Search PubMed⌕ Search

Biomedical subjects

Y Robitaille

Publications and source records attributed to Y Robitaille.

At least 73 records · Page 4Linked to original sources
PubMed1993

Cortical vascular abnormalities in the syndrome of celiac disease, epilepsy, bilateral occipital calcifications, and folate deficiency.

The pathological changes in the syndrome of celiac disease, folate deficiency, bilateral occipital calcifications, and intractable epilepsy have not been previously described. A child with this disorder had a field defect correlating with active lateralized epileptic discharges and asymmetrical lesions. After resection of the right occipital lobe she was seizure free for 4 years. A cortical vascular abnormality with patchy pial angiomatosis, fibrosed veins, and large jagged microcalcifications was found. These pathological abnormalities were similar though not identical to those found in the Sturge-Weber syndrome.

Calcinosis↗
PubMed1993

Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or consequence of repeated seizures?

We studied 70 epileptic patients by using magnetic resonance imaging volumetric measurements of amygdala (AM) and hippocampal formation (HF). Fifty patients presented with intractable temporal lobe epilepsy (TLE), 10 patients had focal extratemporal lobe epilepsy, and 10 had generalized epilepsy. In 91% of the 45 TLE patients without foreign tissue lesions, there was significant smallness of the AM and/or HF coinciding with the side of electroencephalographic seizure onset. No significant smallness or asymmetry was demonstrated in patients with focal extratemporal or generalized epilepsy. We performed a linear regression analysis, plotting the number of years of recurrent seizures and the estimated seizure frequency against the volumes of the AM and HF. There was no correlation between either of these two parameters and AM or HF volume (p > 0.9). There was also no correlation between the patient's age and volumetric measurements of AM or HF, nor did these measurements correlate with the occurrence of generalized seizures. On the other hand, patients with antecedent prolonged febrile convulsions in early childhood had significantly smaller AM and HF, compared with those without such a history (p < 0.001). The findings indicate that repeated seizures or longer duration of epilepsy do not cause increased atrophy of AM or HF that is measurable by volumetric magnetic resonance imaging.

Adolescent↗
PubMed1993

Stages and patterns of centrifugal arrest of diffuse neuronal migration disorders.

Centrifugal migration of newly generated neuroblasts toward the cortical surface can be arrested at different levels, resulting in anatomically different disorders. This is illustrated by three patients with diffuse or generalized neuronal migration disorders (NMDs): pachygyria, subcortical laminar heterotopia ('double-cortex' syndrome), and periventricular laminar heterotopia. All had medically intractable partial and generalized epileptic seizures, but there was no close correlation between the type of dysplasia and intelligence or clinical pattern. The low intelligence found in these patients may relate to the epileptic syndrome, rather than to the NMDs alone. MRI suggested that in this spectrum of disorders the migration process was arrested at different stages, depending on the extent, timing and site of damage to radial glial fibres.

Adult↗
PubMed1993

Elevated stimulatory and reduced inhibitory G protein alpha subunits in cerebellar cortex of patients with dominantly inherited olivopontocerebellar atrophy.

Although guanine nucleotide binding proteins (G proteins) are one of the critical components of signal transduction units for various membrane receptor-mediated responses, little information is available regarding their status in brain of patients with neurodegenerative illnesses. We measured the immunoreactivity of G protein subunits (Gs alpha, Gi alpha, Go alpha, Gq/11 alpha, and G beta) in autopsied cerebellar and cerebral cortices of 10 end-stage patients with dominantly inherited olivopontocerebellar atrophy (OPCA) who all had severe loss of Purkinje cell neurons and climbing fiber afferents in cerebellar cortex. Compared with the controls, the long-form Gs alpha (52-kDa species) immunoreactivity was significantly elevated by 52% (p < 0.01) in the cerebellar cortex of the OPCA patients, whereas the Gi1 alpha concentration was reduced by 35% (p < 0.02). No statistically significant differences were observed for Go alpha, Gi2 alpha, G beta 1, G beta 2, or Gq/11 alpha in cerebellar cortex or for any G protein subunit in the two examined cerebral cortical subdivisions (frontal and occipital). The cerebellar Gs alpha elevation could represent a compensatory response (e.g., sprouting, reactive synaptogenesis) by the remaining cerebellar neurons (granule cells?) to neuronal damage but also might contribute to the degenerative process, as suggested by the ability of Gs alpha, in some experimental preparations, to promote calcium flux. Further studies will be required to determine the actual functional consequences of the G protein changes in OPCA and whether the elevated Gs alpha is specific to OPCA cerebellum, because of its unique cellular pattern of morphological damage, or is found in brain of patients with other progressive neurodegenerative disorders.

