Orofacial Muscle Weakening in Facioscapulohumeral Muscular Dystrophy (FSHD) Patients

Background: Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. Methods: Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman’s correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. Results: A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. Conclusions: Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype–phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients.

Rituximab and intravenous immunoglobulin treatment in PM/Scl antibody-associated disease: case-based review

Autoantibodies to the 75-kDa and 100-kDa subunits of the PM/Scl nucleolar protein complex are associated with an overlap syndrome, manifesting with clinical features of systemic sclerosis and idiopathic inflammatory myopathy. We describe the diverse clinical features in a series of 4 cases with anti-PM/Scl-75 and/or anti-PM/Scl-100 antibodies, including severe proximal muscle weakness, oesophageal dysfunction, respiratory weakness requiring mechanical ventilation, Raynaud’s, calcinosis cutis, sclerodactyly and critical digital ischaemia. Despite the severity of striated and oesophageal muscle weakness, all patients responded very well to immune suppression, and calcinosis cutis in one case regressed substantially. We highlight the efficacy of Rituximab and intravenous immunoglobulin therapy (IVIg) in these cases, enabling return to normal muscle function within six months. Rituximab was preferentially chosen for cases with hyper-gammaglobulinemia and multiple autoantibodies in addition to anti-PM/Scl, and IVIg was utilised for cases where a rapid onset of effect was required, such as severe ventilator-dependent respiratory muscle weakness and oesophageal dysfunction.

Long COVID symptoms and duration in SARS-CoV-2 positive children — a nationwide cohort study

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0–17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%). An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6–17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04–0.06), loss of smell RD 0.01 (CI 0.01–0.01), loss of taste RD 0.01 (CI 0.01–0.02) and muscle weakness RD 0.01 (CI 0.00–0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12–0.13), loss of taste RD 0.10 (CI 0.09–0.10), fatigue RD 0.05 (CI 0.05–0.06), respiratory problems RD 0.03 (CI 0.03–0.04), dizziness RD 0.02 (CI 0.02–0.03), muscle weakness RD 0.02 (CI 0.01–0.02) and chest pain RD 0.01 (CI 0.01–0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1–5 months.Conclusions: Long COVID in children is rare and mainly of short duration. What is Known:• There are increasing reports on ‘long COVID’ in adults.• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group. What is New:• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.• In most cases ‘long COVID’ symptoms resolve within 1-5 months.

Efficiency and Stability of Step-To Gait in Slow Walking

As humans, we constantly change our movement strategies to adapt to changes in physical functions and the external environment. We have to walk very slowly in situations with a high risk of falling, such as walking on slippery ice, carrying an overflowing cup of water, or muscle weakness owing to aging or motor deficit. However, previous studies have shown that a normal gait pattern at low speeds results in reduced efficiency and stability in comparison with those at a normal speed. Another possible strategy is to change the gait pattern from normal to step-to gait, in which the other foot is aligned with the first swing foot. However, the efficiency and stability of the step-to gait pattern at low speeds have not been investigated yet. Therefore, in this study, we compared the efficiency and stability of the normal and step-to gait patterns at intermediate, low, and very low speeds. Eleven healthy participants were asked to walk with a normal gait and step-to gait on a treadmill at five different speeds (i.e., 10, 20, 30, 40, and 60 m/min), ranging from very low to normal walking speed. The efficiency parameters (percent recovery and walk ratio) and stability parameters (center of mass lateral displacement) were analyzed from the motion capture data and then compared for the two gait patterns. The results suggested that step-to gait had a more efficient gait pattern at very low speeds of 10–30 m/min, with a larger percent recovery, and was more stable at 10–60 m/min in comparison with a normal gait. However, the efficiency of the normal gait was better than that of the step-to gait pattern at 60 m/min. Therefore, step-to gait is effective in improving gait efficiency and stability when faced with situations that force us to walk slowly or hinder quick walking because of muscle weakness owing to aging or motor deficit along with a high risk of falling.

Clinical and Pathological Features of Immune-Mediated Necrotising Myopathies in a Single-Centre Muscle Biopsy Cohort

Objective Immune-mediated necrotising myopathy (IMNM) is a recently entitled novel subset of idiopathic inflammatory myopathies (IIM) characterized by significant elevated creatine kinase (CK) level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in our single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed in according with 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). Among IIM patients, polymyositis (PM), dermatomyositis(DM), amyopathic dermatomyositis, juvenile DM, and inclusion body myositis were 182(21.2%), 236(27.4%), 83(9.7%), 18(2.1%) and 3(0.3%), respectively. In PM subgroup, 59 patients met serological and pathological characteristics of IMNM according to 2018 ENMC criteria including 29 anti-SRP-positive patients,10 anti-HMGCR-positive patients and 20 MSA-negative patients. Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) were 29 and 16 respectively, which present similar manifestations of IMNM with elevated CK levels and muscle weakness among non-IIM group. IMNM patients had older age of onset (mean: 42.25 vs 21.66 and 24.56, p<0.0001), shorter duration of diseases (mean: 22.56 vs 66.69 and 48.94, p<0.0001) and more frequent of dysphagia (33.9% vs 3.4% and 6.3%, p<0.0001) compare to patients with LGMD 2B and LSM. Muscle biopsy from IMNM patients showed frequent muscle fibre necrosis (96.6% vs 72.4% and 56.3%, p<0.0001), overexpression of MHC-I on sarcolemma (81.4% vs 37.9% and 12.9%, p<0.0001) and CD4+ T cell endomysial infiltration (89.9% vs 53.6% and 50%, p<0.0001) compared with LGMD 2B and LSM patients. Conclusions It is easy to distinguish IMNM from other subtype of IIM according to clinical symptoms and MSAs profiles. However, distinguishing IMNM from disorders clinically similar non-IIM need to combine with clinical, serological and pathological features.

Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis: A Neuromuscular Surprise

Myasthenia gravis is a neuromuscular autoimmune disease that results in skeletal muscle weakness that worsens after periods of activity and improves after rest. Myasthenia gravis means “grave (serious), muscle weakness.” Although not completely curable, it can be managed well with a relatively high quality of life and expectancy. In myasthenia gravis, antibodies against the acetylcholine receptors at the neuromuscular junction interfere with regular muscular contraction. Although most commonly caused by antibodies to the acetylcholine receptor, antibodies against MuSK (muscle-specific kinase) protein can also weaken transmission at the neuromuscular junction. Muscle-specific tyrosine kinase myasthenia gravis (MuSK-Ab MG) is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. Diagnosis can be challenging due to its atypical presentation as compared to seropositive myasthenia gravis. It responds inconsistently to steroids, but plasma exchange and immunosuppressive therapies have shown promising results. We report a case of a 49-year-old female who presented with acute hypoxic respiratory failure. Our patient experienced progressive, undiagnosed MuSK-Ab MG for years without a diagnosis.

Low-Dose Collagenase Chemonucleolysis Combined with Radiofrequency in the Treatment of Lumbar Disc Herniation: A 10-Year Retrospective Study

Objective. This study explored the 10-year efficacy, safety, and prognostic factors of low-dose collagenase chemonucleolysis (CCNL) combined with radiofrequency (RF) in the treatment of lumbar disc herniation (LDH). Methods. The data of 167 LDH patients were collected. Modified MacNab criteria, Numerical Rating Scale (NRS), and Japanese Orthopedic Association (JOA) scores were, respectively, used to evaluate patients’ excellent and good rates, pain degree, and nerve function. The preoperative and 10-year postoperative patients’ pain, numbness, and muscle weakness were compared. Patients’ complications in perioperative period, recurrent/reappeared LDH, and reoperations were recorded. Finally, the independent risk factors affecting the long-time efficacy were assessed. Results. A total of 126 patients were included. The patients’ excellent and good rates were 86.51%–92.86% with no significant difference P > 0.05 . Postoperative NRS and JOA scores significantly improved P < 0.01 , most obvious within 6 months postoperatively. At 10 years postoperatively, 65.08%, 83.95%, and 93.02% of patients’ pain, numbness, and muscle weakness were completely relieved P < 0.05 . Perioperative complications occurred in three patients with the rate of 2.38%. Recurrent/reappeared LDH patients were 11 with the ratio of 8.73%; nine of them underwent reoperations with the rate of 7.14%. And patients’ probability of fair and poor efficacy at 10 years postoperatively with the course of disease >12 months and the responsibility disc ≥2 were, respectively, 6.005 and 4.227 times that of patients with the course of disease ≤12 months and the responsibility disc = 1 P < 0.05 . Conclusion. The combined treatment is effective and safe in the long term. A course of disease >12 months and responsibility disc ≥2 independently reduce efficacy, and a course of disease >12 months has a more significant impact.

Prevalence and predictive factors for bilateral carpal tunnel syndrome by electrodiagnosis: A retrospective study

Introduction Carpal tunnel syndrome (CTS) is the most common compressive neuropathy. Patients who have unilateral symptoms are frequently found to have bilateral CTS by electrodiagnostic (EDx) study. We aimed to (a) study the prevalence and identify the predictive factors for bilateral CTS diagnosed by EDx; and (b) develop a model to predict bilateral CTS. Methods The retrospective clinical and EDx data of patients with CTS were collected and analyzed using the Chi-squared test and multiple logistic regression analysis. A model was fitted, and the best cutoff point determined. Calibration and discrimination performance of the model were performed. Results A total of 327 patients with a mean age of 50.0 years were enrolled. Most were women (82.6%), and the most common presenting symptom was hand numbness (93.6%). The median duration of symptoms was 60 days. The prevalence of bilateral CTS was 80.7%. In the multivariate analysis, the predictive factors for bilateral CTS were the presence of bilateral symptoms (AOR 6.7 [95%CI 3.1–14.3]), thenar muscle weakness (AOR 3.9 [95%CI 1.3–11.6]), and age ≥ 45 years (AOR 2.5 [95%CI 1.3–4.6]). The logistic regression model was fitted, and the best cutoff point determined. The area under the receiver operating curve (AUC) was 0.76. The respective optimism-corrected C index and Somers’ D was 0.762 and 0.524. Conclusion The prevalence of bilateral CTS was 80.7%. Our findings suggest bilateral CTS was predicted with adequate diagnostic accuracy by bilateral symptoms, age ≥ 45 years, and thenar muscle weakness.