Autonomic alterations as a clinical manifestation of encephalopathy associated with autoimmune thyroid disease.

Encephalopathy associated with autoimmune thyroid disease (EAATD), also known as Hashimoto's encephalopathy, is a rare neurological condition that may occur in patients with clinical or sub-clinical autoimmune thyroid disease. The pathogenesis of EAATD has been not clearly elucidated yet. The diagnostic criteria include neurological or psychiatric symptoms, high levels of anti-thyroid antibodies, and exclusion of other possible causes of encephalopathy. In the large majority of cases, EAATD patients respond to immunosuppressant therapies, in particular to corticosteroids. We report the case of a patient with Hashimoto's thyroiditis and recurrent manifestations of encephalopathy over the previous few years responding to corticosteroid treatment. The patient presented with language and cognitive impairment, ataxia, and neurovegetative/autonomic symptoms. She was euthyroid with mildly raised anti-thyroid peroxidase antibodies. An extensive diagnostic work-up, including electroencephalogram, brain magnetic resonance, hormonal assessment, and an exhaustive panel of antibodies possibly associated with autoimmune encephalopathy, was carried out and excluded other possible etiologies of encephalopathy. The diagnosis of EAATD possibly affecting the hypothalamus and/or the neurovegetative regulatory centers was made and treatment with prednisolone was timely commenced with a dramatic and rapid improvement with progressive normalization of the symptoms. To the best of our knowledge, this is the first report of neurovegetative/autonomic alterations in the setting of EAATD.

A preliminary investigation into the psychometric properties of the Dublin Extrapersonal Neglect Assessment (DENA): A novel screening tool for extrapersonal neglect.

Extrapersonal neglect is one clinical manifestation that can occur following stroke. Existing neglect assessment procedures have been criticised for lengthy administration and do not assess how extrapersonal space is affected. This study investigated the psychometric properties of a new, time-efficient screening tool for extrapersonal neglect. Full ethical approval was granted and consent obtained from 50 participants with first-time stroke. Participants were screened for extrapersonal neglect on two consecutive days by two raters using the Dublin Extrapersonal Neglect Assessment (DENA) to test inter-rater reliability. Construct validity of the DENA was investigated by comparing the DENA to the Catherine Bergego Scale (CBS). Additional analyses were calculated between the DENA and the extrapersonal items of the CBS (CBS-E). The kappa statistic, intraclass correlation coefficients (ICCs) and Bland Altman analyses were calculated to determine excellent inter-rater reliability (ICC 0.971, κ = .876) and significant correlation between the DENA and the CBS and CBS-E (ICC 0.870, 0.934, κ = .793, .833, respectively). Bland Altman analyses demonstrated acceptable levels of agreement between the DENA raters, and the DENA and CBS, with no systematic differences evident. The DENA provides clinicians with a quick and psychometrically sound screening tool for extrapersonal neglect to ensure this impairment is addressed in stroke rehabilitation.

Rates, Predictors, and Outcomes of Early and Late Recurrence After Stroke: The North Dublin Population Stroke Study.

BACKGROUND AND PURPOSE: Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population-based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). METHODS: Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. RESULTS: Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype (P<0.001). On multivariable Cox regression, hyperlipidemia (adjusted hazard ratio, 3.32; P=0.005) and prior stroke (adjusted hazard ratio, 2.92; P=0.01) were independent predictors of 2-year recurrence in 28-day survivors. CONCLUSIONS: Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Closing the tau loop: the missing tau mutation.

Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem-loop model was first proposed and no mutations have been found within the 'loop' region as expected. Therefore we 'close the tau loop' having 'opened the loop' 21 years ago.

Rates and Determinants of 5-Year Outcomes After Atrial Fibrillation-Related Stroke: A Population Study.

