C'est avec une appréhension certaine que j'ai accepté le redoutable honneur d'être le conférencier cette année de la Société Canadienne de Neurologie dont je fais partie depuis trente ans.

C'est avec la même appréhension que j'ai choisi d'évoquer certains aspects de la carrière d'un grand de I'histoire du 20e siècle des sciences neurologiques, Joseph Babinski.

Je souhaite que vous soyiez indulgents à l'endroit de l'apprenti historien que je voudrais être.

It is well known that pure absence epilepsy is a benign form of seizure disorder, while most others, particularly partial and convulsive seizures may have transient or permanent deleterious consequences and are more difficult to bring under therapeutic control by anticonvulsants. The hypothesis is proposed that the preservation of GABA-ergic inhibition in absence attacks and its breakdown in most other seizures may explain these differences. Breakdown of GABA-ergic inhibition allows NMDA receptors to become active. This opens the way for Ca2+ to enter the cell. Such Ca2+ entry is a long-lasting phenomenon. It is likely to be massive during most seizures except during absence attacks, and may therefore damage the neuron transiently or permanently. It may even destroy it. Ca2+ entry is also a crucial factor in the activation of the second messenger cascade which involves cytosolic as well as nuclear (genomic) components. Activation of this cascade converts short-lived electrophysiological processes occurring at the membrane into much longer-lasting intracellular processes. These may include plastic changes at the synaptic and receptor level and may account for kindling and the increasing therapy-resistance of long-standing seizure disorders. Changes resulting from massive Ca2+ entry into the neuron may explain why most seizures, except absence attacks, may have deleterious consequences of various kinds, some short-lived, some of longer duration, and some even permanent.

Patients with tumors of the central nervous system (CNS) remain difficult to treat despite recent advances in surgical, chemotherapeutic and radiotherapeutic techniques. A better understanding of the molecular and cellular biology of neoplasia is providing neuroscientists with a framework on which to devise novel therapies for these patients. It thus becomes imperative that neurologists and neurosurgeons be aware of these advances in basic science that may eventually have a positive impact on patient management. This paper reviews our present knowledge of the process of CNS oncogenesis and the roles that chemicals, viruses, oncogenes, growth inhibitor genes, and growth factors play in the process.

Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currently investigating intrathecal thrombolytic therapy with human, recombinant, tissue plasminogen activator (rt-PA) in a primate model of subarachnoid hemorrhage (SAH) and cerebral vasospasm (VSP). In the present study 16 monkeys were divided into 4 groups of 4, and each group received a different dose of sustained-release gel rt-PA at the time of experimental SAH. Cerebral angiography seven days later showed that whereas no VSP occurred in the groups receiving 0.5 or 0.75 mg of rt-PA, mild to moderate VSP occurred in the groups receiving 0.125 or 0.25 mg of rt-PA. Analysis of the combined 2 smaller dosage groups revealed significant (P<0.05) reduction of lumen caliber in the clotside internal carotid (C3 and C4), proximal anterior cerebral (A1) and middle cerebral (MCA) arteries. Gross subarachnoid clot remained in all of the animals in the 0.125 and 0.25 mg dose groups, in 2 of the animals in the 0.5 mg dose group, and none of the animals in the 0.75 mg dose group. It was concluded that 0.75 mg of gel rt-PA is sufficient to completely lyse a 4.25 ml SAH and prevent VSP in our primate model. The literature on fibrinolysis and erythrocyte clearance in cerebrospinal fluid (CSF) is reviewed.

Study of dendritic morphology through Golgi impregnation techniques has significantly furthered our understanding of neuronal development, maturation, and senescence. It has also provided insight into the pathogenesis of a wide spectrum of disease processes ranging from brain malformations to degenerative disorders. Golgi impregnation remains virtually the only method for demonstrating dendritic morphology. It delineates the profile of the individual neuron and its dendritic ramifications with unsurpassed clarity. Although it has been widely applied to experimental neuroscience involving animal tissue, its application to human material has been limited. This review summarizes the information on dendritic development and pathology in the human brain revealed by the use of the Golgi method.

