Sex differences in neuromuscular disorders.

The prevalence, onset, pathophysiology, and clinical course of many neuromuscular disorders (NMDs) may significantly differ between males and females. Some NMDs are more frequently observed in females, and characterized to show a higher grade of severity during or after the pregnancy. Meanwhile, others tend to have an earlier onset in males and exhibit a more variable progression. Prevalently, sex differences in NMDs have a familiar character given from genetic inheritance. However, they may also influence clinical presentation and disease severity of acquired NMD forms, and are represented by both hormonal and genetic factors. Consequently, to shed light on the distinctive role of biological factors in the different clinical phenotypes, we summarize in this review the sex related differences and their distinctive biological roles emerging from the current literature in both acquired and inherited NMDs.

Effect of the COVID-19 pandemic on patients with inherited neuromuscular disorders.

BACKGROUND: The COVID-19 pandemic has brought substantial challenges for current practices in treating hereditary neuromuscular disorders (hNMDs). However, this infection has not been the only concern for these patients. Social distancing has compromised multidisciplinary assistance and physical activity, and has brought about several mental health issues. We presented a follow-up on 363 patients with hNMDs at a Brazilian tertiary center during the peak of the COVID-19 pandemic. OBJECTIVE: We aimed to show the frequency and severity of SARS-CoV-2 infection among hNMD patients and to demonstrate the effects of the pandemic on life habits, disease progression and multidisciplinary supportive care status. METHODS: Three hundred and sixty-three patients (58% male and 42% female) were followed for three months through three teleconsultations during the peak of the COVID-19 pandemic in Brazil. RESULTS: There were decreases in the numbers of patients who underwent physical, respiratory and speech therapies. For several patients, their appetite (33%) and sleep habits (25%) changed. Physical exercises and therapies were interrupted for most of the patients. They reported new onset/worsening of fatigue (17%), pain (17%), contractions (14%) and scoliosis (7%). Irritability and sleep, weight and appetite changes, and especially diminished appetite and weight loss, were more frequent in the group that reported disease worsening. There was a low COVID-19 contamination rate (0.8%), and all infected patients had a mild presentation. CONCLUSION: The isolation by itself was protective from a COVID-19 infection perspective. However, this isolation might also trigger a complex scenario with life habit changes that are associated with an unfavorable course for the NMD.

Frailties and critical issues in neuromuscular diseases highlighted by SARS-CoV-2 pandemic: how many patients are still "invisible"?

Almost 90% of neuromuscular diseases (NMDs) are classified as rare diseases, defined as conditions affecting less than 5 individuals in 10.000 (0.05%). Their rarity and diversity pose specific challenges for healthcare and research. Epidemiological data on NMDs are often lacking and incomplete. The COVID-19 pandemic has further highlighted the management difficulties of NMDs patients and the necessity to continue the program of implementation of standard of care. This article summarizes the Italian experience during pandemic.

How to define and enhance diagnostic and assistance pathways in neuromuscular diseases during the COVID-19 pandemic: the concept of network.

The main consequence of the COVID-19 pandemic has been to increase the distance between patients and their doctors and to limit the opportunities to compare experiences and clinical cases in the medical community. Based on this, we adopted a strategy to create networks with the ambition to break down these distances and to unify the process of care and management. Here we report the results and perspectives of our efforts and studies. A summary of the presentations on the topic, held during the webinars organized for macro-areas by the Italian Association of Myology with the aim of raising awareness among "non-expert doctors" who deal with neuromuscular disorders in the era of COVID-19 was collected and here reported. Although the macro-areas responded in different way to the problems of neuromuscular patients in the era of COVID-19, they all have tried to create a network between doctors and opportunity for education and information, with the secondary outcome to have shared process of care and management. Telemedicine, virtual meetings and the strengthening of national and international networks, through research projects, were the nodal and common points. Due to their complexity, neuromuscular diseases had already taught clinicians the importance of multidisciplinary confrontation. COVID-19 has further strengthened the need to create links between clinicians and experts, even of different nationalities, in order to guarantee to patients the best possible care, but above all, access and continuity of care even in critical periods. Adequate answers have been given to these problems, though there is still a lot to improve.

