Transient forebrain ischemia was induced in rats whose brain temperature was 31, 33, 35, 38, or 40°C. The development of regional injury was followed using magnetic resonance (MR) imaging, with the ultimate extent of neuronal injury quantified histopathologically. Animals in the hypothermic groups showed minimal changes in MR images over 4 days; normothermic animals snowed intensity enhancement attributed to progressive edema developing in the striatum and, later, in the hippocampus. Ischemia at 40°C resulted in widespread edema formation by I day post-ischemia; animals in this group did not survive beyond 30 hours. Histopathological analysis at 4 days (1 day for the hyperthermic group) post-ischemia showed that neuronal damage in the normothermic group was confined to the hippocampus and striatum. Minimal damage was found in the hypothermic groups; damage in the hyperthermic group was severe throughout the forebrain. There were no differences in the pre-ischemia 31P MR spectra for the different groups. During ischemia, the increase in intensity of the Pi peak and the fall in tissue pH increased with temperature in the order hypothermic < normothermic < hyperthermic group of animals. Post-ischemia energy recovery was similar in all groups, while pH recovered more rapidly in hypothermic animals.

Cerebral vasospasm may result from lipid peroxidation induced by oxyhemoglobin in the subarachnoid space after subarachnoid hemorrhage. To test this theory, vasospasm was induced in monkeys by intrathecal injections of oxyhemoglobin or supernatant fluid from autologous blood incubated in vitro. Concentration of malondialdehyde (MDA), a product of lipid peroxidation, was elevated in cerebrospinal fluid (CSF) in association with vasospasm caused by oxyhemoglobin and supernatant fluid. Intrathecal injections of methemoglobin or bilirubin did not cause vasospasm or increased CSF MDA. Activity of glutathione peroxidase in CSF increased significantly after injection of oxyhemoglobin and methemoglobin. There were no significant changes in CSF superoxide dismutase activity although there was a trend towards higher activities in animals treated with oxyhemoglobin, methemoglobin, bilirubin, and supernatant fluid. These results show oxyhemoglobin-induced vasospasm is associated with MDA and lipid peroxidation in the subarachnoid space. Furthermore, detection of peroxidation products after injection of oxyhemoglobin in the absence of erythrocyte membranes indicates that oxyhemoglobin may directly damage cerebral arteries and brain by inducing lipid peroxidation in these structures. Depletion of free-radical scavenging enzymes in CSF did not seem necessary for development of vasospasm. In fact, there was a tendency for vasospasm to elevate enzyme activities, as if production of scavengers was induced by excess free radicals in the subarachnoid space.

Trained telephone interviewers contacted 1,573 adults across Canada about the nature and frequency of headaches suffered by them or by others in their households. Using a table of pain symptoms and other characteristics abstracted from the International Headache Society (IHS) classification, the headaches were assigned to migraine headache, tension-type headache or other diagnostic groups. Of the households sampled, 59% had at least one headache sufferer in residence. The proportion of headache sufferers with migraine was 14%; with tension-type, 36%; and with both, 14%. Migraine headache caused more disability than tension-type headache, with nearly 20% of migraine sufferers taking time off work and disability lasting for a mean of 1 day. It is concluded that the current prevalences of migraine and tension-type headache in Canada fall around the mean of previous studies, that the IHS criteria can form a basis for diagnostic classification and that the functional impact of migraine has been seriously underestimated in the past.

This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51 % of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile.

A 15-year experience with paraneoplastic sensory neuronopathy at the Mayo Clinic is reviewed. Of 26 patients with paraneoplastic sensory neuronopathy, 19 had small cell lung cancer, 4 had breast cancer, and 3 had other neoplasms. There was a striking predominance of females (20:6). Neuropathic symptoms (pain, paresthesia, sensory loss) were asymmetric at onset, with a predilection for the upper limbs; in three patients, symptoms were confined to the arms. Electrophysiologic testing revealed absent sensory responses and normal or minimally altered motor responses. Slightly more than half the patients had associated autonomic, cerebellar, or cerebral abnormalities. In some patients, treatment of the neoplasm seemed to halt progression of the neuronopathy, but none had neurologic improvement and most continued to worsen, even when the oncologic response was good. Distinguishing between paraneoplastic and nonparaneoplastic sensory neuronopathies can be difficult, but prominent neuropathic pain, neurologic dysfunction involving more than the peripheral sensory system, or an increased cerebrospinal fluid protein value should prompt a careful search for a cancer.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