Cerebral blood flow (CBF), cerebral blood volume (CBV), the CBF/CBV ratio – an index of the hemodynamic reserve capacity – the rate of oxygen metabolism (CMRO2), and the fractional extraction of oxygen by the brain (OEF) were studied by positron emission tomography (PET) in the cortical territory of both internal carotid arteries in 15 cases of transiently symptomatic or progressive extracranial atherosclerotic carotid disease. None of the patients had a major stroke or had a significant neurological deficit except 1 whose damaged hemisphere is excluded from study. All were asymptomatic at the time of PET scanning. Values were obtained in the middle cerebral artery (MCA) distribution, and in the anterior and posterior borderzone regions. Eight cases had unilateral carotid stenosis of 80% or greater and 7 had unilateral or bilateral occlusion of the origin of the internal carotid artery. Results obtained in patients were compared using Student's t-test, to those obtained in neurologically normal, elderly volunteers. Patients with carotid stenosis had a significantly decreased CBF (p<.025) and CBF/CBV ratio (p<.025) selectively in the anterior borderzone regions. This was accompanied by a trend toward elevated OEF and declining CMRO2 values. Patients with carotid occlusion had significantly decreased CBF (p<.005), decreased CBF/CBV ratio (p<.005) and decreased CMRO2 (p<.025) in the ipsilateral anterior borderzone and MCA territories. Similar changes were present in the opposite hemisphere of patients with bilateral carotid disease. These results indicate that carotid stenosis is associated with hypoperfusion and diminished hemodynamic reserve capacity in the anterior borderzone, and that carotid occlusion produces more widespread hypoperfusion and metabolic depression.

Altered efficacy, from change in receptor discharge with different positions of the knee, was investigated in a heteronymous lb reflex of the human leg. The electrical stimulus was low threshold, to the common peroneal nerve. The divergence of the group I afferents was studied in the electromyograms (EMGs) of ipsilateral and contralateral thigh muscles. The stimulus evoked ipsilateral, short latency, excitation in the three quadriceps muscles studied and inhibition in the knee flexor semitendinosus (ST), with prior contraction of target muscles. This excitation and inhibition did not alter when studied over the range of the knee joint. The stimulus did not evoke responses in contralateral thigh muscles, contracted or relaxed. It is concluded that (1) any change in convergence from discharge of receptors, during extension of the limb, is small and sub-threshold, and (2) this spinal proprioceptive level of neural control appears to be directed primarily to the single limb.

Vascular headache of migraine-type may be a presenting symptom of multiple sclerosis (MS), a condition usually not considered in the differential diagnosis of a severe headache accompanied by neurological signs. We reviewed records of 1,113 patients with MS seen from 1967-1987 and found 44 cases whose initial attack or subsequent exacerbations were heralded by a migraine-type headache. Twenty-seven patients had no prior history of migraine, and of these, 12 presented simultaneously with their first headache and MS attack. Twenty-three patients had symptoms of a posterior fossa mass lesion. The significance of these results and possible pathogenesis is discussed.

A 53 year old man developed symptoms of motor neuron disease in childhood. There was a family history of a similar disorder and it was felt to represent a form of Kugelberg-Welander disease. In addition to the motor deficits, sensory abnormalities in his legs were documented during life. Autopsy revealed anterior horn cell loss throughout the length of the spinal cord, with preservation of the phrenic nucleus. The lumbar dorsal root ganglia showed active degeneration of sensory neurons, with nuclear changes exceeding cytoplasmic ones. The fasciculus gracilis showed Wallerian degeneration. The findings provide direct evidence that sensory neurons can degenerate in some forms of motor neuron disease, and that the “demyelination” or “degeneration” of posterior columns sometimes seen in the various forms of motor neuron disease may actually be secondary to cell body disease in the dorsal root ganglia.

