[Neurological complications of HIV-1 infection in an infant born to a seropositive mother].
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Brain Diseases↗
Biomedical subjects
M Tardieu
Publications and source records attributed to M Tardieu.
Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis.
We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS involvement early in the time course of HLH. Four additional patients who did not have initial CNS disease, who did not die early from HLH complications, and who were not transplanted, also developed a specific CNS disease. Therefore, all surviving and nontransplanted patients had CNS involvement. Initially, CNS manifestations consisted of isolated lymphocytic meningitis in 20 patients and meningitis with clinical and radiological neurological symptoms in nine patients. For these nine patients, neurological symptoms consisted of seizures, coma, brain stem symptoms, or ataxia. The outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor, as all died following occurrence of multiple relapses or CNS disease progression in most cases. Bone marrow transplantation (BMT) from either an HLA identical sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients, once first remission of CNS and systemic disease was achieved. Seven are long-term survivors including three who received an HLA partially identical marrow. All seven are off treatment with normal neurological function and cognitive development. In four other patients, BMT performed following CNS relapses was unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT appears, therefore, to be the only available treatment procedure that is capable of preventing HLH CNS disease progression and that can result in cure when performed early enough after remission induction.
Ataxia↗
Patterns of disclosure and perceptions of the human immunodeficiency virus in infected elementary school-age children.
OBJECTIVE: To investigate the patterns of disclosure and perceptions of human immunodeficiency virus (HIV) status in a group of HIV-infected elementary school-age children. DESIGN: A survey. SETTING: A referred care university hospital center. PATIENTS: All HIV-infected children born before August 31, 1985, and scheduled for ambulatory follow-up between 1984 and 1993 were eligible for the study. A total of 35 HIV-infected (21 asymptomatic and 14 symptomatic) elementary school-age children (aged 5-10 years) were examined between 1990 and 1993. MAIN OUTCOME MEASURES: Semistructured qualitative interviews were used, 1 with the children and 1 with their parents or caregivers. In addition, 3 drawings per child were also analyzed. RESULTS: Partial disclosure was observed in 14 (40%) of the children, and full disclosure of the diagnosis of acquired immunodeficiency syndrome was given to 6 (17%) of the children. Secrecy regarding serostatus was the strategy used by 15 (43%) of the parents or caregivers involving either complete nondisclosure (n = 8) or deception by means of attributing the symptoms to another condition, medical or other (n = 7). Perceived health status and clinical status differed for 11 (31%) of the children. Eight children did not identify any illness causality, and most of the others gave prelogical or concrete-logical explanations. Few children were aware of their parent's infection or disease. CONCLUSION: Human immunodeficiency virus-infected elementary school-age children were exposed to various disclosure patterns regarding their HIV infection or disease, and most children (26/35 [74%]) reported stressful experiences due to HIV regardless of the disclosure patterns.
Art↗
Human immunodeficiency virus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human neurons.
Detection of apoptotic neurons and microglial cells in the brains of human immunodeficiency virus type 1 (HIV-1)-infected patients has suggested that programmed cell death may be implicated in the physiopathology of HIV-1 encephalopathy. To analyze in vitro the intracellular signals induced by HIV-1 in human neurons and the associated neuronal death, we tested cultured human central nervous system (CNS) cells for apoptosis induced by HIV-1 and gp120 and for signaling pathways activated by gp120. HIV-1 and gp120 induced apoptosis of neurons and microglial cells but not of astrocytes or transformed microglial cells. Gp120 activated c-Jun N-terminal kinase (JNK) and p42 extracellular-regulated kinase (ERK) in primary CNS cells, with an early peak of activation at 2 to 5 minutes that was not present when pure microglial or astrocyte cultures were tested, followed by a late and sustained activation (10 and 60 minutes) in primary and enriched glial cell cultures as well as in transformed microglial cells. This demonstrates that gp120 could be an effector of HIV-1-induced apoptosis in the CNS and act directly on neuronal and glial cells.
AIDS Dementia Complex↗
[Central pontine myelinolysis: apropos of 2 case in children].
