Stroke thrombolysis is limited by the “last-seen well” principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were “last-seen well” at the time they went to bed implying an interval that is most often greater than three hours.

A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death.

Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10).

Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.

To learn more about the needs and experiences of young carers for patients of frontotemporal dementia (FTD) in order to create a relevant support website for young caregivers to dementia patients.

Two focus groups were held with a total of fourteen young carers aged 11-18. The data corpus was collected through a semi-structured interview facilitated by a medical journalist who had prior experience as a caregiver to a patient with FTD. The transcripts were narrowed to a dataset for descriptive analysis using a coding scheme to reveal the main themes of their responses.

Seven overlapping theme areas were: emotional impact of living with a parent with FTD, caregiving, coping, symptoms, diagnosis, relationships, and support. Based on the participants' responses, a website was launched providing supportive information and counsel for young carers.

Young carers saw the experience of caring for a parent with early-onset dementia as positive overall, but identified opportunities for professionals to assist them in overcoming stigma and the challenge of balancing childhood and adolescent development within this context.

Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research.

We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset.

We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS.

The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.

The clinical manifestations of drug-induced parkinsonism (DIP) and Parkinson disease (PD) are nearly indistinguishable, making it difficult to differentiate DIP from PD, especially in the early stages. We compared non-motor symptoms between patients with DIP and those with drug-naïve PD in the early stages using the Non Motor Symptoms Scale (NMSS).

We prospectively enrolled 28 patients with DIP, 35 patients with drug-naïve PD, and 32 controls with no history of neurological diseases or related medical problems. We investigated demographic characteristics, medical and drug history, parkinsonian motor symptoms, and non-motor symptoms. We used the NMSS to evaluate non-motor symptoms in all patients.

The total NMSS scores were higher in patients with PD than those with DIP, as were the scores for certain domains, including the cardiovascular, sleep/fatigue, urinary, sexual, and miscellaneous domains. When controlling for age and gender, the correlation analysis revealed that scores for urinary symptoms (urgency, frequency and nocturia), sleep disturbances (daytime sleep, restless legs), concentration, taste or smell were significantly associated with PD.

Our data suggest that non-motor symptoms, particularly urinary symptoms, excessive daytime sleepiness, restless leg syndrome, attention deficit and hyposmia may be helpful to differentiate between DIP and PD in the early stages.

The prevalence of unhealthy lifestyle habits such as smoking has seldom been described in neuromuscular disorders, including myotonic dystrophy type 1 (DM1). However, it is essential to document the unhealthy lifestyle habits as they can exacerbate existing impairments and disabilities. The objectives are: 1) To determine the prevalence of risk factors among individuals with DM1; 2) To compare the prevalence among classic and mild phenotypes.

A survey was done on a sample of two-hundred (200) patients with DM1 as part of a larger study. Lifestyle risk factors included being overweight or obese, tobacco smoking, illicit drug use, excessive alcohol consumption and physical inactivity. A registered nurse administered the validated public health survey. Categorization of risk factors were based on national standards and compared with provincial and regional prevalences.

50% of DM1 patients were overweight or obese, 23.6% were regular smokers, and 76% were physically inactive. Except for overweight and obesity, significant differences were observed between patients with classic and mild phenotypes for all the other lifestyle risk factors: those with the classic phenotype being more often regular smokers, consuming more often illicit drugs and being less physically active.

The results of this study will provide guidance for the development of better adapted and focussed health promotion interventions in the future.

The surgical removal of the epileptogenic zone in medically intractable seizures depends on accurate localization to minimize the neurological sequelae and prevent future seizures. To date, few studies have demonstrated the use of depth electrodes in a pediatric epilepsy population. Here, we report our study of pediatric epilepsy patients at our epilepsy center who were successfully operated for medically intractable seizures following the use of intracranial depth electrodes. In addition, we detail three individuals with distinct clinical scenarios in which depth electrodes were helpful and describe our technical approach to implantation and surgery.

We retrospectively reviewed 18 pediatric epilepsy patients requiring depth electrode studies who presented at the University of Alberta Comprehensive Epilepsy Program between 1999 and 2010 with medically intractable epilepsy. Patients underwent cortical resection following depth electrode placement according to the Comprehensive Epilepsy Program surgical protocols after failure of surface electroencephalogram and magnetic resonance imaging to localize ictal onset zone.

