PubMed Health⌕ Search

Biomedical subjects

A Legido

Publications and source records attributed to A Legido.

At least 19 recordsLinked to original sources
PubMed2004

Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature.

Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.

Acyclovir↗
PubMed2003

Hypoxia-induced caspase-3 activation and DNA fragmentation in cortical neurons of newborn piglets: role of nitric oxide.

Hypoxia results in generation of nitric oxide (NO) free radicals, activation of caspase-3, and genomic DNA fragmentation. The present study tests the hypothesis that hypoxia-induced caspase-3 activation and DNA fragmentation are nitric oxide mediated. Studies were conducted in newborn piglets, divided into normoxic (n = 5), hypoxic (n = 5), and hypoxic-7-NINA (n = 6). Hypoxic-7-NINA group received the neuronal nitric oxide synthase inhibitor, 7-Nitroindazole (7-NINA). Caspase-3 activity was determined spectrofluorometrically using enzyme-specific substrates. Sections from the neocortex were stained with an antiserum recognizing active caspase-3. Purified DNA was separated by gel electrophoresis. Administration of 7-NINA resulted in decreased immunoreactivity of caspase-3 (mean LI: 20.2%) as compared to the untreated hypoxia group (mean LI: 57.5%) (P < 0.05). 7-NINA attenuated caspase-3 enzymatic activity as well in comparison to the untreated hypoxia group (P < 0.05). Furthermore, multiple low molecular weight bands corresponding to DNA fragments were present in the hypoxic but not in the normoxic or hypoxic-7-NINA groups. Inhibition of nNOS abates the hypoxia-induced increase in active caspase-3 immunoreactivity, as well as enzymatic activity in cortical neurons, and DNA fragmentation in brain homogenates. We conclude that the coordinate increase of capase-3 activity and fragmentation of nuclear DNA in the hypoxic newborn piglet brain are NO mediated.

Adenosine Triphosphate↗
PubMed2001

Acute hypoxia-induced alterations of calbindin-D28k immunoreactivity in cerebellar Purkinje cells of the guinea pig fetus at term.

Purkinje cells (PCs) are vulnerable to hypoxic/ischemic insults and rich in calcium and calcium-buffering/sequestering systems, including calcium-binding proteins (CaBPs). Calbindin-D28k is an EF-hand CaBP, which is highly expressed in PCs where it acts primarily as a cellular Ca++ buffer. Elevation of [Ca++] in the cytosol and nuclei of PCs is pivotal in hypoxic/ischemic cell death. We hypothesize that hypoxia results in decreased concentration, or availability of calbindin-D28k in PCs, thereby decreasing their buffering capacity and resulting in increase of intracellular and intranuclear [Ca++]. Cerebellar tissues from normoxic fetuses were compared to fetuses obtained from term pregnant guinea pigs exposed to hypoxia [7% FiO2] for 60 min. The pregnant guinea pigs were either killed upon delivery immediately following hypoxia (Hx0h) or were subsequently allowed to recover for 24 h (Hx24h) or 72 h (Hx72h). Fetal brain hypoxia was documented biochemically by a decrease in brain tissue levels of ATP and phosphocreatine. Compared to normoxic fetuses, there is a predominantly somatodendritic loss or decrease of calbindin-D28k immunohistochemical staining in PCs of Hx0h (p < 0.005), Hx24h (p < 0.05), and Hx72h (p < 0.005) fetuses. Hypoxia-induced alterations of calbindin-D28k immunoreactivity are qualitatively similar at all time points and include a distinctive intranuclear localization in subpopulations of PCs. A similar trend is demonstrated by immunoblotting. Subpopulations of TUNEL+/calbindin-D28k- PCs lacking morphologic features of apoptosis or necrosis are demonstrated in Hx24h and Hx72h fetuses. The present study demonstrates an abrogating effect of perinatal hypoxia on calbindin-D28k immunoreactivity in cerebellar PCs. The perturbation of this Ca++ buffer protein in hypoxia-induced neuronal injury may herald delayed cell death or degeneration.

