Severe papilloedema with vision loss secondary to Guillain-Barré syndrome.

We discuss a patient who presented with bilateral VI and VII cranial nerve palsies, symmetric upper and lower limb weakness and areflexia, 2 weeks following an flu-like illness. At presentation, there was no papilloedema, and her visual function was normal. Cerebrospinal fluid analysis and electrophysiology supported the diagnosis of Guillain-Barré Syndrome (GBS). She received intravenous immunoglobulins. She subsequently developed headaches and vision loss. Funduscopy demonstrated severe papilloedema with visual acuity of 6/18 right eye, 6/12 left eye with bitemporal visual field depression. Lumbar puncture revealed elevated opening pressure with high protein and normal cell count. She received acetazolamide. There was resolution of papilloedema and normal visual function at 3 months. Of note, the patient's body mass index was 17 kg/m2Our case highlights the rare occurrence of papilloedema in GBS, reiterating the importance of performing funduscopy on patients with any neurological diagnosis. Early detection and prompt management of papilloedema can prevent permanent vision loss.

Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease characterized by proximal muscle weakness, loss of tendon reflexes, and autonomic dysfunction. Muscle weakness usually starts in the upper legs and can progress to oculobulbar and in severe cases respiratory muscles. P/Q-type voltage-gated calcium channels (VGCCs) localized in the presynaptic motor nerve terminal and in the autonomic nervous system are targeted by antibodies in LEMS patients. These antibodies can be detected in about 90% of patients, and the presence of decrement and increment upon repetitive nerve stimulation is also a highly sensitive diagnostic test. Rapid diagnosis is important because of the association with SCLC in 50%-60% of patients, which stresses the need for vigorous tumor screening after diagnosis. Clinical parameters can predict tumor probability and guide frequency of tumor screening. Treatment of the tumor as well as symptomatic treatment and immunosuppression can effectively control symptoms in the majority of patients.

Muscle strength during pregnancy and postpartum in adolescents and adults.

Adolescent childbirth is associated with worse physical function over the long-term. Differential loss of muscle strength during pregnancy and postpartum for adolescents compared to adults may be one explanation for this, but research examining these differences is lacking. The objective of this study as to assess hand grip strength and hip adduction muscle strength in adolescents and adults during pregnancy and postpartum. A prospective cohort study was carried out with adolescent (13 to 18 years) and adult (23 to 28 years) primigravid women. Assessments were performed at three timepoints: before the 16th gestational week, during the third trimester, and between the fourth and sixth week postpartum. Hand grip strength (continuous and muscle weakness if ≤ 20.67 kgf) and hip adductor measures (continuous and muscle weakness if ≤ 13.8 kgf) were assessed using dynamometry. Generalized estimating equations modelled longitudinal relationships between muscle weakness and age group. More adolescents had hip adductor weakness than adults in the third trimester of pregnancy (62.5% vs. 31.8%, p < 0.005), which was corroborated by the longitudinal analyses. For all women, there were higher odds of hip adductor weakness in the third trimester (OR = 4.35; p< 0.001) and postpartum (OR = 9.45; p < 0.001) compared to the 16th gestational week. No significant difference in HGS was observed between age groups or across the different timepoints. The higher proportion of hip adductor weakness among adolescents may indicate a need for resistance training during and after pregnancy and physical therapy if weakness or injury is noted.

Differences in Glenohumeral Joint Contact Forces Between Recovery Hand Patterns During Wheelchair Propulsion With and Without Shoulder Muscle Weakness: A Simulation Study.