BACKGROUND AND PURPOSE: Demographic trends in atrial fibrillation (AF) incidence may yield a substantial rise in the societal burden of AF-related stroke (AF-stroke). Accurate population-wide outcome data are essential to inform health service planning to improve AF-stroke prevention, and provision of rehabilitation, nursing home, and community supports for AF-stroke survivors. METHODS: We investigated rates and determinants of 5-year fatality, stroke recurrence, functional outcomes, and prescribing of secondary prevention medications in AF-stroke in the North Dublin Population Stroke Study. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using lifetables and Kaplan-Meier survival curves, and Cox proportional hazard modeling was performed to identify predictors of death and recurrent stroke. RESULTS: Five hundred sixty-eight patients with new stroke were identified, including 177 (31.2%) AF-stroke. At 5 years, 39.2% (confidence interval, 31.5-46.8) of ischemic AF-stroke patients were alive. Congestive heart failure, hypertension, age <65, 65-74 years, and ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease and female sex (CHA2DS2-VASc) score (hazard ratio [HR], 1.34; P<0.001), CHADS2 score (HR 1.42, P=0.004), National Institute of Health Stroke Scale (HR, 1.09; P<0.0001), and subtherapeutic international normalized ratio (<2.0) at stroke onset (HR, 3.29; P=0.003) were independently associated with 5-year fatality, whereas warfarin (HR, 0.40; P=0.001) and statin use after index stroke (HR, 0.52; P=0.005) were associated with improved survival. The 5-year recurrence rate after ischemic AF-stroke was 21.5% (confidence interval, 14.5-31.3). Trends toward greater risk of recurrence were observed for persistent AF (HR, 3.09; P=0.07) and CHA2DS2-VASc score (HR, 1.34; P=0.07). Nursing home care was needed for 25.9% of patients. CONCLUSIONS: AF-stroke is associated with considerable long-term morbidity, fatality, stroke recurrence, and nursing home requirement. Adequately resourced national AF strategies to improve AF detection and prevention are needed.

Subclinical myocardial dysfunction in multiple sclerosis patients remotely treated with mitoxantrone: evidence of persistent diastolic dysfunction.

BACKGROUND: Mitoxantrone is an effective disease-modifying therapy in multiple sclerosis (MS), but its use is limited by cardiotoxicity. We evaluated global myocardial function, including myocardial performance index (MPI), on echocardiography in MS patients after remote mitoxantrone treatment. METHODS AND RESULTS: Consecutive patients (n = 50) treated with standard-protocol mitoxantrone from 2002 to 2010 in our center were identified. After exclusion of those who had died (n = 4; all noncardiac) or had developed interim cardiovascular disease or risk factors (n = 3), 33 (mean age 49 ± 11 years, 45% male, median follow-up 77 months, mean cumulative dose 72 mg/m(2)) of the remaining patients (77%) underwent 2-dimensional echocardiography. A comparison group of 17 age- and sex-matched control subjects were included. No significant differences occurred in standard echocardiographic parameters between groups. However, mean MPI (defined as isovolumic contraction time plus isovolumic relaxation time (IVRT) divided by ejection time) was significantly higher in patients (0.51 ± 0.12 vs 0.39 ± 0.06; P = .02) owing to a significantly prolonged IVRT (81 ± 25 vs 60 ± 9 ms; P = .04). Overall MPI was >0.5 in 18 patients compared with none of the control subjects (54.5% vs 0%; P < .001). CONCLUSIONS: A subclinical form of global myocardial dysfunction reflecting primarily diastolic dysfunction may be present in MS patients after remote standard-dose mitoxantrone treatment.

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

OBJECTIVE: Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. METHODS: Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. RESULTS: Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). INTERPRETATION: In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.

Long-term risk of leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis.

BACKGROUND: Mitoxantrone has been extensively used as a disease-modifying therapy for multiple sclerosis. However, estimates of the associated risk of therapy-related acute leukaemia and cardiomyopathy have been derived from short-term studies. This study aimed to ascertain the long-term risk of therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis. METHODS: Between 2002 and 2010, 50 patients were treated with mitoxantrone at a single centre using a standard protocol (12 mg/m(2) body surface area monthly for 6 months as tolerated to a maximum of 72 mg/m(2) body surface area). Follow-up haematologic and echocardiographic data were collected in March 2011. RESULTS: Fifteen patients (30%) were excluded from analysis either because of lack of follow-up data, death due to non-cardiac and non-haematologic causes, or comorbid cardiovascular disease. The remaining 35 patients (70%) were followed for a median of 75 months (range: 9-103). The median cumulative mitoxantrone dose given was 72 mg/m(2) body surface area (range: 24-123). At the end of follow-up, no patients had developed therapy-related acute leukaemia. One patient suffered an asymptomatic drop in left ventricular ejection fraction from 55 to 47%. CONCLUSION: This series of patients followed for up to 8.5 years suggests that the risk of either therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis is low when patients are treated within standard protocol.

