The incidence and prevalence of multiple sclerosis (MS) in Newfoundland and Labrador (NL) had been reported in 1984 and was considered to be relatively low at that time. This study revisits the incidence and prevalence of MS in NL for the year 2001.

Case searches through patient files of neurologists in NL were conducted. A complete list of patients billed for MS in NL between 1996 and 2003 was obtained and all cases were confirmed via chart review.

There were 493 living MS patients yielding a prevalence of 94.4/100,000 which is significantly higher than previously reported. Of the living patients, 330 had relapsing remitting (RRMS), 94 had secondary progressive, 66 had primary progressive (PPMS) and three had unspecified MS. The total female to male ratio was 2.7:1. There was no difference between the female to male ratios for RRMS vs PPMS. Patients with PPMS had a later onset compared to RRMS (p<0.00001). Yearly incidences were relatively constant from 1994 to 2001 (5.6/100,000). Significant delays between first symptoms and final diagnosis were common and the delay time has not changed over the past 15 years. A prevalence of 88.9/100,000 was estimated from survival and incidence trends and was not significantly different than the measured prevalence (p=0.38).

The increase in incidence and prevalence are accounted for through both better access to diagnostic facilities and more practicing neurologists. The revised prevalence and incidence are more in keeping with recently reported values throughout Canada.

L’augmentation de l’incidence et de la prÉvalence se justifient par une plus grande accessibilitÉ aux moyens diagnostiques et par la prÉsence d’un plus grand nombre de neurologues. La prÉvalence et l’incidence que nous rapportons sont plus conformes à celles rapportÉes rÉcemment à travers le Canada.

Newfoundland and Labrador, Canada, have been almost exclusively populated by immigrants from southwest England and southeast Ireland. The province’s population grew largely by natural increase from 20,000 people in 1835 to half a million at present. Very little interregional migration occurred within the province. This uniquely-populated region and its subsequent founder effect provide the basis to develop models of disease prevalence.

To develop a model for the regional prevalence of multiple sclerosis (MS), accounting for settlement patterns and geographic location (latitude).

All living MS patients with confirmed addresses (438 patients) in the province were mailed a survey requesting their place of birth. Regional prevalences were calculated from a 75% rate of return of the survey. Theoretical regional prevalences were proportionally calculated from the source prevalences of southwest England, southeast Ireland, Scotland and the Channel Islands based on settlement patterns. These theoretical regional prevalences were corrected for geographical variations of latitude based on observations in the United Kingdom. Theoretical and actual regional prevalences were compared.

When actual regional prevalences were compared with theoretical prevalences, very little variation was noted, especially after correcting for variation in latitude.

A regional variation in MS prevalence is noted in the island portion of Newfoundland and Labrador. This regional variation can be modeled by using both migration patterns and latitudinal position. This model demonstrates that the prevalence of MS is influenced by both genetic and environmental contributions.

We compared the functional status and survival time of patients with malignant gliomas.

This retrospective review included 143 patients diagnosed with malignant gliomas. Patients were grouped according to histopathological diagnosis. To measure functional status, patients were assigned a Karnofksy performance status (KPS) score at the time of presentation and at one, three, six, nine, 12 months and yearly intervals thereafter. Data were analyzed using descriptive methods as well as Kruskal-Wallis tests, Chi-square tests, Log-Rank tests and Cox’s proportional hazards modeling.

Eighty-four patients were male. The median age of patients was 63 years. One hundred and seven patients had a histopathological diagnosis of glioblastoma multiforme, 23 of anaplastic astrocytoma and 13 of anaplastic oligodendroglioma. Twenty-nine patients received aggressive multimodal treatment, 83 received intermediate treatment and the remaining 31 patients received conservative therapy. Significant treatment complications occurred in 33% of patients including four post-operative deaths. The anaplastic oligodendroglioma group had lower mortality and maintained better KPS scores over time, as did patients receiving full treatment. The most significant prognostic factors for functional status included age, pretreatment KPS, and type of treatment received. The most significant factors associated with time until death included age, severity of comorbidities, pretreatment KPS, presence of confusion, histopathological diagnosis and type of treatment received.

In patients with malignant gliomas, younger age, better functional status at presentation and aggressive multimodal treatment were associated with improved longer-term functional status and survival. Confirmation of the effect of multimodal treatment on patient functional status would require a randomised controlled clinical trial.

To reduce postoperative hydrocephalus following surgery in the region of the fourth ventricle.

We describe the use of a conventionally placed lateral ventricular catheter to facilitate anterograde ventricular irrigation during surgery in the region of the fourth ventricle. This technique offers a safe alternative to more conventional approaches to fourth ventricular irrigation and obviates the need for placement of a third or fourth ventricular catheter and/or serial lumbar punctures by thoroughly flushing blood and tissue debris from the operative field at the time of surgery.

