The Annual Carrell-Krusen Neuromuscular Symposium is a unique conference attended by more than 200 each year in Dallas, Texas. Its name honors Dr. Brandon Carrell who retired as physician-in-chief at Texas Scottish Rite Hospital in 1978 and Dr. Ed Krusen who organized the first Muscular Dystrophy Association clinic in Dallas. This Symposium began in 1978 under the leadership of Dr. Jay Cook as a Muscular Dystrophy Clinic Directors' meeting and is now jointly sponsored by the hospital, the Muscular Dystrophy Association, Childrens' Medical Center of Dallas, and the University of Texas Southwestern Medical Center. The Symposium has grown to be the most popular clinical meeting for neuromuscular specialists in the country. During the 2 day meeting, attendees participate in lively discussions while meeting interesting and challenging patients. Attendees are invited to contribute interesting electrodiagnostic and histopathologic cases to review with the group. The visiting professor, the recipient of the Carrell-Krusen Award, gives the keynote lecture. Currently, the Program Director is Dr. Susan T. Iannaccone and Co-Directors Dr. Jaya Trivedi and Dr. Diana Castro.
This publication represents a key component of the live conference that has been approved for AMA PRA Category 1 Credit. The University of Texas Southwestern Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. All final accreditation, credit designation, and disclosure information is available at https://cme.utsouthwestern.edu/rp2102a as well as the final conference registration materials.
Susan Iannaccone, MD
Jaya Trivedi, MD
Diana Castro, MD
Sharon Nations, MD
Lauren Phillips, MD
Steven Vernino, MD, PhD
L/V-1 An Infant With Arthrogryposis and Weakness
B. Rhem, D. Castro, Dallas, TX.
M.C. is a 3 year old girl with history of arthrogryposis, hypotonia, weakness and mild hypoxic ischemic encephalopathy (HIE) secondary to birth trauma who was referred to Neurology at 4 months of life due to concern for an underlying neuromuscular disorder. She was born via induction at 36 weeks gestation due to oligohydramnios and required resuscitation in the delivery room including intubation, ventilation, chest compressions and epinephrine. She required neonatal cooling protocol for HIE at birth. Her family history is negative for any known neuromuscular conditions. On initial physical exam, she is noted to be alert. She has multiple contractures present at elbows, wrists and fingers. She has reduced muscle bulk and hypotonia with decreased proximal limb movement. Deep tendon reflexes are absent. M.C. has slowly made progress in her motor development and is now sitting independently. She had speech delay but now speaks in full sentences and remains alert and interactive. At 8 weeks of age, M.C. underwent a limited EMG/NCS which revealed diffuse axonal polyneuropathy. Initial workup also included a chromosomal microarray (negative), MRI brain which demonstrated evidence of HIE with periventricular leukomalacia, creatine kinase level (normal at 104) and spinal muscular atrophy genetic panel (negative). Whole exome sequencing was subsequently sent and revealed variants that explain her phenotypic presentation. Clinical and genetic findings along with pathophysiology will be discussed in this case.
L/V-2 Upper Extremity Weakness and Ataxia in a Child
D. Brock, M. Wright, Aurora, CO.
Objective: To describe the presentation and treatment response of a rare, progressive, and treatable childhood-onset neuromuscular disorder.
Case: We present a 3-year-old girl seen initially for global developmental delays and breath-holding spells, who developed rapidly progressive, upper extremity predominant weakness and atrophy as well as progressive gait instability over 6-8 months. Pertinent findings on initial examination included pronounced cervicothoracic kyphoscoliosis, mild diffuse hypotonia, and a wide-based, ataxic gait. Follow-up examination 8 months later was notable for new shoulder girdle muscle atrophy with marked upper extremity weakness, receptive language deficits, apparent dysarthria, areflexia, and worsening gait instability. MRI of her brain and cervical spine revealed a Chiari I malformation without evidence of syringomyelia. A limited EMG/NCS was compatible with a mild, chronic sensorimotor polyneuropathy. Initial laboratory work-up—including CK, thyroid studies, and metabolic screening labs—were unrevealing.
Conclusions: Further evaluation revealed the presence of a rare, potentially treatable disorder and the patient has shown significant improvement following 12 months of therapy. Here we present serial video examinations to improve awareness and diagnosis of this treatable disorder.
L/V-3 Four Sisters With Progressive Weakness
K. Batley, D. Castro, Dallas, TX.
JT presented to the Neuromuscular Clinic at the age of 10 years old for evaluation of progressive weakness and difficulty with ambulation. She met her early motor milestones appropriately, but parents noted frequent tripping and falls that began at the age of 5 years old. Her lower extremity weakness progressed to the point of requiring a rolling walker for ambulation at presentation. She had begun to develop upper extremity weakness by this time as well. Her cognition was normal, and she was doing well in mainstream classes at school. Her parents report that 3 of her 4 older sisters have similar symptoms, with varying degrees of weakness and ambulation difficulties. The sister with the most severe weakness required tracheostomy after developing chronic respiratory failure following scoliosis surgery. Her exam is significant for distal loss of sensation to pinprick in all extremities, hypotonia, and weakness most prominent in the lower extremities with hip flexion and ankle dorsiflexion. Reflexes are 2+ at her bilateral patella but absent elsewhere. She has severe equinovarus contractures of bilateral feet, with high arches and hammertoes. The skin of her distal extremities is cold and mottled. She is unable to walk without support, and gait is hyperlordotic and wide-based, with flexion at the hips and knees. Nerve conduction studies showed an axonal motor polyneuropathy affecting the lower extremities more significantly than the upper. Initial genetic testing included a Charcot-Marie-Tooth Disease Comprehensive Panel, which was unrevealing. After continued decline, loss of ambulation, and progressive difficulty with activities of daily living, whole exome sequencing was performed, yielding a diagnosis. Clinical findings, diagnosis, and pathophysiology will be discussed.
L/V-4 An Infant With Hypotonia and Fatigability and Response to Pyridostigmine
M. Lopez-Chacon, N. kuntz, A. Buehner, V. Rao, Chicago, IL.
Three month-old female presented for evaluation of hypotonia and gross motor delays. Infant was a 3.23 kg product of a 41 week gestation notable for decreased fetal movements to a 30 years old Gravida 2 Para 2 mother. Neonatal course significant for constipation and tendency to easily overheat irrespective of environmental temperature. Family history positive for autoimmune disorders (maternal hypothyroidism, maternal GGF with myasthenia gravis, maternal grandmother with polymyalgia rheumatica). Height/Weight/Head circumference within normal limits. Exam notable for an alert child with blonde hair, blue eyes, fair skin (unlike family members) Also noted were an elongated face with limited facial expression; high-arched palate with a soft cry, EOM full with variable right esotropia. Axial and appendicular hypotonia were present with frog-leg position, significant head-lag and poor head control when seated with support. Muscle stretch reflexes were diminished throughout. Evaluation included normal results for CBC, Chem14, ammonia, thyroid functions, creatine kinase, chromosomal microarray, urine OA, carnitine and acylcarnitine profile, free fatty acids, lactate and pyruvate. Comprehensive Neuromuscular Panel demonstrated 3 VOUS (1 on MYH2 gene, 2 on AGRN gene, all maternally inherited). Infant received PT and OT and made developmental gains. Fatigability during activity and fluctuating right ptosis led to neurophysiologic studies which showed normal motor and sensory NCS for age, 13% decrement on 2 Hz RNS of right accessory nerve. AchR and anti Musk antibodies were absent. A trial of oral pyridostigmine (9.6 mg twice daily) was started and within 5 days, mother reported improvement in infant's activity level and ptosis. Whole exome sequencing was ordered to further investigate the etiology of her symptoms.
