Objective: Primary progressive multiple sclerosis (PPMS) does not respond well to immunomodulatory or immunosuppressive treatment. Chronic activation of microglia has been implicated in the pathophysiology of PPMS. The antimalarial drug hydroxychloroquine (HCQ) reduces the activity of human microglia and has neuroprotective effects in vitro. Methods: We conducted a single-arm, phase II futility trial of 200 mg oral HCQ twice daily for 18 months. In an effort to investigate disability worsening in the absence of overt focal inflammation, we excluded participants with contrast enhancing lesions on a screening magnetic resonance imaging (MRI). The primary end point was ≥20% worsening on the timed 25-foot walk measured between 6 and 18 months of follow-up. Results: Based on original trial data, 40% of the cohort were expected to worsen. We used a Simon 2-stage design to compare a null hypothesis of 40% of the cohort worsening against the one-sided alternative of 20%. Using a 5% type 1 error rate and 80% power, HCQ treatment would be deemed successful if fewer than 10 of 35 participants experienced clinically significant worsening. The study met its primary end point, as only 8 of 35 participants worsened between 6 and 18 months. HCQ was overall well-tolerated, with adverse events in 82% and serious adverse events in 12% of participants. All serious adverse events were unlikely related to HCQ use. Interpretation: HCQ treatment was associated with reduced disability worsening in people with PPMS. HCQ is a promising treatment candidate in PPMS and should be investigated further in randomized controlled clinical trials.
A 34-year-old woman presented with acute onset left facial weakness and dysarthria. Examination showed diffuse livedo racemosa (figure, A). Brain MRI demonstrated right frontal acute stroke (figure, B), with numerous chronic ischemic lesions in the deep white matter (figure, C). CT angiogram revealed multiple irregularities along the cortical branches of intracranial vessels (figure, D and E). Skin biopsy was nonspecific. 1 Extensive immunologic, hematologic, and infectious workup was unremarkable. 2 The patient was diagnosed with Sneddon syndrome and discharged on aspirin.Sneddon syndrome is a noninflammatory arteriopathy presenting classic neurovascular and dermatological signs. Often associated with antiphospholipid syndrome or autoimmune disorders, its pathophysiology remains unknown.
IntroductionVirtual teaching sessions during the coronavirus disease 2019 pandemic were challenging for students and teachers but were also an opportunity to find creative ways to teach physical examination skills, including the neurologic examination. We examined expert opinions of the pros and cons that arise using a virtual platform to teach the neurologic examination and strategies to best address these challenges.MethodsThis was a qualitative study incorporating a focus group of faculty and resident neurologists. Data were coded using conventional content analysis. An interpretivist, social constructionist approach was used to look for interesting or novel ideas, rather than testing a specific hypothesis. Three independent auditors performed a dependability and confirmability audit to confirm that the themes accurately reflected the data.ResultsA single focus group was used. Four of the 6 participants were faculty neurologists and 2 were neurology residents. Five themes were identified: (1) learning the neurologic examination is complex, (2) lack of physical contact is the most important drawback of virtual teaching, (3) virtual teaching can effectively emphasize the organization of the examination, (4) virtual sessions can facilitate combined teaching of technique and demonstration of abnormalities, and (5) virtual platforms do not necessarily imply reduced participation.ConclusionTeaching the neurologic examination is a multifaceted process that should emphasize not only technique but also an overall approach to performing and documenting the examination. Many aspects of the neurologic examination can be appropriately taught virtually using various strategies, although there may always be some limitations. Virtual education can play a useful role for future curriculum design and global education.
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