Proximal Limb Weakness Research Articles

AUTOIMMUNE & INFLAMMATORY NMD: EP.01 Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies in the first year of life

Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (SRP ANM) has been rarely reported in childhood. Case Reports. We report 2 patients with onset in the first years of life. Both received corticosteroids, immunoglobulins, methotrexate, hydroxychloroquine and tacrolimus. Patient 1 has clearly improved. Patient 2 was misdiagnosed as muscular dystrophy for 15 years; nevertheless, after 4 months of therapy there was mild motor improvement. Patient 1. A 6-year-old girl presented with weakness, but her parents could not recall the beginning. She had axial as well as mild to moderate limb girdle weakness. There was no systemic/skin involvement. CK levels were 2.400 UI/l. The DMD MLPA test and next-generation sequencing (NGS) did not reveal any pathogenic mutation. Muscle weakness progressed quickly in the next 3 months, suggesting an acquired myopathy, and SRP antibodies were detected. Muscle biopsy was compatible with ANM. Patient 2. A 4-year-old girl presented with weakness in lower limbs for months. Her family was consanguineous. She achieved ambulation after 18 months. She had proximal limb weakness, as well as scapular winging and calf hypertrophy. Her cognitive capacity was borderline. CK levels were >5.000U/l. MRI disclosed posterior thig involvement and focal edema, but based on the rest of clinical findings, a muscular dystrophy was suspected. Muscle biopsy performed at 5 and 10 years of age showed a dystrophic pattern with necrotic fibers and endomysial connective infiltration. Immunochemistry study for muscular dystrophies was normal. Her clinical course has progressed very slowly. She showed rigid spine and maintains independent walking. At 19 year of age, due to the negativity of the all the genetic tests performed over the time (including NGS), myositis specific autoantibodies were tested and SRP antibodies were positive. Review of the second muscle biopsy disclosed C5b-9 expression in muscle fibers. SRP ANM is under-recognized and consequently undertreated in children. Early diagnosis is crucial to improve outcome.

P-NE013. Distal myasthenia gravis – A missed clinical diagnosis

Introduction . What is well known: Myasthenia gravis presents with ocular, bulbar and proximal limb weakness. What is less known: Myasthenia gravis can rarely present with predominant distal weakness of hand muscles. Myasthenia gravis (MG) is an immune mediated, post-synaptic neuromuscular transmission disorder, presenting with predominant ocular, bulbar and/or proximal fluctuating weakness and fatiguability. Distal and asymmetric onset of symptoms in MG is rare and could lead to delay in diagnosis especially when fatiguability or fluctuation is not clearly reported as a prominent initial symptom - as seen in our patients. Results . We report 3 cases of distal MG who presented with predominant distal asymmetric hand weakness. Their clinically diagnoses for referral to the electrodiagnostic (EDx) laboratory were chronic inflammatory demyelinating polyneuropathy, C8T1 motor radiculopathy and multifocal motor neuropathy. It was in the EDx laboratory that the diagnosis of MG was suspected in these patients. Since the routine EDx tests were normal in all 3 patients - a repetitive nerve stimulation test (RNST) was done - which was positive in the affected muscles and hence a diagnosis of distal MG made (This is the protocol followed in our laboratory). These patients were then found to have high serum levels of antibodies to acetylcholine receptors - confirming the diagnosis of MG. RNST is not routinely done in all patients sent for electrodiagnostic testing and none of these patients had a reference for the same – however using a protocol based method of EDx testing, leading to the diagnosis of a treatable condition. Conclusion . Electrodiagnosticians need to be aware of this presentation of MG and follow protocols or else the diagnosis could be missed.

