One hundred and fifteen patients with definite multiple sclerosis (M.S.) and chronic persistent fatigue were studied. This ten-week cross-over study consisted of a 2-week baseline period and two 3-week treatment periods separated by a 2-week washout. Patients received either amantadine 100 mg bid or matching placebo capsules. Fatigue, the effect of fatigue on an individually pre-selected activity and its effect on activities of daily living, were evaluated. Amantadine produced a small but statistically significant decrease in fatigue. An important placebo effect was noted. Mean fatigue during the washout period was lower than during the placebo run-in period, independently of which treatment had been given first. Side effects were numerous both on amantadine and on placebo. Only insomnia was significantly more common with amantadine.

This report describes the results of microsurgical discectomy in a prospective study of 200 consecutive patients with intractable sciatica, followed independently by a pain clinic. Post operative morbidity was minimal, the complication rate very low, and patients were discharged home early. Leg pain was relieved in almost all patients, but back pain was relieved in only 72% of patients. The rate of return to work at one, three and twelve months post-operatively was 50%, 83% and 95% respectively. Microsurgical discectomy is an effective and safe procedure.

Neurotransmitters of the basal ganglia are of three types: I, amino acids; II, amines; and III, peptides. The amino acids generally act ionotropically while the amines and peptides generally act metabotropically. There are many examples of neurotransmitter coexistence in basal ganglia neurons. Diseases of the basal ganglia are characterized by selective neuronal degeneration. Lesions of the caudate, putamen, subthalamus and substantia nigra pars compacta occur, respectively, in chorea, dystonia, hemiballismus and parkinsonism. The differing signs and symptoms of these diseases constitute strong evidence of the functions of these various nuclei. Basal ganglia diseases can be of genetic origin, as in Huntington's chorea and Wilson's disease, of infectious origin as in Sydenham's chorea and postencephalitic parkinsonism, or of toxic origin as in MPTP poisoning. Regardless of the etiology, the pathogenesis is often regionally concentrated for reasons that are poorly understood. From studies on Parkinson and Huntington disease brains, evidence is presented that a common feature may be the expression of HLA-DR antigen on reactive microglia in the region where pathological neuronal dropout is occurring.

Although carotid endarterectomy is a common surgical procedure in North America, controversies exist regarding the type of anesthesia, the use of indwelling shunts and the need for intraoperative cerebral monitoring. We present a prospective study of 100 carotid endarterectomies performed over a three year period by a single surgeon without the use of indwelling shunts, patch grafts, or EEG monitoring. The combined stroke and mortality rate was 1%. Our results confirm those of other authors; that indwelling shunts and EEG monitoring are not absolutely essential for a satisfactory outcome in carotid endarterectomies.

The optimal timing of definitive aneurysm repair following subarachnoid hemorrhage remains a controversial issue. In order to examine whether the timing of surgery alters the incidence of certain technical difficulties and complications associated with intracranial aneurysm repair, data from two recent co-operative studies were examined. The cases submitted to the International Co-operative Study on Timing of Aneurysm Surgery by the University of Toronto hospitals, and the cases submitted from multiple centres to the Three-Dose Multicentre Randomized Double-Blind Nimodipine Study were evaluated with regard to operative difficulties and complications, comparing early (≤ 3 days) and late (≥ 4 days) surgery following subarachnoid hemorrhage. No significant differences were found in the incidence of such technical problems between the early and late surgical groups. If differences in outcome occur between comparable groups of patients operated early and late after aneurysm rupture, factors other than surgical technical complications may be responsible.

Twenty-six (41%) of 63 consecutive patients with triphasic waves had various types of metabolic encephalopathies while 37 patients (59%) had non-metabolic encephalopathies, usually senile dementia. Triphasic waves were not found to be specific for any single type of metabolic encephalopathy.

