Clinical Reasoning: A 22-Year-Old Woman With Episodic Weakness and Jaundice.

We report a case of a 22-year-old woman who presented with recurrent episodes of quadriparesis, often accompanied by jaundice. Neurologic examination showed symmetrical proximal predominant quadriparesis with generalized hyporeflexia. The differential diagnoses included were of metabolic, inflammatory, genetic (including channelopathies), and autoimmune causes. Serum creatine phosphokinase levels and electrophysiologic studies helped narrow the differential. The final diagnosis was one that was responsive to vitamin supplementation. This report provides a systematic clinical approach to a case of episodic weakness with jaundice and respiratory failure.

The effects of inspiratory muscle training on biomarkers of muscle damage in recovered COVID-19 patients after weaning from mechanical ventilation.

Background: COVID-19 patients experience respiratory muscle damage, leading to reduced respiratory function and functional capacity often requiring mechanical ventilation which further increases susceptibility to muscle weakness. Inspiratory muscle training (IMT) may help mitigate this damage and improve respiratory function and functional capacity. Methods: We studied the effects of IMT on muscle damage biomarkers, respiratory function, and functional capacity in COVID-19 recovered young adults, successfully weaned from mechanical ventilation. Participants were randomly allocated to either an IMT (n = 11) or control (CON; n = 11) intervention for 4 weeks. The IMT group performed 30 dynamic inspiratory efforts twice daily, at 50% of their maximal inspiratory mouth pressure (PMmax) while the CON group performed 60 inspiratory efforts at 10% of pMmax daily. Serum was collected at baseline, week two, and week four to measure creatine kinase muscle-type (CKM), fast skeletal troponin-I (sTnI) and slow sTnI. Results: Time × group interaction effects were observed for CKM and slow sTnI, but not for fast sTnI. Both were lower at two and 4 weeks for the IMT compared to the CON group, respectively. Time × group interaction effects were observed for forced expiratory volume in 1s, forced vital capacity, PMmax and right- and left-hand grip strength. These were higher for the IMT compared to the CON group. Conclusion: Four weeks of IMT decreased muscle damage biomarkers and increased respiratory function and grip strength in recovered COVID-19 patients after weaning from mechanical ventilation.

Claw Hand in Acute Motor Axonal Neuropathy Variant.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy with various subtypes, including the acute motor axonal neuropathy (AMAN) variant. Distal muscle weakness is typically rare in AMAN. Myositis, an inflammatory muscle condition, is infrequently documented in GBS. This case report presents an unusual presentation of GBS with unilateral claw hand and myositis. CASE DESCRIPTION: A 55-year-old male presented with bilateral limb pain and weakness, progressing to significant motor impairment over 5 days. Symptoms began after a brief febrile illness with gastrointestinal distress. Upon examination, the patient exhibited decreased muscle strength in all limbs, dysphagia, and partial clawing of the left hand. Neurological assessment showed cranial nerve involvement and dysautonomia. Blood tests revealed elevated creatine phosphokinase (CPK) levels, and cerebrospinal fluid (CSF) analysis showed high protein without cellular abnormalities. Diagnosed with the AMAN variant of GBS, the patient was treated with intravenous immunoglobulin (IVIG) and antibiotics. Physiotherapy for speech, limbs, chest, and swallowing was initiated. Gradual improvement was observed, with increased limb power by the third week, although swallowing difficulties persisted longer. CONCLUSION: This case highlights a rare presentation of the AMAN variant of GBS with unilateral claw hand and myositis. The findings suggest that elevated CPK levels in GBS may not directly indicate myositis but could be secondary to the syndrome. Prompt diagnosis and treatment of the patient for recovery have been emphasized. This report underlines the need to consider GBS in patients presenting with atypical motor impairments and elevated CPK levels.

The other face of facioscapulohumeral muscular dystrophy: Exploring orofacial weakness using muscle ultrasound.

