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.

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.

[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.

[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.

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.

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.

Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor that targets the programmed cell death-1 protein and is effective in treating advanced cancer. However, it is also associated with various immune-related neurological complications, including myasthenia gravis, Guillain-Barré syndrome, and demyelinating polyneuropathy. These complications can easily mimic other neurological diseases and have greatly varying therapeutic approaches depending on the underlying pathophysiology. CASE PRESENTATION: Here, we report a case of nivolumab-induced demyelinating peripheral polyneuropathy involving the brachial plexus in a patient with Hodgkin lymphoma. Approximately 7 months after nivolumab treatment, the patient experienced muscle weakness with a tightness and tingling sensation in the right forearm. Electrodiagnostic studies showed features of demyelinating peripheral neuropathy with right brachial plexopathy. Magnetic resonance imaging revealed thickening with a diffuse enhancement of both brachial plexuses. The patient was eventually diagnosed with nivolumab-induced demyelinating polyneuropathy involving the brachial plexus. Oral steroid therapy improved motor weakness and sensory abnormalities without aggravation. CONCLUSION: Our study indicates the possibility of nivolumab-induced neuropathies in cases involving muscle weakness with sensory abnormalities of the upper extremity following nivolumab administration in patients with advanced cancer. Comprehensive electrodiagnostic studies and magnetic resonance imaging are helpful in the differential diagnosis of other neurological diseases. Appropriate diagnostic and therapeutic approaches may prevent further neurological deterioration.

Myositis with prominent B cell aggregates may meet classification criteria for sporadic inclusion body myositis.

The objective of this study was to report the clinical, serological and pathological features of patients with autoimmune myositis other than dermatomyositis, who displayed both muscle weakness on physical examination and prominent B cell aggregates on muscle pathology, defined as ≥ 30 CD20+ cells/aggregate. Specifically, the presence of a brachio-cervical inflammatory myopathies or a sporadic inclusion body myositis (sIBM) phenotype was recorded. Over a three-year period, eight patients were identified from two university neuropathology referral centers. Seven of 8 (88%) patients had an associated connective tissue disease (CTD): rheumatoid arthritis (n=3), systemic sclerosis (n=2), Sjögren's syndrome (n=1) and systemic lupus erythematosus (n=1), while one patient died on initial presentation without a complete serological and cancer investigation. A brachio-cervical phenotype, i.e. neck weakness, proximal weakness more than distal and shoulder abduction weakness greater than hip flexors, was seen in two patients (25%), while one patient had both proximal and diaphragmatic weakness. In contrast, an IBM-like clinical phenotype was seen in the last five patients (63%), who either had finger flexor weakness and/or quadriceps weakness ≤ 4 on the manual muscle testing MRC-5 scale. Although these 5 patients met at least one set of classification criteria for sIBM, an integrated clinico-sero-pathological approach argued against a diagnosis of sIBM. In summary, in a weak patient with myositis plus an associated CTD and lymphoid aggregates at muscle pathology, B cell predominant aggregates may represent a morphological biomarker against a diagnosis of sIBM.

Expanding the MYOD1 Phenotype: A Case Report of a Patient Diagnosed Whilst Pregnant.

A 38-year-old pregnant woman presented at 30 weeks gestation in respiratory distress with pre-eclampsia. This was on the background of slowly progressive dyspnoea over six years, with generalised weakness and previous surgery for ptosis and prognathia. After successful caesarean delivery at 31 weeks, the patient was found to have a homozygous likely pathogenic variant in the MYOD1 gene. This case presents a milder phenotype for MYOD1 congenital myopathy, usually associated with diaphragmatic defects, respiratory insufficiency and dysmorphic facies. It also highlights the difficulties of managing an undiagnosed patient through pregnancy.

Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report.

BACKGROUND: HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. CASE PRESENTATION: A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. CONCLUSIONS: Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

Challenging case of tumour-induced osteomalacia.

Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is an uncommon paraneoplastic syndrome which poses a diagnostic challenge. The hallmark feature is severe acquired hypophosphataemic osteomalacia due to renal phosphate wasting because of increased secretion of fibroblast growth factor 23 (FGF-23). A man in his 30s, presented with a 4-year history of severe muscle aches, bone pain and proximal muscle weakness, was referred for evaluation. His laboratory examination revealed severe hypophosphataemia as a result of urinary phosphate wasting, low 1,25-dihydroxyvitamin D, high alkaline phosphatase and elevated FGF-23. We could localise the tumour to his right femur and the biopsy showed a mesenchymal origin. The treatment with pharmacotherapy and radiofrequency ablation helped in the normalisation of blood chemistry and resulted in significant clinical improvement. Hypophosphataemia, phosphaturia, elevated FGF-23 and low 1,25-dihydroxyvitamin D level with severe musculoskeletal pain and muscle weakness necessitate careful evaluation of TIO.

A Single mtDNA Deletion in Association with a LMNA Gene New Frameshift Variant: A Case Report.

BACKGROUND: Proximal muscle weakness may be the presenting clinical feature of different types of myopathies, including limb girdle muscular dystrophy and primary mitochondrial myopathy. LGMD1B is caused by LMNA mutation. It is characterized by progressive weakness and wasting leading to proximal weakness, cardiomyopathy, and hearth conduction block. OBJECTIVE: In this article, we describe the case of a patient who presented with limb-girdle weakness and a double trouble scenario -mitochondrial DNA single deletion and a new LMNA mutation. METHODS: Pathophysiological aspects were investigated with muscle biopsy, Western Blot analysis, NGS nuclear and mtDNA analysis and neuromuscular imaging (muscle and cardiac MRI). RESULTS: Although secondary mitochondrial involvement is possible, a "double trouble" syndrome can not be excluded. CONCLUSION: Implication deriving from hypothetical coexistence of two different pathological conditions or the possible secondary mitochondrial involvement are discussed.

Dermatomyositis Identified During Palliative Care Management for Chemotherapy-Associated Pain: A Case Report.

Background: Skin disorders and neuropathy often occur as side effects of chemotherapy. We encountered a patient who was treated for drug-induced skin symptoms, but the symptoms did not improve, and he was eventually diagnosed as having dermatomyositis. Case presentation: A 71-year-old man underwent chemotherapy with regorafenib in February 2020 for the postoperative recurrence of sigmoid colon cancer, but treatment was discontinued after about 2 months owing to the appearance of skin symptoms, which were thought to be side effects of regorafenib. Subsequently, his symptoms further worsened, and he was hospitalized 3 weeks after the appearance of the initial skin symptoms, and a palliative care team was asked to relieve his back pain caused by the drug-induced skin symptoms. Erythema was widely observed on the lower back and limbs, and he experienced needle stick-like pain. Furthermore, the patient demonstrated difficulty in lifting both upper limbs. As acetaminophen was effective for his pain, the dose was slowly increased with careful observation. The cause of the patient's muscle weakness was unclear, and after careful discussion of the possible causes among specialists in dermatology, neurology, and rheumatoid arthritis, a diagnosis of dermatomyositis associated with the malignant tumor was made about 10 days after his admission. The patient's symptoms gradually improved with steroid pulse treatment (methylprednisolone 1 g/day for 3 days) followed by high-dose gamma globulin treatment (2.5 g/day for 5 days), and the patient was discharged 48 days after admission. Discussion: Because this patient was referred to a palliative care team for the purpose of relieving pain caused by skin symptoms associated with chemotherapy, a crucial point is the symptoms were treated as side effects of the chemotherapy from the beginning. As neuropathy can occur as a result of chemotherapy, the pain and muscle weakness could be explained at the time; however, the symptoms continued to worsen even after the chemotherapy was stopped. Because the symptoms were not typical of polymyositis/dermatomyositis, diagnosis of the patient was delayed, even though he was treated in each specialized department. Our present case indicates that paraneoplastic syndrome should always be kept in mind when treating cancer patients.

Non-Musculoskeletal Benefits of Vitamin D beyond the Musculoskeletal System.

Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most tissues and cells in the body, the mounting understanding of the role of vitamin D in humans indicates that it does not only play an important role in the musculoskeletal system, but has beneficial effects elsewhere as well. This review summarizes the metabolism of vitamin D, the research regarding the possible risk factors leading to vitamin D deficiency, and the relationships between vitamin D deficiency and numerous illnesses, including rickets, osteoporosis and osteomalacia, muscle weakness and falls, autoimmune disorders, infectious diseases, cardiovascular diseases (CVDs), cancers, and neurological disorders. The system-wide effects of vitamin D and the mechanisms of the diseases are also discussed. Although accumulating evidence supports associations of vitamin D deficiency with physical and mental disorders and beneficial effects of vitamin D with health maintenance and disease prevention, there continue to be controversies over the beneficial effects of vitamin D. Thus, more well-designed and statistically powered trials are required to enable the assessment of vitamin D's role in optimizing health and preventing disease.

Pain as a significant symptom in patients with periodic paralysis-A cross-sectional survey.

INTRODUCTION: Periodic paralysis (PP) is thought to be limited to episodes of muscle weakness, but there are reports of fibromyalgia-like pain in PP. We aimed to evaluate pain and comorbid sleep, fatigue, and mood disorders in PP patients. METHODS: We administered a cross-sectional survey to PP patients at the 2019 Periodic Paralysis Conference. The survey consisted of the Brief Pain Inventory, Widespread Pain Index, Pittsburgh Sleep Quality Index, Modified Fatigue Impact Scale, and ten-question Center for Epidemiologic Studies Depression Scale (CESD-10). Descriptive statistics for PP patients were calculated and compared with earlier studies. RESULTS: Forty-four individuals with PP took the survey. Of these patients, 52.3% reported a moderate to severe interference of pain on their lives, and 45.5% met the study criteria for fibromyalgia. Patients with SCN4A mutations had higher rates of fibromyalgia than the next most prevalent gene mutation, CACNA1S. In patients with pain, there were increased rates of comorbid fatigue, depression, and poor sleep quality. DISCUSSION: Pain, akin to fibromyalgia, is a significant symptom of PP and can affect quality of life. Pain in PP was more prevalent than in the general population, at a rate comparable with other chronic neuromuscular disease groups. PP patients could benefit from a multidisciplinary approach to assess their pain, sleep, fatigue, and mood.

Association of low back pain with muscle weakness, decreased mobility function, and malnutrition in older women: A cross-sectional study.

BACKGROUND: Low back pain (LBP) and decreased mobility function are common problem among older people. Muscle weakness has been reported as a risk factor for these conditions, and exercise therapy can improve them. We created a novel exercise device that also measures abdominal trunk muscle strength. Malnutrition has also emerged as a major problem among older people. Muscle is a direct key linking decreased mobility function and malnutrition. This study aimed to examine the associations of LBP with not only decreased physical function and muscle weakness but also nutritional status of older people. METHODS: We examined the associations of LBP with muscle weakness, decreased mobility function (locomotive syndrome [LS]), and malnutrition among older women. The study included 101 female patients aged 60 years or older scheduled to undergo surgery for degenerative lower extremity diseases. Preoperatively, physical tests including abdominal trunk muscle strength assessment using the device and laboratory tests were conducted. Subjects with LBP (numerical rating scale ≥2; range, 0-4) during the preceding month were allocated to the LBP group (n = 36). Other subjects were allocated to the non-LBP group (n = 65). RESULTS: The LBP group had lower abdominal trunk and knee extensor muscle strength, lower serum albumin, and hemoglobin levels as blood biomarkers associated with malnutrition risk, and higher LS test scores than the non-LBP group. A multivariate analysis showed that abdominal trunk muscle weakness and advanced LS were associated with LBP. LBP intensity was negatively correlated with abdominal trunk and knee extensor muscle strength and positively correlated with the LS test score. The serum hemoglobin level was negatively correlated with the LS test score. CONCLUSION: Abdominal trunk muscle weakness and decreased mobility function were associated with LBP among older women.