Criteria for Treatment Optimization Recommendations (TOR) for patients with multiple sclerosis (MS) identify suboptimal response to disease-modifying treatment (DMT). The Canadian TOR (CanTOR) were used to indicate recommendations for treatment switches or treatment maintenance based on relapse, disease progression and magnetic resonance imaging (MRI) criteria in patients. We assessed concordance between the TOR and clinicians' decisions regarding treatment response and identified prevalence of patients with MS receiving DMT meeting medium/high levels of concern according to TOR.

Prospective baseline and end-of-study assessments of patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome were conducted in this open-label, 12-month, Phase IV, observational Canadian study.

Data were reported for 184 patients (female 72%, mean age 39 years) of which 96% had RRMS. The TOR criteria identified 19 (10.3%) patients with suboptimal response to treatment. Twelve patients had ≥1 high level of concern. Two patients had ≥2 medium levels of concern. Concordance between TOR and clinician decision in maintaining treatment was 95.3%. Where treatment change was recommended by the TOR, concordance was 29.4%. Clinicians identified the TOR as the principal reason for changing treatment in 50.0% of cases where the TOR identified suboptimal response. The TOR were considered useful by 70.6% of clinicians when treatment optimization was recommended and by 55.3% when maintaining treatment was recommended.

The TOR criteria can identify suboptimal response in this patient cohort. Concordance between TOR and clinician decision was high when maintaining treatment was recommended. Usefulness of the TOR was most apparent when treatment optimization was recommended.

Meningiomas account for approximately 24-30% of primary intracranial neoplasms. Histopathologic grade and degree of resection are two major prognostic factors. The aim of this study was to determine the factors associated with the prognosis of meningioma.

We used immunohistochemistry to analyze the expression levels of Vav3, SPARC, p-Akt, cyclin D1, and Ki-67 in 287 meningiomas of all grades.

The expression of Vav3, SPARC, p-Akt, cyclin D1, and Ki- 67 significantly increased with meningioma grade (p<0.01), and was higher in brain-invasive meningiomas compared to non-invasive meningiomas (WHO grade I) (p<0.05). Furthermore, the expression of Vav3, p-Akt, and Ki-67 was higher in recurrent meningiomas compared to non-recurrent meningiomas (WHO grade I) (p<0.05).

The expression of Vav3, SPARC, p-Akt, cyclin D1, and Ki-67 in meningiomas appears to correlate with meningioma invasiveness, aggressiveness, and recurrence.

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 current methods to predict recurrence and aggressive behaviour of meningiomas rely mainly on histological grading, histological subtype, proliferative index, as well as brain invasion. In many instances, histological grade alone fails to predict recurrence in the grade I and grade II meningiomas. Deletions of 1p and 14q have previously been reported to correlate with poor prognosis in terms of either recurrence or higher histological grades. The Her2neu (ErbB2) amplification has been shown to be a useful predictor of aggressive behaviour in breast and ovarian tumours, but its significance in meningioma is so far uncertain.

In order to determine the cytogenetic differences between 22 recurrent and 25 non-recurrent meningiomas of all grades, we used fluorescent in situ hybridization (FISH) DNA probes for 1p36, 14q11.2 and 17q11.2-12 (Her2neu) on formalin fixed paraffin embedded (FFPE) tissue from the Brain Tumour Tissue Bank (BTTB), London Health Science Center (LHSC).

We showed a positive association for meningioma recurrence correlated with 1p36 deletion plus or minus 14q 11.2 deletions in all grades of meningiomas. The Her2neu amplification was strongly associated with 1p/14q co-deletion in cases of recurrent meningiomas, especially the higher grade tumours.

These cytogenetic markers can be applied in addition to histological grading for predicting the risk of recurrence and biological behaviour.

In this study, we conducted a retrospective investigation of our initial single-centre experience with the clinical use of functional magnetic resonance imaging (fMRI) of hemisphere dominance for language processing (i.e., language lateralization). We demonstrated its association with surgical outcome and its potential impact on surgical planning and patient management.

Fifty-two cases were reviewed, covering the period from July 2007 to July 2010. Clinical fMRI reports were examined to determine the hemisphere dominance for language processing. Neurological reports were examined to determine if new language deficits were present post-surgery. Neurosurgeon notes were also reviewed to determine if fMRI had an impact on surgical planning.

Of the cases reviewed, 49 (94%) generated conclusive fMRI. Eleven (22%) patients exhibited fMRI language lateralization contralateral to pathology; zero of nine of these patients that had surgery experienced post-surgical deficits. Twenty-two (44%) patients exhibited fMRI language lateralization ipsilateral to pathology; three of 13 of these patients that had surgery experienced post-surgical deficits. Sixteen (34%) patients exhibited bilateral lateralization of language; five of 13 of these patients that had surgery experienced post-surgery deficits. Several post-fMRI reports indicated that fMRI results had an impact on surgical planning.

