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Y Robitaille

Publications and source records attributed to Y Robitaille.

At least 37 records · Page 2Linked to original sources
PubMed1997

Psychogeriatric clinical, electro-encephalographic and autopsy findings.

Demographic, psychiatric, and electro-encephalographic (EEG) data were compared with brain autopsy findings for 73 elderly psychiatric patients. A late onset of depression (60+ years) was more likely than early onset to be accompanied by Alzheimer's disease. There were strong associations between clinical and histopathological indicators of Alzheimer's disease. This was particularly evident for diffuse EEG slowing. Clinical as well as histopathological indicators of Alzheimer's disease were intensely related to EEG features, mainly EEG slowness (positive), reactivity to eye opening (negative) and dominant frequency (negative). Cerebrovascular pathology showed fewer EEG correlations. The results support the usefulness of the clinical electro-encephalogram in patients suspected to have Alzheimer's disease.

Age Factors↗
PubMed1997

Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen's syndrome?

Chronic encephalitis and epilepsy (Rasmussen's encephalitis) is a rare progressive disorder of uncertain etiology that usually occurs in children, producing focal epilepsy, hemiparesis, and intellectual deterioration. We identified 13 patients in whom seizures developed in adolescence or adulthood with a pathologic picture of chronic encephalitis. The clinical characteristics were more variable than those occurring in children, with the patients falling into three groups: five patients developed seizures in adulthood, but otherwise showed many resemblances to the childhood form; five developed seizures in adolescence, with similar presentation but rather more benign course than in the younger patients; and three presented with clinical features initially suggestive of a tumor. Occipital onset to the seizures appeared to be more common than in the childhood form, and bilateral disease also occurred.

Adolescent↗
PubMed1997

Striatal dopamine nerve terminal markers but not nigral cellularity are reduced in spinocerebellar ataxia type 1.

We previously reported markedly reduced (-76%) dopamine (DA) levels in the putamen of seven patients with spinocerebellar ataxia type 1 (SCA1) who had no evidence of nigral cell loss or parkinsonism. To determine whether the DA reduction was accompanied by loss of DA nerve terminals, we measured levels of the DA transporter ([3H]WIN, 35,428 binding; DA transporter protein) and the vesicular monoamine transporter ([3H]DTBZ binding) in the putamen of these patients. As compared with the controls (n = 14), mean putamen concentrations of [3H]WIN 35,428 binding (-45%), dopamine transporter protein (-61%), and [3H]DTBZ binding (-48%) were significantly reduced in this SCA1 subgroup. We conclude that the degeneration in nigrostriatal DA neurons begins at the nerve ending in SCA1.

Adult↗
PubMed1996

Limits of clinical assessment in the accurate diagnosis of Machado-Joseph disease.

BACKGROUND: Machado-Joseph disease (MJD) is a type of autosomal dominant spinocerebellar ataxia for which molecular diagnosis is available. We identified 4 families segregating the MJD mutation in which no unequivocal clinical diagnosis could be established prior to molecular testing. Ethnic background, clinical, and molecular characteristics of 19 individuals carrying the MJD mutation in these 4 families were compared with a group of 32 Portuguese families who were clinically diagnosed as having MJD and were found to carry the MJD mutation. RESULTS: Several factors seemed to have an impact in the accuracy of the clinical diagnosis, such as ethnic origin; the number of affected individuals available for examination in each family; the absence of patients showing specific clinical features, such as extrapyramidal signs; and the size of the expanded CAG repeat in the MJD gene. CONCLUSION: Since the recognition of MJD based solely on clinical grounds might sometimes be misleading, a search for the MJD mutation should be performed in patients with a clinical diagnosis of spinocerebellar degeneration.

Adult↗
PubMed1996

Somatic mosaicism in the central nervous system in spinocerebellar ataxia type 1 and Machado-Joseph disease.