L/V-5 Casper the Mercurial Ghost
B. Putko, C. Phan, Edmonton, AB, Canada.
A 41-year-old male presented with 5 weeks of progressive symptoms. He complained of fatigue yet could not sleep due to aching pain in the shoulder and hip girdles, as well as paresthesiae in the legs. He had diffuse muscle twitching, which was constant in the lower legs, drenching night sweats every few hours, and urinary retention. Review of systems was otherwise negative. On examination, cranial nerves were normal. Muscle bulk was normal, but he had myokymia in gastrocnemius bilaterally with frequent fasciculations in deltoids, triceps, and quadriceps. Power was 5/5 in the upper and lower extremities. Reflexes were 2+ and symmetric with flexor plantar responses. He had hyperpathia in the distal lower extremities. Coordination and gait were normal. C-reactive protein, T3, and T4 were modestly elevated, but the remaining serum and cerebrospinal fluid chemistries and cellular constituents were normal. Standard 2-limb nerve conduction studies were normal. Electromyography demonstrated fasciculations in numerous muscles, most evident in gastrocnemius, while voluntary motor units were normal. The differential diagnosis included peripheral nerve hyperexcitability syndromes, stiff-person syndrome, and thyrotoxicosis. Contactin-associated protein-like 2 (CASPR2) antibodies returned medium-positive. Malignancy screen was negative. He was admitted to hospital for treatment with 5 cycles of plasma exchange, high-dose prednisone, and carbamazepine. His hyperhidrosis improved, but other symptoms were unchanged. During admission, he volunteered that he was taking native medicines from his home country. Twenty-four-hour urine mercury was 40 times the upper limit of normal. After chelation therapy with dimercaptosuccinic acid, symptoms improved in intensity and frequency. Repeat 24-hour urine mercury was 8 times the upper limit of normal and CASPR2 antibody titre was weak-positive.
L/V-6 Congenital Myasthenic Syndromes
N. McGraw, R. Barohn, S. Chandrashekhar, M. Dimachkie, D. Jabari, O. Jawdat, M. Pasnoor, J. Statland, C. Farmakidis, Kansas City, KS.
Objective: Describe the phenotype, rate of misdiagnosis, diagnostic delay, and treatment response in congenital myasthenic syndromes (CMS) and compare to the literature.
Background: CMSs are a heterogeneous group of rare genetic disorders sharing presynaptic, synaptic, and postsynaptic disruption in neuromuscular transmission. Clinical presentation is variable, and diagnosis is often delayed.
Methods: Retrospective chart review of patients with a clinical presentation compatible with CMS and confirmatory genetic testing seen at our tertiary care neuromuscular clinic.
Results: Four patients were identified (2 female). All had postsynaptic defects in neuromuscular transmission. Two had mutations in endplate proteins encoded by the DOK7 and RAPSN genes. The others had mutations in acetylcholine receptor subunit genes, one in the alpha subunit (CHRNA1 gene), one in the epsilon subunit (CHRNE gene). Symptom onset was at birth (DOK7 and CHRNE), infantile (RAPSN), and childhood (CHRNA1). Average age at genetic diagnosis was 36 (range 20–63) years. The average diagnostic delay was 26.5 (range 19–32) years. Three patients presented with initial symptoms of limb-girdle weakness while one (CHRNA1) presented with a distal myopathy phenotype. Three patients were previously misdiagnosed: limb-girdle muscular dystrophy (DOK7), distal myopathy (CHRNA1), and seronegative myasthenia gravis (RAPSN). The DOK7 patient has shown increased strength with escalating doses of albuterol compatible with prior reports. Two patients were treated with pyridostigmine: RAPSN patient showed mild subjective improvement in symptoms with stable MG-ADL scores, compatible with current literature; CHRNE patient continues to show fatiguability and an albuterol trial is ongoing. The CHRNA1 patient elected to defer treatment due to mild symptoms.
Conclusions: CMS in our clinic population appears to be rare. Misdiagnosis is common and diagnostic delay is between 20 and 30 years. Responses to pharmacotherapy are comparable to the literature. The CHRNA1 patient presented with a distal myopathy phenotype which is a rare phenotype in CMS presentation.
S-1 Inclusion Body Myopathy in HIV: Clinical Spectrum
Saurabh Shukla, Ashok Averma, Flowood, MS.
Objective: To report 2 cases of Inclusion body myositis (IBM) and human immunodeficiency virus infection (HIV) and review previously reported 23 similar cases.
Background: IBM is the most common acquired myopathy after the age of 50. The etiopathogenesis of IBM is poorly understood consisting of components of inflammation and degeneration. A spectrum of myopathies including inflammatory myositis, nemaline myopathy, toxic myopathy, tropical myositis, sarcopenia, and muscle wasting have been described in HIV population.
Design/Methods: Case#1: A 61-year-old man was diagnosed HIV seropositive at age 28. He developed walking difficulty at age 36, followed by shoulder and wrist and finger flexor weakness in his 40s. He received various combination antiretroviral treatments (cART) with variable results; most recently Emtricitabine, Tenofovir and Reltegravir with effective viral suppression. Case#2: 63-year-old man was diagnosed with HIV infection at age 30 and received various cART regimens since age 41; most recently Discovy and Issentres with effective viral control. He reported asymmetric hip and knee weakness at age 55, followed by arm weakness. In both cases, the topography of muscle weakness, serum creatinine kinase (CK), muscle imaging, electromyography, cytosolic nucleotidase 1A antibody levels, and muscle biopsy were consistent with IBM.
Results: Including these 2 cases, we found 25 patients of IBM in conjunction with HIV infection in English and French Literature. These cases were younger than those who suffer from IBM without HIV (median age of onset 46: range 28–67 years), they were almost all men (24) with significant CK elevation (median 1521 IU/L, range 465–10,270 IU/L) and most of them received long term cART.
Conclusions: Occurrence of IBM with HIV infection does not appear co-incidental. The etiology of IBM in HIV infected individuals is unclear with possibility of interaction of immune dysregulation of Treg cells, chronic cART use, and ageing process related to long-standing HIV infection.
S-2 Outcomes in Neuromuscular Genetic Testing
H. Al Sultani, K. Hafeez, A. Shaibani, Houston, TX.
Genetic testing is an effective and reliable modality in clinical neuromuscular diagnosis. Both single-gene sequencing and next-generation sequencing are widely used among neuromuscular clinicians. The recent developments in testing methods and increasing reliance on genetic testing in clinical practice require more studies to examine the benefits and advantages of such tests. We examined the results of single-gene sequencing/repeat analysis, panels, and whole-genome sequencing (WES) of 514 tests of 393 patients who visited a tertiary neuromuscular clinic from 2014 through 2020. The results were either positive, negative, or variations of uncertain significance (VUS) and were categorized by disease type. Twenty-eight percent (n.147) of the tests were positive and 23% (n.122) were VUS. The result was positive in 23% of the single-gene sequencing/repeat analysis, 43% of the panels, and 30% of WES. Regarding disease type; we observed the following positive rates: 39% positive for myopathy, 20% for neuropathy, 18% for MND, and 27% for the rest disorders such as myasthenia gravis, cerebellar ataxia, etc. Our results showed consistency with current studies and the improvement trends of genetic testing results over time. Despite obstacles, the diagnostic benefit of genetic testing is confirmed. Providing statistical data can inform the judicious utilization of genetic testing among physicians.
S-3 Non-dystrophic Myotonia: 2 Year Longitudinal Data
T. Fullam, S. Chandrashekhar, C. Farmakidis, D. Jabari, O. Jawdat, M. Pasnoor, M. Dimachkie, J. Statland, Kansas City, KS.
Objective: Determine 2 year trends in a large group of genetically proven non-dystrophic myotonia (NDM) participants.
Background: NDMs, a heterogeneous group of rare neuromuscular disorders, share symptoms of episodic myotonia and muscle weakness. Prospective data examining disease impact is limited.
Design/Methods: Prospective observational study of definite/clinically suspected NDM participants from 6 sites (USA, UK, Canada; CINCH consortium) between March 2006 and March 2009. Outcomes included standardized symptom interview/physical exam, Short Form-36/Individualized Neuromuscular Quality of Life instruments, electrophysiological short/prolonged exercise tests, manual muscle testing (MMT, average composite 24 muscles), grip strength, and modified get-up-and-go test (GUG). Standard descriptive statistics and one-way ANOVA were used for comparison.
Results: Comparisons were restricted to confirmed sodium (baseline, year 1, year 2: n = 34, 19, 13), chloride (n = 32, 26, 18), and myotonic dystrophy type 2 (n = 9, 6, 2) mutations. Muscle stiffness was the most predominant symptom over time (54.7%–64.7%). Eyelid myotonia and paradoxical handgrip/eyelid myotonia were more frequent in SCN4A. Grip strength and combined MMT (average baseline CLCN1 4.49, SCN4A 4.67, DM2 4.36) were stable over time. Modified GUG showed less improvement between 4 repeated trials at each timepoint in SCN4A (range −0.17 to −0.37 seconds) compared to CLCN1 (−0.98 to −1.42 seconds) but was stable over time. Median short exercise decrement from baseline amplitude at room temperature was 27.22% (range 6.60–45.59) CLCN1 and 6.54% (range −3.69 to 21.79) SCN4A. Decrement post-cooling was increased for SCN4A [36.19% (0.66–50.1)]. The mean post short exercise decrement was stable over time, except for SCN4A [baseline to Year 2 decrement difference 16.2% (3.02–29.38)]. Fournier patterns were inconsistent over time. INQoL total score showed higher disease impact for SCN4A and DM2 than CLCN1 with total scores stable over time.
