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Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder resulting from loss of dystrophin. In addition to its role in muscle, isoforms of dystrophin are expressed in different cell types of the brain, and DMD has been linked to language delays, behavioral abnormalities and learning disabilities. Objective: To determine whether disruption of specific DMD isoforms, age, corticosteroid use, ambulation status, or country are associated with behavioral and/or learning concerns in DMD. Methods: De-identified data were collected from the Duchenne Registry from 2007–2019. Females, patients with BMD, and those without genetic testing reports were excluded from the cohort. For the genetic analysis, patients were divided into four subgroups based on the location of their mutation and the predicted isoforms affected. Bivariate analysis was conducted using chi-square for categorical variables. Two multivariate logistic regressions were used to assess independent associations with behavioral and learning concerns, respectively, and to estimate the effect size of each variable. Results: DMD mutations disrupting expression of Dp140 and Dp71 were associated with a higher likelihood of reported behavioral and learning concerns. Corticosteroid use, categorical age, and country were other factors associated with behavior and learning concerns. Conclusion: This data adds to our current understanding of DMD isoforms, their mutational consequence and impact on behavior and learning.

Background and PurposeSkeletal muscle symptoms and elevated creatine kinase (CK) levels have been consistently reported as part of the COVID-19 disease process. Previous studies have yet to show a consistent relationship between CK levels and skeletal muscle symptoms, disease severity, and death from COVID-19. The purpose of this study is to determine whether elevated CK is associated with a COVID-19 course requiring intubation, intensive care, and/or causing death. Secondary objectives: To determine if there is a relationship between elevated CK and (1) skeletal muscle symptoms/signs (2) complications of COVID-19 and (3) other diagnostic laboratory values.MethodsThis is a retrospective, single center cohort study. Data were collected from March 13, 2020, to May 13, 2020. This study included 289 hospitalized patients with laboratory-confirmed SARS-CoV-2 and measured CK levels during admission.ResultsOf 289 patients (mean age 68.5 [SD 13.8] years, 145 [50.2%] were men, 262 [90.7%] were African American) with COVID-19, 52 (18.0%) reported myalgia, 92 (31.8%) reported subjective weakness, and 132 (45.7%) had elevated CK levels (defined as greater than 220 U/L). Elevated CK was found to be associated with severity of disease, even when adjusting for inflammatory marker C-reactive protein (initial CK: OR 1.006 [95% CI: 1.002-1.011]; peak CK: OR 1.006 [95% CI: 1.002-1.01]; last CK: 1.009 [95% CI: 1.002-1.016]; q = .04). Creatine kinase was not found to be associated with skeletal muscle symptoms/signs or with other laboratory markers.ConclusionsCreatine kinase is of possible clinical significance and may be used as an additional data point in predicting the trajectory of the COVID-19 disease process.

Background and ObjectivesSpinal muscular atrophy (SMA) was added to the Recommended Uniform Screening Panel in July 2018 largely on the basis of the availability and efficacy of newly approved disease-modifying therapies. New York State (NYS) started universal newborn screening for SMA in October 2018. The authors report the findings from the first 3 years of screening.MethodsStatewide neonatal screening was conducted using DNA extracted from dried blood spots using a real-time quantitative PCR assay. Retrospective follow-up data were collected from 9 referral centers across the state on 34 infants.ResultsIn the first 3 years since statewide implementation, nearly 650,000 infants have been screened for SMA. Thirty-four babies screened positive and were referred to a neuromuscular specialty care center. The incidence remains lower than previously predicted. The majority (94%), including all infants with 2–3 copies of survival motor neuron (SMN) 2, have received treatment. Among treated infants, the overwhelming majority (94%; 30/32) have received gene replacement. All infants in this cohort with 3 copies of SMN2 are clinically asymptomatic posttreatment based on early clinical follow-up data. Infants with 2 copies of SMN2 are more variable in their outcomes. Electrodiagnostic outcomes data obtained from a subgroup of patients (n = 11) demonstrated either improvement or no change in compound muscle action potential (CMAP) amplitude at last clinical follow-up compared with pretreatment baseline. Most infants were treated before 6 weeks of age (median = 34.5 days of life; range 11–180 days). Delays and barriers to treatment identified by treating clinicians followed 2 broad themes: medical and nonmedical. Medical delays most commonly reported were the presence of AAV9 antibodies and elevated troponin I levels. Nonmedical barriers included delays in obtaining insurance and insurance policies regarding specific treatment modalities.DiscussionThe findings from the NYS cohort of newborn screen-identified infants are consistent with other reports of improved outcomes from early diagnosis and treatment. Additional biomarkers of motor neuron health including EMG can potentially be helpful in detecting preclinical decline.

