Long-term glioblastoma multiforme survivors (LTGBMS) are uncommon. The frequency which these occur in an unselected population and factors which produce these unusually long survivors are unknown.

To determine in a population- based study 1) the frequency of LTGBMS in a population and 2) identify which patient, treatment or tumor characteristics would predict which glioblastoma (GBM) patient would become a LTGBMS.

The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in southern Alberta between 1/1/75 - 12/31/91. Patient charts were reviewed and histology re-examined by a blinded neuropathologist. LTGBMS were defined as GBM patients surviving ≥ 3 years after diagnosis. Each LTGBMS was compared to three age-, gender-, and year of diagnosis-matched controls to compare patient, treatment, and tumor factors to GBM patients without long-term survival.

There were 279 GBMs diagnosed in the study period. Five (1.8%) survived ≥ three years (range, 3.2-15.8 years). Seven additional long-term survivors, who carried a diagnosis of GBM, were excluded after neuropathologic review; the most common revised diagnosis was malignant oligodendroglioma. LTGBMS (avg. age = 45 years) were significantly younger when compared to all GBM patients (avg. age = 59 years, p - 0.0001) diagnosed in the study period. LTGBMS had a higher KPS at diagnosis (p = 0.001) compared to controls. Tumors from LTGBMS tended to have fewer mitoses and a lower Ki-67 cellular proliferative index compared to controls. Radiation-induced dementia was common and disabling in LTGBMS.

These data highlight the dismal prognosis for GBM patients who have both a short median survival and very small chance (1.8%) of long-term survival. The LTGBMS were younger, had a higher performance status, and their tumors tended to proliferate less rapidly than control GBM patients. When long-term survival does occur it is often accompanied by severe treatment-induced dementia.

Supraclinoid carotid aneurysms have traditionally been classified according to their relation to the major carotid branches, but considerable variation exists with respect to site of origin, projection, and relationship to the skull base. Distal internal carotid aneurysms with a superior or medial projection are uncommon vascular lesions, with an unusually high incidence of operative complications.

Surgical experience with five patients suffering from subarachnoid hemorrhage due to ruptured aneurysms of the dorsomedial wall of the distal internal carotid artery is presented, with emphasis on their angiographic appearance, anatomical features, and operative management.

All five patients underwent surgical clipping. Intra-operative rupture occurred in two cases, with avulsion of the aneurysm from the internal carotid artery in both. A third patient experienced recurrent subarachnoid hemorrhage three days after uneventful surgery, due to the clip shearing off of the parent vessel.

Distal internal carotid aneurysms do not conform to the usual principles of aneurysm formation and are unique in their dorsomedial location unrelated to an arterial bifurcation. Although their anatomy is straightforward and exposure is not restricted by bone or dural structures of the skull base, they possess extremely fragile necks which make surgical management particularly hazardous.

To determine the current recovery rates and causes for morbidity and mortality in patients suffering aneurysmal subarachnoid hemorrhage (SAH).

We reviewed a recent consecutive series of 95 patients with ruptured intracranial aneurysms who presented to our hospital between 1994 and 1995. When administered, active treatment consisted of early surgery for aneurysm clipping and aggressive prevention and treatment of SAH-related complications.

Eighty-eight (93%) of the patients were admitted within 24 hours of rupture. One-quarter of the patients in this series did not undergo aneurysm clipping due to poor neurological condition on presentation. Of the 75 patients initially considered for active treatment, 83% underwent surgery within 48 hours of rupture, all received nimodipine, 16% received tissue plasminogen activator to lyse subarachnoid or intraventricular clots, 40% underwent hypertensive treatment, and 7% underwent transluminal balloon angioplasty for vasospasm. At one year followup, 29% of patients had died, 7% had severe disabilities, 13% had moderate disabilities, 51% had made a good recovery, and 64% of all surviving patients had returned to their previous work status. Primary and contributing causes of death and disability, affecting 47 patients at one year, were: direct effects of the initial hemorrhage (79% of affected patients), surgical complications (13%), vasospasm (11%), rebleeding (11%) and medical complications (13%).