Etiology was more closely linked to conscious level at recording than any morphological or distributional feature of the triphasic waves themselves. Thus, all 31 alert patients had non-metabolic encephalopathies while all 13 comatose patients had metabolic encephalopathies.

The second, positive, component (Wave II) most often had the highest voltage while equally maximal Waves I and II occurred next most commonly. Triphasic waves were most often maximally expressed anteriorly.

Among patients with metabolic encephalopathies, a posterior-anterior delay or lag of the wave II peak occurred more commonly than did the better known anterior-posterior lag. Lags occurred with both metabolic and nonmetabolic conditions, but were more common with the former. No difference in quantity or mode of appearance existed between the metabolic and non-metabolic groups when matched for conscious level.

Prognosis for patients with either metabolic or non-metabolic encephalopathies was unfavourable. Only 4 of 24 metabolic and one of 35 non-metabolic patients were well at follow-up over 2 years later.

Forty percent of EEGs with sharp and slow wave complexes (slow spike waves) had sporadically-appearing triphasic waves. The relative amplitudes of the 3 components differed from triphasic waves in other conditions: equally maximal Waves II and III were the most usual form.

Fifty-one patients were enrolled in a double-blind, parallel group, multicentre study conducted to assess short-term efficacy and tolerance of bromocriptine (Parlodel®) or L-DOPA/carbidopa (Sinemet®) in patients never treated with amantadine, ergot alkaloids or L-DOPA-based drugs. An attempt to use the lowest effective dose was made. The responder rate for each group was approximately 78%; the mean daily dose for responders was 22.5 mg of bromocriptine or 250 mg of L-DOPA/carbidopa. The overall clinical improvement in each group was 62% (bromocriptine) and 55% (L-DOPA/carbidopa) for neurological assessment and 36% (bromocriptine) and 31% (L-DOPA/carbidopa) for functional disability. Comparison between groups did not show any significant difference for both neurological and disability assessments. The most frequent side effect was nausea (L-DOPA, N = 3; bromocriptine, N=6).

This paper reviews current concepts concerning the anatomical organization and functions of the basal ganglia focusing mainly on the role of the basal ganglia in control of movement. Results of several studies which have been carried out on patients with Parkinson's disease are also reviewed and discussed as examples of altered normal physiological mechanisms.

We make use of the unique combination of a homogeneous genetic and racial origin in the rural population of Quebec and the facilities of free and universal access to medical care, to study the distribution of the prevalence of Parkinson's disease in the 9 rural hydrographic regions of the Province. Through 3 different methods of ascertainment, confirmed by two control probes, we demonstrate that the prevalence of Parkinson's disease is of uneven distribution within rural areas. We further investigated the characteristics of the regions of high prevalence. These regions which are predominantly agricultural and areas of intensive market gardening were also the areas with the highest use of pesticides.

A battery of colour vision tests was employed to evaluate visual function in patients with multiple sclerosis (M.S.). Colour deficits were found in 45% of patients tested with the Ishihara plates and 42.5% of patients tested with the FM 100-Hue test. 65% of M.S. patients failed at least one of the tests.

The colour vision deficits were not restricted to patients with optic neuritis or with visual evoked potential (VEP) abnormalities and there was no significant correlation between an abnormal VEP latency and a colour vision deficit. Colour vision testing may be a useful option to consider in the investigation of M.S. patients, even if there is no other evidence of visual system involvement.

Purified botulinum A exotoxin was used in the treatment of forty seven patients with benign essential blepharospasm, 11 patients with hemifacial spasm and 2 patients with age-related entropion. The treatment was effective in all three groups for an average of 3-4 months when symptoms recurred and repeated chemodenervation with toxin was needed. The commonest complication was transient ptosis with an overall frequency of 7.8%. This incidence increased to 11.1% with toxin doses higher than 25 units per orbicularis. The treatment was well accepted by the patients, who were subsequently able to return to pre-blepharospasm lifestyles.

