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Published By Ovid Technologies (Wolters Kluwer) - American Academy Of Neurology

1526-632x, 0028-3878
Updated Saturday, 16 October 2021

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012910
Author(s):  
Jonathan Broomfield ◽  
Micki Hill ◽  
Michela Guglieri ◽  
Michael Crowther ◽  
Keith Abrams

Objective:Duchenne Muscular Dystrophy (DMD) is a rare progressive disease, which is often diagnosed in early childhood, and leads to considerably reduced life-expectancy; due to its rarity, research literature and patient numbers are limited. To fully characterise the natural history, it is crucial to obtain appropriate estimates of the life-expectancy and mortality rates of patients with DMD.Methods:A systematic review of the published literature on mortality in DMD up until July 2020 was undertaken, specifically focusing on publications in which Kaplan-Meier (KM) survival curves with age as a time-scale were presented. These were digitised and individual patient data (IPD) reconstructed. The pooled IPD were analysed using the Kaplan-Meier estimator and parametric survival analysis models. Estimates were also stratified by birth cohort.Results:Of 1177 articles identified, 14 publications met the inclusion criteria and provided data on 2283 patients, of whom 1049 had died. Median life-expectancy was 22.0 years (95% CI: 21.2, 22.4). Analyses stratifying by three time-periods in which patients were born showed markedly increased life-expectancy in more recent patient populations; patients born after 1990 have a median life-expectancy of 28.1 years (95% CI 25.1, 30.3).Conclusions:This paper presents a full overview of mortality across the lifetime of a patient with DMD, and highlights recent improvements in survival. In the absence of large-scale prospective cohort studies or trials reporting mortality data for patients with DMD, extraction of IPD from the literature provides a viable alternative to estimating life-expectancy for this patient population.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012767
Author(s):  
Cheryl Carcel ◽  
Katie Harris ◽  
Sanne AE Peters ◽  
Else Charlotte Sandset ◽  
Grace Balicki ◽  
...  

Objective:Women have been under-represented in clinical trials areas of cardiovascular disease but there is less certainty over the level of disparity specifically in stroke. We examined the participation of women in trials according to stroke prevalence in the population.Methods:Published randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 were identified from ClinicalTrials.gov. To quantify sex disparites in enrolment we calculated the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial against the prevalence of women in the disease population.Results:There were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4 % were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] (0.81 to 0.87)). The greatest differences were observed in trials of intracerebral hemorrhage (PPR 0.73; 95% CI 0.71 to 0.74), trials with a mean age of participants <70 years (PPR 0.81; 95% CI (0.78 to 0.84)), non-acute interventions (PPR 0.80; 95% CI (0.76 to 0.84)) and rehabilitation trials (PPR 0.77; 95% CI 0.71 to 0.83)). These findings did not significantly change over the period from 1990 to 2020 (p for trend = 0.201).Conclusion:Women are disproportionately underrepresented in stroke trials relative to the burden of disease in the population. Clear guidance and effective implementation strategies are required to improve the inclusion of women and thus broader knowledge of the impact of interventions in clinical trials.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012950
Author(s):  
Andrew M. Agostini ◽  
Michael R. Halstead ◽  
Arun Venkatesan ◽  
Deanna R. Saylor

Interest in global health is increasing among neurology residents. However, funding, time, and, recently, COVID-19 travel restrictions, remain barriers to widespread participation. To meet this need, we instituted virtual global neurology morning reports with the objectives of (1) improving knowledge about neurological diseases common in sub-Saharan Africa; and (2) developing clinical reasoning skills through consideration of diagnostic and therapeutic limitations in resource-limited settings. Interactive case-based sessions were presented from Zambia via videoconference by a Johns Hopkins faculty member or Zambian neurology trainee. An anonymous cross-sectional survey was conducted among Johns Hopkins neurology residents. Of eligible participants, 69% (n=30) completed the survey, 66% of whom were female, and 33% reported prior in-person global health experience. While most participants did not anticipate a career in global health, the majority (85%) reported that exposure to global health was important. All but one participant (96%) reported satisfaction with the global neurology morning reports, with 100% reporting they were useful to their clinical knowledge and 86% reporting they were useful to their clinical practice. All respondents felt morning reports should continue, and 69% ranked the educational value of the experience in the top quartile of the residency curriculum. Resident satisfaction with and perceived utility of global neurology morning reports were high even though the majority did not plan to pursue global neurology opportunities as part of their career. Remote learning opportunities may increase interest in global health among neurology residents.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012918
Author(s):  
Sebastian Luger ◽  
Kimberly Koerbel ◽  
Ariane Martinez Oeckel ◽  
Hauke Schneider ◽  
Christoph J. Maurer ◽  
...  

