Alemtuzumab, an anti-CD52 monoclonal antibody, was recently approved for treatment of MS in Canada, having shown to significantly reduce relapses and disability in patients, particularly those who relapsed despite first line treatment. Offsetting its benefit however, is the development of novel secondary autoimmune disease, particularly affecting the thyroid gland in up to 36% of patients. The incidence of Alemtuzumab induced thyroid dysfunction (AITD) will likely rise as alemtuzumab becomes more widely used for treating MS. We review the clinical and investigational cues that help delineate the aetiology and management of thyrotoxicosis and hypothyroidism in ATID. AITD can be easily managed and we present a simple approach for its evaluation and management by neurologists that should be implemented prior to considering a referral to an internist or endocrinologist for further opinion or treatment.

Background: There is strong evidence that clinical outcomes are improved for stroke patients admitted to specialized Stroke Units. The Toronto Western Hospital (TWH) created a Neurovascular Unit (NVU) using resources from General Internal Medicine, Neurology, and Neurosurgery for patients with stroke and acute neurovascular conditions. Under resource-constrained conditions, the operational and economic impacts of the Neurovascular Unit were unknown. Methods: Retrospective patient-level data was studied from two years prior and one year post NVU implementation. Descriptive statistical analysis and non-parametric testing were conducted on the acute length of stay (LOS), alternate level of care LOS, total cost per bed-day and per visit, and patient flow within each medical service and hospital wide. Results: The median acute LOS per hospitalization for NVU-eligible patients decreased significantly (p=0.001). For Neurology patients, mean acute LOS decreased from 9.1 days pre-Neurovascular Unit to 7.6 days post and median acute LOS decreased from 6 to 5 days (p=0.002); however, mean alternate level of care LOS per visit more than doubled (from 1.6 to 4.1 days, p=0.001). For the Neurology service, the mean cost per visit decreased by $945, representing a 5% reduction (p=0.042) and the mean cost per bed-day decreased by $233, or 12.5% (p=0.026). Hospital wide, a saving of over C$450 000 was achieved. Conclusions: During the first year of operation, the NVU at TWH achieved decreased acute LOS per visit and lowered the total hospitalization cost per year for NVU-eligible patients. Addressing the issue of increased alternate level of care LOS could result in additional efficiencies.

Background: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. Materials and Methods: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. Results: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). Conclusions: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

Background: Intensive care unit (ICU) patients with neurological impairments often require neuroimaging. However, the relative sensitivity of various imaging modalities of the brain has not yet been explored in this population. Methods: In this study, we compare the findings of CT and MRI scans in ICU patients to (1) identify the number and rate of clinically relevant lesion detected by MRI while missed by CT and vice versa and (2) determine specific lesion types for which CT versus MRI discrepancies exist. A review of medical records included CT and MRI reports of patients who underwent these procedures while they were patients in our ICUs between July 2004 and July 2009. MRI and CT were compared regarding their ability to detect clinically relevant abnormalities. Odds ratios with 95% confidence limits were calculated to compare diagnostic categories regarding the rate of discrepant MRI versus CT findings, followed by power analyses to estimate sample sizes necessary to allow for further testing in a larger trial. Results: MRI revealed clinically relevant additional abnormalities over CT in 129 of 136 patients (95%) that included the detection of additional finding for 15/27 hemorrhagic lesions (55.6%), 33/36 (92%) ischemic strokes, 19/27 (70%) traumatic lesions, 8/14 (57%) infections, 15/24 (62.5%) metabolic abnormalities, and all seven neoplasms. Odds ratio analysis revealed the added sensitivity of MRI to be greater for ischemic and neoplastic lesions than for trauma, metabolic-related abnormalities, infection, or hemorrhage. Conclusions: MRI is more sensitive than CT in identifying clinically meaningful lesions in at least a subset of ICU patients, regardless of pathology.

Background: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.