Proximal Limb Muscles Research Articles

Compound heterozygous CAPN3 variants identified inafamily with limb-girdle muscular dystrophy recessive 1.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), a rare subtype of muscular dystrophy, is characterized by progressive muscle weakness and degeneration with a predominant presentation on the shoulder, pelvic and proximal limb muscles. Variants in calcium-activated neutral proteinase 3 (CAPN3), which encodes an enzyme, calpain 3, are considered the major cause of LGMDR1. The present study was conducted to identify the variants responsible for clinical symptoms in a Chinese patient with limb-girdle muscular dystrophies (LGMDs) and explore its genotype-phenotype associations. A series of clinical examinations were conducted, including blood tests and magnetic resonance imaging scans of the lower legs, electromyography and muscle biopsy on the proband diagnosed with muscular dystrophies. Genomic DNA was extracted from the peripheral blood of a three-person family with LGMDs and pathogenic variants detected by whole-exome sequencing (WES) were verified by Sanger sequencing. The WES of this patient revealed compound heterozygous variants in CAPN3, c.2120A>G/p.(Asp707Gly) in exon 20 and c.2201_2202delAT/p.(Tyr734*) in exon 21, which were inherited from his parents and absent from 200 control individuals of similar ethnic origin, indicating that these variants are the pathogenic triggers of the LGMDR1 phenotype. Notably, these CAPN3 sequence variants were related to LGMDR1 pathogenesis in this three-person family. The newly discovered c.2201_2202delAT/p.(Tyr734*) expands the current CAPN3 variant spectrum, improving the understanding of the conditions required to develop molecular diagnostic tools and for genetic counseling, particularly for families with a history of autosomal recessive LGMDs.

Anti-transcription intermediary factor 1 gamma (TIF1\u03b3) antibody-positive dermatomyositis associated with ascending colon cancer: a case report and review of the\xa0literature

BackgroundAnti-transcriptional intermediary factor 1 gamma (TIF1γ) antibody is a marker for predicting cancer association in patients with dermatomyositis (DM). The overall survival rate in DM patients with cancer was reported to be considerably worse than that in DM patients without cancer. However, the treatment for cancer-associated DM remains controversial, because the treatment priority between surgical resection for the tumor and internal treatments, including glucocorticoids, immunosuppressive agents, and intravenous immune globulin, has not been established.Case presentationWe report the case of a 57-year-old Japanese man diagnosed with anti-TIF1γ antibody-positive DM associated with ascending colon cancer. His clinical symptoms included facial and brachial edema, muscle weakness, dysphagia, myalgia, and rash. Physical examination revealed periorbital edema and Gottron's papules over his knuckles with brachial edema, and tenderness and weakness of the proximal limb muscles. The findings of hyperintense muscles in T2-weighted sequences of brachial contrast-enhanced magnetic resonance imaging and the infiltration of lymphocytic cells and CD4-positive lymphocytes from muscle biopsy were compatible with the diagnostic criteria for dermatomyositis. Anti-TIF1γ antibody was positive by immunoprecipitation assay. He first started internal treatment including intravenous immunoglobulin, steroid pulse, prednisolone, and azathioprine, followed by surgical resection for the tumor because of the elevation of creatine kinase and progression of dysphagia. However, clinical symptoms did not improve, and the patient died 6 months later.ConclusionsWe faced difficulties in determining the treatment priority between surgical resection and internal treatment for our case; therefore, this case would be educational for readers. We searched PubMed to identify English-language case reports of anti-TIF1γ antibody-positive dermatomyositis with malignancy and found 21 reported cases. We herein review and summarize previously reported cases of anti-TIF1γ antibody-positive DM with malignancy. Cancer screening is essential in patients with anti-TIF1γ antibody-positive dermatomyositis because it is associated with a high prevalence of malignancies. Our review revealed that initial surgical treatment should be recommended for better prognosis if the general condition allows.

Preserved eye movements in adults with spinal muscular atrophy.