Conclusions: MMT, GUG, and short exercise test decrements were stable over time. QOL was impacted in the majority of NDMs. Symptomatic therapies may be important for disease altering/symptomatic control.
S-4 A 10 Year Single Center Experience On Juvenile Myasthenia Gravis
O. Hamid, E. Caron, Memphis, TN.
Juvenile Myasthenia gravis (JMG) is an autoimmune disease in which antibodies are directed against the postsynaptic membrane of the neuromuscular junction (NMJ). Initial symptoms include drooping eyelids, double vision, fatigability, choking or difficulty swallowing and subsequent weight loss. Some children experience shortness of breath, speech impairment, or changes in facial expression. Diagnosis in children can often be delayed on the order of months to years as symptoms can often be ignored or attributed to something else. Patients can therefore present in crisis and respiratory failure requiring intubation and intensive care (ICU) admission. Anecdotally we have had several patients present in crisis with symptoms going on for several months to a year. Early diagnosis and treatment is crucial to prevent permanent damage to the NMJ as well as prevent ICU admission.
Objective: We aim to identify areas for improvement and improve time to diagnosis and treatment.
Methods: We aim to retrospectively chart review and evaluate our center's JMG patients over the past 10 years looking at variables such as age at diagnosis, initial symptoms, time to neurology consultation, time to diagnosis and time to treatment. We will also evaluate whether other specialties that may have been consulted such as ENT, Ophthalmology, Speech therapy, Gastroenterology and Endocrinology.
S-5 McArdle Disease: Lessons From Delayed Diagnosis
S. Bhai, R. Haller, Carrollton, TX.
Diagnosis of McArdle disease is often delayed by several years. The purpose of this study was to evaluate the time to diagnosis, misdiagnoses, and lessons to aid in earlier diagnosis. The duration of diagnostic delay, clinical categories of misdiagnoses, and clinical features were assessed in 76 patients with McArdle disease. In the 32 male patients, 55% were diagnosed at least 10 years after symptom onset, whereas in the 44 female patients, 84% were diagnosed at least 10 years after symptom onset. Clinically, 62% had contractures, 54% had myoglobinuria, and 62% had the second wind phenomenon. There were 12 patients that became pregnant with 19 deliveries, 3 of which were cesarian sections in one patient. Of the vaginal deliveries, fatigue post-delivery was reported by one patient, while another patient had one episode of pigmenturia. Overall, reported misdiagnoses most often related to liver disease (30%) due to abnormal liver function tests or renal disease (19%) due to pigmenturia. Other misdiagnoses included myositis (17%), cardiac etiologies (9%), asthma (7%), and muscular dystrophies (6%). To our knowledge, this is the largest case series of McArdle disease patients to evaluate for the time to diagnosis and misdiagnoses. This study demonstrates the prolonged time to diagnosis, particularly in female patients, and common misdiagnoses due to misinterpretation of liver function tests, CK, and pigmenturia. Appropriate diagnosis can help prevent unnecessary procedures and treatment.
S-6 Clinicians Preference of Virtual Vs. Physical Visit
K. Hafeez, H. Al Sultani, A. Shaibani, Houston, TX.
In this era of rapidly changing practice and adoption of tele-neurology in clinical practice due to COVID-19 pandemic, we looked at the physician and patient preference for in-person vs virtual visits to guide clinical decisions about using telemedicine after the crisis is over. Data collected from 520 patient surveys revealed that 50% preferred in-person visits and 26% preferred virtual visits. Sixty-four percent reported physical face-to-face interaction as “very important.” For receiving a new diagnosis, 55% preferred in-person. Forty percent were worried about not being physically examined. Eighty-four percent believed virtual visits were sufficiently private. Sixty-eight percent did not consider expenses a factor in their decision. While 92% were comfortable with using technology, 55% preferred video communications, and 19% preferred phone calls. The visit preference was not significantly associated with gender, diagnosis, disease severity, and symptom management. Ninety-four neuromuscular specialists across the USA and Canada were phone surveyed in September 2020. 90.43% preferred physical visits when seeing new patients while 45% chose virtual visits for follow-ups. The majority thought that telemedicine reduces revenue (58.51%), quality of service (57.45%), and quality time spent with patients (62.77%). Nevertheless, most surveyed physicians agreed that telemedicine is time-efficient (84.04%), improves patient compliance (70.21%), and will be a long-term solution in clinical practice (67.02%). Fifty-eight percent revealed that telemedicine does not affect workload. The majority of neuromuscular physicians and patients preferred in-person visits for first interaction. Initial visit mandates physical exam that is key for diagnosis, but from patient perspective the significance of face-to-face interaction and non-verbal communication was higher. The importance of telemedicine for follow up visits can improve compliance, and may be beneficial for social and economic reasons. The prospect of improving the quality of care during a virtual interaction is an important factor to consider if we intend to increase satisfaction in the future.
S-7 Four Autonomic Presentations of a Multisystem Disease
K. Tarpara, S. Vernino, E. Golden, J. Elliott, Dallas, TX.
We present 4 cases of a multisystemic disease presenting with autonomic symptoms which highlight the range of presentations and the challenging diagnostic and therapeutic approaches required. Two cases presented with exercise intolerance, including exercise-induced hypotension, which may not be captured by standard resting autonomic reflex tests. These cases demonstrate the importance of obtaining a careful history and of reproducing the symptoms during a diagnostic evaluation whenever possible. The third case presented with severe GI dysfunction, and developed progressive neuromyopathy including autonomic involvement. The last case had the evolution of a multifocal sensory neuropathy to a predominantly autonomic neuropathy. The presenting autonomic symptoms coincided with cardiac involvement which ultimately led to the diagnosis.
P-1 A 15 Year Old Boy With Acute Onset Paralysis
R. Bass, N. Kuntz, J. Rubin, V. Rao, E. Graham, Chicago, IL.
A 15-year-old male presented with acute onset bilateral lower extremity weakness. He felt a “pop” in the left side of his lower back while turning in bed, followed by weakness and numbness in the left lower extremity that progressed to involve his right leg. Denied sick contacts, ingestion, or significant family history. Initial exam 6 hours after symptom onset demonstrated 0/5 strength in bilateral lower extremities, lax rectal tone, and absent lower extremity muscle stretch and cremasteric reflexes. MRI thoracic and lumbar spine with/without contrast within 24 hours of symptom onset was unremarkable. Nerve conduction studies done within 12 hours of onset demonstrated absent peroneal and tibial F waves, present median F wave, and normal motor and sensory responses in upper and lower extremities. Cerebrospinal fluid cell counts, glucose, and protein were normal. Serum studies including inflammatory markers, ANA, ds-DNA, copper, vitamin B12, methylmalonic acid, NMO and MOG antibodies were unremarkable. Nasopharyngeal COVID-19 testing was negative. Patient received 2 days of IVIG and 5 days of IV methylprednisolone. He required intermittent catheterization for neurogenic bladder prior to discharge to inpatient rehabilitation. Exam 2 months after presentation showed proximal left lower extremity strength of 4/5, distal left lower extremity strength of 2/5, with normal right lower extremity strength. Exam also showed hyperreflexia in bilateral lower extremities. Repeat MRI spine revealed a short segment of T2 hyperintensity involving T12-L1, mainly affecting the central gray matter with no enhancement. MRI brain and orbits was normal. Repeat MRI performed 1.5 months later showed decreased extent of signal abnormality limited to the anterior horns, greater on the left. Previously published cases with similar MR findings suggested an etiology for the patient's acute onset paralysis. Video recordings of the patient are available.
