Medical and mental health comorbidity in Alzheimer's disease and other dementias presents difficult challenges for health service delivery. However, existing studies have been conducted in clinical samples and may not be informative for planning community services. The Canadian Community Health Survey (CCHS) provides an opportunity to characterize associations between dementias and mental and physical comorbidity in a household population aged 55 and over.

Data were obtained from the 2005 CCHS-cycle 3.1. Weighted estimates for mood and anxiety disorders and other characteristics in Canadian population with dementia were calculated and were compared to those in people without the condition.

According to the CCHS, the prevalence of Alzheimer's disease and other dementia increases with age, more or less doubling every decade. The increase among women is monotonic, whereas among men in the household population the rate of dementia peaks at age 85-89 and falls thereafter. Mood and anxiety disorders were found to be substantially more frequent among people with Alzheimer's disease and other forms of dementia compared to those without the disease (mood disorders: 19.5% vs. 5.3% and anxiety disorders: 16.3% vs. 4.0%). Heart disease, stroke and obesity were associated with dementia as was a lower level of education. Furthermore, people with dementia were more likely than those without the disease to report activity restrictions.

The high prevalence of mood and anxiety disorders in household population with Alzheimer's disease and other dementia demonstrates the burden of disease that is likely to worsen quality of life over time.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood.

To assess the current care of paediatric DMD patients in Canada, a questionnaire was mailed to 17 physicians who were members of the Canadian paediatric neuromuscular group. Areas of enquiry included; 1) multidisciplinary team composition; 2) means of DMD diagnosis; 3) corticosteroid use; surveillance and management for: 4) orthopaedic, 5) respiratory and 6) cardiac complications and 7) health maintenance (nutrition & immunizations).

Completed surveys were returned by 14/17 (82%) of physicians. Twelve respondents followed DMD patients. All centres had multidisciplinary teams, including respirology (11/12), child neurology or physiatry (11), physiotherapy (9), occupational therapy (9) and orthopaedic surgery (7). Deflazacort 0.9mg/kg/d was used at all centres, which was continued after loss of independent ambulation (11), along with routine calcium and vitamin D supplementation (10). Night splints were prescribed at all centres. Routine surveillance studies included pulmonary function testing (11), sleep studies (10), EKG/echocardiogram (10), bone density (DEXA) scans (10), spine radiography (9), and dietician referral (4).

Paediatric DMD patients are receiving relatively consistent care in multidisciplinary clinics across Canada, in accordance with recommended guidelines for DMD.

The expansion of neurosurgery and neurology in Montreal and Toronto in the early 20th century was the stimulus for the development of neuropathology in Canada. Rooted in the disciplines of the neurosciences and laboratory medicine, neuropathology evolved into an independent discipline with the founding of the Canadian Association of Neuropathologists in 1960, and the recognition as a specialty by the Royal College of Physicians and Surgeons in Canada in 1965, fostering the development of several successful training programs. Nonetheless, a paucity of data remains concerning the background of training, scopes of practice, and career paths.

We conducted a survey of all physicians in Canada who have either practiced neuropathology or undergone relevant training.

In 2009, 53 physicians were engaged in the practice of neuropathology, either exclusively or a substantial proportion of their time. Most work in tertiary hospitals, but a few service non-academic medical centers. Three routes of training were identified: direct from medical school (often with relevant research training), indirect from another clinical neuroscience specialty, and following or in conjunction with certification in one of the other pathology specialties. Practice profiles differ slightly, and some of the neuropathologists entering from pathology have mixed anatomical pathology/neuropathology responsibilities. Many of those with prior exposure in the neurosciences are more productive with regard to research and publications.

Existing multiple options for neuropathology training have facilitated recruitment and allowed development of a mosaic of specialists able to fulfill the diversity of needs in Canadian medical and scientific communities.

Diagnostic considerations for juvenile onset Parkinsonism (onset at <21 years of age) include juvenile Huntington disease, Wilson disease, dentatorubral-pallidoluysian atrophy (DRPLA), storage diseases, and mitochondrial cytopathies. Neuronal Intranuclear Inclusion Disease (NIID) must also be considered.

We present a case of juvenile onset NIID with a predominantly Parkinsonian presentation, followed later by corticospinal, cerebellar, and lower motor neuron symptoms.

Diagnosis of NIID can be made antemortem through rectal biopsy, however it was missed in this case. Rectal biopsy should be performed in all suspected cases, reviewed by an experienced neuropathologist and repeated if the suspicion for NIID is high. Pathologically, SUMO-1 immunohistochemistry appears to reliably label the neuronal inclusions and abnormal SUMOylation may play a part in the pathogenesis.

To present a new semiological description of unruptured middle cerebral artery (MCA) aneurysms.

We present a series of three MCA aneurysms presenting with progressive or paroxystic somatosensory symptoms in combination with visceral, motor, language or autonomic symptoms.

A surgical approach was proposed for two aneurysms, and both patients experienced complete resolution of their symptoms. The third aneurysm was successfully excluded by endovascular coiling but the symptoms persisted.

To our knowledge this is the first description of unruptured aneurysms presenting with insular-related symptoms.

It has been shown previously that S-100β levels in serum correspond with the severity of central nervous system (CNS) trauma. It also has been suggested that S-100β in CNS tissue is involved in neuroprotection and neuroregeneration. We have previously shown that administration of quercetin results in improved motor function in an animal model of spinal cord trauma.