Spinal muscular atrophy (SMA) most prominently affects proximal limb and bulbar muscles. Despite older case descriptions, ocular motor neuron palsies or other oculomotor abnormalities are not considered part of the phenotype. We investigated oculomotor function by testing saccadic eye movements of 15 patients with SMA. Their performance was compared with that of age-matched healthy controls. Horizontal rightward and leftward saccades were recorded by means of video-oculography, whereas subjects looked at light-emitting diode targets placed at ±5°, ±10°, and ±15° eccentricities. No differences in saccade amplitude gains, peak velocities, peak velocity-to-amplitude ratios, or durations were observed between controls and patients. More specifically, for 5° target eccentricities, patients had a mean saccadic peak velocity of 153°/s, whereas for 10° and 15° these values were 268°/s and 298°/s, respectively. The corresponding mean peak velocities of the control group were 151°/s, 264°/s, and 291°/s. Our results indicate that patients with SMA perform fast and accurate horizontal saccades without evidence of extraocular muscle weakness. These quantitative oculomotor data corroborate clinical experience that neuro-ophthalmic symptoms in SMA are not common and, if present, should prompt suspicion for an alternative neuromuscular disorder.

Chloroquine and Hydroxychloroquine Myopathy: Clinical Spectrum and Treatment Outcomes.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. In this retrospective study, we aimed to define the clinical phenotype, laboratory features, and treatment outcomes of CQ/HCQ myopathy, as well as the safety profile of these drugs. We identified 13 patients seen between 2000 and 2019, with a median age at presentation of 66 years (range 53–89); 11 were females. At onset of symptoms, patients were on CQ or HCQ for a minimum of 6 months and up to 21 years. Diagnosis was often delayed by a median of 6 months (range 3–48). At presentation, 13 patients reported limb weakness, with five requiring assistance in walking. Ten reported dysphagia, often severe, resulting in marked weight loss or aspiration pneumonia. Nine reported respiratory symptoms, which were multifactorial in four, and four reported severe neck weakness. Myopathy clinical phenotype showed predominant involvement of one or more of the following: proximal limb muscle weakness (12 patients), dysphagia (9), axial weakness (4), and respiratory failure (5). Eleven patients had a cardiac evaluation showing prolonged QT interval in 10 and CQ/HCQ cardiomyopathy (CMP) in four. Ten out of 12 patients markedly improved after discontinuing the medication, but most were left with some residual weakness. Eleven patients had a muscle biopsy showing a myopathy with rimmed vacuoles and marked acid phosphatase reactivity. Nine had elevated creatine kinase level up to 1,199 U/L. Twelve patients had an electromyography (EMG), which showed myopathic motor unit potentials with fibrillation potentials in 11 and myotonic discharges in 3. Higher cumulative dose and longer exposure duration were associated with more severe disability and more common cardiac and swallow involvement, indicating a cumulative dose effect. Herein, we demonstrate that long-term exposure to CQ and HCQ may result in a myopathy with a wide spectrum of clinical presentation and predilection for swallowing, respiratory, and cardiac muscles, often with marked associated morbidity. Once accurately diagnosed and the drug is discontinued, patients usually improve but often fail to return to baseline.

Synergistic Activation Patterns of Hand Muscles in Left-and Right-Hand Dominant Individuals.

Handedness has been associated with behavioral asymmetries between limbs that suggest specialized function of dominant and non-dominant hand. Whether patterns of muscle co-activation, representing muscle synergies, also differ between the limbs remains an open question. Previous investigations of proximal upper limb muscle synergies have reported little evidence of limb asymmetry; however, whether the same is true of the distal upper limb and hand remains unknown. This study compared forearm and hand muscle synergies between the dominant and non-dominant limb of left-handed and right-handed participants. Participants formed their hands into the postures of the American Sign Language (ASL) alphabet, while EMG was recorded from hand and forearm muscles. Muscle synergies were extracted for each limb individually by applying non-negative-matrix-factorization (NMF). Extracted synergies were compared between limbs for each individual, and between individuals to assess within and across participant differences. Results indicate no difference between the limbs for individuals, but differences in limb synergies at the population level. Left limb synergies were found to be more similar than right limb synergies across left- and right-handed individuals. Synergies of the left hand of left dominant individuals were found to have greater population level similarity than the other limbs tested. Results are interpreted with respect to known differences in the neuroanatomy and neurophysiology of proximal and distal upper limb motor control. Implications for skill training in sports requiring dexterous control of the hand are discussed.