The ictal onset zone was successfully identified in all 18 patients. Treatment of all surgical patients resulted in successful seizure freedom (Engel class I) without neurological complications.

Intracranial depth electrode use is safe and able to provide sufficient information for the identification of the epileptogenic zone in pediatric epilepsy patients previously not considered for epilepsy surgery.

There is controversy among neurosurgeons regarding whether double burr hole craniostomy (DBHC) is better than single burr hole craniostomy (SBHC) in the treatment of chronic subdural hematoma (CSH), in terms of having a lower revision rate. In order to compare the revision rates after SBHC versus DBHC, we performed a meta-analysis of the available studies in the literature.

Multiple electronic health databases were searched to identify all the studies published between 1966 and December 2010 that compared SBHC and DBHC. Data were processed in Review Manager 5.0.18. Effect sizes were expressed in pooled odds ratio (OR) estimates, and due to heterogeneity between studies we used random effect of the inverse variance weighted method to perform the meta-analysis.

Five observational retrospective cohort studies were identified: four published studies and one unpublished, describing the outcomes of 355 DBHC and 358 SBHC to evacuate 713 CSH in 631 patients. Meta-analysis showed that there was no significant difference in the revision rates between double burr hole craniostomy and single burr hole craniostomy when performed to evacuate CSH. Pooled odds ratio for all the studies was 0.62 (95% confidence interval 0.26 - 1.46).

The results of this meta-analysis suggest that SBHC is as good as DBHC in evacuating chronic subdural hematoma and is not associated with a higher revision rate compared to DBHC.

The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability.

Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin.

A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin.

The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.

Differences in Multiple sclerosis (MS) disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored.

To examine concentrations of prescribing patterns and to assess if MS-specialists use a broader range of DMTs relative to general neurologists.

We conducted a cross-sectional study using administrative claims databases in Ontario, Canada to link neurologists to 2009 DMT prescription data. MS specialization was defined using both practice location and prescription patterns. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns, separating neurologist characteristics dichotomously and separating Avonex from the other standard DMTs (Betaseron, Rebif and Copaxone). Gini coefficient 95% confidence intervals (CIs) were derived using jack-knife statistical techniques.

Prescriptions were highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. There was a trend towards Avonex being more commonly prescribed relative to the other DMTs. When MS specialization was defined by DMT prescribing, high-volume prescribing neurologists showed a broader range of DMT prescribing (Gini 0.38-0.44) in comparison to low-volume prescribers (Gini 0.57-0.66).

The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribing MS-specialists show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD.

We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender.

Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72).

In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

The aim of the study is to explore the association of serum bilirubin levels with admission severity and short term clinical outcomes among acute ischemic stroke patients.

Data were collected from 2361 acute ischemic stroke patients in four hospitals of Shangdong Province during January 2006 and December 2008. National Institutes of Health Stroke Scale (NIHSS) was used to assess admission and discharge severity. NIHSS≥10 at discharge or in-hospital death was defined as short-term clinical outcomes. Logistic regression and trend test were used to examine the association of serum bilirubin levels with admission severity and short term clinical outcomes.

Serum bilirubin levels were significantly and positively associated with admission severity (P for trend <0.05). The age-sex adjusted odds ratios (95% confidential intervals) of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.245 (0.873, 1.777)/1.276 (0.895, 1.818), 1.484 (1.048, 2.102)/1.628 (1.158, 2.289) and 2.869 (2.076, 3.966)/2.765 (1.996, 3.828), respectively, compared with the lowest quartile; the multivariate adjusted odds ratios of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.088(0.711, 1.665)/1.436(0.94, 2.193), 1.328(0.877, 2.011)/1.647(1.092, 2.485) and 2.336(1.579, 3.458)/3.079 (2.049, 4.623), respectively, compared with the lowest quartile. However, no association between serum bilirubin levels and short-term clinical outcomes was observed in our study.

Serum bilirubin levels were associated with initial stroke severity closely. Nevertheless, there is no significant relationship between serum bilirubin levels and short-term clinical outcomes among acute ischemic stroke patients.