BACKGROUND: Central pontine myelinolysis has been rarely reported in children. This report concerns two children, aged 4 1/2 years. CASE REPORTS: The main clinical features were altered level of consciousness, tetraplegia and signs of brain stem dysfunctions. In both cases, magnetic resonance imaging (MRI) revealed hypersignal of protuberance in association with cerebellar lesion in one case and occipital lesion in the other, compatible with central and extrapontine myelinolysis. No underlying disease or electrolytic disorders was identified. Clinical outcome was good. Mental status was normal after 9 months for patient one and 4 months for patient two. The MRI abnormality was reduced at 9-month follow-up in patient two and unchanged at 4 months in patient one. CONCLUSION: The incidence of central pontine myelinolysis is probably underestimated in children. MRI allows a greater sensitivity in identifying areas of focal demyelination where diagnosis was previously only established by post mortem studies.
Brain↗
[Ischemic cerebral vascular accident caused by vertebral artery dissection].
BACKGROUND: Strokes due to vertebral artery lesions are not yet well known in children. CASE REPORT: We report on a case of post-traumatic vertebral artery dissection responsible for ischemic stroke in a 8-year old boy. Headache, vomiting and a brief loss of consciousness were the main initial signs. Neurological examination showed a locked-in syndrome. Cerebral imaging revealed lesions in cortical cerebellar hemisphere, cerebral pedoncular and protuberance. An arteriogram performed on day 10 showed left vertebral artery occlusion at C2 levels consistent with vertebral dissection. Antiagregants treatment was given. Neurological recovery was good. Pertinent clinical data of 24 children who had strokes due to a vertebral artery dissection are analysed. CONCLUSION: Vertebral artery dissection is presently a well-known cause of childhood strokes. Benefits from anticoagulants are now established.
Aortic Dissection↗
HIV-1 induces apoptosis in cultured human neurons and microglial cells but not in astrocytes.
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Apoptosis↗
Plasma exchange in Rasmussen's encephalitis.
The authors observed a 4-year-old girl who has Rasmussen's encephalitis. She started with frequent localized and generalized seizures. Standard antiepileptic treatment was almost ineffective. The frequency of the generalized seizures decreased, but the myoclonic jerks of the left part of the body persisted. An EEG showed partial status epilepticus. The results of the CT scan were normal. Antibodies to viruses were absent from the blood and cerebrospinal fluid. An MR scan showed a T2-weighted hypersignal zone in the right frontal region. Intravenous bolus injections of corticosteroids and drips of immunoglobulins were inefficient, and we started plasma exchanges which have continued for 9 months. The clinical state stabilized, and the images on the MR scan improved, but the results of the EEG did not improve. The authors discuss the effect of the plasma exchange, the use of which is questionable in this disease.
Brain↗
High dose methylprednisolone in severe acute transverse myelopathy.
No effective treatment has been shown for patients with acute transverse myelopathy. In an open study five children with severe acute transverse myelopathy were treated with intravenous methylprednisolone and compared with a historical group of 10 patients. The results show that in the methylprednisolone treatment group compared with the historical group of 10 patients: the median time to walk independently was significantly reduced (23 v 97 days); the proportion of patients with a full recovery within 12 months was significantly higher (80 v 10%); all patients had complete motor recovery within one year in contrast with only two of 10 patients in the historical group; and serious adverse effects did not occur. This pilot study suggests that high dose methylprednisolone is effective in the treatment of acute transverse myelopathy.
Acute Disease↗
[Cystic compression of the suprascapular nerve. Value of imaging. Apropos of 6 cases and review of the literature].
Six cases of suprascapular nerve entrapment by a ganglion cyst within the spinoglenoid notch or developed from the glenoid labrum are reported. Causes of injury or entrapment of the suprascapular nerve are described including traction or kinking of the nerve, trauma, repetitive exercise, or compression by ganglion cyst. The patients had non specific pain, weakness, and atrophy of the spinatus musculature. Electromyography showed evidence of denervation atrophy. Patients had plain radiographs, arthrography, CT-arthrography, magnetic resonance imaging (MRI) and MR-arthrography. Masses that caused suprascapular nerve entrapment were well localized and characterized wit magnetic resonance imaging, reflecting the superior soft-tissue contrast of this modality. In addition, MRI may demonstrate atrophy of the spinatus muscles. MR-arthrography allows to visualize lesions of the glenoid labrum and in some cases, demonstrates cysts filling.