P-2 Seventy-three Year Old Man With Leg Weakness
S. Bhai, V. Ganesh, A. Amato, Carrollton, TX.
A 73-year-old man with chronic lymphocytic leukemia (CLL), IgM polyclonal paraproteinemia, and pulmonary sarcoidosis presented with ten years of progressive fatigue and lower extremity weakness, both worsened more quickly 6 months prior to presentation. He had difficulty with walking, climbing stairs, and standing from a seated position. He was noted to have hypercalcemia and despite correction of his calcium level, his weakness progressed. He had no sensory symptoms. He had no family history of neuromuscular disorders. He never smoked or used illicit drugs. He drank alcohol socially. Medications: aspirin, atenolol, amlodipine, irbesartan, tamsulosin, IVIG, and ibrutinib.
Exam: normal mental status, cranial nerves, sensory, and cerebellar testing. Motor exam: normal bulk and tone and no fasciculations. Strength exam showed (MRC grades, R/L): neck flexion/extension 5; shoulder abduction 5/5; elbow and wrist flexion and extension 5/5; superficial and deep finger flexors 5/5; finger extension 5/5; flexor pollicis longus 5/5; hip flexion 4/4, abduction 3−/3−, and extension 2/2; knee extension and flexion 5/5; ankle dorsiflexion 4+/5; and ankle plantarflexion 5/5. He had 1+ and symmetric reflexes at the triceps and biceps, 2+ and symmetric in the brachioradialis and knees, and absent in the ankles with downgoing toes. He had a slow stride with a narrow base.
Labs: CK 56 U/L, aldolase 8.9 U/L, SPEP—IgM polyclonal hypergammaglobulinemia without monoclonal gammopathy, serum free light chains—normal ratio, ESR 80 mm/hr, CRP 4 mg/L, ANA negative, 25-OH vitamin D 8 ng/mL, PTH 21 pg/mL, PTHrP negative, and VEGF 98.5 pg/mL (normal <96 pg/mL). Bone marrow flow cytometry showed CD5+ B cells (consistent with his known CLL). Cytometric analysis also showed clonal expansion of T-cell large granular lymphocytes. Fat pad biopsy was negative. Body PET/CT showed heterogenous signal uptake in the proximal muscles of all limbs. EMG showed muscle membrane irritability. Motor unit action potential morphology and recruitment were normal. Additional testing was performed.
P-3 A Rare Cause of Mononeuropathy Multiplex
T. Fullam, J. Jacobsohn, S. Chandrashekhar, C. Farmakidis, D. Jabari, O. Jawdat, M. Pasnoor, J. Statland, M. Dimachkie, Kansas City, KS.
Objective: Present a case of mononeuropathy multiplex (MNM) due to a rare entity.
Case Presentation: Fifty-eight-year-old male presented with a 4-month history of progressive, multifocal sensory disturbances in all extremities and acute onset right foot drop without systemic symptoms. Examination showed multifocal loss of pinprick sensation, distal weakness in the left upper extremity and right ankle dorsiflexion and plantarflexion weakness. Electrodiagnostic testing confirmed an asymmetric sensorimotor axonal polyneuropathy consistent with MNM. Neuroimaging of the brain and lumbar spine were unremarkable. Vasculitic, infectious, nutritional and immunologic laboratory studies were unrevealing to include negative myeloperoxidase (MPO) and serine protease 3 (PR3) antibody testing. Cerebrospinal fluid analysis was unremarkable. A fat pad biopsy was negative. Full body PET scan revealed hypermetabolic lesions in the left upper and lower lobes and a right lower lobe pleural based mass. Tissue biopsies were performed of the lung and right peroneus brevis muscle and sural nerve. Empiric treatment with corticosteroids and mycophenolate mofetil was discontinued within 1 month due to side effects and concerns related to the COVID-19 pandemic. Lung pathology results were ultimately diagnostic of lymphomatoid granulomatosis (LyG) with complementary findings of an inflammatory neuropathy with poorly formed, non-caseating granulomas on the sural nerve biopsy. Fite stain on the sural nerve biopsy was negative for Mycobacterium leprae.
Conclusions: LyG is an extremely rare angiodestructive lymphoproliferative disease. In patients with pulmonary lesions and multifocal sensorimotor symptoms, LyG should be suspected as a cause of granulomatous MNM.
P-4 A Case Presenting With Skin Changes and Weakness
M. Rahman, M. Pasnoor, C. Farmakidis, M. Dimachkie, O. Jawdat, D. Jabari, J. Statland, S. Chandrashekhar, Overland Park, KS.
A 76-year-old woman presented with subacute onset of pain, swelling, skin tightness, “bumpy rashes” on both legs. In September 2015, onset was marked by whole body muscle pain. She had skin changes initially diagnosed as actinic keratosis and had a chemical peel therapy, after which she noticed thickening of the skin. Around the same time, she had rash on the back after starting rosuvastatin, which resolved after switching to simvastatin. There was no rash on the face or other areas of the body. Within few months after onset of the rash, she developed weakness in proximal muscles in the arms and legs. Her initial examination revealed edema with induration of the skin and proximal weakness. Laboratory testing showed elevated absolute eosinophil count (1,022 cells/micro Liter), with normal creatine kinase, myositis antibody panel, and electrodiagnostic study. Skin biopsy revealed sclerosis with thickening and close packing of collagen bundles in the deep reticular dermis and subcutaneous septa. Muscle biopsy showed mild perifascicular atrophy and perivascular inflammation. She was initially started on prednisone and later methotrexate was added, however due to increased infections this was stopped and later started on mycophenolate which she did not tolerate. Her muscle weakness improved after institution of intravenous immunoglobulin. While myositis with perivascular inflammation and eosinophilic infiltration has been reported in Shulman syndrome, perifascicular atrophy is a rather unusual finding in the absence of other evidence of dermatomyositis.
Conclusions: This is a rare case of Shulman syndrome presenting as a dermatomyopathy with unusual finding of perifascicular atrophy on muscle biopsy.
P-5 Variable Presentation of a Rare Antibody Syndrome
P. Patel, A. Undavia, S. Jatwani, E. Gupta, Philadelphia, PA.
A 64-year-old female with diabetes, chronic respiratory failure and peripheral vascular disease presented with 1 year of progressive arm and leg weakness. She had a creatine phosphokinase (CPK) elevation of >3000. Magnetic resonance imaging (MRI) of the lower extremities revealed multicompartmental muscle atrophy and edema, consistent with chronic myopathy. There were no paresthesias, weight loss, or myalgias. She was temporarily treated with high-dose steroids to no avail. On examination there were no skin findings or evidence of mechanic's hands. There was limited shoulder range of motion with synovitis of the second/third metacarpophalangeal and proximal interphalangeal joints, wrists and knees. Strength was 3/5 proximally and 4/5 distally in the lower extremities and 4/5 proximally and 5/5 distally in the upper extremities with poor grip strength. Labs demonstrated elevated anti-nuclear antibody (ANA) titer and positive rheumatoid factor. Muscle biopsy showed markedly atrophic skeletal muscle with extensive endomysial adipose tissue and fibrosis. Chest imaging showed scattered ground glass opacities. Electromyography/nerve conduction studies showed evidence of an irritative myopathy with a proximal muscle predominance. There was also a superimposed, polyneuropathy. Myositis panel revealed positive melanoma-differentiation-associated protein-5 (MDA5), which was later negative and positive anti-threonyl-tRNA synthetase (anti-PL-7) antibodies. Her treatment plan involved oral steroids with a transition to Cellcept. We present an interesting case of an auto-immune condition with findings of interstitial lung disease, myositis, skin changes and arthritis. Anti-PL-7 is a rare antibody associated with this condition where antibodies are directed against aminoacyl-transfer-RNA synthetase. This is only the second reported case with concurrent anti-PL-7 and anti-MDA5 antibodies, although the significance of the latter is unclear and is to be re-tested. This case highlights the diverse presentation of this entity. Specific antibodies may be diagnostic and help direct treatment when biopsy and imaging findings are nonspecific.
