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Background: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS)., Objective: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects., Methods: Prospective 2-year study including two cohorts of young (18-35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay., Results: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration ( p = 0.05), smoking ( p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT ( p = 0.00007), high-efficacy therapies ( p = 0.001), brain lesion volume (BLV) ( p = 0.011), and number of T2 lesions ( p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm 3 and white matter volume 1.78 cm 3 ., Conclusion: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Most contemporary data concerning the frequency and causes of multiple sclerosis (MS) misdiagnosis are from North America and Europe with different healthcare system structure and resources than countries in Latin America. We sought to determine the frequency, and potential contributors to MS misdiagnosis in patients evaluated at an MS referral center in Argentina., Methods: The study was a retrospective medical record review. We included patients evaluated at the MS Clinic at Fleni between April 2013 and March 2021. Diagnoses prior to consultation, final diagnoses after consultation, demographic, clinical and paraclinical data, and treatment were extracted and classified., Results: Seven hundred thirty-six patients were identified. Five hundred seventy-two presented with an established diagnosis of MS and after evaluation, misdiagnosis was identified in 89 (16%). Women were at 83% greater risk of misdiagnosis ( p  = 0.034). The most frequent alternative diagnoses were cerebrovascular disease, radiological isolated syndrome (RIS), and headache. Seventy-four (83%) of misdiagnosed patients presented with a syndrome atypical for demyelination, 62 (70%) had an atypical brain magnetic resonance imaging (MRI), and 54 (61%) were prescribed disease-modifying therapy., Conclusion: Sixteen percent of patients with established MS were subsequently found to have been misdiagnosed. Women were at higher risk for misdiagnosis. Expert application of the McDonald criteria may prevent misdiagnosis and its associated morbidity and healthcare system cost.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Several lines of evidence suggest that multiple sclerosis (MS), like other autoimmune diseases, may be triggered by microbial infections. Pathogens associated with development or exacerbation of MS include bacteria, such as Chlamydia pneumoniae, Staphylococcus aureus-produced enterotoxins that function as superantigens, and viruses of the Herpesviridae (Epstein-Barr virus and human herpes virus 6) and human endogenous retrovirus families. However, to date, no single pathogen has been accepted as causal agent. In addition, common upper respiratory, gastrointestinal, and urogenital tract infections have also been associated with MS exacerbations. Although evidence of an infectious etiology as cause of MS in humans remains inconclusive, microbial agents may modulate the neuroimmunological system of genetically susceptible individuals. Decoding the epidemiological contribution of different microorganisms to MS, along with their pathogenic mechanisms, may help develop new treatment strategies and prevent relapses.

Background and Purpose: Although incidence rates vary, infectious, autoimmune, and neoplastic diseases can all cause chronic and subacute meningitis (CSM). We report a Latin-American, single center, CSM case series, analyzing the main clinical characteristics as well as ancillary diagnostic methods differentiating neoplastic from non-neoplastic etiologies., Methods: Retrospective review of CSM cases from a single center in Buenos Aires, Argentina., Results: Seventy patients with CSM diagnosis were identified, 49 with neoplastic and 21 with non-neoplastic meningitis. A history of previous cancer was significantly higher in neoplastic cases, whereas prevalence of autoimmune disease and fever was more common in non-neoplastic meningitis. C-reactive protein values were higher in non-neoplastic CSM, as was pleocytosis in cerebrospinal fluid analysis. The most frequent etiologies were breast and lung cancer for neoplastic meningitis cases; and idiopathic, tuberculous, and fungal infection for non-neoplastic cases., Conclusions: Chronic and subacute meningitis diagnosis is challenging in daily neurological practice. The results we report contribute information from Latin America regarding etiologies of CSM, which can be identified after a comprehensive evaluation in a majority of cases., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and purpose Identifying embolic strokes of undetermined source (ESUS) patients likely to harbor atrial fibrillation may have diagnostic and therapeutic implications. Our aim was to examine differences between ESUS and cardioembolic strokes, to evaluate stroke recurrence rate among ESUS and to identify baseline characteristics of ESUS patients who were later diagnosed with atrial fibrillation. Materials and methods We assessed all ischemic stroke patients admitted between June 2012 and November 2013. ESUS were compared to cardioembolic strokes at discharge. After at least 12-month follow-up, ESUS patients diagnosed with atrial fibrillation were compared to those who remained as ESUS. Results There were 236 ischemic strokes, 32.6% were ESUS. Compared to cardioembolic strokes, ESUS were younger (p < 0.0001), had milder strokes (p < 0.05), less prevalence of hypertension (p < 0.05), peripheral vascular disease (p < 0.05), and previous ischemic stroke (p < 0.05). After follow-up, 15% of ESUS patients had stroke recurrences and 12% evidenced paroxysmal atrial fibrillation. ESUS patients diagnosed with atrial fibrillation in the follow-up were older (p < 0.0001), had higher erythrocyte sedimentation rate (p < 0.05), and were more likely to have ≥2 infarcts in the same arterial territory in the initial magnetic resonance imaging (p < 0.05). Conclusions Older age, small-scattered infarcts on initial magnetic resonance imaging and high erythrocyte sedimentation rate levels appear to identify ESUS patients more likely to be diagnosed of atrial fibrillation during follow-up.

Intravenous thrombolysis improves outcomes in acute ischemic stroke in a time-dependent fashion. As in teaching hospitals, clinical outcomes may worsen due to the arrival of new inexperienced house staff early in the academic year (July effect, JE), we evaluated the impact of the "JE" on the door-to-needle time for intravenous thrombolysis and other stroke outcomes. In this retrospective cohort study, we assessed all acute ischemic strokes treated with intravenous thrombolysis between July 2003 and June 2016. Among 101 patients, there was no detrimental July effect on the door-to-needle time, rate of thrombolysis within 60 minutes of arrival, thrombolysis of stroke mimics, post-thrombolysis intracranial hemorrhages, National Institutes of Health Stroke Scale, and modified Rankin Scale outcomes., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

MS incidence has significantly increased during the second half of the 20th century, generating considerable interest in analyzing the basis for this rise in the developed world. Particular emphasis is being placed on the role infections might play in exacerbating or preventing disease onset. Epidemiological data suggest that improvement in sanitation conditions and reduced exposure to infection might explain, at least in part, these changes. The hygiene hypothesis is not new and is currently used to explain the increasing incidence of allergies and other autoimmune diseases. Because helminths are powerful modulators of host immunity, some authors hypothesize that reduced parasite exposure due to improved hygiene conditions may favor MS development. We discuss epidemiological, experimental, clinical and molecular data supporting the protective role of helminthes against MS. Better understanding of host-parasite interactions caused by specific parasite molecules with immunomodulatory effects will help combat allergies and autoimmune disease without the price of untoward infection as a side-effect.