Recent observations indicate that antibodies to gangliosides are found in many patients with amyotrophic lateral sclerosis (ALS). If antigen-antibody complexes occur in ALS, elevations of cytokine levels might be expected, among them the cytokine interleukin-6 (IL-6). IL-6 is secreted by activated monocytes and other cell types and is an important mediator of the inflammatory response. We have measured cerebrospinal fluid (CSF) IL-6 levels in patients with ALS and compared them with those in psychiatric and neurodegenerative disorders not believed to be due to immune disorders of the central nervous system. We found no significant differences in CSF IL-6 levels between these groups.

We propose a new approach to staging the disease based on clinical and immunological response to treatment. We oppose clinical remission to immunological remission and define total clinical remission as the goal of therapy. We describe the use, side effects and indications of established therapies. Acetycholine esterase inhibitors are only a symptomatic treatment as is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and immunosuppressants are described here. Their goal is to reduce the auto-immune process. Long-term hazards from these medications are described and methods to reduce their potential risks are suggested. We suggest the number of patients having life threatening complications while undergoing aggressive immunosuppression can be reduced by a systematic approach to follow-up. In the second part of this review article, adapting management to specific situations is emphasized in refractory disease, respiratory failure, neonatal and juvenile forms of the disease. The special situation of seronegative myasthenia is discussed.

We report experience with 11 patients misdiagnosed for years, on the basis of computed tomography (CT) and angiography, as harbouring brainstem tumours in whom magnetic resonance imaging (MRI) demonstrated cavernous angiomas. Seven had undergone external irradiation, 2 had a ventriculo-peritoneal shunt, 2 developed aseptic femur necrosis following corticosteroid treatment, 1 had undergone a biopsy with a pathological diagnosis of glioma. CT had depicted ill-defined, hyperdense, faintly enhancing lesions. Angiography was normal, or showed an avascular mass or subtle venous pooling. MRI delineated discrete lesions, typical of cavernous angiomas, with a mixed hyperintense, reticulated, central core surrounded by a hypointense rim. Six patients subsequently underwent stereotactic radiosurgery without changes in clinical status or lesion. Although hemorrhagic neoplasms may mimic the clinical course and MRI appearance of cavernous angiomas, MRI is useful in the diagnosis of brainstem cavernous angiomas and should be performed in patients with suspected brainstem tumours.

The stiff-person syndrome is a disorder of persistent, painful muscle contractions predominately affecting the axial musculature. We describe a patient with this disorder and review its pathophysiology. Molecular biologic and immunologic techniques have recently added to the understanding of the mechanism of this disorder. Association with diseases such as diabetes, vitiligo and hypothyroidism have strengthened the auto-immune nature of this syndrome. Auto-antibodies against glutamic acid decarboxylase (GAD), an intraneuronal enzyme, have been implicated in the etiology of this unique disease. Therapeutic intervention with agents such as benzodiazepines that modify central GABAergic activity have demonstrated significant benefit in patients with stiff-person syndrome.

Spontaneous disappearance of an intracranial aneurysm after subarachnoid hemorrhage is an uncommon event and usually associated with severe cerebral vasospasm, giant aneurysms or the use of antifibrinolytics. We present a young woman who suffered a grade 5 subarachnoid hemorrhage with severe vasospasm caused by a small anterior communicating artery aneurysm. The patient underwent a slow recovery and two years later requested surgery. Angiography demonstrated complete disappearance of the aneurysm. The neurosurgeon should be aware that spontaneous thrombosis of cerebral aneurysms can occur and ensure that angiography is repeated when surgery is significantly delayed.

A case of central neurocytoma treated surgically is described. The authors review the literature. Emphasis is placed on radiological and pathological features not previously described. In particular, the intra-operative ultrasound appearance is described. The role of adjunctive radiotherapy is also discussed.