brain CT and MRI reveal cerebral ventricular enlargement and diffuse white matter depletion, less often changes in the thalamus and basal ganglia [3, 4]. Children have calcification of the basal ganglia or their atrophy. When puncturing the biopsy, small (less than 1 cm in diameter) foci are determined [3]. The EEG reveals a bilateral diffuse slowing of the rhythm [5, 6].
Vacuolar 10-25% of AIDS patients suffer from myelopathy [4, 6]. Progressive vacuolar myelopathy is associated with the development of degenerative changes in the conduction pathways (especially the lateral and posterior columns) of the spinal cord, with maximum changes in the region of the middle and lower thoracic regions [5]. The disease usually develops against a background of severe immunosuppression [4]. It is believed that this pathology is caused by the direct effect of HIV on the spinal cord [5, 6]. Manifested by spastic lower paraparesis, sensitive ataxia, paresthesia, a sharp dysfunction of the pelvic organs, there is no pain syndrome. The disease progresses over several weeks or months with an unfavorable
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outcome [4-6]. MRI may show atrophy in the cervicothoracic spinal cord. Antiretroviral therapy (ARVT) is sometimes effective [4].
Lesions of the peripheral nervous system (PNS) are observed in more than 50% of patients [4]; they are observed in all patients with a CD4-lymphocyte count of 0.2-0.29 X 109/l and lower [9]. peripheral polyneuropathy is symmetrical. Its occurrence is associated with the direct action of HIV on the peripheral nervous system. The disease begins with paresthesia, then the weakness of the distal extremities and muscle atrophy increase [6]. The course is slowly progressive. Electroneuromyography reveals both myelopathy and axonal lesions.
Acute polyradiculoneuropathy (Guillain-Barre syndrome) often develops during seroconversion [4]. Morphologically, perivascular inflammatory infiltrates and demyelination of nerve trunks are determined [5]. In CSF, an increased content of protein, lymphocytic pleocytosis up to 50 cells / [il [4].
Multiple mononeuropathy with damage to the cranial and spinal nerves manifests itself acutely or subacutely, often ends in spontaneous remission. It can manifest at an early stage of HIV infection, the late stage is characterized by a rapidly progressive course [4]. There are no intoxication symptoms, the pain syndrome is unstable [5].
It is known that the frequency of strokes in young people with HIV infection is 40 times higher than in the general population. Of the many causes, vascular endothelial damage, thrombocytopenia, heart damage, rupture of mycotic aneurysms, and hemorrhage into the tumor are distinguished [4, 7]. With progressive immunodeficiency, susceptibility to bacterial, fungal, viral, and parasitic infections increases, causing brain damage [4, 5].
Cytomegalovirus infection (CMVI) is registered in 20-40% of AIDS patients [3, 4, 10]. Encephalitis has a subacute course with a gradual increase in clinical symptoms. There are frequent mood swings, uncritical attitude to one's condition, sleep and memory disturbances, periodic headache. For 3-4 weeks before the death of patients, headache intensifies, fever becomes more persistent, memory deteriorates significantly, drowsiness and weakness increase, personality disintegration is possible. Focal symptoms increase, visual and auditory hallucinations appear. Meningoencephalitis proceeds more aggressively, with rapid impairment of consciousness and coma [3].
Cytomegalovirus lesions of the spinal cord are often diffuse in nature. Manifested by pain syndrome, lower paraparesis, dysfunction of the pelvic organs, optic neuritis [3, 4]. The development of myelitis is an unfavorable prognostic sign: as a rule, patients die in 1-3 months. Brain CT may show subependymal changes with ventriculitis. Changes in the CSF are characterized by a slight increase in the protein level (0.6-1 g/l), double-digit cytosis, lymphocytic composition, sometimes cytomegalovirus can be isolated from it [3].
Tuberculous meningitis is a common opportunistic disease. The disease is usually severe, against the background of severe immunodeficiency, the typical picture of the disease may be distorted. The prognosis is usually unfavorable [3, 7].
Toxoplasmosis is widespread in HIV infection. The main and most common form of the disease is cerebral toxoplasmosis, which develops in AIDS patients in different countries in 340% of cases and is successfully (compared to other CNS infectious lesions) treatable [3, 1 1 ]. An acute or subacute onset is characteristic, the clinical picture is dominated by symptoms of focal encephalitis, indicating damage to the hemispheres, cerebellum, or brainstem [3, 6, 12].
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Convulsions of a focal or generalized nature, headache, fever, mental disorders are noted. Meningeal symptoms are rare [3, 12]. In 20-30% of patients, the composition of the CSF is normal, it is possible to increase the protein content to 1-2 g / l and above, two- and three-digit lymphocytic pleocytosis [3, 4]. Used to determine the antigen in the cerebrospinal fluid. Serological methods, as a rule, are not very informative [6]. On CT, it is possible to detect seals in the cortex, thalamus, and basal ganglia. The optimal imaging method in these cases is MRI [3, 6, 12].
