Although carotid endarterectomy is considered the ‘gold standard’ for standard risk symptomatic patients, the treatment of choice for asymptomatic patients remains controversial. Carotid stenting has demonstrated real-world outcomes consistent with established guidelines for carotid endarterectomy in asymptomatic high-surgical risk patients in recent prospective multicenter trials. We describe our experience with asymptomatic patients who underwent carotid stenting at our center in a routine clinical setting.

This is a retrospective, longitudinal cohort study of patients who underwent carotid angioplasty and stenting at the Foothills Medical Center, Calgary, Canada between 1997 and 2007. The qualifying events were categorized as symptomatic and asymptomatic. The procedures were performed by four experienced neurointerventionists. The primary outcome was stroke or death at 30-day follow- up.

243 patients underwent 255 carotid stenting procedures. Their ages ranged from 50 to 83 years; the mean age was 72.0 ± 9.3 years; 67(26.3%) were women. Forty one patients (16.1%) were asymptomatic; 214 patients (83.9%) were symptomatic. The patients in the asymptomatic group were significantly younger - 66.0 ± 8.8 years compared to patients in the symptomatic group 73.2 ± 8.9 years (p<0.0001). Intraprocedurally one minor stroke (2.4%) occurred in the asymptomatic group. At 30-day follow-up, no deaths or further strokes were noted in the asymptomatic group; while eight deaths, six major and seven minor strokes occurred in the symptomatic group (p=0.22).

Carotid stenting appears to be a safe procedure in asymptomatic patients with severe carotid stenosis in routine clinical settings as witnessed in this single center study.

Blunt cerebrovascular injury (BCVI) to the carotid and vertebral arteries is a potentially devastating injury in trauma patients. The optimal management for BCVI has not been standardized. At our institution, 64-slice multi-detector computed tomographic angiography (CTA) has been used as the initial screening exam for BCVI in patients who met predefined screening criteria. The purpose of this study is to review the incidence of CTA-diagnosed BCVI in at-risk patients and to evaluate the treatment and clinical outcome of patients with BCVI.

This study included trauma patients with a positive diagnosis of BCVI on CTA during a 41-month study period. The medical records and relevant radiographic findings were retrospectively reviewed.

Twenty seven of 222 blunt trauma patients evaluated with CTA had a positive diagnosis of BCVI, with an occurrence rate of 12.2%. Traumatic brain injury (72.2%) and basal skull fractures (55.6%) were the most frequent associated injuries with carotid trauma while 100% of blunt vertebral injuries occurred in the setting of cervical fractures. Fourteen (51.8%) patients received medical therapy; Eleven (40.7%) patients received conservative treatment. Endovascular treatment was attempted in a single case of vertebral arteriovenous fistula. BCVI-related stroke was found in four patients (14.8%), one of whom developed an infarct while on medical treatment.

BCVI is found in a significant portion of blunt trauma patients with identifiable risk factors, and screening CTA has high diagnostic yield in detecting these lesions. Medical therapy is the mainstay of treatment at our institution; however, BCVI-related stroke may occur despite treatment.

The prevalence of migraine headache varies somewhat across geographic regions. The last Canadian population-based study of migraine was in 1994. We report the findings of the Canadian Women and Migraine Survey. In addition to reporting migraine prevalence in Canadian women, the survey identified current consultation and treatment practices of women with migraine, and the psychological burden of migraine.

The survey was conducted with a population-based sample of 1210 women using standard telephone research methods. Headache diagnoses were based on the International Headache Society (IHS) Classification.

Calculated prevalence of migraine headache was 26%. Only 51% of women with migraine had consulted a physician about their headaches. Women with migraines rely on over-the-counter medications and non-specific prescription medications. Less than 10% of women with migraine use triptans/dihydroergotamine for primary treatment. Ninety seven percent of women with migraine reported at least one psychosocial impact resulting from migraines.

The prevalence of migraine in Canadian women appears static, and is again shown to be slightly higher than that reported in the United States. As in other epidemiologic studies, many women with migraine do not seek medical help for their headaches and perhaps as a result, few are using migraine-specific medications to treat their headaches. The impact of migraine on Canadian women is substantial with almost all women with migraine reporting adverse psychosocial effects of migraines on their lives.