Adult↗
PubMed1993

Reduced cerebral cortical but elevated striatal concentration of somatostatin-like immunoreactivity in dominantly inherited olivopontocerebellar atrophy.

Somatostatin-like immunoreactivity (SLI) was measured in the brains of nine patients with dominantly inherited olivopontocerebellar atrophy (OPCA), who all had a marked deficit of the cholinergic marker choline-acetyltransferase (ChAT) in the cerebral cortex and striatum. Mean concentrations of SLI in OPCA were significantly reduced by 42-58% in parietal and occipital cortices and frontal cortical eye fields, but were normal in other cortical areas, including two subdivisions of the temporal cortex which show marked depletions of both SLI and ChAT in Alzheimer's disease. This dissociation of SLI and ChAT indicates that a cortical cholinergic deficit does not invariably lead to reduction of somatostatin. In the caudate nucleus, the region of OPCA brain having the most severe ChAT deficit (-81%), SLI levels were significantly elevated by 46% and were negatively and significantly correlated with ChAT activities (r = -0.66). The SLI alterations could be due to abnormal somatostatin metabolism or release, or an increased number of somatostatin-containing neurons and could contribute to the brain dysfunction of OPCA.

Adult↗
PubMed1993

Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study.

We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35%) had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.

Adolescent↗
PubMed1993

Spinal angiolipomas. Report of three cases.

Spinal angiolipomas are distinct, benign lesions composed of mature lipocytes admixed with abnormal blood vessels. Three new cases of spinal angiolipoma are presented and 34 previously reported cases are analyzed. The 37 total cases (23 females and 14 males) ranged in age from 17 to 73 years (mean 43 years; median 45 years). The mean age of the female patients was older than that for the males (45.0 vs. 41.6 years; p < 0.001, Student's t-test) and most were peri- or postmenopausal. Prior to diagnosis, 97% of the patients had weakness of the lower extremities, 94% had sensory dysfunction, 84% had hyperreflexia and spasticity, 51% had sphincter dysfunction, and 41% had back pain lasting from 1 to 180 months (mean 28 months). Five (22%) of the 23 female patients were pregnant and two had exhibited significant weight gain coincident with the onset of symptoms. The angiolipomas were extradural in 35 patients and intramedullary in two; seven of the extradural lesions infiltrated the surrounding bone. The tumors extended from C-6 to L-4 and had a predilection for the midthoracic region (53% of cases). Plain radiographs were abnormal in 11 (39%) of 28 patients and in all patients with bone infiltration. Myelograms were abnormal in 97% of 32 patients and showed a complete block in 63% of patients. Computerized tomography (CT) and magnetic resonance (MR) imaging revealed the fat-density lesions in all cases studied. There was vascular enhancement in three of five cases with contrast-infused CT and in the one case with gadolinium-infused MR imaging. All patients improved following resection of the epidural lesions and internal decompression of the intramedullary lesions. It is concluded that spinal angiolipomas predominantly affect women. They involve the thoracic (especially the midthoracic) region, and produce symptoms and signs of spinal compression and, in some cases, bone erosion and pathological fractures. Their symptomatology can be exacerbated by pregnancy and weight gain, suggesting that vascular engorgement and the presence of obesity influence their evolution. Their preponderance in older, peri-, or postmenopausal women, and their clinical exacerbation in pregnant women support a role for hormonal influence. Magnetic resonance imaging is the investigation of choice for the diagnosis of these lesions. Surgery is universally successful in relieving symptoms.