INTRODUCTION/AIMS: One of the most distinct clinical features of facioscapulohumeral muscular dystrophy (FSHD) is facial weakness. It leads to diminished facial expression and functional impairments. Despite its clinical relevance, little else is known about orofacial muscle involvement. We therefore evaluated orofacial muscle involvement in a sizeable cohort of FSHD participants with muscle ultrasound. METHODS: Muscle ultrasound images of the following orofacial muscles were scored visually and quantitatively: depressor anguli oris (DAO), orbicularis oris (OO), buccinator, temporalis, masseter, digastric, zygomaticus major and minor bilaterally, and the geniohyoid. Reliability analyses of both visual and quantitative evaluations were performed. Ultrasound results were correlated with other measures: the FSHD clinical score, facial weakness score, and facial function scale. RESULTS: We included 107 FSHD participants (male 54%; age 52 ± 14 years), of whom 92% showed signs of facial weakness. The reliability of visual ultrasound analysis varied widely (κ 0.0-1.0). Quantitative ultrasound reliability was high (intraclass correlation analysis ≥ 0.96). The DAO, buccinator, OO, temporalis, and zygomaticus minor muscles were affected most often (15%-39%). The digastric, geniohyoid, zygomaticus major, and masseter muscles were least often affected (<5%). The ultrasound compound score correlated weakly to moderately with other outcome measures used (ρ = 0.3-0.7). DISCUSSION: This study adds to the understanding of orofacial weakness in FSHD, confirming the involvement of the muscles of facial expression in FSHD using ultrasound. We showed that orofacial muscle ultrasound is feasible and reliable when quantitatively assessed. Future studies should evaluate orofacial muscle ultrasound longitudinally, alongside clinical and patient-reported facial weakness outcome measures, to assess their potential as outcome measures.

Clinical Reasoning: A 32-Year-Old Man With Painless Bilateral Shoulder Girdle Weakness and Atrophy.

We report a case of 32-year-old man with progressive, asymmetric, proximal weakness of both upper limbs for 14 months. On examination, he had gynecomastia and wasting and weakness of his deltoid, supraspinatus, infraspinatus, pectoralis, biceps, and triceps muscles, along with sensory loss of his left C5-C8 dermatomes. Deep tendon reflexes were depressed in the upper limbs and normal in the lower limbs. There was a history of a road traffic accident 2 years ago without any neurologic deficits. We discuss the clinical approach, differential diagnosis, investigations, and treatment options for bibrachial weakness.

Clinical Reasoning: A 61-Year-Old Man With Progressive Right Leg Numbness and Weakness.

Approaching patients with lumbosacral plexopathies or radiculoplexus neuropathies can be challenging and a well-defined strategy considering specific etiologies is necessary to arrive at the correct diagnosis. In this case, a 61-year-old man presented with a 10-year history of slowly progressive right lower extremity numbness and weakness. His examination was marked by right lower extremity weakness, decreased temperature/pinprick and proprioceptive/vibratory sensations, hypotonia, muscle atrophy, and absent right patellar, and ankle deep tendon reflexes. His workup was notable for electrodiagnostic findings of chronic lumbosacral radiculoplexus neuropathy and neuroimaging revealing marked enlargement, T2 signal abnormality, and faint contrast enhancement in multiple nerves. A targeted fascicular nerve biopsy yielded the final diagnosis of a rare disease. This case highlights the differential diagnoses of lumbosacral plexopathies or radiculoplexus neuropathies, including a guided workup. We also discuss the typical features of a rare diagnosis and its therapeutic options.

Dysphagia Revealing a Pharyngeal-cervical-brachial Variant of Guillain-Barré Syndrome in Pediatric Cases.

We report the case of a 13-year-old child presenting an unusual case of Guillian-Barre Syndrome (SGB). Its presentation is usually a progression of symmetrical muscle weakness that ascends from the lower extremities, moves toward a more proximal pathway, and is accompanied by absent or depressed tendon reflexes. Here, the patient presented with a rare presentation of Pharyngeal-Cervical-Brachial (PCB) variant of Guillain-Barré syndrome, where the symptomatology began with dysphagia and dyspnea, and the weakness was descending paralysis. The objective of this clinical case report is to highlight this extremely rare presentation of PCB variant of Guillain-Barré syndrome.

RésuméNous décrivons le cas d'un enfant âgé de 13 ans présentant une manifestation inhabituelle du syndrome de Guillain-Barré (SGB). Habituellement, le SGB se caractérise par une faiblesse musculaire symétrique ascendante des deux membres inférieurs, accompagnée d'une perte des réflexes ostéotendineux. Dans ce cas, le patient présentait une variante rare du SGB, appelée la variante Pharyngo-Cervico-Brachiale, où les symptômes ont débuté par une dysphagie et une dyspnée, et la faiblesse musculaire était descendante. L'objectif de cet article est de documenter cette présentation extrêmement rare de la variante Pharyngo-Cervico-Brachiale du syndrome de Guillain-Barré.

