Limb Muscle Weakness Research Articles

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

Clinical characteristics of idiopathic inflammatory myopathies related to anti-SRP: a single center experience

Idiopathic inflammatory myopathy (IIM) with autoantibodies recognizing the signal recognition particle (SRP) is characterized by prominent proximal weakness, infrequent extramuscular involvement, dramatically elevated creatine kinase levels, and myofiber necrosis with few inflammatory cell infiltrates in muscle tissue. To enhance understanding of the clinically used diagnosis and treatment of this disease, this study presents a single-center experience and analysis of a Chinese cohort with anti-SRP IIM. The most recent European Neuromuscular Center criteria were used to include Anti-SRP IIM patients from September 2016 to November 2019. Prior to treatment initiation, all sera were collected for the detection of anti-SRP autoantibodies and other myositis-related autoantibodies. Muscle strength, concurrent autoimmune conditions, comorbidities like interstitial lung disease (ILD), treatment outcomes, and follow-up results were also documented. Univariate logistic regression was employed to determine factors affecting prognosis. Among 271 patients with IIM, we identified 23 (8.5%) patients with anti-SRP IIM. Lower limb muscle weakness was frequently more severe. Interstitial lung disease (ILD) was observed in 50% of anti-SRP IIM patients. The presence of ILD may serve as a predictor of a poor prognosis, as revealed by univariate logistic regression analysis (odds ratio, 3.8, 95% CI: 1.0-6.8, p = 0.05).This Chinese Anti-SRP IIM cohort from Hunan province seems to have higher incidences of ILD, and associated ILD may be a risk factor for a poor prognosis. To fully understand the specific role of the anti-SRP autoantibody in this unique subset with ILD, further research is necessary.

Comparison of the long-term efficacy of ROI-C and conventional cage-plate in treatment of spinal cord injury without fracture or dislocation: a retrospective study

BackgroundThe self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in the treatment of cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been conducted on the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD.MethodsA total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. The cohort comprised 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients exhibited symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. The preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study.ResultsA total of 48 patients underwent ACDF with ROI-C, while 35 patients received a conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). However, statistical difference was found in disc height of fused segment and T1 slope between the two groups (P < 0.05). No statistical difference was in the incidence of cage subsidence (P > 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up.ConclusionOur study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. All affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J-domain may predict a more severe phenotype.

EXPLORING FACTORS FOR PRESCRIPTION AND VALIDATION OF ACTUATED UPPER LIMB DEVICES: A CROSS-SECTIONAL SURVEY OF ALLIED HEALTH PROFESSIONALS