Adult↗
PubMed1993

Magnetic resonance imaging in the diagnosis of dominantly inherited cerebello-olivary atrophy: a clinicopathologic study.

To facilitate the study of cerebellar degenerative disorders, improved clinical diagnosis is needed. Cerebello-olivary atrophy is pathologically distinct, but until now its diagnosis has been thought to require postmortem examination. This condition was considered as a possible diagnosis in two patients from different families with dominantly inherited ataxia. The affected members of each family demonstrated a stereotyped, progressive, "pure" cerebellar syndrome, which began with gait ataxia followed years later by dysarthria and limb ataxia. The autopsy findings for the first patient's father revealed paleocerebellar and olivary atrophy, characteristic of cerebello-olivary atrophy. Magnetic resonance imaging (MRI) of the brain of both patients revealed medullary, vermian and, to a lesser extent, cerebellar hemispheric atrophy but a normal pons. Dominantly inherited cerebello-olivary atrophy was diagnosed in both patients. Characteristic clinical and MRI features thus permit a confident clinical diagnosis of dominantly inherited cerebello-olivary atrophy. Recognition of this entity during life should advance the classification of cerebellar degenerative disorders.

Brain↗
PubMed1992

Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy.

Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA.

Adult↗
PubMed1992

Ubiquitin profile and amyloid enhancing factor activity in Alzheimer and 'normal' human brain extracts.

Tris-HCl or Laemmli sample buffer extracted frontal lobe and hippocampal samples from normal aged and Alzheimer's disease (AD) subjects were used to determine total ubiquitin (Ub), distribution of monomeric Ub and Ub-protein conjugates and amyloid enhancing factor (AEF) activity using the dot-blot, Western blot and mouse AEF bioassay techniques, respectively. The AD samples, as compared to the normals, demonstrated a 1.7-fold increase in total Ub, elevated levels of Ub-protein conjugates and an appreciably enhanced AEF activity. Many of the hippocampal Ub-protein conjugates were found to be soluble only in the Laemmli sample buffer. The possible roles of elevated Ub levels and of the association of AEF activity with Ub are discussed in regard to pathogenesis of brain amyloidosis.

Aged↗
PubMed1992

Deficits in the somatostatin SS1 receptor sub-type in frontal and temporal cortices in Alzheimer's disease.

The aim of this study was to evaluate the possible differential alterations of somatostatin (SRIF) receptor sub-types in Alzheimer's disease (AD). Consequently the binding profile of cortical SRIF receptors were examined in normal and AD brains using non-selective ([125I]Tyr0, D-Trp8-SRIF14) and SS1 receptor sub-type-selective ([125I]SMS204-090) radioligands. Maximal binding capacities, but not affinities, were reduced for both ligands in the temporal cortex. In contrast, only the maximal binding capacity of [125I]SMS204-090 was significantly reduced (68%) in the frontal cortex; no alterations were detected using the non-selective probe. This reveals that while the maximal binding capacity of the SS1 receptor sub-type is altered in frontal and temporal cortices in AD, other putative cortical SRIF receptor classes (such as SS2 sites) are not as broadly affected. This could be of significance for eventual therapeutic approaches using SRIF-related analogues.

Aged↗
PubMed1992

Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases.

