The brain functions as an integrated multi-networked organ. Complex neurocognitive functions are not attributed to a single brain area but depend on the dynamic interactions of distributed brain areas operating in large-scale networks. This is especially important in the field of neurosurgery where intervention within a spatially localized area may indirectly lead to unwanted effects on distant areas. As part of a preliminary integrated work on functional connectivity, we present our initial work on diffusion tensor imaging tractography to produce in vivo white matter tracts dissection.

Diffusion weighted data and high-resolution T1-weighted images were acquired from a healthy right-handed volunteer (25 years old) on a whole-body 3 T scanner. Two approaches were used to dissect the tractography results: 1) a standard region of interest technique and 2) the use of Brodmann's area as seeding points, which represents an innovation in terms of seeds initiation.

Results are presented as tri-dimensional tractography images. The uncinate fasciculus, the inferior longitudinal fasciculus, the inferior fronto-occipital fasiculus, the corticospinal tract, the corpus callosum, the cingulum, and the optic radiations where studied by conventional seeding approach, while Broca's and Wernicke's areas, the primary motor as well as the primary visual cortices were used as seeding areas in the second approach.

We report state-of-the-art tractography results of some of the major white matter bundles in a normal subject using DTI. Moreover, we used Brodmann's area as seeding areas for fiber tracts to study the connectivity of known major functional cortical areas.

Stereotactic radiosurgery offers a unique and effective means of controlling cavernous sinus meningiomas with a low rate of complications.

We retrospectively reviewed all cavernous sinus meningiomas treated with Gamma Knife (GK) radiosurgery between November 2003 and April 2011 at our institution.

Thirty patients were treated, four were lost to follow- up. Presenting symptoms included: headache (9), trigeminal nerve dysesthesias/paresthesias (13), abducens nerve palsy (11), oculomotor nerve palsy (8), Horner's syndrome (2), blurred vision (9), and relative afferent pupillary defect (1). One patient was asymptomatic with documented tumor growth. Treatment planning consisted of MRI and CT in 17 of 30 patients (56.7%), the remainder were planned with MRI alone (44.3%). There were 8 males (26.7%) and 22 females (73.3%). Twelve patients had previous surgical debulking prior to radiosurgery. Average diameter and volume at time of radiosurgery was 3.4 cm and 7.9 cm3 respectively. Average dose at the 50% isodose line was 13.5 Gy. Follow-up was available in 26 patients. Average follow-up was 36.1 months. Mean age 55.1 years. Tumor size post GK decreased in 9 patients (34.6%), remained stable in 15 patients (57.7%), and continued to grow in 2 (7.7%). Minor transient complications occurred in 12 patients, all resolving. Serious permanent complications occurred in 5 patients: new onset trigeminal neuropathic pain (2), frame related occipital neuralgia (1), worsening of pre-GK seizures (1), and panhypopituitarism (1).

GK offers an effective treatment method for halting meningioma progression in the cavernous sinus, with an acceptable permanent complication rate.

Recent reports raise concern that physician knowledge of the identification and management of concussion may be deficient. There is little information known about the adequacy of concussion education provided to physicians or medical students. The present study assesses the concussion curriculum offered at medical schools in Canada.

We asked all 17 Canadian medical schools to complete a questionnaire on their concussion curriculum, including the following: year of medical school offered; format/setting; and estimated teaching hours. The responses were organized into three categories: (1) concussion-specific education; (2) head injury education incorporating a concussion component; and (3) no concussion education.

Replies were received from 14 (82%) of the 17 medical schools in Canada. Of the 14 responding schools, four (29%) provided concussion-specific education, six (43%) offered head injury education that incorporated a concussion component, and four (29%) reported no concussion teaching in their curriculum.

We found deficiencies in the concussion education curriculum provided in the majority of Canadian medical schools. To address this issue, we recommend that all medical schools should, at a minimum, include a one-hour formal concussion-specific teaching session in an early year of their curriculum to be followed by clinical exposure to concussed patients in the later years of medical school. Future studies will be necessary to evaluate if these recommended curricular enhancements are effective in remedying the reported gaps in physicians' concussion knowledge and whether the improved curriculum translates into better care for patients suffering concussion.

Vasospasm is a known complication of aneurysmal subarachnoid hemorrhage and is a major cause of neurological morbidity and mortality. It is infrequently associated with pituitary adenoma surgery. We report three cases and present a systematic review of the literature with a view towards guiding neurosurgeons in the prevention and management of this complication.

Including our experience, vasospasm complicating pituitary adenoma surgery has been documented in 29 patients (mean age of 45). All cases occurred in the setting of a postoperative hemorrhage: 21 had a subarachnoid hemorrhage and 10 had a postoperative hematoma requiring evacuation. Initial clinical appearance of delayed cerebral ischemia attributable to vasospasm occurred from postoperative Days 2-13 (most commonly Day 5). Digital subtraction angiography and medical management were the most common diagnostic and therapeutic strategies, respectively. Glasgow Outcome Scores were ≤3 in 59% of cases. Univariate logistic regression identified later diagnosis of vasospasm and surgery for hematoma evacuation to be independently associated with better outcomes.