Involuntary movement in stiff-person syndrome with amphiphysin antibodies: A case report.

Rationale:Stiff-person syndrome (SPS) is a rare neurological immune disorder characterized by progressive axial and proximal limb muscle rigidity, stiffness, and painful muscle spasms. Amphiphysin antibodies are positive in approximately 5% of SPS patients. To date, there have been no relevant reports on involuntary movement in cases of SPS with amphiphysin antibodies.Patient concerns:We describe the case of a 69-year-old man with a 2-year history of progressive stiffness in the neck, bilateral shoulders, and chest muscles, and a more-than-a-year history of dyspnea accompanied by mandibular involuntary movement. The patient was a vegetarian and had good health in the past. The family's medical history was unremarkable.Diagnoses:He was diagnosed with SPS based on the progressive muscle stiffness, the amphiphysin antibody seropositivity, the continuous motor activity on electromyography, and the effective treatment with benzodiazepines.Interventions:The patient was orally administered clonazepam and baclofen, and corticosteroid IV followed by prednisone orally.Outcomes:In the hospital, after treatment with methylprednisolone, clonazepam, and baclofen, the patient's rigidity, stiffness, and dyspnea significantly improved. The involuntary movement of the mandible persisted throughout the treatment process. Currently, under oral treatment with baclofen and clonazepam, the patient's symptoms of muscle stiffness and dyspnea exist, and follow-up is continued.Lessons:We report a rare and novel case of involuntary movement in SPS with amphiphysin antibodies. The present report explores the relationship between SPS and involuntary movement and expands the spectrum of clinical manifestations of SPS.

Parsonage turner syndrome: a common syndrome usually missed

Background: Parsonage-turner syndrome (PTS) is a rare syndrome that can occur in normal healthy individuals with sudden, rather abrupt, unilateral shoulder pain that may begin rather insidiously but quickly amplifies in severity and intensity. The acute period of pain is subsequently replaced over a course of a few days to weeks with progressive weakness, reflex changes, and sensory abnormalities in varying presentations that typically involve the shoulder girdle musculature and proximal upper limb muscles. There are no definite etiological factors present in causation of this syndrome.Methods: Prospective multicentric cohort study covering period from 2010 to 2020. 10 young male patients were included in the study group, all of them presented with winging of scapula and pain. Initial evaluation was done at neurology department and after failure of conservative treatment of average period of six month they were referred to plastic surgery department. All patients had ENMG findings preoperatively.Results: 10 male patients were studied with average age of 24.8 years. Partial paralysis present for an average of 1 year. Repeated micro trauma was the most common aetiology. Intraoperatively 7 patients had anomalous vascular compression of long thoracic nerve (LTN) and three had compression due to fibrous sheath. All patients had complete recovery at end of one year.Conclusion: Isolated LTN paralysis is a rare condition that is not well known. If conservative management fails, then neurolysis of the distal segment of LTN gives good result if performed within 6-12 months of paralysis.

EP23 Symptomatic sarcoid myopathy: a rare extra-pulmonary manifestation of sarcoidosis

EP23 Symptomatic sarcoid myopathy: a rare extra-pulmonary manifestation of sarcoidosis

A novel pathogenic variant in DYNC1H1 causes various upper and lower motor neuron anomalies

ObjectiveTo perform genotype-phenotype, clinical and molecular analysis in a large 3-generation family with autosomal dominant congenital spinal muscular atrophy. MethodsUsing a combined genetic approach including whole genome scanning, next generation sequencing-based multigene panel, whole genome sequencing, and targeted variant Sanger sequencing, we studied the proband and multiple affected individuals of this family who presented bilateral proximal lower limb muscle weakness and atrophy. ResultsWe identified a novel heterozygous variant, c.1826T > C; p.Ile609Thr, in the DYNC1H1 gene localized within the common haplotype in the 14q32.3 chromosomal region which cosegregated with disease in this large family. Within the family, affected individuals were found to have a wide array of clinical variability. Although some individuals presented the typical lower motor neuron phenotype with areflexia and denervation, others presented with muscle weakness and atrophy, hyperreflexia, and absence of denervation suggesting a predominant upper motor neuron disease. In addition, some affected individuals presented with an intermediate phenotype characterized by hyperreflexia and denervation, expressing a combination of lower and upper motor neuron defects. ConclusionOur study demonstrates the wide clinical variability associated with a single disease causing variant in DYNC1H1 gene and this variant demonstrated a high penetrance within this large family.

Neck rotation modulates motor-evoked potential duration of proximal muscle cortical representations in healthy adults

Transcranial magnetic stimulation (TMS) produces motor-evoked potentials (MEP) used to infer changes in corticomotor excitability. In humans, neck rotation can probe reticulospinal input on corticomotor output. This study investigated the effect of neck rotation on MEP duration in a proximal and distal upper limb muscle and compared responses between rest and preactivation. Single-pulse TMS to motor cortex was used to evoke MEPs at two stimulus intensities in 18 healthy adults (20-40years). Surface electromyography recorded MEPs from the non-dominant biceps brachii (BB) and first dorsal interosseous (FDI). Participants were seated with the target muscle at rest or 10% preactivated, and head rotated ipsilateral, contralateral, or in neutral position. The primary outcome was MEP tail, defined as the mean difference in MEP duration between active and rest trials. Secondary outcomes were MEP duration and amplitude. MEP tail was modulated by neck rotation in the proximal BB (P = 0.03) but not distal FDI (P > 0.19), with shorter duration during ipsilateral or contralateral rotation relative to neutral. In a neutral neck position, MEP duration was prolonged by muscle preactivation and higher TMS intensities in the FDI and BB (P < 0.03). Neck rotation attenuated the prolongation of MEP duration during preactivation in the BB, but not the FDI. Neck rotation had no effect on MEP amplitude for either muscle (P > 0.05). Modulation of the late portion of the MEP by rotation of the neck could indicate subcortical projections to alpha-motoneuron pools are stronger in proximal than distal upper limb muscles. These findings may have relevance for using MEP duration as a neural biomarker in neurological diseases.

Proximal Upper Limb Sensorimotor Integration in Response to Novel Motor Skill Acquisition.

Previous studies have shown significant changes in cortical and subcortical evoked potential activity levels in response to motor training with the distal upper-limb muscles. However, no studies to date have assessed the neurological processing changes in somatosensory evoked potentials (SEPs) associated with motor training whole-arm movements utilizing proximal upper-limb muscles. The proximal upper-limb muscles are a common source of work-related injuries, due to repetitive glenohumeral movements. Measuring neurophysiological changes following performance of a proximal motor task provide insight into potential neurophysiological changes associated with occupational postures and movements involving proximal upper limb muscles. This study sought to assess the impact of a novel motor skill acquisition task on neural processing of the proximal upper-limb muscle groups, through the measurement of short-latency median nerve SEPs. One group of 12 participants completed a novel motor training task, consisting of tracing a sinusoidal waveform varying in amplitude and frequency. Baseline SEP measurements were recorded from each participant, followed by a mental recitation control task. Pre-test SEP measurements were then recorded, followed by the motor training task, and post-test SEP recordings. The participants completed the tracing with their right thumb, using glenohumeral rotation only to move their hand. Significant improvements in task accuracy were demonstrated, indicating that motor acquisition had occurred. Significant changes were also seen in the N11, N13, N20, N24, P25, and the N30 SEP peaks were seen following the motor training task. Conclusion: Early SEPs appear to be a sensitive measure of changes in sensorimotor integration in response to novel motor skill acquisition within the proximal upper-limb muscles.

Save your Boat from Sinking Earlier: Don’t be Hurry for Direct Laryngoscopic Assessment in a Dysphagia Patient

Myasthenia gravis (MG) is a relatively rare autoimmune disorder caused by an antibody-mediated blockade of neuromuscular transmission resulting in skeletal muscle weakness. The autoimmune attack occurs when autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles. Patients with myasthenia, usually presents with painless, specific muscle weakness. Typically it affects extra ocular, bulbar, or proximal limb muscles. Approximately 50% to 80% patients presents with ocular and 20% patient presents with bulbar symptoms. Though some specific clinical and serological tests are there to confirm the diagnosis, a high index of suspicion and detail clinical history brings the utmost importance. In this article we highlighted 02 cases of MG; a boy of 15 years and a male farmer 42 year presented with the presentation of MG

STIFF PERSON SYNDROME (SPS) THE IMPORTANCE OF EXTENSIVE PHYSICAL EXAMINATION

Stiff Person Syndrome (SPS) is a rare condition with a prevalence of one to two cases per million and an incidence of one case per year. Characterized by progressive muscle stiffening, rigidity and spasm, mainly involve the axial muscles, resulting in severely impaired ambulation. The pathogenesis is not that clear. Classic SPS presents with extreme and persistent rigidity and stiffness of truncal and proximal limb muscles, significant lumber/cervical lordosis resulting from simultaneous actions of opposing paraspinous muscles are the hallmark. Wide and unsteady gait (Frankenstein’s gait) resulting from stiff muscles increases the risk of fall and fracture. Patient’s ADLs get severely restricted progressively. Startle reflex which is a superimposed episodic muscle spasm precipitated by sudden movement, noise, or emotional upset is a sensitive and specific feature of SPS and can be visible and palpable. Autonomic dysfunctions are common and are common cause of death in patients with SPS. In cases of partial SPS, we can find that truncal muscles are spared and limb muscles are affected, hence the term stiff-limb syndrome is used sometimes. Can involve a limb or focal part of a limb. As for treatment, symptom control and improving mobility and overall functionality is the primary target. High dose benzodiazepine is the best initial treatment. Those who are refractory can be benefit from Baclofen, IVIG, Plasma exchange, biological agent, e.g. Rituximab. Treatment of primary malignancies in paraneoplastic SPS can achieve remission. Keywords: Stiff Person Syndrome, clinical features, diagnosis and treatment.

SAT-LB81 Carbohydrate Crash: A Rare Case of Thyrotoxic Periodic Paralysis

IntroductionThyrotoxic Hypokalemic Periodic Paralysis (TPP) is an uncommon diagnosis in the western world and may be the initial presentation of hyperthyroidism. CaseA healthy 37 year old Asian male was visiting the US when he had sudden onset lower limb weakness after carbohydrate rich meal on Saturday night. He reported hand tremors for 1 month and a 10kg weight loss. On examination he was anxious with a fine hand tremor, BP 158/80mmHg, and HR 106bpm. He had grade 2/5 power to lower limb proximal muscles and brisk reflexes. Thyroid and eyes were normal. Laboratory results significant for potassium (K) 3.2mmol/l, TSH 0.005 (0.270-4.4uiu/ml), FT4 2.6 (0.8-2.2ng/dl), FT3 12.4 (2.77-5.27 pg/ml) and TSH Receptor antibody was 23.9% (<16%). Thoracolumbar MRI was normal. Repletion of K resulted in total resolution of paresis. He was given propranolol and methimazole and chose to complete workup in China.Clinical LessonTPP results in paralysis due to hypokalemia and hyperthyroidism and can be the initial presentation of hyperthyroidism. It is most common in Asian males 20-40 years with incidence 1.9%, but only 0.2% in the west. Proximal muscles are affected more. Attacks may be precipitated by carbohydrate load, rest after exercise, or stress. Patients tend to present on weekends between 2100-0900hrs. It is hypothesized that K metabolism is diurnal, with influx to muscle at night or at rest. Once euthyroid, TPP will not recur unlike familial hypokalemic periodic paralysis which is recurrent and of earlier onset. The underlying reason remains unclear. It may be related to the action of thyroxine on Na/K-ATPase pump. TPP is usually associated with Graves’ disease, but other causes of hyperthyroidism have been reported. TPP is a treatable rare illness in Asians, and very uncommon in the West. Physicians must be aware of its subtleties, as it may be confused with other more common conditions.ReferencesChang-Hsun Hsieh, Shi-Wen Kuo, Dee Pei, Yi-Jen Hung, Sandra Chyi-Fan, Ling-I Wu, Chih-Tsueng He, Tsao-Chin Yang, Wei-Cheng Lian, and Chien-Hsing Lee, Thyrotoxic periodic paralysis: an overview, Ann Saudi Med. 2004 Nov-Dec; 24(6): 418-422. doi:10.5144/0256-4947.2004.418Annie W. C. Kung, CLINICAL REVIEW: Thyrotoxic Periodic Paralysis: A Diagnostic Challenge, The Journal of Clinical Endocrinology and Metabolism 91(7):2490-2495, Copyright © 2006 by The Endocrine Society doi: 10.1210/jc.2006-0356

Clinical phenotype and genotype of early-onset facioscapulohumeral muscular dystrophy type 1

Objective: To explore the clinical, pathological and genetic characteristics of early-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1), in order to increase awareness of the disease. Methods: In this retrospective study, the history of 3 patients, who were diagnosed with early-onset FSHD1 by molecular genetic test in Pediatric Outpatient Department of Peking University First Hospital from 4(th) June 2012 to 4(th) June 2018, were collected. Their clinical data, genotypes, phenotypes and pathological features of muscle biopsy were analyzed. Results: All the three patients were males at the age of 14 years, 11 years and 9 years 11 months, respectively, whose onset age was between infancy and early childhood and they got confirmed diagnosis within 4 to 10 years after the onset of illness. Their molecular genetic testing indicated that the number of D4Z4 repeat arrays located in 4qA were 2, 3 and 4, which was consistent with the characteristics of early-onset FSHD1. Their common clinical manifestations were facial, scapular and proximal lower limb muscle progressively and asymmetrically weakness. All patients had different severity of spine deformity and high-frequency dominant sensorineural hearing loss, however, the phenotype of the third patient with 4 D4Z4 repeats was significantly the most severe. Conclusions: Early-onset FSHD1 usually concealed onset and is difficult to diagnose. Its precise diagnosis depends on molecular genetic techniques, but the genotypes of 3 patients here are not corresponding to phenotypes strictly and it is necessary to accumulate more cases for further analysis in order to provide a more reliable basis for the relationship of genotype-phenotype and prognosis evaluation of the disease.

The Efficacy of Pralidoxime in the Treatment of Organophosphate Poisoning in Humans: A Systematic Review and Meta-analysis of Randomized Trials.

IntroductionThe benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain. Pralidoxime is the most often used oxime worldwide. In vitro experiments have consistently shown that oximes are effective reactivators of human acetylcholinesterase enzyme, inhibited by OP compounds. However, the clinical benefit of pralidoxime is still unclear. A recent meta-analysis has found that pralidoxime provides no significant improvement in outcome and rather may cause harm while increasing the economic burden in low-income communities where its use is the most prevalent.ObjectivesThis study aimed to provide an updated evaluation of the efficacy of pralidoxime in addition to atropine alone in the treatment of patients with acute OP poisoning in terms of mortality, need for ventilator support, and the incidence of intermediate syndrome. The intermediate syndrome is a clinical syndrome that occurs 24 to 96 hours after the ingestion of an OP compound and is characterized by prominent weakness of neck flexors, muscles of respiration, and proximal limb muscles. Materials and methodsWe searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases until January 2019 for randomized controlled trials (RCTs) in the English language that evaluated the use of pralidoxime in individuals of any age, gender or nationality presenting with an alleged history of OP intake. The primary outcome was mortality. Secondary outcomes were the need for ventilator support and the incidence of intermediate syndrome. The risk of bias in included studies was assessed using the tool recommended by the Cochrane Handbook of Systematic Review of Interventions. Treatment/control differences in these outcomes across included studies were combined using risk ratios (RR).ResultsSix randomized controlled trials (n = 646) fulfilled the inclusion criteria, including one further trial missed from the most recent systematic review. The risk of bias varied across studies, with Eddleston 2009 being of the lowest risk and Cherian 2005 being of high risk. The risk of mortality (RR = 1.53, 95% confidence interval (CI) 0.97 to 2.41, P = 0.07) and the need for ventilator support (RR = 1.29, 95% CI 0.97 to 1.71, P = 0.08) were not significantly different between the pralidoxime and the control group. There was a significant increase in the incidence of intermediate syndrome in the pralidoxime group (RR = 1.63; 95% CI 1.01 to 2.62, P = 0.04).ConclusionsBased on our meta-analysis of the available RCTs, pralidoxime was not shown to be beneficial in patients with acute OP poisoning. Our findings are consistent with the other literature.

A Rare Case of Statin-Induced Necrotizing Autoimmune Myopathy

Necrotizing autoimmune myopathy (NAM) is a rare side-effect of statin therapy. We report the case of a patient who developed statin-induced NAM with a review of the clinical presentation and management of this rare entity. The case illustrates the importance of including NAM in the differential diagnosis of persistent myopathy in a statin-exposed individual. A 74-year-old male was referred to endocrinology for hypercholesterolemia management in the context of a statin contraindication. He previously developed myositis and rhabdomyolysis secondary to statin therapy, but continued to have persistent proximal lower limb muscle weakness despite statin discontinuation. Rheumatologic and metabolic work-up were negative and neurologic work-up was negative except for a myopathic pattern in the glutei found on electromyography. Due to the persistence of proximal myopathy despite statin discontinuation and myopathic pattern seen on electromyography, NAM was suspected and antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase were sent and came back positive. The patient was treated with the immunosuppressant azathioprine, which resulted in clinical improvement. The patient was started on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolucumab for hypercholesterolemia, which resulted in significant improvement in his lipid panel. The case illustrates the presentation and management of statin-induced NAM. We demonstrate the necessity for prompt diagnosis and timely management, as statin therapy is contraindicated and immunosuppressive therapy is warranted. Statin-induced NAM is rare however, it should be included in the differential diagnosis of persistent myopathy despite statin discontinuation. PCSK9 inhibitors are the only alternative therapy for hypercholesterolemia management in patients with statin-induced NAM.

Acetylcholine Receptor-Antibody-Positive Myasthenia Gravis Presenting with Early Atrophy and Nonfluctuating Weakness of Proximal Limb Muscles.

Acetylcholine Receptor-Antibody-Positive Myasthenia Gravis Presenting with Early Atrophy and Nonfluctuating Weakness of Proximal Limb Muscles.

Early respiratory involvement leading to respiratory failure in a case of Systemic sclerosis - Polymyositis overlap

Polymyositis is an autoimmune myopathy with a preponderance to involve proximal limb muscles in a symmetrical manner. Type two respiratory failure and severe bulbar weakness is not a common mode of initial presentation of polymyositis – systemic sclerosis overlap syndrome. We present a case of a middle age female , who presented with dysphagia, nasal regurgitation, aspiration of food and proximal muscle weakness, worsening over 6 months duration. The disease was rapidly progressing and culminated in severe respiratory muscle weakness and respiratory arrest necessitating invasive ventilation. The diagnosis of sero- negative polymyositis and systemic sclerosis overlap syndrome was made and she achieved a remarkable recovery with intensive care and meticulous immunosuppressive therapy. Physicians should be aware of the rapid respiratory muscle involvement in systemic sclerosis and Polymyositis overlap since timely initiation of treatment is life saving.

Myopathy associated with anti-signal recognition peptide antibodies: Five case reports

Five patients with myopathy associated with anti-signal recognition peptide antibodies, admitted to our hospital from December 2015 to June 2018, were chosen in our study, and their clinical and pathological manifestations and treatments were retrospectively analyzed. Five patients showed subacute or chronic onset and proximal limb muscle weakness. Serum creatine kinase level was significantly elevated. Immunoblotting assay confirmed the positive anti-signal recognition particle antibody. EMG prompted myogenic damage. Pathological features included muscle degeneration, necrosis with regeneration, visible atrophy and hypertrophic of muscle fiber, connective tissue hyperplasia and a small amount of inflammatory cell infiltration. Immunohistochemical staining showed necrotizing muscle fiber infiltrated with CD4-positive and CD8-positive lymphocytes and CD68-positive macrophages, and no CD20-positive lymphocytes and CD303-positive dendritic cells were observed. Two patients had expressed a bit of c5b-9 positive capillary. Anti-sarcoglycans staining, anti-dysferlin staining and dystrophin staining showed continuous strong positive expression. Follow-up study found that all patients were response to glucocorticoid, and a combination therapy of immunoglobulin and immunosuppression were necessary for some patients.