Acute Disease↗
PubMed2001

Presence of oligoclonal T cells in cerebrospinal fluid of a child with multiphasic disseminated encephalomyelitis following hepatitis A virus infection.

We have investigated the clonality of beta-chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified beta-chain TCR transcripts by nonpalindromic adaptor (NPA)-PCR-Vbeta-specific PCR. TCR transcripts from only five Vbeta families (Vbeta13, Vbeta3, Vbeta17, Vbeta8, and Vbeta20) were detected in CSF. The amplified products were combined, cloned, and sequenced. Sequence analysis revealed in the CSF substantial proportions of identical beta-chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major Vbeta13.3 Dbeta2.1 Jbeta1.3 clonal expansion. Six of 35 (17%) transcripts were also 100% identical, revealing a second Vbeta13 clonal expansion (Vbeta13.1 Dbeta2.1 Jbeta1.2). Clonal expansions were also found within the Vbeta3 family (transcript Vbeta3.1 Dbeta2.1 Jbeta1.5 accounted for 5 of 35 transcripts [14%]) and within the Vbeta20 family (transcript Vbeta20.1 Dbeta1.1 Jbeta2.4 accounted for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infection with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myelin basic protein-reactive T-cell clones. In contrast, all Vbeta TCR families were expressed in peripheral blood lymphocytes. Oligoclonal expansions of T cells were not detected in the peripheral blood of this patient. It remains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.

Amino Acid Sequence↗
PubMed2001

Aberrant localization of the neuronal class III beta-tubulin in astrocytomas.

BACKGROUND: The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of betaIII in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of this isotype in certain nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is associated with anaplastic potential. OBJECTIVE: To test the generality of this observation, we investigated the immunoreactivity profile of betaIII in astrocytomas. DESIGN: Sixty archival, surgically excised astrocytomas (8 pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-betaIII monoclonal (TuJ1) and polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) was used as a marker for cell proliferation. Antibodies to glial fibrillary acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used as glial and neuronal markers, respectively. RESULTS: The betaIII immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile range [IQR], 20%-47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%-21%) (P <.0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%-0.5%) (P <.0001 vs high-grade astrocytomas; P <.01 vs diffuse fibrillary astrocytomas). A highly significant, grade-dependent relationship was observed between betaIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for betaIII (betaIII, P <.006; Ki-67, P <.0001). There was co-localization of betaIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. CONCLUSIONS: In the context of astrocytic gliomas, betaIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of betaIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, betaIII expression is not neuron specific, calling for a cautious interpretation of betaIII-positive phenotypes in brain tumors.

Adolescent↗
PubMed2000

West syndrome in tuberous sclerosis complex.

West syndrome occurs commonly in children with tuberous sclerosis complex and is associated with a grave prognosis for cognitive and seizure outcomes. We sought to determine the epilepsy outcome of children with tuberous sclerosis complex and West syndrome and whether EEG, MRI, or steroid therapy duration were different in those whose epilepsy improved compared with those with intractable seizures. Seventeen patients with tuberous sclerosis complex and West syndrome were identified. For each patient, two sets of clinical evaluations, EEG and MRI data, and treatment information separated by at least 12 months were obtained. The patients were divided into two seizure outcome groups. EEG, MRI, and treatment data were compared between the groups. The intellectual deficiency was either severe (76%) or moderate (24%). Seizure control improved in 10 and worsened in seven, without mortality (follow-up range = 12-216 months). No significant differences in EEG background, MRI findings, or steroid treatment duration were evident between the groups. The difference in EEG-sleep approached statistical significance (P = 0.06). Our findings did not confirm reports of high mortality and poor epilepsy outcome in intellectually deficient children with West syndrome and tuberous sclerosis complex. EEG sleep was the best indicator of seizure control and approached statistical significance. The duration of steroid therapy had no influence on seizure control.

Adolescent↗
PubMed2000

Comparison of MRI and MRA findings in children with a variety of neurologic conditions.