We examined platelet aggregability during nocturnal sleep and daytime wakefulness in patients with a history of sleep-related stroke onset (SOS) and compared it to that of matched awake-onset stroke (AOS) patients and controls without evidence of vascular disease. Aggregability was evaluated in-vitro at least seven weeks following stroke onset. Platelets were more aggregable to ADP, collagen and arachidonic acid (AA) during both sleep and wakefulness in patients with AOS (p<0.01). No significant difference in the mean aggregation thresholds during sleeping or waking periods were found between SOS and control groups. However, platelets were significantly more responsive to AA during sleep than during wakefulness in the SOS patients (p<0.01). This difference was confined to the subgroup of SOS patients who had experienced nocturnal as opposed to daytime sleep-related stroke onset, suggesting that the observed difference in platelet responsiveness to AA may be related to a circadian fluctuation in platelet aggregability rather than to a sleep-related fluctuation. Significant sleep-related changes in platelet aggregability were not identified in the other two groups.

We report 12 patients with Sturge-Weber-Dimitri disease treated surgically between January 1975 and December 1987. Hemispherectomy was performed on ten, two others underwent occipital lobectomy for intractable seizures. All operations were performed between the ages of 3 months and 20 months, except in two at age 8 and 9 years. The onset of seizures in all was between 2 and 8 months of age, except for two at 15 months. There were no postoperative deaths. Postoperative shunt procedures were required in 3 out of 12 (25%). Postoperative seizure control for one year or more was achieved in 11 out of 12 patients. The remaining patient is on medication with no seizures, but follow-up is less than a year. Intellectual deterioration was not seen after surgery except in 2 patients who had late operations. We conclude that patients with Sturge-Weber-Dimitri syndrome who have intractable seizures in the first 6 months of life and unilateral hemispheric involvement should be considered for early resection of the involved hemisphere.

Most vascular injuries to the brain secondary to blunt head trauma involve the internal carotid circulation. A case of isolated basilar occlusion secondary to a clival fracture is described and compared to three other cases in the literature.

Encystment of the fourth ventricle, due to occlusion of the aqueduct as well as the foramina of Magendie and Luschka has been described previously. Partial sequestration such as that encountered in two cases described is a less common entity. In these two cases, the aqueduct of Sylvius was occluded, but the basal foramina (Magendie and Luschka) were patent. We discuss this partial sequestration or communicating hydrocephalus of the fourth ventricle on the basis of MR and CT scan findings. Although computed tomography following water soluble cisternography did diagnose the entity indirectly MRI proved to be a superior tool. It permitted direct visualization of the basal foramina noninvasively.

Phenotype Variability in Myotonic Dystrophy Myotonic dystrophy, best known in the French literature as Steinert disease, is a dominantly inherited disorder. When the gene is fully expressed, it shows a characteristic clinical picture. Myopathy and myotonia are the main features, but this is a systemic disease which may involve many other organs such as the central nervous system, eyes, bones, endocrine system, etc. With the complete picture, physical and behavioral features make the diagnosis easy, only to be confirmed by neurological and ophthalmologic examination and/or electromyography. This work reviews the main clinical signs seen in the classical form of the disease. We also want to stress the variability of that picture. Finally, we describe a new dysmorphic sign in myotonic dystrophy: large prominent cupped auricles. Although not recognized, prominauris has been illustrated in a number of publications on myotonic dystrophy. Three of our adult male patients presenting the congenital form of the disease at birth have been investigated to rule out concomitant fragile-X syndrome. Both syndromes include mental retardation and dysmorphic ears. Our patients show the usual testicular atrophy, whereas the fragile-X syndrome includes testicular hypertrophy. Cytogenetic studies were normal. Old clinical description and new physical signs may lack prestige in the perspective of recent molecular biological breakthroughs, but to recognize the disease and help patients live with it will always be the role of practitioners.

