Migraine is a significant cause of suffering and disability in the Canadian population, and imposes a major cost on Canadian Society. Based on current medical science, much more could be done to provide better comprehensive medical care to the millions of individuals with migraine in Canada.

To propose and design a national Canadian Migraine Strategy which could be implemented to reduce migraine related disability in Canada.

A multidisciplinary task force of the Canadian Headache Society met for a Canadian Migraine Summit Meeting in Halifax, Nova Scotia in June, 2009. Pertinent literature was reviewed and a consensus document was produced based upon the round table discussion at the meeting.

The outline of a national Canadian Migraine Strategy was created. This strategy is based on the chronic disease management model, and would include: an outline of what constitutes appropriate migraine care for Canadians, educational programs (for health care professionals, individuals with migraine, and the general public), research programs, and the development of the necessary organizations and partnerships to develop further and implement the Canadian Migraine Strategy.

Based upon the medical literature and expert discussion at the meeting, a national Canadian Migraine Strategy with a patient self-management focus has the potential to improve patient care and reduce headache related disability in Canada.

Previously we showed that 6-hydroxydopamine lesions of the substantia nigra eliminate corticostriatal LTP and that the neuroimmunolophilin ligand (NIL), GPI-1046, restores LTP.

We used cDNA microarrays to determine what mRNAs may be over- or under-expressed in response to lesioning and/or GPI-1046 treatment. Patch clamp recordings were performed to investigate changes in NMDA channel function before and after treatments.

We found that 51 gene products were differentially expressed. Among these we found that GPI-1046 treatment up-regulated presenilin-1 (PS-1) mRNA abundance. This finding was confirmed using QPCR. PS-1 protein was also shown to be over-expressed in the striatum of lesioned/GPI-1046-treated rats. As PS-1 has been implicated in controlling NMDA-receptor function and LTP is reduced by lesioning we assayed NMDA mediated synaptic activity in striatal brain slices. The lesion-induced reduction of dopaminergic innervation was accompanied by the near complete loss of NDMA receptor-mediated synaptic transmission between the cortex and striatum. GPI-1046 treatment of the lesioned rats restored NMDA-mediated synaptic transmission but not the dopaminergic innervation. Restoration of NDMA channel function was apparently specific as the sodium channel current density was also reduced due to lesioning but GPI-1046 did not reverse this effect. We also found that restoration of NMDA receptor function was also not associated with either an increase in NMDA receptor mRNA or protein expression.

As it has been previously shown that PS-1 is critical for normal NMDA receptor function, our data suggest that the improvement of excitatory neurotransmission occurs through the GPI-1046-induced up-regulation of PS-1.

Environmental reduplication which is characterized by reduplication of places has been reported in right hemispheric lesions, particularly but not only in the right frontal region. However, spatial delirium may follow right sub-cortical lesions.

We describe a 53 years-old man who had a reduplicative paramnesia for event alone after an intracerebral haematoma of the right caudate nucleus.

MRI Scan showed also an extension of the right caudate nucleus haemorrhage into the ventricular system. Regional cerebral blood flow studied with 99Tcm-HMPAO showed a decrease of perfusion in the right dorso-lateral frontal cortex. To our knowledge, we reported the first case of reduplicative paramnesia of event associated with a right caudate nucleus injury. Similar right frontal deactivation was observed in two cases of reduplicative paramnesia for place, one of them after an infarction of the retro-lenticular portion of the right internal capsulae, the other after a right thalamo-capsular haemorrhage.

We suggest that reduplicative paramnesia for event, like the previous cases reported of reduplicative paramnesia for place, may be linked to a subcortical lesion of the frontal lobe inducing a right functional frontal deactivation.

To determine the outcomes of patients with Parkinson disease (PD) with pathological gambling (PG) from one Canadian Movement Disorders Clinic.

Assessments were performed in-person during routine clinic visits of all patients currently followed by one neurologist (OS). Pathological gambling was defined according to DSM-IV-TR criteria. Chart review was performed to obtain details on medication use, dosages, and patient demographics. Follow-up of patients with PG collected information on gambling behavior, PG management interventions, medications, treatment, and psychosocial outcomes.