The majority of manual wheelchair users (MWCU) develop shoulder pain or injuries, which is often caused by impingement. Because propulsion mechanics are influenced by the recovery hand pattern used, the pattern may affect shoulder loading and susceptibility to injury. Shoulder muscle weakness is also correlated with shoulder pain, but how shoulder loading changes with specific muscle group weakness is unknown. Musculoskeletal modeling and simulation were used to compare glenohumeral joint contact forces (GJCFs) across hand patterns and determine how GJCFs vary when primary shoulder muscle groups are weakened. Experimental data were analyzed to classify individuals into four hand pattern groups. A representative musculoskeletal model was then developed for each group and simulations generated to portray baseline strength and six muscle weakness conditions. Three-dimensional GJCF peaks and impulses were compared across hand patterns and muscle weakness conditions. The semicircular pattern consistently had lower shear (anterior-posterior and superior-inferior) GJCFs compared to other patterns. The double-loop pattern had the highest superior GJCFs, while the single-loop pattern had the highest anterior and posterior GJCFs. These results suggest that using the semicircular pattern may be less susceptible to shoulder injuries such as subacromial impingement. Weakening the internal rotators and external rotators resulted in the greatest increases in shear GJCFs and decreases in compressive GJCF, likely due to decreased force from rotator cuff muscles. These findings suggest that strengthening specific muscle groups, especially the rotator cuff, is critical for decreasing the risk of shoulder overuse injuries.

Progressive Keratoconus in a Patient With Severe Pectus Excavatum and a Cartilage Oligomeric Matrix Protein Gene Mutation: A Case Report.

INTRODUCTION: Keratoconus is a progressive ocular disorder associated with numerous systemic diseases, many of which affect the musculoskeletal system. Although the etiology and pathophysiology of the disorder remain elusive, recent studies suggest a significant role of genetic predisposition in the pathogenesis of keratoconus. This case report aims to elucidate a potential genetic association in a patient presenting with keratoconus, severe pectus excavatum, generalized muscular weakness, and skeletal deformities. CASE DESCRIPTION: A 31-year-old Iranian man presented with progressively diminishing vision in both eyes over the years, eventually diagnosed with keratoconus. The patient's history and further examination indicated generalized muscular weakness, skeletal deformities, and severe pectus excavatum with cardiac and large vessel displacement. Whole-exome sequencing identified two heterozygous gene variants: one in the Cartilage Oligomeric Matrix Protein (COMP) gene and another in the Regulating Synaptic Membrane Exocytosis 1 gene. The patient's systemic and ocular symptoms, combined with the gene variants identified, suggested a connective tissue systemic disorder, potentially within the clinical spectrum of COMPopathies. CONCLUSION: This is the first documented case of bilateral progressive keratoconus associated with severe pectus excavatum, generalized musculoskeletal dystrophy, and a COMP gene mutation. It highlights the necessity of continued search into the pathogenic genes of keratoconus, particularly in cases with coexisting systemic manifestations, to further our understanding of the etiology and pathogenesis of this complex disease.

Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage.

Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD+/-). MnSOD+/- mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability.

Dermatomyositis presenting with diffuse calcinosis.

We present the case of a woman in her early 50s who initially presented to an orthopedist for nodules located near the posterior knee. Imaging revealed diffuse subcutaneous calcifications and she was subsequently referred to rheumatology. Additional testing included myositis panel, electromyography (EMG) and muscle biopsy which indicated the presence of an inflammatory myopathy. It was determined that this patient had an uncommon presentation of dermatomyositis in which her primary complaint was calcinosis cutis. While rash and muscle weakness are often the symptoms most commonly associated with dermatomyositis, it is essential to have a wide differential for patients presenting with calcium deposition in soft tissues. This is particularly important in patients with certain antibodies, including the NXP-2 antibody, which can be associated with malignancy and should prompt an appropriate malignancy workup.

Causal influence of muscle weakness on cardiometabolic diseases and osteoporosis.