Mid-thoracic spinal cord compression injury was produced in adult maleWistar rats. Serum and tissue samples were acquired from quercetin-treated animals (25 μmol / kg) and saline controls at 6, 12 and 24 hours after the trauma. S-100β levels were measured using a luminometric assay in the damaged tissue and in the serum of the animals.

The increase in serum S-100β levels seen in saline controls after spinal cord trauma was ameliorated in the quercetin-treated animals at all time points, although the difference to saline controls became statistically significant only at 24 hrs after the trauma. Compared to tissue S-100β levels in healthy animals, values were significantly decreased in saline controls at all three time points, while they were decreased at 6 hrs and increased at both 12 and 24 hrs in quercetin-treated animals. At all three time points tissue S-100β levels were significantly higher in quercetin-treated animals than in saline controls.

Administration of quercetin results in modification of S-100β levels in the setting of experimental spinal cord trauma. The kinetic patterns of the S-100β fluctuations in serum and tissue suggest that post-traumatic administration of quercetin decreases the extent of CNS injury.

Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture.

We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the Annexin V-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA.

We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly.

Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.

Idiopathic intracranial hypertension (IIH) can be an elusive diagnosis, and poor visual outcomes may occur. Currently, the only means of accurately diagnosing and following these patients is with repeated lumbar puncture. Previous work has shown that transcranial doppler measurements of pulsatility correlate accurately with elevated intracranial pressure (ICP). This study is designed to assess whether pulsatility index (PI) correlates with ICP in patients newly diagnosed with IIH.

Seven patients with clinical suspicion of IIH were included in this study. Clinical suspicion was based on history of recurrent headaches and papilledema. All patients had otherwise normal examinations and imaging. Middle cerebral arteries were insonated to obtain average PI values. Cerebrospinal fluid (CSF) was then withdrawn, and closing pressures were recorded. Pulsatility index values were then obtained again, within ten minutes after completing CSF withdrawal. PI values were correlated with ICP values, and pre and post CSF withdrawal values were compared.

All seven patients had elevated opening pressures (average 39 cm H2O, range 27-70). The average closing pressure after approximately 30 cc of CSF withdrawal was 11.9 cm H2O. The average PI before CSF withdrawal was 0.95, which dropped to 0.70 after CSF withdrawal (p = 0.02). The change in ICP was found to be correlated with a change in PI (p = 0.004).

These findings suggest that PI may be useful for following patients with IIH non-invasively. Further study with larger groups and blinded assessments should be useful in better characterizing the accuracy of this technique.

The safety and effectiveness of intra-arterial thrombolysis (IAT) in comparison to intravenous thrombolysis (IVT) for the treatment of ischemic stroke is uncertain. Our study aims to assess and compare IAT to IVT for clinically relevant outcomes in patients with occlusion of the anterior cerebral circulation.

Patients with acute ischemic stroke were enrolled for either treatment; those whose symptoms occurred within 4.5 hrs after stroke were treated with IVT, whereas those who presented <4.5 hrs but had contraindications to IVT or presented between 4.5 and 6 hrs were treated with IAT. Evaluated endpoints included: disability at 90 days as measured by the modified Rankin Scale (mRS), incidence of mortality, and incidence of symptomatic intracranial haemorrhage.

78 patients with anterior cerebral circulation occlusion were included in the study (55 in IVT, 23 in IAT). After 90 days, 82.6% patients treated with IAT reached independence in comparison to 56.4% in the IVT group (P=0.028, RR=2.66, 95% CI: 1.10-7.04). The incidence of all intracranial haemorrhages in the IAT and IVT groups respectively were 30.4% and 12.7% (P=0.103, RR=2.391, 95% CI: 0.946-6.047); symptomatic intracranial haemorrhage occurred in 8.7% and 9.1% of patients (P=1.00, RR= 0.957, 95% CI: 0.200-4.579), and mortality in 8.7% and 16.4% (P=0.492, RR=1.882, 95% CI: 0.440-8.045).

Results suggest that IAT is more effective than IVT in allowing patients to achieve independence. While inconclusive, the safety of IAT within 6 hrs is comparable to IVT within 4.5 hrs.

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.

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.

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.

Two prospective studies in patient with brain tumours were performed comparing the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The first assessed their feasibility and the second compared their diagnostic accuracy against a four-hour neuropsychological assessment (NPA). The introduction of the NPA decreased accrual and retention rates. We were therefore concerned regarding potential selection bias.

Ninety-two patients were prospectively accrued and subsequently divided into three categories: a) no NPA required b) withdrew consent to NPA c) completed NPA. In order to quantify any potential bias introduced by the NPA, patient demographics and cognitive test scores were compared between the three groups.

There were significant differences in age (p<0.001), education (p=0.034), dexamethasone use (p=0.002), MMSE (p=0.005), and MoCA scores (p<0.001) across the different study groups. Furthermore, with increasing involvement of the NPA, patients' cognitive scores and educational status increased, while their age, dexamethasone use, and opioid use all decreased. Individuals who completed the NPA had higher MoCA scores than individuals who were not asked to complete the NPA (24.7 vs. 20.5; p < 0.001). In addition, this relationship held when restricting the analyses to individuals with brain metastases (p < 0.001).

In this study, the lengthy NPA chosen introduced a statistically and clinically significant source of selection bias. These results highlight the importance of selecting brief and well tolerated assessments when possible. However, researchers are challenged by weighing the improved selection bias associated with brief assessments at the cost of reduced diagnostic accuracy.