P-MU004. A rare treatable cause of dropped head syndrome

Introduction . Dropped head syndrome results from neck extensor weakness, and is commonly due to neuromuscular disorders such as inflammatory myopathies, myasthenia gravis, or amyotrophic lateral sclerosis. We describe, with neck muscle imaging findings, a man presenting with neck extensor weakness due to hypothyroidism that resolves with thyroxine replacement. Results . A 60-year-old man without any past medical history of note presented with neck pain for 7 years. On examination, he was noted to have head drop, without limb weakness, bulbar symptoms nor fatiguability. Neurologic examination was otherwise normal. Creatine kinase (CK) was raised at 2480 U/L. Thyroid-stimulating hormone (TSH) was high at 64.50 mIU/L (Normal 0.45-4.50 mIU/L), and T4 was low at < 3.2 pmol/L (Normal 8-16 pmol/L). Thyroid peroxidase and anti-thyroglobulin antibodies were positive. Antiacetylcholine receptor and myositis-specific antibodies were negative. Repetitive nerve stimulation was negative. Needle electromyography showed evidence of an irritable myopathy in the deltoid, iliopsoas and neck extensors. Computed Tomography of the neck showed hypertrophy of the splenius capitis. He was diagnosed with myopathy due to hypothyroidism and started on levothyroxine replacement. 6 months’ later, there was resolution of his dropped head with normalization of his CK levels. Conclusion . Hypothyroidism more commonly presents with proximal limb weakness or raised CK. Associated axial myopathies are very rarely described. Hypothyroidism is a treatable cause of dropped head syndrome that reverses with thyroxine replacement. It is a rare cause of neck extensor muscle hypertrophy and irritable myopathy. Recognizing this entity is important to avoid unnecessary invasive investigations, such as muscle biopsy, or unnecessary immunomodulatory treatment in a neck extensor myopathy that will self-resolve with normalization of thyroid function. Muscle imaging can be helpful in its diagnosis.

Risk factors and diagnostic methods of intensive care unit-acquired weakness

To explore the risk factors of intensive care unit-acquired weakness (ICU-AW) and the characteristics of Medical Research Council (MRC) score and electromyogram. A case control study was conducted. Patients with mechanical ventilation ≥ 7 days and MRC score admitted to department of respiratory and critical care medicine of China-Japan Friendship Hospital from September 2018 to January 2020 were enrolled, and they were divided into ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48) according to MRC score. The general situation, past medical history, related risk factors, MRC score, respiratory support mode, laboratory examination results, electromyogram examination results, ICU-AW related treatment, outcome and length of ICU stay were collected, and the differences between the two groups were compared. The risk factors of ICU-AW were analyzed by binary multivariate Logistic regression, and the characteristics of MRC score and electromyogram were analyzed. A total of 60 patients were enrolled in the analysis, including 17 patients in ICU-AW group and 43 patients in non-ICU-AW group. Univariate analysis showed that there were significant differences in acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) on the first day of ICU admission and the ratio of invasive mechanical ventilation between ICU-AW group and non-ICU-AW group [APACHE II score: 21 (18, 25) vs. 18 (15, 22), SOFA score: 7 (5, 12) vs. 5 (3, 8), BNP (ng/L): 364.3 (210.1, 551.2) vs. 160.1 (66.8, 357.8), BUN (mmol/L): 9.9 (6.2, 17.0) vs. 6.0 (4.8, 9.8), invasive mechanical ventilation ratio: 88.2% vs. 46.5%, all P < 0.05]. Binary multivariate Logistic regression analysis showed no independent risk factor for ICU-AW. The average MRC score of 17 ICU-AW patients was 33±11. The limb weakness was symmetrical, and the proximal limb weakness was the main manifestation. Electromyography examination showed that the results of nerve conduction examination in ICU-AW patients mainly revealed that the amplitude of compound muscle action potential (CMAP) and sensory nerve action potentials (SNAP) were decreased, and the conduction velocity was slowed down; needle electromyography showed increased area of motor unit potential (MUP), prolonged time limit and a large number of spontaneous potentials. Prognosis evaluation showed that compared with non-ICU-AW group, patients in ICU-AW group underwent more tracheotomy (70.6% vs. 11.6%), longer length of ICU stay (days: 57±52 vs. 16±8), and more rehabilitation treatment (58.8% vs. 14.0%), and the differences were statistically significant (all P < 0.01). The occurrence of ICU-AW may be related to high APACHE II score and SOFA score, high levels of BNP and BUN on the first day of ICU admission and the proportion of invasive mechanical ventilation, but the above factors are not independent risk factors for ICU-AW. The MRC score of ICU-AW patients was characterized by symmetrical limb weakness, mainly proximal limb weakness; in electromyography examination, the nerve conduction examination results mainly showed that CMAP and SNAP amplitude were decreased, and conduction velocity was slowed down; needle electromyography examination showed increased MUP area, prolonged duration and a large number of spontaneous potentials.

