The epidemiology of multiple sclerosis (MS) and the planning and interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome.

CQA 206-291, a new ergot derivative with a “biphasic” dopaminergic profile, was studied in 6 patients with longstanding Parkinson's disease suffering from pronounced fluctuations in hourly mobility. On alternate days, up to seven single doses, escalating from 0.2 to 20 mg, were given as replacement for the usual first morning dose of levodopa. At the most effective dosage, four of the six patients obtained as good a peak response to CQA (8-20 mg) as to L-dopa. Side effects were common and similar to other ergot derivatives, suggesting that the initial weak dopamine antagonist properties of the parent compound, documented in animals, may be of little clinical significance. However, comparative studies will be needed to confirm this suspicion. The addition of domperidone successfully reduced the incidence and severity of side effects. CQA 206-291 has potent anti-parkinsonian properties; further longer-term treatment trials are indicated.

We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur.

That non-rheumatic atrial fibrillation is an independent risk factor for cerebral infarction has not been established with certainty. The rationale underlying contemporary clinical trials of warfarin therapy for the prevention of stroke in patients who have non-rheumatic atrial fibrillation is that the majority of strokes in such patients are due to cardiogenic cerebral embolism. However, there is evidence to suggest that the increased probability of stroke attributed to this arrhythmia is due to its association with other risk factors such as hypertension, diabetes mellitus, and atherosclerosis. The question of who should be anticoagulated is a major public health issue since atrial fibrillation is present in approximately ten per cent of the general population aged 65 or more years.

There has been a recent renewal of interest in the extracranial repair of cerebrospinal fluid rhinorrhea because of the relatively high morbidity associated with the transcranial approach. The authors describe an extracranial approach that involves packing of the sphenoid and ethmoid sinuses on the side of the CSF leak. A case of successful treatment of CSF rhinorrhea by this method is presented. The extracranial approach may be advantageous for the repair of CSF rhinorrhea and the authors advocate an increase in its utilization by neurosurgeons and otolaryngologists working as a team.

Next to acoustic neuromas, meningiomas are the most common benign tumour of the posterior fossa. This paper reviews the personal experience of one of the authors with the management of 26 posterior fossa meningiomas and 212 acoustic neuromas. The aim was to compare the clinical and radiological features of these two types of posterior fossa tumours to determine whether they can be differentiated preoperatively. The study also aimed at analysing the surgical treatment of posterior fossa meningiomas. The results showed that posterior fossa meningiomas can usually be differentiated from acoustic neuromas on the basis of clinical and radiological features. Preoperative differentiation aids surgical management, especially for selection of surgical approach. In most instances, posterior fossa meningiomas can be totally resected with minimal morbidity and mortality.

Immunohistochemical stains for cytokeratins, vimentin, epithelial membrane antigen, carcinoembryonic antigen and S-100 were performed on nine ecchordoses and 10 chordomas. 100% of the ecchordoses were positive for cytokeratin, vimentin and epithelial membrane antigen. 78% were S-100 positive. 100% of the chordomas stained positively for cytokeratin, vimentin and S-100 and 90% were positive for epithelial membrane antigen. No ecchordosis or chordoma was carcinoembryonic-antigen positive. These findings are interesting for two reasons. First, the similar staining properties of chordoma and ecchordosis physaliphora support the embryologic hypothesis of their common origin from the fetal notochord. Second, they indicate that when an ecchordosis causes symptoms prompting surgical resection, differentiation of the lesion from chordoma with routine immunohistochemistry would not be helpful.

An understanding of the mechanisms responsible for tumor-associated edema involves the elucidation of the role played by a number of intra-related processes. These include (i) the permeability of new tumor microvessels that are associated with tumor angiogenesis; (ii) alterations in microvascular permeability due to factors secreted by tumor cells; (iii) immunological mechanisms and (iv) increased microvessel permeability associated with inflammation. The rationale for a role for inflammatory processes in tumor-associated edema has been outlined and the role of non-steroidal anti-inflammatory drugs in modulating experimental and human tumor-associated edema has been explored.

Two patients with congenital anomaly of the craniovertebral junction causing disabling hemifacial spasm (HFS) are presented. In one patient, complete cessation of the HFS occurred for a period of two years following simple bony decompression of the craniovertebral junction raising unanswered questions as to the exact pathogenesis of HFS. Eventually both patients required microvascular decompression at the root entry zone of the facial nerve.

A case of paraneoplastic encephalomyelitis and subacute pandysautonomia associated with an occult atypical carcinoid tumour of the lung is described. The main clinical features were lethargy, impaired memory, constipation, and orthostatic hypotension. Neurological investigation was unremarkable except for mononuclear pleocytosis and increased protein level in the cerebrospinal fluid (CSF). Tests of autonomic function revealed a low plasma norepinephrine level, a marked drop of blood pressure (BP) to vertical tilt and Valsalva maneuver, and a marked rise of BP to dilute norepinephrine infusion. A few days prior to death, the patient became hypothermic and had repeated episodes of respiratory arrest associated with transient atrioventricular block on the electrocardiogram (ECG). A polysomnography study confirmed a sleep apnea syndrome. Autopsy revealed an atypical carcinoid tumour in one tracheobronchial lymph node, widespread lymphocytic infiltrates and loss of neurones in the cerebral, cerebellar and brainstem gray matter, the spinal cord and roots, and the paravertebral sympathetic ganglia as well as microglial and astrocytic proliferation in the central nervous system.

During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty-sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates.