Preliminary results spanning a five-year period show a lower incidence in the need for early ventriculo-peritoneal shunts (5%) and delayed ventriculo-peritoneal shunts (10%).

This technique represents a safe method of reducing hydrocephalus following operative procedures in the region of the fourth ventricle.

Repinotan is a potent, serotonin (5-HT1A) full receptor agonist that interferes with ischemia-mediated neuronal cell death in animal models. This double-blind, placebo-controlled phase II study examined the safety, tolerability, and dose of repinotan in patients with acute ischemic stroke.

Patients with acute hemispheric ischemia and a National Institutes of Health Stroke Scale of 4 to 25 were randomized to placebo or repinotan 0.5, 1.25, or 2.5 mg/day (d) given by continuous intravenous infusion for 72 hours. Treatment was started within six hours of symptom onset. Evaluations were performed at four weeks and three months.

Among 240 patients in the safety analysis, repinotan was well-tolerated, with adverse events appearing more frequently in the highest dose group (2.5 mg/d). The most common adverse event was headache (21.3% to 35% with repinotan and 24.1% with placebo). Most (75%) adverse events were of mild or moderate severity. The most common severe adverse events were neurological worsening, cerebral hemorrhage, and brain edema. The number of deaths and serious adverse events were similar among placebo and repinotan groups. Compared to the placebo group, the proportion of patients with good outcomes at three months was greatest in the group receiving repinotan 1.25 mg/d, although the difference was not statistically significant.

This study indicates that the incidence of adverse events was comparable with all doses of repinotan and placebo, and no safety issues were observed. A trend toward better tolerability with evidence of efficacy was observed with the repinotan 1.25 mg/d dose.

Dans cette Étude, l’incidence des incidents thÉrapeutiques Était comparable quelle que soit la dose de repinotan par rapport au placebo et aucun problème reliÉ à la sÉcuritÉ du produit n’a ÉtÉ observÉ. On a observÉ l’efficacitÉ du repinotan à la dose de 1,25 mg/j. et une tendance à une meilleure tolÉrance du mÉdicament.

Recently, a single base pair substitution (G1747A) mutation of the neurofilament M (NF-M) gene was reported in a French-Canadian patient with early onset Parkinson’s disease (PD). Three unaffected siblings were found to be heterozygotes for the NF-M Gly336Ser mutation but, to date, no other affected PD individuals have been found with a similar mutation. No other individuals with Parkinson’s disease and of similar ethnic background have been screened for this mutation.

We screened 102 French-Canadian patients with definite PD and 45 French-Canadian controls for this substitution in the NF-M gene using a PCR-restriction enzyme digestion method.

None of the patients or controls carried this mutation.

Our results would indicate that this mutation is not common even in a PD population of similar ethnic background and suggest this change represents a rare variant. However, these results do not exclude the possibility that other mutations in this gene could be present.

To describe the results, technical feasibility, efficacy and challenges encountered in our preliminary experience using a self-expandable microstent, optimized for intracranial use, as an adjunct in the endovascular treatment of wide-necked aneurysms.

Only broad-necked aneurysms (dome-to-neck ratio £2, or an isolated neck size > 4.5 mm) were treated with Neuroform microstent from July 2003 to May 2004. The techniques used for stent deployment were either parallel or sequential. Angiographic results were recorded immediately for all patients and classified as Class 1 (complete occlusion), Class 2 (neck remnant) or Class 3 (sac remnant) by three interventional neuroradiologists not involved in the procedure. Follow-up angiography at six months was obtained for one case. Modified Rankin Score scale was assessed for all patients.

Seventeen intracranial aneurysms in a total of 18 patients were treated (mean age, 52.2 yr). Eight patients (44.4%) presented with acute subarachnoid hemorrhage. Eleven aneurysms (61.1%) were in the posterior circulation. Average dome size was 10.2 mm (range, 3.7-19.8 mm) and average neck size was 5.36 mm (range, 3.0-10.0 mm). Six out of seven aneurysms of the anterior circulation were approached with parallel technique. Eight aneurysms of the posterior circulation were approached with sequential technique. Average number of coils deployed was 9.64 (range, 4-23 coils). Eleven aneurysms (64.8%) resulted in Class 1 and/or Class 2. One technical failure was observed. Technical complications were recognized in four patients (23.5%), all of them with unruptured aneurysms in the anterior circulation. Two patients (11.7%) presented transient immediate clinical complications. One patient (5.8%) had minor permanent neurological complication. Neither major clinical complications nor death were encountered. Favorable clinical outcome (Modified Rankin Scale score 0-2) was observed in 88.2% of the patients (average follow-up time, 4.72 months).

Absence of major permanent complications and satisfactory immediate obliteration degree in our preliminary experience indicates that microstent-assisted coiling technique is useful for the minimally invasive treatment of broad-necked complex aneurysms that are not ideal for conventional endovascular treatment and are at a high risk for conventional surgical treatment.