P-6 Dysferlin Diagnostic Difficulties
J. Loeb, S. Khan, C. Cai, E. Golden, Dallas, TX.
A 28-year-old previously healthy female presented with 3 months of painless progressive weakness. She described trouble lifting her arms above her head, walking up stairs, and holding her head up. She denied shortness of breath, orthopnea, vision changes, trouble swallowing or sensory abnormalities. No preceding infections, though she did give birth to a healthy boy 3 months prior to symptom onset. Other than prenatal vitamins, she took no medications. She had no family history of similar issues. She did not drink, smoke or use illicit substances. On neurological exam, she had normal extraocular movements, no ptosis or pupillary abnormalities. Facial and tongue strength was normal. Motor exam showed mild bilateral scapular winging with neck flexion of 4-/5, and limbs with proximal more than distal symmetric weakness (4-/5 in deltoids and 3/5 in hip flexors). Knee flexion/extension and ankle dorsiflexion was 4/5. Plantar flexion was 5/5. Sensation and reflexes were intact. Creatine kinase (CK) was 13,750 U/L, aldolase was 224.3 U/L. A 6-week trial of prednisone 40 mg daily yielded small improvement in strength, and CK fell to 5112 U/L. A comprehensive genetic myopathy panel revealed a heterozygous variant of uncertain significant in the DYSF gene. Muscle biopsy of the right quadriceps showed attenuated dysferlin expression in most myofibers and was negative for expression of MHC class 1. Though ancillary data seemed to support Limb Girdle Muscular Dystrophy type 2B, a dysferlinopathy, clinical course and further data revealed a different diagnosis.
P-7 A Muscular Man With Thin Calves
S. Milani-Nejad, T. Mozaffar, Laguna Niguel, CA.
Objective: To illustrate a case of distal hereditary neuropathy associated with a rare gene mutation.
Background: Protein homeostasis is maintained by proper expression of chaperone and co-chaperone proteins. The heat shock proteins, along with their co-chaperone, the J-Domain proteins (JDP) are an important part of the cell's machinery for protein folding. DNAJB6 is a subclass of this family that has been described as a cause of autosomal dominant limb girdle muscular dystrophy. DNAJB2, another subclass has only recently been proposed as a rare causative agent for distal hereditary motor and sensorimotor neuropathies.
Case: A 44-year-old man presented with gradual onset of bilateral symmetric lower extremity weakness starting in 2004. He initially had trouble with standing up on his toes, followed by bilateral calf atrophy and walking difficulty. Further questioning revealed multiple sprained ankles in his early 20s. Exam was notable for distal symmetric lower extremity weakness, absent ankle reflexes, and mild decreased sensation to vibration at toes and ankles. Neurodiagnostic workup revealed axonal motor greater than sensory, length dependent polyneuropathy without demyelinating features. Given the long- standing history and gradual progression, we suspected an inherited neuropathy, likely of Charcot Marie Tooth (CMT) phenotype. However, CMT testing at the time was inconclusive. Repeat testing in 2018 through InVitae comprehensive neuropathies panel revealed one pathogenic variant (c.352+1G>A) and one likely pathogenic variant (c.230-2A>G) identified in DNAJB2, associated with autosomal recessive distal hereditary motor neuropathy: distal spinal muscular atrophy 5 and CMT type 2T.
Conclusions: DNAJB2 associated hereditary neuropathies have been described in only a few families. In particular the c.352+1G>A mutation has been described in thirteen families, while the c.230-2A>G has been classified as likely pathogenic by the ClinVar genetics in 3 cases. Taken together with our case, this is suggestive that DNAJB2 is a rare, but detectable cause of hereditary neuropathies.
P-8 An Infiltrative Neuropathy With a CMT Phenotype
J. Hidrogo, K. Pokala, Austin, TX.
We present a 44 year old man who presented to the emergency department due to worsening pain and bilateral lower extremity weakness progressively worsened over the previous 3 years. Initial symptoms include bilateral foot pain which slowly progressed to lower extremity weakness. For the past 1.5 years he has developed worsening dysphagia associated with vomiting in addition to severe constipation that ultimately has led to an unintentional weight loss of greater than 30 pounds. He described “curling” of his toes over the last year and more recently loss of strength in his hands in addition to nearly daily falls. He added to the history that his father had died of a similar constellation of symptoms in Mexico at age 46. Initial exam noted 2/5 distal weakness in the legs with and 3/5 weakness in the hands with 4/5 proximal weakness. He had obvious wasting of the intrinsic hand and foot muscles with high arched feet. Electrodiagnostic studies showed a severe mixed demyelinating-axonal, length dependent peripheral neuropathy that was manifested by predominantly demyelinating greater than axonal changes in the sensory nerves with predominantly axonal greater than demyelinating changes in the motor nerves with neurogenic changes seen in nearly every muscle on Needle EMG without myopathic changes or myotonic discharges. Genetics ultimately revealed the patient's diagnosis, which was later confirmed with ancillary testing. This is an interesting phenotypic presentation of an infiltrative familial polyneuropathy whose clinical picture and examination inclusive of EDX presenting as a possible Charcot Marie Tooth hereditary neuropathy versus a Chronic Inflammatory Demyelinating Polyneuropathy.
P-9 Interesting Case of Progressive Neuropathy
C. Barbour, T. Pike-Lee, Jackson, MS.
Background: POEMS syndrome is characterized as a paraneoplastic syndrome due underlying plasma cell dyscrasia. Major criteria include polyradiculoneuropathy, clonal plasma cell disorder, elevated vascular endothelial growth factor, sclerotic bone lesions and presence of Castleman Disease. Although bone lesions are a defining feature of this syndrome, we present an interesting POEMs case without evidence of sclerotic bone lesions on radiographic assessment.
Case Presentation: Thirty-six-year old female with a 10 month history of paresthesias which progressed to bilateral foot drop and gait instability requiring the use of a walker. She was initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and treated with intravenous immunoglobulin and prednisone for several months without improvement. Electromyography showed evidence of severe generalized sensorimotor polyneuropathy with mixed demyelinating and axonal features. Hereditary transthyretin amyloidosis testing revealed a heterozygous mutation for Val142Ile which is exclusively associated with cardiomyopathy. Further testing revealed an IgA lambda monoclonal gammopathy, significantly elevated vascular endothelial growth factor, and thrombocytosis with platelet count of 550 TH/cmm. Clinically she was noted to have areas of hypopigmentation on her back and face. CT chest/abdomen/pelvis revealed wedge-shaped hypodensities in the spleen, liver, and kidney. Interestingly there was no evidence of sclerotic bone lesions on CT or osseous survey. PET full body scans did not reveal any FDG-avid disease. Bone marrow biopsy revealed 5%–10% plasma cells. FISH positive for gain in 1q21 and 1p with normal cytogenetics. She was started on treatment with Lenalidomide and dexamethasone.
Conclusions: POEMS syndrome is rare diagnosis that is often delayed due to misdiagnosis of other neuromuscular disorders such as CIDP. It is important to consider this diagnosis in patients not responding to typical treatments for CIDP. While sclerotic bone lesions are a defining feature of POEMS syndrome in up to 97% of cases, this diagnosis should not be excluded if there is a lack of radiographic evidence of such lesions.
P-10 Misdiagnosis of CIDP: Misleading Conduction Block
A. Smith, T. Nguyen, Houston, TX.
Our patient is a 46 year old Indian male with recent diagnosis of CIDP presenting with bilateral numbness in the hands and feet with progressive gait imbalance and distal greater than proximal weakness. His symptoms began approximately 2 years prior to presentation and have progressed over that time period. He began with numbness in the hands which progressed to weakness with decreased grip strength and difficulty with fine motor tasks. Over 6 months, he developed tingling and numbness in the bilateral feet to the knees followed by increased difficulty with walking and imbalance. One month prior to presentation, he began having intermittent double vision and intermittent facial twitching. He describes electric pain over the extremities as well as the face. Physical examination shows distal greater than proximal weakness, stocking-glove sensory loss and flaccid areflexia. A high steppage gait was seen bilaterally. He was noted to have high arches with hammer toes. Fasciculations were seen in the bilateral masseters, biceps and gastrocnemius. Recent EMG/NCS showed absent sensory responses with prolonged latencies, low CMAP amplitudes, conduction block at noncompressible sites and dispersed potentials consistent with a severe sensorimotor demyelinating acquired polyneuropathy such as CIDP. He was scheduled for 2 g/kg of IVIG divided over 5 days, however the infusions were halted after 2 doses due to side effects. The patient had only minimal subjective improvement after his treatment. With concern for lack of improvement as well as anatomical changes in the feet, genetic testing was sent. Testing returned positive for a homozygous pathogenic variant in SH3TC2, which is associated with autosomal recessive CMT 4C. This case highlights that conduction block should not preclude genetic testing for neuropathies.