Explants of 21 neurofibromas from 16 patients with Von Recklinghausen neurofibromatosis (NF-I) plus tumour tissue from 5 comparison patients and normal tissue from one of the NF-I patients were assayed for neuronal growth factor(s) using dissociated embryonic sensory neurons from chick embryo. Twenty-one of 21 neurofibroma explants released detectable quantities of neuronal growth factors, but only 2 of 8 non-neurofibroma tissue explants released activity.

While antiserum to mouse nerve growth factor (NGF) fractionally inhibited neurite outgrowth induced by some of the neurofibromas, overall differences between assays containing antibody and controls reached statistical significance in 3 cases; in one case, explants of a separate tumourfrom the same patient had no detectable NGF-like activity.

These data support the hypothesis that local release of neuronal growth factors in neurofibromas are responsible for neurites observed within these tumours. Further evidence that endoneurial tissue of peripheral nerve is a rich source of heterogeneous neuronal growth facts has been provided by these studies.

Spontaneous dissection of a major subarachnoid artery is an uncommon cause of stroke in young and apparently healthy individuals. Such dissection does not correlate well with systemic conditions such as emboli, thrombotic or hemorrhagic tendencies or hypertension, nor with disease of blood vessels such as atherosclerosis, fibromuscular dysplasia, cystic medial necrosis or Moya-Moya disease. Unusual exertion has been implicated as a factor in some cases. Gap defects were found in the internal elastic lamina near the site of dissection in three of four cases of spontaneous dissection reported here. It is suggested that such defects, because of their unusual size or number, may be responsible for initiating dissection in susceptible individuals. A detailed study of the major cerebral arteries in cases of dissection and control cases to document the size and frequency of such defects could shed light on the pathogenesis of spontaneous dissection. The subsequent course of events tends to differ in the internal carotid and vertebro-basilar systems. In most cases, the dissection in the internal carotid system is sub-intimal leading to thrombosis and cerebral infarction, while in the vertebrobasilar system dissection lies between the media and adventitia leading to subarachnoid hemorrhage. It is not known what structural differences of the two arterial systems may underlie this difference in the pattern of arterial dissection.

We reviewed the CT findings of 387 patients with new-onset seizures after the age of 50. Seizures were generalized in 212 patients, focal in 160, and indeterminant in 15. CT scanning revealed cerebral atrophy in 113 cases, ischemic lesions in 75, cerebral neoplasms in 20, and no abnormality in 177 cases. Tumours were found in only three patients with generalized seizures, and all three had focal neurological deficits at the time of CT diagnosis, while 17 neoplasms were discovered in patients with a focal seizure disorder. The majority of patients with late-onset epilepsy have a normal CT scan with cerebral atrophy being the most common abnormality detected. Cerebral vascular disease appears to be the most frequently identified cause of late-onset epilepsy, while cerebral neoplasms are uncommon.

L'observation d'une poly-neuropathie associée à une cryoglobuline et à un syndrome sec est rapportée chez une femme âgée de 76 ans. La biopsie de nerf montre une démyélinisation très importante. Une vascularité est mise en évidence sur le prélèvement musculaire. La discussion envisage les neuropathies périphériques dans le cadre du syndrome de Gougerot-Sjögren et dans celui des cryoglobulines. Les traitements doivent être entrepris sans tarder et surtout les plasmaphérèses.

Disruption of neural activity within the basal ganglia of experimental animals causes selective learning deficits in tasks requiring switching between response strategies. These data along with reports of both general and specific intellectual impairment in patients with neurodegenerative disorders such as Parkinson's disease, appear to support the theory of cognitive functions of the basal ganglia. Recent studies have failed to confirm general cognitive or memory deficits in parkinsonian patients, but have identified deficiencies in devising and executing certain cognitive strategies. Following the lead of theorists such as Squire and Mishkin, this brief review emphasizes the distinction between procedural and declarative knowledge and examines the possible role of the basal ganglia in the acquisition and retention of procedural knowledge.

