The presence of residual neurological deficits after neurological symptoms is important information for making a diagnosis of Transient Ischemic Attack (TIA) versus stroke. The purpose of this study was to establish the reliability of the referring physician (non neurologist) to report focal neurological deficits in the context of an urgent referral for TIA.

Prospectively recorded urgent physician-to-physician phone referrals for TIA through the Southern Alberta TIA hotline from March 2009 to July 2010 were reviewed. “Has the neurological deficit completely resolved?” was asked to the referring physician (family or emergency room physician) and recorded prospectively as a yes/no response. Patients were included if a neurological examination was performed by a neurologist on the same day as referral. The neurologist's assessment of whether the deficit had resolved was compared to that of the referring physician.

78 patients were included in this study. 62 patients had resolved as per the referring physician's assessment. Of these 62 patients, 16 (25.8% 95%CI 16-38) had evidence of persisting neurological deficits on the neurologist's assessment. A wide variety of mild neurological deficits were identified. None of these deficits appeared to be explained by progression of symptoms.

Physicians referring patients with TIA syndromes for emergent assessment do not reliably detect mild residual deficits in one-quarter of patients. We are questioning the validity of neurological deficit resolution as a triage rule. The findings suggest that studies of TIA likely include a proportion of minor stroke patients and this should be remembered when extrapolating the results to other populations.

The ISAT and ISUIA studies, along with the improvement of endovascular treatment (EVT) have strongly influenced the management of intracranial aneurysms (IAs). We present our experience in the microsurgical treatment of unruptured IAs (UIAs) in this context.

We retrospectively reviewed a consecutive series of non-giant UIAs selected for surgery during a five-year period. Patients and aneurysms characteristics, surgical results and outcome assessed by the Glascow Outcome Scale (GOS) at three month follow-up were studied.

Eighty-five patients underwent 93 surgical procedures to obliterate 113 UIAs. Those were incidental in 89% of the cases and mainly located on the middle cerebral artery (65%). Patients were assigned to surgery according to their medical history (young, previous subarachnoid haemorrhage), aneurysm characteristics (wide neck, branch at the neck, “small” size, associated “surgical” aneurysm) or failure of EVT (5%). Operatively, 48% of UIAs had thin wall or blebs and 71% were occluded with one titanium clip. Thrombectomy or temporary clipping were necessary in 4% and 11% of the cases, three aneurysms peroperatively ruptured, four were deemed unclippable, three paraclinoid UIAs had an intracavernous residue and 16% were wrapped because of a small neck remnant (class 2). The mortality rate was 0% and 4% of the patients experienced a definitive major neurological deterioration. Final GOS was unchanged in 96% of the patients.

Despite reduction in operative cases and in appropriately selected patients ineligible to EVT, microsurgical clipping of non-giant anterior circulation UIAs can still achieve good outcome with very low mortality and neurological morbidity.

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.

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.

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.

To determine if fine-motor eye exercises can be used for treatment of unilateral, idiopathic cranial nerve VII paresis to improve rate of recovery.

In this prospective, randomized controlled trial, eligible patients were randomized to perform fine-motor eye exercises (n=18) or to do no exercise (n=9) for a period of four weeks. Orbicularis oculi muscle strength was measured in paretic and unaffected eyes at baseline, two weeks and four weeks using an Orbicularis Oculi Pressure Sensor.

The average initial strength of the paretic orbicularis oculi muscle was 34±10 mm Hg compared to the unaffected muscle which was 103±17 mm Hg at baseline (n=27). By four weeks, patients who performed eye exercises improved more than those who did not (74.4 versus 47.4 mm Hg, p=0.029). While there was some loss to follow-up, 63.8% of patients performing exercises (7/11) achieved functional recovery at four weeks compared to 12.5% (1/8) of those who did not (p=0.059). Steroids and antivirals were found to have independent positive effects on improving functional outcome.

Eye exercises have a potential role in the treatment of idiopathic cranial nerve VII paresis and warrant consideration in the management of these patients.

The majority of children with chronic neurodevelopmental disabilities are surviving to adulthood. Our goal was to assess how prepared and comfortable adult neurologists are in treating young adults with childhood onset chronic neurological conditions and evaluate the difficulty pediatric neurologists experience when transferring these patients to adult care.

We conducted a cross-sectional study using two postal surveys of all pediatric and adult neurologists in the province of Quebec, Canada.

The response rate was 51.5%, with 119 neurologists completing the survey. Half of neurologists agreed that adult neurologists may not have adequate training in childhood onset disorders to prepare them to manage the disorders in adulthood, and 60% of pediatric neurologists reported having difficulty finding an adult provider for their patients. Adult neurologists were least comfortable treating patients with autism, chromosomal or metabolic disorders, and cognitive or behavioral disorders.

