Disease-modifying therapies and progressive multifocal leukoencephalopathy in multiple sclerosis: A systematic review and meta-analysis.

Background High efficacy disease modifying therapies (DMT) in the management of Multiple Sclerosis (MS) have a favorable effect on relapse rate and disability progression; however, they can expose patients to significant risks, such as progressive multifocal leukoencephalopathy (PML). Objective The study aims to investigate prognostic factors that can determine outcome in MS-related PML patients. Methods We conducted a literature review and meta-analysis of 194 patients from 62 articles in PubMed, SCOPUS and EMBASE. Results Out of 194 patients (66.5% women, 33.5% men), 81% had progression in their EDSS score by at least 1 point from the time of PML diagnosis (EDSS-P group). The remaining patients had either stable or improved EDSS (EDSS-S group). In univariate analysis, older age at the time of PML diagnosis was associated with higher probability of disability accumulation and worsening of EDSS by at least 1 point (mean age = 44.8, p = 0.046). After adjusting for other variables, age at time of PML diagnosis remained a significant predictive variable in the multivariable logistic model (OR = 0.93, 95% CI: 0.88-0.99, p = 0.037). Natalizumab is the most commonly associated DMT linked to PML, followed by fingolimod and others including dimethyl fumarate, ocrelizumab, alemtuzumab. Among the different treatments used, no therapeutic agent was found to be superior in improving post-PML EDSS. Conclusions Younger age and lower JCV viral load at the time of PML diagnosis were associated with better outcome in MS-associate PML, while none of the PML therapies was superior over the others or associated with favorable outcome.

Prevalence, Predictors, and Outcomes of Prolonged Mechanical Ventilation After Endovascular Stroke Therapy.

BACKGROUND: To investigate the rates, predictors, and outcomes of prolonged mechanical ventilation (≥ 96 h) following endovascular treatment (EVT) of ischemic stroke. METHODS: Hospitalizations with acute ischemic stroke and EVT were identified using validated codes in the National Inpatient Sample (2010-2015). The primary outcome was prolonged mechanical ventilation defined as ventilation ≥ 96 consecutive hours. We compared hospitalizations involving prolonged ventilation following EVT with those that did not involve prolonged ventilation. Propensity score matching was used to adjust for differences between groups. Clinical predictors of prolonged ventilation were assessed using multivariable conditional logistic regression analyses. RESULTS: Among the 34,184 hospitalizations with EVT, 5087 (14.9%) required prolonged mechanical ventilation. There was a decline in overall intubation and prolonged ventilation during the study period. On multivariable analysis, history of heart failure [OR 1.28 (95% CI 1.05-1.57)] and diabetes [OR 1.22 (95% CI 1-1.50)] was independent predictors of prolonged ventilation following EVT. In a sensitivity analysis of anterior circulation stroke only, heart failure [OR 1.3 (95% CI 1.10-1.61)], diabetes [OR 1.25 (95% CI 1.01-1.57)], and chronic lung disease [OR 1.31 (95% CI 1.03-1.66)] were independent predictors of prolonged ventilation. The weighted proportions of in-hospital mortality, post-procedural shock, acute renal failure, and intracerebral hemorrhage were higher in the prolonged ventilation group. CONCLUSIONS: Among a nationally representative sample of hospitalizations, nearly one-in-six patients had prolonged mechanical ventilation after EVT. Heart failure and diabetes were significantly associated with prolonged mechanical ventilation following EVT. Prolonged ventilation was associated with significant increase in in-hospital mortality and morbidity.

Antiplatelet therapy and the risk of ischemic and hemorrhagic complications associated with Pipeline embolization of cerebral aneurysms: a systematic review and pooled analysis.

BACKGROUND: Pipeline embolization devices (PEDs) are increasingly used in the treatment of cerebral aneurysms. Yet, major ischemic or hemorrhagic complications after PED treatment associated with antiplatelet regimens are not well-established. OBJECTIVE: To investigate the risk of ischemic and hemorrhagic complications associated with common antiplatelet regimens following PED treatment, and to examine whether platelet function testing (PFT) is associated with a lower risk of these complications. METHODS: We searched Medline, Embase, and Cochrane from 2009 to 2017. Twenty-nine studies were included that had reported a uniform antiplatelet regimen protocol and had provided data on major ischemic and hemorrhagic complications following PED treatment. Random-effect meta-analysis was used to pool overall ischemic and hemorrhagic event rates across studies. The rate of these complications with respect to the antithrombotic regimen and PFT was assessed by χ2 proportional tests. RESULTS: Overall, 2002 patients (age 55.9 years, 76% female) were included. A low-dose acetylsalicylic acid (ASA) regimen before and after PED treatment was associated with a higher rate of late ischemic complications than with high-dose ASA therapy (2.62 (95% CI 1.46 to 4.69) and 2.56 (1.41 to 4.64), respectively). Duration of post-procedure clopidogrel therapy <6 months was associated with greater rates of ischemic complications (1.56, 95% CI 1.11 to 2.20) than a clopidogrel regimen of ≥6 months. Performing PFT before PED treatment was not associated with the risk of ischemic complications (1.27, 95% CI 0.77 to 2.10). CONCLUSION: High-dose ASA therapy and clopidogrel treatment for at least 6 months were associated with a reduced incidence of ischemic events, without affecting the risk of hemorrhagic events.

Network meta-analysis of patent foramen ovale management strategies in cryptogenic stroke.

OBJECTIVE: To compare the outcomes of patent foramen ovale (PFO) closure vs antiplatelet agent (APA) vs oral anticoagulation therapy (OAT) for secondary prevention of stroke in patients with cryptogenic stroke, using direct and indirect evidence from existing randomized data. METHODS: Relevant randomized controlled trials were identified by a systematic review. The efficacy outcome was stroke recurrence, and safety outcomes were atrial fibrillation and bleeding complications at the end of follow-up. Bayesian network meta-analysis was performed to calculate risk estimates and the rank probabilities using APA therapy as the reference. RESULTS: In a network meta-analysis of 6 randomized controlled trials consisting of 3,497 patients (1,732 PFO closure, 1,252 APA, 513 OAT), PFO closure and OAT were associated with lower rates of recurrent stroke (odds ratio [OR] 0.30, 95% credibility interval [CrI] 0.17-0.49 and OR 0.42, 95% CrI 0.22-0.78, respectively) with equal efficacy of OR 0.70 (95% CrI 0.37-1.49). PFO closure had the highest top rank probability of atrial fibrillation and OAT had the highest risk of bleeding complications. CONCLUSIONS: These findings suggest that closure and OAT may be equally effective in recurrent stroke prevention in patients with PFO. There is an increased risk of atrial fibrillation and bleeding with closure and OAT therapy, respectively. A randomized trial is needed to identify patients who would benefit most from each strategy.