The causal roles of muscle weakness in cardiometabolic diseases and osteoporosis remain elusive. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of muscle weakness in the risk of cardiometabolic diseases and osteoporosis. 15 single nucleotide polymorphisms (SNPs, P < 5 × 10-8) associated with muscle weakness were used as instrumental variables. Genetic predisposition to muscle weakness led to increased risk of coronary artery disease (inverse variance weighted [IVW] analysis, beta-estimate: 0.095, 95% confidence interval [CI]: 0.023 to 0.166, standard error [SE]:0.036, P-value = 0.009) and reduced risk of heart failure (weight median analysis, beta-estimate: - 0.137, 95% CI - 0.264 to - 0.009, SE:0.065, P-value = 0.036). In addition, muscle weakness may reduce the estimated bone mineral density (eBMD, weight median analysis, beta-estimate: - 0.059, 95% CI - 0.110 to - 0.008, SE:0.026, P-value = 0.023). We found no MR associations between muscle weakness and atrial fibrillation, type 2 diabetes or fracture. This study provides robust evidence that muscle weakness is causally associated with the incidence of coronary artery disease and heart failure, which may provide new insight to prevent and treat these two cardiometabolic diseases.

Ultrasound assessment of muscle mass and correlation with clinical outcomes in critically ill patients: a prospective observational study.

PURPOSE: Muscular atrophy implies structural and functional alterations related to muscular force production and movement. This condition has been reported to be the main reason for generalized muscle weakness; it reflects the severity of the disease and can have a profound impact on short- and long-term clinical outcomes. The purpose of this study was to determine whether muscle atrophy ultrasound parameters early predict muscle weakness, morbidity, or 28-days mortality. METHODS: This was a prospective, observational single center cohort study. Ultrasound was used to determine the cross-sectional area and muscle thickness of the rectus femoris on the first and third day of ICU stay. The main outcome was the incidence of significant muscle atrophy (≥ 10%). RESULTS: Ultrasound measurements were made in 31 patients, 58% (18/31) of which showed significant muscle atrophy. The relative loss of muscle mass per day was 1.78 at 5% per day. The presence of muscle atrophy presents increased risk for limb muscle weakness and handgrip weakness. The 28-days mortality rate was similar in both subgroups. CONCLUSION: The presence of muscle atrophy presents an increased clinical risk for the development of limb ICUAW and handgrip, although these observations were not statistically significant. The results could be used to plan future studies on this topic.

Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.

[A case of Charcot-Marie-Tooth disease type 2 caused by homozygous MME gene mutation].

The patient is a 44-year-old man. His parents are consanguineous. He experienced muscle weakness in his toe and distal tingling sensation in his feet at 42 years of age, which gradually progressed. Additionally, a marked cyanotic discoloration of the feet appeared and worsened progressively. Neurological examination revealed loss of tendon reflexes and distal muscle weakness in the lower extremities. Findings from nerve conduction studies indicated axonal polyneuropathy. Upon detection of the MME gene mutation, the patient was diagnosed with autosomal-recessive Charcot-Marie-Tooth disease 2T (ARCMT2T). In this case, cyanosis of the lower extremities possibly was associated with ARCMT2T, and it was suggested to be due to neprilysin deletion linked with the MME mutation. This represents the first documented occurrence of cyanosis as a distinctive feature of CMT with MME mutation.

[Two cases of anti-nuclear matrix protein 2 antibody-positive dermatomyositis sine dermatitis with severe diffuse subcutaneous edema and dysphagia].

Case 1 involved a 68-year-old woman who was admitted to our hospital because of muscle weakness, diffuse subcutaneous edema, dysphagia, and an elevated serum creatine kinase level that had worsened within the previous month. Case 2 involved a 78-year-old woman who was admitted to our hospital because of muscle weakness, bilateral shoulder pain, diffuse subcutaneous edema, and dysphagia that had gradually worsened during the past 5 months. Both patients showed severe diffuse subcutaneous edema and dysphagia and underwent enteral tube feeding. Although they had no skin lesions consistent with dermatomyositis, muscle biopsies showed myxovirus resistance protein A (MxA) expansion, and blood tests showed positivity for anti-nuclear matrix protein 2 (anti-NXP-2) antibody. Therefore, both presents were diagnosed with anti-NXP-2 antibody-positive dermatomyositis sine dermatitis (DMSD). Anti-NXP-2 antibody-positive dermatomyositis has been reported to be closely associated with DMSD, severe edema and dysphagia. Differential diagnosis for patients who develop myositis with severe subcutaneous edema and dysphagia should include anti-NXP-2 antibody-positive dermatomyositis, and it is important to consider measurement of anti-NXP-2 antibody.