The coexistence of Neuromyelitis Optica spectrum disorder (NMOSD) with other autoimmune diseases (AD-NMOSD) presents worse clinical outcomes and healthcare costs than NMOSD alone (NMOSD-only). NMOSD and other autoimmune diseases also have a higher prevalence and morbidity in Black. We aim to compare clinical features and treatment responses in NMOSD patients with and without overlapping autoimmunity in a predominantly Black cohort. We further identify predictors associated with each clinical subtype.AD-NMOSD (n = 14) and NMOSD-only (n = 27) patients were identified retrospectively. Demographic, clinical, laboratory, imaging, and response to treatment data were examined.Our cohort was predominately Black (82.9%). The prevalence of grouped-comorbidities, history of infections, sensory symptoms, Expanded Disability Status Scale (EDSS) before treatment, double-stranded DNA, antinuclear, ribonucleoprotein, and antiphospholipid antibodies, spinal-cord edema, white matter occipital lesions, and the levels of C-reactive protein, urine protein/creatinine, white blood cell count in cerebrospinal fluid (CSF), were higher in AD-NMOSD patients (p 0.05 and/or Cramer's V 30, Cohen's d 50), whereas the age of males, visual symptoms, serum albumin, platelet count, and optic nerve enhancement were lower. EDSS after treatment improved in both groups being more evident in NMOSD-only patients (p = 0.003, SE = 0.58 vs p = 0.075, SE = 0.51). Other variables had a close to moderate SE, and others did not differ between NMOSD subtypes. A higher frequency of grouped-comorbidities, lower serum albumin, and platelet count were independently associated with a higher risk for AD-NMOSD.Some clinical features between AD-NMOSD and NMOSD-only patients were similar, while others differed. Comorbidities, serum albumin, and platelet count may be independent predictors of AD-NMOSD.

Pain is a under-recognized association of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. Of 147 patients with these autoantibodies, pain was experienced by 17 of 33 (52%) with CASPR2- versus 20 of 108 (19%) with LGI1 antibodies (p = 0.0005), and identified as neuropathic in 89% versus 58% of these, respectively. Typically, in both cohorts, normal nerve conduction studies and reduced intraepidermal nerve fiber densities were observed in the sampled patient subsets. In LGI1 antibody patients, pain responded to immunotherapy (p = 0.008), often rapidly, with greater residual patient-rated impairment observed in CASPR2 antibody patients (p = 0.019). Serum CASPR2 antibodies, but not LGI1 antibodies, bound in vitro to unmyelinated human sensory neurons and rodent dorsal root ganglia, suggesting pathophysiological differences that may underlie our clinical observations. ANN NEUROL 2021;90:683-690.