Impaired gastrointestinal motility in Parkinson’s disease may affect absorption of levodopa and contribute to the disabling response fluctuations (RF). In this study gastric myoelectric activity was recorded with electrogastrography in patients with PD and correlated with the duration, severity and the presence of RF.

Electrogastrography (EGG) was performed in 36 patients with PD of which 22 were men. The mean age was 67 years (48-81), mean duration of disease was 7.07 years (1-20), and mean duration of treatment with levodopa was 5.07 years (1-20). Gastric dysrrythmia was diagnosed when either preprandial or postprandial dysrrythmia for more than 30% of the recording period was detected.

The EGG was abnormal in 24 of 36 patients. Significant association was found between preprandial dysrrythmia and duration of disease (P=0.002); duration of levodopa treatment (P=0.003), severity of 86RF (P=0.001), but not with age (P=0.076). Out of 18 patients with RF, 17 had at least one pattern of dysrrythmia. In 11 out of the 18 patients without RF, the EGG was normal while the remaining seven had at least one pattern of dysrrythmia.

Abnormal EGG was quite common in this group of patients with PD, particularly in those with RF. The most common pattern of abnormality was preprandial dysrrythmia, which was positively associated with disease duration and length of levodopa treatment. Although frequently asymptomatic, preprandial dysrrythmia leading to impaired gastric emptying may contribute to irregular absorption of levodopa from the small intestine and contribute to disabling response fluctuations.

Although severe traumatic brain injury (sTBI) is a devastating condition with tremendous public health implications, the epidemiology of this disease has not previously been described in Canada. We sought to define the incidence, risk factors and outcome of patients suffering sTBI in a large Canadian region.

A population-based surveillance cohort design was utilized to identify all Calgary Heath Region residents who were victims of trauma with an injury severity score ³12. Subsequent application of a specific sTBI case definition defined the final cohort.

The annual incidence of sTBI was 11.4 per 100,000 population. The incidence of sTBI was significantly higher for males as compared to females [17.1 vs. 5.9 per 100,000; relative risk (RR) = 2.91, 95% confidence interval; 2.17, 3.94; p<0.0001]. There was a striking increase in the annual age specific population incidence of sTBI observed among those older than 74 years of age. The relative risk among the highest risk group of elderly (>85 years) males as compared to the lowest risk female group (50-64 years) was 19.78 (95% CI; 6.27, 62.3; p<0.0001). One hundred and eight patients died prior to hospital discharge for a mortality rate of 5.1 per 100,000 per year.

Severe traumatic brain injury is common among residents of the Calgary Health Region and is associated with a high mortality rate. Males and the elderly are at the highest risk for acquiring sTBI and may represent target groups for preventive efforts.

Les lÉsions cÉrÉbrales par traumatisme crânien sÉvère sont frÉquentes parmi les rÉsidents de la rÉgion sanitaire de Calgary et sont associÉes à une mortalitÉ ÉlevÉe. Les hommes et les personnes âgÉes sont les groupes les plus à risque et constituent des groupes cibles pour les interventions à visÉe prÉventive.

Clobazam is a benzodiazepine with known antiepileptic action; however, it is not considered first line therapy in the treatment of epilepsy. The objective of this study was to evaluate the efficacy of clobazam as add-on therapy in adults with temporal lobe epilepsy associated with MRI evidence of hippocampal sclerosis (HS).

This is a retrospective study, conducted at our epilepsy clinic which evaluated clobazam as add-on therapy in patients with temporal lobe epilepsy and MRI signs of HS. Clobazam was prescribed based on the minimum effective dose up to the maximum tolerated dose.

Seventy-eight patients met the inclusion criteria (51 women), ages ranging from 16 to 76 years old (mean=42.2). Dosage of clobazam ranged from 5 to 60 mg/day (mean=22.6 mg/day). Clobazam was used from one month to eight years (mean=29 months). Sixteen (20.5%) patients were seizure-free, 20 (25.5%) had more than 75% improvement in seizure control, eight (10%) had more than 50% and 20 (26%) were non responders to clobazam. In 14 (18%) we could not determine seizure frequency during follow-up. The improvement in seizure control lasted for more than one year in 30 (68%) patients.

Our data suggest that clobazam should be considered as add-on therapy in the treatment of patients with temporal lobe epilepsy associated with MRI signs of HS.

Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones.

Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI. Discussion: We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.

We report a case of selective loss of emotional facial movements which resulted from bilateral acute infarcts. No etiology was discovered, and the syndrome was reversible.

The available literature, and findings in this case, suggest that voluntary and automatic facial movements have distinct pathways, and damage to the insula bilaterally may lead to the selective loss of emotional facial movements. The clinical presentation of this inverse automatic/voluntary dissocation needs to be recognized as a rare syndrome with bilateral localization, so that patients at higher risk of further stroke can quickly be identified.