Almost two-thirds of patients suffering aneurysm rupture make a satisfactory recovery with modern treatment. While vasospasm has become a less common cause of poor outcome following SAH, surgical complications remain an important problem.

Results from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (MS)-Phase 1 (CCPGSMS-Phase 1) together with other family data published since 1982 have led to the following conclusions about the etiology of MS: (i) genetic and non-genetic (environmental) factors are involved in the etiology of MS on a population basis; (ii) the familial aggregation of MS is genetic; (iii) maternal factors do not influence the risk for siblings to develop MS; and (iv) MS appears to be oligogenic. The present paper describes the rationale and methodology for the CCPGSMS-Phase 2.

The CCPGSMS-Phase 2 is a nation-wide collaborative effort involving all the 15 Canadian MS clinics. A series of structured questionnaires is administered to MS index cases, spouse controls and mothers of index cases and spouse controls (if available) by trained interviewers. Blood samples are taken for molecular genetic studies. This national effort is coordinated by the MS Clinics in Vancouver and London.

The CCPGSMS-Phase 2 is in progress so specific results are not available. The study is designed to (i) increase the database for genetic epidemiological/molecular genetic research and (ii) gather population-based data to further our understanding of the non-genetic factors in the etiology of MS.

It is anticipated that the results from this study will impact on the eventual prevention, cure and treatment of MS.

Intravenous methylprednisolone (IVMP) is the treatment of choice for multiple sclerosis (MS) patients undergoing acute exacerbation of disease symptoms and yet its cost has not been accurately determined. Determination of this cost in different settings is also pertinent to consideration of cost-saving alternatives to in-patient treatment.

Cost analysis from the point of view of the health care system of IVMP treatment of MS patients receiving treatment in association with a selected Toronto teaching hospital in fiscal year 1994/95 was carried out. Costs of any concurrent treatments were excluded.

Total cost for 92 patients, based on a 4 dose regime, was estimated to be $78,527. The the cost per patient was $1,1181.84 for in-patients (IP), $714.64 for out-patients of the MS Clinic (OP) and $774.21 for patients whose treatment was initiated in the Clinic, but completed in the home (HC). Sensitivity analyses indicated: 1) IP treatment was in all cases more expensive than that of OP or HC; 2) the cost savings of OP vs. HC was sensitive to assumptions made regarding Clinic overhead, Clinic nursing costs and Home Care Program overhead.

Alternatives to in-patient care must be considered carefully. In this study, both out-patient and in-home treatment were cost-saving alternatives to in-patient treatment, but large differences in the cost of hospital out-patient vs. in-home care could not be demonstrated.

Despite the common association of psychiatric morbidity and multiple sclerosis (MS), population-based prevalence estimates of these disorders are limited. Such estimates are of particular importance to those conducting trials of interventions for the treatment of MS. This study examined the prevalence of bipolar disorder, depression, and attempted suicide among hospital service utilizers in Nova Scotia and compared these measures for the MS and non-MS population.

Data regarding diagnosis and utilization were extracted from two linked databases which included all hospital separation records for Nova Scotia over a 3 year period (1992/93-1994/95).

The prevalence of bipolar disorder in hospitalized MS patients was 1.97% and depression was 4.27%. These rates were significantly higher than the 0.92% and 2.04%, respectively, for the non-MS hospital utilizers. These diagnoses also accounted for more than half of the primary diagnostic codes for psychiatric service separations by MS patients. The proportion of total hospital utilization which was accounted for by psychiatric services did not differ between MS and non-MS utilizers. While suicide attempts were rare, the estimated frequency of suicide attempts in the total MS population was more than three times that of the general population.

Bipolar disorder and depression were twice as prevalent in hospitalized MS patients as in the general population of hospital utilizers while the estimated frequency of suicide attempts was at least three times greater. These results illustrate that psychiatric morbidity and service utilization are important considerations in the care of MS patients.

Myasthenia gravis (MG) is a specific autoimmune disease characterized by weakness and fatigue. MG may affect also the respiratory muscles causing symptoms that may vary from dyspnea on severe exertion to dyspnea at rest. This study was undertaken in order to determine the effects of respiratory muscle training on respiratory muscle performance, spirometry data and the grade of dyspnea in patients with moderate to severe generalized MG.