We have recently reported on the differential alterations of various cholinergic markers in cortical and subcortical regions in Alzheimer's disease (AD). The main purpose of the present study was to determine if cholinergic deficits observed in patients with AD are unique to this disorder or can be generalized to others such as idiopathic Parkinson's disease (PD) and PD with Alzheimer-type dementia (PD/AD). Muscarinic M1, M2, and nicotinic receptor binding parameters (KD and Bmax) were determined in various cortical and subcortical areas using selective radioligands ([3H]pirenzepine, [3H]AF-DX 116, and N[3H]methylcarbamylcholine). Choline acetyltransferase activity was also determined as a marker of the integrity of cholinergic innervation. Alterations of cholinergic markers are comparable in cortical areas in AD, PD, and PD/AD brains. In frontal and temporal cortices, as well as in the hippocampus, choline acetyltransferase activity and binding capacities of M2 and nicotinic binding sites are similarly decreased in these three disorders compared with age-matched control values. M1 receptor binding parameters are not significantly modified in cortical areas in patients with these disorders. In contrast, important differences between AD and PD brain tissues are found in subcortical areas such as the striatum and the thalamus. The density of M1 sites is significantly increased in striatal areas only in patients with AD, whereas densities of nicotinic sites are decreased in thalamus and striatum in PD and PD/AD, but not AD, brain tissues. The binding capacity of M2 sites is apparently unchanged in subcortical areas in all three disorders, although tendencies toward reductions are observed in the striatum of PD and PD/AD patients. Thus, although comparable alterations of various cholinergic markers are observed in cortical areas in the three neurological disorders investigated in the present study, important differences are seen in subcortical areas. This may be relevant to the respective etiological and clinical profiles of AD and PD.

Aged↗
PubMed1992

Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene.

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families.

Adult↗
PubMed1992

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.

Biogenic Amines↗
PubMed1992

Cerebral hemorrhage from amyloid angiopathy and coronary thrombolysis.

Coronary thrombolysis with streptokinase or tissue plasminogen activator is useful for the treatment of acute myocardial infarction in selected patients. This treatment is associated with local hemorrhagic complications and age-related cerebral hemorrhage. Coronary thrombolysis is contraindicated in patients with transient cerebral ischemia and stroke, arterial hypertension, cerebral trauma, cerebral aneurysms, and arteriovenous malformations, because of the risk of cerebral hemorrhage. We report the occurrence of a cerebral hemorrhage related to cerebral amyloid angiopathy in a patient who underwent thrombolysis and treatment with heparin for acute myocardial infarction. Despite normal coagulation parameters, the cerebral hematoma enlarged over 36 hours, as documented by sequential computed tomographic scans, to produce significant mass effect, which prompted surgical evacuation. Histological examination of the resected specimen demonstrated the strong affinity for Congo red and yellow-green birefringence that are characteristic of cerebral amyloid angiopathy. Hemostasis was difficult to achieve, as the divided or disrupted amyloid-laden cortical vessels failed to vasoconstrict, their contractile elements replaced by amyloid beta protein. The patient died of recurrent myocardial ischemia 3 days postoperatively. The incidence of cerebral amyloid angiopathy increases with advancing age. It must be considered as a potential source of cerebral hemorrhage in elderly patients undergoing thrombolysis for cardiac ischemia. Such an occurrence presents a difficult challenge because cardiac function is compromised, the coagulation profile may be altered, the cerebral hematoma is life threatening, and intracranial hemostasis is difficult to achieve.

Aged↗
PubMed1991

Retrovirus-induced spongiform myeloencephalopathy in mice: regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons.

The Cas-Br-E murine leukemia virus (MuLV) induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis. We have used in situ hybridization with a Cas-Br-E MuLV-specific probe to study viral expression in the central nervous system. Infected cells were concentrated in regions where spongiform lesions and gliosis are detected (lumbosacral spinal cord, brainstem, deep cerebellar regions), suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease. However, viral expression was not in itself sufficient to cause disease, since significant viral expression was observed in regions that did not exhibit pathological changes (cerebellar cortex, hippocampus, corpus callosum, peripheral nervous system). In both diseased and nondiseased regions, endothelial and glial cells were identified as the main target cells. Neurons in diseased regions did not show viral expression. The regional distribution of the spongiform changes appears to be laid down very early following infection, since expression could be detected at 10 days postinfection in regions that become diseased. These results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells.

Animals↗