Spinocerebellar ataxia type 1 and Machado-Joseph disease are two autosomal dominant cerebellar ataxias caused by expansions of unstable CAG repeats in the coding region of the causative genes. The selectivity of cell death and the resulting characteristic neuropathological features in each of these diseases are not explained by the gene expression patterns. Since the repeat size correlates with age at onset and severity of these diseases, somatic mosaicism, the result of mitotic instability of the CAG repeat, could be the basis for specificity of neurodegeneration; brain structures with larger expanded repeats would be more severely affected. To study the association between neuropathological changes and somatic mosaicism of the CAG repeat size in the central nervous system of patients with these two ataxias, we determined the size of the (CAG)n expansion in 20 different regions of the brain, brainstem, cerebellum, and spinal cord from 3 patients with spinocerebellar ataxia type 1 and 3 with Machado-Joseph disease; these regions were selected for their differential neuropathological involvement in the two disorders. We observed a considerable homogeneity of repeat size ranges in all but 1 of the 20 regions examined: The cerebellar cortex showed slightly smaller (CAG)n tracts in all specimens from both groups of patients. Our results suggest that the pattern of repeat size mosaicism, similar in spinocerebellar ataxia type 1 and Machado-Joseph disease, reflects the developmental pathways and cell composition of different central nervous system regions and is not the cause of selective cell death in these disorders.

Age of Onset↗
PubMed1996

Immunoreactive levels of alpha-ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type 1.

Enzyme activities of a alpha-ketoglutarate dehydrogenase complex (alpha KGDHC) and one of its constituent subunits, dihydrolipoamide dehydrogenase (E3), are reported to be reduced in non-CNS tissues of some patients with Friedreich's ataxia (FA); however, the results are highly conflicting. To determine whether an enzyme abnormality occurs in brain, we measured immunoreactive levels of the three alpha KGDHC subunits, namely, alpha-ketoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and E3 in postmortem frontal, occipital and cerebellar cortices of 18 control subjects, 9 patients with FA and, for comparison, 12 patients with spinocerebellar ataxia type 1 (SCA1). Decreased (-20 to -31%) levels of E3 were observed in all three examined areas of the patients with FA with the changes statistically significant in cerebellar and frontal cortices. The E3 reduction could be explained by a loss of alpha KGDHC or other dehydrogenase complexes (e.g. pyruvate dehydrogenase complex) which utilize this subunit. In SCA1, enzyme changes were limited to E2 in cerebellar (-26%) and frontal (-19%) cortices. Although the E3 and E2 reductions are only slight, and may represent secondary events, the changes in this key Krebs cycle enzyme could exacerbate degenerative processes in both of the spinocerebellar ataxia disorders.

Acyltransferases↗
PubMed1996

Alzheimer's disease: preliminary study of spatial distribution at birth place.

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by a progressive loss of memory and the alteration of cognitive functions. At least three chromosomal segments have been associated with early-onset AD in genetic linkage studies. These results argue for a certain degree of heterogeneity in the genetic origin of some forms of AD, although environmental risk factors cannot be ruled out in late-onset AD. In this preliminary study, we analyzed the geographical distribution of the birth places of a sample of 235 AD cases born in a defined region of Quebec (Canada), between 1895 and 1935. We wished to test the hypothesis that risk factors acting at, or around birth place and time play a role in the etiology of AD. The field of study was divided into rural and urban areas. A reference population of live births was used to compute a measure of odds ratio (OR). The OR results showed a statistically significant excess of AD cases in the rural area as compared to the reference population. When stratified for sex, the OR results showed a global excess of female AD cases in both the rural and the urban areas. For men, only the urban area presented a statistically significant deficit. We also analyzed the structures of the genealogical kinships of the rural and urban sub-groups. Although AD cases from the rural sub-group were more closely related to each other than those from the urban one, removal of the kin pairs from the OR analysis seemed to have little effect on the rural/urban distribution of cases. Therefore, the OR results would not appear to be due primarily to a difference in the kinship structures of the two sub-groups. This could mean that some risk factors for AD afflict women more strongly than men, the effect being different depending on the urban or rural origin. However, potential biases such as a higher rate of report for women, differential migration between birth places or a differential mortality ratio between sexes could produce spurious results in the direction of what we have observed in this preliminary study.

Aged↗
PubMed1996

Season of birth and Alzheimer's disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project).

The birth distribution of 399 cases of Alzheimer's disease (AD) identified in the region of Saguenay-Lac-St-Jean (Québec) was compared with that of: (a) the population currently living in the area; and (b) the population born during the same period in the same area. AD cases have been recruited since 1986 by the IMAGE Project. Cases and controls were grouped according to the month of birth and according to the day of birth using density estimation. Analyses showed a significant deficit of births in the month of May. We believe these preliminary results deserve further attention and we suggest two possible explanations that could lead to a deficit of AD births at specific periods during the year.

Aged↗
PubMed1996

Specific pathological Tau protein variants characterize Pick's disease.