Patients with chronic migraine and medication overuse are significant consumers of health care resources.

To determine whether botulinum toxin type A prophylaxis reduces the cost of acute migraine medications in patients with chronic migraine and triptan overuse.

In this multicenter, open-label study, patients with chronic migraine (≥15 headache days/month) who were triptan overusers (triptan intake ≥10 days/month for ≥3 months) received botulinum toxin type A (95-130 U) at baseline and month three. Headache (HA) frequency and medication use were assessed with patient diaries, and headache-related disability by means of the MIDAS and Headache Impact Test-6 questionnaires.

Of 53 patients enrolled (mean age ± standard deviation, 46.5 years ± 8.4; 47 [88.7%] females), 48 (90.6%) completed the study at month six. Based on headache diaries, significant (P≤0.0002) decreases from baseline were observed for days per month with headache/migraine, days with any acute headache medication use, days with triptan use, and triptan doses taken per month. A significant (P<0.0001) increase from baseline in headache-free days per month was also observed. Prescription medication costs for acute headache medications decreased significantly, including significant reductions in triptan costs (mean reduction of -C$106.32 ± 122.87/month during botulinum toxin type A prophylaxis; P<0.0001). At baseline, 78% of patients had severe disability (MIDAS score) and 86.8% had severe impact due to headache (HIT-6 scores); at month six, this decreased to 60% and 68%, respectively.

Botulinum toxin type A prophylactic therapy markedly decreased costs related to acute headache medication use in patients with chronic migraine and triptan overuse.

In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.

To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.

Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.

Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.

The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

Primitive reflexes and parkinsonian signs are used by clinicians to differentiate among dementias. We reviewed our clinical sample to determine whether primitive reflexes were more prevalent in frontally-based dementias and whether parkinsonian signs were more common in dementia with Lewy bodies (DLB) than in other types of dementia.

We retrospectively reviewed charts from 204 patients with dementia who presented for consultation at Baycrest's Ross Memory Clinic between April, 2003, to December, 2007.

A greater proportion of subjects with DLB and dementia of the Alzheimer type with cardiovascular disease had primitive reflexes than subjects with frontotemporal dementia (FTD). Primitive reflexes were not positively predictive of FTD or vascular dementia (VaD). Dementia with Lewy bodies subjects were more likely to have parkinsonian signs than the other dementias, and bradykinesia and rigidity were positively predictive of FTD. The palmomental reflex was the most common primitive reflex in the sample, and cogwheeling was the most common parkinsonian sign. There was no significant difference between early- and late-stage groups in presence of primitive reflexes or parkinsonian signs.

Primitive reflexes appear not to be clinically discriminative of frontally-based dementias such as FTD and VaD.

Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients.

Sixty two MS patients [51 female, mean age= 41 (sd=9.6) years, median expanded disability status scale (EDSS)=2.5] meeting modified McDonald criteria for MS underwent neuropsychological testing using the Neuropsychological Screening Battery for MS (NSBMS) and magnetic resonance imaging (MRI, 1.5T GE) that included DTI sequences. Total T1 hypointense and T2 hyperintense lesion volumes were obtained using semi-automated software. Lesion volumes were subtracted from whole-brain parenchyma to obtain measures of NAWM and NAGM. Fractional anisotropy (FA) of NAWM and mean diffusivity (MD) of NAGM were obtained.

Cognitive impairment was present in 11 patients (18%). These patients had higher EDSS scores, were less educated, and were more likely to have secondary progressive MS. They also had higher hypointense (p=0.001) and hyperintense (p=0.004) lesion volumes, greater NAWM atrophy (p=0.007), lower FA of total NAWM (p=0.003), and higher MD of total NAGM (p=0.015). Using a logistic regression analysis, and after controlling for demographic and disease-related differences between groups, FA of NAWM emerged as a significant predictor of cognitive impairment adding to the variance derived from lesion and atrophy data.

This study underlies the important role of normal-appearing brain tissue in the pathogenesis of MS-related cognitive impairment.