Recent Progress in Oculopharyngeal Muscular Dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset intractable myopathy, characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness. It is caused by the abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the exon 1 of the polyadenosine (poly[A]) binding protein nuclear 1 gene (11–18 repeats in OPMD instead of the normal 10 repeats). As the disease progresses, the patients gradually develop a feeling of suffocation, regurgitation of food, and aspiration pneumonia, although the initial symptoms and the progression patterns vary among the patients. Autologous myoblast transplantation may provide therapeutic benefits by reducing swallowing problems in these patients. Therefore, it is important to assemble information on such patients for the introduction of effective treatments in nonendemic areas. Herein, we present a concise review of recent progress in clinical and pathological studies of OPMD and introduce an idea for setting up a nation-wide OPMD disease registry in Japan. Since it is important to understand patients’ unmet medical needs, realize therapeutically targetable symptoms, and identify indices of therapeutic efficacy, our attempt to establish a unique patient registry of OPMD will be a helpful tool to address these urgent issues.

Upper Motor Neuron Signs in the Cervical Region of Patients With Flail Arm Syndrome.

Objective: We investigated upper motor neuron (UMN) signs in the cervical region in a Chinese clinic-based cohort of patients with flail arm syndrome (FAS) by clinical examination and neurophysiological tests such as triple stimulation technique (TST) and pectoralis tendon reflex testing.Methods: A total of 130 consecutive FAS patients from Peking University Third Hospital underwent physical examination and neurophysiological tests at baseline and 3 months, 6 months, 9 months, and 12 months later. Pyramidal signs, pectoralis tendon reflex and TST results were evaluated to estimate the function of cervical spinal UMNs.Results: At the first visit, weakness of the bilateral proximal upper limbs was found in 99 patients, while weakness of a single proximal upper limb was found in 31 patients. There were 49 patients with tendon hyperreflexia, 42 patients with tendon hyporeflexia and 39 patients with tendon areflexia. All except 4 of the patients had brisk pectoralis tendon reflex. The UMN score of the cervical region was 1.7 ± 0.4, and the lower motor neuron score of that region was 3.5 ± 0.3. The TSTtest/TSTcontrol amplitude ratio was 65.7 ± 7.5%. The latency of quantitative detection of the pectoralis tendon reflex was 7.7 ± 1.2 ms. In the follow-up study, the UMN score and the TSTtest/TSTcontrol amplitude ratio decreased, while the lower motor neuron score increased, and the latency of quantitative detection of the pectoralis tendon reflex remained steady.Conclusion: Although the signs of cervical spinal UMN dysfunction in patients with FAS were often concealed by muscle atrophy in the progression of the disease, TST and pectoralis tendon reflex could reveal it.

Central Core Disease - A Disease That Is Easily Misdiagnosed as Duchenne Muscular Dystrophy

As a kind of congenital myopathy (CM), central core disease (CCD) is mainly characterized by low muscle tension, slow progressive or static proximal limb weakness. CM can be characterized by no symptoms to be unable to walk independently in the clinic, pathological changes can be manifested as only significant type 1 muscle fiber dominant type to typical central axial space structure, and there are also many genetic ways. Duchenne muscular dystrophy (DMD) is a common congenital myopathy, which is mainly manifested in the typical pathological changes of early progressive myasthenia and muscular dystrophy. Both CCD and DMD show similar clinical symptoms and their serum creatine kinase can be increased, which is often difficult to distinguish them through clinical characterization and laboratory examination. In this study, we report the clinical and genetic characteristics of two patients with progressive muscle weakness with elevated creatine kinase. They are the product of a first-cousin marriage and seek medical treatment due to asymptotic walking difficulties, muscle atrophy, joint contracture, scoliosis, and elevated creatine kinase levels. It was previously suspected as Duchenne muscular dystrophy. After that, the patient's DNA was sequenced by whole-exome sequencing (WES), and all coding regions were investigated. It was found that a new heterozygous missense mutation c.5092g > A in the RYR1 gene. Similar mutations have not been reported in the literature before. Bioinformatics software predicts that they have the possibility of pathogenesis, which is highly correlated with CCD. The purpose of this case is to report a new heterozygous mutation of the RYR1 gene, summarize the similarities and differences of clinical manifestations, genetic characteristics, and pathological changes of CCD and DMD, and provide a new idea for its differential diagnosis.

Collagen Ⅵ‐related myopathy with subacute presentation of hypercapnic respiratory failure following pneumonia

AbstractBethlem myopathy, the mild form of collagen Ⅵ‐related myopathy, gradually affects pulmonary function without causing symptoms. We report a case of a 38‐year‐old woman presenting with subacute deterioration of hypercapnic respiratory failure following pneumonia. She had posterior instrumentation and fusion for scoliosis during adolescence. Mild muscle weakness of trunk and proximal lower limbs, representing atrophic changes in imaging, and flexion contractures were present. The muscle pathology showed moderate variation in fiber size with mild endomysial fibrosis. The heterozygous COL6A1 mutation was identified. We made the diagnosis of collagen Ⅵ‐related myopathy. Noninvasive positive pressure ventilation improved the respiratory failure.