Clinical impact of COVID-19 on Turkish children with neurological and neuromuscular diseases: One center experience.

ABSTRACT: This study aims to explore the effects of new type of coronavirus disease (COVID-19) in children with neurological and/or neuromuscular diseasesA retrospective study was conducted at State Hospital of Denizli. Pediatric patients diagnosed with COVID-19 who were hospitalized between March 18, 2020 and January 18, 2021 were included in the study. Children were divided into two groups: those with (group I) and without neurological and /or neuromuscular disorders (group II).Male cases were more than female cases in group I. The difference between group I and group II was significant in terms of seizure (47.3%; 1.7%), dyspnea (36.8%, 6.2%) and number of days with fever (2.6 ±â€Š1.9; 1.58 ±â€Š1.42) (P < .01, P < .01, P = .02). Hypoxemia (7, 11; 36.8%, 4.5%) and abnormal auscultation findings (8, 44; 42.1%, 18.1%) were more common in children in group I, hypertension was more common in group II (0, 8; 0%, 3.3%). Lung involvement of COVID-19 was found to be more severe in group I (P = .04). The frequency of hospitalization in the intensive care unit (P < .01) and application of noninvasive mechanical ventilation (NIMV) (P < .01); the number of days followed-up in the intensive care (P < .01) and in the hospital (P = .02) of the patients in group I were higher than those in group II.It is recognized that children with underlying neurological and/or neuromuscular diseases are severely affected by COVID-19.

A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases.

BACKGROUND: Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. RESULTS: Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. CONCLUSION: During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.

Teleneurology in a center for neuromuscular diseases during the COVID-19 pandemic.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has urged the adoption of telemedicine services as a measure of greater patients' safety. This study aims to investigate efficacy and feasibility of teleneurology care for patients with neuromuscular diseases (NMD). METHODS: All patient visits from 4th March 2020 to 27th March 2021, the period of COVID-19 lockdown requiring partial transition to tele-consultation, were reviewed. Demographic data and medical records during the implementation of the "hybrid model" of both remote and in-person visits during COVID-19 era were analyzed and compared to those of the pre-pandemic era. RESULTS: A total of 2179 tele-consultation contacts for 182 patients (mean age 46.4 years, 42.3% female) were conducted. Tele-consultation was primarily performed by telephone calls. During that period, 1745 telephone calls were conducted, resulting in a 4.5 mean increase/patient compared to 2019. There was a 15.1% decrease in first time in-person consultations compared to 2019. However, the mean number of monitoring visits per person during pandemic was no different from previous years. With the exception of 3 patients with advanced stage of amyotrophic lateral sclerosis, no other patients required an unscheduled appointment or hospitalization for unforeseen reasons related to tele-consultation restrictions. CONCLUSION: Monitoring of NMD patients could benefit from tele-provided multidisciplinary services. The experience gained during COVID-19 pandemic could be useful for further development of tele-medicine.

Early effects of the COVID-19 pandemic on the acute flaccid paralysis surveillance in East and Southern African countries.

