Search

Objectives We aimed to develop and internally validate a measure of multimorbidity burden using data from the Canadian Longitudinal Study on Aging (CLSA). Design Data from 40 264 CLSA participants (52% men) aged 45–85 years (a mean of 63 years) were analysed. We used logistic regression models to predict overnight hospitalisation in the last 12 months in the development dataset (random two-thirds of the total) and used these to construct 10 multimorbidity indices (5 models, each treated with and without an age interaction term). Thirty-five chronic conditions were considered for inclusion in these models, in addition to age and sex. We assessed predictive and convergent validity for these 10 different multimorbidity indices in the validation dataset (remaining one-third of the total). Results The absolute count of chronic conditions plus an interaction with age, displayed strong calibration properties, outperforming other candidate indices. Discrimination was modest for all of the indices that we internally validated, with C-statistics ranging from 0.66 to 0.68. The indices showed weak correlations (ie, convergent validity) with satisfaction with life, functional disability and mental health (absolute Pearson’s correlation coefficients ranging from 0.11 to 0.30) but generally moderate correlations with self-rated general health (0.32–0.45). Conclusions We investigated alternative methods to measure the multimorbidity burden of individuals, tailored to the CLSA. Our findings show that an absolute count of conditions, along with an age interaction term, has the strongest calibration for overnight hospitalisation in the last 12 months. The utility of an age interaction term in measuring multimorbidity burden may be applicable to the study of chronic disease in cohorts other than the CLSA. [ABSTRACT FROM AUTHOR]

Background and purpose: Our objective was to study the association between the presence of a neurological disease and the comorbidity burden as well as healthcare utilization (HCU). Methods: Using baseline data from the Canadian Longitudinal Study on Aging (CLSA), we examined the burden of five neurological conditions. The CLSA is a population‐based study of approximately 50 000 individuals, aged 45–85 years at baseline. We used multivariable Poisson regression to identify correlates of comorbidity burden and HCU. Results: The lifetime prevalence of five neurological diseases is presented: epilepsy, Parkinson's disease/parkinsonism, stroke/transient ischaemic attack, multiple sclerosis and migraine. We found the somatic and psychiatric comorbidity burden to be higher in those individuals with a neurological disease (an 18–45% mean increase in the number of chronic conditions) as compared with the comparison group without a neurological disease, except for Parkinson's disease/parkinsonism. The presence of a neurological disease was associated with only a modest increase in the probability of visiting a general practitioner but was associated with a greatly increased probability of visiting a medical specialist (up to 68% more likely) or an emergency department (up to 79% more likely) and an overnight hospitalization (up to 108% more likely). Conclusions: We found striking associations between our neurological diseases and increased comorbidity burdens and HCU. These findings are important for informing public policy planning as well as driving avenues for future research. The present study established the CLSA as an important research platform for the study of neurological conditions in an aging general population. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia is associated with acute neurological complications during pregnancy, but the subsequent risk of developing a neurological disorder is unclear. We determined if preeclampsia was associated with the long-term risk of neurological morbidity., Methods: We conducted a longitudinal cohort study of 1,460,098 pregnant women with and without preeclampsia in Quebec, Canada, between 1989 and 2023. The main exposure measure was preeclampsia diagnosed in any pregnancy. Outcomes included hospitalization for cerebrovascular disease, epilepsy, and other neurological disorders up to three decades after pregnancy. Using Cox regression models adjusted for confounders, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between preeclampsia and neurological disorders during 27,659,555 person-years of follow-up., Results: There were 1,460,098 women in the cohort, including 73,890 (5.1%) with preeclampsia. Women with preeclampsia had a higher incidence of neurological disorders than women without preeclampsia (113.2 vs. 79.3 per 100,000 person-years). Compared with no preeclampsia, preeclampsia was associated with 1.49 times the risk of later neurological hospitalization (95% CI 1.41-1.57). Preeclampsia was primarily associated with cerebrovascular disease (HR 1.89, 95% CI 1.76-2.03) and epilepsy (HR 1.39, 95% CI 1.24-1.57). A link with other neuropathology was less apparent, although severe preeclampsia was associated with neurodegenerative disorders. Severe hypertension, including early onset (HR 2.35, 95% CI 2.06-2.68), recurrent (HR 2.47, 95% CI 2.13-2.86), and superimposed preeclampsia (HR 2.60, 95% CI 2.17-3.12), was more strongly associated with neurological hospitalization overall., Conclusion: Preeclampsia is associated with the long-term risk of developing cerebrovascular disease and epilepsy, but associations with other neurological disorders are less prominent., (The Author(s). Published by S. Karger AG, Basel.)

Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To report the current elastography methods used to quantify back muscles' biomechanical characteristics in patients with musculoskeletal disorders (MSKd) and inform on their reliability, validity, and responsiveness., Methods: MEDLINE, Embase, CINAHL, Cochrane library and grey literature were consulted. Predefined criteria allowed for study selection and data extraction. The quality of evidence was rated using the COSMIN tool. Data were meta-analyzed in terms of pooled intraclass correlation coefficient (pICC) for reliability and pooled standardized mean difference (pSMD) for validity and responsiveness. Heterogeneity was assessed., Results: Seventy-nine studies were included in the meta-analysis (total number of participants N = 3178). Three elastography methods were identified: strain imaging (SI; number of cohorts M = 26), shear wave imaging (SWI; M = 50), and vibration sonoelastography (VSE; M = 3). Strain imaging and SWI studies reported good reliability measurement properties (pICC > 0.70) and a medium pSMD (0.58 for SI and 0.60 for SWI; p ≤ 0.020) in discriminating MSKd from controls' condition (validity). Strain imaging studies reported a medium pSMD (0.64; p = 0.005) in detecting within-group changes over time, whereas SWI pSMD was very high (1.24; p = 0.005). Only SWI reported significant but small pSMD (0.30; p = 0.003) in detecting between-group changes over time. The small number of VSE studies could not be meta-analyzed. Heterogeneity was high (I-squared > 90%; p < 0.001)., Conclusions: Elastography presents good reliability results and a medium pSMD in discriminating MSKd from control conditions. Responsiveness data suggest detectable changes within groups over time using SI and SWI, calling for long-term longitudinal studies. Assessing changes between groups over time using elastography still needs to be proven. Highly significant heterogeneity limits meta-analytic results., Critical Relevance Statement: While still in its early-stage exploration phase, musculoskeletal ultrasound elastography may reliably quantify back muscles' biomechanics in asymptomatic individuals, moderately discriminate back musculoskeletal disorders and detect biomechanical changes over time in these conditions, calling for long-term longitudinal studies., Key Points: Ultrasound elastography is reviewed for back pain and related musculoskeletal disorder assessments. Growing literature supports good reproducibility, some validity and responsiveness. Back muscle elastography considers assumptions calling for standardized protocols., (© 2024. The Author(s).)

Introduction: Hypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A variety of surgical approaches and technologies are available for the treatment of HH-related pharmacoresistant epilepsy. There remains, however, a paucity of literature directly comparing their relative efficacy and safety. This protocol aims to facilitate a systematic review and meta-analysis that will characterise and compare the probability of seizure freedom and relevant postoperative complications across different surgical techniques performed for the treatment of HH-related pharmacoresistant epilepsy., Methods and Analysis: This protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data guidelines. Three major databases, PubMed, Embase and Scopus, will be systematically searched from database inception and without language restrictions for relevant articles using our predefined search strategy. Title-abstract and full text screening using inclusion and exclusion criteria created a priori will be performed by two independent reviewers to identify eligible articles. Conflicts will be resolved via discussion with a third team member. Following data extraction of both study-level and individual patient data (IPD), a study-level and IPD meta-analysis will be performed. Study-level analysis will focus on assessing the degree of heterogeneity in the data and quantifying overall seizure outcomes for each surgical technique. The IPD analysis will use multivariable regression to determine perioperative predictors of seizure freedom and complications that can guide patient and technique selection., Ethics and Dissemination: This work will not require ethics approval as it will be solely based on previously published and available data. The results of this review will be shared via conference presentation and submission to peer-reviewed neurosurgical journals., Prospero Registration: CRD42022378876., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We evaluated the effectiveness and tolerability of brivaracetam (BRV), an adjunctive antiseizure medication, as a treatment for focal epilepsy in adults. In this prospective study, we enrolled 51 participants from 3 sites across Canada. At 6 months, 68% (26/38) of participants were still taking BRV, among whom 35% (8/23) attained seizure freedom and 48% (11/23) saw their seizure frequency reduced by over 50%. We did not measure any significant change in irritability, quality of life, depression, and anxiety while treated with BRV. Our findings suggest BRV is effective in reducing seizure frequency among adults with focal epilepsy.

