A review of some of my personal recollections and research into the early development of neuroscience in Canada seems particularly appropriate at this time since we have just celebrated the 50th anniversary of the founding of the Montreal Neurological Institute which not only played a leading role in the early development of neuroscience in Canada, but also had considerable impact upon the development of both clinical and basic neuroscience throughout the world. The concept of the fusion of all the varied disciplines concerned with studies of the nervous system into one integrated “neuroscience” as we know it today in the Society for Neuroscience was not known when Dr. Penfield established the Montreal Neurological Institute with this in mind. He recruited colleagues in neurochemistry, neurophysiology, neuroanatomy, pathology, and neuropsychology to work in close association with clinical neurologists and neurosurgeons. Fellows were attracted from many countries for training in all of these disciplines and shared his dream of an integrated neuroscience aimed at a better understanding of the function of the nervous system underlying behaviour and mental function and more rational treatment of neurological diseases.

The inspiration, enthusiasm, and tireless determination of Dr. Penfield during the difficult times for the initial few years and during the most productive years of rapid growth following World War II, helped develop the Institute into a leading centre for research and training of neuroscientists in Canada, and also served as a catalyst for the rapid development of neuroscience in other centres throughout Canada and the United States. As one of my French colleagues has expressed it, the Institute was the “mother house” of neuroscience in Canada. It soon became a truly international institute of worldwide reknown.

The Hannah Institute for the History of Medicine and Science, with the Royal College’s Section on the History of Medicine, asked me for a contribution to the Annual Meeting (1984) in Montreal dealing with the history of Canadian neurosurgery. I soon discovered that the material available to me, from my own files and from colleagues who sent me information, was too extensive for a paper of the required length. I have therefore excluded from this article the balanced review of the scientific and clinical contributions of Canadians in neurosurgery that I had hoped to prepare. What remains is a collection of events and developments that have involved or interested me during my career.

William Osier’s bibliography includes over 1400 papers, monographs, and notes touching on almost every subspecialty of medicine (Abbott 1939). He has been claimed by gastroen-terologists (Cunha 1948), pediatricians (McGovern et al 1970; Robbinsetal 1963), medical librarians, (Bett 1949), veterinarians (Giltner 1926–27) (Murphy 1960) obstetricians (Rucker 1952) and members of other disciplines as one of their own.

Osier published close to 200 papers, reviews, editorials and monographs dealing with neurology, but it is not widely recognized that his contributions to neurology exceed those to many of the other fields. For example, Osier’s interest in neuropathology was entirely omitted from the recent excellent monograph “An Oslerian Pathology” (Rodin 1981). The purpose of this paper is to bring into focus his impressive neurological contributions and to document his substantial interest in the neurosciences.

Osier’s activities in neurology constituted a microcosm of his overall medical contributions. His interests in the neurosciences began early. In 1884 he wrote on the comparative anatomy of the brain of the seal (Osier 1884a), having given a lecture on “the brain as a thinking organ” in the previous year (Osier 1883a).

Pituitary adenomas may produce local endocrine and neurological effects, as well as systemic metabolic complications due to hormonal hypersecretion. Medical therapy with pharmacological agents has been developed and is based on the neurotransmitter regulation of normal pituitary hormonal secretion. 189 patients with secretory pituitary adenomas underwent medical therapy for the hypersecretory state. 156 of these were prolactin-secreting adenomas, 16 of which were in males. The response of bromocriptine was almost universal with lowering of serum prolactin and reversal of the clinical symptoms, as well as tumor shrinkage of most large adenomas with suprasellar extension. 23 patients with acromegaly were treated with bromocriptine, with 11 noting clinical improvement, and decreased tumor size in two. Five patients with Cushing’s disease were treated with cyproheptadine, with only one showing a biochemical and clinical improvement. Two patients with Nelson’s syndrome each had progressive tumor growth stabilized with cyproheptadine and bromocriptine in one, and sodium valproate in the other. There appears to be a role for medical therapy in the majority of prolactin-secreting pituitary tumors, some growth hormone secreting pituitary tumors, and selected adrenocorticotropin secreting-pituitary tumors.

We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5%unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects.