Vasospasm should be considered in the differential diagnosis of patients demonstrating altered mental or neurological status following pituitary surgery, particularly if there has been postoperative hemorrhage of any degree. Prompt treatment should be instituted to optimize outcome.

Patients with dementia benefit from early assessment and diagnosis. In an attempt to identify factors leading to delay in referral, we investigated socio-demographic, clinical, and functional predictors of greater severity of cognitive impairment in dementia patients presenting to a memory clinic in Saskatoon, Saskatchewan.

Data collection began in 2004 at the Rural and Remote Memory Clinic in Saskatoon, where non-institutionalized patients were referred by their family physicians. The patient and caregiver questionnaires and assessments administered at the clinic day appointment provided the socio-demographic, clinical, and functional patient variables, as well as the caregiver stress and burden variables. The dependent variable was patient cognitive impairment, as measured by Modified Mini-Mental State Examination (3MS) scores. Variables underwent univariate linear regression with 3MS scores in order to determine possible associations. A multiple regression analysis was conducted to determine predictors of cognitive impairment severity at clinic presentation.

Our sample included 198 patients (62% female). The mean age was 73.9 years (SD=9.2). We found that an age and gender interaction, years of formal education, Functional Activities Questionnaire score, and Brief Symptom Inventory score were significantly associated with 3MS scores (p<0.05).

Increased cognitive impairment at presentation was predicted by fewer years of formal education, poorer functional ability, and less caregiver psychological distress. There was a significant interaction between age and gender: younger females were more cognitively impaired than younger males at clinic day, while in older patients, males were more cognitively impaired than females.

Abnormal movements are frequently associated with psychiatric disorders. Optimized management and diagnosis of these movements depends on correct labeling. However, there is evidence of reduced accuracy in the labeling of these movements, which could result in sub-optimal care.

To determine the consensus inter-rater reliability between a movement disorders neurologist and physicians referring from the community for phenomenology and diagnoses of individuals with co-existing psychiatric conditions and movement disorders.

Charts of all consecutive patients seen in a combined Movement Disorders and Neuropsychiatry Clinic between 2001-2009 were reviewed retrospectively. Consensus estimates and kappa values for inter-rater reliability were determined for phenomenology and diagnostic terms for the respective referring source and movement disorders neurologist for each patient.

A total of 106 charts were reviewed (62 men and 44 women). Agreement for phenomenology terms ranged from 0% (psychogenic) to 73% (tremor). Only 3 terms had kappa values that met or exceeded criteria for moderate inter-rater reliability. Agreement for diagnosis terms was highest for tardive dyskinesia (83%), drug induced tremor (33%), and drug induced parkinsonism (20%). In 18 of the 22 charts (82%), a diagnosis was made of drug induced movement disorder (DIMD) by the referring physician. In contrast, a diagnosis of DIMD was made in only 54 of 106 charts (51%) after the patients were assessed in the clinic.

A movement disorders specialist frequently disagreed with referring physicians' identification of patient phenomenology and diagnosis. This suggests that clinicians would benefit from educational resources to assist in characterizing abnormal movements.

The benefits of intravenous recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke is time dependent. Guidelines recommend a door-to-needle (DTN) time of less than 60 minutes.

A retrospective audit of 730 stroke charts from 2008 - 2011 was conducted at Health Sciences Centre. 158 patients treated with IV rt-PA were identified. The time intervals between Emergency Department (ED) arrival, administration of rt-PA and uninfused brain computed axial tomographic scan (CT) were recorded. From this, CT to needle times were calculated. During November 2010 to January 2011 feedback was given to neurologists, ED physicians, ED nurses, and CT technologists. This raised awareness and emphasized the importance of this time driven protocol.

The median DTN times for 2008, 2009, and 2010 were 69, 71 and 76 minutes respectively. The median CT-to-needle time for this time period was 47 minutes. In 2011 (n =58) the median DTN time was 49 minutes and the median CT-to-needle was 18 minutes, which were marked improvements (p<0.00005 and p<0.005, respectively). In 2008-2010 only 31% of treated patients (n=100) received rt-PA within 60 minutes, whereas in 2011 this increased to 64%.

Dramatic improvements in DTN times and in the percentage of patients receiving rt-PA treatment within 60 minutes were observed in 2011 after feedback was provided regarding the suboptimal performance. Prior to receiving feedback, DTN times were similar to national median DTN times. All centres administering rt-PA for acute ischemic stroke should monitor their clinical performance and give feedback on a regular basis.

Longitudinal, patient-level data on resource use and costs after an ischemic stroke are lacking in Canada. The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs.

