The concept that “denervation” or “pharmacological disuse” supersensitivity develops in central neuronal systems subsequent to sustained attenuation of normal neurohumoral mechanisms is reviewed. Particular emphasis is placed on biochemical and electrophysiological parameters of supersensitivity in dopaminergic (striatal) neuronal systems. The possible applicability of theories invoking changes in receptor sensitivity to the phenomenon of narcotic tolerance and physical dependence and to psychoactive drug therapy is discussed.

The present paper analyses the new data accumulated since 1972 concerning the etiology and pathogenesis of Huntington’s chorea. Particular attention is paid to the respective roles of the dopaminergic and GABA-ergic systems.

The study of 3H leucine incorporation into skeletal muscle of mouse muscular dystrophy (129 ReJ/dy Bar Harbour strain) shows the uptake of isotope into myofibrils. The techniques employed were light and EM autoradiography before and after glycerination (Szent-Gyorgyi 1947). The results indicate a marked drop in uptake of the 3H-Leucine into myofibrils in the dystrophic animals, supporting the contention of Nihei et al (1971) that reduced myosin synthesis occurs in mouse muscular dystrophy.

This paper reviews some recent developments concerning the “non-essential” amino acid Taurine. It is shown that taurine is important in metabolic regulations within the heart, muscle and brain. Particular attention is paid to the neuropharmacology of taurine, such as its possible role in epilepsy.

The history of the control of epileptic disturbances by conditioning techniques is reviewed. The preliminary results of a three year trial of feedback techniques in 13 epileptic patients are presented.

Thirteen epileptic patients (age 2.5 → 39 mean, 15.1 years) with lateralized focal discharges in the EEG were given repeated trials of feedback, the focal discharges being used to trigger auditory and somatosensory stimuli. Dosages and serum levels of medication were unchanged throughout the experimental period. The number of epileptic spikes per 15 seconds was assessed by automatic trend analysis during 20 to 30 minute control, biofeedback and post-feedback epochs. Ongoing EEG activity was quantified by 8 channel frequency analysis over 10 second epochs. The patients made efforts to increase and decrease the number of spike discharges with and without feedback and the results of both triggered and random auditory, somatosensory, photic and combined stimulation were compared at various intervals over a period of up to three years. A marked reduction in the number of focal discharges was noted in eight (61.5%) patients during and immediately following the sessions.

Intermittent biofeedback sessions were not associated with a serial reduction in the number of focal EEG discharges. There was a reduction in the number of clinical epileptic disturbances in six patients (46%) and possible reasons for this improvement are discussed.

One patient suffered an increase in focal temporal lobe discharges during triggered and random auditory stimulation whereas there was a marked reduction in the number of discharges during minimal electrical stimulation of the contralateral arm. The need for careful assessment of each patient to determine appropriate feedback stimulation is stressed.

One aim of this research has been to assess the feasibility of using miniature units for continuous feedback of focal discharges in epileptic patients.

Electrophysiological studies have been carried out on five patients with neuropathies of different etiologies. In each patient serial estimates were made of the numbers of functioning motor units in various muscles. It was found that the intensity of the neuropathic process and the rate of recovery differed in a consistent way among the motoneuron pools investigated. The lesion was more severe in extensor digitorum brevis neurons than in thenar neurons, while the hypothenar ones were least affected. A stage of partial synaptic failure has been recognized in which a motoneuron appears to be no longer able to excite a muscle fiber, but still capable of maintaining certain trophic activities. By comparing the number of functioning motor units with the size of the maximum evoked muscle response it has been possible to detect the adoption of denervated muscle fibers by axonal sprouts from ‘healthy’ surviving neurons (collateral reinnervation). Lastly, in some muscles it appears that the adopted muscle fibers may subsequently be recaptured by the original motoneurons following recovery of the latter from the neurotoxic insult.

The specific behavioral manifestation associated with the different disorders producing the syndrome of dementia have remained poorly investigated. We examined the memory performance of three distinct groups of patients with dementia secondary to Alzheimer's disease (AD) multiple-infarctions (MID) and vertebrobasilar insufficiency (VBI) on the ten subtests of the Wechsler Memory Scale (WMS). Statistical methods of analysis were used to maximize the differences between the groups. Univariate statistical procedures revealed that the AD group performed significantly and consistently lower than the two cerebrovascular groups. There were no significant differences between the two cerebrovascular disease groups, even though the MID group tended to perform consistently more poorly than the VBI group. For heuristic and conceptual purposes as well as to determine which combination of the ten WMS variables produced the “best” statistical model differentiating the groups the data was analyzed by multivariate techniques. A discriminate function analysis obtained a 100% valid positive hit rate in discriminating among the three groups. One hundred percent diagnostic accuracy was also obtained in discriminating between MID and AD as well as AD and VBI. The two cerebrovascular groups tended to overlap in their probability distributions with an 81% hit rate. Different predicitive statistical models were identified to differentiate the various diagnostic groups. It was possible to discriminate the three diagnostic groups by different patterns of memory performance.

