Guillain-Barre syndrome related to COVID-19: muscle and nerve biopsy findings

Background: The involvement of the peripheral nervous system (PNS) in COVID-19 is rare and, to date, morphological aspects from muscle and nerve biopsies have not been reported. Here, we describe a case of Guillain-Barré Syndrome (GBS) related to COVID-19 and demonstrate findings from peripheral nerve and skeletal muscle biopsies. A 79-year-old man presented with progressive weakness in both legs over one-week, evolving to both arms and urinary retention within 6 days. Four days earlier, he had a cough, febrile sensation and mild respiratory discomfort. On admission, his was afebrile, and without respiratory distress. A neurological examination disclosed asymmetric proximal weakness, diminished reflexes and no sensitive abnormalities. Three days later, the patient presented with bilateral facial weakness and proximal muscle strength worsened. Deep tendon reflexes and plantar responses were absent. Both superficial and profound sensitivity were decreased. From this point, oxygen saturation worsened, and the patient was placed on mechanical ventilation. CSF testing revealed one cell and protein 185 mg/dl. A chest CT showed the presence of ground-glass opacities and RT-PCR for SARS-CoV-2 was positive. The muscle biopsy revealed moderate neuromyopathic findings with positive expression for MHC-class I, C5b9, CD8 and CD68. The nerve biopsy showed inflammatory infiltrates predominantly with endoneurial compound formed by CD45 and CD68. The patient was treated with Oseltamivir for 9 days followed by IVIG for 5 days and died three days later of septic shock. Discussion: This is the first documented case of GBS associated with COVID-19 with a muscle and nerve anatomopathological study. A systematic review about neurological complications caused by COVID-19 described 11 patients with GBS. The morphological features reported in our patient showed signs of involvement of the immune system, suggesting that direct viral invasion could have played a role in the pathogenesis of peripheral nerve injury. Hereafter, further research will be necessary to understand the triggers for these cells migrating into the peripheral nerve

New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

Backgroung: There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane. Methods: We analysed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analysed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC). Results: 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution. Discussion: Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.Introdução: Existem poucos relatos sugerindo que a expressão gênica e a ativação de várias metaloproteinases de matriz (MMPs) estão desreguladas. MMP-2 e MMP-9 representam as duas MMPs, que degradam o colágeno tipo IV, o componente da membrana basal. Método: Analisamos o envolvimento das gelatinases, MMP-2 e MMP-9, na patogênese da miopatia miofibrilar (MFM). Amostras de músculos de 23 pacientes bem diagnosticados com MFM foram imunocoradas por MMP-2 e MMP-9. Analisamos qualitativamente a imunoexpressão em três compartimentos: subsarcolemal (SSC), intracitoplasmático (ICC) e perinuclear (PNC). Resultados: 95,7% e 100% das amostras apresentaram ICC de regulação positiva de MMP-2 e MMP-9, respectivamente. PNC mostrou regulação MMP-2 (82,6%) e MMP-9 (8,7%) (p <0,001). SSC e ICC não apresentaram significância estatística. Não houve correlação entre o gene mutado e a distribuição do padrão imunohistoquímico. Discussão: Nossos resultados sugerem que MMP-2 e / ou MMP-9 podem participar do patomecanismo da MFM, causando dano ao sarcômero e deposição de agregados proteicos

Chronic inflammatory polyneuropathy associated with ulcerative colitis: a reported case in literature

AbstractBackground: Peripheral neuropathy is known to be related to inflammatory bowel disease and it is one of the most frequently reported neurologic complications. Various studies have found peripheral nervous system complications, rather than central nervous system involvement, to be predominant. In the literature, there are a few cases of inflammatory polyneuropathy developed in the course of ulcerative colitis : 5 cases of Guillain-Barré syndrome, one case of chronic inflammatory demyelinating polyneuropathy, 10 cases of neuropathy and one case of perineuritis. Case presentation: We describe a case of chronic inflammatory polyneuropathy associated with ulcerative colitis. Conclusion: Peripheral neuropathy is not a common manifestation of IBD, highlighting the need for careful exclusion of other causes of neuropathy when both conditions are encountered in clinical practice. Â