Objective We evaluated pain in leucine-rich glioma inactivated1(LGI1) and contactin-associated protein2(CASPR2)-antibody positive(Ab+) patients, to evaluate clinical associations and pathophysiology of treatable pain syndromes. Methods 108 LGI-Ab+, 33 CASPR2-Ab+, and 6 LGI1/CASPR-Ab+patients were phenotyped. Pain questionnaires were undertaken to identify neuropathic pain using the Douleur Neuropathique(DN4), patient reported outcome measurement information system(PROMIS), and quality of life(EQ5D). Skin biopsies, and serum binding to cell-based assays, sensory neuronal cocultures, and dorsal root ganglion(DRG) cultures were undertaken. Results 39/147 patients described pain, including 17/33 CASPR2-Ab+(52%), 20/108 LGI1-Ab+(19%), and 2 LGI/CASPR2-Ab+patients. Questionnaires completed in 23/39(59%) revealed comparable DN4 scores(p=0.319) with 58% of LGI1-Ab+ and 67% of CASPR2-Ab+patients having neuropathic pain. Patients rated >50% response in 8/30(27%) analgesia trials, versus 20/40(55%) immunotherapy trials(p=0.045). PROMIS ratings were similar between LGI1-Ab+ and CASPR2-Ab+patients at nadir(p=0.662), but showed more improvement following immunotherapy in LGI1-Ab+(p=0.008) than CASPR2-Ab+patients(p=0.125). At follow-up(median 57 months) CASPR2-Ab+patients showed more impairment in mobility(p=0.014), daily activities(p=0.019), and anxiety/depression(p=0.043); and lower overall health(p=0.019) on the EQ5D compared to LGI1-Ab+patients. Intraepidermal nerve fibre density was reduced in 2 LGI1-Ab+ and 1 CASPR2-Ab+patients. Serum immunoglobulin G(IgG) from 6/16 CASPR2-Ab+patients bound to sensory neuronal cocultures compared to 0/14 LGI1-Ab+patients(p=0.019) and 0/12 healthy controls. Serum IgG from 10/16 CASPR2-Ab+patients bound to DRG cultures compared to 1/14 LGI1-Ab+patients(p=0.0024) and 1/12 healthy controls. Conclusion Neuropathic pain may be present in both LGI-Ab+ and CASPR2-Ab+patients, and is immunotherapy responsive. Serum IgG from CASPR2-Ab+patients more frequently bound sensory neurons and dorsal root ganglia, suggesting pathophysiological differences which may underlie the more severe pain in these patients.

In this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

Objectives To report a case of isolated third nerve palsy from pituitary apoplexy and perform a systematic literature review. Materials and methods MEDLINE/EMBASE databases were searched up to September 2020. Inclusion criteria: Age≥18, isolated third nerve palsy from pituitary apoplexy. Exclusion criteria: Age Results Case report: A 76-year-old woman presented with headache and right-sided ptosis. Right-eye exam revealed complete ptosis, absent pupillary constriction and accommodation, depressed and abducted eye on primary gaze, and -1 impaired depression, adduction, elevation, without other neurological findings. Brain MRI was suggestive of pituitary apoplexy. Pathology after transsphenoidal resection revealed an infarcted pituitary adenoma. Third nerve palsy resolved completely in 21 days. Systematic review: Twenty-three studies reporting 35 patients were selected from 182 abstracts. Twenty-nine (83%) had complete isolated third nerve palsy. Headache was reported in 31 (97%). Thirty-one had hemorrhage and 1 had infarction of pituitary. Cavernous sinus invasion occurred in 14 (50%). Twenty-eight were managed surgically (80%) and 7 medically (20%). Nerve palsy resolved completely in 27 (82%) and partially in 4 (11%). Conclusions Pituitary apoplexy is an important differential diagnosis in patients with isolated third nerve palsy. Isolated third nerve palsy in apoplexy appears to have favorable prognosis.

Background Data on the prevalence and correlates of restless legs syndrome (RLS) in people with HIV are limited. This study sought to determine the prevalence of RLS, associated clinical correlates, and characterize sleep-related differences in men with and without HIV. Methods Sleep-related data were collected in men who have sex with men participating in the Multicenter AIDS Cohort Study (MACS). Demographic, health behaviors, HIV status, comorbidities, and serological data were obtained from the MACS visit coinciding with sleep assessments. Participants completed questionnaires, home polysomnography, and wrist actigraphy. RLS status was determined with the Cambridge-Hopkins RLS questionnaire. RLS prevalence was compared in men with and without HIV. Multinomial logistic regression was used to examine correlates of RLS among all participants and men with HIV alone. Sleep-related differences were examined in men with and without HIV by RLS status. Results The sample consisted of 942 men (56% HIV+; mean age 57 years; 69% white). The prevalence of definite RLS was comparable in men with and without HIV (9.1% vs 8.7%). In multinomial regression, HIV status was not associated with RLS prevalence. However, white race, anemia, depression, and antidepressant use were each independently associated with RLS. HIV disease duration was also associated with RLS. Men with HIV and RLS reported poorer sleep quality, greater sleepiness, and had worse objective sleep efficiency/fragmentation than men without HIV/RLS. Conclusions The prevalence of RLS in men with and without HIV was similar. Screening for RLS may be considered among people with HIV with insomnia and with long-standing disease.

