[Non-infectious neurological involvement in HIV-1 infection in children].
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Biomedical subjects
Publications and source records attributed to M Tardieu.
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DESIGN: Advances in neuroimaging have allowed correlations between radiological patterns and clinical features of brain malformations. This paper reports clinical, prognosis, and electroencephalographic features of six children with a previously unrecognised neuroimaging picture of unilateral widening and verticalisation of the sylvian fossa associated with an abnormal ipsilateral perisylvian cortex. RESULTS: All children had reduced hemisphere size and thalamostriatal hypoplasia ipsilateral to the cleft and hemiplegia. Cognitive development was mostly impaired. Epilepsy occurred in two patients and was mainly characterised by partial seizures. Studies with EEG showed hemispheric slowing of background activity homolateral to the perisylvian dysplasia. Occurrence of the malformation among their siblings was not found. CONCLUSION: Similar brain malformations occasionally reported in older patients confirm the clinical picture, sporadic occurrence, and prognosis found, allowing the validation of a unilateral perisylvian syndrome.
We diagnosed Cruetzfeldt-Jakob disease in 34 patients (16 definite, 18 probable) who had received human growth hormone extract for various period of time (mean +/- SD, 2.9 years), but particularly during the period between January 1984 and July 1985, a potential high-risk factor. Disease duration for deceased patients (n = 30) was 17 +/- 9 months. The clinical picture was homogeneous, starting with cerebellar ataxia and ocular motor disorders in about 90% of the patients. Neurologic deterioration, including dementia and myoclonic jerks, occurred within months. The high number of cases (1.5% of those treated between 1959 and 1988, 3% of those treated during the putative high-risk period) is still unexplained. We discuss the possibility that new cases will be detected,the risk of contaminating the general public, and the sanitary measures undertaken to prevent this.
Five children with human immunodeficiency virus type-1 (HIV-1) infection, aged 4 to 13 years, manifested extrapyramidal dysfunction characterized by rigidity/stiffness, ambulation difficulties/shuffling gait, dysarthria/drooling/swallowing dysfunction, hypomimetic/inexpressive facies, and bradykinesia. Levodopa therapy caused an initial improvement in all symptoms, and the effect was sustained in most patients. Levodopa is a useful adjunctive therapy in HIV-1-infected children with extrapyramidal syndromes, by enhancing motor function and improving their quality of life.
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Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which involves predominantly the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopical examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 HIV-positive asymptomatic cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 seronegative asymptomatic controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all the AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative appreciation of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. Experimental studies tend to support our in vivo findings. Infection by HIV of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.
The envelope glycoprotein gp120 of the human immunodeficiency virus HIV-1 has been proposed to cause neuron death in developing murine hippocampal cultures and rat retinal ganglion cells. In the present study, cultured human embryonic cerebral and spinal neurons from 8- to 10-week-old embryos were used to study the neurotoxic effect of gp120 and gp160. Electrophysiological properties as well as N-methyl-D-aspartate (NMDA)-induced current were recorded from neurons maintained in culture for 10-30 days. Neither voltage-activated sodium or calcium currents nor NMDA-induced currents were affected by exposure of neurons to 250 pM gp120 or gp160. In contrast, when neurons were subjected to photometric measurements using the calcium dye indo-1 to monitor the intracellular free Ca2+ concentration ([Ca2+])i, gp120 and gp160 (20-250 pM) potentiated the large rises in [Ca2+]i induced by 50 microM NMDA. The potentiation of NMDA-induced Ca2+ responses required the presence of Ca2+ in the medium, and was abolished by the NMDA antagonist D-2-amino-5-phosphonovalerate (AP5) and the voltage-gated Ca2+ channel inhibitor nifedipine. Moreover, exposure of a subpopulation of spinal neurons (25% of the cells tested) to 20-250 pM gp120 or gp160 resulted in an increase in [Ca2+]i that followed three patterns: fluctuations not affected by AP5, a single peak, and the progressive and irreversible rise of [Ca2+]i. The neurotoxicity of picomolar doses of gp120 and gp160 cultures was estimated by immunofluorescence and colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced gp120-induced toxicity by 70 and
Four continuous cell lines of human microglial cells were obtained by transfection of enriched cultures of human embryonic brain-derived macrophages with a plasmid encoding for the large T antigen of SV40. The transformed cells had the macrophagic characteristics of adherence and intra-cytoplasmic non-specific esterase activity. They could phagocytize zymosan particles but the phagocytic activity remained low. They expressed several macrophagic antigens but not the monocytic markers CD14, CD4, CD68/Ki-M6 and CD11c. The cells could be activated to express class II major histocompatibility complex antigens after interferon-gamma activation. Finally, interleukin-6 was produced spontaneously by the cells and this production was further increased after interleukin-1 alpha stimulation.