Background: Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic performances of computed biomarkers for epilepsy in individuals undergoing rEEG., Methods: We searched MEDLINE, EMBASE, EBM reviews, IEEE Explore and the grey literature for studies published between January 1961 and December 2022. We included studies reporting a computational method to diagnose epilepsy based on rEEG without relying on the identification of interictal epileptiform discharges or seizures. Diagnosis of epilepsy as per a treating physician was the reference standard. We assessed the risk of bias using an adapted QUADAS-2 tool., Results: We screened 10 166 studies, and 37 were included. The sample size ranged from 8 to 192 (mean=54). The computed biomarkers were based on linear (43%), non-linear (27%), connectivity (38%), and convolutional neural networks (10%) models. The risk of bias was high or unclear in all studies, more commonly from spectrum effect and data leakage. Diagnostic accuracy ranged between 64% and 100%. We observed high methodological heterogeneity, preventing pooling of accuracy measures., Conclusion: The current literature provides insufficient evidence to reliably assess the diagnostic yield of computational analysis of rEEG., Significance: We provide guidelines regarding patient selection, reference standard, algorithms, and performance validation., Competing Interests: ÉL is supported by a scholarship from the Canadian Institute of Health Research (CIHR). BR wishes to acknowledge financial support from the Centre for Clinical Brain Sciences of the University of Edinburgh, the CIHR, the Fonds de recherche du Québec—Santé (FRQS) and the Ministère de la Santé et des Services sociaux du Québec, and the Power Corporation of Canada Chair in Neurosciences of the University of Montreal. MRK and DKN report unrestricted educational grants from UCB and Eisai, and research grants for investigator-initiated studies from UCB and Eisai. DKN and FL are supported by the Canada Research Chairs Program, the Canadian Institutes of Health Research, and Natural Sciences and Engineering Research Council of Canada. OG is supported by the Institute for Data Valorization (IVADO). EBA is supported by IVADO (51628), the CHUM research center (51616), and the Brain Canada Foundation (76097). Funding sources had no role in the design or conduct of the study., (© 2023 The Authors.)

On June 24, 2022, Dobbs vs Jackson Women's Health Organization was decided by the Supreme Court effectively overturning the former precedent of Roe v. Wade . This ruling has direct consequences for the care of persons with epilepsy of childbearing potential. Now more than ever we need to provide informed and comprehensive care to our patients with epilepsy who are particularly vulnerable to the impact of this legislation on their reproductive decision-making. Important areas to understand include (1) the current state of affairs on abortion in the United States; (2) contraception options, their effectiveness, and interactions with anti-seizure medications (ASM); (3) teratogenic effects and adverse neurocognitive outcomes of ASMs; (4) folic acid supplementation; (5) the effect on perinatal and pediatric care; and (6) unique issues related to people of color., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: The diagnosis of epilepsy frequently relies on the visual interpretation of the electroencephalogram (EEG) by a neurologist. The hallmark of epilepsy on EEG is the interictal epileptiform discharge (IED). This marker lacks sensitivity: it is only captured in a small percentage of 30 min routine EEGs in patients with epilepsy. In the past three decades, there has been growing interest in the use of computational methods to analyse the EEG without relying on the detection of IEDs, but none have made it to the clinical practice. We aim to review the diagnostic accuracy of quantitative methods applied to ambulatory EEG analysis to guide the diagnosis and management of epilepsy., Methods and Analysis: The protocol complies with the recommendations for systematic reviews of diagnostic test accuracy by Cochrane. We will search MEDLINE, EMBASE, EBM reviews, IEEE Explore along with grey literature for articles, conference papers and conference abstracts published after 1961. We will include observational studies that present a computational method to analyse the EEG for the diagnosis of epilepsy in adults or children without relying on the identification of IEDs or seizures. The reference standard is the diagnosis of epilepsy by a physician. We will report the estimated pooled sensitivity and specificity, and receiver operating characteristic area under the curve (ROC AUC) for each marker. If possible, we will perform a meta-analysis of the sensitivity and specificity and ROC AUC for each individual marker. We will assess the risk of bias using an adapted QUADAS-2 tool. We will also describe the algorithms used for signal processing, feature extraction and predictive modelling, and comment on the reproducibility of the different studies., Ethics and Dissemination: Ethical approval was not required. Findings will be disseminated through peer-reviewed publication and presented at conferences related to this field., Prospero Registration Number: CRD42022292261., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intervention time (IT) in response to seizures and adverse events (AEs) have emerged as key elements in epilepsy monitoring unit (EMU) management. We performed an audit of our EMU, focusing on IT and AEs., Methods: We performed a retrospective study on all clinical seizures of admissions over a 1-year period at our Canadian academic tertiary care center's EMU. This EMU was divided in two subunits: a daytime three-bed epilepsy department subunit (EDU) supervised by EEG technicians and a three-bed neurology ward subunit (NWU) equipped with video-EEG where patients were transferred to for nights and weekends, under nursing supervision. Among 124 admissions, 58 were analyzed. A total of 1293 seizures were reviewed to determine intervention occurrence, IT, and AE occurrence. Seizures occurring when the staff was present at bedside at seizure onset were analyzed separately., Results: Median IT was 21.0 (11.0-40.8) s. The EDU, bilateral tonic-clonic seizures (BTCS), and the presence of a warning signal were associated with increased odds of an intervention taking place. The NWU, BTCS, and seizure rank (seizures were chronologically ordered by the patient for each subunit) were associated with longer ITs. Bedside staff presence rate was higher in the EDU than in the NWU (p < 0.001). AEs occurred in 19% of admissions, with no difference between subunits. AEs were more frequent in BTCS than in other seizure types (p = 0.001)., Conclusion: This study suggests that close monitoring by trained staff members dedicated to EMU patients is key to optimize safety. AE rate was high, warranting corrective measures.

