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.

Sporadic Jakob-Creutzfeldt disease (sCJD) and dementia with Lewy bodies (DLB) have overlapping clinical symptoms that can lead to their misdiagnosis. We delineated the clinical overlap between sCJD and DLB, and assessed the value of magnetic resonance imaging (MRI) to differentiate between them.

Medical records, MRI, electroencephalogram (EEG) and cerebrospinal fluid (CSF) were reviewed from 56 sCJD and 30 DLB subjects.

46% of sCJD subjects met probable DLB criteria and 40% of DLB subjects met probable CJD criteria. A greater proportion of sCJD subjects had cerebellar signs (66% vs. 10%, p<0.001), myoclonus (64% vs. 30%, p=0.002), and visual symptoms (other than hallucinations) (61% vs. 7%, p<0.001), whereas more DLB subjects had hallucinations (70% vs. 39%, p=0.007) and fluctuations (57% vs. 23%, p=0.002). Cortical and/or basal ganglia MRI diffusion weighted imaging hyperintensities consistent with sCJD were seen in 96% of sCJD subjects but in none with DLB. Logistic regression in sCJD revealed that those meeting probable DLB criteria were more likely to have occipital lobe involvement on MRI (OR 1.4, p=0.058, model p=0.022). Parietal lobe involvement on MRI was a predictor of “Other Focal Cortical signs” (OR 1.9, p=0.021). EEG and CSF assessments lacked sensitivity for sCJD as 48% of sCJD patients had a negative EEG; 67% of the 36 sCJD patents with a CSF evaluation had a negative or inconclusive 14-3-3 result. Too few DLB patients had EEG or CSF to assess their utility.

Sporadic CJD and DLB have significant symptom overlap. MRI helps differentiate these diseases and is related to the signs/symptoms observed in sCJD.

Fatigue is common and disabling in multiple sclerosis, yet its physiologic substrates remain poorly defined. The aim of this study was to determine the relationship between fatigue and an objective measure of alertness in MS patients.

This study enrolled 49 consecutive MS clinic patients at two academic hospitals in Toronto. Alertness was assessed with the psychomotor vigilance test (PVT), a ten-minute reaction-time test that measures attention and is sensitive to sleep loss. Patients with visual impairment or arm weakness were excluded. Validated tools were used to assess fatigue, disability, mood, and pain.

The average age was 43; 65% were women. Median EDSS was 2.0 (range 0-7.5). Fifty-five percent reported a high impact of fatigue on their lives. Psychomotor vigilance test performance was worse than in an age- and sex-matched population, with a mean reaction time of 315 msecs and 3.98 lapses >500 msec (p<0.001). In a multiple regression analysis, fatigue was the most significantly correlated factor with mean PVT reaction time (p<0.05), and disability was also significantly correlated (p<0.01). Mood and pain did not correlate with the PVT. Eighteen (37%) reported often experiencing restlessness in their legs at night.

Subjective fatigue and disability were associated with poor performance on alertness testing in MS patients. This research highlights a potential role for psychomotor vigilance testing in providing a standardized assessment tool for an important aspect of MS-related fatigue.

Levodopa-induced dyskinesias (LID) are amongst the most disabling side-effects of levodopa therapy for Parkinson's disease (PD). It has been suggested that that N-Methyl-D-Aspartate (NMDA)-receptor antagonist may reduce peak-dose dyskinesia in PD patients and may lead to motor improvement. In this study, we compared the efficacy of NMDA receptor antagonists versus placebo in the treatment of LID in PD through a meta-analysis of controlled trials.

Electronic search of Pubmed (1990 - 2010), Medline (1966-2010), EMBASE (1974-2010) and other databases for relevant studies were performed. Controlled clinical trials of the effects of NMDA antagonists on LID that fulfill the study protocol were selected. Pooled data from included studies was then used to perform random and fixed effect models meta-analysis.

The search resulted in 11 randomized, placebo controlled clinical trials that involved a total of 253 PD patients with peak-dose LID. The outcome measures were various dyskinesia rating scales and the Unified Parkinson Disease Rating Scale (UPDRS) subscales III and IV. The analysis showed significant reduction in Standard Mean Difference (SMD) for UPDRS IV (SMD -1.45; 95% CI -2.28 to -0.63) and UPDRS III (SMD -0.41; 95% CI -0.69 to -0.12) after treatment with amantadine. Other included drugs did not show significant change in the outcomes measured.

This meta-analysis provides an update on the clinical trials and confirms the short-term benefits of amantadine therapy in the treatment of dyskinesia. The effects of other NMDA receptor antagonists need to be evaluated further in clinical trials.

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.

Stress-induced central effects are regulated by brain neurotransmitters, glucocorticoids and oxidative processes. Therefore, we aimed to evaluate the simultaneous alterations in the monoamine and antioxidant systems in selected brain regions (frontal cortex, striatum and hippocampus) at 1 hour (h) and 24h following the exposure of restraint stress (RS), to understand their initial response and possible crosstalk.

RS (150 min immobilization) significantly increased the dopamine levels in the frontal cortex and decreased them in the striatum and hippocampus, with selective increase of dopamine metabolites both in the 1h and 24h RS groups compared to control values. The serotonin and its metabolite levels were significantly increased in both time intervals, while noradrenaline levels were decreased in the frontal cortex and striatum only. The activities of superoxide dismutase, glutathione peroxidase and the levels of lipid peroxidation were significantly increased with significant decrease of glutathione levels in the frontal cortex and striatum both in the 1h and 24h RS groups. There was no significant change in the catalase activity in any group. In the hippocampus, the glutathione levels were significantly decreased only in the 1h RS group.