Eighteen patients with MG were studied and divided into 2 groups: Group A included 10 patients (3 males and 7 females aged 29-68) with moderate MG, and Group B that included 8 patients (5 males and 3 females aged 21-74) with severe MG. Patients in Group A received both inspiratory and expiratory muscle training for 1/2 h/day, 6 times a week, for 3 months, while patients in Group B followed the same protocol but had inspiratory muscle training only.

Mean PImax increased significantly from 56.6 ± 3.9 to 87.0 ± 5.8 cm H20 (p < 0.001) in Group A, and from 28.9 ± 5.9 to 45.5 ± 6.7 cm H20 (p < 0.005) in Group B. The mean PEmax also increased significantly in patients in Group A, but remained unchanged in the patients in Group B. The respiratory muscle endurance also increased significantly, from 47.9 ± 4.0 to 72.0 ± 4.2%, p < 0.001, in patients of Group A, and from 26.0 ± 2.9 to 43.4 ± 3.8, p < 0.001, in patients in Group B. The improved respiratory muscle performance was associated with a significant increase in the FEV, values, and in the FVC values, in patients of both groups. Mean dyspnea index score also increased significantly from 2.6 ± 0.8 to 3.6 ± 0.4 (p < 0.005) in Group A, and from 0.7 ± 0.2 to 2.0 ± 0.2 (p < 0.001) in Group B.

Specific inspiratory threshold loading training alone, or combined with specific expiratory training, markedly improved respiratory muscle strength and endurance in patients with MG. This improvement in respiratory muscle performance was associated with improved lung function and decreased dyspnea. Respiratory muscle training may prove useful as a complementary therapy with the aim of reducing dyspnea symptoms, delay the breathing crisis and the need for mechanical ventilation in patients with MG.

Previous studies demonstrated controversial results regarding monoamine oxidase B (MAO-B) activity in platelets in the periphery in parkinsonian patients (PD).

Therefore we determined platelet MAO-B activity in three age- and sex-matched groups of 17 untreated, so called “de novo” patients with Parkinson's disease (PD), 17 parkinsonian patients, receiving levodopa, and 17 controls by a radio enzymatic assay.

No significant differences of MAO-B activity appeared.

This result suggests that phenotypic determination of MAO-B activity in platelets may not be used as peripheral marker in PD and that levodopa treatment does not alter MAO-B activity in the periphery.

Pathological laughter can be a sign of epilepsy, psychiatric illness, effect of toxins or psychotropic drugs or of structural brain disease.

Case Studies.

Two patients developed inappropriate uncontrollable laughter following intravenous sodium valproate for treatment of epilepsy.

Pathological laughter can be a side effect of intravenous sodium valproate.

There are only rare reports of myasthenia gravis complicating human immunodeficiency virus infection. The role of immunomodulatory therapy is unknown.

Case report and literature review.

The diagnosis of human immunodeficiency virus infection followed that of myasthenia gravis in a 35-year-old man. Clinical and electrophysiological features were diagnostic of generalized myasthenia gravis but two edrophonium chloride tests and acetylcholine receptor antibodies were negative. Prednisone therapy and intravenous gamma globulin were associated with rapid clinical recovery.

Prednisone therapy and intravenous gamma globulin may be helpful in patients with generalized myasthenia gravis complicating HIV infection.

The thromobolytic drug, tissue plasminogen activator (tPA) has been approved in the United States for the treatment of acute ischemic stroke amid controversy and concern about the balance of risk and benefit. The Canadian Stroke Consortium (CSC), a national network of neurologists who collaborate on joint projects in stroke medicine, including clinical trials and consensus statements, has developed guidelines for the use of tPA in Canada.

The CSC Board of Directors wrote a preliminary report based on existing publications, including randomized drug trials and the report of a special committee struck by the Stroke Council of the American Heart Association. This draft was circulated to the CSC membership-at-large for suggestions or amendments, to produce this final draft.

The present guidelines have been devised to represent a Canadian viewpoint of management. The Health Protection Branch of the Ministry of Health of Canada has not yet produced an evaluation. Further modification of these guidelines may be necessary when more data from clinical trials and experience with the drug become available.