Our results suggest that fMRI demonstrations of language processing within the hemisphere ipsilateral to pathology (either ipsilateral alone or bilateral) is associated with a greater risk for post-surgical language deficits, and in these cases, fMRI results should be taken into consideration for pre-surgical planning.

Electromyography (EMG) for suspected cervical or lumbosacral root compression is often negative, producing expense and physical discomfort that could have been avoided. To improve patient selection for testing, we sought to identify clinical features that would accurately predict presence of radiculopathy on EMG.

Adult patients consecutively evaluated for suspected cervical or lumbosacral root compression at an academic clinical neurophysiology laboratory were prospectively enrolled. Presence of clinical features suggesting root disease (neck or back pain, dermatomal pain or numbness, myotomal weakness, segmental reflex loss, and straight leg-raising) was recorded prior to testing. EMG examination to confirm root compression was conducted per standard protocols. Analysis was based on computation of sensitivity, specificity, predictive values, and accuracy.

A total of 200 patients (55% male; mean age 46.4 years; 38% suspected of cervical and 62% of lumbosacral disease) were included. EMG evidence of root disease was detected in 31% of cervical and 62% of lumbosacral referrals. Dermatomal pain was the most sensitive, and segmental reflex loss and myotomal weakness the most specific individual predictors of root disease. Combined presence of dermatomal pain or numbness with segmental reflex loss and myotomal weakness approached specificities of 78% (lumbosacral disease) and 99% (cervical disease). In all cases, myotomal weakness was the most accurate predictor of root disease.

The diverse symptoms and signs of cervical and lumbosacral root compression predict a positive electrodiagnosis of radiculopathy with varying degrees of accuracy, and may be used to guide patient selection for EMG testing.

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.

To explain relatively common phenomenon of laughing during sleep and help to better define criteria for differentiating between physiological and pathological sleep-laughing.

Observational study of patients who underwent a sleep assessment in a referential tertiary health facility.

A total of ten patients exhibited sleep laughing, nine of whom had episodes associated with rapid eye movement (REM) sleep. Also, in one of the patients sleep-laughing was one of the symptoms of REM sleep Behaviour Disorder, and in another patient sleep-laughing was associated with NREM sleep arousal parasomnia.

The collected data and review of literature suggests that hypnogely in majority of the cases presents as a benign physiological phenomenon related to dreaming and REM sleep. Typically, these dreams are odd, bizarre or even unfunny for a person when awake. Nevertheless, they bring a sense of mirth and a genuine behavioural response. In a minority of cases, sleep-laughing appears to be a symptom of neurological disorders affecting the central nervous system. In these patients the behavioural substrate differs when compared to physiological laughing, and the sense of mirth is usually absent.

Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD).

Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence.

The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour.

FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

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.

Ultrasonic assessment of optic nerve sheath diameter (ONSD) as a non-invasive measure of intracranial pressure (ICP) has been evaluated in the literature as a potential valid technique for rapid ICP estimation in the absence of invasive intracranial monitoring. The technique can be challenging to perform and little literature exists surrounding intra-operator variability.

In this study we describe the creation of a novel model of ONSD to be utilized in ultrasound training of this technique. We demonstrate the realistic ultrasonographic images created utilizing this novel model.

We designed ocular models composed of gelatin spheres and variable three dimensional printed cylinders, which simulate the globe of the eye and variable ONSD's respectively. These models were suspended in a gelatin background and ultrasound of the ONSD was conducted using standard techniques described in the literature.

This model produces clear and accurate representation of ONSD that closely mimics in vivo images. It is affordable and easy to produce in large quantities, portending its use in an educational environment.

Utilizing the standard linear array ultrasound probe for ONSD measurements in our model provided realistic images comparable to in vivo. This provides an affordable and exciting means to test intra- and inter- operator variability in a standardized environment. Knowing this, we can further apply this novel model of ONSD to ultrasound teaching and training courses with confidence in its ability and the technique's ability to produce consistent results.

Determining factors predictive of the natural risk of rupture of cerebral aneurysms is difficult. We studied morphological factors associated with rupture in a study model of patients with mirror location intracranial aneurysms, one aneurysm that had ruptured and one that had not, each patient served as their own control attempting to eliminate confounding variables.

We collected five one-dimensional measurements and four two-dimensional indices from three-dimensional rotational digital subtraction angiography images of patients in the proposed study model and explored their correlation with aneurysm rupture. Parameters were analyzed with a paired Student's t test for significance and significant parameters were further examined by multivariate conditional logistic regression analysis.

Fifty-two patients with 52 pairs of intracranial aneurysms in a mirror location were studied. The maximum perpendicular height, neck diameter, maximum width, maximum height, aspect ratio, size ratio, and bottleneck factor were significantly associated with ruptured aneurysms on bivariate analysis. A logistic regression analysis showed that only size ratio, which was defined as the ratio of the maximal height to parent artery average diameter, is independently correlated with ruptured intracranial aneurysms.