[Foot drop and cyclic sensory disturbance of the right lower limb due to endometriosis].

We report the case of a 40-year-old woman, with endometriosis, who presented with a history of foot drop and cyclic sensory disturbance of the right lower limb. She was initially diagnosed with lumbar disc herniation. Neurological examination revealed muscle weakness and sensory disturbance associated with the right sciatic nerve. Nerve conduction studies revealed a low amplitude sensory nerve action potential in the right superficial fibular and sural nerves. Pelvic magnetic resonance imaging revealed an endometriotic cyst in the right ovary, and an endometriotic lesion extending from the right ovary, pelvis, and the right sciatic nerve. Though her symptoms moderately improved with hormonal therapy, the foot drop remained. Our case and previous reports suggest that endometriosis with sciatic neuropathy shows cyclic neurological symptoms during menstruation, with a higher incidence on the right extremity. This case highlights that endometriosis should be considered as a potential differential diagnosis in women of reproductive age with sciatic nerve dysfunction. Its cyclic neurological manifestations should be investigated.

Preoperative inspiratory muscle weakness as a risk factor of postoperative pulmonary complications in patients with esophageal cancer.

OBJECTIVE: We examined whether preoperative inspiratory muscle weakness (IMW) is a risk factor for postoperative pulmonary complications (PPCs) in patients with esophageal cancer who underwent subtotal esophagectomy. METHODS: This single-center retrospective cohort study enrolled patients with esophageal cancer who underwent a scheduled subtotal esophagectomy between June 2020 and May 2022. Maximal inspiratory pressure (MIP) was measured as inspiratory muscle strength using a respiratory dynamometer, and we defined IMW as MIP < 80% of the predicted value. Our primary outcome comprised overall PPCs. We investigated the relationship between IMW and PPCs using the Bayesian logistic regression model. RESULTS: After exclusion, 72 patients were included in this study. IMW was identified in 26 patients (36%), and PPCs developed in 28 patients (39%). Among patients with IMW, 15 (58%) developed PPCs. Preoperative IMW was associated with PPCs (mean odds ratio [OR]: 3.58; 95% credible interval [95% CrI]: 1.29, 9.73) in the unweighted model. A similar association was observed in the weighted model adjusted for preoperative and intraoperative contributing factors (mean OR: 4.15; 95% CrI: 2.04, 8.45). CONCLUSIONS: Preoperative IMW was associated with PPCs in patients with esophageal cancer who underwent subtotal esophagectomy. This association remained after adjusting for preoperative and intraoperative contributing factors.

Critical illness-associated weakness and related motor disorders.

Weakness of limb and respiratory muscles that occurs in the course of critical illness has become an increasingly common and serious complication of adult and pediatric intensive care unit patients and a cause of prolonged ventilatory support, morbidity, and prolonged hospitalization. Two motor disorders that occur singly or together, namely critical illness polyneuropathy and critical illness myopathy, cause weakness of limb and of breathing muscles, making it difficult to be weaned from ventilatory support, commencing rehabilitation, and extending the length of stay in the intensive care unit, with higher rates of morbidity and mortality. Recovery can take weeks or months and in severe cases, and may be incomplete or absent. Recent findings suggest an improved prognosis of critical illness myopathy compared to polyneuropathy. Prevention and treatment are therefore very important. Its management requires an integrated team approach commencing with neurologic consultation, creatine kinase (CK) measurement, detailed electrodiagnostic, respiratory and neuroimaging studies, and potentially muscle biopsy to elucidate the etiopathogenesis of the weakness in the peripheral and/or central nervous system, for which there may be a variety of causes. These tenets of care are being applied to new cases and survivors of the coronavirus-2 disease pandemic of 2019. This chapter provides an update to the understanding and approach to critical illness motor disorders.

