Patients with chromosome 22q11.2 deletion syndrome (22q11DS) are at a seven fold increased risk of developing seizures. However, only a fraction of these patients exhibit structural abnormalities such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH) that are known to cause seizures and to be associated with 22q11DS. In this study we used a dedicated seizure imaging protocol to look for additional structural abnormalities in these individuals that may explain the elevated risk of seizure disorder in this patient group.

Nineteen consecutive adult subjects with 22q11DS underwent a 3 Tesla MRI with a dedicated high-resolution seizure protocol. Neurological exam was performed in all patients. Genome-wide analysis excluded the presence of other pathogenic microdeletions or duplications.

Structural abnormalities were found in 11 of 14 subjects with sufficient image quality. These included three patients with PNH, one of whom had associated PMG. In addition, there was a surprisingly high prevalence of unilateral hippocampal malrotation (HIMAL), observed in 9 of 14 cases (64%). EEG findings showed interictal epileptiform discharges with focal distribution in four patients and generalized discharges in one patient.

The results suggest that, in addition to other known structural abnormalities, 22q11DS is associated with HIMAL. It has been suggested that this developmental abnormality of the hippocampus may predispose or otherwise contribute to epileptogenesis. However in this study we observed HIMAL in a large proportion of patients, with and without epilepsy. Therefore, other as yet unknown factors may contribute to the high prevalence of epilepsy in this population.

Visual hallucination (VH) is a common psychotic symptom in patients with Parkinson's disease (PD) and may be a significant predictor of cognitive impairment (CI) in such patients.

This study aimed to investigate the pattern of glucose metabolism of VH and the relationship between VH and CI in PD.

We studied 28 PD patients, including 15 with VH (PD-VH) and 13 without VH (PD-NVH). Of the 15 PD-VH patients, 8 patients had cognitive impairment (PD-VHCI) whereas 7 did not (PD-VHNCI). All patients underwent [18F] fluorodeoxyglucose positron emission tomography ([18F] FDG PET) followed by statistical parametric mapping (SPM) analyses.

Compared to the patients with PDNVH, PD-VHNCI patients showed glucose hypometabolism in the inferior and middle temporal cortices, fusiform gyri, and frontal areas, suggesting the involvement of the ventral visual pathway. Compared to the patients with PDNVH, PD-VHCI patients showed glucose hypometabolism in the temporoparietal association cortices with scattered frontal areas.

Dysfunction of ventral visual pathway involving the temporal lobe may play a key role in VH development in PD patients. The evolving distribution from the ventral visual pathway to more extensive posterior cortices in PD-VHCI patients suggests that VH may be a prodromal symptom occurring prior to CI in PD patients.

One the greatest challenges of BoNT A therapy for tremor lies in the complexity and variation of components involved in tremor movement, and the lack of objective measures to determine these components. This 3 month open-label single injection study aims to couple clinician best judgment with kinematics to improve effect of BoNT A (incobotulinumtoxinA) injection in 7 patients with upper limb Parkinson's disease (PD) tremor.

Injection was guided with clinical and kinematic assessment of tremor using angular wrist position in 3 degrees of freedom: flexion/extension, pronation/supination, and radial/ulnar deviation. Overall tremor severity and change were measured by linear finger acceleration.

Kinematic data from static and functional tasks demonstrate no improvement at one month post-injection, but significant improvement at two and three months. Clinical scales across UPDRS Items 20 (1, 2, 3 months post) and 21 (2 months), and spiral drawings (3 months) showed significant improvement from baseline, while line drawings did not.

This study suggests injection of BoNT A as a viable focal management option for upper limb PD tremor. In addition to clinical judgment, objective quantification of tremor dynamics by kinematics may be a feasible assessment and guidance tool which can be used to optimize injection conditions for focal tremor therapy. Kinematic analysis of tremor across a variety of joints in all degrees of movement may provide important insight into tremor dynamics, allowing optimized, targeted focal therapy.

The current study sought to determine if the Kaplan-Baycrest Neurocognitive Assessment (KBNA) was capable of discriminating individuals with subjective memory complaints associated with depression from individuals with mild cognitive impairment (MCI).

Scores on 12 subtests of the KBNA were compared for 27 participants with MCI and 28 participants being treated for depression using Bonferroni correct between-group comparisons for each subtest. KBNA subtest scores were corrected for age and education.

Significant between-group differences were obtained on six subtests with large effect sizes (Cohen's d) ranging from 1.19 - 1.58. The six subtests involved encoding and delayed episodic memory for verbal and visual information. Using logistic regression analysis, five subtests of the KBNA were able to correctly classify 96.4% of study participants.

The results from this preliminary investigation indicate that the KBNA has the potential to serve as a brief and reliable assessment tool capable of distinguishing individuals with subjective memory complaints associated with depression from individuals with MCI in a clinical setting. Limitations of the current study and future research are discussed.

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.

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.

Polymorphisms of genes participating in iron transportation have been associated with Alzheimer's disease (AD) risk. The association between transferrin (TF) gene rs1049296 (P570S) polymorphism and AD is controversial.

We performed meta analysis on data from 19 studies with 6310 cases and 13661 controls to reexamine the association between the TF gene rs1049296 polymorphism and AD. We applied a fixed-effects model to combine the odds ratio (OR) and 95% confidence intervals (95% CI). Egger's test was carried out to evaluate the potential publication bias.