Spinal muscular atrophy (SMA) was added to the Recommended Uniform Screening Panel (RUSP) in July 2018, following FDA approval of the first effective SMA treatment, and demonstration of feasibility of high-throughput newborn screening using a primary molecular assay. SMA newborn screening was implemented in New York State (NYS) on 1 October 2018. Screening was conducted using DNA extracted from dried blood spots with a multiplex real-time quantitative polymerase chain reaction (qPCR) assay targeting the recurrent SMN1 exon 7 gene deletion. During the first year, 225,093 infants were tested. Eight screened positive, were referred for follow-up, and confirmed to be homozygous for the deletion. Infants with two or three copies of the SMN2 gene, predicting more severe, earlier-onset SMA, were treated with antisense oligonucleotide and/or gene therapy. One infant with ≥4 copies SMN2 also received gene therapy. Newborn screening permits presymptomatic SMA diagnosis, when treatment initiation is most beneficial. At 1 in 28,137 (95% confidence interval [CI]: 1 in 14,259 to 55,525), the NYS SMA incidence is 2.6- to 4.7-fold lower than expected. The low SMA incidence is likely attributable to imprecise and biased estimates, coupled with increased awareness, access to and uptake of carrier screening, genetic counseling, cascade testing, prenatal diagnosis, and advanced reproductive technologies.

Background Neuromyelitis Optica Spectrum disorders (NMOSD) is a rare autoimmune disease characterized by optic neuritis (ON) and/or longitudinal extensive transverse myelitis (LETM). It is commonly associated with other autoimmune diseases (OAD). Recent reports suggested racial differences in clinical phenotype and presentation of NMOSD. However, data on Black population is scarce. Objectives We aim to characterize, in our largely Black population, the clinical, laboratory and radiologic features of patients with NMOSD and OAD. We also aim to ascertain differences in clinical presentation between NMOSD patients with and without OAD. Methods In a retrospective analysis, patients ≥ 18 years of age with a confirmed diagnosis of NMOSD as per the International Panel for NMOSD Diagnosis Criteria, seen at 2 NYC urban hospitals from 1/2005 to 4/2017 were identified. Demographic, clinical, and laboratory data were extracted together with expanded disability status scales (EDDS) and imaging studies. Brain magnetic resonance imaging (MRI) was reviewed by a neuro-radiologist who applied the NMOSD Radiological criteria to identify typical findings of the disease. Results Forty-one patients fulfilled NMOSD criteria. 85.4% were women with a mean age of 44.7±2.03 years. 82.9% of the patients were Black and 34.1% (14/41) had an associated OAD. Systemic lupus erythematosus (SLE) was the most common OAD present prior to NMOSD diagnosis, followed by thyroid disease and Sjogren’s syndrome. Aquaporin 4 immunoglobulin G (AQP4IgG) was positive in 82.9% of the entire cohort and in 76.9% (10/13) of patients with NMOSD and OAD. Hypertension (33.3% vs. 15.3%), and cardiovascular disease (13.3% vs. 4%) were more frequent in NMOSD with OAD, compared with the NMOSD only group. On initial presentation of the NMOSD only group, visual changes (40% vs. 28.5%) and ON (38.4% vs. 20%)were predominant. In the intial presentation of NMOSD with OAD group, sensory loss (78.5% vs. 57.7%), acute myelitis (40% vs. 23.1%), and elevated C reactive protein (CRP) (20.85±11.2 vs. 3.2±1.85mg/d/L) were more freuent. Disability scores (EDDS) were 5.5 for each group. Brain MRI revealed lesions affecting corpus callosum in a marble pattern, (21.4% vs. 13.6%), the hemispheres in a spindle like pattern(33%vs 22.7%), the dorsal medulla (50% vs. 39.1%), the area postrema (38.5% vs. 27.3%) and the pons (21.4% vs. 13.4) for NMOSD with OAD and without respectively. LETM with predilection for the thoracic region was (66.7% vs 54.5%), cord edema (69.2% vs. 40.9%) and gadolinium enhancement (69.2% vs. 59.1%) for NMOSD with OAD and NMOSD only patients respectively. Conclusion AQP4IgG-positivity was observed in most of the cases in our predominantly Black NMOSD population. Over a third of the NMOSD patients had OAD. SLE was the most commonly reported. NMOSD with OAD patients tended to present with sensory loss, acute myelitis, and elevated CRP, while in NMOSD without OAD presented more with visual changes and ON. The NMOSD with OAD group had more MRI lesions involving corpus callosum, hemispheres, brainstem and LETM, compared to those with NMOSD only group. References [1] Katz S I. NMOSD. Multiple Sclerosis and Other Demyelinating Diseases p. 864896.June2016, Vol.22, No.3. Doi: 10.1212/CON.0000000000000337 Disclosure of Interests None declared