Objective:To establish serum concentration of protein S100B as an objective biomarker surrogate for astroglial tissue damage after mechanical thrombectomy in patients with acute ischemic stroke.Methods:This prospective two-center study recruited patients with acute middle cerebral artery infarctions caused by large vessel occlusion treated with mechanical thrombectomy. Blood samples were collected at day 2 after intervention and analyzed for S100B serum concentrations using ELISA techniques. Infarct size was determined on follow-up brain imaging, and functional outcome according to modified Rankin scale (mRS) was assessed at 90 days.Results:171 patients were included (mean age ±SD: 70±14 years, 42% female). S100B levels correlated with infarct size. Median S100B concentrations at day 2 after intervention were lower in patients with favorable outcome (mRS score 0-1) at 90 days compared to patients with unfavorable outcome (mRS score 2-6) (median 0.10 µg/L [IQR 0.07-0.14] vs. 0.20 µg/L [0.11-0.48], p<0.001). Younger age (OR 1.120 [CI 1.068-1.174; p<0.001), lower NIHSS 24h after symptom onset (OR 1.232 [CI 1.106-1.372; p<0.001) and lower S100B serum concentrations (OR 1.364 [CI 1.105-1.683]; p=0.004) were independently associated with a favorable outcome. S100B was able to eliminate the lateralization bias associated with the use of mRS for functional outcome assessment at 90 days after stroke.Conclusion:S100B serum concentrations after mechanical thrombectomy indicate the extent of ischemic tissue damage. It can be rapidly assessed, independent of brain imaging and clinical outcome scales. Following prospective validation in further studies, it may provide an objective surrogate outcome parameter both in clinical routine and interventional trials.Classification of Evidence:This study provides Class I evidence that S100B 2 days following mechanical thrombectomy for acute ischemic stroke accurately distinguishes favorable from unfavorable functional outcome.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012919
Author(s):  
Yanjun Guo ◽  
Iyas Daghlas ◽  
Padhraig Gormley ◽  
Franco Giulianini ◽  
Paul M Ridker ◽  
...  

Background and Objective:To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.Methods:We evaluated phenotypic associations between migraine and 19 lipoprotein subfractions measures in the Women’s Genome Health Study (WGHS, N=22,788). We then investigated genetic relationships between these traits using summary statistics from the International Headache Genetics Consortium (IHGC) for migraine (Ncase=54,552, Ncontrol=297,970) and combined summary data for lipoprotein subfractions (N up to 47,713).Results:There was a significant phenotypic association (odds ratio=1.27 [95% confidence interval:1.12-1.44]) and a significant genetic correlation at 0.18 (P=0.001) between migraine and triglyceride-rich lipoproteins (TRLP) concentration but not for LDL or HDL subfractions. Mendelian randomization (MR) estimates were largely null implying that pleiotropy rather than causality underlies the genetic correlation between migraine and lipoprotein subfractions. Pleiotropy was further supported in cross-trait meta-analysis revealing significant shared signals at four loci (chr2p21 harboring THADA, chr5q13.3 harboring HMGCR, chr6q22.31 harboring HEY2, and chr7q11.23 harboring MLXIPL) between migraine and lipoprotein subfractions. Three of these loci were replicated for migraine (P<0.05) in a smaller sample from the UK Biobank. The shared signal at chr5q13.3 colocalized with expression of HMGCR, ANKDD1B, and COL4A3BP in multiple tissues.Conclusions:The current study supports the association between certain lipoprotein subfractions, especially for TRLP, and migraine in populations of European ancestry. The corresponding shared genetic components may be help identify potential targets for future migraine therapeutics.Classification of Evidence:This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012933

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012915
Author(s):  
Gaspard Gerschenfeld ◽  
Didier Smadja ◽  
Guillaume Turc ◽  
Stephane Olindo ◽  
François-Xavier Laborne ◽  
...  

ObjectiveTo investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes (LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC).MethodsWe retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent a brain angiography. The main outcome was 3-month functional independence (modified Rankin scale score ≤ 2). Recanalization (revised Treatment in Cerebral Ischemia score 2b-3), was evaluated before (pre-MT) and after MT (final).ResultsWe included 588 patients (median age 75 years [interquartile range (IQR) 61-84]; 315 women [54%]; median NIH Stroke Scale [NIHSS] score 16 [IQR 10-20]), of which 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95%CI 43.0-51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95%CI 17.2-23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 [20.6%]; secondary transfer, n = 106/520 [20.4%]; p > .99) despite a shorter median IVT-to-puncture time in directly admitted patients (38 [IQR 23-55] vs 86 [IQR 70-110] minutes; p < .001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4-86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95%CI 1.4-4.1).ConclusionsTenecteplase before MT is safe, effective and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy.Classification of EvidenceThis study provides class IV evidence that tenecteplase within 270 minutes of LVO-AIS is increases the probability of functional independence.


Neurology ◽  
2021 ◽  
Vol 97 (15) ◽  
pp. 747.1-747
Author(s):  
Noushin Chini Foroush ◽  
Peter Kempster ◽  
Udaya Seneviratne

Neurology ◽  
2021 ◽  
Vol 97 (15) ◽  
pp. 745.1-745
Author(s):  
James E. Siegler ◽  
Steven Galetta

Neurology ◽  
2021 ◽  
Vol 97 (15) ◽  
pp. 746-746
Author(s):  
Roland Faigle ◽  
Rebecca Gottesman

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