In a case-control study of patients with mirror location intracranial aneurysms, size ratio was identified as the unique morphological factor associate with the rupture of cerebral aneurysms.

Estimates of incidence and prevalence are needed to determine disease risk and to plan for health service needs. Although the province of Nova Scotia, Canada is located in a region considered to have a high prevalence of multiple sclerosis (MS), epidemiologic data are limited.

We aimed to validate an administrative case definition for MS and to use this to estimate the incidence and prevalence of MS in Nova Scotia.

We used provincial administrative claims data to identify persons with MS. We validated administrative case definitions using the clinical database of the province's only MS Clinic; agreement between data sources was expressed using a kappa statistic. We then applied these definitions to estimate the incidence and prevalence of MS from 1990 to 2010.

We selected the case definition using ≥7 hospital or physician claims when >3 years of data were available, and ≥3 claims where less data were available. Agreement between data sources was moderate (kappa = 0.56), while the positive predictive value was high (89%). In 2010, the age-standardized prevalence of MS per 100,000 population was 266.9 (95% CI: 257.1- 277.1) and incidence was 5.17 (95% CI: 3.78-6.56) per 100,000 persons/year. From 1990-2010 the prevalence of MS rose steadily but incidence remained stable.

Administrative data provide a valid and readily available means of estimating MS incidence and prevalence. MS prevalence in Nova Scotia is among the highest in the world, similar to recent prevalence estimates elsewhere in Canada.

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients.

Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing.

The rs2104286G frequency in the IL2RA gene was significantly higher in NMO patients than in controls (puncorr=0.013, pcorr=0.026, OR:1.942, 95%CI:1.146-3.291).

The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population.

Admission to an Epilepsy Monitoring Unit (EMU) is essential for pre-surgical evaluation of patients with medically-refractory epilepsy; however, prolonged referral times and resource limitations are significant access barriers. Therefore, identification of pre-EMU variables that predict potential surgical candidates can assist in the triage of patient admissions to the EMU.

In this hypothesis-generating study, a retrospective analysis of patients admitted for pre-surgical evaluation to the Toronto Western Hospital EMU (2004-2011) was performed. Univariate and multivariate logistic regression was used to identify variables that could independently predict subsequent surgical candidacy following EMU evaluation.

Four hundred and fourteen patients were admitted to the EMU. Overall, 259 patients (62.5%) were identified as potential surgical candidates. One hundred and seven patients (25.8%) required invasive electroencephalogram (iEEG) implantations; of 75 patients consenting to iEEG analysis 39 underwent a subsequent resective procedure. Male patients and those with a lesion on MRI were 1.9 times more likely to be surgical candidates (95% CI 1.18-2.98 and 0.94-3.80, respectively), while patients with non-localizable seizures were seven times less likely (95% CI 0.02-1.25).

In this retrospective, hypothesis-generating study male gender, presence of a lesion on MRI and localizable seizures on routine outpatient EEG analysis independently predicted subsequent resective epilepsy surgical candidacy in EMU patients. Upon validation by other studies, these variables may be considered by clinicians referring patients to the EMU in order to improve wait times and optimize patient care.

Gamma Knife (GK) radiosurgery for pituitary adenomas can offer a means of tumor and biologic control with acceptable risk and low complication rates.

Retrospective review of all the patients treated at our center with GK for pituitary adenomas from Nov 2003 to June 2011.

We treated a total of 86 patients. Ten were lost to follow-up. Mean follow was 32.8 months. There were 21 (24.4%) growth hormone secreting adenomas (GH), 8 (9.3%) prolactinomas (PRL), 8 (9.3%) adrenocorticotropic hormone secreting (ACTH) adenomas, 2 (2.3%) follicle stimulating hormone/luteinizing hormone secreting (FSH/LH) adenomas, and 47 (54.7%) null cell pituitary adenomas that were treated. Average maximum tumor diameter and volume was 2.21cm and 5.41cm3, respectively. The average dose to the 50% isodose line was 14.2 Gy and 23.6 Gy for secreting and non-secreting adenomas respectively. Mean maximal optic nerve dose was 8.87 Gy. Local control rate was 75 of 76 (98.7%), for those with followup. Thirty-three (43.4%) patients experienced arrest of tumor growth, while 42 (55.2%) patients experienced tumor regression. Of the 39 patients with secreting pituitary tumors, 6 were lost to follow-up. Improved endocrine status occurred in 16 (50.0%), while 14 (43.8%) demonstrated stability of hormone status on continued pre-operative medical management. Permanent complications included: panhypopituitarism (4), hypothyroidism (4), hypocortisolemia (1), diabetes insipidus (1), apoplexy (1), visual field defect (2), and diplopia (1).

Gamma Knife radiosurgery is a safe and effective means of achieving tumor growth control and endocrine remission/stability in pituitary adenomas.