The role of MRA in the evaluation of children is evolving. We compared MRA and MRI in children with a variety of neurologic conditions to determine when MRA provides positive, cost-beneficial information. A total of 114 patients were retrospectively studied. MRA and MRI were performed and compared. MRA was abnormal in 34 (30%) of 114 patients: five (83%) of six with Menkes' disease, four (33%) of 12 with sickle cell disease, 12 (38%) of 32 with vascular malformations, one (6%) of 17 with headaches, seven (24%) of 24 with new focal deficits, one (10%) of 10 with seizures, and four (31%) of 13 with miscellaneous diagnoses. MRA and MRI were concordant in 73 (64%) of 114. Maximum concordance was in patients with Menkes' disease (100%) and minimum in those with new focal deficits (50%). The best MRA cost/benefit ratios were obtained in patients with Menkes' disease, vascular malformations, and sickle cell disease. A normal MRI usually forecasted a normal MRA. However, abnormal MRI findings did not always predict MRA abnormalities. Positive, cost-beneficial information is provided by MRA mostly in conditions known to involve the cerebral vasculature. Indications to perform MRA should be based on the neurologic diagnosis and MRI findings.

Adolescent↗
PubMed2000

Long-term computer-assisted outpatient electroencephalogram monitoring in children and adolescents.

The aims of this study were (1) to define the role of long-term computer-assisted outpatient electroencephalographic monitoring (COEEG) in children and adolescents with known or suspected epilepsy, and (2) to compare COEEG data with routine interictal electroencephalograms (EEG). We performed 18-channel COEEG in 84 children and adolescents with diagnosed (group 1, n = 49) or suspected (group 2, n = 35) epilepsy. Mean recording time was 1.4 days. Overall, COEEG was useful in 87% of patients. In group 1, events were recorded in 73% of patients and were electrographic seizures in 45%. In group 2, events were detected in 86% of patients and were electrographic seizures in 17%. Nocturnal and partial seizures predominated. Seizure diagnosis and classification by COEEG was concordant with interictal EEG findings in 19% and discordant in 63% of patients. COEEG is a useful technique for the diagnosis of epileptic and nonepileptic events among selected children and adolescents. When compared to routine interictal EEG, COEEG could offer additional accuracy in the classification of seizures in pediatric patients.

Adolescent↗
PubMed2000

Tuberous sclerosis complex and epilepsy: prognostic significance of electroencephalography and magnetic resonance imaging.

Tuberous sclerosis complex is a disease that affects many organs, including the central nervous system. Nervous system involvement in the form of hamartomas often results in seizures. In this study we wanted to determine the outcome of epilepsy in tuberous sclerosis complex and determine whether interictal electroencephalograms (EEGs) and hamartoma burden as seen with magnetic resonance imaging (MRI) are predictive of degree of seizure control. The study population consisted of 30 patients. For each patient two sets of EEG and MRI data, separated by at least 12 months, and information on seizure frequency at time of data collection were obtained. Sensitivity, specificity, and positive and negative predictive values of various EEG and MRI findings were determined. Seizure control improved in 20 and worsened in 10 patients. In relation to seizure control, the specificity of an abnormal sleep EEG and the positive predictive value of normal sleep EEG were 100%. MRI and EEG background were neither sensitive nor specific for predicting seizure control. A majority of children with tuberous sclerosis complex can achieve good seizure control. The sleep EEG is helpful in predicting eventual seizure control.

Brain Diseases↗
PubMed1999

Angiocentric CD3(+) T-cell infiltrates in human immunodeficiency virus type 1-associated central nervous system disease in children.