The Economic Burden of Ischemic Stroke (BURST) Study was a one-year prospective study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres. Clinical history, disability, health preference and resource utilization information was collected at discharge, three months, six months and one year. Resources included direct medical costs (2009 CAN$) such as emergency services, hospitalizations, rehabilitation, physician services, diagnostics, medications, allied health professional services, homecare, medical/assistive devices, changes to residence and paid caregivers, as well as indirect costs. Results were stratified by disability measured at discharge using the modified Rankin Score (mRS): non-disabling stroke (mRS 0-2) and disabling stroke (mRS 3-5).

We enrolled 232 ischemic stroke patients (age 69.4 ± 15.4 years; 51.3% male) and 113 (48.7%) were disabled at hospital discharge. The average annual cost was $74,353; $107,883 for disabling strokes and $48,339 for non-disabling strokes.

An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS. Costs during the hospitalization to three months phase were the highest contributor to the annual cost. A “back of the envelope” calculation using 38,000 stroke admissions and the average annual cost yields $2.8 billion as the burden of ischemic stroke.

Symptomatic intracranial atherosclerosis (ICAS) is a dynamic disease that frequently progresses. Statins have been shown to have anti-atherosclerotic activity. We therefore investigated whether statins could prevent progression of ICAS.

This retrospective cohort study assessed 55 patients with acute ischemic stroke and symptomatic ICAS in the middle cerebral or basilar arteries as shown on magnetic resonance angiography (MRA), with follow-up MRA performed more than 1 year after the index stroke. Change in ICAS was classified as progressive, regressive, or stable. Baseline clinical characteristics and risk factor control during follow-up were assessed, and laboratory tests were performed at the time of follow-up MRA. The statin group was defined as patients regularly treated with statins for more than 75% of the follow-up period; the remaining patients were defined as the non-statin group.

At a median follow-up time of 21.8 months (range, 11.8-66.1 months), the statin group consisted of 26 (47.3%) patients and the non-statin group of 29 (52.7%). During follow-up, 6 (10.9%) patients progressed, 14 (25.5%) regressed, and 35 (63.6%) remained stable. Statin treatment was significantly associated with non-progression of ICAS (p=0.024). Two patients in the non-statin group had recurrent strokes. Border-zone infarcts were associated with progression of ICAS (3/6, 50%; p=0.007), whereas risk factors and inflammatory biomarkers were not related to progression.

Treatment with statins may prevent progression of symptomatic ICAS. Prospective randomized controlled trials are required to confirm that statins protect against such progression.

Chronic migraine is a significant cause of disability world-wide and occipital region stimulation (OS) has been proposed to treat it. While participating in an industry-sponsored pilot trial of OS, we aimed to collect data regarding our surgical complications and long term usage of OS in our chronic migraine patients.

Ten patients (8 female, median age 46.5 years) were enrolled based on criteria established by the sponsoring company, screened in the headache clinic, and followed for a median of 33 months. We did not access data collected by industry for this report and instead collected our own data prospectively, including predominant location of headache, location of paresthesia evoked by OS, and complications.

Adverse events included three possible early infections requiring antibiotics but not hardware removal, one late implantable pulse generator erosion requiring removal, one generator malfunction requiring revision, and loss of paresthetic coverage requiring four revisions in four patients. Two patients experienced new symptoms requiring psychiatric intervention. Five patients had no benefit and have been explanted. Of those who remain using their device, the proportion of their pre-operative pain located in the occipital region was 0.62 ± 0.14, whereas in those patients who have been explanted, the proportion was 0.31 ± 0.18 (t = 3.15, p=0.01).

Complication rates with OS are higher than those seen with other stimulation techniques, despite identical hardware and similar surgery. The location of migraine pain did predict outcome, and suggests that only those with primarily occipital region headache are candidates for this therapy.

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown.

To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity.

CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).

CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027).

The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Hemangioblastomas are benign vascular tumors of the central nervous system that occur sporadically or in association with von Hippel-Lindau disease. These tumors are characteristically composed of a dense capillary network with intervening stromal/interstitial cells. To date, the histogenesis of hemangioblastoma remains unclear. We hypothesize that hemangioblastomas arise from a defective mesodermal stem cell, which gives rise to the atypical vasculature.

To test our hypothesis, we have characterized the cellular composition of hemangioblastomas by immunophenotyping pluripotent and committed stem cells and vascular endothelial cells.

Our findings show that hemangioblastoma endothelial cells are positive for CD133, a stem and progenitor cell marker. Vascular endothelial cells also expressed nuclear Oct4. In addition to the endothelium, both CD133 and Oct4 were present in stromal and perivascular cells. Interestingly, neither the endothelium nor the stromal cells expressed Sox2 or Nanog suggesting a committed stem cell phenotype.

From these findings, we believe that hemangioblastoma stromal cells are committed stem cells producing both vascular cell types. The findings also show an unusual CD133-positive endothelial phenotype in hemangioblastoma.