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 internal spinal cord blood flow was measured in dogs at the site of local cooling using hydrogen polarography. Blood flow decreased to 50% of the normothermic values during cooling of the cord to a central temperature of 16 degrees Celsius. Upon cessation of cooling internal blood flow rapidly returned to normal values. Implications of this finding for the treatment of spinal cord injury are discussed.

Hypotheses concerning the etiology of Alzheimer’s disease are numerous but perhaps two of the most probable involve either an unconventional infectious agent of the scrapie, Creutzfeldt-Jakob family or an error in gene expression. Strong circumstantial evidence supports both hypotheses; however, definitive evidence will require an extensive understanding of the molecular biology of this common cause of senile and presenile dementia.

Diseases of the aorta and surgery of the aorta can produce spinal cord damage. There are major variations in blood supply to the spinal cord between individuals. The spinal cord may be tamponaded by increased spinal fluid pressure subsequent to clamping the aorta. Both of these factors may contribute to spinal cord infarction. The available methods and procedures to protect the spinal cord during surgery are discussed.

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.

The planarian is the simplest living animal having a body plan of bilateral symmetry and cephalization. The brain of these free-living flatworms is a biiobed structure with a cortex of nerve cells and a core of nerve fibres including some that decussate to form commissures. Special sensory input from chemoreceptors, photoreceptor cells of primitive eyes, and tactile receptors are integrated to provide motor responses of the entire body, and local reflexes. Many morphological, electrophysiological, and pharmacological features of planarian neurons, as well as synaptic organization, are reminiscent of the vertebrate brain. Multipolar neurons and dendritic spines are rare in higher invertebrates, but are found in the planarian. Several neurotransmitter substances identified in the human brain also occur in the planarian nervous system. The planarian evolved before the divergence of the phylogenetic line leading to vertebrates. This simple worm therefore is suggested as a living example of the early evolution of the vertebrate brain. An extraordinary plasticity and regenerative capacity, and sensitivity to neurotoxins, provide unique opportunities for studying the reorganization of the nervous system after injury. Study of this simple organism may also contribute to a better understanding of the evolution of the human nervous system.

The basic principles of nuclear magnetic resonance (NMR) are reviewed and the appearances of some lesions of the skull base are discussed. NMR is a valuable diagnostic study for skull base lesions and it provides information that is not shown on the CT scan. The modern investigation of unusual skull base lesions should include both CT and NMR.

Since Binswanger’s description of subcortical arteriosclerotic encephalopathy in 1894, numerous cases have been reported. Several authors doubt the validity of this malady, although the majority consider it to be a disease entity. We report seven cases with this type of pallor of myelin, only two of which are accompanied by a history of dementia. Among the seven cases, two had arteriosclerosis of penetrating arteries and arterioles in cerebral white matter. Electron microscopy showed splitting of myelin sheaths, probably the result of edema. In reviewing the blood supply of the cerebral white matter, we conclude that no pathological alterations of medullary branches of the cerebral arteries, the same vessels supplying the white matter, can give rise to such diffuse pallor of white matter and spare the arcuate fibres. This pallor can only be due to cerebral edema, most likely of hypoxic-ischemic, hypotensive, or acidotic origin. We also contend that arteriosclerosis can only cause dementia through multiple infarcts or lacunae, if it indeed leads to dementia.

Positron emission tomography provides a method for the quantitation of regional function within the living human brain. Studies of cerebral metabolism and blood flow in patients with Huntington’s disease, Parkinson’s disease and focal dystonia have revealed functional abnormalities within substructures of the basal ganglia. Recent developments permit assessment of both pre-synaptic and post-synaptic function in dopaminergic pathways. These techniques are now being applied to studies of movement disorders in human subjects.

Early detection of visual loss caused by tumours of the base of the skull is accomplished by systematic tests of the pregeniculate optic pathway. Even when central acuity is relatively preserved, a relative afferent pupillary defect and reduced color perception yield evidence of impaired optic nerve conduction. Although confrontation tests of the visual fields are useful screening techniques, unexplained symptoms should be pursued with static and kinetic perimetry. Patterns of optic nerve and chiasmal field loss and atrophy of the disc or retinal nerve fibers are imprecise guides to the location of basal skull tumours. Regardless of the pattern of visual field defect, unexplained progressive loss of vision demands intensive neuroradiologic study of the basal cisterns and skull.

A retrospective study of neonatal seizures in a tertiary care neonatal intensive care unit determined a 3.2% incidence, and confirmed the relatively poor efficacy of the traditional anticonvulsants phenobarbital and phenytoin. Only 33% responded to an initial adequate loading dose of phenobarbital, while 56% responded to either or both anticonvulsants. Although multifocal clonic seizures were most common (42%), tonic seizures were next in freqency (30%). Tonic seizures which did not respond to phenobarbital responded quite poorly to the addition of phenytoin compared to other seizure types. Tonic seizures may be the result of brainstem release phenomena and require a different strategy for management. Among nonresponders in this study, there was a 56% mortality rate but only 33% of responders died. There is a critical need for studies to find more efficacious agents than phenobarbital and phenytoin to treat seizures in the newborn.