Granulomatous acanthamoeba encephalitis is caused by the protozoan Acanthamoeba. spp. Characteristic signs - a violation of the psyche up to a change in personality, increasing headache, fever. Meningeal symptoms are mild or absent. The disease ends with the development of a cerebral coma. The diagnosis is confirmed by the detection of trophozoites or amoeba cysts in CSF during its cultivation.
The causative agent of non-Glerious meningoencephalitis is Naegleria fowleri. Meningoencephalitis occurs with an acute onset, severe headache, high body temperature, nausea and vomiting, severe meningeal and focal symptoms, generalized convulsions, purulent nature of the CSF, and death of the patient within 1 week from the onset of the disease [3].
Herpetic encephalitis in HIV-infected people is atypical. The disease begins subacutely and slowly progresses; a headache appears, meningeal symptoms increase, a change in personality gradually occurs. In some patients, however, a typical course of the disease is also possible: an acute onset, high body temperature, severe headache, symptoms of damage to the temporal lobe and cranial nerves, then impaired consciousness, coma and death. In the cerebrospinal fluid, nonspecific changes are usually found: increased protein content and lymphocytic pleocytosis.
CNS lesion caused by Varicella virus zoster, most often has the character of encephalitis. The main symptoms are headache, nausea, vomiting, ataxia, tremor, impaired consciousness. CNS damage may be cerebral vasculitis, multiple cranial nerve lesions, and myelopathy.
Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by one of the papovaviruses, the polyoma type C (Jakob-Creutzfelt) virus. PML in HIV infection can develop in about 4-5% of patients, and it is clinically manifested in 25% of them. The process develops over several weeks. The clinical symptoms of PML are changes in mental status, decreased visual acuity up to complete blindness, aphasia, hemiparesis, hemianesthesia, ataxia [3, 6], and pseudobulbar syndrome [4]. The disease progresses over several months [3]. CT and MRI reveal foci of demyelination in the hemispheres or in the substance of the brain of the posterior cranial fossa [4, 6]. Lethal outcome occurs within a year.
Cryptococcal meningitis is the most common fungal infection of the CNS in HIV infection and develops in 2-10% of patients [3, 4]. The disease has an acute course. The most common symptoms of the disease are headache, fever, nausea and vomiting. There may be meningeal symptoms, swelling of the nipple of the optic nerve, paralysis of the VI pair of cranial nerves. The level of CD4-lymphocytes is less than 0.1 X 109 / l. Laboratory diagnosis of infection is based on the detection of the pathogen in the blood, CSF, and urine and on the detection of antigen in high titers in these materials [3, 6]. MRI reveals hyperintense foci (in the basal ganglia, midbrain, cerebellum) that do not accumulate contrast agent, and hydrocephalus [4].
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Bacterial lesions of the CNS in HIV infection are relatively rare [3]. With HIV infection, CNS lesions caused by Escherichia, Listeria, meningococcus, nocardia, rochalimia, etc. are described. Treatment regimens for these lesions are similar to those for disseminated forms of the corresponding infections. Neurosyphilis is observed in about 1.5% of patients with AIDS, about 50% of patients with neurosyphilis are infected with HIV. Usually the picture develops in a more severe way meningitis with headache, fever and meningeal symptoms, possibly myelopathy and/or dementia. The definitive diagnosis of neurosyphilis depends on the identification of T. pallidum in the CSF.
Tumor lesions of the nervous system are represented by the following neoplasms: primary CNS lymphoma, systemic lymphoma with cerebral metastasis, less often Kaposi 's sarcoma. Cerebral lymphoma in patients with AIDS is an extranodal lymphomatous infiltration (B-cell lymphoma) with a high degree of malignancy. Most researchers associate the formation of cerebral lymphomas with the action of the Epstein- Barr virus. The clinical picture of a focal brain lesion has no specific symptoms. It is believed that the development of lymphomas is characteristic of the transition of HIV infection to the stage of AIDS [5].
Patients with HIV infection have a wide range of neurotic disorders: anxiety, asthenic, depressive syndromes and their combinations [13-15]. Hypochondriacal manifestations, maladaptive behavior in the form of rental attitudes are observed [15, 16]. The severity of the impairment of the functional state of the nervous system depends to a greater extent on the stage of HIV infection than on its duration [1,7].
Damage to the nervous system in children is associated with the direct effect of HIV on brain tissue cells [2]. Before the widespread use of combined ARVT, CNS lesions in HIV infection/AIDS occurred in 80-90% of children [6, 18].