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Monocytes but not unstimulated lymphocytes adhered to human neurons and astrocytes in primary culture, as demonstrated by double labeling. The expression of VCAM-1 was higher on neurons than on astrocytes, whereas that of beta 1, alpha 1, alpha 2, alpha 4 and alpha 5 chains from the integrins and of ICAM-1 was identical on both types of cells. The expression on neurons of ICAM-1, but not of integrins, was up-regulated by exogenous tumor necrosis factor (TNF) alpha, interleukin (IL)-1 alpha and interferon (IFN)-gamma. The same was observed on astrocytes associated with a sharp increase in the expression of VCAM-1. Adhesion between monocytes and neurons or astrocytes was 80% inhibited by mAbs directed against the CR3 determinant on monocytes or against ICAM-1 on neural cells but not by any of the other mAbs against adhesion proteins that were tested. Finally, the level of endogenous production of IL-1 alpha and TNF alpha was greatly increased after the adhesion of monocytes to CNS cells.
BACKGROUND: Neuroradiological features of hypertensive encephalopathy are not yet well-known. PATIENTS AND METHODS: The clinical manifestations, neuroradiological aspects and treatment of four patients suffering from hypertensive encephalopathy were studied; special attention was paid to manifestations presented by one patient which appeared representative of the usual manifestations of hypertensive encephalopathy. RESULTS: The main clinical features were visual disturbances (n = 4); altered consciousness (n = 2) and seizures (n = 3). Visual disturbances resulted from cortical lesions (n = 4) associated with optic nerve damage and retinopathy (n = 2). Cerebral imaging showed low density images (CT scan) and hypersignal (MRI, T2 sequence) located in parieto-occipital cortical ribbon and adjacent white matter from the first 24 hours following the onset of neurologic symptoms. In the studied patient, the abnormal images resolved within 1 month after the onset of the disease. Unilateral infarction of the anterior visual pathway affected two patients in whom: 1) hypertension remaining undetected for a long time was revealed by neurological signs; 2) visual impairment was preceded by an hypotensive episode induced by antihypertensive therapy. CONCLUSIONS: Neuroradiological features of hypertensive encephalopathy are useful in establishing the diagnosis. A gradual reduction of blood pressure could prevent the risk of visual complications.
Thirty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1), who were born before 1985, were followed in a single center, and had reached the age of 6 years, were studied and tested for school achievement. Of these 33 children, 24 were also tested for cognitive abilities, fine motor and language skills, and emotional adaptation. Of the 33 patients, 22 (67%) had normal school achievement at a mean age of 9.5 +/- 1.6 years. The mean IQ was 95 +/- 11, but 54% of the patients (13/24) had abnormal results on visual-spatial and time orientation tests, 44% had speech and/or language delay or articulation disorders, and 29% of the children and 42% of the parents had psychoaffective disturbances of intermediate or high severity. Normal school performance was positively correlated with results of the different cognitive tests and to a lesser extent with the absence of psychoaffective symptoms, but was independent of the mode of maternal infection or the parents' educational level. Children with normal school achievement had a higher percentage of circulating CD4+ lymphocytes during the course of infection. We conclude that children whose HIV-1 infection is maternally acquired have better cognitive abilities and school achievement than was initially thought, and that the percentage of circulating CD4+ lymphocytes during the first years of life appears to be predictive of future school adaptation or cognitive abilities.
We report five children who had recurrent central nervous system signs after conventional acyclovir therapy for herpes simplex encephalitis. Secondary exacerbation was characterized clinically by severe ballismic movement disorder in all five children, associated with fever, impairment of consciousness, and seizures. Biologic analysis in all children and magnetic resonance imaging and neuropathology studies of the brain in three cases were compatible with inflammatory reaction. In contrast, all viral cultures remained negative, herpes simplex virus antigen in one child and DNA tested by polymerase chain reaction in four children were undetectable in the first samples of cerebrospinal fluid during the relapse, suggesting a postinfectious, immune-mediated mechanism of relapse in these patients.
