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Myasthenia Gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID19. Management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID19 and discuss prognosis and treatment based on a literature review. Most patients were female (7/8), with an average age of 47.1 years. Treatment was immunoglobulin (IVIG) in 3 patients, plasma exchange (PLEX) in 2 patients, and adjustment of baseline drugs in 3. In-hospital mortality was 25% and 37.5% in 2-month follow-up. This is the largest case series of MG exacerbation or myasthenic crisis due to COVID19 to this date. Mortality was considerably higher than in myasthenic crisis of other etiologies. Previous treatment for MG or acute exacerbation treatment did not seem to interfere with prognosis, although sample size was too small to draw definitive conclusions. Further studies are needed to understand the safety and effectiveness of interventions in this setting, particularly of PLEX, IVIG, rituximab and tocilizumab.

TANK-binding kinase 1 (TBK1) gene mutations cause ALS and frontotemporal dementia (FTD). We report a novel TBK1 mutation in a Brazilian patient with ALS. Symptoms started at age 44 (lower-limb onset). Despite treatment with riluzole, his condition progressed over 5 years to aphemia, dysphagia, gastrostomy and tracheostomy. A diagnostic test panel for neurodegenerative disorders disclosed a novel likely pathogenic heterozygous intronic mutation in the TBK1 gene: c.1189 + 1G gt; T (Splice donor), intron 9. This mutation is expected to disrupt RNA splicing and lead to loss of protein function. Disruption of this splice site has been observed in patients with TBK1-related disorders. Separate and additional C9ORFF72 testing was negative. To our knowledge, this is the second patient with a TBK1 mutation (novel splice donor intronic mutation) reported in Brazil, and the first to include a full description of the clinical course. Further studies are necessary to establish the frequency of TBK1 mutations in Brazilian ALS patients (and worldwide) and to evaluate the possible different clinical phenotypes and the disease course.

Background: Bleeding in hemophiliacs can cause complications in the central and peripheral nervous system (CNS and PNS). The incidence of intracranial hemorrhage has reduced after the introduction of prophylactic treatment with factor VIII or IX, but the benefits of this therapy have not yet been evaluated on PNS complications. Objective: The aim of this study was to determine the prevalence of neurological complications in hemophiliacs and verify the effect of prophylactic therapy in these patients, including PNS disorders. Methods: We retrospectively evaluated the prevalence of CNS and PNS disorders caused by bleeding in hemophiliacs seen at the Hemocentro Regional Norte, Ceará, Brazil, from 1992 to 2018, and we compared the incidence in different periods (before and after the introduction of prophylactic treatment in 2011). Results: Of 75 hemophilia A patients evaluated (4.61/100.000 population), 13.3% (n=10) had either CNS (n=5) or PNS (n=5) disorders secondary to bleeding. Patients submitted to factor VIII replacement prophylactic therapy were less likely to have CNS events: from 1992 to 2011, 5 of 63 patients had CNS disease, while from 2011 to 2018, there were no new cases (p=0.0181). From 2011 to 2018, 5 PNS events occurred in patients without prophylactic therapy, whereas none occurred in those covered by prophylactic therapy (5/20 versus 0/29, p=0.0081). Conclusions: The prevalence of neurological complications in hemophiliacs in our cohort is similar to other studies. Similar to CNS, prophylactic therapy also reduces the risk of PNS complications. This is the first report in the literature showing this benefit. RESUMO Antecedentes: O sangramento em hemofílicos causa complicações no sistema nervoso central e periférico (SNC e SNP). A incidência de hemorragia intracraniana diminuiu após a introdução da profilaxia com fator VIII ou IX, entretanto esse benefício ainda não foi avaliado no SNP. Objetivo: O objetivo deste estudo foi determinar a prevalência de complicações neurológicas em hemofílicos, verificando o efeito da terapia profilática também no SNP. Métodos: Avaliamos retrospectivamente a prevalência de complicações neurológicas causadas por sangramentos em hemofílicos atendidos no Hemocentro Regional Norte, Ceará, Brasil, de 1992 a 2018, comparando a incidência em diferentes períodos (antes e depois da introdução do tratamento profilático em 2011). Resultados: Foram avaliados 75 pacientes com hemofilia A (4,61/100 mil habitantes). Deles, 13,3% (n=10) tinham distúrbios do SNC (n=5) ou do SNP (n=5) secundários a hemorragias. Os pacientes submetidos à terapia profilática com fator VIII apresentaram menor probabilidade de eventos do SNC: de 1992 a 2011, cinco de 63 pacientes apresentaram hemorragia no SNC, enquanto de 2011 a 2018 não ocorreram novos casos (p=0,0181). De 2011 a 2018, cinco eventos no SNP ocorreram entre pacientes sem terapia profilática, e nenhum ocorreu entre aqueles cobertos pela profilaxia (5/20 × 0/29, p=0,0081). Conclusões: A prevalência de complicações neurológicas em hemofílicos em nossa coorte é similar à de outros estudos. Assim como no SNC, a terapia profilática também reduz o risco de complicações no SNP. Este é o primeiro relato na literatura a mostrar esse benefício.

Introduction Peripheral neuropathy is an uncommon complication in patients with hemophilia, usually characterized by mononeuropathies, caused by hematoma and compartmental syndrome. The femoral nerve is the most affected, but several other locations have been described. The purpose of this article is to describe four cases of peripheral nerve injury in hemophiliacs comparing with data from the literature. Methods This is a descriptive study, carried out by reviewing the medical record of four hemophiliac patients diagnosed with peripheral nerve injury, performed at a hematology and hemotherapy center in the state of Ceara, Brazil. The literature review was performed on the PubMed platform. All four patients underwent imaging and electromyography studies. The data collected were compared with those of the literature. Results The first case involves a male patient, twenty-nine years old, with a massive hematoma encapsulated in the right thigh (pseudotumor), and associated with paresthesia and a sensory and motor NCS evidencing sciatic nerve involvement. The second case refers to a male patient, forty-seven years old, with chronic hemophilic arthropathy at the right elbow, presenting with tactile-painful hypoesthesia at the medial border of the hand and the fifth finger. The study of nerve conduction revealed ulnar neuropathy at the elbow. In this case, the probable pathophysiology involves the stretching of the ulnar nerve by the pronounced valgus of the elbow. The last two patients were a man of forty-two and a boy of sixteen, both with left iliopsoas hematoma, accompanied by paresthesia in the anterior and lateral aspect of the thigh. The evaluation of the sensory e motor NCS revealed the involvement of the sensory branch of the femoral nerve (saphenous) and acute denervation in quadriceps muscle on needle EMG. Conclusion Even in a limited sample, the four reported cases are in accordance with the literature data. The main publications on the subject indicate the nerves of the lower limbs as the most affected ones, predominating the femoral nerve, followed by the sciatic nerve.