BACKGROUND: Actuated devices can be beneficial for individuals with upper limb muscle weakness, offering extra force and grip. Utilising this type of assistive device can facilitate daily activities, thereby enhancing independence and overall quality of life. The development of actuated assistive devices has been growing, and current literature shows promise in their clinical use. However, they are not yet medically recommended by global guidelines and councils. Studies have suggested why assistive devices have barriers to access, but actuated devices have not been a focus in these discussions. OBJECTIVE(S): To address this issue, a survey was conducted among professionals who prescribe and assess upper limb assistive devices. The survey aimed to gather their opinions and quantify the factors that might contribute to the limited use of actuated devices in the field. METHODOLOGY: A web-based cross-sectional study was designed using Qualtrics, contained 25 items and was conducted between October 2023 and January 2024. The survey was piloted, validated, and ethically approved. Results were statistically analysed, and open questions underwent thematic analysis. FINDINGS: 87 Allied Health Professionals (AHPs) contributed to the survey, with a completion rate of 69% (60/87). Survey respondents predominately worked from the USA (72%). The survey revealed that 66% of respondents felt they did not have sufficient access to assistive devices and 58% indicated that outcome measures could be improved. They also noted that actuated devices needed to better meet user-centric needs. Barriers to prescribing these devices included a lack of awareness, experience and standardised prescription methods. In addition, the limited time with patients made decision-making and validation of an actuated device difficult. CONCLUSION: AHP’s have experience prescribing assistive devices but do not have access, knowledge, or clinical methods to assess the use of actuated devices. Future designs for actuated devices should focus on wearability, comfort, user satisfaction, safety and ease of use. Layman's Abstract Powered support devices can be helpful for persons with muscle weakness in their arms. These devices can provide support by giving additional strength to the hands. This helps with everyday tasks such as self-care, which in turn also improves quality of life. The development of powered and motorized assistive devices has been growing and current research shows promise in their clinical use. Yet they are not medically recommended by global guidelines and councils. Studies have suggested why all assistive devices have barriers to access, but powered devices have not been a focus in these discussions. This study aims to explore which devices medical professionals use, their opinions on them and how they test them using outcome measures. The survey included 25 questions which were assessed by external researchers and clinicians. The survey was also ethically approved. Overall, 60 people completed the survey. Occupational therapists and hand therapists responded the most and tended to be from the USA. Factors such as lack of awareness, access, and prescription methods were described as barriers to providing powered devices. In addition, the design of the device, function and relevance were concerns. 58% of respondents voted that outcome measures could also be improved. Therefore, prescribers and assessors of assistive devices do not have access to and awareness of current powered devices. Results also showed the function of these devices did not match respondents' opinions on the wearer's needs. The priority should be to make devices that are comfortable and easy to use. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/43790/33062 How To Cite: Galbert A, Buis A. Exploring factors for prescription and validation of actuated upper limb devices: A cross-sectional survey of allied health professionals. Canadian Prosthetics &amp; Orthotics Journal. 2024; Volume 7, Issue 1, No.4. https://doi.org/10.33137/cpoj.v7i1.43790 Corresponding Author: Professor Arjan Buis, PhDDepartment of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland.E-Mail: arjan.buis@strath.ac.ukORCID ID: https://orcid.org/0000-0003-3947-293X

Microhemorrhages in diquat-induced encephalopathy identified using susceptibility-weighted imaging

Introduction Intracerebral bleeding that predominantly affects the pons, midbrain, cerebral peduncle, basal ganglia, and thalamus may occur in severe diquat poisoning. We employed magnetic resonance-susceptibility-weighted imaging to highlight the presence of microhemorrhages in a patient with diquat poisoning. Case summary: A 15-year-old female patient presented with kidney and liver damage after ingesting diquat. Three days later, she developed coma. She received seven sessions of hemoperfusion and was discharged with residual cognitive impairment and right limb muscle weakness after 66 days of hospitalization. Images: Cranial computed tomography on day 5 and magnetic resonance imaging on day 8 revealed swelling in the pons, midbrain, and thalamus without evidence of hemorrhage. However, susceptibility-weighted imaging on day 8 demonstrated multiple punctate low signals, suggesting the presence of microhemorrhages. Conclusion Susceptibility-weighted imaging is a useful technique for detecting microhemorrhages in patients with diquat-induced encephalopathy, as microhemorrhages are often not detectable on computed tomography or conventional magnetic resonance imaging.

A novel variant of biallelic MME gene associated with autosomal recessive late-onset distal hereditary motor neuropathy in Chinese families

Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous diseases and previous studies have reported that the compound heterozygous recessive MME variants cause dHMN. Our study found a novel homozygous MME variant and a reported compound heterozygous MME variant in two Chinese families, respectively. Next-generation sequencing and nerve conduction studies were performed for two probands. The probands in two families presented with the muscle weakness and wasting of both lower limbs and carried a c.2122 A > T (p.K708*) and c.1342 C > T&c.2071_2072delinsTT (p.R448*&p.A691L) variant, respectively. Prominently axonal impairment of motor nerves and slight involvement of sensory nerves were observed in nerve conduction study. Our study reported a “novel” nonsense mutation and a missense variant of autosomal recessive late-onset dHMN and reviewed reported MME variants associated with dHMN phenotype.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Charcot-Marie-Tooth (CMT) is a heterogeneous group of genetic neuropathies and is typically characterized by distal muscle weakness, sensory loss, pes cavus and areflexia. Herein we describe a case of CMT2CC presenting with proximal muscle weakness and equivocal electrophysiological features, that was misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). A 30-year-old woman complained of proximal muscle weakness with difficulty climbing stairs. Neurological examination showed weakness in lower limb (LL) muscles, that was marked proximally and mild distally, and absence of deep tendon reflexes in the ankles. Nerve conduction studies (NCS) showed sensory-motor neuropathy with non-uniform NC velocity and a partial conduction block (CBs) in peroneal nerve and tibial nerves. Thus, a diagnosis of CIDP was entertained and the patient underwent ineffective treatment with intravenous immunoglobulins. At electrophysiological revaluation CB in peroneal nerve was undetectable as also distal CMAP had decreased whereas the CBs persisted in tibial nerves. Hypothesizing a hereditary neuropathy, we examined the proband's son, who presented mild weakness of distal and proximal muscles at lower limbs. Neurophysiological investigation showed findings consistent with an intermediate-axonal electrophysiological pattern. A targeted-NGS including 136 CMT genes showed the heterozygous frameshift mutation (c.3057dupG; p.K1020fs*43) in the NEFH gene, coding for the neurofilament heavy chain and causing CMT2CC. Diagnosis of a genetic neuropathy may be challenging when clinical features are atypical and/or electrophysiological features are misleading. The most common misdiagnosis is CIDP. Our report suggests that also CMT2CC patients with proximal muscle weakness and equivocal electrophysiological features might be misdiagnosed as CIDP.

SIGMAR1 targets AMPK/ULK1 pathway to inhibit SH-SY5Y cell apoptosis by regulating endoplasmic reticulum stress and autophagy.

Distal hereditary motor neuropathy (dHMN) is a progressive neurological disease characterized by distal limb muscle weakness and amyotrophy. Sigma 1 receptor (σ1R), a gene product of SIGMAR1, mutations have been reported to induce dHMN, but its mechanism remains unknown. This study aims to explore the effect of C238T and 31_50del mutations in σ1R on neuronal SH-SY5Y cell functions. The SH-SY5Y cells that overexpressed σ1R, C238T mutant σ1R (σ1RC238T) or 31_50del mutant σ1R (σ1R31_50del) were constructed by pEGFPN1 vectors. We used Western blot (WB) and immunofluorescence (IF) staining to detect the expression of σ1R and green fluorescent proteins (GFP). Then, we evaluated the impact of σ1R mutation on apoptosis, autophagy, endoplasmic reticulum stress, and the involvement of the unfolded protein response (UPR) pathway in SH-SY5Y cells. We found that σ1RC238T and σ1R31_50del downregulated σ1R and promoted the apoptosis of SH-SY5Y cells. σ1RC238T and σ1R31_50del increased p-PERK, p-eIF2α, p-JNK, BIP, ATF4, CHOP, ATF6, XBP1, Caspase3, Caspase12 expressions and Ca2+ concentration, whereas decreased ATP content in SH-SY5Y cells. Besides, the expressions of LC3B, Lamp1, ATG7, Beclin-1 and phosphorylation of AMPK and ULK1 were increased, while the p62 level decreased after C238T or 31_50del mutation of σ1R. Additionally, AMPK knockdown abolished the apoptosis mediated by σ1RC238T or σ1R31_50del in SH-SY5Y cells. Our results indicated that C238T or 31_50del mutation in σ1R promoted motor neuron apoptosis through the AMPK/ULK1 pathway in dHMN. This study shed light on a better understanding of the neurons pathological mechanisms mediated by σ1R C238T and σ1R 31-50del in dHMN.

An unusual presentation of dermatomyositis: dermatomyositis sine dermatitis presenting with rapidly progressive myositis

Dermatomyositis sine dermatitis (DMSD) is a rare variant of dermatomyositis where progressive muscle weakness presents without the characteristic rash but with muscle histology of dermatomyositis. A 55-year-old woman presented with progressive severe proximal limb, neck, pharyngeal and respiratory muscle weakness, without dermatologic manifestations. Elevated muscle enzymes and myopathic electromyogram pointed towards inflammatory myositis while the muscle biopsy confirmed DMSD. Her condition improved with steroids, intravenous immunoglobulin, methotrexate, and rituximab. This case emphasises the necessity of maintaining a high index of suspicion for dermatomyositis, even when a classic skin rash is absent and the criticality of early aggressive treatment. Anti-NXP-2 antibody positivity could indicate severe disease.