We studied 43 children with extensive brain gyral anomalies diagnosed radiologically and defined by (a) the absence or paucity of sulci over cortical areas affecting at least two lobes in each hemisphere, and (b) the absence or reduction of interdigitation between gray and white matter. We correlated the clinical, EEG, and genetic findings with the imaging features. A seemingly homogeneous group of patients (group A, n = 30) presented a common imaging pattern characterized by four features: (1) a thickened neocortex, (2) widened lateral ventricles, (3) apparent verticalization and widening of sylvian fissures, and (4) bilateral and symmetric distribution of the abnormalities. Another group of patients (group B, n = 13) exhibited heterogeneous imaging anomalies, termed "nonlissencephalic brain malformation," differing in at least one of the following four ways from the radiologic criteria defining group A: absence of verticalization of sylvian fissures (n = 12), thin neocortex (n = 2), normal-size lateral ventricles (n = 2), and asymmetric brain defects (n = 3). In group A, some clinical features had a significantly lower frequency (p < or = 0.01) than in group B: microcephaly, a complete lack of postural development, and intractable epilepsy. There was a significant relationship, but only in group A, between the degree of gyral anomalies and the extent of neurodevelopmental delay. Some EEG patterns (rapid rhythms and delta-theta rhythms) were highly specific for the group A patients. There was lower risk of familial recurrence in group A (recurrence of convolutional anomalies was 3.5% of sibship in group A versus 44% of sibship in group B, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of the study is to compare normal PLC anatomy and its MRI appearance, with the various lesions observed in MRI, from the simple popliteus tendinous contusion to the complete PLC rupture. For this specific work on PLC lesions, we selected 61 examinations among the traumatic knees explored during the last 3 years. Surgical correlation is obtained for the 61 patients. MRI examinations are performed on a 0.5 T. unit with gradient echo T1, T1 and T1 GD-DOTA IV. Normal PLC anatomy is compared to the dissection of 4 anatomic subjects. Normal MRI slices are evaluated with this reference analysis. The principle anatomical structures of the PLC include the lateral collateral ligament, the popliteus tendon, the arcuate ligament, the fabello fibular ligament, the posterolateral condylar capsule, and the posterior horn of the lateral meniscus. Surgical findings confirm PLC lesion for 58 patients with 3 false positive. Diagnosis of these lesions is important because chronical posterolateral laxity is secondary to the destabilisation of lateral condyle. Unrecognised and untreated posterolateral instability may result in failure of ACL reconstruction. When clinical tests are doubtful or complex, or the examination very painful, MRI evaluates completely the traumatic knee and particularly the PLC.
UNLABELLED: The aim of this work was to study cerebral function in vertically infected children with human immunodeficiency virus 1 (HIV-1). METHODS: PET with 18F-labeled fluorodeoxyglucose (FDG) was performed in eight children (2.5-5.5 yr): three with severe neurological symptoms and five without. Quantitative analysis was based on gray matter cortical and subcortical regions of interest for which glucose utilization was measured. RESULTS: Diffuse hypometabolism and subcortical hypermetabolism were found in the three children with severe neurological signs; the five other children had temporo-occipital cortical hypometabolism, mainly on the right side. CONCLUSION: Functional cerebral abnormalities seem to precede clinical symptoms in HIV-1infection of the brain in children.
OBJECTIVE: To study the causes of stroke and cerebral infarcts in children infected with the human immunodeficiency virus (HIV)-type 1. DESIGN: Case series. PATIENTS: Four of 380 HIV-infected children followed up in a 10-year period in our department who had a stroke with evidence of cerebral infarcts on radiological imaging. RESULTS: The four patients were severely immunodepressed, but their clinical status and outcome were different. Aneurysmal dilation of major cerebral arteries and thrombosis of these arteries or of small cortical vessels were discovered in two patients. Both patients had a history of frequent infections and had suffered repeated neurological events that resulted in severe clinical deterioration or death. An infectious causative agent was strongly suspected but was not detected. The other two patients had a more favorable outcome. An isolated cerebrovascular thrombosis was found in one patient, while in the other, HIV-1-related focal necrosis was suggested by the lack of permanent cerebrovascular abnormalities or thrombosis and by signs of necrosis in biopsy specimens of the brain. CONCLUSION: Stroke and cerebral infarcts in HIV-1 infected children have different causes and different prognoses.
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