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.

To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating focally recurrent high grade glial neoplasms of World Health Organization (WHO) grade III or IV.

We conducted a retrospective cohort review of all patients treated with GK for focally recurrent high grade gliomas at our institution between November 2003 and April 2013. Data on age, sex, tumor volume, location and maximal diameter, presenting clinical status, complications and clinical outcome was recorded.

A total of 33 patients were identified. Four were lost to follow-up. Average post-GK and overall survival was 20.4 months (range: 3 – 72) and 63.3 months (range: 10 – 214) respectively. For WHO grade IV gliomas, the average post-GK and overall survival was 15.8 months (range: 3 – 77) and 40.1 months (range: 13 – 148) respectively. Similarily, for WHO grade III gliomas, the average post-GK and overall survival was 34.9 months (range: 6 – 72) and 136.4 months (range: 22 – 214) respectively. Twenty-two patients (75.9%) had post-GK edema, with 14 requiring dexamethasone and eight being asymptomatic. Four patients (13.8%) had imaging defined radiation necrosis.

Gamma Knife SRS affords an extension of local tumor control, acceptable morbidity, and potentially prolonged survival, for highly selected patients with focally recurrent high grade glial neoplasms.

Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM).

To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates.

We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician.

AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%.

Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.

The goal of this study was to quantify the impact of the suggested education correction on the sensitivity and specificity of the Montreal Cognitive Assessment (MoCA).

Twenty-five outpatients with dementia and 39 with amnestic mild cognitive impairment (aMCI) underwent a diagnostic evaluation, which included the MoCA. Thirty-seven healthy controls also completed the MoCA and psychiatric, medical, neurological, functional, and cognitive difficulties were ruled out.

For the total MoCA score, unadjusted for education, a cut-off score of 26 yielded the best balance between sensitivity and specificity (80% and 89% respectively) in identifying cognitive impairment (people with either dementia or aMCI, versus controls). When applying the education correction, sensitivity decreased from 80% to 69% for a small specificity increase (89% to 92%). The cut-off score yielding the best balance between sensitivity and specificity for the education adjusted MoCA score fell to 25 (61% and 97%, respectively).

Adjusting the MoCA total score for education had a detrimental effect on sensitivity with only a slight increase in specificity. Clinically, this loss in sensitivity can lead to an increased number of false negatives, as education level does not always correlate to premorbid intellectual function. Clinical judgment about premorbid status should guide interpretation. However, as this effect may be cohortspecific, age and education corrected norms and cut-offs should be developed to help guide MoCA interpretation.

To examine time delays and identify factors that affect wait times from index neurological event to carotid endarterectomy in patients with symptomatic carotid stenosis treated at a regional neurosurgical referral centre.

We performed a retrospective audit over two years of all patients who underwent a carotid endarterectomy at University Hospital, London, Ontario. The number of days was calculated from first neurological event through until surgery.

Eighty-nine carotid endarterectomies (CEAs) were performed by four surgeons during the years 2006 and 2007. From the first neurological event, the median wait time for surgery was 111 days, while from the last event the median wait time was 83 days. There was 19 days' wait between specialist / TIA clinic appointment and the receipt of neurosurgical referral. Median wait time for diagnostic imaging was eight days for carotid Doppler ultrasound and 15 days for CT or MR angiography. There was a 44 day wait from receipt of neurosurgical referral to the date of surgery. Only three patients (4%) received CEA within two weeks of their last neurological event. There was a trend towards a difference in wait times between inpatients and outpatients, but no difference between females compared with males, or between patients presenting with stroke versus TIA.

Median wait times for CEA after first neurological event was over three months at our center, reflecting the diagnostic workup required in TIA as well as the lack of a systematic approach. This is the subject of continued study at our institution.

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.

We investigated patient socio-demographic, clinical and functional factors predicting cholinesterase inhibitor discontinuation by patients presenting to a memory clinic in Saskatoon, Saskatchewan.

Data collection began in March 2004 at the Rural and Remote Memory Clinic where family physicians referred their non-institutionalized patients. Neurological and neuropsychological assessment, patient and caregiver questionnaires provided the socio-demographic, clinical and functional variables. Univariate logistic regression analysis was used to examine possible associations between each independent variable and the binary outcome variable of treatment discontinuation. Multivariate logistic regression was used to determine predictors of cholinesterase inhibitor discontinuation within six months of drug initiation.

Our sample consisted of the first 63 patients (60.3% female) for whom we prescribed a cholinesterase inhibitor. The mean age at clinic day was 74.56 years (SD=7.78). We found that years of formal education was the only variable significantly associated with cholinesterase inhibitor discontinuation by six months. The more years of formal education, the lower the rate of drug discontinuation by six months.

Likelihood of cholinesterase inhibitor discontinuation by six months was predicted by fewer years of formal education.

We describe the internal cerebral vein (ICV) sign, which is a hypo-opacification of the ICV on computed tomogram angiography (CTA) as a new marker of increased cerebral blood transit-time in ipsilateral internal carotid artery occlusions (ICAO).

A retrospective analysis of 153 patients with acute unilateral M1 middle cerebral artery (MCA) occlusions ± ICAOs was performed. The degree of contrast opacification of the ICV on the ipsilesional side was compared to that of the unaffected side.