Foodborne botulism outbreak with potential new management options.

To shed some light on a potential therapeutic modality that may facilitate resolution of botulism symptoms, namely 3,4-diaminopyridine (3,4-DAP). In Riyadh, Saudi Arabia, we recently encountered a foodborne botulism outbreak that, luckily, was discovered early. In Prince Sultan Military Medical city, we admitted, during a period of approximately 3 weeks, 15 probable cases, 2 of which were excluded due to more likely alternative diagnoses. We report in this case series 13 highly suspected cases of botulism that we encountered during the outbreak. A total of 12 out of 13 patients required intensive care unit (ICU) admission, one of which required intubation. Symptoms included cranial nerve palsies, gastrointestinal symptoms, limb and respiratory muscle weakness. Patients showed clinical improvement when received botulinum antitoxin and 3,4-DAP if given early in the course of the disease. Early admisntration of 3,4-DAP may facilitate recovery and prevent disease progression. Larger prospective trials should be carried out to confirm that.

Multidisciplinary approach on divergent outcomes in spinal muscular atrophies: comparing DYNC1H1 and SMN1 gene mutations.

Spinal Muscular Atrophy (SMA) emerges as a prominent genetic neuromuscular disorder primarily caused by variants in the survival motor neuron (SMN) gene. However, it is noteworthy that alternative variants impacting DYNC1H1 have also been linked to a subtype known as spinal muscular atrophy lower extremity predominant (SMA-LED). This observation underscores the complexity of SMA and highlights the necessity for tailored, gene-specific management strategies. Our study elucidates how similar approaches to managing SMA can yield distinct outcomes, emphasizing the imperative for personalized gene-based interventions in effectively addressing these conditions.Two patients were referred for further management due to clinical suspicion of type-3 SMA. The definitive diagnosis was confirmed through the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique, as well as whole-exome sequencing (WES).The analysis revealed deletions in exon-7 and 8 of SMN1 in the first patient and a likely pathogenic mutation (NM_001376.5(DYNC1H1):c.1867T > C (NP_001367.2: p.Phe623Leu)) in DYNC1H1 in the second patient. Both patients presented with lower limb muscle weakness. However, while the first patient exhibited a gradual increase in severity over the years, the second patient displayed no progressive symptoms. The management was adjusted accordingly based on the genetic findings.Our observation underscores the complexity of SMA and highlights the necessity for tailored, gene-specific management strategies. Our study elucidates how similar approaches to managing SMA can yield distinct outcomes, emphasizing the imperative for personalized gene-based interventions in effectively addressing these conditions.

Chest Dynamic MRI as Early Biomarker of Respiratory Impairment in Amyotrophic Lateral Sclerosis Patients: A Pilot Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. Methods: We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. Results: We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Conclusions: Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. We identified 166 patients with neurological symptoms appearing in less than 1month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1year follow-up. One patient died, and 15% of patients relapsed. Age > 70years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12months. No predictors of relapse were identified. This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: a case report and literature review

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain-Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

FUNCTIONAL ELECTRICAL STIMULATION COMBINED WITH VOLUNTARY CYCLING ACCENTUATES VO2 RESPONSE IN PEOPLE WITH ADVANCED MULTIPLE SCLEROSIS: A PILOT STUDY