Lymphocytes of 29 subjects were assayed for MIF production in response to P2 peripheral nerve protein, crude human peripheral nerve and human central nervous system Al basic myelin protein. Seven were performed in normal control subjects, 12 in Guillain-Barré patients (GB), 5 with other polyneuropathies and 5 in patients with multiple sclerosis (MS). Only GB patients with acute illness produced MIF in response to neuritogenic P2 protein and crude human nerve. Two MS patients in the acute phase of an exacerbation and one GB patient produced MIF in Response to Al protein. The results of this study demonstrate cellular hypersensitivity to a neuritogenic constituent in peripheral nervous tissue and support the concept that this may be important in the pathogenesis of GB.

A study has been made of the neurophysiological changes that follow spinal cord lesions in man. The Achilles tendon reflex (ATR) is used to estimate transmission in the la monosynaptic pathway, and the tonic vibration reflex (TVR) to estimate transmission in the la polysynaptic pathway to motoneurons. The inhibition of the H reflex by vibration is used as an estimate of presynaptic inhibition of the la monosynaptic pathway. Immediately following a complete lesion of the spinal cord presynaptic inhibition of the la monosynaptic pathway appears to be greatly increased. This enhanced inhibition may last several months but it eventually declines and in some instances becomes less than normal. Transmission in the la polysynaptic pathway is permanently abolished by a complete spinal lesion. A hypothesis is developed from these findings to explain the evolution of some of the clinical features that follow complete spinal lesions in man. Distinct differences are observed when the spinal lesion is incomplete. Transmission in the la polysynaptic pathway may be preserved and there may be no increase in presynaptic inhibition. These differences may depend upon the integrity of certain spinal long tracts which cannot be tested clinically.

A double-blind, double-observer study was carried out in twenty-five patients with Parkinson’s disease. Alpha methyldopahydrazine in combination with L-dopa was compared to placebo with L-dopa. Combination therapy resulted in a reduction in L-dopa dosage to 1/3 of the amount required during the baseline. There were no side effects attributed directly to the alpha methyldopahydrazine. The overall incidence of side effects in the two groups was similar but the combination therapy significantly reduced the incidence of nausea and vomiting. The limiting factor in the combination therapy was the presence of L-dopa induced dyskinesias.

This is a report of the first recorded observation of displacement of temporal cortex into the central spinal canal in an infant with the Arnold Chiari malformation, platybasia, aqueductal atresia, hydrocephalus and meningomyelocele. The combination of an absent tentorium, absent right cerebellar hemisphere and malformed fourth ventricular roof provided the anatomical background for this unique event.

The aim of this experiment was to investigate the reaction of peripheral nerve tissue to a synthetic absorbable suture material. Polyglycolic acid suture material was placed within the sciatic nerve of rats and the absorption of the material was investigated by means of electron photomicrographs. It was concluded that placement of polyglycolic acid into the peculiar environment of endoneurial tissues results in minimal scarring and in minimal disturbance of the surrounding nerve fibers. The material was progressively absorbed with minimal disturbance of intrafascicular structures.

This is a review of the total care of those acute spinal cord injury patients in Ontario during the years 1969 and 1970, from extrication and transportation following the accident to death, or the completion of primary definitive rehabilitation.

Information was extracted from the available ambulance records, the patients and many of the responsible physicians were interviewed personally. The study was detailed and intensive and included a review of each patient's hospital records in each hospital up to discharge from the rehabilitation programme into the community, or to a chronic care unit. The data was compiled in accordance with a detailed and lengthy questionnaire developed for this study.

The incidence of acute cord injuries in Ontario in 1969 and 1970 amounted to 244; in 1969, 15.9 per million population and in 1970, 13.6 per million. As in other studies road accidents took first place, followed by falls from a height; sports injuries ranked third and 65.7% of these were caused by diving into shallow water. Age incidence, and incidence by month, day of week and time of day were identified. Fridays and Saturday afternoons in July and August are particularly hazardous.

The study continued to the end of 1974 by which time 34 deaths had been recorded. Peak incidence of death occurred within fourteen days of injury. The most common cause of death was respiratory in origin.

Geographical distribution was identified and the type of hospital treating the acutely injured patient.

Fourteen percent of persons with spinal column injury suffered progressive or sequential spinal cord damage both prior to and following medical contact. The incidence of pressure sores and genitourinary sepsis and calculosis was high in all types of hospitals. The effect of operative treatment was noted in the cases of complete quadriplegia and paraplegia.

Of the 133 survivors who undertook a rehabilitation program, 84% returned to their homes and 59% achieved gainful employment or ongoing education.

The cost was determined of general hospital services and rehabilitation programmes.

A new model for the care of the spinal cord injury patients in Ontario was proposed.

The ultrastructural responses of cerebral tissue following temporary periods (½, 1, 2, 3, or 4 hour) of right, middle cerebral artery, (MCA) occlusion were studied acutely after a 3 day or 7 day interval following the removal of the MCA clip. Cortical and basal ganglia tissues for each ischemic duration were compared at 3 post-occlusive periods (acute, 3 days, 7 days).