P-11 An Unusual Case of Multiple Cranial Neuropathies
Y. Liao, R. Zaza, S. Austin, Austin, TX.
A diabetic cranial neuropathy is one of many neurological complications related to diabetes. To have multiple cranial nerves involved is unusual. According to one study, multiple cranial neuropathies due to diabetes accounts for 2% of all cases. The cranial nerves that are typically affected are III, IV, and VI which leads to ophthalmoplegia. Another neurological complication of diabetes is diabetic amyotrophy. Classically, this consists of subacute unilateral or bilateral but asymmetric lower extremity pain, weakness, and muscle atrophy. Our case illustrates a complicated clinical presentation that is reminiscent of the expected course of diabetic amyotrophy, but involves multiple lower cranial nerves. There are several features that set our patient apart from the usual course of diabetes-related cranial neuropathy. (1) She did not have subjective or objective evidence of ophthalmoplegia. (2) Her symptoms started with severe unilateral facial pain that resolved followed by weakness. (3) Later her symptoms of pain and weakness spread to the contralateral side. (4) She had significant atrophy of her tongue. (5) Her recovery has been longer than expected for a typical diabetes-related cranial neuropathy. Other than the location, these features are more commonly seen with diabetic amyotrophy. Diabetic amyotrophy can involve the thoracic and cervical regions as well, but during our literature search there were no similar cases published with cranial nerve involvement. This is a unique case that may suggest a similar pathophysiology underlying both diabetic amyotrophy and diabetic cranial neuropathies.
P-12 Forty-Nine Year Old Woman With Leg Weakness
S. Bhai, S. Khan, Carrollton, TX.
A 49-year-old woman with a history of seizures, C4-6 ACDF, and DVT/PE was admitted with intractable nausea and vomiting. Her CK at that time was 984 that returned to normal prior to discharge. Her symptoms resolved and one month after discharge, she noticed trouble walking. She was having falls due to weakness. She began using a combination of a walker and wheelchair. She developed dysphagia for which she needed a feeding tube. She presented to multiple hospitals without an etiology of her symptoms. Work-up included: ANA, ANCA, ENA panel, dsDNA, HIV, HBV, AChR antibody, MuSK, aldolase, CSF WBC 0 and protein 74, and CSF Lyme, WNV, VDRL, all of which were normal. CK fluctuated from normal to <1000 U/L. MRI C-spine showed paraspinous muscle edema with mild degenerative changes and previous ACDF. MRI T/L-spine showed multilevel degenerative changes. MRI thighs did not show muscle edema. She was on pravastatin that was stopped. Other medications included pantoprazole, cyclobenzaprine, zonisamide, carbamazepine, apixaban, lamotrigine, and pregabalin. She has no family history of neuromuscular disorders. EMG was performed and showed an irritative myopathy and sensorimotor axonal neuropathy. She had a muscle biopsy that reported mild chronic endomysial inflammation with MHC1 upregulation. There was additional note of rare ragged red fibers, myofibrillar abnormalities, lipid storage with cytoplasmic vacuolation, esterase-positive angulated myofibers, and few basophilic myofibers with internal nuclei positive for alkaline phosphatase. Electron microscopy was not done. She was treated without IVIG and prednisone without improvement. She then presented to UT Southwestern for further evaluation. Exam: normal mental status and cranial nerves. Motor: hip flexion 2/5 bilaterally, otherwise 5/5 elsewhere. Reflexes: 1+ and symmetric throughout, except 0 at the knee bilaterally. She was able to stand and take a few steps before needing to rest. Diagnostic tests were ordered and she was started on treatment.
P-13 Value of Diaphragm EMG and Phrenic NCS
D. Shah, S. Loeb, R. Abhyankar, S. Khan, S. Vernino, Dallas, TX.
Objective: To identify whether diaphragm electromyography and phrenic nerve conduction studies alter diagnosis and/or management of patients with suspected diaphragm paresis and to characterize the symptoms, diagnostic workup, and management of patients with suspected diaphragm paresis.
Introduction: Diaphragm dysfunction can occur due to a wide variety of conditions involving the central and peripheral nervous systems. Bilateral diaphragm paresis typically presents with dyspnea and immediate orthopnea in the supine position. In contrast, patients with unilateral diaphragm paresis are typically asymptomatic at rest with mild orthopnea and dyspnea on exertion. While pulmonary function tests and sniff fluoroscopy can help identify paresis, these tests do not identify etiology. Diaphragm electromyography (EMG) and phrenic nerve conduction studies (NCS) are specialized tests used for peripheral nervous system lesion localization. However, the potential benefits of these tests must be weighed against the risk of complications such as pneumothorax and bleeding as well as patient discomfort. While these specialized tests have theoretical diagnostic benefit in suspected diaphragm paresis, there is scant evidence to suggest that they guide diagnostic and therapeutic decision making.
Methods: We conducted an IRB approved retrospective chart review study utilizing our electronic medical records database of patients who had a diaphragm electromyography and phrenic nerve conduction study performed in the Neuromuscular clinic at UT Southwestern Medical Center, Dallas, from 2015 to current time. Data from 54 patients was obtained. Patient demographics such as sex, age, symptoms, radiological and laboratory studies prior to EMG/NCS were collected, as well as the diagnosis and management prior to diaphragm EMG and phrenic NCS, EMG and NCS values, and post-procedure changes in diagnosis and management, if any. The data collected will be analyzed by simple statistical methods.
Discussion: Results are pending review and analysis of data and will be presented at time of the conference.
P-14 Neuromuscular Therapy for Carriers Too?
A. Witt, S. Shukla, T. Pike-Lee, Jackson, MS.
Our clinic has followed a symptomatic female carrier patient, now 32, since she was diagnosed at the age of 18 months. Muscle biopsy, karyotyping, and studies for lyonization were all done at the time to confirm her diagnosis. We repeated genetic studies in adulthood and confirmed a dystrophin deletion mutation of exons 49 and 50. Her clinical course progressed from mild toe walking and falls in her teen years to significant toe walking, poor balance, frequent falls, and weakness with sit to stand transfers in her twenties. She has a masters degree in education but struggled to find an employer willing to engage her with her disability. She has now had 11 months of Exondys therapy weekly with noted improvement in gait quality, fewer to no falls, and enough proximal strength improvement that she can now climb stairs and keep up with the physical demands of her new job. We have now had to request an exception for her ongoing treatment since she is a female carrier and there is research in this clinical group. With the new influx of neuromusclar medications, treatment of a symptomatic carrier state will become more of an issue and would benefit from discussion and possible collaboration between specialists.
P-15 Rare Cause of Muscular Dystrophy in Adults
V. Vedanarayanan, V. Sreenivasan, Austin, TX.
Objective: Present clinical features of 2 adults limb-girdle muscular dystrophy from laminin alpha-2 (LAMA2) gene mutations.
Background: LAMA2 gene associated muscular dystrophy is an autosomal recessive disorder, presenting in babies with hypotonia, progressive weakness, joint contractures and periventricular white matter hypomyelination.
Clinical Data: We present 2 adults with progressive muscular dystrophy. They were normal birth and their motor milestones were normal. Progressive lower extremity weakness started in teens followed several years later with mild upper extremity weakness. Scapular winging was present in one patient. Contractures of the hips were noted in one patient and he became wheelchair dependent by the age of 41 years. The other patient is ambulant at 40 years with a modified gait at. Both had absent tendon reflexes. Serum CK was elevated 2–3 times the upper limits of normal. Nerve conduction studies in one showed a mild, sensorimotor demyelinating neuropathy and EMG a non-irritable myopathy. MRI of the brain of both patients demonstrated extensive T2 signal hyperintensity in the periventricular white matter. They had no cognitive issues or evidence of corticospinal dysfunction. Genetic testing in one patient demonstrated a previously described pathogenic mutation, c.7658del, and a previously described variant of uncertain significance, c.1670A>C, in the LAMA2 gene. The second patient had a pathogenic mutation c.8553_8557del, and a variant of uncertain significance, c.2176T>C. These are novel mutations presenting with later onset and slow progression.
Conclusions: This clinical report further expands the spectrum of myopathies occurring with mutations in LAMA 2 gene.
P-16 Muscle Mysteries of Mississippi
M. Zulfiqar, S. Shukla, P. Natteru, Jackson, MS.
Objective: Early diagnosis of lipid storage myopathy.