In this review, we present an overview of the role of exercise in neuromuscular disease (NMD). We demonstrate that despite the different pathologies in NMDs, exercise is beneficial, whether aerobic/endurance or strength/resistive training, and we explore whether this benefit has a similar mechanism to that of healthy subjects. We discuss further areas for study, incorporating imaginative and novel approaches to training and its assessment in NMD. We conclude by suggesting ways to improve future trials by avoiding previous methodological flaws and drawbacks in this field. Muscle Nerve, 2013

Neuromyelitis Optica (NMO) is a potentially devastating, complex autoimmune disease of the central nervous system that differs clinically and pathologically from the more common Multiple Sclerosis (MS). In this paper, we briefly describe our clinical experience with NMO patients treated in an inner city hospital in central Brooklyn, New York, and offer a an up-to-date discussion of diagnosis, treatment, and prognosis of this rare condition.

In this review, we present an overview of the role of exercise in neuromuscular disease (NMD). We demonstrate that despite the different pathologies in NMDs, exercise is beneficial, whether aerobic/endurance or strength/resistive training, and we explore whether this benefit has a similar mechanism to that of healthy subjects. We discuss further areas for study, incorporating imaginative and novel approaches to training and its assessment in NMD. We conclude by suggesting ways to improve future trials by avoiding previous methodological flaws and drawbacks in this field.

Hyperkalemia has been described as a rare and under recognized cause of acute quadriplegia.A 52-year-old man with end-stage renal disease presented with ascending quadriplegia and dyspnea for 2 days. He had life-threatening hyperkalemia (9.0 mEq/L). His electrocardiogram showed typical features of hyperkalemia. His symptoms improved in 30 minutes and completely resolved in 5 hours after emergent treatment of hyperkalemia. He admitted eating large amounts of high potassium foods and taking ibuprofen in uncertain quantities. We reviewed 62 articles and identified 73 patients with secondary hyperkalemic paralysis. Common presentations were diminished reflexes, quadriparesis/paralysis, respiratory involvement, and sensory loss. Almost half of all patients had potassium levels higher than 9 mEq/L. Complete recovery, achieved in 89% of patients, did not correlate either with the absolute potassium level or the degree to which it was corrected.Hyperkalemia is a rare but treatable cause of acute flaccid paralysis that requires immediate treatment. Late diagnosis can delay appropriate treatment leading to cardiac arrhythmias and arrest.

Duchenne muscular dystrophy (DMD), an inherited X-linked recessive disorder, is characterized by progressive symmetric muscle weakness and gait disturbance, with onset in early childhood. DMD is the most common muscular dystrophy in children, and incidence ranges from 1 in 3600 to 4700 live male births. Early diagnosis (screening, confirmation, and genetic counseling), treatment, and long-term follow-up of affected individuals in routine pediatric practice can be challenging and are the focus of this review.

by Hubert H. Fernandez, Stephan Eisenschenk, Anthony T. Yachnis, and Michael S. Okun, 544 pp., Demos Medical Publishing, LLC, 2006, 2006, $79.95 The Boards. Those two words evoke distant memories for seasoned neurologists and disquieting trepidation for soon-to-be graduating senior residents. In recent years, there has been a plethora of Board review books promising quick, concise reviews and guaranteeing success on the Boards. There are two Board exams for which to prepare, the written and the oral, each needing a different approach. Methods of preparation include long-term studying and short-term cramming. Ultimate Review for the Neurology Boards by …