Background: Recent progress in multiple sclerosis (MS) management has contributed to a greater life expectancy in persons with MS. Ageing with MS comes with unique challenges and bears the potential to greatly affect quality of life and socioeconomic burden., Objectives: To compare frailty in ageing persons with multiple sclerosis (pwMS) and controls; to correlate frailty with MS clinical characteristics., Methods: PwMS and controls over 50 years old were recruited in a cross-sectional study. Two validated frailty measures were assessed: the frailty index and the Fried's phenotype. Several multiple linear regressions accounting for demographic and clinical characteristics were performed., Results: Eighty pwMS (57 females, mean age 58.5 ± 6 years old) and 37 controls (24 females, mean age 61 ± 6.5 years old) were recruited. Multivariable analysis identified significantly higher frailty index in pwMS (0.21 ± 0.12 vs 0.11 ± 0.08, p < 0.0001). Similarly, according to Fried's phenotype, a significantly higher percentage of pwMS were frail compared to controls (28% vs 8%). In pwMS, frailty index was independently associated with expanded disability status scale (EDSS), comorbidities, education level and disease duration., Conclusion: Our results suggest that frailty can be routinely assessed in pwMS. Increased frailty in MS patients suggests that, along with MS therapeutics, a tailored multidisciplinary approach of ageing pwMS is needed.