We report the case of a patient with idiopathic aqueductal stenosis and hydrocephalus who had several episodes of akinetic mutism, each preceded by shunt malfunction, that resolved with shunt revision. She also developed a parkinson’s syndrome resistant to shunt revision but responsive to antiparkinsonian medications. The Parkinson’s syndrome and the episodes of akinetic mutism may be related to a reduction of dopaminergic input to the striatum and to the cingulate and frontal cortex brought about or worsened by ventricular dilatation.

Early hemorrhagic changes in the spinal cord were compared in three experimental spinal cord injury models in the rat in order to determine the nature and consistency of spinal cord hemorrhage following specific and quantitated forces of injury. The spinal cords were injured by weight-dropping, aneurysm clip and extradural balloon compression techniques. Hemorrhagic changes were assessed quantitatively by the image analyser at 1 and 3 hours after injury. Tissue damage was assessed by determining the percentage of total cross sectional area containing hemorrhage. The extent of hemorrhage at site of injury in the clip and balloon preparations was equal, but several times lower in the weight-drop induced injury. Within each experimental group no appreciable differences were observed at the site of injury between the 1 and 3 hours preparations. The variability of damage within experimental groups was most in the weight-dropping and balloon and least in the clip preparations. Differences were also indicated with respect to the distribution of hemorrhage in grey versus white matter. These findings may be of significance when functional recovery is considered in various experimental acute spinal cord injury models.

The role of the carotid siphon as a source of embolic material has had limited morphological or clinical study. The morphologic data available suggests that the siphon plays only a small role in embolic cerebrovascular disease. Clinical studies, however, suggest that it has a significant ischemic potential. To clarify this apparent discrepancy, we have designed a scanning electron microscope study of the carotid siphon. Eighty percent of the specimens from the carotid bifurcation and 30% of the siphon specimens showed evidence of damaged endothelium with attached red cell and platelet debris. The embolic potential of the siphon is estimated to be between ⅓ to ½ that of the carotid bifurcation. This supports the most recent clinical studies.

A retrospective study of 100 patients with spontaneous intracerebral haemorrhage was carried out, to identify clinical factors which have a predictive value for outcome. Numerical equivalents for the admission level of consciousness (the Glasgow Coma Scale), ventricular rupture, partial pressure of oxygen in the blood, the electrocardiogram, clot location, and clot size were combined into equations predicting outcome. The best single parameter for prediction was the Glasgow Coma Scale.

The association of idiopathic Parkinson’s disease and Creutzfeldt-Jakob disease has not been reported previously. We describe the clinical findings in a patient with both disorders, confirmed at autopsy. The differential diagnosis of parkinsonism with cognitive and psychiatric disturbances is reviewed with emphasis on conditions which may complicate the course of idiopathic Parkinson’s disease. The etiological implications of this combination are considered.

The demonstration of low arylsulfatase-A (ASA) activity in leucocytes or fibroblasts is used often to establish the diagnosis of metachromatic leucodystrophy (MLD). However, low ASA activity is observed also in pseudo-ASA deficiency which may be as common as MLD. We report two patients with pseudo ASA deficiency who had abnormal neurological findings consistent with atypical MLD. Because the measurement of ASA activity is neither a sensitive nor specific method with which to establish a diagnosis of MLD, this diagnosis should be confirmed by nerve biopsy, measurement of urinary sulfatide or a cerebroside sulfate loading test, using cultured fibroblasts.

A review of the literature on primary diffuse meningeal gliomatosis (DMG) yielded three cases and we report a fourth. DMG is a syndrome characterized by extensive basal and spinal chronic meningitis with mental confusion, headaches, diplopia, papilledema and cranial nerve palsies. The cerebrospinal fluid (CSF) has a markedly elevated protein content, moderate mononuclear pleocytosis and a normal or low glucose. This picture invariably leads to the diagnosis and treatment of tuberculous or fungal meningitis despite persistently negative cerebrospinal fluid (CSF) cultures. Reaction of exfoliated CSF cells with glial fibrillary acidic protein (GFAP) immunoperoxidase labelled antibody is suggested as a diagnostic tool. A basal meningeal biopsy appears to be the only alternative diagnostic approach.