COVID-19 infection in myasthenia gravis: Clinical course and outcomes.

INTRODUCTION/AIMS: Myasthenia gravis (MG) patients have been predicted to have high rates of coronavirus disease-2019 (COVID-19) complications due to frequent involvement of respiratory muscles in MG and frequent use of immunosuppressive therapies. We investigated outcomes of MG patients infected with SARS-CoV-2 to identify risk factors for exacerbation and severe disease. METHODS: This was a retrospective analysis of 39 MG patients with SARS-CoV-2 infection from January March 1, 2020 to October 25, 2021 at Emory University. Patients' records were queried for demographic data, MG history, and COVID-19 treatments and hospitalizations. RESULTS: At the time of infection, 8 of 39 were vaccinated, 30 of 39 unvaccinated, and 1 unknown. Average age was 52.6 years. Twenty-seven patients were receiving immunomodulatory treatments at the time of infection. Thirty-five of 39 were symptomatic, 21 were hospitalized, and 7 required ventilations. MG exacerbations occurred in 5 and were treated with therapeutic plasma exchange (n = 1), intravenous immunoglobulin (IVIg) (n = 1), and prednisone taper (n = 5). Four hospitalized patients died from COVID-related lung injuries. No deaths were attributed to MG exacerbation; however, one patient receiving IVIg for MG exacerbation had a pulmonary embolism. There were no deaths in fully vaccinated patients, and only one vaccinated patient was admitted to the intensive care unit. DISCUSSION: High rates of COVID-19 complications and death were observed in this cohort of MG patients. Some patients with MG and COVID-19 also had an exacerbation during infection. Further studies are needed to determine whether MG patients are at higher risk for complications than the rest of the population.

Article Topic: Neuropathies Due to Infections and Antimicrobial Treatments.

Purpose of eview: The aim of this review is to discuss the presentation, diagnosis, and management of polyneuropathy (PN) in selected infections. Overall, most infection related PNs are an indirect consequence of immune activation rather than a direct result of peripheral nerve infection,  Schwann cell infection, or toxin production, though note this review will describe infections that cause PN through all these mechanisms. Rather than dividing them by each infectious agent separately, we have grouped the infectious neuropathies according to their presenting phenotype, to serve as a guide to clinicians. Finally, toxic neuropathies related to antimicrobials are briefly summarized. Recent findings: While PN from many infections is decreasing, increasing evidence links infections to variants of GBS. Incidence of neuropathies secondary to use of HIV therapy has decreased over the last few years. Summary: In this manuscript, a general overview of the more common infectious causes of PN will be discussed, dividing them across clinical phenotypes: large- and small-fiber polyneuropathy, Guillain-Barré syndrome (GBS), mononeuritis multiplex, and autonomic neuropathy. Rare but important infectious causes are also discussed.

Neurosarcoidosis of the Cauda Equina: Clinical Course, Radiographic and Electrodiagnostic Findings, Response to Treatment, and Outcomes.

BACKGROUND AND OBJECTIVES: Sarcoidosis is a multisystem granulomatous disease affecting the nervous system in 3%-5% of cases. It can affect almost any component of the nervous system. Involvement of the cauda equina is an understudied phenotype, and questions remain regarding its natural history and optimal approach to management. This study aims to study the long-term clinical evolution of neurosarcoidosis affecting the cauda equina, response to treatment, and clinical and radiographic outcomes. METHODS: Patients with neurosarcoidosis treated at Emory University between January 1, 2011, and December 8, 2021, were retrospectively evaluated for manifestations of cauda equina disease and included if disease of the cauda equina could be substantiated by MRI or EMG. RESULTS: Of 216 cases, 14 (6.5%) involved the cauda equina. The median age was 49.5 years, and most were female (85.7%) and African American (64.3%). Chronic (>28 days) presentations were most common (78.6%), but acute (<7 days, 14.3%) and subacute (7-28 days, 7.1%) were also seen. The median modified Rankin Scale (mRS) score at nadir was 3 (range 2-4). Symptoms were asymmetric in 78.6% and included leg numbness (85.7%), leg weakness (64.3%), perineal numbness (35.7%), pain (42.3%), and incontinence (21.4%). On MRI, the cauda equina enhanced in 100%, appeared nodular in 78.6%, and was diffusely involved in 71.4%. Coexisting myelitis was common (cervical 28.6%, thoracic 35.7%, and conus medullaris 28.6%). Intracranial inflammation included leptomeningitis (71.4%) and cranial neuropathies (57.1%). Electrodiagnostic studies were conducted in 3 with only one showing features consistent with a radicular process. Serum and CSF angiotensin-converting enzyme levels were elevated in 38.5% and 0.0%, respectively. CSF white blood cell and protein were elevated in 92.9%. Corticosteroids were tried in all patients with durable stabilization or improvement in only 3 (21.4%). Second-line agents associated with improvement included methotrexate/infliximab (3/4, 75%), methotrexate (3/4, 75.0%), and azathioprine (1/1, 100%). During a median follow-up of 22.5 months, the final median mRS score was 3. Relapses occurred at a median of 6 months in 21.4%. In 9 patients with MRI follow-up, 6 improved (66.7%), 1 stabilized (11.1%), and 2 worsened (22.2%). DISCUSSION: Characteristic features of cauda equina involvement by neurosarcoidosis include chronically delayed presentations, nodular enhancement on MRI, poor response to corticosteroids, and substantial resultant neurologic disability.

Childhood-Onset Hereditary Spastic Paraplegia (HSP): A Case Series and Review of Literature.

