Cross-sectional research has demonstrated poorer function and health-related quality of life (HRQOL) in those with multiple sclerosis (MS) but less is known about change over time. The goals of this study were to measure change in HRQOL and identify factors associated with change.

HRQOL was assessed at baseline and annually over two subsequent years using the Multiple Sclerosis Quality of Life Inventory. Function was assessed using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite. Annualized rate of change was calculated for all twenty outcomes. Mixed effects modeling (univariate followed by multivariate) was used to examine the associations among patient characteristics and the age- and sex-adjusted Physical Component Summary (PCS) and Mental Component Summary (MCS) at study initiation and over the two years of follow-up.

Of 300 participants, 288 (96%) provided at least one assessment and are included in this analysis. Although 14 of the 20 outcomes showed a mean decline, only two (SF-36 physical function, p=0.018 and the EDSS, p<0.001) were statistically significant. The SF-36 social function showed a significant improvement (p=0.031). Only two variables were significantly associated with a decreased rate of decline or improvement over two years, including being female (PCS, p=0.001) and use of visiting nurse services (MCS, p<0.001).

HRQOL is relatively stable over two years of follow-up, particularly for mentally-oriented outcomes. Further research with a longer period of follow-up is needed to provide additional insight into factors associated with change in HRQOL in patients with MS.

(1) To examine the variability in diagnosis of mild traumatic brain injury (mTBI) in primary care relative to that of an expert reviewer; and (2) to determine the incidence rate of mTBI in Ontario, Canada.

Potential mTBI cases were identified through reviewing three months of Emergency Department (ED) and Family Physician (FP) health records. Potential cases were selected from ED records using the International Classification of Disease, 9th revision, Clinical Modification and External Cause codes and from all FPs records for the time period. Documented diagnoses of mTBI were compared to expert reviewer diagnosis. Incidence of mTBI was determined using the documented diagnoses and data from hospital catchment areas and population census.

876 potential mTBI cases were identified, 25 from FP records. Key indicators of mTBI were missing on many records (e.g., 308/876 records had Glasgow Coma Scale (GCS) scores). The expert reviewer disagreed with the documented diagnosis in 380/876 cases (kappa=0.19). The expert reviewer was more likely to give a diagnosis if the GCS was 13-14, if there was documented loss of consciousness and/or post-traumatic amnesia, and/or if there was pathology found on an acute brain scan. Calculated incidence rates of hospital-treated mTBI were 426 or 535/100,000 (expert review - hospital diagnosis). Including family physician cases increased the rate to 493 or 653/100,000.

Health record documentation of key indicators for mTBI is often lacking. Notwithstanding, some patients with mTBI appear to be missed or misdiagnosed by primary care physicians. A more comprehensive case definition resulted in estimated incidence rates higher than previous reports.

To evaluate the incidence of hypoglycemia, hyperglycemia and blood glucose (BG) variability in brain-injured patients and their association with clinical outcomes.

Retrospective cohort study of brain-injured patients admitted to an 11- bed neurosciences intensive care unit (ICU) from January 1 to December 31, 2003.

We included 606 patients. Mean age was 52.3 years, 60.6% were male, 11.9% had diabetes mellitus, and 64% were post-operative. Seventy-five (12.4%) received intensive insulin therapy (IIT) for a median (IQR) 72 (24-154) hours. Hypoglycemia and hyperglycemia occurred in 4.6% (96.4% receiving IIT) and 9.6% (77.6% receiving IIT). Median number of episodes per patient was 3 (75% with ≥2) and 4 (81% with ≥2) for hypoglycemia and hyperglycemia. Variable glycemic control occurred in 3.8% (100% receiving IIT) with median number of 13 episodes per patient. In-hospital mortality was 16.7%, median (IQR) ICU and hospital lengths of stay were 2 (1-5) and 8 (3-19) days. Hypoglycemia, hyperglycemia and BG variability showed non-significant but consistent associations with hospital mortality and prolonged lengths of ICU and hospital stay. The rate of recurrence of episodes showed stronger and significant associations with outcome, in particular for BG variability and hyperglycemia.

Hypoglycemia, hyperglycemia and BG variability are relatively common in brain-injured patients and are associated with IIT. An increased frequency of episodes, in particular for BG variability and hyperglycemia, was associated with greater risk of both hospital death and prolonged duration of stay.

Gait apraxia is a gait disorder not attributable to motor, cerebellar, or sensory dysfunction. Gait impairment is common in Multiple Sclerosis (MS), but is mostly attributed to spasticity and ataxia. Impairment ratings scales are designed accordingly and do not separately evaluate apraxia.

To describe 15 patients with gait apraxia resulting from MS as their major functional impairment.