Magnetic Resonance Imaging (MR) and Computer Assisted Tomography (CT) guided stereotaxis combined with intraoperative impedance monitoring and multiple sequential biopsies provides the opportunity to correlate the results of radiologic imaging with impedance and histopathology. The authors present the methods used and preliminary results obtained from 30 stereotactic biopsies with complete correlation in 12 cases. Impedance changes correlate accurately with lesion margins as defined by histology. CT images of enhancing lesions correlate quite closely to the histopathologic lesion margins whereas the appearance of the lesion on MR images is often larger than subsequently identified by either impedance or at pathologic examination. Impedance monitoring is a useful adjunct to stereotactic biopsy as it helps to accurately define lesion margins and can help direct the choice of biopsy sites.

Guamanian amyotrophic lateral sclerosis with parkinsonism-dementia (ALS/PD) has been the subject of intensive study since its discovery in 1947 because of its extraordinarily high incidence in a small ethnic group (Chamorros) whose dietary lack and customs have suggested possible causes. As yet, these and other suspected causes have eluded proof. Because of marked similarities between Guamanian ALS/PD and late onset post-encephalitic (encephalitis lethargica) parkinsonism and ALS it is suggested that they have a common cause. The parkinsonism and ALS in the two disorders are clinically very similar and neuropathological studies have shown a very similar distribution of neurofibrillary tangles in neurons. Some clinical differences, such as ocular features in the post-encephalitic cases and dementia in Guamanian ALS/PD, can be explained by differences in the severity of infection and the interval between the encephalitis and onset of sequelae. Although unproven, influenza A (HswilNl strain) has long been suspected as the cause of encephalitis lethargica because of simultaneous pandemics of the two diseases in the 1920s. Because influenza A can persistently infect cells and has a marked propensity to mutate it is an optimal candidate among other RNA viruses for delayed nervous system infection as a possible cause of ALS/PD.

The long-term follow-up of the transsphenoidal microsurgical treatment in 119 consecutively operated women with a PRL-secreting adenoma is presented. An apparent total removal of the tumor was achieved in 98 cases with an enclosed tumor (58 grade I and 40 grade II). In the remaining cases the removal was considered partial. The achievement of persistent normal PRL basal levels was verified in 61 patients (44 grade I and 17 grade II) who had an apparent total removal of the adenoma. In the 37 remaining patients who were thought at surgery to have had total removal we have distinguished two groups: 30 patients showed a “relapse” or “persistence” of PRL levels below 200 ng/ml without clinical and radiological signs of tumor regrowth, and 7 patients with a PRL level higher than 200 ng/ml who had evidence of PRL-secreting tumor recurrence.

Neurologic complications of the acquired immune deficiency syndrome (AIDS) most often present as brain dysfunction and/or a polyneuropathy. We describe a unique neurological problem of a woman with AIDS who presented with a Cauda equina mass due to primary CNS lymphoma. She subsequently developed a fulminant lymphomatous meningitis and died. Although previously rare, primary spinal cord lymphoma is expected to be encountered more often with the current AIDS epidemic and may be difficult to distinguish from infectious mass lesions.

Canadians are suing their doctors for malpractice, at three times the rate they were 15 years ago, and during that period awards to injured patients have quadrupled in size. Since the middle 1970's when the first medical malpractice “crisis” occurred in the United States, Canadian clinical neuroscientists have felt increasingly threatened by the prospect of a lawsuit for negligence. Since medicine is intrinsically a risk taking business, adverse outcomes are inevitable. Nevertheless, accusations of negligence and carelessness set out in a Statement of Claim causes considerable stress for the defendant physician, who frequently reacts with self-doubt, depression and aggressive behaviour. A “tort” is defined as a wrongful act, and the 4 elements comprising the tort of medical malpractice are: a breech of standard care, the breech was the proximate cause of the injury, the injury produced measurable damage, and it was foreseeable that the injury would have been less injurious to the patient if the caregiver had conducted a different course. In order to put these issues into current perspective, this symposium was convened as part of the XXIV Canadian Congress of Neurological Sciences, held in Ottawa June 17, 1989.

We achieved a unique and timely recording of cerebral activity in a 70 year old woman immediately pre- and post-stroke, while studying the effect of acute cerebral infarction on sleep-electroencephalogram (EEG) patterns. Normal patterns, except for increased wakefulness, were recorded during two pre-infarct polysomnograms. Immediately following cerebral infarction increased delta activity was recorded from the infarcted hemisphere only. Initially, REM sleep could not be recorded from either side; however, on the third post infarct day REM sleep returned. Background EEG levels from both hemispheres became progressively slower, flatter and simpler. In addition, sleep spindles and the distinctive saw-tooth wave forms of sleep almost disappeared. At one year post-stroke sleep-EEG rhythm recordings from both hemispheres became more similar except for persisting delta activity from the left hemisphere. Unexpected deterioration of sleep-EEG pattern recordings from the undamaged hemisphere taken during the patient's clinical recovery remains unexplained. Serial sleep recording may facilitate the study of brain recovery, activity and reorganization following stroke.

Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/I were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect.

The Ommaya Reservoir plays an important role in a select group of neuro-oncology patients with meningeal malignancy. The benefits derived must be balanced against potential complications associated with insertion and use of the apparatus. Side effects may be minimized by careful attention to patient selection, pre-operative CAT scan (or MRI), precise surgical technique, perioperative prophylactic antibiotics and meticulous procedure during use of the reservoir.