Almost half of those surveyed believed that adult neurologists are not adequately trained to care for this growing patient population. Improving treatment comfort and knowledge among adult neurologists in childhood onset chronic neurological conditions may smooth the transition of these young adults from pediatric to adult care.

Community-based studies can describe health status and related variables in people with Multiple Sclerosis (MS) while avoiding biases introduced by help-seeking in specific clinical settings.

To describe general health status, stress perceptions and life satisfaction in people with MS, in comparison to those with other types of disabilities.

The Participation and Activity Limitation Survey (PALS) was a post-censual survey conducted by Statistics Canada in association with the 2006 Canadian Census. PALS collected data from a random sample of n = 22,513 respondents identified as having health-related impairments. Frequencies and quartiles as well as mean values, along with associated 95% confidence intervals, were calculated in the analysis.

PALS identified 245 individuals with MS. Health status, both perceived and when weighted for societal preference, was markedly lower than that of other disabled groups. No differences in self-perceived stress were seen. People with MS reported lower levels of satisfaction with their health but slightly higher levels of satisfaction with their family and friends.

People with MS report lower levels of general health status and more impairment than those with other disabling conditions. Higher levels of satisfaction with friends and family may reflect psychological adaptation to the illness.

The neuropeptide oxytocin, produced in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, is now understood to function as a neurotransmitter critical for various aspects of social cognition and pro-social behaviour. While patients with Frontotemporal dementia (FTD) display prominent and progressive deficits in such social behaviours, the integrity of these nuclei in FTD is not known.

We conducted a quantitative neuropathologic examination of the SON and PVN from patients with FTLD with TDP-43 proteinopathy, Alzheimer's disease, Lewy body disease and controls to determine whether significant pathologic changes or neuronal loss may contribute to the striking behavioural symptoms of FTD.

Contrary to predictions, we found both nuclei to be free of significant pathologic change (TDP-43) in FTLD. In contrast, tau related pathology was found in the PVN in Alzheimer's disease, and alpha-synuclein pathology in the SON in patients with Lewy body dementia.

These results indicate that the SON and PVN are resistant to FTLD TDP-43 pathology. They also support prior suggestions that the SON is resistant to Alzheimer's disease (AD) related pathology, and extend this to demonstrate SON susceptibility to alpha-synuclein pathology in patients with Lewy body dementia.

To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP).

HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein (PLP1) gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by PLP1 mutations.

The SPG2 locus was investigated by linkage analysis in the family. The PLP1 gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy.

Linkage to SPG2 was established and a G to A mutation (M1R) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein.

We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.

The FRG1-transgenic mouse displays muscle dysfunction and atrophy reminiscent of fascioscapulohumeral muscular dystrophy (FSHD) and could provide a model to determine potential therapeutic interventions.

To determine if FRG1 mice benefit from treatments that improve muscle mass and function, mice were treated with creatine alone (Cr) or in combination with treadmill exercise (CrEX).

The CrEx treatment increased quadriceps weight, mitochondrial content (cytochome c oxidase (COX) activity, COX subunit one and four protein), and induced greater improvements in grip strength and rotarod fall speed. While Cr increased COX subunits one and four protein, no effect on muscle mass or performance was found. Since Cr resulted in no functional improvements, the benefits of CrEx may be mediated by exercise; however, the potential synergistic action of the combined treatment cannot be excluded.

Treatment with CrEx attenuates atrophy and muscle dysfunction associated with FRG1 overexpression. These data suggest exercise and creatine supplementation may benefit individuals with FSHD.

To compare the clinical features of our sero-negative and sero-positive neuromyelitis optica (NMO) patients.

Thirty-nine patients with NMO were recruited and analyzed retrospectively. Serum aquaporin 4 (AQP4) antibody status was determined by a cell-based assay. For the sero-negative patients, cerebrospinal fluid (CSF) and serum samples were re-tested using the cell-based assay and an indirect immunofluorescence assay.

By the cell-based assay, 30 patients (76.92%, 30/39), were positive for AQP4 antibodies in serum and 37 patients (94.9%, 37/39), had a CSF-positive antibody status. Seven NMO patients (17.9%, 7/39) were sero-negative by the cell-based assay but demonstrated positive CSF results. By indirect immunofluorescence, the remaining two patients, who had no AQP4 antibodies in serum or CSF by the cell-based assay, were positive for IgG antibodies in serum, which selectively targeted the central nervous system microvessels, pia, subpia, Virchow-Robin space, kidney, and stomach. There were no significant differences between the sero-positive and sero-negative NMO groups among their demographic and clinical data.

Repeating the test using a different assay or CSF is helpful to clarify whether sero-negative NMO patients do in fact carry AQP4 antibodies.