The Kinematics of 3D Arm Movements in Sub-Acute Stroke: Impaired Inter-Joint Coordination is Attributable to Both Weakness and Flexor Synergy Intrusion.

BACKGROUND: It has long been of interest to characterize the components of the motor abnormality in the arm after stroke. One approach has been to decompose the hemiparesis phenotype into negative signs, such as weakness, and positive signs, such as intrusion of synergies. We sought to identify the contributions of weakness and flexor synergy to motor deficits in sub-acute stroke. METHODS: Thirty-three sub-acute post-stroke participants and 16 healthy controls performed two functional arm movements; one within flexor synergy (shoulder and elbow flexion), and the other outside flexor synergy (shoulder flexion and elbow extension). We analyzed upper limb 3D kinematics to assess both overall task performance and intrusion of pathological synergies. Weakness and spasticity were also measured. RESULTS: Both tasks produced similar impairments compared to controls. Analysis of elbow and shoulder multi-joint coordination patterns revealed intrusion of synergies in the out-of-synergy reaching task based on the time spent within a flexion-flexion pattern and the correlation between shoulder and elbow angles. Regression analysis indicated that both weakness and synergy intrusion contributed to motor impairment in the out-of-synergy reaching task. Notably, the Fugl-Meyer Assessment (FMA) was abnormal even when only weakness caused the impairment, cautioning that it is not a pure synergy scale. CONCLUSIONS: Weakness and synergy intrusion contribute to motor deficits in the sub-acute post-stroke period. An abnormal FMA score cannot be assumed to be due to synergy intrusion. Careful kinematic analysis of naturalistic movements is required to better characterize the contribution of negative and positive signs to upper limb impairment after stroke.

A Reversible Etiology of Progressive Motor Decline in a Previously Healthy Child.

We describe the clinical presentation and evaluation of a 10-year-old boy who presented to our medical center with years of progressive proximal muscle weakness, muscle atrophy, and weight loss. In addition to a myopathic phenotype, he was found to have tachycardia, tremor, and learning difficulties. Electromyography revealed chronic myopathic changes and laboratory screening was notable for undetectable thyroid stimulating hormone. Follow-up testing revealed elevated thyroid peroxidase antibodies and thyroid stimulating immunoglobulins. Ultrasound examination revealed an enlarged heterogeneous thyroid gland. Four weeks after treatment with atenolol and methimazole, his strength and cognition began to improve. This case highlights the importance of evaluating for potentially reversible toxic-metabolic etiologies in children presenting with any progressive neurologic symptoms.

Ventilator-induced diaphragm dysfunction: phenomenology and mechanism(s) of pathogenesis.

Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field.

Respiratory muscle strength in stroke: a case-control study.

AIM: The aim of the study was to determine the respiratory muscle strength of stroke patients and compare them with healthy individuals. METHOD: The study was conducted with 171 patients who had a stroke between 2017 and 2021 and 32 healthy controls. Respiratory muscle strength and inspiratory and expiratory mouth pressure (MIP and MEP) were measured using the portable MicroRPM device (Micro Medical, Basingstoke, UK). RESULTS: The stroke group exhibited significantly lower values in both MIP for men (p<0.001) and women (p=0.013) and maximal expiratory pressure for men (p<0.001) and women (p=0.042), compared with the healthy control group. Notably, there was a significant difference in the MIPmen (p=0.026) and MEPmen (p=0.026) values when comparing the reference values, which were calculated based on age and sex, with those of the healthy group. The baseline values calculated according to age for stroke patients were as follows: MIPmen 31.68%, MIPwomen 63.58%, MEPmen 22.54%, and MEPwomen 42.30%. CONCLUSION: This study highlights the significant respiratory muscle weakness experienced by stroke patients, with gender-specific differences. It highlights the importance of incorporating respiratory assessments and interventions into stroke rehabilitation protocols to improve the overall health and well-being of stroke patients.