The corpus callosum (CC) is frequently compromised in patients with multiple sclerosis (MS). Structural and functional measurements of the CC may be useful to monitor the progression of the disease. The aim of this pilot study was to determine if bimanual tactile temporal thresholds correlates with CC volume. A tactile temporal threshold is the longest temporal interval that separates the onsets of two tactile stimuli when they are judged by the observer as simultaneous. Judgments to bimanual stimulations require interhemispheric transfer via the CC.

Thresholds were examined in MS patients and matched controls. Magnetic resonance (MR) images were acquired on a 3T MR system within 48 hours of clinical assessment and measurement of thresholds.

Corpus callosum volume was assessed by using a semiautomatic livewire algorithm. The CC volume was smaller (by 21% on average, p < 0.01) and thresholds were higher (by 49% on average, p < 0.03) in MS patients when compared to controls. A significant correlation (r = -0.66, p = 0.01) between CC volume and thresholds emerged for the MS patients.

Measuring treatment benefits of neuroprotective and repair therapies is a well recognized challenge in MS research. The overall findings of this study suggest that these measurements, which involve the transfer of information interhemispherically via the CC, may be promising outcome measures that warrant further scientific exploration to develop a model to measure recovery.

The goal of this study was to optimize intraoperative neuropathology consultations by studying trends and sources of diagnostic error. We hypothesized that errors in intraoperative diagnoses would have sampling, technical, and interpretive sources. The study also audited diagnostic strengths, weaknesses and trends associated with increasing experience. We hypothesized that errors would decline and that the accuracy of “qualified” diagnoses would improve with experience.

The pathologist's first 100 cases (P1), second 100 (P2), and most recent 100 (P3, after ten years in practice) formed the data set. Intraoperative diagnoses were scored as correct, minor error or major error using the final diagnosis as the gold-standard. Incorrect diagnoses were re-examined by two reviewers to identify sources of error.

Among the 300 cases there were 22 errors with 11 in P1, 9 in P2 and 2 in P3. Sampling contributed to 17 errors (77%), technical factors to 7 (32%) and interpretive factors to 16 (73%). Improvement in diagnostic accuracy between P1 and P2 (p=0.8143), or P2 and P3 (p=0.0582) did not reach significance. However, significant improvement was found between P1 and P3 (p=0.0184).

The present study was a practical and informative audit for the pathologist and trainees. It reaffirmed the accuracy of intraoperative neuropathology diagnoses and informed our understanding of sources of error. Most errors were due to a combination of sampling, technical and interpretive factors. A significant improvement in diagnostic proficiency was observed with increasing experience.

To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM).

Tissue specimens were analyzed for p53 mutations, EGFR amplification, loss of PTEN and p16, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Demographic and clinical data were gathered from medical records.

Clinical and pathological data of 125 patients were collected and analysed. MGMT promoter methylation was associated with improved median overall survival (OS) (61 vs. 42 weeks, p = 0.01) and was an important prognosticator independent of age at diagnosis, extent of resection and post-operative ECOG performance status (HR 2.04, 95% CI 1.11-3.75). Among patients with MGMT promoter methylation, survival was significantly improved with chemoradiotherapy (CRT) over radiotherapy (RT) alone (71 vs. 14 weeks, p < 0.01). Furthermore, amongst those treated with temozolomide (TMZ) based CRT, the presence of EGFR amplification, maintenance of PTEN and wild-type p53 and p16 were each associated with trends towards improved survival.

MGMT promoter methylation is a strong, independent prognostic factor for OS in GBM. EGFR amplification, maintenance of PTEN, wild-type p53 and p16 all appear to be associated with improved survival in patients treated with CRT. However, the prognostic value of these biomarkers could not be ascertained and larger prospective studies are warranted.

To determine whether the duration of relief from symptoms in patients with essential blepharospasm (EB) or hemifacial spasm (HFS) who receive serial treatments with botulinum toxin type A (BtA) changes over the long-term.

Retrospective longitudinal comparative analysis. The main outcome measure is the mean duration of relief from symptoms after an injection with BtA. Participants included 34 patients who received 30 or more serial BtA treatments for facial dyskinesia (EB or HFS). Repeated measures and linear regression analyses were used to determine trends and the mean duration of relief from symptoms was compared between early (first ten effective treatments) and late (last ten treatments) sessions in each group.

