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.

Stroke and transient ischemic attack (TIA) have a high personal and financial cost to society and prevention is critical. Outside of registries in Ontario, there has been little effort to determine whether care gaps exist for secondary preventative care within Canada. The objective of this study was to evaluate inpatient medical team compliance to four secondary stroke prevention interventions: antithrombotic therapy, antihypertensive therapy, lipid lowering therapy and smoking cessation.

Adults admitted to the University of Alberta Hospital stroke service with a diagnosis of stroke or TIA between August 1st, 2005 and July 31st, 2006 were identified using International Classification of Diseases (10th Revision) codes. Two hundred charts were randomly selected for retrospective review. Compliance, defined as achievement of therapeutic targets or appropriate therapy for subtherapeutic targets, was assessed.

Among 190 eligible patients (mean age 67 years, 55 % male), 147 (77.4%) had a non-cardioembolic cerebral event while 43 (22.6%) had a cardioembolic cerebral event. We found high compliance for antithrombotic (92% [174/190]) and antihypertensive (95% [136/143]) agents, but suboptimal compliance for lipid lowering agents (68% [107/158]) and smoking cessation (27% [17/64]).

There is room for improvement in early risk factor management for secondary prevention, even in specialized stroke centres. To optimize stroke preventative care, more interdisciplinary collaboration, investigation of reasons for suboptimal care, development of strategies to minimize care gaps and ongoing stroke care audits for quality improvement are needed.

Statins have been shown to increase endothelial progenitor cells (EPCs) in patients with cardiovascular disease. However, there is no similar study that has been done on the patients recovering from cerebrovascular disease. We present the largest prospective study of statin therapy on EPC levels of patients recovering from stroke.

Our study subjects were treated with rosuvastatin (10 mg/day) over a period of 12 weeks. Blood was collected from these patients periodically and EPC levels were measured along with other biochemical parameters.

Our study shows that rosuvastatin treatment significantly reduces the low density lipoprotein (LDL) levels in the patients over the 12 weeks. However, we did not find any corresponding changes in the EPC levels during this time period. Earlier reports indicated that statin use could increase EPC proliferation. Our research, however, indicates that the in-vivo effects of rosuvastatin are not similar to those of previous reports. There may be several reasons for this lack of congruence between these two studies, including age of the study population, predominantly low high density lipoprotein (HDL) levels in our subjects and effects from other concomitant medications.

Central nervous system (CNS) involvement is a common and less understood aspect of systemic lupus erythematosus (SLE). Microembolic signals (MES) have been reported in SLE. We conducted a prospective study to evaluate the frequency of MES among patients with CNS involvement and those without. The main aim of the study is to clarify the pathophysiology of the CNS involvement in SLE.

Sixty eight patients with a diagnosis of SLE (60 females, 8 males) participated in the study. Both middle cerebral arteries were monitored using transcranial Doppler for 60 min to detect MES. All cases underwent neurology and psychiatry assessments.

MES were detected in 7/68 patients (10.3%) with the mean number of 3.5 per hour. MES were significantly higher in patients with CNS involvement (6/24, 25%) than those without (1/44, 2.2%) (P=0.006). SLE disease activity index, duration of disease, plaque formation, intima-media thickness, and antiphospholipid antibodies were not associated with MES. MES were more frequent in patients receiving Aspirin and/or Warfarin (p=0.02).

MES may be a predictor for CNS involvement in SLE patients at risk for neuropsychiatric syndromes. Cerebral embolism may be implicated in the pathophysiology of neuropsychiatric SLE.

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.

Secondary prevention of cerebrovascular disease through dedicated stroke clinics has been shown to decrease recurrent vascular events in patients. However, there is limited literature describing such stroke clinic experiences from low and middle income countries. This study describes patient characteristics and observations made at the first systematized stroke clinic in Pakistan.

Aretrospective audit of medical records of all patients presenting between September 2006 and August 2008 with a cerebrovascular event was conducted. Information about clinical presentation, modifiable risk factors and laboratory and radiological investigations was collected. Burden of disability was assessed using Modified Rankin score. Data was entered and analyzed using SPSS 14.0.

159 patients with a mean age of 57.0 ± 13.9 years were included in this study and 34.6% of all patients were women. 108 patients were diagnosed with ischemic stroke (67.9%) while 34 patients presented with hemorrhagic stroke (21.4%) and 17 patients presented with transient ischemic attacks (10.7%). Hypertension was the most common modifiable risk factor seen in 78.0%, followed by diabetes in 40.3% and dyslipidemia in 31.5%. At presentation to clinic, only 26.0% patients with dyslipidemia and 64.5% patients with hypertension were on appropriate medications.

A high prevalence of modifiable risk factors such as hypertension in stroke patients was observed and it presents an opportunity for conventional interventions in Pakistan. Systematized clinics for stroke and an algorithmic approach in primary care towards stroke may improve the implementation of evidence based secondary prevention strategies in developing countries.

Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cerebrovascular complications. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine with a central role in inflammation. To investigate whether polymorphisms of the TGF-β1 gene can modify the risk of ischemic stroke (IS) in Chinese population, we conduct this hospital-based, case-control study.

Transforming growth factor-β1 genotype was determined in 450 Chinese patients (306 male and 144 female) with IS and 450 control subjects (326 male and 124 female).