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).

Awake, unrestrained monkeys were trained to reach out with the forelimb and touch a button. Extracellular spike trains were recorded from pairs of neurons in contralateral precentral cortex with the same or separate microelectrodes. The neurons were located in the same or different functional columns as defined by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed patterns consistent with synaptic excitation and/or inhibition between members of the cell pairs during the voluntary movement. The strength of correlation was inversely related to distance between columns, with the strongest correlations found between cells within the same column. Inhibitory correlations were virtually restricted to cell pairs within a single column. Temporal analysis showed that direct synaptic interaction and shared input patterns could be clearly distinguished in this physiologic setting. Spatial analysis indicated that shared input was concentrated among columns in the same and adjacent joint controlling zones as well as within a single column. No directional preference of shared input was present, a finding which was consistent with the observed nested organization of the forelimb area.

Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.

Simultaneous extracellular unit recordings were made from each cell of 237 pairs in two awake monkeys, during a voluntary reaching movement of the forelimb. The cells were located in contralateral precentral cortex and functionally coupled to single forelimb joints, as indicated by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed that 72 of these pairs exhibited significant event-related correlation over periods of up to 780 ms, comparable to and coincident with the forelimb movement. Spatial analysis showed that such correlation extended across contiguous portions of all four forelimb joint zones of precentral cortex, over distances up to 3.5 mm. No preferred direction of correlation was observed. The data confirm the previously described nested organization of the forelimb area of precentral cortex. Findings are discussed in terms of mechanisms by which columns of neurons in motor cortex participate in the reaching movement.

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.

Visual evoked response (VER), auditory brainstem evoked response (ABER), somatosensory evoked response (SSER), blink reflex and electronystagmographic (ENG) investigative methods were applied to a group of 89 patients with Multiple Sclerosis (MS) and Optic Neuritis (ON). The MS patients were classified as definite (n = 31), probable (n = 31) and possible (n = 27).

The aim of this study was to determine the diagnostic value of the five electrophysiological tests in MS. VER and ABER recordings were found to reveal the highest number of asymptomatic abnormalities (33 and 31 percent respectively). The combination of VER, ABER and ENG revealed all possible electrophysiological disorders. As these tests are completely non-invasive it is proposed, that a combination of two of these three tests is useful for the detection of a second silent lesion in patients with suspected MS showing purely spinal signs (VER, ENG, ABER) and/or a history of uncomplicated ON (ABER, ENG).

We studied multimodal evoked potentials (EPs) longitudinally in a series of children with Friedreich’s ataxia and ataxia telangiectasia to determine both their diagnostic utility and their correlation with clinical regression.

The auditory brainstem responses (ABRs) were abnormal only in the children with Friedreich’s ataxia. The abnormality seen in these patients was a rostral-caudal loss of the ABR waves. The visual EPs (VEPs) were abnormal in many of the patients; those with ataxia telangiectasia had unusually low amplitude or absent VEPs, occasionally with increased latencies, whereas those with Friedreich’s ataxia had normal amplitude VEPs, often at increased latencies. The somatosensory EPs were usually of increased latency or absent in these patients. Unlike the ABR and VEPs, they did not serve to differentiate the groups.

Changes in the EPs appeared to reflect clinical deterioration; patients with little change in their EPs over several years were regressing very slowly, whereas others had rapid deterioration in both EPs and clinical status. We suggest that the EPs are diagnostically of value in degenerative ataxias and may be of value in monitoring these patients and their response to therapy.

Despite advances in instrumentation and the use of microsurgical techniques, neurosurgical procedures involving extensive areas of skull base or other critical areas of brain still carry significant risk for neurological injury. The use of intraoperative recording of sensory evoked potentials (SEP) has been advocated to monitor neurologic function during these major neurosurgical procedures to reduce the risk of injury to neural structures.

This report summarizes our experience with intraoperative monitoring of SEP in over 200 patients, and details our findings in a group of 12 patients with skull base and posterior fossa tumours. Somatosensory evoked potentials (SSEP) were monitored in all patients, and brain stem auditory evoked potentials (BAEP) in five. While minor changes in BAEP and SSEP parameters were noted in most patients, significant changes occurred in five. Irreversible loss of BAEP in one patient was associated with complete hearing loss postoperatively. Marked, persistent alteration of both BAEP and SSEP was associated with postoperative brainstem dysfunction. No patient with stable BAEP and SSEP at the end of the procedure suffered additional neurological deficit.

We conclude that intraoperative SEP monitoring may be valuable in minimizing neural injury during major neurosurgical procedures.