In the EB group (18 patients), the mean duration of relief was 13.5 weeks for the early and 11.4 weeks for the late sessions (P=0.04). In the HFS group (16 patients) the mean duration of relief was 12.4 weeks in both treatment periods (P=0.91). The duration of relief had a small negative correlation with mean late session BtA dose in the EB group (P=0.03) but no correlation in the HFS group (P=0.12).

There was a trend towards a decreased duration of relief from symptoms in patients with EB over the long-term, but no changes for HFS. The treatment remains effective in relieving symptoms and signs for both conditions.

While the cause of Parkinson's disease (PD) remains unknown, evidence suggests certain environmental factors, such as well water drinking, herbicides, pesticides exposure and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause Parkinsonism. To investigate the possible impact of environmental risk factors for idiopathic PD, a case-control study was performed in the Eastern India.

During the period from January 1st, 2006 and December 10th, 2009, 175 PD patients (140 men, 35 women) and 350 non-Parkinson age-sex matched controls were included in the study. Subjects were given a structured neurological examination and completed an administered questionnaire which elicited detailed information on demographic data, pesticides, herbicides family history, occupation, dietary and smoking habits.

The multivariate analysis revealed that family history of PD, pesticide exposure, exposure to toxins other than pesticides and herbicides, rural living and previous history of depression were associated with increased risk of PD, whereas, smoking appeared to be a protective factor. Well water drinking for at least five years, though a significant risk factor on univariate analysis (OR=4.5, 95% CI=2.1-9.9), could not be proved significant in multivariate analysis. Head trauma, vegetarian dietary habit, occupation involving physical exertion and exposure to domestic pets were not as significant risk factors.

Results of our study support the hypothesis of multifactorial etiology of PD with environmental factors acting on a genetically susceptible host.

To investigate whether nestin would be a useful marker for retinal injury and also to ascertain a better understanding of the roles of Müller cells in the injured retina by the use of damaged rat retina.

A total of 33 adult female Wistar rats were used in this study. Three were used as controls and the remaining as retinal injury modes (6 for hypoxia; 15 for experimental glaucoma and 9 for optic nerve transection). Double immunofluorescence labeling was carried out between nestin and glutamine synthetase (GS), and between glial fibrillary acidic protein (GFAP) and GS antisera in normal and pathological retinae.

The results showed that there were no nestin nor GFAP staining in mature Müller cells of the normal retina. A major finding was that nestin expression was induced in Müller cells subjected to hypoxia, glaucoma and optic nerve transection.

These results suggest that nestin as well as GFAP (even more sensitive than GFAP) are useful and reliable biomarkers for retinal damage. The more intense expression of nestin, GFAP and GS in the end-feet of Müller cells suggest that they may help to maintain the retinal structural integrity and to enhance functional recovery in various retinal diseases.

Post-operative cerebrospinal fluid (CSF) leaks are a common complication of endoscopic pituitary surgery and account for a significant proportion of hospital costs associated with this procedure. Tisseel® is a tissue glue commonly used as an adjunct in dural repair but is not optimal for this purpose. DuraSeal® has several properties advantageous for dural repair but is not widely accepted in Canada partly due to its increased cost.

A cost analysis of DuraSeal® versus Tisseel® in endoscopic pituitary surgery.

A cost analysis was performed based on typical endoscopic pituitary surgery cases performed at our tertiary care institution. Operating room, hospital admission, and surgical sealant costs were obtained directly while estimates of patient recovery time and post-operative CSF leak rates were based on consensus values reported in the literature. Outcomes were reported for various possible clinical scenarios of sealant use.

In a model where surgical sealant is employed only in high-risk cases, use of DuraSeal® allows for a yearly cost savings of at least $4486.72. If surgical sealant is used in all cases, regular use of DuraSeal® versus Tisseel® either marginally reduces yearly costs or increases them by a maximum of $7619.25, depending on the case volume and estimated post-operative CSF leak rate.

In most clinical scenarios, use of DuraSeal® in endoscopic pituitary surgery may reduce overall yearly hospital costs compared to Tisseel®.