With the short periods of ischemic insult (½, 1, 2, 3, and 4 hour), the temporal and insular cortex contained no greater changes in the 7 day group than in the 3 day group.

The basal ganglia were more susceptible to MCA occlusion as indicated by more marked cytological changes and/or necrosis in all intervals of ischemia.

In 1975, medical neurology is a well established, viable, growing specialty in Canada. There are now almost 250 neurologists scattered across the country, congregated largely in the hospitals associated with our 16 medical schools. Neurology is a major component of the undergraduate curriculum in each of these schools, and the majority of schools are approved for postgraduate training in our specialty. The Royal College has certified an average of 18 new neurologists each year for the past five years. In our hospitals we work closely with our internist and neurosurgical colleagues and we receive the support of highly competent teams of neuropathologists, clinical electrophysiologists and neuroradiologists. We believe that we provide a generally high standard of consultation service to our medical and surgical colleagues. We accept direct responsibility for patients suffering from a host of acute neurological problems, but we accept long term responsibility for very few. We do a great deal of teaching at both the undergraduate and graduate levels. In fact, the major role which neurology plays in undergraduate curricula, and the stimulus of postgraduate education, probably have been the two most influential factors shaping the number, work patterns and distribution of Canadian neurologists. Many of us are engaged in clinical investigation, but relatively few medical neurologists in Canada make fundamental research contributions.

Since the description by Galen in the 2nd Century, A.D., clinical neurology has acknowledged the existence of two types of tremor: that which occurs at rest and that occuring during the execution of movement. With the help of refined methods of analysis, E.M.G. and cinephotography, the authors have carried out a detailed clinical assessment in more than 400 patients.

The basic criterion used to define a tremor was the classical definition of Dejerine: “An involuntary, rhythmical and symmetrical movement about an axis of equilibrium.”

As a result of this study, the conclusion has been reached that there are two types of tremor: postural tremor and tremor of attitude. Both are present while the limb remains immobile, whether by wilful design or when at rest in a position of posture and subject only to the action of gravity.

During voluntary movement, tremor is not present. Irregular, asymmetrical and non-rhythmic oscillations may appear however — as in so-called intention tremor, of cerebellar origin — but this abnormal movement can hardly be called a real tremor. It is merely a manifestation of ataxia.

As a consequence of this study, it is suggested that further understanding of the basic mechanism of tremor can be reached by the investigation of the central neural structures which are involved in the physiology of posture and attitude.

The effect of diazepam on presynaptic inhibition in man has been examined in 5 patients with complete spinal transections and 7 patients with incomplete lesions. The inhibition of the H reflex by vibration applied to the tendo Achilles was used to assess presynaptic inhibition of the la monosynaptic pathway. Diazepam increased this inhibition in the patients with incomplete lesions, but had no significant effect on the inhibition in the patients with complete spinal transections.

Evidently diazepam can enhance presynaptic inhibition in man. The effect, however, cannot be demonstrated in patients with longstanding complete spinal lesions possibly because of some alteration in the segmental presynaptic inhibitory mechanism in this group.

A retrospective analysis of 274 patients with intracranial aneurysms, diagnosed either angiographically or at autopsy between 1968 and 1973 at the University of Alberta, was carried out. One hundred and forty-six patients had intracranial clipping of the aneurysm. Clinical and radiologic data were abstracted from the chart and the angiographic studies. Probability of survival curves were constructed. Associations between various clinical factors and survival at two months were demonstrated. The most important prognostic factors were the clinical grade at angiography or surgery, followed by the presence of preoperative spasm, hematoma or focal edema, elevated blood pressure on admission, time interval from hemorrhage to surgery and age. The data lends some support to the policy of operating on patients in good neurological condition, even if their pre-operative angiogram shows spasm.

A method of internal fixation of adjacent vertebrae that have been dislocated or subluxed has been presented. In the author's hands and in the hands of associates this has proven to be a satisfactory method of fixation in this type of injury. It has the advantage over many other posterior techniques that only two vertebrae are fixed together.

Thirty-nine patients with a variety of diseases, including essential tremor, Parkinsonߣs Disease, olivopontocerebellar degeneration, ataxia telangiectasia, and cervical cord injury with action tremor, were evaluated for the effect of one ounce of absolute alcohol ingestion. Tremor significantly subsided in 61.9% of E.T.; 46.6% of P.D.; one patient with A.T.; and one patient with C6 lesion. The tremor became worse in one patient with O.P.C.D. Twenty of these patients were treated with propranolol, an average dose of 92 mgm. per day, and re-evaluated three to six months later. All those who improved on alcohol improved on propranolol and the one whose tremor accentuated with alcohol had a similar response to propranolol. It is concluded that the tremorilytic effect of alcohol is neither specific for, nor limited to, essential tremor and is of no value in differentiating various neurological disorders which manifest as action tremor. It is recommended that one ounce of absolute alcohol by mouth be used as an office procedure to predict the response of patientsߣ tremor to propranolol.