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Brief Reports Indian Pediatrics 2003; 40:230-234 |
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Neurological Manifestations of HIV Infection |
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Globally, there has been a rise in the incidence of HIV infection over the past decade(1). Organ-involvement in HIV has been well described. However, the diag- nosis of HIV-encephalopathy is made un-commonly. Progressive and static encephalo-pathy with cognitive, behavioral and motor manifestations has been described in HIV-infected children. The present study was undertaken to analyze the neurological manifestations and neuroimaging features in children with HIV infection. Subjects and Methods This study was carried out in a tertiary care teaching hospital. The case records of HIV-infected children with neurological manifesta-tions admitted in the 24-month period begin-ning from January 2000 were analyzed. HIV infection was diagnosed on the basis of seropositivity in two different EL1SA antibody tests. The cases were diagnosed to have HIV encephalopathy on the basis of CDC revised classification system(2): presence of one or more progressive neurological findings for at least two months (in the absence of other identifiable causes) from amongst the following: failure to attain or loss of milestones or of intellectual ability, verified by standard, developmental scale or neuropsycho-logical tests; Impaired brain growth or acquired micro-cephaly as demonstrated by head circum-ference measurements or brain atrophy on CT scan/MRI with serial imaging in children less than two years of age; acquired symmetric motor deficits with two or more of the following: paresis, pathologic reflexes, ataxia or gait disturbance. The clinical history and examination findings and investigations including features on neuroimaging were recorded. Results Eight patients (13.8%) fulfilling the diagnostic criteria for HIV encephalopathy from amongst 58 HIV-antibody positive patients admitted in 24 months were enrolled in the study. Seven of these were males. The youngest child was one year old while the oldest was ten years old. HIV infection was confirmed on the basis of PCR test in the child aged one year. In seven children, the infection was acquired perinatally, while the mode of transmission could not be ascertained in one child. None of these eight patients were previously diagnosed to have HIV infection. The details of the clinical manifestations and investigations in these eight children are presented in Tables I and II. The fundus examination was normal in all the cases. The Mantoux test was negative in all the patients. Sputum examination and or gastric lavage examination done in four patients with pneumonia/ bronchopneumonia were negative for acid-fast bacilli. Chest radio-graphic abnormalities were seen in four patients while cardiomyopathy was diagnosed on color doppler examination in one patient. Other CNS infections were ruled out on the basis of relevant investigations that included cerebrospinal fluid (CSF) studies (normal in all the patients), CSF India ink preparation for cryptococcus (negative in all the patients) and CSF fungal culture (negative in all the patients). Serological studies for cytomegalo-virus and toxoplasma could not be done. The results of neuroimaging studies (CT scan/ MRI) are presented in Table II. Table I__Clinical Manifestations in Patients with HIV Encephalopathy
Table II__Investigations in patients with HIV encephalopathy
Discussion HIV encephalopathy is a known clinical entity. However, there are hardly any reports of this condition in the Indian literature. Most studies reported from India have identified growth failure, diarrhea, lymphadenopathy, hepatomegaly, splenomegaly and opportun-istic infections as the predominant presenting features of HIV infection. Our study has demonstrated that HIV encephalopathy can be a presenting feature in HIV-infected children. The true incidence of central nervous system involvement is not known, although it is thought to occur in most HIV- infected children(3) and its incidence in children is at least three times more than that in adults(4). HIV encephalopathy is especially common in HIV-infected children who present in early infancy and have rapid downhill course(3). The risk of HIV encephalopathy is also correlated directly with the severity of HIV-related symptoms, depression of CD4+ counts and p24 antigen levels in the mother(3). The cumulative incidence of HIV-1-related encephalopathy at 7 years post- infection was noted to be 16% in children and the incidence of encephalopathy was 9.9% in the first year of life, 4.2% in the second year and less than 1% per year thereafter(4). This underscores the fact that HIV encephalopathy can occur very early in the course of HIV infection and that 88.1% of children who develop ence-phalopathy do so within first two years of life. The virus probably enters the CNS through infected macrophages(3). The neuro-logical manifestations may be effected through the direct effects of the virus or through cells of macrophage lineage and toxic cytokines(3). Developmental delay (motor as well as cognitive) is a common feature. The encephalopathy may manifest suddenly as a loss of attained milestones or failure to attain new milestones. This may be interspersed with periods of relative stability or rapid deterioration(3). Other neurological mani-festations include pyramidal tract involve-ment (spastic paraparesis, hypertonicity, hyperreflexia), static encephalopathy with developmental delay without loss of previously attained milestones, progressive encephalopathy with progressive deteriora-tion of milestones and skills, acquired microcephaly, seizures, behavioral decline and cerebral arteriopathy with intracerebral aneurysms(3,5,6). Our case series also reveals a variety of neurological manifestations of HIV infection. Loss of vision seen in two patients in our series could be related to development of lesion in visual cortex of the brain or optic neuritis. Although most affected children do not have an identifiable pathogen other than HIV, other CNS processes like opportunistic infections, inflammatory disease, vascular disease or neoplastic process can cause ence-phalopathy(2). Diffuse cortical atrophy, attenuation of white matter, ventricular dilata-tion, intra- cerebral calcification (especially in the basal ganglia), etc. seen in our series, have also been noted in other series(2,5,7). CSF studies are required for diagnosing opportunistic infections and neoplasms(2). Abnormalities in neurophysiologic tests like the EEG and BAEP have been shown to be reliable tools for the diagnosis of HIV ence-phalopathy(8). In a study, the severity of cortical atrophy appeared to reflect the level of viral load in the CSF while such an association was not observed with intracerebral calci-fications, suggesting a different neuro-pathologic process(9). The presence of hepatomegaly, spleno-megaly, or lymphadenopathy in the first 3 months of life and increased viral load increase the likelihood of development of HIV-encephalopathy(2). In the early postnatal period, high viral load (>5 log10 copies/mL) and lower CD8+ T-lymphocyte percentage (<20% CD8+ T-lymphocytes) have a higher risk of developing neurological impair-ment(10). Being a manifestation of advanced disease, encephalopathy increases the risk of death 28-fold(2). Over half of the patients succumb to the illness within 3 years of diagnosis and the median survival rate in patients with HIV-encephalopathy is about 11 months from the diagnosis(3). Though we tried to exclude all the possible opportunistic infections presenting with neurological manifestations in HIV infected patients, all the laboratory tests (especially the serological investigations) could not be performed. Hence, our cases could be considered to have neurological manifesta- tions of HIV infection with strong possibility of HIV encephalopathy. Our study has demonstrated that CNS manifestations can be a presenting feature of HIV infection in children. One should suspect HIV infection in children presenting with neurological mani-festations and growth failure. The involvement of other organ systems is variable and CNS involvement may be the solitary manifestation of HIV infection. Absence of other systemic features of HIV infection does not eliminate the possibility of HIV-encephalopathy. Hence, one should undertake diagnostic study for HIV infection in a child with unexplained neurological abnormality. Pediatricians will have to be alert to the possibility of HIV as an etiological agent in infants and children presenting with mental subnormality and unexplained neurological deficits. Acknowledgement The authors thank Dr. N.A. Kshirsagar, Dean, Seth G.S. Medical College and KEM Hospital, Mumbai for granting permission to publish this manuscript. Contributors: VSU, MST and VBS participated in data collection, analysis and drafting the paper. SBB and JRK participated in data analysis and interpretation, supervision of data collection and revision of the manuscript and will act as Guarantors for the said manuscript. PRH participated in data collection, reporting the CT scans and MRIs and revised the manuscript. Funding: None. Competing interests: None declared.
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