Yvon Robitaille

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.

Excitatory amino acids are elevated in human epileptic cerebral cortex

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)—epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)—temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (μmol/g protein, mean ±: SEM): glutamate—spiking 109.8 ±: 1.8, nonspiking 87.4 ±: 2.0 (p < 0.001); aspartate—spiking 15.2 ±: 0.9, nonspiking 12.2 ±: 0.5 (p < 0.05); GABA—spiking 15.0 ±: 1.0, nonspiking 13.9 ±: 1.4 (NS); taurine—spiking 14.5 ±: 0.8, nonspiking 12.2 ±: 0.8 (NS); and glycine—spiking 11.5 ±: 0.8, nonspiking 7.4 ±: 0.6 (p < 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.

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

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimers 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 = 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.

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

Article abstract-Chronic encephalitis and epilepsy (Rasmussens 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. NEUROLOGY 1997;48: 418-424

Double pathology in Rasmussen's syndrome A window on the etiology?

The syndrome of chronic encephalitis with epilepsy (Rasmussens syndrome) typically occurs in children and is characterized by the development of intractable focal seizures, progressive hemiparesis and intellectual deterioration. The etiology is unknown, and the pathological abnormalities vary from those of active disease, with numerous microglial nodules, with or without neuronophagia, perivascular round cells and glial scarring, to those of remote disease, demonstrated by neuronal loss, gliosis and perivascular round cells but few microglial nodules. We describe five patients presenting with clinical features typical of Rasmussens syndrome, in whom pathological examination showed a second, previously unsuspected pathology in addition to the changes of chronic encephalitis. Two of the patients had vascular abnormalities bearing some resemblance to cavernous angiomata, one had a tumor, one had tuberous sclerosis, and one the forme fruste of tuberous sclerosis. The coexistence of a second pathology in these patients may provide information about the underlying mechanism of this rare condition.

Enzyme changes in actively spiking areas of human epileptic cerebral cortex

Five enzymes involved in glutamic acid, GABA, and catecholamine metabolism were measured in epileptic human brain. Electrocorticographically defined areas of focal spiking were compared with samples from surrounding nonspiking cortex. Comparative enzyme activities were as follows (μmol/h/g wet wt): glutamic acid dehydrogenase (GDH)-spiking 135.77 ± 10.22 (mean ± SEM), nonspikingll8.58 ± 9.42 (p < 0.001, N = 17); gluotamicacid decarboxylase—spiking 10.63 ± 0.95, nonspiking 9.96 ± 1.10 (NS, N = 13); GABA-aminotransferase—spiking 36.49 ± 1.05, nonspiking 36.46 ± 1.48 (NS, N = 12); glutamine synthetase-spiking 96.94 ± 3.81, nonspiking 96.52 ± 4.10 (NS, N = 20); and tyrosine hydroxylase (TH; nmol/h/g)-spiking 16.23 ± 2.39, nonspiking 10.67 ± 1.95 (p < 0.001, N = 14). Increased activity of GDH and TH may prove useful to characterize further areas of active spiking in human focal epilepsy.

Electroencephalography, Magnetic Resonance Imaging and Pathology in Patients Treated Surgically for Temporal Lobe Epilepsy

In a consecutive series of 40 patients selected by EEG studies for surgical treatment of temporal lobe seizures, magnetic resonance imaging showed structural lesions in 25% and signal abnormalities, usually in the mesial temporal region, in another 35%. Pathological changes included structural lesions in over 30% of patients and sclerosis of the amygdala in almost half of the series. These findings further substantiate the implication of the amygdala in the pathogenesis of temporal lobe seizures with automatism and amnesia.

Familial mixed oligodendrocytic-astrocytic gliomas.

We present the first reported cases of mixed oligodendrocytic-astrocytic gliomas to occur in two members of the same family, a father and a son. These tumors had common biological and histological characteristics, and their occurrence supports the concept of genetic determination in some gliomas.

Transformation of the neurofilamentous network components into PHF-like strands and PHF paracrystals

The threshold theory of the causation of Alzheimer’s disease (AD), as formulated by Roth et al.1 has important implications for diagnosis, clinicopathological correlation and scientific inquiry. The theory is based on determination of the intensity of tangle formation and plaque counts carried out at the light microscope level, on one hand, and measures of dementia, on the other. Twenty years have passed since this theory was formulated. During this period of time fundamental advances have been made in three areas of importance for the theory. First, modern electron microscopic (EM) techniques provide the means to resolve the tangles into the specific and complex components of a modified neuron cytoskeleton.2–5 Second, clinical and neuropsychological assessment of dementia has become increasingly precise and stringent in recent years. Finally, availability of frontal lobe biopsies from early Alzheimer patients provides the opportunity to define the threshold state and, thus, the beginning of the disease with greater accuracy.6

Stability of alpha-1 adrenoceptors in surgically excised human brain

Alpha-1 adrenoceptor sites were measured in membranes prepared from nonepileptic superficial cortex following temporal lobectomy for lesions in deep medial structures. There was no significant change in receptor density (Bmax) or affinity (Kd) when paired samples were either frozen immediately or kept at room temperature for 24 hours before freezing and storage at -70 degrees C. Regional variability in the Bmax or Kd of alpha-1 adrenoceptor binding was not observed in serial samples from lateral temporal cortex. We previously reported a localized decrease in alpha-1 adrenoceptors in epileptic foci when compared to adjacent nonepileptic tissue obtained from the same patient. As nonepileptic control tissue from an adjacent gyrus is frequently not available in the same specimen, the stability of alpha-1 adrenoceptors justifies the use of postmortem brain for comparative studies.