Pick's disease (PiD) is characterized by a pan-laminar frontotemporal cortical atrophy, widespread degeneration of the white matter, chromatolytic neurons, and Pick bodies (PB). Microtubule-associated Tau proteins are the main cytoskeletal components modified during the neurodegenerative changes. In the present study, pathological alterations of Tau proteins were investigated in the brains of five PiD cases at both neuropathological and biochemical levels, using the monoclonal antibody AD2 which recognizes a phosphorylation-dependent Tau epitope and strongly labeled PB. A large number of cortical and subcortical regions were studied on frozen materials. Tau proteins were analyzed on mono- and two-dimensional gel electrophoreses using a quantitative western blot approach. In all specimens, a 55 and 64 kDa Tau doublet was observed in limbic, frontal, and temporal cortices as well as in striatum and substantia nigra. In contract, Alzheimer's disease (AD) brains are characterized by the presence of the 55, 64, and 69 kDa Tau triplet whereas the 64 and 69 kDa doublet is more typical of the progressive supranuclear palsy and corticobasal degeneration. Thus, the 55 and 64 kDa doublet appears to be specific to PiD, less acidic than AD Tau proteins, and well correlated with the presence of PB.

Aged↗
PubMed1996

Familial and sporadic Alzheimer's disease: neuropathology cannot exclude a final common pathway.

Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue. We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid percursor protein gene), and 11 sporadic AD (SAD) patients. There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group. However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology. These differences may reflect differences in age at onset rather than different etiopathologic mechanisms. The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD.

Age of Onset↗
PubMed1995

Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases.

Cytochrome oxidase (CO) is the terminal complex of the mitochondrial respiratory chain which generates ATP by oxidative phosphorylation. We have measured CO activity in six different brain regions of patients with senile dementia of Alzheimer type (SDAT, n = 10), presenile dementia of Alzheimer type (PDAT, n = 10), Lewy body dementia with SDAT (LBD, n = 5), cerebrovascular dementia (CVD, n = 10), Parkinson dementia (PD, n = 5), and in controls (n = 8), as all confirmed by neuropathological evaluation. CO activity was lower in the frontal and parietal cortex of SDAT patients compared to controls. Patients with PDAT, LBD, CVD or PD showed no significant reduction of the enzymatic activity in the six regions studied. Our results show that reduced CO activity might play a role in the physiopathology of senile dementia of Alzheimer type.

Aged↗
PubMed1995

Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy.

We measured the levels of dopamine, tyrosine hydroxylase (TH) protein, and dihydroxyphenylalanine (DOPA) decarboxylase (DDC) protein in the striatum of 10 patients with idiopathic Parkinson's disease (PD) and 23 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The levels of dopamine were markedly reduced (2% of control) in the striatum of the patients with PD, whereas striatal dopamine in the patients with OPCA ranged from normal (> 60% of control) to moderately reduced (20-60% of control) to severely depleted (< 20% of control). Both TH and DDC protein levels were significantly lower than those of the controls in the striatum of all of the patients with PD and in the subgroup of patients with OPCA having severely depleted dopamine. In contradistinction, TH but not DDC protein levels were reduced in those patients with OPCA having moderately reduced dopamine levels. This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated. Unexpectedly, from the blot immunolabeling analysis an additional DDC-immunoreactive band of slightly lower apparent molecular mass was detected in two of the patients with PD and in 12 of the patients with OPCA. This additional DDC band, which was not present in any of the control subjects, may reflect posttranslational modification(s) of DDC related to the neurodegenerative process.

Aged↗
PubMed1995

Structural and immunocytochemical features of olivopontocerebellar atrophy caused by the spinocerebellar ataxia type 1 (SCA-1) mutation define a unique phenotype.

Neuropathological investigations performed on autopsied brain and spinal cords from 11 patients showed that spinocerebellar ataxia type 1 (SCA-1) can be distinguished from autosomal dominant spinocerebellar ataxia linked to SCA-2 and -3 loci on chromosomes 12 and 14, spinopontine, and the multisystem atrophies. The major diagnostic criteria were: absence of significant pars compacta nigral and locus coeruleus lesions, severe degeneration of olivocerebellar and dentatorubral pathways, extensive loss of Purkinje cells with partial sparing of flocculonodular lobes, severe atrophy of specific cranial nerve nuclei, mostly the third and 12th, extensive loss of motor neurons in anterior horns and Clarke's columns, and lack of oligodendroglial or neuronal cytoplasmic cytoskeletal inclusions. None of the brains displayed any significant immunoreactivity for the amyloid precursor protein or beta-amyloid peptide throughout the cortex. In conclusion, the type and neuroanatomical distribution of structural lesions were similarly reproduced in all probands at the end stage of SCA-1, to the point that they appeared to constitute a unique phenotype.