INTRODUCTION: the World health organisation (WHO) African Region reported the first confirmed COVID-19 case caused by the SARS-CoV-2 on 25th February 2020, and the first case for the East Southern Africa (ESA) sub-region was on 5th March 2020. Almost all countries in the ESA sub region implemented the WHO-recommended preventive measures variably after the notification of community transmission of the COVID-19 disease. This resulted in the disruption of the outpatient, immunization surveillance, and the related supply chain activities. METHODS: a comparative analysis study design of secondary acute flaccid paralysis (AFP) surveillance data received from the East and Southern Africa sub-region countries to evaluate the effect of the COVID-19 pandemic in the AFP field surveillance for the same time period of March to December 2019 and 2020. RESULTS: we observed that 52.4% of second stool samples were received in the laboratory within 72 hours from March to December 2019, and only 48.1% in the same period of 2020. A 4.3% decline with a p-value of <0.0001 (95% CI, ranges from 2.326% to 6.269%). Similarly, we noted a 4.7% decline in the number of reported AFP cases in the ESA sub-region for March to December 2020 compared to the same period in 2019, a p-value of less than 0.001 (95% CI ranges from 2.785 to 6.614). For the percentage of stool adequacy, we observed a 3.37% decline for April in 2020 compared to April 2019 with a p-value of less than 0.001 (95% CI ranges from 2.059 to 4.690). CONCLUSION: we observed a decline in the core AFP surveillance (non polio) NP-AFP rate, and percentage of stool adequacy in countries severely affected by the COVID-19 disease. These countries implemented stringent transmission prevention measures such as lock-down and international transportation restrictions.

Impact of COVID-19 on the quality of life of patients with neuromuscular disorders in the Lombardy area, Italy.

INTRODUCTION: /AIMS: Patients with neuromuscular disorders (NMDs), including many elderly, immunosuppressed, and disabled individuals, may have been particularly affected during the coronavirus disease 2019 (COVID-19) pandemic in Lombardy, a COVID-19 high-incidence area between February and May 2020. We aimed to evaluate the effects of the COVID-19 pandemic on the quality of life (QoL) and perceived disease burden of this group of patients. METHODS: We conducted a cross-sectional phone-based survey study between June 1 and June 14, 2020, on a sample of 240 NMD patients followed at our clinic in Milan, Italy. We asked about perceived NMD burden and QoL before and during the COVID-19 pandemic. We collected responses on access to outpatient care and ancillary services. We investigated the presence of symptoms suggestive of COVID-19 infection and confirmed cases. RESULTS: We collected 205 responses: 53 patients (25.9%) reported a subjective worsening of the underlying NMD. QoL measures showed a significant worsening between pre and pandemic time frames (odds ratio, 2.14 95%; confidence interval, 1.82-2.51). Outpatient visits were postponed in more than half of cases (57.1%), with 104 patients (50.7%) experiencing a cancellation of scheduled diagnostic tests. 79 patients (38.5%) reported at least one symptom attributable to COVID-19 infection. Among the 10 patients tested with nasopharyngeal swabs, 6 tested positive and 3 died from respiratory failure, including 2 patients on corticosteroid/ immunosuppressive therapy. DISCUSSION: The COVID-19 pandemic affected QoL and limited access to outpatient care and ancillary services of NMD patients in Lombardy between February and May 2020.

Neuromuscular complications of coronavirus disease-19.

PURPOSE OF REVIEW: Since its outbreak in Wuhan, China in late 2019, coronavirus disease-19 (COVID-19) has become a global pandemic. The number of affected cases and deaths continues to rise. Primarily a respiratory illness, COVID-19 is now known to affect various organ systems including peripheral nerve and skeletal muscle. The purpose of this review is to discuss the scope of neuromuscular manifestations and complications of COVID-19. RECENT FINDINGS: Several neuromuscular conditions, including Guillain-Barré syndrome, rhabdomyolysis, and myositis, have been reported in patients infected with COVID-19, but even with a temporal association, a causal relationship remains unproven. Direct invasion of neurons or myocytes by the virus, and immune-mediated injury have been speculated but not consistently demonstrated. In addition to potentially causing the above conditions, COVID-19 can trigger exacerbations of preexisting neuromuscular conditions such as myasthenia gravis, and severe infections can lead to critical illness myopathy/polyneuropathy. SUMMARY: COVID-19 appears to be potentially associated with a wide range of neuromuscular manifestations and complications. Further studies are needed to examine these possible associations, understand the pathogenesis, and develop preventive and treatment strategies.

Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis.

Acute flaccid myelitis (AFM) recently emerged in the United States as a rare but serious neurological condition since 2012. Enterovirus D68 (EV-D68) is thought to be a main causative agent, but limited surveillance of EV-D68 in the United States has hampered the ability to assess their causal relationship. Using surveillance data from the BioFire Syndromic Trends epidemiology network in the United States from January 2014 to September 2019, we characterized the epidemiological dynamics of EV-D68 and found latitudinal gradient in the mean timing of EV-D68 cases, which are likely climate driven. We also demonstrated a strong spatiotemporal association of EV-D68 with AFM. Mathematical modeling suggested that the recent dominant biennial cycles of EV-D68 dynamics may not be stable. Nonetheless, we predicted that a major EV-D68 outbreak, and hence an AFM outbreak, would have still been possible in 2020 under normal epidemiological conditions. Nonpharmaceutical intervention efforts due to the ongoing COVID-19 pandemic are likely to have reduced the sizes of EV-D68 and AFM outbreaks in 2020, illustrating the broader epidemiological impact of the pandemic.

Doctor-Should I get the COVID-19 vaccine? Infection and immunization in individuals with neuromuscular disorders.

The clinical course of neuromuscular disorders (NMDs) can be affected by infections, both in immunocompetent individuals, and in those with reduced immunocompetence due to immunosuppressive/immunomodulating therapies. Infections and immunizations may also trigger NMDs. There is a potential for reduced efficacy of immunizations in patients with reduced immunocompetence. The recent vaccination program for coronavirus disease-2019 (COVID-19) raises several questions regarding the safety and efficacy of this vaccine in individuals with NMDs. In this Practice Topic article, we address the role of vaccine-preventable infections in NMDs and the safety and efficacy of immunization in individuals with NMDs, with emphasis on vaccination against COVID-19.

COVID-19 in children with neuromuscular disorders.

OBJECTIVE: Children with neuromuscular disorders have been assumed to be a particularly vulnerable population since the beginning of COVID-19. Although this is a plausible hypothesis, there is no evidence that complications or mortality rates in neuromuscular patients are higher than in the general population. The aim of this study is to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. METHODS: A registry of children with neuromuscular conditions and laboratory-confirmed-SARS-CoV-2 infection was set up by the Neuromuscular Working Group of the Spanish Pediatric Neurology Society (SENEP). Data to be collected were focused on the characteristics and baseline status of the neuromuscular condition and the course of COVID-19. RESULTS: Severe complications were not observed in our series of 29 children with neuromuscular disorders infected by SARS-CoV-2. Eighty-nine percent of patients were clinically categorized as asymptomatic or mild cases and 10% as moderate cases. Patients with a relatively more severe course of COVID-19 had SMA type 1 and were between 1 and 3 years. CONCLUSIONS: The course of COVID-19 in children with neuromuscular disorders may not be as severe as expected. The protective role of young age seems to outweigh the risk factors that are common in neuromuscular patients, such as a decreased respiratory capacity or a weak cough. Further studies are needed to know if this finding can be generalized to children with other chronic diseases.

Neurological presentations of COVID-19: Findings from the Spanish Society of Neurology neuroCOVID-19 registry.