A significant proportion of brain tissue specimens from children with AIDS show evidence of vascular inflammation in the form of transmural and/or perivascular mononuclear-cell infiltrates at autopsy. Previous studies have shown that in contrast to inflammatory lesions observed in human immunodeficiency virus type 1 (HIV-1) encephalitis, in which monocytes/macrophages are the prevailing mononuclear cells, these infiltrates consist mostly of lymphocytes. Perivascular mononuclear-cell infiltrates were found in brain tissue specimens collected at autopsy from five of six children with AIDS and consisted of CD3(+) T cells and equal or greater proportions of CD68(+) monocytes/macrophages. Transmural (including endothelial) mononuclear-cell infiltrates were evident in one patient and comprised predominantly CD3(+) T cells and small or, in certain vessels, approximately equal proportions of CD68(+) monocytes/macrophages. There was a clear preponderance of CD3(+) CD8(+) T cells on the endothelial side of transmural infiltrates. In active lesions of transmural vasculitis, CD3(+) T-cell infiltrates exhibited a distinctive zonal distribution. The majority of CD3(+) cells were also CD8(+) and CD45RO+. Scattered perivascular monocytes/macrophages in foci of florid vasculitis were immunoreactive for the p24 core protein. In contrast to the perivascular space, the intervening brain neuropil was dominated by monocytes/macrophages, microglia, and reactive astrocytes, containing only scant CD3(+) CD8(+) cells. Five of six patients showed evidence of calcific vasculopathy, but only two exhibited HIV-1 encephalitis. One patient had multiple subacute cerebral and brainstem infarcts associated with a widespread, fulminant mononuclear-cell vasculitis. A second patient had an old brain infarct associated with fibrointimal thickening of large leptomeningeal vessels. These infiltrating CD3(+) T cells may be responsible for HIV-1-associated CNS vasculitis and vasculopathy and for endothelial-cell injury and the opening of the blood-brain barrier in children with AIDS.

AIDS Dementia Complex↗
PubMed1998

Inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis.

We have examined the localization of inducible nitric oxide synthase (iNOS) and nitrotyrosine (the product of nitration of tyrosine by peroxynitrite, a highly reactive derivative of nitric oxide [NO]) in demyelinating lesions from (i) two young adult patients with acute multiple sclerosis (MS), (ii) a child with MS (consistent with diffuse sclerosis), and (iii) five adult patients with chronic MS. Previous reports have suggested a possible correlation between iNOS, peroxynitrite, related nitrogen-derived oxidants, and the demyelinating processes in MS. We have demonstrated iNOS-immunoreactive cells in both acute-MS and diffuse-sclerosis-type lesions. In acute-MS lesions, iNOS was localized in both monocytes/macrophages and reactive astrocytes. However, foamy (myelin-laden) macrophages and the majority of reactive astrocytes were iNOS negative. In specimens from the childhood MS patient, iNOS protein was present only in a subpopulation of reactive or hypertrophic astrocytes. In contrast, no iNOS staining was detected in chronic-MS lesions. Immunohistochemical staining of acute-MS lesions with an antibody to nitrotyrosine revealed codistribution of iNOS- and nitrotyrosine-positive cells, although nitrotyrosine staining was more widespread in cells of the monocyte/macrophage lineage. In diffuse-sclerosis-type lesions, nitrotyrosine staining was present in hypertrophic astrocytes, whereas it was absent in chronic-MS lesions. These results suggest that NO and nitrogen-derived oxidants may play a role in the initiation of demyelination in acute-MS lesions but not in the later phase of the disease.

Acute Disease↗
PubMed1998

Rasmussen encephalitis: complementary role of multitechnique neuroimaging.

Rasmussen encephalitis is a chronic, progressive inflammation of the brain of unknown origin. Early diagnosis and treatment with immunoactive agents and/or hemispherectomy are sought to prevent the progressive cognitive decline that accompanies this disease. Combined anatomic and functional neuroimaging may serve to focus the diagnostic workup and to hasten brain biopsy for definitive diagnosis. Two biopsy proved cases of Rasmussen encephalitis are presented. The importance of MR imaging, single-photon emission computed tomography, and proton MR spectroscopy in the workup of this disease is discussed.

Child↗
PubMed1997

[Intrauterine exposure to drugs].

