We present a case of recurrent glioma, previously treated with maximal surgery and radiation in which a high dose of tamoxifen has stabilized the tumour clinically and has resulted in it's radiologic regression. Given tamoxifen's relative lack of toxicity, it might serve as a useful adjuvant in the treatment of recurrent glioma.

Between December 1986 and June 1990, 112 patients (116 lesions), underwent treatment with dynamic stereotactic radiosurgery at McGill University. Of the treated lesions, 59 were arteriovenous malformations and 53 were a variety of other neoplastic or non-neoplastic conditions. In 86 lesions, the treatment was delivered in a single fraction and the treatment of the remaining 30 lesions was fractionated. Complications attributed to treatment developed in seven of the 112 patients (6.3%). No relationship was found between complications and prescribed dose, fractionation, collimator diameter, type and anatomical region of the lesion that was treated, or previous irradiation. Although extensive clinical experience will be necessary to determine optimal total doses, the potential role of fractionated treatment, and the tolerance of critical structures to radiosurgery, the relatively low incidence of complications in our series allows us to conclude that radiosurgery is well tolerated by the vast majority of patients.

This manuscript reviews a series of experiments which support the notion that the cerebellum and more specifically the cerebellar cortex is principally involved in real time operations required for the regulation of coordinated motor activity. Experiments are reviewed which illustrate: (1) that the climbing fiber inputs to Purkinje cells can induce a short-lasting enhancement of their responses to mossy fiber-granule cell-parallel fiber inputs, (2) that the cerebellum is not essential for the acquisition and performance of the classically conditioned nictitating membrane reflex (NMR) of the rabbit, and (3) that the observations resulting from the microinjection of lidocaine and multiple single unit recordings within the brainstem support the notion that cell populations in this region may participate in establishing the modifications in neuronal interactions required for the acquisition of the conditioned NMR. In addition, preliminary data are shown comparing the capacity of a normal subject and a patient with a massive ipsilateral cerebellar stroke to learn certain tracing tasks and to redraw these learned tracing movements 90° to the orientation of the original image. The data support the notion that the cerebellum is essential, not for the initial learning of the tracing movement, but rather for performing the learned movement with the required rotation of the original image.

The pathophysiology of the movement disorders arising from basal ganglia disorders has been uncertain, in part because of a lack of a good theory of how the basal ganglia contribute to normal voluntary movement. An hypothesis for basal ganglia function is proposed here based on recent advances in anatomy and physiology. Briefly, the model proposes that the purpose of the basal ganglia circuits is to select and inhibit specific motor synergies to carry out a desired action. The direct pathway is to select and the indirect pathway is to inhibit these synergies. The clinical and physiological features of Parkinson's disease, L-DOPA dyskinesias, Huntington's disease, dystonia and tic are reviewed. An explanation of these features is put forward based upon the model.

Intracellular recording was made from dentate nucleus neurons (DNNs) in anesthetized cats, to investigate cerebral inputs to DNNs and their responsible pathways. Stimulation of the medial portion of the contralateral pericruciate cortex most effectively produced EPSPs followed by long-lasting IPSPs in DNNs. Stimulation of the pontine nucleus (PN), the nucleus reticularis tegmenti pontis (NRTP) and the inferior olive (IO) produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. The results indicate that the excitatory input from the cerebral cortex to DNNs is at least partly relayed via the PN, the NRTP and the 10. Intraaxonal injection of HRP visualized the morphology of mossy fibers from the PN to the DN and the cerebellar cortex. The functional significance of the excitatory inputs from the PN and the NRTP to the DN is discussed in relation to the motor control mechanisms of the cerebellum.

Low-intensity repetitive electrical stimulation such as dorsal column and transcutaneous electrical nerve stimulation (TENS) reportedly decreases spasticity and improves voluntary motor control. However, the mechanisms mediating these effects are unclear. Recent findings suggest that spasticity may be characterized more appropriately by a decrease in the stretch reflex threshold than by an increase in gain. Our objectives were: (1) to examine possible changes in stretch reflex excitability following 45 min of TENS, (2) to map out the time course of possible post-stimulation effects via both latency and magnitude (amplitude or area) measurements, and (3) to determine the role of segmental versus non-segmental mechanisms involved in mediating these changes. The effects of 45 min of segmentally and heterosegmentally applied TENS on lower limb reflexes in ten spastic hemiparetic subjects were contrasted with those resulting from placebo stimulation. We found that both segmentally and heterosegmentally applied TENS caused an immediate increase in soleus H reflex latencies that was evident for up to 60 minutes post-stimulation in over 75% of the subjects. Similar increases for up to 60 and 40 minutes post-stimulation was noted for the stretch reflex latencies in 50% and 67% of the subjects respectively for segmental and heterosegmental stimulation. These results suggested that manipulation of segmental and heterosegmental afférents for 45 min may lead to a decrease of the otherwise augmented stretch reflex excitability accompanying hemiparetic spasticity.

A relationship between epilepsy and damage to mesial temporal structures has long been recognized. Recent advances have clarified somewhat the issue of whether the pathological changes seen in mesial temporal sclerosis represent the cause or the effect of seizures. This paper reviews mesial temporal sclerosis from an historical perspective and summarizes recent developments in the fields of excitotoxicity, selective vulnerability, and synaptic reorganization as they pertain to the pathogenesis of mesial temporal sclerosis.