146 patients were surveyed with an overall prevalence of PG of 4.1% (6/146). The rate of pathological gambling for those patients on dopamine agonist therapy (DA) was 8.1% (6/74). Only patients who were recreational gamblers prior to starting DA developed PG. All PG patients discontinued, decreased, or switched to another DA, and experienced a partial or full remission of PG. 3 (50%) patients described financial losses of $100,000 or more, and 75% (3/4) patients described significant marital stresses. At follow-up (August 2008), 4 of the 6 patients with PG continued to gamble in a controlled fashion despite medication changes. No significant difference in levodopa equivalent daily dose (LEDD) pre- and post-PG were observed; however, the relative amount of DA was decreased (p= 0.0593), while levodopa was relatively increased (p= 0.5277). Despite control of PG, patients still experience financial and marital strains.

DA (in combination with levodopa) was associated with a significantly higher prevalence of PG in PD, particularly in patients who were recreational gamblers previously. Despite control of PG, patients continued to experience significant financial and marital stresses that should be regularly enquired upon in follow-up care and managed appropriately.

A possible influence of estrogens on the dopaminergic system has been hypothesized and investigated by several studies, and fluctuations in motor symptoms related to the menstrual cycle have been reported in some movement disorders patients. We designed a survey to quantify how frequently female patients with various movement disorders are affected by this phenomenon and its impact on symptom severity.

A questionnaire was sent to 104 women between 18- and 60-years-old diagnosed with movement disorders and regularly followed at our centre.

From a total of 65 subjects who completed the questionnaire, 54 women reported the onset of their movement disorders before menopause. Twenty of them (37%) experienced changes in their movement disorders during the menstrual cycle. In particular, there was a significant worsening of symptom severity before (p=0.0005) and during menses (p=0.0004).

The possible role of such changes should be taken into account when evaluating the efficacy of various therapeutic interventions in movement disorder patients.

Treatment options for Chiari I malformations include posterior fossa decompression (PFD) with additional techniques including laminectomy, intradural exploration, and duraplasty. Neuroimaging findings of cisterna magna volume, syringomyelia, and intraoperative ultrasonography may tailor surgical intervention.

We developed an algorithm classifying symptomatic Chiari I patients into three groups to define minimum operation. Without syringomyelia, the presence of cisterna magna defined Group A and the absence defined Group B. Patients with syrinx formed Group C. Mild structural pathology (Group A) or adequate space following PFD (Group B, normal intraoperative ultrasound (IOUS)) should be treated by PFD alone. Conversely, presence of syringomyelia (Group C) or inadequate space following PFD (Group B, abnormal IOUS) should additionally have duraplasty. We applied this algorithm to patients treated at a single institution over 16 years.

Twenty-four symptomatic Chiari I malformation patients were divided into three groups that did not differ by age, gender, or extent of tonsillar ectopia. All patients treated by this algorithm experienced clinical and radiographic improvement. This included eight Group B patients who underwent PFD only (n=6) or additional duraplasty (n=2) decided by IOUS.

Treatment of symptomatic Chiari I malformation may have inadequate outcome with conservative strategy or complications with aggressive strategy. This algorithm utilizes preoperative neuroimaging and intraoperative ultrasound to tailor intervention, with excellent clinical outcome and radiographic syrinx resolution on application to 24 patients. Further validation requires prospective multicenter evaluation with larger patient population.

The ability to predict conversion to multiple sclerosis (MS) accurately when assessing a patient with a clinically isolated syndrome (CIS) is of paramount importance.Magnetic resonance imaging (MRI) is the best paraclinical tool currently available; however the significance of a history of an event suggestive of demyelination prior to CIS presentation has not been evaluated.

Aretrospective chart review of all optic neuritis cases presenting as CIS to a single neuro-ophthalmologist in London, Ontario between 1990 to 1998 was performed. Data were collected regarding demographics, past medical history, history of present illness, and family history. Conversion to MS was determined by the McDonald criteria after ten years of follow-up. Bayesian statistics and logistic regression were used to determine the best predictors of conversion to MS from CIS.

One hundred and sixteen optic neuritis subjects were included in the analysis. After ten years, 42.2% had converted to MS. The best predictor of future conversion remained at least one brain lesion, disseminated in space, on MRI (sensitivity 0.90, specificity 0.75). However, if the subject additionally had a history suggestive of a demyelinating event in the past that had not been confirmed clinically, the specificity increased to 0.96. These two traits taken together had an odds ratio of 27.8 for conversion to MS in the next ten years (p<0.001).