Background: The benefit of acute carotid stenting compared with no acute stenting on clinical outcomes among patients with tandem lesions (TL) undergoing endovascular thrombectomy (EVT) remains unknown., Methods: We conducted a a systematic review and meta-analysis of studies comparing acute carotid stenting versus no stenting among TL patients undergoing EVT with regards to 90 day modified Rankin Scale (mRS) score, symptomatic intracerebral hemorrhage (sICH), and mortality. Four reviewers screened citations for eligibility and two assessed retained studies for risk of bias and data extraction. A random effects model was used for the synthesis of aggregated data., Results: 21 studies (n=1635 patients) were identified for the systematic review; 19 were cohort studies, 1 was a post-hoc analysis of an EVT trial, and 1 was a pilot randomized controlled trial. 16 studies were included in the meta-analysis. Acute stenting was associated with a favorable 90 day mRS score: OR 1.43 (95% CI 1.07, 1.91). No significant heterogeneity between studies was found for this outcome (I 2 =17.0%; χ 2 =18.07, p=0.26). There were no statistically significant differences for 3 month mortality (OR 0.80 (95% CI 0.50, 1.28)) or sICH (OR 1.41 (95% CI 0.91, 2.19))., Conclusions: This meta-analysis suggests that among TL patients undergoing EVT, acute carotid stenting is associated with a greater likelihood of favorable outcome at 90 days compared with no stenting., Competing Interests: Competing interests: AYP is the principal investigator for a forthcoming trial of patients with tandem lesions, Endovascular Acute Stroke Intervention–Tandem OClusion study (EASI-TOC), for which he has received a networking grant from the Canadian Stroke Trials for Optimized Results (CaSTOR) initiative., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: A web-based intervention was developed to support epilepsy self-management. A mixed methods study was undertaken to evaluate the intervention's extent of utilization, acceptability and preliminary effects, and to assess user perception of it., Methods: First, a pilot parallel-group randomized controlled trial was conducted with a convenience sample of 75 adult with epilepsy who had Internet access allocated on a 1:1 ratio into an experimental group that received the intervention (experimental group (EG), n = 37) and a control group invited to consult epilepsy-related websites (control group (CG), n = 38). Self-management, knowledge, and quality of life (QoL) outcomes were measured at baseline and one and three months later. Descriptive statistics of extent of utilization and acceptability were computed. Linear mixed models were conducted to assess change in outcomes over time and between groups. Subsequently, an exploratory qualitative study was carried out with 15 EG participants. Qualitative data were subjected to thematic analysis., Results: Participants had a mean age of 40 years (range: 18-73), 45% were female, and mean time since diagnosis was 18 years (range: less than a year to 60 years). In the EG, 70% of the participants completed the intervention. Regarding acceptability, participants (n = 25) were satisfied overall (88%) and found content clear (92%) and the information reliable (100%). EG participants experienced greater improvement in QoL compared with CG participants, least-squares means (95% CI): 0.41 (0.06, 0.76). Three major themes emerged from the interviews (n = 15): intervention provides certain personal benefits; clinical content is of general interest but should be tailored; and intervention should target "new" patients early in the care trajectory., Discussion: The web-based intervention shows promise in terms of usefulness in enhancing QoL, and user experience showed that it is acceptable and helpful. It could constitute a complementary service in support of existing services for people with epilepsy and their families., Competing Interests: Declaration of Competing Interest JC declares granting of licensing options for marketing of VIH-TAVIE. The remaining authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear. This is an update of a review first published in 2011., Objectives: To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism., Search Methods: On 30 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register (30 March 2013), CENTRAL (2013, Issue 3) in The Cochrane Library, MEDLINE (January 1966 to March 2013) and EMBASE (January 1980 to March 2013). We reviewed bibliographies and contacted authors and experts., Selection Criteria: Randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine., Data Collection and Analysis: Two authors independently selected studies, assessed risk of bias and extracted data onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events., Main Results: A single randomized controlled trial met the inclusion criteria. We found no additional trials when we updated the searches in 2013. This trial evaluated human-derived botulinum immune globulin (BIG) for the treatment of infant botulism and included 59 treatment participants as well as 63 control participants. The control group received a control immune globulin which did not have an effect on botulinum toxin. In this trial there was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among those participants admitted to the intensive care unit (ICU) and mechanically ventilated, but overall we judged the risk of bias to be low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on mean duration of hospitalization (BIG: 2.60 weeks, 95% CI 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) 3.10 weeks, 95% CI 1.68 to 4.52), mechanical ventilation (BIG: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (BIG: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (BIG: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11)., Authors' Conclusions: There is evidence supporting the use of human-derived botulinum immune globulin (BIG) in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding with BIG treatment. This evidence was of moderate quality for effects on duration of mechanical ventilation but was otherwise of high quality. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

Background: Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear., Objectives: To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism., Search Strategy: We searched the Cochrane Neuromuscular Disease Group Specialized Register (10 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (10 January 2010 in The Cochrane Library, Issue 4 2010), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011). We reviewed bibliographies, and contacted authors and experts., Selection Criteria: We included randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine., Data Collection and Analysis: Two authors selected studies, assessed risk of bias and extracted data independently onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events., Main Results: A single randomized controlled trial met the inclusion criteria. This trial evaluated human-derived botulinum immune globulin for the treatment of infant botulism. This study included 59 treatment patients and 63 control patients. There were no deaths in either group making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on duration of hospitalization (mean difference (MD) 3.10 weeks, 95% confidence interval (CI) 1.68 to 4.52), mechanical ventilation (MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (relative risk reduction 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11)., Authors' Conclusions: There is good evidence supporting the use of human-derived botulinum immune globulin in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding among treated patients. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

FTY720 (Fingolimod) reduces multiple sclerosis disease activity by inducing lymphopenia and inhibiting lymphocyte re-entry from lymph nodes. Peripheral lymphocyte reconstitution following drug discontinuation has been considered relatively rapid (2-4 weeks), based on short-term studies. We investigated the kinetics of lymphocyte reconstitution in MS patients in open label extension phases of FTY720 clinical trials who discontinued therapy after prolonged use (>1-5 years), and examined histological features of a mediastinal lymph node obtained from a lymphopenic FTY720 patient. Although three patients showed reconstitution of peripheral lymphocytes within the predicted timeline, two patients continued to be lymphopenic 9 and 34 months after therapy cessation. Lymph nodes from the latter patient showed preserved architecture. Notwithstanding preserved lymph node integrity, time for lymphocyte reconstitution after prolonged FTY720 therapy can be significantly greater than predicted by shorter-term studies. This is relevant for clinical decisions regarding management of patients using this therapy and for introducing alternate therapies., (Copyright © 2010 Elsevier Inc. All rights reserved.)