PREVALENCE AND FACTORS ASSOCIATED WITH DEPRESSION IN MEDICAL STUDENTS

Introduction: depression, besides causing great psychological distress, may lead to poor academic performance and social relationships. Objective: to examine the prevalence of depressive symptoms in medical students from a northeastern region of Brazil. Methods: the population comprised 1024 students from first to twelfth semesters of two medical schools in Cariri, Ceará, Brazil. We used the questionnaire on sociodemographic characteristics and the Beck Depression Inventory II version. Results: the prevalence in this population for the diagnosis of depression was 28.8%.652 (63.7%) complied with all protocols to stay in research. After logistic regression, had a negative impact on studentsmental health: female Odds Ratio adjusted (ORa) (95% CI): 1.83 (1.19 to 2.82), reasonable physical health ORa (95% CI): 3.15 (2 0.09 to 4, 73), uncertainty about professional future ORa (95% CI): 2.97 (1.65 to 5.34), desire to change course ORa (95% CI): 2.51 (1.63 to 3.86), good social relationship but without participation in social activities ORa (95% CI): 1.96 (1.27 to 3.04), relationship difficulties ORa (95% CI): 11.40 (4.32 to 30.14) and rare leisure activities (95% CI): 2.45 (1.49 to 4.04) or eventual leisure activities ORa (95% CI): 3.04 (1.70 to 5.42 ). Conclusion: there was a high prevalence of depression among medical students in this region. Female, reasonable physical health, uncertainty over future career, desire to change course, do not participate in social activities and / or difficulties in relationships, sporadic or rare leisure activity were associated with increased risk of developing depressive symptoms

A marcha de base alargada na síndrome de Down e a relação com o engatinhar e os primeiros passos: um estudo transversal

Introduction: Down syndrome individuals have different gait patterns, which include specific characteristics such as foot rotation asymmetry. Objective: The aim of this study was to analyze the relationship between this asymmetry and the previous acquisition of hands-and-knees crawling in Down syndrome children, as well as the probable association of this gait to gender, ethnicity, comorbidities, physiotherapy, and occupational therapy interventions. Methods: In this cross-sectional study, 361 children with or without foot rotation asymmetry were selected. An online questionnaire was administered to the parents or guardians of those children. Results: Hands-and-knees crawling decreased the prevalence of foot rotation asymmetry in Down syndrome children. The longer it took for walking onset, the higher the prevalence of this asymmetry. Indeed, for each month of delay there was a 7% increase in prevalence. There was a significant relationship between orthopedic alterations in knees or flat feet and foot rotation asymmetry. There was no significance related to gender, ethnicity, other comorbidities, physiotherapy or occupational therapy interventions. Conclusion: The findings in this study revealed that foot rotation asymmetry may be related to the acquisition of the motor skills described above, especially with regards to hands-and-knees crawling and walking onset.Introdução: As pessoas com síndrome de Down apresentam diferentes padrões de marcha, incluindo algumas características específicas como a marcha de base alargada. Objetivo: O objetivo deste estudo foi analisar a relação entre a marcha de base alargada e a aquisição motora prévia engatinhar em quatro apoios em crianças com síndrome de Down, bem como a provável associação desta marcha com gênero, etnia, comorbidades e tratamentos de fisioterapia e terapia ocupacional. Método: Neste estudo transversal, foram selecionados 361 indivíduos que apresentaram ou não marcha de base alargada. Um questionário on-line foi administrado para pais / responsáveis destas crianças. Resultados: O engatinhar em quatro apoios diminuiu a prevalência da marcha de base alargada em crianças com síndrome de Down. Quanto maior o tempo em meses para os primeiros-passos, maior a prevalência de base alargada, sendo que, a cada mês de atraso, a prevalência aumenta em 7%. Foi observada significância entre as alterações ortopédicas em joelhos e pés planos e a marcha de base alargada. Conclusão: Os achados deste estudo mostraram que o aparecimento da base alargada pode estar relacionado às aquisições motoras descritas acima, em especial ao engatinhar em quatro apoios, e aos primeiros passos

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Newborn screening for spinal muscular atrophy - what have we learned?

peer reviewed[en] INTRODUCTION: Over the last decade, the treatment of spinal muscular atrophy (SMA) has become a paradigm of the importance of early and accurate diagnosis and prompt treatment. Three different therapeutic approaches that aims to increase SMN protein are approved now by Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of SMA; their efficacies have been demonstrated in pivotal trials. AREAS COVERED: The authors report on the two controlled studies and real-world evidence that have demonstrated that the treatment of patients pre-symptomatically ensures normal or only slightly sub-normal motor development in children who would otherwise develop a severe form of the disease. Furthermore, the authors highlight the several newborn screening (NBS) methods that are now available, all of which are based on real-time PCR, that reliably and robustly diagnose SMA except in subjects with disease caused by a point mutation. EXPERT OPINION: Pre-symptomatic treatment of SMA has been clearly demonstrated to prevent the most severe forms of the disease. NBS constitutes more than a simple test and should be considered as a global process to accelerate treatment access and provide global management of patients and parents. Even though the cost of NBS is low and health economics studies have clearly demonstrated its value, the fear of identifying more patients than the system can treat is often reported in large middle-income countries