A history of an event suggestive of demyelination prior to presenting with optic neuritis as CIS increases the ability of the clinician to predict conversion to MS in the next ten years.

In Canada, ancillary tests, such as selective four vessels angiography (S4VA), are sometimes necessary for brain death (BD) diagnosis when the clinical exam cannot be completed or confounding factors are present. Recent Canadian guidelines assert that brain death is supported by the absence of arterial blood flow at the surface of the brain and that venous return should not be considered. However, neuropathologic and angiographic studies have suggested that arteries might still be patent in BD patients. Current clinical practices in BD diagnosis following S4VA need to be better understood.

We conducted a retrospective study of all S4VA performed for the determination of BD in a level 1 NeuroTrauma centre from 2003 to 2007. The objective of the study was to describe the prevalence of intracranial arterial, capillary (parenchymogram) and venous opacification in our study population. All tests were reviewed independently by two neuroradiologists. Disagreements were resolved by consensus.

Thirty two patients were declared BD following S4VA during the study period. Nine of these patients (28%) presented some proximal opacification of intracranial arteries (95% CI 15-45%). As opposed, none had a cerebral capillary and deep venous drainage opacification (95% CI 0-10%).

The absence of cerebral deep venous drainage or parenchymogram might represent a better objective marker of cerebral circulatory arrest for brain death diagnosis when the use of S4VA is required. These findings open the path for further research in enhancing our interpretation of angiographic studies for brain death diagnosis.

To compare the reproducibility of semi-automated vessel analysis software to manual measurement of carotid artery stenosis on computed tomography angiography (CTA).

Two observers separately analyzed 81 carotid artery CTAs using semi-automated vessel analysis software according to a blinded protocol. The software measured the narrowest stenosis in millimeters (mm), distal internal carotid artery (ICA) in mm, and calculated percent stenosis based on NASCET criteria. One observer performed this task twice on each carotid, the second analysis delayed two months in order to mitigate recall bias. Two other observers manually measured the narrowest stenosis in mm, distal ICA in mm, and calculated NASCET percent stenosis in a blinded fashion. Correlation coefficients were calculated for each group comparing the narrowest stenosis in mm, distal ICA in mm, and NASCET percent stenosis.

The semi-automated vessel analysis software provided excellent intraobserver correlation for narrowest stenosis in mm, distal ICA in mm, and NACSET percent stenosis (Pearson correlation coefficients of 0.985, 0.954, and 0.977 respectively). The semi-automated vessel analysis software provided excellent interobserver correlation (0.925, 0.881, and 0.892 respectively). The interobserver correlation for manual measurement was good (0.595, 0.625, and 0.555 respectively). There was a statistically significant difference in the interobserver correlation between the semi-automated vessel analysis software observers and the manual measurement observers (P < 0.001).

Semi-automated vessel analysis software is a highly reproducible method of quantifying carotid artery stenosis on CTA. In this study, semi-automated vessel analysis software determination of carotid stenosis was shown to be more reproducible than manual measurement.

We previously reported that Arsenic trioxide (ATO) can inhibit glioma growth both in vitro and in vivo. While the use of ATO alone for solid tumor treatment sometimes was found to be ineffective which may be due to the protective pathways including heat shock proteins (HSPs) response induced by ATO. In this study, we modified HSPs expression to investigate whether HSPs had some effect on ATO induced glioma cell death.

Trypan bule exclusion assay, mitochondrial membrane potential (MMP) Assay, and SubG1 detection were used to evaluate cell viability and western-blot was employed to detect HSPs and some apoptosis markers expression induced by ATO. Heat pre-treatment, HSPs inhibitor, or Heat Shock factor-1 (HSF1) knockdown by SiRNA was employed to modify HSPs levels.

It was showed that KNK437 (HSPs inhibitor) or HSF1 knockdown significantly enhanced cell death, MMP disruption, JNK phosphorylation and caspase-3 cleavage induced by ATO, which was accompanied by abrogation of HSPs induction, while heat pre-treatment with clear HSPs induction had strong protection on the effects mentioned above.

Those data suggested that HSPs play protective roles on ATO induced cell death in glioma. Inhibition of HSPs may have a synergistic effect with ATO on glioma treatment.