Adult↗
[Experimental study of mechanisms of neuronal death in the course oh HIV infection].
The HIV1 virus and its envelope glycoprotein gp120 are toxic for human neurones in vitro. This neurotoxicity is, at least partially, of an apoptotic nature, resulting from the interaction of gp120 with the neuronal membrane which leads to perturbations of intracellular signaling systems. These latter bring about on the one hand a raising of [Ca2+]i partly due to the potentiation of the NMDA receptor response to endogenous glutamate and on the other hand the activation of certain MAP kinases (ERK and JNK) which lead to the initiation of the cell death program.
Acquired Immunodeficiency Syndrome↗
[Physiopathology of with HIV-1-related cerebral involvement].
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AIDS Dementia Complex↗
[Neuronal apoptosis in the central and peripheral nervous system in HIV infection].
Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which predominantly involves the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopic 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 asymptomatic HIV-positive cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 asymptomatic seronegative controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative assessment 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. We also looked for apoptotic neurons in spinal ganglia of 20 AIDS cases, 5 of whom had a terminal sensory distal neuropathy, and 10 seronegative controls devoid of neuropathy. Apoptotic neurons were found in 6 of the AIDS patients and in none of the seronegative controls. However, no correlation was found between the severity of neuronal apoptosis in the spinal root ganglia and the presence of absence of a terminal distal sensory neuropathy. Experimental studies tend to support our in vivo findings. HIV-infection of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.
AIDS Dementia Complex↗
Transmural endothelialization of vascular prostheses is regulated in vitro by Fibroblast Growth Factor 2 and heparan-like molecule.
Endothelialization of vascular prostheses may result from transmural migration of endothelial cells. Angiogenesis is controlled by growth factors like Fibroblast Growth Factor 2 (FGF2) and regulators like heparan-like molecules. To that end, we used heparan-like molecules named RGTA for ReGeneraTing Agent. The RGTA11 used was a chemically derived dextran obtained by successive substitutions with carboxymethyl, benzylamide, and benzylamide sulfonate groups on glucose residues. This agent was further selected for its ability to bind, stabilize and protect FGF2. We defined firstly the angiogenic capability of FGF2 in combination with RGTA11 on bovine aortic endothelial cells (BAEC) cultured on collagen I gels. Secondly, the role of FGF2 and RGTA11 in transmural endothelialization was assessed in a three-dimensional in vitro model using a polyethylene terephtalate prosthesis included in collagen gel. BAEC seeded on the external face can migrate to the luminal face of the prosthesis. Microscopic and histological evaluations were performed at 4 and 7 days. Results showed that the addition of RGTA11 alone did not promote angiogenesis while FGF2 alone did. However, RGTA11 combined with FGF2 produced a significant acceleration in angiogenesis compared to FGF2 alone. This combination magnifies and enhances the angiogenic processes leading to endothelialization of luminal face through transmural cellular migration. Our data demonstrates that in vitro transmural endothelialization of porous vascular prostheses by BAEC cultured on collagen I gels is upregulated by RGTA11 combined with FGF2.
Animals↗
Endogenous nitric oxide activates prostaglandin F2 alpha production in human microglial cells but not in astrocytes: a study of interactions between eicosanoids, nitric oxide, and superoxide anion (O2-) regulatory pathways.