The overall ORs with 95% CIs showed statistical association between the TF gene rs1049296 polymorphism and the risk of AD in the allele contrast, the recessive model and the dominant model for allele C2 (fixed-effects pooled OR 1.11; 95% CI 1.05 to 1.17, pooled OR 1.13; 95% CI 1.06 to 1.21, and pooled OR 1.23; 95% CI 1.03 to 1.47, respectively). In the contrast of C2C2+C2C1 vs C1C1, large heterogeneity among the Asian subgroup (p=0.041, I2= 68.6%) was observed but not among the overall population (p = 0.184, I2= 22.4%). No publication bias was observed.

The present meta analysis demonstrated that TF gene rs1049296 polymorphism is a genetic determinant of AD.

Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.

We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).

The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.

The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

The Neuromuscular Registry of Saguenay-Lac-Saint-Jean (SLSJ), Québec, Canada was established for epidemiological surveillance of neuromuscular disorders including amyotrophic lateral sclerosis (ALS). The objectives of this study are to analyze the ALS clinical characteristics of the SLSJ population and to determine the incidence rate over time by five year periods since 1985.

The Registry was validated by a review of the medical records maintained at the CSSS de Chicoutimi, the regional university hospital and, by the estimation of the number of hospitalizations for ALS patients using the Quebec Hospital inpatient database (MED-ECHO).

A total of 109 patients were included. Overall, the clinical features of ALS observed in SLSJ population are similar to those described in the literature. We observed a significant increase in the incidence rate of ALS during the 2005-2009 period compared with the previous periods. This is due to a significant increase in the incidence rate among the ≥65 years old group, from 4.68 per 100,000 persons/year (CI 95% 2.88-6.48) during 1985-2004 period to 12.22 (CI 95% 7.43-17.02) during 2005-2009 period.

Given the small size of the SLSJ population, a longer observation period will be needed to confirm a new steady state incidence of ALS in this region.

Helmets have been shown to decrease the risk of brain injury; however, helmets must be worn correctly and fit well in order to be effective. The objective of this study is to determine whether kindergarten-aged children could learn and retain appropriate helmet wearing technique through an educational bicycle safety program.

Retrospective analysis of scores in questionnaires administered before and after an educational intervention to kindergarten students four to six years of age. The study took place in Prince Edward Island, Canada. A Wilcoxon Sign-Rank Test was used to determine if there was a significant overall increase in knowledge; McNemar chi-square tests were used to determine if there was an increase in knowledge for individual questions.

There was significant improvement in pre-test to immediate post-tests scores and pre-test to delay post-test scores when the results were stratified by age, sex, bike riding status, and helmet wearing status (p<0.001 for all comparisons). In particular, correct responses for the questions regarding appropriate helmet distances from the eyes increased from 38.9% in the pre-test to above 90% in the post-tests (p<0.001). Correct responses for the question pertaining to appropriate fitting of helmet straps increased from 71.7% pre-test to above 90% in the post-tests (p<0.001).

There was improved knowledge of appropriate helmet-wearing technique among kindergarten-aged children as a result of the educational intervention, and knowledge gains were retained for at least one month.

The spontaneous blink rate (SBR) is variable in humans. It increases rapidly during childhood before reaching a plateau in adulthood at 10-20 blinks/minute. Our aim was to compare the SBR during different visual tasks in children.

Thirty-nine healthy participants (mean age(SD):13.6(3.5)years, M=21), made horizontal and vertical visually-guided saccades, tracked a horizontal and vertical target, performed horizontal and vertical active sinusoidal head rotations in light and darkness while looking straight ahead (VOR task) or fixated straight ahead and in four directions of gaze. The eyes of each participant were videotaped and reviewed twice to determine the SBR. Parametric and non-parametric tests were used to analyze the data.

The median SBR during fixation straight ahead was seven blinks/minute, which was similar to the SBR during horizontal saccades and horizontal smooth pursuit tasks. The median SBR during vertical smooth pursuit and vertical saccades were significantly lower than during fixation (p≤0.042). The median SBR during the VOR task in light and horizontal VOR in darkness were significantly higher than during fixation (p=0.019-0.024).

The median SBR during visual fixation was lower than that reported previously in 5-14 years-old children during rest or 11-20 years-old subjects during quiet conversation. The median SBR was even lower during vertical smooth pursuit and saccades tasks. This may be due to differences in concentration required for visual fixation in general and vertical visual tasks more specifically. The higher SBR during the VOR may be due to drying of the eyes during head shaking.

Calcitonin gene related peptide (CGRP), which has a vasodilator effect, is held responsible for neurogenic inflammation and vasodilatation of the cranial vessels in migraine pathophysiology. In this study, we investigated the association between alpha CGRP gene polymorphism (CALCA T-692C) and migraine.

One hundred and thirty-four female migraineurs and 96 healthy female cases were enrolled in the study. The patient group was further subdivided into migraine with and without aura groups. The CALCA T-692C gene polymorphism was identified using polymerase chain reaction (PCR) technique and restriction fragment length polymorphism (RFLP).

The genotype and allele frequencies of CALCA T-692C gene polymorphism did not differ between the migraine and control groups. Between the migraine with and without aura subgroups, there was no difference. No association was seen between the CALCA T-692C gene polymorphisms and migraine attack severity and frequency.

Our study did not show any association between CALCA T-692C gene polymorphism and migraine.