Erysipelothrix rhusiopathiae Prosthetic Joint Infection in an Immunocompromised Patient: A Case Report.

CASE: We report the case of an immunosuppressed 65-year-old man with prosthetic joint infection (PJI) 23 years postoperatively because of Erysipelothrix rhusiopathiae, through hematogenous seeding of cutaneous erysipeloid. Immunotherapy was discontinued, washout was performed, and antimicrobial therapy was guided by laboratory sensitivities. The patient was discharged on suppressive oral ciprofloxacin monotherapy. First-stage revision was performed at 5 months after presentation-subsequent aspiration at 1 year postoperatively demonstrated no organisms and no leucocytes. At 18-month follow-up, the patient continues to do well and has elected not to proceed with second-stage surgery. CONCLUSION: E. rhusiopathiae is a rarely seen pathogen in PJI-it should be considered with immunosuppression and relevant exposure risks. The patient achieved good clinical outcome and has experienced no sequelae to date.

Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation.

Two siblings who developed fifth-decade-onset, concurrent progressive sensory ataxia, dysarthria, and ophthalmoparesis were found to be homozygous for the p.A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability. The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation.

Percutaneous vascular interventions for acute ischaemic stroke.

BACKGROUND: Most disabling strokes are due to blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called percutaneous vascular interventions can cause bleeding in the brain. OBJECTIVES: To assess the safety and efficacy of percutaneous vascular interventions in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Trials Registers of the Cochrane Stroke Group and Cochrane Peripheral Vascular Diseases Group (last searched May 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 5), MEDLINE (1980 to May 2010), EMBASE (1980 to May 2010) and eight additional databases. We also searched trials registers, screened reference lists, contacted researchers and equipment manufacturers, and handsearched journals and conference proceedings. SELECTION CRITERIA: Randomised, controlled and unconfounded trials of any percutaneous vascular intervention compared with control in patients with definite ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We obtained both published and unpublished data if available MAIN RESULTS: We included four trials involving 350 patients. Not all trials contributed data to each outcome. The trials tested either intra-arterial urokinase or recombinant pro-urokinase versus an open control. One trial used guidewire-mediated clot disruption in some patients randomised to the intervention group. Most data came from trials that started treatment up to six hours after stroke; one small trial started treatment up to a median of 12.5 hours after stroke. Most data came from trials of middle cerebral artery territory infarction. Compared with non-thrombolytic standard medical treatment, the intervention administered up to six hours after ischaemic stroke significantly increased the proportion of patients with favourable outcome (modified Rankin 0 to 2) three months after stroke (relative risk (RR) 1.47, 95% confidence interval (CI) 1.07 to 2.02). The intervention also significantly increased the risk of symptomatic intracranial haemorrhage within 24 hours of treatment (RR 3.85, 95% CI 0.91 to 16.36). There was no significant heterogeneity between the included trials. AUTHORS' CONCLUSIONS: Overall, intervention results in a significant increase in the proportion of patients with a favourable outcome, despite a significant increase in intracranial haemorrhage. Further trials are needed to confirm or refute these findings and, given the cost and practical difficulties, to establish whether percutaneous techniques are feasible and cost effective in wider clinical practice.

A systematic review of treatments for post-traumatic stress disorder among refugees and asylum-seekers.

