Studies which have attempted to define the outcome of multiple sclerosis (MS) have methodologic difficulties arising from patient referral biases and the length of follow-up required, which make prospective studies of an inception cohort unrealistic. Means to improve the validity of retrospective natural history studies are suggested. Results of existing series are summarized and compared. Survival is only rarely shortened by MS, but disability to the point of requiring aids for ambulation occurs in 30-70% of patients by 15 years from onset of symptoms. Disagreement as to the percentage of patients who are ultimately bedridden by MS likely arises in large part due to differences in patient ascertainment and follow-up. The need to develop early clinical markers for the patient at high risk for rapid development of major disability is stressed.

Sleep apnea (Ondine's Curse) is an uncommon but potentially fatal complication of percutaneous cervical cordotomy. The authors have had the opportunity to review the case histories of 6 patients who have died of sleep apnea following this procedure. In a series of 112 patients, 144 cervical percutaneous cordotomies were performed from 1977 to 1985 — 80 unilateral cordotomies and 32 staged bilateral cordotomies. Six (5%) patients died as the result of sleep apnea. Five patients (16%) died following bilateral cordotomy and one (1%) patient with pulmonary disease died following unilateral cordotomy. The clinical data of these 6 patients are presented and unique spinal cord pathology is described in this report. The pathophysiology of the sleep apnea syndrome is also discussed.

We analyzed the charts and CT scans of 49 cases of civilian .22 caliber gunshot wounds of the brain admitted to the University of Alberta and Royal Alexandra Hospitals between 1975 and 1985. The average age of the patients was 30 years, 88% were males, 88% were suicide attempts. There were no deaths among patients with an initial coma score above 12 whereas the mortality rate was 85% for those admitted with a score of 7 or less. All those with fixed pupils on admission died. The overall mortality rate of 61% is comparable to that of other series of civilian gunshot wounds including those in which more aggressive surgical management was undertaken. We recommend that no treatment be given those cases with an admission coma score of 3 and/or fixed pupils and that simple scalp wound debridement be employed with those having a coma score of 7 or less. Tract exploration and retrieval of bullet fragments is not indicated, as retained fragments carry a very low incidence of complications (e.g. abscess formation). In patients in good condition (GCS ≥ 12) the management of intracranial hematomas should be independent of their etiology and approached aggressively.

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.

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.

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.

Two children born with birth defects after intrauterine exposure to valproic acid are reported. The mothers took the drug throughout pregnancy as sole treatment for primary generalized epilepsy. The first baby showed facial dysmorphism, arachnodactyly and triphalangeal thumbs. The second had facial dysmorphism, severe laryngeal hypoplasia, tracheomalacia and an aberrant innominate artery that caused tracheal compression. A left superior vena cava, abnormal pulmonary lobulation, and unilateral hydronephrosis were also found at autopsy. Valproic acid has probable teratogenic potential in humans but the number of reported cases is few and the spectrum of anomalies is broad so it is not possible to delineate a definite fetal valproate syndrome.

A patient is described who, while on valproic acid monotherapy, developed reversible shrinkage of the brain, documented by computerized tomography with associated cognitive deficit. Although pseudoatrophy has been reported with steroid therapy, this is the first implication of an anticonvulsant drug in the etiology of that condition.

We have modified the techniques of Lindstrom and of Tindall to measure serum acetylcholine receptor antibody using human antigen bound to 125I-alpha Bungarotoxin. By using 10 ä1 of serum and precipitating antigen-antibody complexes with an excess of staph A, we found that only one out of 43 patients with clinically diagnosed active generalized Myasthenia Gravis had no antibodies. In pooling these results with the results of tests done for diagnostic purposes we found positive results in 54/55 generalized active MG, 8/21 MG in remission, 16/37 ocular MG and 0/55 healthy controls. Two out of 38 non MG were also positive and their clinical diagnosis of botulism and penicillamine treated rheumatoid arthritis have been confirmed by a one year follow-up. Most of these sera were also tested for reactivity with fetal calf AchR. Six out of 49 samples positive with the human receptor were negative with calf receptor. We conclude that our technique is extremely useful for the diagnosis of Myasthenia Gravis and that fetal calf antigen cannot replace human antigen in the assay.

We report here six families with Parkinson's disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinson's disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system.

We describe a child with a cerebellar astrocytoma who presented with paroxysmal segmental rhythmic myoclonus. The movement disorder was characterized by focal onset in the left eyelid followed by a sequential march of clinical events. There were no clinical or laboratory findings to suggest brainstem infiltration or cerebral involvement. Marked clinical improvement followed tumour resection. We suggest that the cerebellar lesion was primarily responsible for the movement disorder.

Three patients presented with hand wasting and weakness secondary to mid-cervical spinal cord compression. This was due to cervical spondylosis in two patients and a meningioma in one case. This phenomenon is probably similar to that seen with foramen magnum lesions and may be due to spinal cord ischemia distal to the compression, secondary to venous stasis.

Herpes zoster ophthalmicus can be complicated by a delayed ipsilateral cerebral angiitis which may cause infarction and a smoldering meningoencephalitis. We describe such a case treated successfully with steroids and acyclovir. It is important to consider the diagnosis of this disorder early since therapeutic intervention may prevent an otherwise high morbidity and mortality. Steroids may have to be continued for some time after clinical resolution, using the ESR as a guideline for decreasing dosages.

We report the seventh case of a self-limiting syndrome of brain, inner ear and retinal microangiopathy which affects adult women producing mild to moderate mental status and personality changes, mild pyramidal and cerebellar dysfunction, patchy and asymmetrical visual loss secondary to non-inflammatory retinal infarctions, and asymmetrical neurosensory hearing loss. There is no clinical or laboratory evidence of involvement beyond the brain, the eyes and the ears. Magnetic resonance imaging or brain biopsy in previously reported cases best outline the brain pathology: multiple microinfarcts. All cases have been treated with steroids or cyclophosphamide. The etiology is unknown but may be related to systemic lupus erythematosus.