Roles of programmed death-1 and muscle innate lymphoid cell-derived interleukin 13 in sepsis-induced intensive care unit-acquired weakness.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a syndrome characterized by a long-term muscle weakness often observed in sepsis-surviving patients during the chronic phase. Although ICU-AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death-1 (PD-1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU-AW remains to be elucidated. Here, we study how PD-1 deficiency affects sepsis-induced skeletal muscle dysfunction in a preclinical sepsis model. METHODS: Chronic sepsis model was developed by treating wild-type (WT) and PD-1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15-17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL-13) and PD-1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow-twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). In an in vitro study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL-13 followed by gene expression measurements. RESULTS: WT septic mice exhibited decreased muscle weight (quadriceps, P < 0.01; gastrocnemius, P < 0.05; and tibialis anterior, P < 0.01) and long-term muscle weakness (P < 0.0001), whereas PD-1 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow-twitch specific mRNAs, including myoglobin (Mb), troponin I type 1 (Tnni1), and myosin heavy chain 7 (Myh7) were decreased in WT skeletal muscle (Mb, P < 0.0001; Tnni1, P < 0.05; and Myh7, P < 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (Mb, not significant; Tnni1, P < 0.0001; and Myh7, P < 0.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow-twitch mRNAs, which was restored by IL-13 (Mb, P < 0.0001; Tnni1, P < 0.001; and Myh7, P < 0.05). IL-13 production was significantly higher in ILC2s compared to T cells in skeletal muscle (P < 0.05). IL-13-producing ILC2s in skeletal muscle were examined and found to increase in PD-1 KO septic mice, compared with WT septic mice (P < 0.05). ILC2-derived IL-13 was increased by PD-1 KO septic mice and thought to protect the muscles from experimental ICU-AW. CONCLUSIONS: Long-term muscle weakness in experimental ICU-AW was ameliorated in PD-1 KO mice. ILC2-derived IL-13 production in skeletal muscles was increased in PD-1 KO mice, thereby suggesting that IL-13 alleviates muscle weakness during sepsis. This study demonstrates the effects of PD-1 blockade in preserving muscle strength during sepsis through an increase in ILC2-derived IL-13 and may be an attractive therapeutic target for sepsis-induced ICU-AW.

Knee flexor strength at 6 months after anterior cruciate ligament reconstruction using hamstring tendon can be predicted from that at 3 months.

PURPOSE: This study aimed to identify factors influencing persistent muscle weakness in knee flexor strength after anterior cruciate ligament (ACL) reconstruction using the hamstring tendon and establish a clear cut-off value at 3 months postoperatively for the limb symmetry index (LSI) to exceed 90% at 6 months postoperatively. METHODS: One hundred forty-eight patients undergoing ACL reconstruction were included and categorised into two groups based on knee flexor strength at 6 months postoperatively: patients with LSI of 90% or greater (achieved group: n = 114) and patients with LSI less than 85% (nonachieved group: n = 34). Items with significant differences between the two groups (preoperative waiting period, LSI to body weight ratio of knee flexor and extensor strength at 3 months postoperatively and peak torque angle of knee flexor muscle) were included in the multiple logistic regression analysis. Additionally, a receiver operating characteristic curve was used to calculate the cut-off value of the LSI at 3 months postoperatively, which was required to achieve the LSI criteria for knee flexor strength 6 months postoperatively. RESULTS: Multiple logistic regression analysis extracted the preoperative waiting period and LSI for knee flexor strength at 3 months postoperatively. The cut-off value at 3 months postoperatively was 76.9% (area under the curve value, 0.82; sensitivity, 0.76; and specificity, 0.81) of the LSI. CONCLUSION: The LSI of at least 76.9% for knee flexor strength at 3 months after ACL reconstruction was an indicator for achieving the 6 months postoperatively. This is a criterion to aim for, considering the stress on the graft and the regeneration process of the semitendinosus tendon. LEVEL OF EVIDENCE: Level III.

Case report: A patient with brachio-cervical inflammatory myopathy was misdiagnosed as flail arm syndrome.

Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment.

Clinical Reasoning: A 60-Year-Old Woman With Rapidly Progressive Muscle Weakness and Ophthalmoparesis.

The clinical assessment of patients with proximal muscle weakness represents a frequent yet intricate challenge. We present the case of a 60-year-old woman who experienced a progressive, symmetrical weakness in proximal limbs and bulbar muscles over 6 months. Notable clinical findings included bilateral ophthalmoparesis; widespread muscle atrophy; and pronounced weakness in craniobulbar, cervical, and proximal muscles, more severe than in distal ones. We elucidate a methodical diagnostic approach, focusing on constructing a comprehensive differential diagnosis and identifying potential causes of proximal muscle weakness. Special emphasis is placed on exploring the etiologies in cases presenting with both progressive muscle weakness and ophthalmoparesis. We further describe the role of muscle biopsy results and their integration with genetic testing outcomes.