Recent years have seen a consensus emerge on the treatment of post-traumatic stress disorder (PTSD) in the general population. No such consensus exists for refugees, although the rate of PTSD among refugees is 10 times that of the general population. We conducted a systematic review of randomized controlled trial of treatment of PTSD among refugees and asylum-seekers. We rated trials with a risk of bias table and drew conclusions about the evidence for individual therapies. Ten randomized, controlled trials (n = 528) met our search criteria. Trials were small, and allocation concealment and blinding were inadequate. No treatment was firmly supported, but there was evidence for narrative exposure therapy and cognitive-behavioral therapy. Future trials should evaluate interventions that are developed within refugees' cultures, based on a local understanding of trauma and psychological distress.

Safety and efficacy of IV-TPA for ischaemic stroke in clinical practice--a Bayesian analysis.

BACKGROUND: Observational studies of new treatments in routine practice are clinically important but may be limited by bias. We used a Bayesian approach to interpret and sequentially combine phase 4 studies of IV-TPA within 3 h for acute ischaemic stroke to quantify the cumulative evidence for the efficacy and safety of this therapy in clinical practice. METHODS: Prior probability distributions for favourable outcome (modified Rankin Score, mRS, 0-1), symptomatic intracerebral haemorrhage, and mortality 3 months after IV-TPA were derived from the NINDS trial. Phase 4 studies from observational case series and from regulator-mandated large registries were included. A cumulative analysis was performed to quantify the increase in the total evidence base over time, unadjusted and adjusted for potential bias. RESULTS: The cumulative analysis indicated that IV-TPA <3 h was associated with 3-month favourable outcome in 37.1% (95% credible interval, CrI, 36.1-38.0%, n = 9,578) compared to 26% (95% confidence interval, CI, 19.6-32.9%, n = 165) in placebo-treated patients in NINDS, symptomatic intracranial haemorrhage in 6.6% (95% CrI 5.9-7.4%, n = 10, 834) compared to 6.4% (95% CI 4.0-9.4%) in the NINDS IV-TPA group, and 3-month mortality in 13.6% (95% CrI 12.6-14.8%, n = 9, 901) compared to 20.5% (95% CI 16.0-25.0%, n = 312) in the NINDS placebo group. CONCLUSION: A Bayesian approach provides further confirmatory evidence of the efficacy and safety of IV-TPA for treatment of acute ischaemic stroke within 3 h in diverse clinical practice settings, after adjusting for potential observational bias.

Societal costs of multiple sclerosis in Ireland.

AIMS: This paper evaluates the impact of multiple sclerosis (MS) in Ireland, and estimates the associated direct, indirect, and intangible costs to society based on a large nationally representative sample. MATERIALS AND METHODS: A questionnaire was developed to capture the demographics, disease characteristics, healthcare use, informal care, employment, and wellbeing. Referencing international studies, standardized survey instruments were included (e.g. CSRI, MFIS-5, EQ-5D) or adapted (EDSS) for inclusion in an online survey platform. Recruitment was directed at people with MS via the MS Society mailing list and social media platforms, as well as in traditional media. The economic costing was primarily conducted using a 'bottom-up' methodology, and national estimates were achieved using 'prevalence-based' extrapolation. RESULTS: A total of 594 people completed the survey in full. The sample had geographic, disease, and demographic characteristics indicating good representativeness. At an individual level, average societal cost was estimated at €47,683; the average annual costs for those with mild, moderate, and severe MS were calculated as €34,942, €57,857, and €100,554, respectively. For a total Irish MS population of 9,000, the total societal costs of MS amounted to €429m. Direct costs accounted for just 30% of the total societal costs, indirect costs amounted to 50% of the total, and intangible or QoL costs represented 20%. The societal cost associated with a relapse in the sample is estimated as €2,438. LIMITATIONS AND CONCLUSIONS: The findings highlight that up to 70% of the total costs associated with MS are not routinely counted. These "hidden" costs are higher in Ireland than the rest of Europe, due in part to significantly lower levels of workforce participation, a higher likelihood of permanent workforce withdrawal, and higher levels of informal care needs. The relationship between disease progression and costs emphasize the societal importance of managing and slowing the progression of the illness.

The patient knows best: significant change in the physical component of the Multiple Sclerosis Impact Scale (MSIS-29 physical).