The effectiveness of indomethacin treatment (1 mg/kg) as an antipyretic was tested in patients after cranial trauma or brain surgery involving the centromedial forebrain. Indomethacin was effective in reducing temperature in 10 of 11 cases which showed a dipyrone-resistant hyperthermia developing in the first 24 hours after brain damage, while no significant antipyretic effect was seen in hyperthermic cases developing more than 72 hours after cranial trauma or brain surgery. Biochemical tests estimating the effect of indomethacin, and pyrazolone derivatives on the arachidonic acid metabolism showed significant effects of indomethacin only in influencing cyclooxygenase activity and no effect of any drugs on lipoxy — genase actions. In view of these observations, the use of indomethacin is recommended as a treatment for neurogenic hyperthermia.

In an attempt to overcome some of the difficulties inherent in vascular anastomosis using standard suture methods, we have developed a technique that allows for rapid non-suture anastomosis of blood vessels. The technique has been used in over 400 anastomoses, including interposition vein grafts in rat, rabbit and dog vessels ranging in size from 0.7 mm to 3 mm in diameter. Animals have been followed for over 1 year ostoperatively with serial angiography and histological evaluation including scanning electron microscopy. Stress studies have compared the biomechanical properties of both non-suture and suture anastomosis. The overall patency rate in non-suture end-to-end anastomoses using an interposition vein graft was 85% at 1 year follow up. Histological evaluation revealed a healing pattern that was temporally similar to that of the suture technique. Stress tests revealed no significant difference between suture and non-suture technique. These studies reveal that the non-suture technique compares favourably with the suture technique, and demonstrate the feasibility of applying this technique to man.

The incidence of primary intracranial tumors in Manitoba, Canada was reviewed. From 1980 through 1985,657 tumors were diagnosed. The crude incidence rates were 10.2/100,000 for males and 10.8/100,000 for females. The three most common tumors were: astrocytoma 281 (43%), meningioma 145 (22%), and pituitary adenoma 111 (17%). Average annual incidence rates for all tumors showed a bimodal distribution with one peak in the 0-4 age group (4.2/100,000), and the other in the 60-69 age group (27.2/100,000). For malignant astrocytoma, the age-specific annual incidence rate increased to the seventh decade where it reached a peak of 14.3/100,000. The incidence of benign astrocytoma remained relatively constant with age at 1.1/100,000. The annual incidence of meningioma increased with age up to the eighth decade reaching 7.2/100,000. Of the 145 meningiomas, 56 (39%) were meningotheliomatous, 48 (33%) transitional, 10 (7%) malignant, 7 (5%) fibroblastic, 6 (4%) psammomatous, 3 (2%) angioblastic, and 15(10%) lacked pathologic diagnosis. The annual incidence of pituitary adenoma showed two peaks, the first occurring in the third decade (2.6/100,000) and the second in the eighth decade (3.2/100,000). Although the incidence of meningioma was relatively high, the clinical features and pathologic patterns of these tumors were not unlike those previously reported in the literature.

The major input and output pathways of the mammalian striatum have been well established. Recent studies have identified a number of neurotransmitters used by these pathways as well as by striatal interneurons, and have begun to unravel their synaptic connections. The major output neurons have been identified as medium spiny neurons which contain ɣ-aminobutyric acid (GABA), endogeneous opioids, and substance P. These neurons project to the pallidum and substantia nigra in a topographic and probably chemically organized manner. The major striatal afferents from the cerebral cortex, thalamus, and substantia nigra terminate, at least in part, on these striatal projection neurons. Striatal interneurons contain acetylcholine, GABA, and somatostatin plus neuropeptide Y, and appear to synapse on striatal projection neurons. In recent years, much activity has been directed to the neurochemical and hodological heterogeneities which occur at a macroscopic level in the striatum. This has led to the concept of a patch-matrix organization in the striatum.