The neurological and ophthalmological investigation of 602 members of 88 Saguenay kindreds affected by myotonic dystrophy (MyD) revealed 130 persons with a partial syndrome. These patients, whose average age was 34.1 years, showed different abnormalities such as particular ophthalmic and/or neuro-muscular signs, suggesting MyD in the absence of myotonia or typical lens abnormalities. After an average period of 2,4 years, 44 of these 130 patients were reassessed by the same neurologists and ophthalmologists. Thirty still had a partial syndrome, 8 showed a typical form of MyD and 6 no longer presented any identifiable anomaly. This preliminary follow-up study of the partial MyD syndrome did not allow us to identify any clinical anomaly from which the presence of the MyD gene could be predicted in a significant way. It furthermore suggested that the identification of equivocal or unspecific signs among these patients can sometimes lead to misdiagnosis. This must be taken into account when providing genetic counselling. It furthermore indicates that the use of DNA probes is essential for a reliable identification of asymptomatic MyD gene carriers.

The Mother and Infant with Myotonic Dystrophy Pregnancy and delivery present a number of risks for the mother suffering from myotonic dystrophy, and for her infant. Most of the time, she does not even know that she is affected by the disease and a carrier of the gene. We review the complications of pregnancy and delivery in myotonic patients, and propose a simple management with specific items for each gestational period. The child of a dystrophic mother has a 50% risk of inheriting the abnormal gene. He may also exhibit a developmental and malformation syndrome called "congenital myotonic dystrophy". From the beginning, he may show respiratory distress, thereafter inability to swallow and severely hypotonia. Later, he may demonstrate mental retardation. Some of the most obvious signs found in neonates in our practice are illustrated. We also add a few tests to the list of those already recommended for these children.

Myotonic Dystrophy: I Socio-Economic and Home-Environment Characteristics of the Patients. Myotonic dystrophy is a dominantly inherited genetic disorder which, in medical literature, has been linked to peculiar socio-economical conditions. In order to document this assertion, a sociological study was conducted in the Saguenay-Lac-Saint-Jean region (Quebec), using a representative sample (N = 218) drawn from the myotonic dystrophy population. A study of the patients' places of residence was also carried out. The results clearly indicate that myotonic dystrophy patients exhibit a socio-economic profile associated with disadvantaged milieux: high unemployment, low income and limited schooling. Many of these patients must rely on social welfare. Two families out of five (42%) live beneath the poverty line. The wage-earning history of these persons is closely linked to their self-evaluation of their working capabilities. After the age of forty, a high proportion of these people are unable to hold down a paying job and claim they are unable to do so. Within a well-screened urban area, a study of the patients' places of residence indicates census tracts where myotonic dystrophy is concentrated (ecological niches). These social areas are close to the downtown area and display characteristics of disadvantaged milieux. Accordingly, the My D gene seems to be confined to a specific socio-economic and socio-geographical environment, through which the spread of the gene is channelled among the population.

Myotonic Dystrophy: II Marriage, Fertility and Gene Transmission. A sociological study, using a representative sample (N = 218) of the myotonic dystrophy population, made possible an analysis of the relationship between certain demographic characteristics (marriage, fertility) and the mechanisms involved in the transmission of the deleterious gene. The results show a clear differentiation between the marriage rate of women and men affected by myotonic dystrophy. Whereas men show a considerable decline in marriage eligibility, women continue to marry at a young age and in a proportion almost equal to that of the unaffected population. The study also indicates that the average fertility rate among married patients in the Saguenay-Lac-Saint-Jean exceeds the fertility rate reported from affected populations found in other countries. Our study shows an above-normal male fertility rate. This demographic fact explains the overrepresentation of male transmitters noted in the affected population. However, if present trends remain unchanged, women will be more likely to transmit myotonic dystrophy to future generations. These conclusions illustrate how the transmission and spread of a dominant gene follow a pattern that cannot be dissociated from the socio-cultural characteristics taken as a whole, particularly demographic characteristics. They also provide us with useful avenues for setting up future prevention programmes.