Case 1: Seventy-year-old man presented with 1 year of difficulty walking with no associated radicular back pain or any limb paresthesias. On exam, he had weakness only in in hip flexors (MRC 3/5) and hip abductors (MRC 2/5). Aldolase and creatine kinase were elevated to 10.9 and 809 u/L respectively. Magnetic resonance imaging of brain & entire spine was unremarkable. Electromyography (EMG) and nerve conduction studies (NCS) showed evidence of bilateral lower limbs proximal irritative myopathy but no large fiber polyneuropathy or motor neuronopathy. Muscle biopsy of vastus lateralis was suggestive of lipid storage myopathy. Several acylcarnitine species were elevated on the serum acylcarnitine panel with heterozygous ETFDH mutation on genetic testing. This was felt to be a late onset form of multiple acyl-CoA dehydrogenase deficiency, which is crucial to recognize early given good responsiveness to riboflavin.
Case 2: Thirty-seven-year-old woman presented with 6 years of progressive generalized myalgias and episodic flares of proximal muscle weakness with myoglobinuria mostly precipitated with sustained exertion. Creatinine Kinase was elevated in the range of 500–40000 U/L. On exam, she had mild neck flexion (MRC 4/5), shoulder abduction (MRC 4/5) and hip flexion weakness (MRC 4/5). EMG & NCS suggested myopathy. A muscle biopsy pursued around time of rhabdomyolysis episode was reported as necrotizing myopathy. This prompted evaluation for exploring malignancy and testing anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG Co-A) antibodies; all of which was unremarkable. Limb-girdle muscular dystrophy panel and a screening metabolic myopathy panel (30 genes) was unremarkable. A repeat muscle biopsy was pursued (outside of flare episode) as the clinical presentation did not fit necrotizing myopathy. This confirmed a metabolic lipid storage myopathy pending genetic testing results for rare forms of lipid storage myopathy (ACADS, AMPD1, PNPLA2, PTRF, and ABHD5).
P-17 Patient Burden of Generalized Myasthenia Gravis
S. Muley, D. Gelinas, J. Mohd Sani, K. Ruzhansky, Phoenix, AZ.
Purpose: As it is well-established that patients with generalized myasthenia gravis (gMG) have substantial physical impairment, the objective of this study was to explore the lesser known mental, emotional, and quality of life impacts of gMG.
Methods: A cross-sectional study was conducted in June 2020 among U.S. adults with a self-reported diagnosis of gMG. Respondents were recruited from online panels and completed an online survey assessing the gMG diagnosis process, burden of disease, and burden of treatment. The study received IRB exemption.
Results: Of the 150 patients with gMG surveyed, most were female (89%), mean age of 49.4, and diagnosed with gMG ten years earlier. Despite taking an average of 2.3 treatments for gMG, patients reported continued physical symptoms: fatigue (83%), limb weakness (76%), brain fog (74%), difficulty sleeping (69%), double/blurred vision (63%), drooping eyelids (61%), and difficulty walking/standing (58%) which further impacted QOL. Approximately half experienced depression (51%) and anxiety (48%) and 35% underwent psychological counseling due to gMG. Patients exhibited poor well-being according to the WHO-5 Well-Being Index (mean score 45.6) and poor quality of life per the MG-QOLr. The personal lives of patients were negatively affected with most (87%) giving up hobbies because of their gMG and worrying that limitations from gMG hurt their relationships (68%). Professional lives of patients were also affected with half of patients having to stop working entirely due to gMG. Many patients (64%) worry about their lifespan and almost 7 in 10 patients report COVID-19 at least somewhat impacting the management of their gMG. Almost all (92%) agreed there is a significant need for new gMG treatments and are hopeful for ones with fewer side effects (96%).
Conclusions: Despite availability of treatments to control symptoms, patients with gMG experience substantial negative physical, mental, social, and emotional impacts; isolation due to COVID-19 may further exacerbate these issues.
P-18 A Patient Presenting With Distal Weakness
N. McGraw, R. Barohn, S. Chandrashekhar, M. Dimachkie, D. Jabari, O. Jawdat, M. Pasnoor, J. Statland, C. Farmakidis, Kansas City, KS.
Objective: To describe a case of rare cause of distal weakness.
Case Presentation: An 18-year-old male initially presented with lifelong progressive and fixed bilateral arm and hand weakness. There was associated intermittent double vision on distant objects and dyspnea with moderate exertion. Examination revealed mild oculobulbar and neck flexion weakness, moderate to severe weakness in the distal upper extremities, and mild weakness in the proximal arms The family history was notable for a similar pattern of distal weakness in the father and paternal uncle who also had hemidiaphragm weakness. The creatinine kinase was normal and acetylcholine receptor antibody serology was negative. A muscle biopsy in the patient's father was inconclusive. Needle electromyography showed mixed myopathic and neuropathic units in the distal upper extremity muscles without fibrillations. Slow repetitive nerve stimulation at the ulnar nerve showed no decrement. Genetic testing for facioscapulohumeral muscular dystrophy type 1, myotonic dystrophies and limb-girdle muscular dystrophies was negative or non-diagnostic. On follow up at age 32 the patient reported his 2-year-old son had proximal weakness and used a modified Gower's maneuver to stand. New genetic testing using a neuromuscular disorder next generation sequencing showed a pathogenic mutation in CHRNA1 (c517G>A, pGly173Ser) previously shown to cause autosomal dominant slow channel congenital myasthenic syndrome. He was offered a trial of fluoxetine and beta-blockers, however he declined treatment at that time. Genetic testing on his son revealed the same mutation.
Literature: Similar mutations in CHRNA1 have been described (457G>A, G153S; 592G>A, Gly198Ser). These have been associated with autosomal dominant slow-channel congenital myasthenic syndrome (SCCMS), and there have been few cases of SCCMS presenting with distal weakness.
Conclusions: SCCMS have been described as presenting with a limb-girdle pattern of weakness and can present with a distal myopathy pattern of weakness.
P-19 From Wooden Wheelchairs to Heartbreak
J. Mullen, T. Mozaffar, N. Goyal, Irvine, CA.
Background: Myofibrillar myopathy can be caused by a number of different gene mutations, including mutations in the LDB3 gene, (formerly ZASP), a protein important in skeletal and cardiac muscle.
Objectives: To describe a case and review the literature of a rare inherited myopathy.
Methods: Case report.
Results: A 77 year-old man with progressive muscle weakness since his 50's, more recently requiring a power wheelchair for mobility, first presented to our neuromuscular center in 2012 for evaluation of myopathy. Neuromuscular examination was remarkable for proximal and distal limb weakness, most significantly affecting wrist extensors and ankle dorsiflexors, with hyporeflexia and preserved facial/bulbar strength. His evaluation included creatine kinase level of 259 IU/L and electromyography showed an irritable myopathy. Muscular dystrophy genetic testing panel (2015 Emory) was negative. His family history was significant for similar weakness and age of onset (in 50's) affecting his paternal great grandfather (used a wooden wheelchair), grandmother, father, and younger brother. The affected brother had a muscle biopsy which showed rimmed vacuoles, endomysial inflammation, and congophilic deposits. Another brother has had no muscle weakness but a severe cardiomyopathy requiring a pacemaker. Due to evolution of genetic panels, repeat genetic testing was performed (2019 Perkin Elmer) which showed a pathogenic missense mutation in LDB3 c.439G>A (p.Ala147Thr), associated with autosomal dominant myofibrillar myopathy type 4.
Conclusions: Mutations in the LDB3 gene are known to present with 4 phenotypes including distal myopathy, left ventricular noncompaction, and dilated or hypertrophic cardiomyopathy. Here we present a single affected family with different phenotypes, including one family member with isolated cardiomyopathy without muscle weakness. This illustrates the importance of identifying and testing family members who may be at risk despite varied presentations.
P-20 Myasthenia Gravis Amidst COVID-19
P. Guntipalli, R. Pakala, S. Gara, D. Hathaway III, V. Vemireddy, Irving, TX.
Purpose: The aim is to review immunological triggers as well as beneficial treatment regimens and their considerations in managing Myasthenia Gravis patients with varying severity of COVID-19.
Methods: A systematic review was performed on 63 articles through an extensive search of PubMed, Science Direct, Google scholar, JAMA, and Scopus databases from the onset of COVID-19 to date using keywords, “COVID-19,” “Myasthenia Gravis,” “Neuromuscular disease,” “Immunosuppressants,” and “Immunomodulators.” We excluded other neuromuscular disorders and included 18 articles of COVID-19 patients with Myasthenia Gravis. No exclusions were made for age, sex, or geographical regions.