Subjects carrying 869TT were susceptible to IS (odds ratio [OR] =1.58; P=0.003). Further analysis of IS data partitioned by gender revealed the female-specific association with 869T/C (OR=2.64; P=0.001).

Findings suggest that the TT genotype of 869T/C might be a risk factor of IS in Chinese, especially in females.

The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) in patients with different epilepsy syndromes.

We evaluated epileptic patients seen in the previous 18 months, including all patients with present or past exposure to LEV. Tolerability of LEV therapy was evaluated in all patients; efficacy was evaluated only in patients who had received LEV for at least six months. Two hundred and two patients were included in the study. Patients were considered responsive when showing a > 50% reduction in seizures frequency and non-responders when seizure frequency was unchanged, worsened or showed a reduction < 50%.

Thirty patients did not complete six months of LEV treatment and dropped out. 57.4% of the patients with uncontrolled seizures treated for at least six months were responders, with 27.7% seizure free. Adverse effects were observed in 46 patients (23%) and were responsible for early drop out in 26. Adverse effects occurred significantly more often in females than in males (30.6% vs 13.2%); moreover, nearly 30% of women with adverse effects complained of more than one adverse effect, while this was never observed in male patients.

Our study shows LEV as a well tolerated and effective treatment, both in monotherapy and as an add-on. Further investigations on larges samples are needed to investigate the issue of gender-related tolerability.

Optic neuritis (ON) is associated with a 38% ten-year risk of developing multiple sclerosis (MS) in Western populations, but the corresponding risk in non-Western populations is unclear. We conducted this study to estimate the risk of progression to MS after an episode of ON in a South Asian population.

Two hundred and fifty-three patients with idiopathic ON were identified by reviewing records of visual evoked potentials and chart notes from a single academic center spanning the years 1990-2007. A structured telephone interview was then conducted to identify patients who had subsequently received a diagnosis of MS. The diagnosis was corroborated from chart notes, where possible. Cumulative probability of conversion to MS was calculated using Kaplan-Meier survival analysis.

The five-year risk of developing MS was 14.6% and the ten-year risk was 24%. Patients (N=218) who had one or more typical demyelinating lesions on baseline brain magnetic resonance imaging (MRI) had a 68% 10-year risk; those with no lesions or non-typical lesions had a 14% risk (p<0.001). Female gender, recurrent ON, and occurrence of ON in winter months were also associated with increased risk (p≤ 0.001). Severity of ON and likelihood of detecting cerebrospinal fluid (CSF) oligoclonal bands were higher in patients who developed MS.

Idiopathic ON in Pakistan carries a lower risk of progression to MS compared with Western data. As in Western populations, however, presence of abnormal baseline brain MRI and CSF oligoclonal bands correlate with increased MS risk.

Thrombolysis in acute ischemic stroke is usually performed in comprehensive stroke centres. Lack of stroke expertise in remote small hospitals may preclude thrombolysis. Telemedicine allows such management opportunities in distant hospitals.

We report our experience in managing acute stroke over a two-year time period with telestroke. The University of Alberta Hospital acted as the ‘hub’ and seven remote hospitals as ‘spoke’. The neurologist at the ‘hub’ provided stroke expertise to the local physician using either a two-way video link or telephone. Cranial CT scans were transmitted to ‘hub’. Education sessions were held before the initiation of the program.

Of 210 patients 44 (21%) received thrombolysis at the ‘spoke’ sites. In 34/44 (77%) two-way video link was available while in 10/44 (23%) telephone was used. Five (11.4%) patients experienced intracranial hemorrhage after thrombolysis, 2 (4.5%) were symptomatic. Favorable (mRS=0-1) outcome at three months was 16/40 (40%) and mortality was 9/40 (22.5%). Four patients were lost to follow-up. There was no significant three months outcome difference between two-way video link and telephone consultation (P = 0.689). Over two years the number of acute stroke transfers decreased from 144 to 15 at one of the ‘spoke’ sites, a 92.5% decline.

It is possible to successfully treat patients with acute ischemic stroke at remote sites through videoconferencing or telephone consultation. Telestroke can also lead to a significant reduction in the number of patients requiring transfer to a tertiary care centre.

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.

The course of multiple sclerosis may be slowed by use of the disease modifying drugs (DMDs): subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, glatiramer acetate, and natalizumab. We set out to compare utilization of these drugs in the Canadian provinces from 2002-2007.

Using a retrospective cohort analysis, we reviewed population data from International Medical Statistics (IMS) Health between November 2001 and October 2007.

The total annual number of DMD prescriptions increased from 3.9, in 2002, to 5.1, in 2007, per 1,000 Canadians. The total annual cost of prescriptions rose from $187 million to $287 million. Of the four provinces responsible for the majority of prescriptions - Alberta, BC, Ontario, and Quebec - Quebec had the highest average annual prescription rate (7 per 1,000 population) and BC had the lowest rate (3.3 per 1,000 population). Subcutaneous interferon beta-1a was the most commonly used drug whereas glatiramer acetate showed the greatest growth in use from 2002 to 2007.

Disease modifying drugs prescription rates and costs increased by more than 30% between 2002 and 2007. There was wide variation in DMD prescription rates and relative drug preferences across the provinces.

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.