A study of impairments in oculopharyngeal muscular dystrophy.

In this study we aimed to document the prevalence and age of onset of motor impairments and other key symptoms in oculopharyngeal muscular dystrophy (OPMD). Retrospective chart review of patients followed at the Saguenay Neuromuscular Clinic (Quebec, Canada). A total of 333 participants with the (GCN)13 mutation were included. Before the age of 75 years, 27% of them had walking limitations, 14% could not climb stairs independently, and 14% used a wheelchair for long distances or daily living. The median age of onset was 54 years for ptosis and dysphagia and 58 years for lower limb proximal weakness. Other frequent symptoms included fatigue, pharyngeal pooling of thickened secretions, and dysphonia. The median age at death was 77 years and the main cause was respiratory disease. This study provides important information to help anticipatory guidance for affected people and for the development of therapeutic trials in OPMD.

EP06 Successful treatment of alopecia universalis with rituximab therapy

Abstract Background Alopecia universalis (AU) is a severe subtype of alopecia areata (AA), in which there is non-scarring hair loss affecting the whole body. The pathogenesis involves, increased MHC class I expression in hair follicles, loss of hair follicle immune privilege and autoimmune-mediated damage to pigmented hair. There is no cure for alopecia areata, and though mild cases may have a good chance of either spontaneous or treatment-induced recovery, the prognosis of complete hair loss is poor with less than 10% recovery. Treatment remains a challenge with no reliably effective therapy and in the absence of well-evaluated trials, isolated case reports can influence practice. Here, we present the first report of AU being successfully treated with rituximab with remarkably sustained improvement at 6 years follow up. This case is also the first report of AU developing in adult dermatomyositis (DM) and we speculate upon the implications for the aetiopathogenesis of both conditions. Methods A 55-year-old lady, presented with proximal limb weakness, lethargy, a non-itchy rash, pleurisy and breathlessness. The serum creatinine kinase (3369 u/L) and anti-Jo-1 antibodies were elevated consistent with antisynthetase syndrome and a diagnosis of dermatomyositis was made. There was an initial response to corticosteroids and cyclophosphamide. She then relapsed and was treated with IV rituximab. Seventeen months after her initial presentation, she developed widespread hair loss sparing only white hairs (making Telogen Effluvium unlikely), combined with a concurrent relapse of her dermatomyositis. A diagnosis of alopecia universalis (AU) was made. A further course of IV rituximab therapy administered at this stage led to an excellent response in both her dermatomyositis and AU. At three months review, both the AU and the dermatomyositis had entered remission and this has been sustained 6 years on. Results Please refer to the conclusion section. Conclusion Disease activity in dermatomyositis has been linked with the expression of type I Interferon IFN and this may induce MHC class I expression that is identified on muscle biopsy. It may be that similar type I IFN action on hair follicles may have triggered the development of AU in our case. Whilst this is the first report of AU occurring with adult dermatomyositis, there has been a report of AU occurring in juvenile dermatomyositis. There are also other reports of other combinations of autoimmune conditions occurring with both DM &amp; AU. This case also demonstrates that rituximab, an anti-CD 20 B cell therapy, maybe a useful treatment option in alopecia areata and universalis. This has not been reported elsewhere. Despite postulation that AU is a mainly T cell-driven disease, this case demonstrates that B cells may play a role, in much the same way that we now recognise the importance of B cell involvement in RA. Disclosures A.R. Oke None. S. Young-Min None.

Natural History of Adult Patients with GM2 Gangliosidosis.

GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the HEXA (Tay-Sachs disease [TS]) or HEXB (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis. We retrospectively described 12 patients from a French cohort and 45 patients from the literature. We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20 years of disease evolution, half of the patients were wheelchair users. Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. ANN NEUROL 2020;87:609-617.

NCMP-02. MYASTHENIA GRAVIS INDUCED BY AVELUMAB

Abstract Monoclonal antibodies targeting PD- 1 (nivolumab and pembrolizumab) and PD-L1 (avelumab, atezolizumab, and durvalumab) are FDA approved for the treatment of metastatic cancers. Immune-related adverse events (irAEs) are autoimmune diseases which occur following treatment with PD-1 and PD-L1 inhibitors. Neurological irAEs following PD-L1 blockade are rarely reported, and mainly consist of Myasthenia Gravis (MG) and myositis. MG induced by avelumab has not been previously reported. We present a 74-year-old female with stage IV ovarian adenocarcinoma who entered a clinical trial involving avelumab and entinostat after disease progression following extensive resection, chemotherapy with doxorubicin, then docetaxol and cisplatin. She developed progressive generalized weakness and fatigue two months after entering the trial, leading to respiratory weakness and hypoventilation, and resulting in intubation and mechanical ventilation. Exam showed head-drop, diplopia, and proximal &gt; distal upper and lower limb weakness. Antibodies to acetylcholine receptors, muscle specific tyrosine kinase, and voltage-gated calcium channels (P/Q and N type) were negative, and serum creatine kinase was normal. Repetitive nerve stimulation showed significant decrement in the left spinal accessory nerve motor response with recording at trapezius. She was diagnosed with seronegative MG and was treated with IVIG, 2 grams/kg divided over 4 days, prednisone 60 mg daily, and pyridostigmine, which resulted in successful extubation, followed by gradual resolution of MG symptoms over a period of 3 months. At approximately 2 year follow-up, she remains on maintenance IVIG at 0.5 grams/kg every 3 weeks, as she develops proximal lower limb and neck extension weakness at the end of each IVIG cycle. We conclude that MG is a potentially life threatening but treatable irAE associated with avelumab. Our case also adds to the accumulating literature of the role of PD-1 signaling in the pathogenesis of autoimmune diseases of the muscles and neuromuscular junctions.

Mitochondrial localization of PABPN1 in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized by ptosis, dysphagia, and weakness of proximal limbs. OPMD is caused by the expansion of polyalanine in poly(A)-binding protein, nuclear 1 (PABPN1). Although mitochondrial abnormality has been proposed as the possible etiology, the molecular pathogenesis is still poorly understood. The aim of the study was to specify the mechanism by which expanded PABPN1 causes mitochondrial dysfunction in OPMD. We evaluated whether transgenic mouse model of OPMD, by expressing expanded PABPN1, indeed causes mitochondrial abnormality associated with muscle degeneration. We also investigated the mechanism by which expanded PABPN1 would cause mitochondrial dysfunction in the mouse and cell models of OPMD. Mitochondrial localization of PABPN1 was observed in the muscle fibers of patients with OPMD. Moreover, abnormal accumulation of PABPN1 on the inner membrane of mitochondria and reduced expression of OXPHOS complexes were detected in the muscle fibers of the transgenic mice expressing expanded human PABPN1 with a 13-alanine stretch. In cells expressing PABPN1 with a 10-alanine or 18-alanine stretch, both types of PABPN1 accumulated in the mitochondria and interacted with TIM23 mitochondrial protein import complex, but PABPN1 with 18-alanine stretch decreased the cell viability and aggresome formation. We proposed that the abnormal accumulation of expanded PABPN1 in mitochondria may be associated with mitochondrial abnormality in OPMD.

GNE myopathy: Disease progression in a large cohort of genetically confirmed cases from a single centre in India

Disease progression of GNE myopathy is steady, relatively slow and leads to loss of ambulation within 10–20 years from onset. A retrospective study on disease progression in genetically confirmed GNE myopathy patients (2006 to 2018). Informed consent obtained from all patients. Total = 127 of 122 families. Mutation pattern: Compound heterozygous (CH) = 77(69.4%), homozygous (HOM) and only heterozygous (HET) = 17 (15.3%) each, novel = 56 (50.5%). Distal kinase domain affected = 105/111 (94.6%); epimerase domain only = 5. Common Indian mutation V727 M = 93 (83.8%). CH mutations had V727 M in one allele except in one. Roma gypsy founder mutation (I618T) = 5 (HOM-4;CH-1). Other mutations (A555V and L732F in 4 each; Y392H, G502D, P58L and G599 V in 3 each). Ninety-three cases from 88 families were studied for progression. Men = 61(65.5%). Mean age at presentation: 33 ± 7.2 years (20–55), age at onset: 27 ± 6.1 years (14–46), duration of symptoms:6.2 ± 5.1 years (1–24), total duration at presentation: 8.6 ± 5.7 years (1–28); duration of follow-up: 8.9 ± 3.3 years (1–17); age at loss of ambulation in 4 cases = 30.0 ± 6.0 years. At last follow-up, 80 patients were independently ambulant, 11 required maximum support to walk (none ever used a cane), 2 were wheel chair bound. The course was slow in 81 (87.1%) and rapid in 12 (12.9%). The initial symptom was foot drop in 74/93 (79.6%). Hip muscle weakness present in90/93 (96.8%). Distal upper limb weakness = 68 (73.1%), proximal upper limb weakness in 25 (26.9%). Beevor's sign in 57(61.3%). This is the largest series of genetically confirmed GNE myopathy from a single center. Disease progression study shows that majority had a slow progression and were ambulant more than a decade after onset and this is similar to reports from Japan and UK.

1810 Esophageal Cancer-Associated Myositis

INTRODUCTION: The inflammatory myopathies are a group of acquired diseases characterized by a proximal myopathy due to skeletal muscle inflammation. Myositis association with malignancy has been well described, particularly in dermatomyositis (DM).Although dysphagia may be the presenting symptoms for DM given striated muscles at upper esophagus;it has also been associated with increased risk of malignancy.Cancer-associated myositis (CAM) is thought to be a cross-reaction to regenerating muscle tissue as seen in tumor antigen. An estimated 20-30% of DM patients will develop cancer. CASE DESCRIPTION/METHODS: Case of a 70-year-old male who arrived to the emergency department due to three-week history of progressive dysphagia with a 45-pound weight loss in the past 3 months. Also reported skin rash and generalized weakness. Physical examination with lower proximal limb weakness and generalized erythematous patches more prominent over the trunk with scaly violaceous raised papules in the knuckles and in the interphalangeal joints. Laboratories showed elevated muscle enzymes including aldolase, creatinine kinase, transaminases and lactate dehydrogenase.Negative myositis specific antibodies including ANTI-JO1, ANTI-MI2 and ANTI-SRP. MRI showed inflammatory muscle disease. Gastroenterology proceed with esophagogastroduodenoscopy for evaluation of dysphagia with findings of a nodular lesion inside a hiatal hernia. Biopsies were consistent with adenocarcinoma with positive stains for HER2 and AE1/AE3 suggesting advance poorly differentiated adenocarcinoma. Metastatic workup with evidence of retroperitoneal adenopathy. Hematology Oncology started chemotherapy with FOLFOX-6 and radiotherapy. He showed some initial improvement; however, later he succumbed to respiratory tract infection. DISCUSSION: In this case, the patient was found with an underlying esophageal malignancy along with DM which are findings consistent with CAM. The absence of myositis specific antibodies supports the diagnosis. Dysphagia can be the presenting symptom of both DM and esophageal cancer. In DM is due to the involvement of the oropharyngeal striated muscles and upper esophagus.In the setting of an underlying inflammatory myopathy symptoms can be misleading, causing misdiagnosis. It is important that all patients diagnosed with a myopathy along with alarming symptoms undergo evaluation for the possibility of an underlying malignancy since prognosis and life expectancy in CM patients is determined by the underlying malignant disease.

3. Dermatomyositis and underlying bilateral benign endometrioma

IntroductionThe link between ovarian malignancy and paraneoplastic dermatomyositis is well established. Association with underlying benign ovarian pathology is much less certain, with only scarce case report evidence available. This represents the first case of dermatomyositis with associated bilateral ovarian chocolate cysts.Case descriptionA 45-year-old female presented with classical features of dermatomyositis, with a background of hypertension and non-alcoholic fatty liver disease. She had proximal limb weakness, neck flexor weakness, dysphagia and dysphonia, accompanied by a scaly, erythematous rash over her face, chest, abdomen and lateral thighs. Serum creatine kinase (CK) at presentation was 4923 IU/L. An MRI scan of her thighs showed widespread muscle oedema affecting both legs and the pelvis, including the quadriceps, iliacus and psoas muscles. A punch biopsy of the skin on her thigh showed only post inflammatory pigmentation. Lung volumes were reduced (FEV1 69% predicted). Video fluoroscopy confirmed moderate-severe pharyngeal stage dysphagia. CT scan of the chest, abdomen and pelvis revealed enlarged, unilocular cysts in each ovary, the right cyst measuring 7 cm and the left, 5 cm in maximal diameter. Subsequent transvaginal ultrasound confirmed bilateral unilocular, thick walled cysts with a ground-glass appearance, which would be consistent with benign endometriomas. A further interval ultrasound after 1 month showed no change in their appearance or size. Serum CA125 was 104 kU/L.The patient was treated with 3 pulses of 1g intravenous (IV) methylprednisolone, followed by 2 courses of IV immunoglobulin 2g/kg over 5 days. This was followed by a gradually reducing course of oral prednisolone, starting at 50mg OD PO alongside 15mg weekly of oral methotrexate. She has responded well to treatment, with near normalisation of her objective manual muscle testing scores and normalisation of the serum CK value. Surgery is now planned for a total abdominal hysterectomy and bilateral oophorectomy.DiscussionExtensive investigation has not demonstrated any other underlying malignancy to account for the development of dermatomyositis. Initial limited and unsustained clinical response to IV methylprednisolone prompted further treatment with IV immunoglobulin. Surgical histology results are now awaited to confirm the suspected diagnosis. It will be very interesting to see if surgical removal of the cysts has any impact on the clinical manifestation of disease.Key learning pointsBenign ovarian pathology should not be dismissed as a potential underlying mechanism for development of dermatomyositis.Conflicts of interestThe authors have declared no conflicts of interest.

11. An unusual case of dermatomyositis with anti-small ubiquitin-like modifier activating enzyme (SAE) antibodies present

IntroductionIdiopathic inflammatory myopathies (IIM) have long been diagnosed using a defined number of clinical criteria (Bohan and Peter). The emergence of new myositis specific antibodies (MSAs) and their relation to specific disease phenotypes may be useful in establishing a new clinical-serological diagnostic criteria for different disease presentations and thus help to determine management and prognosis. We present a case of dermatomyositis (DM) where limb subcutaneous oedema; a rare manifestation of the disease, and severe dysphagia were prominent clinical features in addition with the presence of anti-small ubiquitin-like modifier activating enzyme (SAE) antibodies.Case descriptionA 63-year-old Pakistani male presented with weight loss, anorexia, odynophagia, and a rash over his scalp, chest, face and flexor surfaces. Initial blood results revealed hypoalbuminaemia, CRP 7mg/L and ESR 37mm/h. A CT chest revealed an anterior mediastinum soft tissue mass suggestive of necrosis, with multiple ill-defined nodes throughout the lungs.An endoscopy revealed severe gastritis. Oropharyngeal examination revealed pooling of saliva and mucositis. Ceftriaxone was commenced for a presumed infective aetiology.Video fluoroscopy confirmed pharyngeal dysphagia with aspiration. Examination demonstrated a non-fatigable bulbar sounding dysarthria. There was no tongue wasting or fasciculations. Power was globally reduced, with marked proximal upper and lower limb weakness.Nerve conduction studies revealed normal sensation, and most motor nerves had normal conduction velocities with small nerve responses. Electromyography showed areas with denervation.With no improvement in the patient’s condition, anti-tuberculosis and anti-fungal therapy were commenced, with pulsed methylprednisolone for three days followed by 80mg daily to cover for an organizing pneumonia. Subsequent cultures were negative.Progressive weight loss with muscle wasting ensued and later, facial hyperpigmentation was noted in addition to the development of facial, lip and arms swelling. He was rheumatoid factor positive >500 iu/ml, with a raised IgE 2912 g/L and IgG 37.6 g/L. A CT-PET scan revealed intense uptake in the muscles posterior of the neck, tongue and masticators.An MRI scan of his arms revealed several abnormal signals around the shoulder girdle, long muscles of the back, and upper arm, which guided the site for muscle biopsy. This revealed highly abnormal skeletal muscle with frequent atrophic and necrotic fibres overrun by macrophages and T-cell rich inflammation. These findings in addition to serology reporting the presence of anti-SAE antibodies confirmed the diagnosis.Pulsed methylprednisolone, immunoglobulin therapy, and azathioprine were initiated with reducing prednisolone dose.DiscussionThis case of DM with a generalised rash, severe dysphagia and limb subcutaneous oedema were salient features in addition to the presence of anti-SAE antibodies. Anti-SAE has been shown to be present exclusively in DM patients where rash and severe dysphagia are common clinical findings. Our patient presented with severe dysphagia, which can be difficult to manage requiring enteral feeding. Video fluoroscopy was particularly useful in this case helping to stratify the severity of dysphagia and we would urge other clinicians to use this tool when investigating patients with suspected dermatomyositis to avoid potential complications of poor swallow including aspiration pneumonia. The additional imaging modality of PET-CT in our case confirmed the involvement of the muscles of mastication thus could prove a useful tool when investigating involvement of swallowing muscles in patients with anti-SAE DM.Skin features are another common finding in the anti-SAE group and our patient had a heliotrophic rash and shawl sign, which responded poorly to treatment. We describe the additional feature of severe subcutaneous limb and facial oedema, a rare manifestation of the disease, described in only a few other cases. Limb subcutaneous oedema is thought to reflect underlying severe muscle disease, is difficult to treat, and often is unresponsive to conventional treatment. Our case, and several other cases with the presence of limb oedema as reported in a literature search, required treatment with intravenous immunoglobulin and glucocorticoids, in addition with azathioprine and methotrexate.This is the first reported case to our knowledge of a patient with positive ANA, RF, anti-ccp, and anti-small ubiquitin-like modifier activating enzyme (anti-SAE) antibodies.Key learning pointsThe finding of anti-SAE in our case where severe dysphagia was present provides further weight to this antibody being a useful serological marker to identify this subgroup of DM patients. Identifying this antibody may be helpful in creating management strategies for these patients and determining disease progression and prognosis.The presence of limb and facial oedema may be an overlying feature of the anti-SAE group; however, previous cases of limb oedema have not identified this antibody as the SAE test was unavailable. The presence of severe dysphagia and subcutaneous oedema suggests the presence of anti-SAE lends itself to a clinical phenotype of DM that is particularly severe and requires multidisciplinary input.Conflicts of interestThe authors have declared no conflicts of interest.

Clinical and electrophysiological characteristics of Guillain-Barré syndrome in Colombia.

Despite the wide literature describing the features of Guillain-Barré syndrome (GBS) in different populations worldwide, Colombian data are very scarce. We aim to characterize patients with GBS in a general hospital setting in Colombia. We conducted a retrospective chart review of GBS cases managed at the Hospital Universitario Fundación Santa Fe de Bogotá, from 2011 to 2016. Twenty-three patients were included. The most commonly reported symptoms were paresthesias (65%), pain (61%), proximal (22%) and distal (74%) limb weakness, and facial palsy (30%). 9% of patients had Fisher syndrome and 21% had other variants: Bickerstaff, pharyngeal-cervical-brachial pattern, and facial diplegia. There was a predominance of the demyelinating form (70%), with only 22% of patients presenting with the axonal variants. Our results are concordant with previous studies in Colombia.

Miastenia gravis y trastornos relacionados con la unión neuromuscular

Myasthenia gravis (MG) is the most common disease of the neuromuscular junction. It is an acquired autoimmune disease, in which several antibodies against postsynaptic receptors are detected. Initial symptoms often manifest focally, mainly ocular weakness resulting in ptosis and diplopia. Subsequently, symptomatology evolves to generalized muscular involvement and bulbar symptoms: dysphagia and dysarthria, cervical musculature and proximal limb weakness. Clinical progression results on myasthenic crisis and respiratory failure. The clinical hallmark of MG is a fluctuating pronounced muscular weakness along the same day and related with physical activity or aggravating factors. Occasionally, spontaneous remissions have been reported. Diagnosis key is clinical suspicion achieving by clinical pattern recognition. Diagnostic confirmation is obtained by serological (MG antibodies) and neurophysiological tests. Thanks to advances in the knowledge about underlying immunopathology, the range of therapeutic strategies has grown (combining acetylcholinesterase inhibitors with immunosuppressant drugs and thymectomy), decreasing its morbidity and mortality.

Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.

Bethlem myopathy represents the milder phenotype of collagen type VI-related myopathies. However, clinical manifestations are highly variable among patients and no phenotype-genotype correlation has been described. We aim to analyse the clinical, pathological and genetic features of a series of patients with Bethlem myopathy, and we describe seven new mutations. A series of 16 patients with the diagnosis of Bethlem myopathy were analyzed retrospectively from their medical records for clinical, creatine kinase (CK), muscle biopsy, and muscle magnetic resonance (MRI) data. Genetic testing was performed through next-generation sequencing of custom amplicon-based targeted genes panel of myopathies. Mutations were confirmed by Sanger sequencing. The most frequent phenotype consisted of proximal limb weakness associated with interphalangeal and wrists contractures. However, cases with isolated contractures or isolated myopathy were found. CK levels did not correlate with severity of the disease. The most frequent mutation was the COL6A3 variant c.7447A>G, p.Lys2486Glu, with either an homozygous or compound heterozygous presentation. Five new mutations were found in COL6A1 gene and other two in COL6A3 gene, all of them with a dominant heritability pattern. From these, a new COL6A1 mutation (c.1657G>A, p.Glu553Arg) was related to an oligosymptomatic phenotype with predominating contractures in the absence of weakness and a normal muscle MRI. Finally, the most common COL6A1 mutation reported to date that leads to an Ullrich phenotype (c. 868G>A, p.Gly290Arg), has been found here as Bethlem presentation. Manifestations of Bethlem myopathy are quite variable, so either contractures or weakness may be lacking, and no phenotype-genotype associations can be brought.