OBJECTIVE: We report the findings from the Spanish Society of Neurology's NeuroCOVID-19 Registry. METHODS: We performed a multicentre study of patients with neurological manifestations of COVID-19. Participating physicians reported demographic, clinical, and paraclinical data and judged the involvement of COVID-19 in causing neurological symptoms. RESULTS: A total of 233 cases were submitted, including 74 different combinations of manifestations. The most frequently reported were stroke (27%), neuromuscular symptoms (23.6%), altered mental status (23.6%), anosmia (17.6%), headache (12.9%), and seizures (11.6%). The mean age of patients was 61.1 years, with 42.1% being women; a higher proportion of women was recorded among patients with altered mental status, anosmia, and headache. The onset of symptoms differed within categories. Onset of anosmia occurred a mean (standard deviation) of 2.9 (2.5) days after the first general symptom, whereas neuromuscular symptoms appeared after 13.9 (10.1) days. Neurological symptoms were persistent in 33% of patients. General symptoms were present in 97.7% of patients, and results from general laboratory studies were abnormal in 99.4% of patients. Cerebrospinal fluid analysis findings were abnormal in 62.7% of the cases in which this test was performed (n = 51), but positive results for SARS-CoV-2 were only found in one case. CONCLUSIONS: The neurological manifestations of COVID-19 are diverse. Anosmia, myalgia, and headache occur earlier in the course of the disease. Altered mental status, neuromuscular symptoms, and stroke are associated with greater severity. COVID-19 must be incorporated into most clinical and radiological differential diagnoses. COVID-19 may cause persistent and disabling neurological symptoms.

Pediatric neuromuscular disorders: Care considerations during the COVID-19 pandemic.

COVID-19, the respiratory and frequently systemic disease caused by the novel SARS-COV-2 virus, was first recognized in December 2019 and quickly spread to become a pandemic and world-wide public health emergency over the subsequent 3-4 months. While COVID-19 has a very low morbidity rate across approximately 80% of the population, it has a high morbidity and mortality rate in the remaining 20% of the population.1 These numbers have put a significant strain on medical systems around the world. Patients with neuromuscular diseases such as those with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), tend to be more medically fragile and have higher health care needs than the general population. Respiratory insufficiency, cardiac disease, obesity, and immunocompromised status due to chronic steroid treatments in certain patient populations with neuromuscular conditions are specific risk factors for severe COVID-19 disease. In general, the pediatric population has shown to be less severely impacted with lower infection rates and lower morbidity and mortality rates than the adult population, however, as expected, children with underlying medical conditions are at higher risk of morbidity from COVID-19 than their peers.2 Many patients with neuromuscular disease also rely heavily on caregiver support through their lifetime and thus maintaining the health of their primary caregivers is also a significant consideration in the health and well-being of the patients. This paper will address routine and emergency medical care, rehabilitation services, and other considerations for the pediatric patient with a neuromuscular condition during the COVID-19 pandemic.

Respiratory management for patients with neuromuscular disorders during the COVID-19 pandemic.

The reviews of this paper are available via the supplemental material section.

Management of patients with neuromuscular disorders at the time of the SARS-CoV-2 pandemic.

The novel Coronavirus disease-19 (COVID-19) pandemic has posed several challenges for neuromuscular disorder (NMD) patients. The risk of a severe course of SARS-CoV-2 infection is increased in all but the mildest forms of NMDs. High-risk conditions include reduced airway clearance due to oropharyngeal weakness and risk of worsening with fever, fasting or infection Isolation requirements may have an impact on treatment regimens administered in hospital settings, such as nusinersen, glucosidase alfa, intravenous immunoglobulin, and rituximab infusions. In addition, specific drugs for SARS-CoV2 infection under investigation impair neuromuscular function significantly; chloroquine and azithromycin are not recommended in myasthenia gravis without available ventilatory support and prolonged prone positioning may influence options for treatment. Other therapeutics may affect specific NMDs (metabolic, mitochondrial, myotonic diseases) and experimental approaches for Coronavirus disease 2019 may be offered "compassionately" only after consulting the patient's NMD specialist. In parallel, the reorganization of hospital and outpatient services may change the management of non-infected NMD patients and their caregivers, favouring at-distance approaches. However, the literature on the validation of telehealth in this subgroup of patients is scant. Thus, as the first wave of the pandemic is progressing, clinicians and researchers should address these crucial open issues to ensure adequate caring for NMD patients. This manuscript summarizes available evidence so far and provides guidance for both general neurologists and NMD specialists dealing with NMD patients in the time of COVID-19.