Secretion of the eicosanoids, nitric oxide (NO.) and superoxide anion (O2.-) was evaluated in human embryonic astrocytes and microglia. An inducible form of cyclo-oxygenase (COX 2) was demonstrated in astrocytes and microglia after IL-1 beta plus IFN-gamma stimulation; since 1) large amounts of PGF2 alpha were released; 2) PGF2 alpha secretion required protein synthesis and was blocked by indomethacin; and 3) the response was delayed and persistent. Using the same inducers, astrocytes, but not microglial cells, produced NO. and had an inducible form of nitric oxide synthase. Conversely, microglial cells were induced by IL-1 beta and IFN-gamma to generate superoxide anions (O2.-) through an NADPH oxidase-dependent pathway. We then investigated interactions between these different pathways of synthesis by inhibition experiments. The cytokine-induced production of PGF2 alpha in astrocytes was not affected by exposure to N-omega-monomethyl-L-arginine, which inhibits NO. production, whereas it was reduced by 40% in microglia. Since microglia did not secrete any detectable NO. in their supernatant, intracellular production of NO. could occur in these cells that positively regulated PGF2 alpha production. Exposure to indomethacin, which prevented PGF2 alpha production in both astrocytes and microglia, resulted in a 64% increase in cytokine-induced NO. production by astrocytes and a 70% inhibition of O2.- generation by stimulated microglia. Finally, superoxide dismutase depletion of O2.- in astrocytes and microglia had no effect on PGF2 alpha production in these cells. These results demonstrate that there are important interactions between the pathways of synthesis of inflammatory mediators in glial cells that could unveil additional regulatory mechanisms.
Astrocytes↗
Triggering of CD23b antigen by anti-CD23 monoclonal antibodies induces interleukin-10 production by human macrophages.
The aim of this study was to evaluate the capacity of human macrophages to produce interleukin (IL)-10 upon stimulation of membrane CD23. An anti-CD23 monoclonal antibody (mAb) was found to elicit the expression of the specific mRNA for IL-10 in CD23-bearing macrophages, and to induce a time-dependent production of this cytokine with a maximal effect reached after 12 h. Inasmuch as we previously reported that CD23 ligation evoked the generation of nitric oxide and of cAMP, the effect of the Rp diastereoisomer of adenosine 3', 5'-cyclic phosphorothioate (Rp-cAMP, an inhibitor of the cAMP pathway) and of NG-monomethyl-L-arginine (L-NMMA, an inhibitor of the nitric oxide pathway) were evaluated on CD23-induced IL-10 production. In the presence of Rp-cAMP, the CD23-induced production of IL-10 and of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was totally abrogated, whereas, in the presence of L-NMMA, IL-10 production was enhanced and TNF-alpha production was suppressed. In addition, neutralization of IL-10 with an anti-IL-10 mAb increased both the magnitude and duration of CD23-driven TNF-alpha production. Such an inducing effect was observed with different anti-CD23 mAb (clone 135, MHM6 and 25), indicating that the triggering of the CD23 molecule at the surface of human macrophages induced the generation of IL-10 through a cAMP-dependent mechanism. Concomitantly this generation of IL-10 was down-regulated by nitric oxide, which was also produced after triggering of the CD23 antigen. Taken together these data indicated that human macrophages produced IL-10 after triggering of the CD23 molecule and that this production could regulate the inflammatory state of these cells.
Base Sequence↗
Interleukin-13 and interleukin-4 act as interleukin-6 inducers in human microglial cells.
The effect of interleukin 4 (IL-4) and IL-13 on IL-6 and IL-1 beta production by human embryonic microglial cells and human peripheral blood monocyte cells (PBMC) was compared. IL-4 or IL-13 increase intra-cellular IL-6 mRNA and IL-6 titres in supernatants of microglial cells whereas they decreased IL-6 production by PBMC tested in the same conditions. IL-4 and IL-13 increased also IL-1 beta production by human microglial cells. Stimulations associating IL-4 or IL-13 and IL-1 beta had an additive effect on IL-6 production by microglial cells, whereas, in the same conditions, an inhibitory effect was observed in PBMC. In contrast, dexamethasone downregulated IL-6 production by microglial cells and PBMC. Finally, IL-1 receptor (IL-1r) type 1 and IL-1r type 2 were detected on human microglial cells but it was demonstrated that IL-13 and IL-4 acted as IL-6 inducers in human microglial cells independently of the IL-1/IL-1r pathway.
Cells, Cultured↗
[The brain in children and the human immunodeficiency virus (HIV-1)].
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AIDS Dementia Complex↗