The Mayo Clinic database (1994-2007) was searched for the terms MS and gait apraxia. Inclusion criteria: Definite MS, significant gait apraxia. Exclusion criteria: alternative disorder causing apraxia, predominantly spastic/ataxic gait disorder.

9 (60%) of the patients were women, and 12 (80%) had a progressive MS course. Gait apraxia was evident at a median of 8 years (range 0-34) following MS onset. Median EDSS at recognition of gait apraxia was 6.5 (range 5-8). Cognitive dysfunction was present in 11 (73%) and neurogenic bladder dysfunction in 14 (93%). The commonest MRI findings were confluent periventricular T2 lesions, T1 hypointensity and generalized cerebral atrophy with symmetrical ex vacuo ventricular enlargement.

Gait apraxia can cause significant functional impairment in MS patients, and may be underrecognized. The natural course of the neurological deficit in such patients is unknown, and may differ from that of MS patients with other ambulatory disabilities.

The angiotensin-1 converting enzyme (ACE) gene is known to have two polymorphic alleles insertion/deletion(I/D). People with the DD genotype have been shown to be at greater risk of cerebral infarction, but only in some studies. Identification of cerebral infarction susceptibility genes and quantification of associated risks have been hampered by conflicting results from underpowered case-control studies. This meta-analysis was made to look specifically into the genetics of cerebral infarction among Han Chinese population.

Genetic associations studies published from January 1, 1990 to December 30, 2007 were collected from databases of MEDLINE, EMBASE, CBM and CNKI. Data were extracted using standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Twenty-nine original case-control studies of Han Chinese population, comprising 3654 patients with cerebral infarction and 3058 controls were included in the meta-analysis. Using the random effects model, the pooled ORs of ACE DD genotype VS ID+ II was 1.91 (95% CI 1.56 to 2.34, P<0.00001).

These data suggest that the ACE DD genotype may be a risk factor for cerebral infarction in Han Chinese population. A large scale case-control study is needed to clarify the functional effect of the polymorphism of the ACE I/D gene in the pathogenesis of cerebral infarction in Han Chinese population.

We studied α-B-crystallin, a small heat shock chaperone protein upregulated by various “stresses”, as an immunocytochemical tissue marker of epileptic foci.

We examined 45 resected brain tissues of epileptic patients, 16 months to 23 years. Postmortem brains of 2 epileptic children and 20 normal fetuses and neonates of 10-41 weeks gestation similarly were studied. Immunocytochemical demonstration of α-B-crystallin was supplemented by neuronal, glial and inflammatory cell markers and electron microscopy (EM) in surgical cases. Autopsy brain tissue of children without epilepsy or neurological disease served as controls.

In all resections, α-B-crystallin was overexpressed in astrocytes and oligodendrocytes, including satellite cells adherent to neurons, and occasionally in neurons of neocortex, hippocampus and amygdala. In six cases, reactivity was most intense at or near the epileptic focus, with a diminishing gradient of intensity for 2-3 cm; similar focal expression was seen in autopsy cases. Presence or absence of histological structural lesions was independent of α-B-crystallin expression. Balloon cells and giant atypical cells in tuberous sclerosis were intensely reactive. Reactivity was present in DNETs. No correlation occurred with microglial activation, inflammation or gliosis; no ultrastructural alterations were seen. No expression was seen in fetal brains at any age.

Immunoreactive α-B-crystallin is a reliable tissue marker of epileptic foci, regardless of presence or absence of structural lesions; at times it maps the extent of a focus.

We examined the effects of various exercise intensities on recovery from middle cerebral artery occlusion (MCAO) in rats.

First, we administered a 120-minute left MCAO to male Sprague-Dawley rats and randomly assigned them to one of four groups: no exercise (Group 1), mild exercise (Group 2), moderate exercise (Group 3), and severe exercise (Group 4). Then, we trained the rats for 30 min per day for one week or two weeks. We used a five-point neurological evaluation scale to measure neurological deficits 1-day, 4-days, 7-days, 10-days and 14-days after MCAO and measured infarct volume by use of 2% 2,3,4-triphenyltetrazolium chloride in exercised brains. We also performed immunohistochemistry analysis of the brain to observe reactive astrocytosis at the peri-infarct region.

Neurological examination indicated that Group 2 and 3 recovered better than Group 1 after one week and two weeks (p<0.05). Moreover, Group 2 and 3 had reduced brain infarct volume compared with Group 1 after one week (p<0.05). There were no significant differences between Group 4 and Group 1. The thickness of the peri-infarct astrocytosis was significantly reduced in Group 4 relative to Group 1 after one week. There was a significant negative correlation between the extent of reactive astrocytosis and neurological recovery (r= -0.648, p<0.01).

This study demonstrates that mild to moderate exercise that begins soon after induced cerebral ischemia promotes recovery and that astrocytes may have an important role in the recovery process.