Results: During this COVID-19 pandemic, we need to be watchful for neuromuscular complications that may be directly or indirectly related to coronavirus infection. Coronavirus, through molecular mimicry, forms autoantibodies against the neuromuscular junction that might trigger immune-mediated disorders such as Myasthenia Gravis (MG). MG patients on immunosuppressive or immunomodulatory therapy are predisposed to COVID-19, manifesting severe complications. Steroids have varied effects on COVID-19 patients depending on their stage of infection, not effective in earlier infection but beneficial in ARDS by inhibiting chemokine production. IL-6 is an inflammatory marker found in COVID-19 and MG patients, which can be associated with a higher mortality rate. Experimental therapies for COVID-19, such as combined use of azithromycin and hydroxychloroquine, may trigger a myasthenic exacerbation or crisis. Hydroxychloroquine is known to result in potential neuromuscular side effects. Diaphragm hemiparesis was possibly induced secondary to the myasthenic crisis in the setting of a viral illness and azithromycin's recent use.
Conclusions: Routine treatment for MG should be tailored depending on the COVID-19 severity. Steroids and immunomodulators should be used with caution in MG patients. However, limited data exist on how COVID-19 affects people with Myasthenia Gravis.
P-21 Upper Extremity Weakness, Head Drop, and a Rash
A. Collins, S. Biliciler, Houston, TX.
Idiopathic inflammatory myopathies are an immune-mediated syndrome that are increasingly being found to be associated with other systemic autoimmune diseases. A growing number of these myositis specific antibodies (MSA) and myositis associated antibodies (MAA), and their clinical importance, are being discovered. Among these is the anti-PM-SCL IgG antibody which has been associated with an inflammatory myopathy syndrome presenting with brachio-cervical involvement, often overlapping with scleroderma in 43%–87% of cases. We present here a brief case series of 2 patients both found to have elevated titers of anti-PM-SCL IgG antibodies and a clinical syndrome of inflammatory myopathy. Case one involves a 52 year old man who presented with gastrointestinal symptoms and interstitial lung disease, later developing profound proximal arm weakness and a prominent rash. Pm-Scl Ab levels were found to be greater than 200, Scl-70 was also elevated. Creatine Kinase (CK) levels were 430. Improvement was seen on cellcept, prednisone. Case 2 involves a 71 year old woman presenting with significant upper extremity weakness progressing later to head drop, scapular winging, mechanic's hands and elevated CK of 1,134. A myositis panel noted only positive for PM-Scl antibodies. Muscle biopsy showed inflammatory changes. Both cases were treated with immunomodulatory therapies. We then discuss the relevant clinical, electrodiagnostic, and pathological findings, the proposed pathophysiologic basis of anti-PM-SCL associated antibodies, and the commonly associated immune-mediated diseases seen with this disorder.
P-22 A Mysterious Case of Myalgias
J. Wu, T. Nguyen, Houston, TX.
Patient is a 39-year-old male with no significant medical history, who presented for evaluation of 4–5 weeks of progressive, worsening, aching and pain of his proximal muscles in bilateral extremities. Symptom onset was preceded by a flu-like illness about 1–2 weeks prior. He described soreness in his upper extremities particularly, when lifting heavy objects. He denied fatigable weakness and symptoms often improved throughout the day. Neurologic exam showed full strength in all muscle groups bilaterally and intact sensation. Reflexes were 2+ throughout and gait was normal. Laboratory investigations were remarkable for elevated inflammatory markers with C-reactive protein 99 and ESR 30. Myositis antibody panel and muscle enzymes, including CK and aldolase, were unremarkable. Electrodiagnostic studies revealed abnormal spontaneous activity with normal motor units on needle electromyography, though findings were limited to bilateral biceps muscles. This was supportive of irritable myopathy. Sensory and motor conduction studies were normal. Muscle biopsy showed some fibers that contained vacuoles with eosinophilic material, but no findings suggestive of an inflammatory myopathy. Further investigation for possible parasitic etiology revealed stool sample positive for Giardia antigen and Giardia lamblia cysts. Patient was treated with tinidazole and oral steroids, with significant improvement in symptoms. Although patient did not have evidence of myopathy on muscle biopsy or abnormal motor units on needle EMG, there was evidence of significant irritability. We believe the findings are due to a para-infectious process.
P-23 Late Diagnosis of a Dystrophinopathy
Y. Karasozen, S. Biliciler, T. NguyenHouston, TX.
We present the case of a 36 year old man who was referred to neuromuscular clinic due to persistently elevated creatinine kinase (CK) levels. He is of Indian descent and born from a consanguineous marriage of first cousins. He was delayed in reaching motor developmental milestones. He had severe exercise intolerance and myalgias throughout his life. He was diagnosed with dilated cardiomyopathy when he was 29 and has chronic heart failure with ejection fraction of 30%–35%. In the past year he was hospitalized twice due to concern for rhabdomyolysis in the setting of febrile illnesses with CK levels up to 5000s. After discharge hyperCKemia persisted in 1000–2000s range, leading to his referral. On our examination he was found to have normal mental status and cranial nerve function, symmetric 4 to 4+/5 weakness of his bilateral deltoid, biceps, hip flexors, and tibialis anterior muscles, normal sensation to all modalities, normal reflexes, waddling gait, and pseudohypertrophy of his calves. EMG showed short motor unit action potentials in all tested muscles. A hereditary muscle disease was suspected and neuromuscular genetic panel was sent, which found a hemizygous, in-frame deletion of exons 3–4 of dystrophin (DMD) gene. Large deletions in the proximal (N-terminus) hotspot (exons 2–20) in DMD can have significant phenotypic variation and could cause both Becker (BMD) or Duchenne Muscular Dystrophy (DMD). Deletion of exons 3–4 causes BMD; deletion of exons 5-7 causes DMD, whereas deletion of exons 3–7 is found commonly in both DMD and BMD. The presentation of our case is consistent with BMD. This was also confirmed with dystrophin immunohistochemistry staining of left vastus medialis biopsy that showed normal staining of C-terminal, robust staining of mid-rod, and very weak to absent staining of N-terminal. Our case demonstrates an uncommon, late diagnosis and the intriguing genotype-phenotype relationship of dystrophinopathies.
P-24 A 45 Year Old Man With Balance Difficulties
S. Bradshaw, A. Lin, S. Bhai, Dallas, TX.
A 45-year-old man with untreated HIV/AIDS and history of disseminated histoplasmosis who presented with 3 months of gait disturbance impairing his ability to walk and climb stairs. He had tingling below his knees to his feet bilaterally. He had lost nearly 40 pounds over the previous 2 months and had chronic diarrhea. He denied limb weakness, myalgias, dysphagia, dysarthria, ptosis, diplopia, or rash. He was not on any medications. He denied tobacco, illicit drug use, and alcohol. He had no family history of neuromuscular disease. Exam: His cranial nerves were intact. He had decreased bulk, but normal tone and no fasciculations. His strength was (Medical Research Council grade) 5/5 in the bilateral upper and lower extremities. Sensation was intact to pinprick throughout with vibration appreciated for 6 seconds at the great toe bilaterally. There was no spinal level to pinprick. Romberg was positive. Reflexes were 2+ throughout with downgoing toes. Cerebellar function revealed normal finger-to-nose testing, but mild dysmetria with heel-to-shin testing. His gait was wide-based. Laboratory values were remarkable for a CD4 count of less than 10 cells/mcL with an HIV viral load of 91,800 copies/mL. Outside of HIV, his infectious work-up was negative, including syphilis (serum and CSF), Hepatitis B and C, fungal infections (urine, serum, and CSF, including histoplasmosis), T-spot, and CSF viral infections (HSV, VZV, CMV, WNV, HTLV). Lumbar puncture revealed 2 nucleated cells with protein 29 mg/dL glucose 53 mg/dL oligoclonal bands and elevated CSF IgG synthesis rate. CSF was flow and cytology were negative for malignancy. Additional labs included HgbA1c 5.4, Vitamin B12 538 pg/mL, Vitamin E 6.3 mg/L, copper 72 μg/dL (normal), ceruloplasmin 14 mg/dL (normal 17–54 mg/dL), zinc 36 μg/dL (normal 60–120 μg/dL), SPEP with a polyclonal gammopathy, elevated kappa (179 mg/L) and lambda (159 mg/L) free chains with a normal ratio, UPEP normal, ESR 55, rheumatologic panel (ANA, Smith, SSA, SSB, RF, ANCA) negative, paraneoplastic panel negative. Further studies were performed, and he was started on a regimen for his HIV along with prophylactic antimicrobials.
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