Our study implies that the frontal cortex and striatum are more sensitive to oxidative burden which could be related to the parallel monoamine perturbations. This provides a rational look into the simultaneous compensatory central mechanisms operating during acute stress responses which are particular to precise brain regions and may have long lasting effects on various neuropathological alterations.

Gastrointestinal involvement is a frequent and early event in the course of Parkinson Disease (PD), and may have a prominent role in the early pathophysiology of the disease. On the other hand, derangement in intestinal permeability could also result from the involvement of the gastrointestinal tract over the course of the disease.

The intestinal permeability of 12 non-selected PD patients was studied using a validated, non-invasive test; these results were compared to predefined age-adjusted reference values.

4/12 PD patients had abnormal gastrointestinal permeability; two had both an abnormal lactulose/mannitol ratio and an abnormal sucrose concentration, and two an isolated abnormal result. An increased lactulose/mannitol ratio is consistent with defect of either the enterocytes or the tight junctions between them.

Intestinal permeability is increased in a significant proportion of unselected PD patients with minimal gastrointestinal symptoms. The significance of this finding needs to be further evaluated.

Postural instability is one of the most disabling features of Parkinson's disease, usually occurring in late and advanced stages. The aim of this study was to investigate the postural performance of early-stage de novo Parkinson's disease patients with no clinical postural instability using computerized dynamic posturography. We sought to understand the relationship between postural sway and disease severity and the relationship between postural instability quantitatively measured by computerized dynamic posturography and cognitive impairment in early-stage Parkinson's disease patients.

Thirty-one subjects with Parkinson's disease and 20 healthy controls were assessed by the computerized dynamic posturography protocol using the sensory organization test and the motor control test. A neuropsychological assessment was also administered.

The mean equilibrium score for sensory organization test and the vestibular input ratio were significantly correlated with Hoehn-Yahr stage. No associations between motor latency for any motor control test condition and Hoehn-Yahr stage were found. The equilibrium score for sensory organization test correlated with the mini-mental status examination scores. There was a significant correlation between motor latency for large backward translation and mini-mental status examination scores. There were significant correlations between visual perception/construction/ memory of the neuropsychological battery test and the equilibrium score for sensory organization test and between verbal word learning test, controlled word association test and motor latency for large backward translation.

These findings showed the postural instability present in early-stage (Hoehn-Yahr stage 2-2.5) Parkinson's disease. We also found a close relationship between postural instability and cognitive function in Parkinson's disease patients.

Iron deficiency anemia (IDA) has been implicated in the etiology of transient ischemic attack and ischemic stroke. This study aimed to: 1) document IDA prevalence in patients ≥ 65 years of age admitted to hospital with transient ischemic attack or first ischemic stroke, and 2) investigate dietary intake as a predictor of iron status.

Ninety-four patients were enrolled. An algorithm containing values for hemoglobin, ferritin, total iron binding capacity, transferrin saturation, and serum transferrin receptor measured at admission was used to identify IDA. Usual dietary intake was assessed with the Clue II food frequency questionnaire.

Prevalence estimates were 6.4% for IDA, 2.1% for iron deficiency without anemia, and 6.4% for anemia from other causes. IDA prevalence was significantly higher than published National Health and Nutrition Examination Survey III (NHANES III) estimates for gender-specific age groups ≥ 70 years (One-Sample Proportion Test; males p = 0.038 [n= 37]; females p = 0.002 [n=44]). A comparison of IDA prevalence against selected controls from the NHANES III database yielded an odds ratio (OR) of 6.3, 95% confidence interval (CI) 0.8 to 53.7, which was not statistically significant (Fisher's Exact Test; n=94; p = 0.118). Multivariate linear regression analysis of dietary intake with indicators of iron status (n=58) revealed only iron supplements (p = 0.013) and heme iron intake (p = 0.038) as negative predictors of total iron binding capacity (p<0.05).

These findings support the initiation of a prospective case control study to investigate IDA as a risk factor for ischemic stroke in elderly patients.

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.

Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country.

MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. Abstracted data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis.

A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis.

An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.

Serotonin, a neurotransmitter synthesized from tryptophan, has been proposed to play a key role in central fatigue. In this study, we examined whether tryptophan itself and/or its two metabolites, kynurenic acid (KYNA) and quinolinic acid (QUIN), are involved in central fatigue.

Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a Morris water maze test. Microdialysis was used to collect samples for measurement of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) and to infuse test agents. To examine the kinetics of release, synaptosomes in the striatum were prepared in vitro to measure intra- and extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA.

The concentration of tryptophan secreted into the extracellular space of the striatum was higher during fatigue only, and quickly returned to basal levels with recovery from fatigue. Running time to exhaustion was reduced by activation of tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a higher extracellular level of striatum tryptophan than SDR. Impaired memory performance in a water maze task after tryptophan treatment was attributable to high levels of KYNA and QUIN in the hippocampus acting synergistically on N-methyl-D-aspartic acid receptors. When branched-chain amino acids were administered, tryptophan transport to the extracellular space of the striatum was drastically inhibited.

Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN.