Proximal Weakness Research Articles

Clinical associations of patients with anti-3-hydroxy-3-methylglutaryl CoA reductase antibody-associated immune-mediated necrotising myopathy.

Anti-3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) antibodies are associated with a subtype of immune-mediated necrotising myopathy (IMNM). To determine clinical associations of anti-HMGCR antibodies for anti-HMGCR-associated IMNM (HMGCR-IMNM) among a cohort of patients in Western Australia and to determine whether serial HMGCR antibody levels parallel disease activity. Adult patients with positive anti-HMGCR antibodies detected by enzyme-linked immunosorbent assay between January 2015 and November 2019 were included. Symptoms, examination findings, imaging findings and blood test results were reviewed retrospectively using patient records and laboratory database results. Among 26 patients with positive anti-HMGCR antibodies, 23 were diagnosed with HMGCR-IMNM representing a positive predictive value (PPV) of 88%. Myopathy was frequently severe at diagnosis with limb weakness graded as Medical Research Council score 3 or below in 78% of patients, bulbar muscle weakness in 39% and an average creatine kinase (CK) at diagnosis of 7986 U/L. The majority (83%) required at least two therapies to maintain remission, 48% had at least one flare of disease and 57% did not achieve CK normalisation. Correlation between CK and anti-HMGCR antibody level at diagnosis was low (r = 0.04). Anti-HMGCR antibodies fell with treatment in 10 of 12 patients, but remained persistently positive in 83% of patients. The PPV of anti-HMGCR antibodies for HMGCR-IMNM in this Western Australian cohort is 88%. Patients typically present with proximal limb weakness, dysphagia and markedly elevated CK,and, despite multiagent immunosuppression, a significant number of patients have evidence of persistent biochemical myositis. Anti-HMGCR antibodies did not correlate with CK levels at diagnosis.

Unique Clinical, Radiological and Histopathological Characteristics of a Southeast Asian Cohort of Patients with Limb-Girdle Muscular Dystrophy 2G/LGMD-R7-Telethonin-Related.

We describe a cohort of five patients with limb-girdle muscular dystrophy (LGMD) 2G/LGMD-R7 in a South-east Asian cohort. LGMD2G/LGMD-R7-telethonin-related is caused by mutations in the TCAP gene that encodes for telethonin. We identified consecutive patients with LGMD2G/LGMD-R7-telethonin-related, diagnosed at the National Neuroscience Institute (NNI) and National University Hospital (NUH) between January 2000 and June 2021. At onset, three patients presented with proximal lower limb weakness, one patient presented with Achilles tendon contractures, and one patient presented with delayed gross motor milestones. At last follow up, three patients had a limb girdle pattern of muscle weakness and two had a facioscapular humeral pattern of weakness. Whole body muscle MRI performed for one patient with a facioscapular-humeral pattern of weakness showed a pattern of muscle atrophy similar to facioscapular-humeral dystrophy. One patient had histological features consistent with myofibrillar myopathy; electron microscopy confirmed the disruption of myofibrillar architecture. One patients also had reduced staining to telethonin antibody on immunohistochemistry. We report the unique clinical and histological features of a Southeast Asian cohort of five patients with LGMD2G/LGMD-R7-telethonin-related muscular dystrophy and further expand its clinical and histopathological spectrum.

Development and Validation of an Outpatient Clinical Predictive Score for the Diagnosis of Duchenne Muscular Dystrophy/Becker Muscular Dystrophy in Children Aged 2-18 Years.

There is no bedside clinical examination-based prediction score for Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in children with neuromuscular diseases (NMDs) presenting with proximal limb-girdle weakness. We compared the details of 200 cases of lower motor neuron type of weakness and had some proximal limb-girdle muscle weakness and divided them into 2 groups: with/without a confirmed diagnosis of DMD/BMD. We determined the predictive factors associated with a diagnosis of DMD/BMD using multivariate binary logistic regression. We assessed our proposed prognostic model using both discrimination and calibration and subsequently used the bootstrap method to successfully validate the model internally. A total of 121 patients had DMD/BMD and the rest of the patients had other diagnoses. Male gender, presence of Gower's sign, valley sign, toe walking, calf pseudohypertrophy, and tongue hypertrophy were independent predictors for a confirmed diagnosis of DMD/BMD and included in the final CVT2MG score (Calf pseudohypertrophy, Valley sign, Toe walking, Tongue hypertrophy, Male gender, and Gower's sign). The final model showed good discrimination (AUC = 87.4% [95% CI: 80.5-92.3%, P < 0.001]) and calibration (P = 0.57). A score of 6 or above appeared to be the best cutoff for discriminating between the DMD/BMD group and the rest of the group with both sensitivity and specificity of 98%. The interrater reliability was almost perfect between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.91 and 0.87). The CVT2MG score has good sensitivity and specificity in predicting a confirmed diagnosis of DMD/BMD in subsequent tests.

A Study of Organophosphorus Induced Delayed Myelopathy: Uncommon Sequelae of a Common Poisoning.

Organophosphorus (OP) compounds, with their lipophilicity, are responsible for a spectrum comprising of acute cholinergic symptoms, intermediate syndrome, as well as delayed neurological sequelae in the form of OP-induced delayed neuropathy and subsequently, myeloneuropathy with predominantly thoracic cord affection, manifested on partial recovery of the neuropathy. The pathogenesis of this myeloneuropathy in humans is still not well perceived. To determine the onset and course of development of delayed myeloneuropathy in patients of OP poisoning. Twelve patients of OP ingestion presenting with delayed myeloneuropathy were evaluated with prior history, examination, MR imaging, nerve conduction and electromyography studies, and various evoked potentials to elicit the pattern of disease manifestation and progression. Among the included patients, a majority had consumed chlorpyrifos and permethrin composition, a majority had undergone gastric lavage. Five (41.7%) had experienced acute worsening and 8 (66.7%) patients had developed intermediate syndrome. OPIDN had appeared after a median of 4 (1-8) weeks after the poisoning. All patients had lower limb hypertonia with wasting and distal more than proximal weakness with pure motor or sensorimotor involvement. MRI showed thoracic cord atrophy in 3 (25%) patients. Motor-evoked potential with reduced amplitude was noted in lower limbs on lumbar stimulation but absent on cortical stimulation. Various animal models have shown similar patterns of neurotoxicity in OP poisoning with predominant thoracic cord pathology. Further research in humans may be undertaken to elicit the pathogenesis, thereby improving the treatment modality.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China

ObjectivesIdiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. ConclusionsAnti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Povezanost mijastenije gravis i imunski-posredovanih miopatija

Introduction/Aim: Myasthenia gravis (MG) is a chronic autoimmune disease of the neuromuscular junction, characterized by muscle weakness and fatigability. Idiopathic inflammatory myopathies (IIM) are an immune-mediated group of diseases characterized by progressive painful proximal weakness of the extremities. The coexistence of these two diseases is extremely rare and so far, only about fifty cases have been reported worldwide. The aim of this study was to analyze the frequency of coexistence of IIM and patients with de novo MG. Material and Methods: The study is retrospective in nature and was conducted at the "Neurology Clinic", University Clinical Center of Serbia. It included 97 patients diagnosed with myasthenia gravis between January 1, 2014 and December 31, 2018. Results: The average age of the MG patients was 54.1±18.9 years. At the time of diagnosis, 19 (19.6%) participants had at least one of the anamnestic data observed as potential indicators for the existence of immune-mediated myopathy. Finally, one patient clinically presented with generalized seropositive (anti-AchR positive) myasthenia gravis associated with the diagnosis of antisynthetase syndrome. In addition, the main characteristics of patients with combined occurrence of de novo MG and antisynthetase syndrome are presented. Conclusion: Although the simultaneous occurrence of MG and IIM is a very rare phenomenon, we need to think about the possibility of combined occurrence of these two autoimmune diseases, with the aim of early recognition and adequate treatment, and thus a better prognosis of both diseases.

An atypical presentation of dermatomyositis sine dermatitis

Dermatomyositis (DM) is a rare autoimmune disorder. This idiopathic inflammatory myopathy (IIM) is characterized by overexpression of major histocompatibility complex I and the formation of autoantibodies. Apart from muscle weakness, dermatological involvement is classically seen in DM. Recently, a few articles have been published documenting a subset of DM with no skin involvement – DM sine dermatitis. Here, we present a 37-year-old male with progressive proximal weakness with no skin involvement. Unlike classical DM, neither muscle enzymes (creatinine phosphokinase and aldolase) were elevated nor myositis-specific autoantibodies were detected. Muscle biopsy, however, was characteristic for DM with positivity for CD3, CD4, CD8, CD20, and CD68. The patient improved with initiation of immunosuppressants. Screening for malignancy and interstitial lung disease was unremarkable.

Progressive Bulbar Palsy with Facial Diplegia and Proximal Weakness Diagnosed as Juvenile-Onset Myasthenia Gravis.

Department of Neurology, King George’s Medical University, Lucknow, Uttar Pradesh, India Address for correspondence: Dr. Rajesh Verma, Department of Neurology, King George’s Medical University, Lucknow - 226 003, India. E-mail: [email protected] Received February 12, 2023 Received in revised form April 08, 2023 Accepted April 11, 2023

Postoperative Lumbar Plexopathy Secondary to Retroperitoneal Liposarcoma: A Case Report

Liposarcoma is a rare malignancy that usually originates in the extremities or the retroperitoneum. The lumbar plexus, a complex neural network formed by divisions of the first four lumbar roots, penetrates the psoas muscle before it exits the pelvis. Owing to their anatomical proximity, neoplasms in the vicinity of the psoas muscle may involve the lumbar plexus. We report a case of postoperative lumbar plexopathy involving the posterior divisions of the lumbar plexus, following the resection of a recurrent retroperitoneal liposarcoma located in the dorsal aspect of the psoas muscle. A 50-year-old man visited a rehabilitation clinic for an evaluation of proximal weakness of the unilateral lower extremity after resection of a recurrent liposarcoma of the left psoas muscle. Physical examination showed weakness of left hip flexion and knee extension accompanied by sensory loss in the left anteromedial thigh and the medial lower leg. An electrophysiological study revealed left lumbar plexopathy with selective involvement of the posterior divisions of the lumbar plexus. The patient could walk independently without a walking aid on level surfaces while he underwent exercise therapy. A comprehensive evaluation, including a physical examination, the use of imaging modalities such as computed tomography for anatomical characterization, and electrophysiological studies, is important for accurate diagnosis.

Delayed Diagnosis in a Patient With Progressive Proximal Weakness: A Clinical Vignette.

Delayed Diagnosis in a Patient With Progressive Proximal Weakness: A Clinical Vignette.

1099 ERGOREFLEX SENSITIVITY IS ASSOCIATED WITH CARDIAC INVOLVEMENT IN BECKER MUSCULAR DYSTROPHY

Abstract Background and aims Becker muscular dystrophy (BMD) is a X-linked recessive inherited skeletal myopathy due to dystrophin deficiency ensuing in a variable phenotype characterized by slowly progressing muscle weakness and, often, the development of dilated cardiomyopathy. The relationship between muscle and cardiac involvement in BMD is yet to be clarified. We aimed to assess the association between ergoreflex sensitivity, a marker of skeletal muscle work regulating ventilatory and autonomic responses to exercise, and cardio-muscular involvement in BMD. Methods Fifteen male BMD patients (median age 37 years [25-42]) underwent a comprehensive evaluation including ECG, biohumoral assessment (high sensitivity troponin T/I [hs-TnT/I], natriuretic peptides, soluble suppression of tumorigenesis 2 [sST2], catecholamines, creatine phosphokinase [CPK], myoglobin), cardiac magnetic resonance (CMR), and ergoreflex determination. Muscular phenotype was distinguished into “classic” (proximal weakness affecting the shoulders and pelvis with waddling gait) or “mild”. Cardiac involvement was defined based on the presence of late gadolinium enhancement (LGE) at CMR. Ergoreflex sensitivity was calculated as the percentage of the ventilatory response to a handgrip exercise maintained by circulatory occlusion through the inflation of a forearm tourniquet (clamp) during the third minute of recovery compared with the third minute of recovery without clamp: [(Rec∕Ex) clamp − (Rec∕Ex) no clamp]∗100, where Ex is the mean ventilation during the last 30 s of exercise, Rec the mean ventilation during the last 30 s of the third minute of recovery. Results Ten patients (67%) had a “classic” muscular phenotype. Nine patients (60%) had LGE at CMR (median number of segments 9 [6-12]). The percentage of patients with cardiac involvement was not different between those with “classic” or mild muscular phenotype. Patients with cardiac involvement had higher ergoreflex sensitivity (24% [8-38] vs. 4% [0-24], p=0.036), hs-TnI (9.8 ng/L [5.9-14.5] vs. 2.1 ng/L [1.7-4.5], p=0.018), and hs-TnT (24 ng/L [20-35] vs. 11 ng/L [5-20], p=0.012), but did not show significant differences in terms of cardiac chamber size or systolic function compared to those without LGE. Ergoreflex sensitivity correlated with biomarkers of both cardiac (hs-TnI, rho=0.654, p=0.008; hs-TnT, rho=0.529, p=0.043; sST2, rho=0.654, p=0.009) and muscular damage (CPK, rho=0.645, p=0.009), as well as with the number of LGE segments (rho=0.583, p=0.022). No difference in ergoreflex sensitivity was detected in patients with “classic” versus mild muscular phenotype. Conclusions In BMD, there is no relationship between cardiac involvement and the muscular phenotype. Nonetheless, cardiac involvement in BMD is characterized by enhanced ergoreflex sensitivity, which is associated with biomarkers of both cardiac and muscular damage.

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.

Neuroblastoma Presentation With Multiple Cranial Nerve Involvement

Objective NA. Background We report a case of neuroblastoma, a pediatric neuroendocrine tumor of the sympathetic nervous system, in a 3-year-old female with multiple cranial nerve involvement. Design/Methods A 3-year-old afebrile, lethargic female presented with bilateral eyelid droop, right head tilt, slurred speech, gagging, abnormal walking and no bowel movement. Neurological examination noted bilateral ptosis, dysarthria, left tongue deviation, proximal weakness in upper and lower extremities, areflexia in biceps and patellar tendons, dysmetria, and wide-based gait. MRI of the brain showed heterogeneous appearance of the clivus and MRI of the spine showed right adrenal mass and heterogeneous enhancement of multiple vertebrae, suggesting possible metastatic disease. Serum and cerebrospinal studies were unremarkable. Patient was treated with intravenous methylprednisolone and plasmapheresis for suspected paraneoplastic syndrome; however, she continued to clinically progress. Adrenal mass biopsy results and elevated urine VMA and HVA levels were consistent with the diagnosis of neuroblastoma. Nuclear imaging and meta-iodobenzylguanidine scan were negative. Paraneoplastic panels and Lambert Eaton panel were negative for autoantibodies. Total resection of the abdominal mass and right adrenal gland with continued steroid taper, resulted in reported near total symptom resolution. Results Our patient presented with antibody negative paraneoplastic polyneuropathy due to neuroblastoma. Cranial nerve involvement in neuroblastoma can result from tumor involvement of the sympathetic chain, paraneoplastic syndromes, or metastasis to the skull. Our patient's initial imaging suggested potential metastatic or inflammatory involvement of the clivus, suspected of causing her cranial nerve symptoms. However, nuclear studies were negative for metastatic disease and patient's symptoms resolved after resection of the main mass suggesting a paraneoplastic etiology. Although her paraneoplastic panel and Lambert-Eaton panel were negative for common associated antibodies, it is likely an unmeasured autoantibody, cytokine, hormones, or peptide was at play. Conclusions Neuroblastoma should be considered as a differential for a neurological presentation involving multiple cranial nerves in a child.

Lambert-Eaton Myasthenic Syndrome and Botulism

This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes. Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment. A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes.

An Interesting Case of Inflammatory Myositis

Background: Idiopathic inflammatory myopathies (IIM) are a class of long-lasting autoimmune diseases that typically affect the proximal muscles. Dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis are the most prevalent kinds. Patients usually have subacute to chronic proximal weakness, which presents as difficulty getting out of a chair, getting up the stairs, lifting objects, and brushing their hair. They are distinguished by their clinical presentation, which includes muscular and extramuscular signs. Elevated serum creatine kinase (CK) levels and myositis-specific antibodies may help distinguish clinical phenotypes and confirm the diagnosis. Biopsy of the muscle, on the other hand, is still the gold standard for determining the cause of the problem. These disorders may be cured with proper diagnosis and treatment. The treatment’s goals are to reduce inflammation, restore muscle performance, and alleviate pain. Methods: 36-year-old man K/C/O dermatomyositis came complaints of redness swelling in the right eye for 3 months, dysphagia, easy fatiguability. Patient was neither hypertensive nor diabetic. Results: This case describes the severity of NXP2 autoantibody and a potential to be life threatening. Patient was started with immunoglobulins, monoclonal antibodies. After which patient improved from his present condition.

Phenotypical statin‐associated immune‐mediated necrotizing myositis with histological features of inclusion body myositis

AbstractIntroductionStatin‐associated immune‐mediated necrotizing myositis (IMNM) is a rare but distinct idiopathic inflammatory myopathy (IIM) that requires early recognition and intervention to prevent irreversible muscle damage. It is typically characterized by active statin use, elevated creatinine kinase (CK) levels, proximal muscle weakness, and at times, a positive 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) antibody. Treatment includes immediate discontinuation of the statin and may include corticosteroids, intravenous immunoglobulin (IVIG), and/or immunosuppressive therapy. Inclusion body myositis (IBM), another distinct IIM, also presents with elevated CK levels but with insidious onset of distal upper and proximal lower extremity weakness and is typically refractory to treatment.Case DescriptionA 64‐year‐old female patient presented with proximal muscle weakness, elevated CK levels, and a positive HMGCR antibody in the setting of statin use with muscle pathology suggestive of both statin‐associated IMNM and IBM. She responded to subcutaneous methotrexate and a slow prednisone taper over several months, however, will require close monitoring for symptoms associated with either disease.ConclusionIn conclusion, we report a case of muscle weakness with muscle pathology demonstrating both statin‐associated IMNM and IBM. This case highlights the importance of understanding the clinical and pathological features of statin‐associated IMNM and IBM.

Neuromyelitis optica presenting as neurogenic bladder

Neuromyelitis optica (NMO) is an immune mediated disease of central nervous system primarily affecting optic nerves, spinal cord and brain stem. This case report describes a 24-year-old male with no comorbidities presented with high grade fever followed by proximal lower limb weakness and bilateral hydrouretero nephrosis without any lower urinary tract obstruction. He had clinical features of conus- cauda lesion with MRI spine showing features of longitudinally extensive transverse myelitis (LETM) and brain MRI showing involvement of splenium of corpus callosum. He improved with steroid therapy with in a period of 2 weeks and oral steroid was tapered of and stopped within a period of two months. There was no relapse of symptoms so far.

307 Phenotypic-genotypic expansion of plectinopathy in a patient with muscular dystrophy and immune-mediated myasthenia gravis

A 26-year-old female presented with blistering skin lesions since infancy, hair loss, proximal motor weakness, nasal tone speech, swallowing problem, and droopy eyes. Upon neurological examination, normal cognition, inability to walk unassisted, bilateral ptosis with a full range of extraocular movements, weak gag reflex, generalized muscle atrophy, and decreased deep tendon reflexes were detected. Her electromyography revealed small polyphasic muscle unit action potentials, minimal insertional activities, myopathic changes, motor, and sensory increased latency, decreased amplitude, reduced velocity, and normal F wave.

Case of anti‐NT5c1A antibody‐seropositive inclusion body myositis associated with severe dysphagia and prominent forearm weakness

AbstractWe report a case of an 82‐year‐old woman with inclusion body myositis (IBM), who presented with severe dysphagia, finger flexor weakness, and respiratory dysfunction. In addition, the patient showed prominent forearm weakness with quadriceps sparing and was seropositive for the anti‐cytosolic 5′‐nucleotidase 1A (NT5c1A) antibody. The presence of the anti‐NT5c1A antibody is presumably associated with dysphagia. We speculate that the anti‐NT5c1A antibody is associated with the large discrepancy between distal upper limb weakness and proximal lower limb weakness in IBM.

PSAT222 Muscle Weakness, Bone Pain, and Stress Fractures: When a Fracture is NOT JUST a Fracture: A Case Report

Abstract Case A previously healthy 46-year-old male presented to orthopedic clinic with bilateral hip pain, and progressive weakness without history of trauma requiring cane for ambulation. X-ray and MRI evaluation revealed stress fractures of left subtrochanteric femur and right basicervical femoral neck, both requiring surgery. In hospital blood work revealed elevated total alkaline phosphatase 167 units/L, mild hypocalcemia 8.5 mg/dL, and low 25-hydroxy Vitamin D 18 ng/mL. The patient was started on calcium/vitamin D supplements upon discharge. Initial endocrinology outpatient work-up revealed low phosphorus level of 2.1 mg/dl and low 1, 25 OH vitamin D of 5.9 pg/ml (19.9–79.3). Bone mineral density revealed normal spine bone density, and 1/3 radius osteopenia (T score -1.1). Physical exam revealed profound proximal weakness with inability to rise independently from sitting position. Follow-up of low phosphorous level demonstrated an elevated FGF-23 level of 186 RU/mL (normal &amp;lt; 180) and elevated fractional excretion of phosphorus 16% (expect &amp;lt; 5% with hypophosphatemia), indicating inappropriate renal phosphate wasting. The patient was started on Calcitriol and phosphorus. Before above evaluation was completed the patient had an ED visit with complaint of small mass just below left knee associated with mild pain and warmth. Ultrasound and MRI showed a complex cyst which was aspirated and showed cystic appearing mass suggestive of hematoma. This was treated with antibiotic course. Due to suspicion of tumor-induced osteomalacia, octreotide scan (Indium-111 pentetreotide) performed showed focal increased activity in the medial left knee. MRI showed a 26 mm cystic lesion within the subcutaneous tissue along the inferomedial aspect of the left knee, which correlated with the site of radiotracer uptake on the octreotide scan. The patient underwent left knee soft tissue tumor resection, and pathology demonstrated phosphaturic mesenchymal tumor. Follow-up several weeks postoperatively showed normalization of phosphorus and FGF-23 level. The patient's mobility and weakness improved significantly within a few months. Discussion Tumor-induced osteomalacia is a rare paraneoplastic condition characterized by chronic hypophosphatemia secondary to excessive tumoral FGF 23 production. Typical presenting symptoms are profound muscle weakness, bone pain, and fractures. Diagnosis is often delayed for several years, as phosphorus levels are not included in a routine metabolic panel. Considering high morbidity of this condition including significant mobility limitation requiring use of assistive devices, healthcare provider vigilance is paramount as this condition is potentially curable if the offending tumor is detectable and amenable to surgical resection. This case illustrates the importance of consideration of an underlying metabolic bone disease in patients with unexplained atraumatic fractures and hypophosphatemia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.