Adolescent↗
PubMed1995

beta-alanine uptake is upregulated in FeCl3-induced cortical scars.

Glial uptake of beta-[14C]alanine (beta-Ala) was studied in male Sprague-Dawley rats after sub-pial iontophoresis of FeCl3 into the right motor strip. Models bearing a 15-day-old scar were selected because of the presence of strongly reactive glia induced by FeCl3. Behavioral seizures were observed by daily visual inspection in one third of the animals. The effects of intraperitoneal (i.p.) injections of DL-alpha-aminoadipic acid (DLaAA), which exerts specific gliotoxicity through glutamine synthetase (GS) inhibition, and of 3-mercaptoproprionic acid (3MP), a potent inhibitor of glutamic acid decarboxylase (GAD: the rate-limiting enzyme in the biosynthesis of gamma-aminobutyric acid [GABA]), were also examined. There was significant enhancement of beta-Ala uptake in the margins of the scars. Further increases of uptake were triggered by 3MP, and there was extensive recruitment of astrocytes within isocortex even at a distance from the edges of the scar. DL-alpha-Aminoadipic acid caused a slight decrease of beta-Ala uptake, which was selectively localized to the scar margins. Seizure activity was unchanged by high i.p. doses of DL alpha AA. Our results strongly suggest that beta-Ala has high affinity for normal and reactive astrocytes, and that the uptake can be significantly enhanced by lowering endogenous GABA levels in abnormal cortical tissues in and around FeCl3-lesions by inhibition of GAD. Enhancement of glial beta-Ala uptake appeared to depend heavily on increased endothelial transport of small neutral amino acids, in a process modulated by perivascular glia. This model of free radical neurotoxicity may help gain more insight into abnormal neuronal-glial interactions caused by lipid peroxidation.

Animals↗
PubMed1995

Retained language in dysgenic cortex: case report.

Since the advent of magnetic resonance imaging, there has been renewed interest in disorders of cortical migration in the cause of focal epilepsy. The function of dysplastic cortex is poorly understood. We report a 46-year-old woman in whom this was assessed by intraoperative stimulation. This left-handed patient had a 30-year history of complex partial seizures with secondary generalization. Prolonged electroencephalographic recordings documented an epileptic focus in the right lateral and inferomesiotemporal lobe. Computed tomographic scanning and angiography suggested a right posterotemporal hamartoma. Amytal testing showed major speech representation in the right hemisphere. At craniotomy, an ivory-colored, posterotemporal lesion originating 5 cm from the temporal tip and 4 cm in diameter occupied the posterotemporal region. Electrical stimulation of this lesion produced speech interference. A histological examination of the resected anterotemporal lobe, amygdala, and hippocampus and biopsy specimens of the lesion showed extensive multifocal cortical microdysgenesis and gliovascular and cortical hamartoma. This case shows that grossly dysplastic cortex can remain functional. Cortical mapping under local anesthesia should be performed before resection of dysplastic lesions in putatively functional areas in patients with intractable epilepsy.

Amygdala↗
PubMed1994

Apo E allele frequencies in Alzheimer's disease, Lewy body dementia, Alzheimer's disease with cerebrovascular disease and vascular dementia.

Apolipoprotein (Apo E) was genotyped using a fluorescent PCR-RFLP assay in 187 patients with a probable or possible clinical diagnosis of sporadic Alzheimer's disease (AD) and in 166 autopsied patients with dementia (21 presenile AD, 70 senile AD, 18 Lewy body dementia (LBD), 38 AD with cerebrovascular disease (AD-CVD), 19 vascular dementia). The relative epsilon 4 allele frequency was 0.472 in LBD, 0.513 in AD-CVD, 0.405 in presenile AD, 0.364 in senile AD, and 0.079 in vascular dementia. The relative epsilon 2 allele frequency was 0.211 in vascular dementia, 0.083 in LBD, 0.047 in presenile AD, 0.100 in senile AD and 0.039 in AD with CVD. We infer that apo E is a major risk factor for structural phenotypes of dementia involving AD, alone or in conjunction with another pathology. In addition, the epsilon 2 allele is likely to represent a risk factor for vascular morbidity, as the relative epsilon 2 allele frequency was 0.211 in patients with vascular dementia compared with 0.144 in elderly controls.

Adolescent↗
PubMed1994

Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies.

Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD.

Aged↗