Despite the general similarity of the course of HIV infection in children and adults, pediatric observations reveal a number of significant features. The clinical course and prognosis of the disease in children appear to be related to the route of infection. Secondary CNS infections in children are less common - in 10-12% of cases [19, 20]. Particularly severe diseases are caused by fungi (Aspergillus, Rhizopus) [2]. The disease in perinatal transmission is characterized by a more rapidly progressive course, as well as a higher frequency of bacterial infections [2, 3, 21]. With intrauterine infection, children are often born prematurely, with various neurological disorders. More than half of the children have a lag in psychophysical development, which is included in the structure of HIV embryofetopathy along with microcephaly, facial dysplasia, IUGR of the dysplastic type [2, 8, 22]. The specificity of embryofetopathy, however, is doubtful due to the possible influence of other pathological factors on the fetus [8]. Early progressive neurological symptoms, clinical manifestations of HIV at birth, developmental disorders, early onset of opportunistic diseases are signs of rapid progression of HIV infection in children during the first months of life [22, 23]. The main neurological manifestations in HIV-infected children are diverse: microcephaly, mental retardation, cognitive decline, pairs of a- and tetraparesis, hypertonicity, ataxia, limb tremor, pathological reflexes, pseudobulbar palsies, extrapyramidal rigidity, less often convulsive syndrome [3, 24]. The main feature of the clinical course of HIV infection in children is the delay in psychomotor development or even the loss of previously acquired skills, which is observed, according to various sources, in 50-90% of cases [3, 20, 24, 25]. Developmental delay is
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associated with HIV brain damage and is morphologically manifested by atrophy of brain structures [3, 24]. Intellectual disorders often precede motor ones [6]. HIV-infected children are also characterized by attention deficit hyperactivity disorder, in some cases without changes in intelligence [18].
In children with a more severe course of HIV infection and more pronounced immunological pathology, more deviations in the neurological status and psychomotor development are detected [26]. There is a correlation between clinical symptoms, including parameters of psychomotor development (mostly motor), EEG changes (diffuse slow waves in the background recording) and brain CT/MRI data (cortical atrophy, calcifications in the basal ganglia, signs of cerebral toxoplasmosis) [ 18, 24].
Tumor processes are rare, older children may develop B - lymphomas, and Kaposi 's sarcoma is extremely rare [6, 8].
In stage A, up to 84% of children have neurological disorders. More than half of the children are diagnosed with astheno -neurotic syndrome, which is expressed in a decrease in the ability for prolonged mental and physical stress and in cephalalgia [6].
At stage B (SB according to Pokrovsky V.I.), manifestations of HIV dementia are often found. The most frequently diagnosed syndrome in the structure of HIV/ AIDS infection is HIV-associated progressive encephalopathy, which is detected in 30-60% of HIV-infected children and adolescents. AIDS debuts in 18% of cases with the development of encephalopathy [6, 14, 23]. Progressive encephalopathy in children is morphologically similar to subacute encephalitis in adults [19]. The disease manifests itself as a progressive neuropsychological deficit with impaired speech, memory, learning, motor activity, slow reaction, depressive states change into delirium [6, 27]. Most children have a wide range of changes of mild to moderate severity: diffuse changes in the bioelectrical activity of the brain of regulatory and organic origin, a delay in the formation of the age-related rhythm, 23% have bilateral asymmetry and EEG asynchrony. At stage C, symptoms of damage to cortical functions dominate in children. The main neurological manifestations of AIDS are HIV encephalopathy with progressive impairment of intellectual development and increasing motor impairment due to degeneration of the pyramidal tracts [6]. Stage C is also characterized by significantly lower rates of cognitive development [28]. For neuroAIDS, convulsive syndrome is pathognomonic. Perhaps the development of polyneuropathy: increasing weakness in the distal limbs, muscle atrophy, hyporeflexia, hypesthesia in the distal limbs. Significant EEG changes are detected in more than half of the children, regulatory disturbances — in all. The changes are combined, the organic character prevails. There is a delay in the formation of the age-related rhythm. Focal changes are mainly represented by bursts of slow -wave activity. Variants of the norm are not registered [6].
As a result of the use of HAART (highly active antiretroviral therapy), a relative improvement in the neurological status and mental development in young children is possible [20, 26, 29]. Improvement in psychomotor development is one of the indicators for assessing the effectiveness of HAART (along with the assessment of physical development, immunological and virological parameters) [30].
Conclusions: The complexity of the problem of diagnosing and treating HIV infection in general and its neurological manifestations in particular should be emphasized. In order to
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improve the quality of life, it is necessary to further search for methods of early diagnosis and prevention of HIV infection in children. An important aspect of the rehabilitation of such patients is not only drug therapy, but also psychological and social assistance.
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