The development of the fetal central nervous system can be effected by drugs. In this paper we review the neurological consequences of intrauterine exposure to alcohol, cocaine, opiates and marijuana. Ethanol causes the fetal alcohol syndrome: mental retardation, intrauterine and postnatal growth retardation, and peculiar dysmorphic features. Is pathogenesis has been explained on the basis of maternal nutritional deficiencies or due to abnormalities in the conversion of ethanol to aldehyde, or abnormalities in the metabolism of prostaglandins or retinoic acid, the neurotransmitter systems, the neuronal excitotoxic activity, the development of the white matter, the production of gangliosides, and/or genetic regulation cell-cell adhesion. Cocaine has been related to congenital malformations, neurologic abnormalities during the neonatal period and psychomotor and cognitive development deficits. Characteristic dysmorphic features and a higher incidence of the sudden infant death syndrome (SIDS) have also been described. The following mechanisms have been implicated in the pathogenesis: vascular effects, superoxide formation, chelation of calcium ion channels, and abnormalities in the production of glycosphingolipids, the synthesis of DNA, the functioning of neurotransmitter systems, the neuronal growth and differentiation, the neuronal excitotoxic activity and/or the expression of early immediate genes. Opiates produce intrauterine and postnatal growth retardation, neonatal abstinence syndrome, and deficits of the psychomotor and cognitive development. They also increase the incidence of SIDS. The pathogenesis has been related to abnormalities in the sensitivity of the locus ceruleus, the functioning of the neurotransmitter systems, and/or the expression of early immediate genes. Marijuana has been associated with intrauterine growth retardation, dysmorphic features, and abnormalities of the behavior during the neonatal period, the psychomotor and cognitive development, and the sleep. The pathogenesis is thought to be due to an action upon specific receptors, or upon the neurotransmitter systems, and/or to an increase in the production of carbon monoxide. The best treatment of the syndrome of intrauterine exposure to drugs in the prophylaxis. The identification of emotional and drug addiction problems in the mother can avoid disastrous consequences. The care of these children is complex and requires a good pediatric follow-up and an early intervention program while the mother on the parents continue with the drug addiction therapy. The coordinations of all the necessary services with the active participation of social workers, physicians, educators and teachers is crucial for a successful treatment.

Cocaine↗
PubMed1995

Cholecystokinin potentiates morphine anticonvulsant action through both CCK-A and CCK-B receptors.

Recent studies have suggested that cholecystokinin may have a role in modulating the effects of the endogenous opioid system in physiological functions such as thermoregulation and pain control. However, the possible interaction of cholecystokinin and morphine in epileptogenesis is unknown. We studied the effect of subcutaneous morphine and intracerebroventricularly administered cholecystokinin octapeptide sulphate ester and receptor antagonists CCK-A (MK 329) and CCK-B (L 365,260) on seizures provoked by maximal electroshock in male Sprague-Dawley rats. Seizures were induced through electrode-gel-coated ear clip electrodes by a high voltage, high internal resistance constant current generator, 30 minutes after morphine administration and 10 minutes after cholecystokinin-8-SE, CCK-A and CCK-B infusion. Morphine decreased the length of the tonic component of the seizure and cholecystokinin potentiated this decrease. Cholecystokinin antagonists blocked the effects of both cholecystokinin and morphine. The results suggest that cholecystokinin acts as an endogenous agonist with opioids in the regulation of seizure susceptibility through both CCK-A and B receptors and may be responsible for part of the anticonvulsant action of morphine.

Animals↗
PubMed1995

Diagnostic value of pediatric outpatient video-EEG.

Outpatient video-electroencephalography (OVEEG) was performed in 100 infants, children, and adolescents with diagnosed (group I, n = 64) or suspected (group II, n = 36) epilepsy. Median monitoring duration was 4 hours. Indications for OVEEG in group I were classification of seizures, reported seizure exacerbation, or onset of new signs. OVEEG indications in group II were repetitive paroxysmal and stereotyped signs of myoclonic movements, fixed gaze, abnormal behavior, or nonmyoclonic motor activity. In group I patients, symptomatic events were recorded in 89%, half of which were seizures. Among group II patients, events were recorded in 67% and were seizures in 22%. Overall, OVEEG was successful in 83% of patients. Compared to a 24-hour inpatient admission for video-EEG monitoring, OVEEG represented cost reductions of 55-80% per patient. We conclude that OVEEG is a cost-effective, useful alternative to continuous inpatient video-EEG monitoring in the investigation of selected infants, children, and adolescents with diagnosed or suspected epilepsy.

Adolescent↗