Pembrolizumab-Induced Fatal Myasthenia, Myocarditis, and Myositis in a Patient with Metastatic Melanoma: Autopsy, Histological, and Immunohistochemical Findings-A Case Report and Literature Review.

Immune checkpoint inhibitors (ICIs) represent a major advance in cancer treatment. The lowered immune tolerance induced by ICIs brought to light a series of immune-related adverse events (irAEs). Pembrolizumab belongs to the ICI class and is a humanized IgG4 anti-PD-1 antibody that blocks the interaction between PD-1 and PD-L1. The ICI-related irAEs involving various organ systems and myocarditis are uncommon (incidence of 0.04% to 1.14%), but they are associated with a high reported mortality. Unlike idiopathic inflammatory myositis, ICI-related myositis has been reported to frequently co-occur with myocarditis. The triad of myasthenia, myositis, and myocarditis must not be underestimated as they can rapidly deteriorate, leading to death. Herein we report a case of a patient with metastatic melanoma who fatally developed myasthenia gravis, myocarditis, and myositis, after a single cycle of pembrolizumab. Considering evidence from the literature review, autopsy, histological, and immunohistochemical investigations on heart and skeletal muscle are presented and discussed, also from a medical-legal perspective.

Magnetic Resonance Imaging-negative Acute Inflammatory Myelopathy following Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

A 55-year-old woman was admitted to our hospital because of gait disturbance and urinary retention that acutely emerged 1 week after severe acute respiratory syndrome coronavirus 2 infection. Acute inflammatory myelopathy was clinically suspected, based on bilateral lower-limb weakness with an extensor plantar response and an elevated immunoglobulin G level in the cerebrospinal fluid. Whole-spine magnetic resonance imaging findings were normal. The central conduction time was extended, based on somatosensory evoked potentials. Her lower-limb weakness was partially ameliorated with immunosuppressive therapy. Postinfectious myelopathy is a rare neurological complication of coronavirus disease 2019 and can develop with normal radiological findings.

[Disseminated herpes zoster complicated by lumbosacral polyradiculoneuritis and fibular neuropathy: A case report].

A 74-year-old woman who presented with a skin eruption involving the left lateral leg along the L5 dermatome and widespread eruptions on the buttocks and trunk was diagnosed with disseminated herpes zoster (HZ). She also had left lower extremity muscle weakness. The pattern of distribution of muscle weakness and gadolinium-enhanced magnetic resonance imaging findings indicated polyradiculoneuritis mainly affecting the L5 spinal root. Moreover, we observed severe weakness of the left tibialis anterior muscle. Weakness of the other L5 myotomes reduced after antiviral treatment; however, left tibialis anterior muscle weakness persisted. We concluded that lumbosacral polyradiculoneuritis was attributable to varicella-zoster virus (VZV) infection, which also caused fibular neuropathy in this case. Retrograde transport of the VZV may have infected the fibular nerve throughout the sites of skin eruption. It is important to be mindful of simultaneous nerve root and peripheral nerve involvement in cases of motor paralysis associated with HZ infection.

Myasthenia gravis with inclusion body myositis: A case report.

We present the case of a 75-year-old man diagnosed with myasthenia gravis (MG) based on lower leg weakness and ptosis for the past 2 months before admission to our hospital. The patient was anti-acetylcholine receptor antibody-positive at admission. He was treated with pyridostigmine bromide and prednisolone, which improved the ptosis, but the lower leg muscle weakness remained. An additional lower leg magnetic resonance imaging examination suggested myositis. Inclusion body myositis (IBM) was diagnosed after a subsequent muscle biopsy. Although MG is often associated with inflammatory myopathy, IBM is rare. There is no effective treatment for IBM, but various treatment possibilities have recently been proposed. This case emphasises that myositis complications, including IBM, should be considered when elevated creatine kinase levels are observed and conventional treatments do not address chronic muscle weakness.