Of 153 patients in our study, 135 had M1 MCA occlusions ± intra-cranial ICAO (M1±iICAO) and 18 had isolated extracranial ICAO (eICAO). In the patients with proximal M1±iICAO, 57/65 (87.1%) showed the ICV sign. Of the 8 patients without the ICV sign in this group, 6 had prominent lenticulostriate arteries arising from the non-occluded M1 segment, 1 had a recurrent artery of Huebner, and 1 had filling of distal ICA/M1 segment through prominent Circle of Willis collaterals. For the 70 patients with isolated distal M1±iICAO, 7/70 (10%) showed the ICV sign, with all 7 showing occluded lenticulostriate arteries. Of the patients with eICAO, 8/18 showed the ICV sign, all 8 with the ICV sign had poor Circle of Willis collaterals.

The ICV sign correlates well with presence of proximal M1±iICAO in patients with either occluded lenticulostriate arteries or poor Circle of Willis collaterals. In patients with eICAO, the sign correlates with reduced Circle of Willis collaterals and may be a marker of increased ipsilateral cerebral blood transit time.

Radiation therapy (RT) is the major component of glioblastoma treatment; however, the time to initiate RT after surgical intervention varies between institutions. Our study examined the time from diagnosis to the initiation of RT and its effects on overall patient survival.

We retrospectively examined 267 patients with glioblastoma who received RT as part of their therapy in two Canadian tertiary care centers. The primary goal of the study is to assess if time to RT can predict/impact survival in glioblastoma patients.

The following variables were associated with an increased risk of death: hazard ratio (HR) of time to RT was 0.95 [95% confidence interval (CI), 0.91–0.99] for every extra week. HRs for the type of surgery (resection or biopsy) and type of management received (standard of care in comparison with RT regardless of chemotherapeutic agents other than concomitant and adjuvant temozolomide) were 0.50 (95% CI, 0.37–0.66) and 0.53 (95% CI, 0.38–0.75), respectively. HR for age was 1.02 (95% CI, 1.01–1.03) for every extra year. Standard 60 Gy RT HR was 0.70 [95% confidence interval (CI), 0.51–0.97] in younger patients.

The time from diagnosis to the initiation of RT was found to be a significant prognostic factor for overall patient survival. The addition of temozolomide to the treatment protocol, age, standard RT dose in younger patients and extent of surgery are others factors associated with longer survival periods.

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.

Performing ‘good work’ in either neurosurgery or neuroscience alone is a challenge. Despite this, a large number of neurosurgeons divide their careers between the two fields, and attempt to excel in both arenas simultaneously. The purpose of this study is to explore perceptions on whether it is possible to do good work in both neurosurgery and research simultaneously, or whether one field suffers at the expense of the other.

This question was put to practicing neurosurgeons via an electronic survey that was distributed to resident and staff neurosurgeons in Canada.

54 surgeons completed the survey, 32 of whom were current or intended neurosurgeon-scientists. Themes explored through the survey included motives behind the pursuit or absence of research in one's neurosurgical career, the quality and feasibility of a dual career, and alternatives to one individual assuming a dual role.

The opinions obtained revealed that it is possible to do good work in both neurosurgery and neuroscience simultaneously, but in reality it is very difficult to do. Alternatives to this dual career, such as collaboration between clinical neurosurgeons and pure scientists for example, may help bridge the gap between clinical and research arenas.

Screening for cognitive impairment is recommended in patients with cerebrovascular disease. We sought to establish the incidence of cognitive impairment using the Montreal Cognitive Assessment (MoCA) in a cohort of consecutive patients attending our stroke prevention clinic (SPC), and to determine whether a subset of the MoCA could be derived for use in this busy clinical setting.

The MoCA was administered to 102 patients. Incidence of cognitive impairment was compared to presenting complaint and final diagnosis. extent of cerebral white matter changes (WMC) was rated using the Age Related White Matter Changes (ARWMC) scale in 80 patients who underwent neuroimaging. A subset of the three most predictive test elements of the MoCA was derived using regression analysis.

63.7% of patients scored <26/30 on the MoCA, in keeping with cognitive impairment. This was unrelated to the final diagnosis or extent of WMC, although a trend for lower MoCA scores was observed in older patients. A mini-MoCA subscore combining the clock drawing test, five-word delayed recall, and abstraction was highly correlated with the final MoCA score (R=0.901). A score of <7/10 using this 10-point mini-MoCA identified cognitive impairment as defined by the MoCA with a sensitivity of 98.5%, and a specificity of 77.6%.

Two-thirds of SPC patients demonstrated evidence for cognitive impairment, irrespective of their final diagnosis or the presence of WMC. A mini-MoCA comprised of the clock drawing test, five-word delayed recall, and abstraction represents a potential alternative to the full MoCA in this population.

Radiosurgery can be delivered through a variety of modalities including robotic and fixed gantry linacbased systems. They appear equally effective and safe. Thus, community need and costs remain the main determinants for choosing a given modality. We performed an economic evaluation to identify settings in which one modality could be preferred over the other.

Using local estimates of resource volumes and unit prices, we computed the incremental cost/patient of robotic radiosurgery compared to fixed-gantry radiosurgery from a payer's perspective. By varying parameters of resource volumes, we performed a probabilistic analysis stratified by number of brain lesions. in addition, we performed sensitivity analyses to examine the effect of patient volume on cost/patient.

The cost of robotic radiosurgery was $4,783/patient, and cost of fixed-gantry radiosurgery was $5,166/patient. The mean incremental cost was $-383 (95% interval: $-670, $110) for all lesions, $78 ($23, $123) for solitary lesions, and $-610 ($-679, $-534) for multiple lesions. The cost/patient of robotic radiosurgery varied from $5,656 (low volume setting) to $4,492 (high volume setting).

in settings of moderate to high volume (6-10 hours of daily operation), and in multiple lesions, robotic radiosurgery is more cost effective than fixed-gantry radiosurgery.