In recognition of the 100th anniversary of Charcot’s death we have reviewed possible pathogenic mechanisms in amyotrophic lateral sclerosis (ALS). Advances in the last 5 years in molecular biology and genetics have identified mutations in the cytosolic dismutase (SODI) gene in some patients with familial ALS raising the possibility that oxidative stress may be involved in the pathogenesis. An excitotoxic pathogenesis has been implicated based on elevated plasma and CSF levels of amino acids and altered contents of amino acids in the nervous system of ALS patients and changes in the number of excitatory amino acid receptors. ALS sera containing antibodies to L-type calcium channels and the development of immune mediated lower and upper and lower motor neuron models have revitalized research efforts focusing on an immune basis for ALS. Other pathogenic mechanisms which have been the subject of recent research include elemental toxicity, apoptosis and programmed cell death and possibly a deficiency or abnormality in growth factors. Pathogenic processes for ALS must account for an increasing incidence of ALS, male preponderance, and the selective vulnerability of the corticomotoneuronal system.

A closed-loop or recurrent neural network was taught to generate output discharges to reproduce the prototypical activations in agonist and antagonist muscles which produce the displacement of a limb about a single joint. By introducing a generalized decrease in the excitability of the pre-output layer in the network, the network made the displacement more slowly and also showed an inability to maintain a repetitive movement. These concepts can be applied to the human nervous system in the understanding of the physical basis of movement and its disorders. It is suggested that a movement represents the output of a closed-loop network, such as the cortical-basal ganglia-thalamic-cortical motor loop, which iterates repetitively to its end point or attractor. The model provides an explanation of how the state of thalamic inhibition seen in Parkinson's disease physically may produce bradykinesia and the inability to maintain a repetitive movement.

Proton nuclear magnetic resonance (NMR) spectroscopy was used to examine cerebrospinal fluid (CSF) from patients (n = 30) with actively progressive multiple sclerosis (MS). Metabolite concentrations obtained from the spectra were compared to those determined from the spectra of CSF from control patients (n = 27) with benign spinal disorders. No significant difference was found between the 2 groups for most constituents, including lactate, glutamine, citrate, creatine and creatinine, and glucose. Acetate levels were significantly higher in MS patients, while formate levels were significantly lower, than the controls. There were no significant differences in metabolite concentrations in CSF from early and longstanding MS patients. A peak due to an unidentified compound was found at 2.82 ppm in the spectra of CSF from patients with actively progressive MS, but not in the spectra of CSF from the controls. The peak was not found in spectra of CSF from patients with AIDS dementia complex (n = 9) or Parkinson's disease (n = 5), but it did appear in spectra of CSF from 1 patient with Jakob-Creutzfeldt disease (out of 3 examined) and from 1 patient (out of 7) with Guillan-Barré disease. The unidentified compound is volatile and, from the chemical shift of the observed NMR peak, is probably an N-methyl compound. As such, it may be an intermediate in the cholino-glycine cycle, in which an abnormality has been proposed to exist in MS patients.

Human T-cell lymphotropic virus type 1 (HTLV-I) is responsible for HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) and for adult T-cell leukemia/lymphoma (ATLL). Both diseases have been well described in individuals living in Japan, West Indies, Seychelles Islands and Columbia where infection with HTLV-I is considered endemic and in persons whose descendants originated from these endemic areas. We report here 4 cases of HAM/TSP in 4 natives from 4 different tribal groups from British Columbia (B.C.). These are the first case reports of HTLV-I linked diseases found among North American Aboriginals. Possible routes of infection for HTLV-I infection included sexual transmission, breast feeding, blood transfusions and IV drug use. The seroprevalence of HTLV-I in North American Native population is unknown and we suggest that it is endemic in this ethnic group.

The rationale, basic considerations, and technique of intraoperative nerve action potential (NAP) recording have been reviewed. Experience using this technique in several thousand patients over a 25 year period has been summarized. The most frequent serious nerve injury is one that leaves it in continuity. Resection of such a lesion that is regenerating does the patient a great disservice as does exploration without repair of one with little or no potential for useful spontaneous recovery. The frequency of lesions in continuity as well as the difficulties in evaluating them in the early months by electromyography let alone by surgical inspection has led to the development of intraoperative NAP recording. Where neurolysis was based on a recordable NAP across a lesion in continuity, 93% recovered good function. Where resection of the lesion was based on absence of an NAP, the injury was, without exception, neurotmetic and/or one with poor potential for useful recovery without repair. Some lesions had an NAP across their lesion but a portion of the cross-sectional area appeared more seriously injured. By use of NAP recordings, a split repair was done and usually with good results.

Most descriptions treat the cerebellum as a uniform structure, and the possibility of important regional heterogeneities in either chemistry or physiology is rarely considered. However, it is now clear that such an assumption is inappropriate. Instead, there is substantial evidence that the cerebellum is composed of hundreds of distinct modules, each with a precise pattern of inputs and outputs, and expressing a range of molecular signatures. By screening a monoclonal antibody library against cerebellar polypeptides we have identified antigens – zebrins – that reveal some of the cerebellum’s covert heterogeneity. This article reviews some of these findings, relates them to the patterns of afferent connectivity, and considers some possible mechanisms through which the modular organization may arise.