AIM: The aims of this study were to determine the reliability, responsiveness and minimally important change score of the Multiple Sclerosis Impact Scale (MSIS)-29 physical using the Expanded Disability Status Scale (EDSS) as an anchor measure. METHODS: 214 patients with multiple sclerosis (MS) (EDSS 0-8.5) had concurrent MSIS-29 and EDSS assessments at baseline and at up to 4 years of follow-up. RESULTS: 116 patients had unchanged EDSS scores. Stability of the MSIS-29 physical (mean change 0.1 points) was better in the 85 patients with EDSS 0-5.0 than in the 31 patients with EDSS 5.5-8.5 in whom the MSIS-29 physical score fell by 8 points, a response shift phenomenon. A floor effect for the MSIS-29 was observed in 5% of stable patients at both time points. 98 patients experienced EDSS change with moderately strong statistically significant correlations between change scores in the EDSS and the MSIS-29 physical (r = 0.523, p<0.0001). Effect sizes for MSIS-29 physical change were moderate to large. Using receiver operating characteristic curves, the MSIS-29 change score which produced a combination of optimal sensitivity and specificity was chosen for both EDSS ranges. For EDSS range 5.5-8, a change score of 8 had a sensitivity of 87% and specificity of 67%. For EDSS 0-5.0, a change score of 7 had a sensitivity of 78% and a specificity of 51%. CONCLUSIONS: The MSIS-29 physical performs well over time, and is suitable for use in trials; a minimal change score of 8 points in the MSIS-29 is clinically significant.

Outcome of beta-interferon treatment in relapsing-remitting multiple sclerosis: a Bayesian analysis.

Observational studies of the effect of beta-interferon (IFNbeta) on accumulation of fixed disability in relapsing remitting multiple sclerosis (RRMS) in clinical practice have been difficult to interpret due to bias. The aim of this study of 175 RRMS patients was to use Bayesian analysis to establish whether IFNbeta attenuates disability relative to a cohort of matched historical control subjects from the Sylvia Lawry Centre for MS Research. A sensitivity analysis was based on a range of prior probability distributions for IFNbeta efficacy derived from a published meta-analysis of randomised controlled trials (RCTs) of IFNbeta, and the data were interpreted both unmodified and using variance inflation and point estimate bias correction; the corrected data interpreted in the light of the most likely prior probability distribution yielded a 95 % posterior credible interval for the odds ratio of accumulation of fixed disability after two years of IFNbeta therapy of 0.52, 0.94. It is concluded that two years of IFNbeta therapy for RRMS reduces accumulation of fixed disability in clinical practice.

Why do transient ischemic attack patients have higher early stroke recurrence risk than those with ischemic stroke? Influence of patient behavior and other risk factors in the North Dublin Population Stroke Study.

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.

Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial.

BACKGROUND: Lowserum vitamin D levels are associated with susceptibility to, and severity of, multiple sclerosis. High dose vitamin D has been proposed as a potential immunomodulator in multiple sclerosis. OBJECTIVES: We performed a single centre, investigator-led, exploratory, double-blind, randomised, placebo controlled, trial of vitamin D3 in clinically isolated syndrome and healthy control participants to assess its immunological effects. Secondary end-points included clinical and magnetic resonance imaging outcomes and safety. METHODS: Clinically isolated syndrome patients and healthy control participants were randomised to: placebo, 5000 IU or 10,000 IU vitamin D3/day (Vigantol oil). Study duration was 24 weeks. RESULTS: The trial did not meet its primary end point, with no difference in the frequency of pro-inflammatory CD4+ T cells (interleukin (IL)-17+/interferon (IFN)-γ+) seen. A higher level of disease freedom (67% versus 50%) was seen in those with serum 1,25 (OH) vitamin D levels>100 nmol/l but this did not reach significance. High dose vitamin D3 was well tolerated with no safety signal. CONCLUSIONS: High dose vitamin D3 over 24 weeks was well tolerated but without immunological, magnetic resonance imaging or clinical evidence of benefit. The hypothesised therapeutic effects in clinically isolated syndrome or multiple sclerosis patients may require longer periods of administration or may only be seen in patients treated with vitamin D3 as an adjunct to established disease modifying therapies.

Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.