INTRODUCTION &amp; AIMS Lower limb muscle weakness and reduced balance due to disease progression in multiple sclerosis (MS) may make robust aerobic exercise difficult. Functional electrical stimulation (FES) cycling combined with voluntary cycling may allow people with advanced MS to enhance the intensity of aerobic exercise. The aim of this study was to investigate the cardiorespiratory, power, and participant perceptions during acute bouts of FES cycling, voluntary cycling, and FES cycling combined with voluntary cycling (FES assist cycling). METHODS Participants with advanced MS (Expanded Disability Status Scale [EDSS] ≥ 6.0) undertook three exercise trials on a leg cycle ergometer. Trial 1: 30 minutes of FES cycling; Trial 2: two 10-minute bouts of voluntary cycling separated by 10 minutes rest; and Trial 3: a combination of trials 1 and 2 (FES assist cycling). Outcome measures included VO2, cycle power output, heart rate, exertion, and post-exercise perceptions of fatigue. RESULTS Ten people with advanced MS participated (9 female; age 52.4±9.98 y; EDSS 7.1±0.6). Average VO2 during the 30-minute trials was significantly higher for FES assist cycling compared to voluntary cycling (429.7 ± 111.0 vs 388.5 ± 101.0 mL/min, 95% CI 23.4 to 113.0 mL/min, p=0.01), with a large effect size (Hedges’ g=1.04). Participants reported similar perceptions of exertion at the end of each trial (p=0.14). There was no difference in self-reported fatigue at the end of each trial (p=0.21). CONCLUSION This study found FES assist cycling produced significantly higher VO2 values than voluntary cycling, although the clinical significance of these differences is unknown. Participants performed FES assist cycling at a self-reported levels of exertion consistent with moderate to vigorous intensity, however it was considered light-intensity exercise when expressed by METS. FES assist cycling was no more fatiguing post-exercise than the other modes.

Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN), an acquired chronic progressive immune-mediated motor neuropathy, is characterized by asymmetrical distal upper limb muscle weakness and muscle atrophy without sensory impairment. Differentiation from amyotrophic lateral sclerosis is usually challenging, and electrophysiological studies show multifocal conduction blocks. Immunoglobulin (Ig)M GM1 antibodies are detected in approximately 50% of patients. In contrast to chronic inflammatory demyelinating polyneuropathy, corticosteroids are ineffective for management of MMN, and IVIg is the sole established treatment.

Functional electrical stimulation combined with voluntary cycling accentuates VO2 response in people with severe multiple sclerosis: A pilot study

BackgroundLower limb muscle weakness and reduced balance due to disease progression in multiple sclerosis (MS) may make robust aerobic exercise difficult. Functional electrical stimulation (FES) cycling combined with voluntary cycling may allow people with severe MS to enhance the intensity of aerobic exercise. The aim of this study was to investigate the cardiorespiratory, power, and participant-reported perceptions during acute bouts of FES cycling, voluntary cycling, and FES cycling combined with voluntary cycling (FES assist cycling). MethodsParticipants with severe MS (Expanded Disability Status Scale [EDSS] ≥ 6.0) undertook three exercise trials on a leg cycle ergometer. Trial 1 involved 30 min of FES cycling; Trial 2 involved two 10-minute bouts of voluntary cycling separated by 10 min rest; and Trial 3 was a combination of trials 1 and 2 (FES assist cycling). Outcome measures included VO2 (volume of oxygen consumption), cycle power output, heart rate, RPE, and post-exercise perceptions of pain and fatigue. ResultsTen people with severe MS participated (9 female; age 52.4 ± 9.98 y; EDSS 7.1 ± 0.6). The average VO2 during the 30-minute trials was significantly higher for FES assist cycling compared to voluntary cycling (429.7 ± 111.0 vs 388.5 ± 101.0 mL/min, 95% CI 23.4 to 113.0 mL/min, p = 0.01), with a large effect size (Hedges' g = 1.04). Participants reported similar rates of perceived exertion at the end of FES cycling (13 ± 2), voluntary cycling (14 ± 2), and FES assist cycling (15 ± 1); p = 0.14. Self-reported pain was higher during both FES cycling (5.4 vs 0.3; 95% CI 3.4 to 6.7, p = 0.01, Hedges’ g = 2.07) and FES assist cycling (4.2 vs. 0.3; 95% CI 2.3 to 5.5, p = 0.01, Hedges’ g = 1.71) than voluntary cycling, both with large effect sizes. There was no difference in self-reported fatigue at the end of each trial (p = 0.21). ConclusionThis study found FES assist cycling produced significantly higher VO2 values than voluntary cycling, although the clinical significance of these differences is unknown. Participants performed FES assist cycling at a self-reported RPE consistent with moderate to vigorous intensity, however it was considered light-intensity exercise when expressed by METS. FES assist cycling was no more fatiguing post-exercise than the other modes.