BACKGROUND: Hereditary spastic paraplegia (HSP) encompasses several rare genetic disorders characterized by progressive lower extremity spasticity and weakness caused by corticospinal tract degeneration. Published literature on genetically confirmed pediatric HSP cases is limited. METHODS: We conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children's and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded. RESULTS: Sixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2). CONCLUSIONS: In our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.

Epidemiology and Outcomes of Ischemic Stroke and Transient Ischemic Attack in the Adult and Geriatric Population.

BACKGROUND: Rate of ischemic strokes and transient ischemic attacks (TIAs) increases with age. There is lack of evidence on how age affects treatment strategies and outcomes. Our aim is to compare epidemiology of ischemic strokes and TIAs in adult and geriatric populations including risk factors, treatment delivered, and outcomes. DESIGN: We designed a retrospective cross-sectional review of patients admitted to neurology with diagnosis of stroke or TIA from 2010 to 2015. Obtained variables were: age, sex, risk factors, acute therapy, National Institutes of Health Stroke Scale on admission and discharge, and disposition. Means, confidence intervals, or percentages were calculated as appropriate. RESULTS: Around 1,457 patients were divided into two groups: younger than 80 (n = 968) and 80 and older (n = 487). Rates of stroke and TIA were similar across younger and older groups (11% versus 12% TIA and 89% versus 88% stroke, respectively). Younger patients had lower admission National Institutes of Health Stroke Scale (mean 4.64 versus 7.84 in older group) and greater improvement on discharge (mean change -1.51 versus -1.29 accordingly). Older patients received tissue-type plasminogen activator (tPA) more often than younger patients, but no difference in rates of thrombectomy between groups. Older patients were more likely to have hypertension, atrial fibrillation, coronary artery disease, and less likely to be a smoker. On discharge, younger patients with stroke were discharged home or to acute rehab more frequently, regardless of tPA administration. CONCLUSIONS: Older patients had more comorbidities, received tPA more often, and had worse outcomes regardless of use of intravenous tPA or thrombectomy, and were more frequently institutionalized after discharge.

Hereditary Motor Neuropathies and Amyotrophic Lateral Sclerosis: a Molecular and Clinical Update.

PURPOSE OF REVIEW: This article provides an overview of recent advancements in the fields of hereditary motor neuropathies and ALS. RECENT FINDINGS: There has been a robust growth in our knowledge and understanding of hereditary and degenerative motor neuronopathies/neuropathies over the last decade. Many breakthroughs in the field of hereditary motor neuropathies (HMN) have been associated with identification and characterization of the genes and molecular mechanisms underlying these disorders. Similar recent breakthroughs on the genetic and molecular underpinnings of the degenerative motor neuronopathy, amyotrophic lateral sclerosis (ALS), have been accompanied by advancements in biomarker research and the development and FDA approval of novel therapies. There is a reasonable hope that the marked and continued growth in our understanding of the molecular pathophysiology of the HMNs will translate into novel therapeutic approaches in the decade to come. Such breakthroughs have already begun in ALS, where novel biomarkers and treatment strategies have translated into a new FDA-approved therapy with a number of promising agents in development and/or in definitive phase 2/3 trials.

CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA).

INTRODUCTION: CANOMAD/CANDA are syndromes characterized by ataxic neuropathy, ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl antibodies. METHODS: A retrospective review of our neuromuscular autoantibody panel database was performed. Anti-GD1b seropositive patients with ataxia were included. RESULTS: Eleven patients were identified. Median age at onset was 56 years. Median disease duration was 6 years. All patients had gait disorders. Nine had ocular motility abnormalities. Most had a monoclonal protein and all had elevated serum IgM. Electrodiagnostic studies showed a mixed axonal/demyelinating pattern (6), an axonal pattern (4), or a pure demyelinating pattern (1). Ultrasounds showed nerve enlargement patterns consistent with acquired demyelination. A nerve biopsy showed near complete loss of myelinated axons with preservation of smaller axons. Rituximab was the most effective immunotherapy. CONCLUSION: CANOMAD/CANDA are rare and debilitating disorders with characteristic clinical and diagnostic findings. In our cohort, nerve ultrasound showed regional nerve enlargement and rituximab was the most effective immunomodulatory therapy.

Nerve ultrasound reliability of upper limbs: Effects of examiner training.

INTRODUCTION: Duration of training to reliably measure nerve cross-sectional area with ultrasound is unknown. METHODS: A retrospective review was performed of ultrasound data, acquired and recorded by 2 examiners-an expert and either a trainee with 2 months (novice) or a trainee with 12 months (experienced) of experience. Data on median, ulnar, and radial nerves were reviewed for 42 patients. RESULTS: Interrater reliability was good and varied most with nerve site but little with experience. Coefficient of variation (CoV) range was 9.33%-22.5%. Intraclass correlation coefficient (ICC) was good to excellent (0.65-95) except ulnar nerve-wrist/forearm and radial nerve-humerus (ICC = 0.39-0.59). Interrater differences did not vary with nerve size or body mass index. Expert-novice and expert-experienced interrater differences and CoV were similar. The ulnar nerve-wrist expert-novice interrater difference decreased with time (rs = -0.68, P = 0.001). DISCUSSION: A trainee with at least 2 months of experience can reliably measure upper limb nerves. Reliability varies by nerve and location and slightly improves with time. Muscle Nerve 57: 189-192, 2018.

Frequency of Radiculopathy in Patients With Carpal Tunnel Syndrome and Paracervical Pain.

OBJECTIVES: Patients with carpal tunnel syndrome (CTS) and paracervical pain (PCP) are often incorrectly diagnosed with cervical radiculopathy. The objective of the study is to determine how frequently such patients have electrophysiologic evidence of radiculopathy. METHODS: We reviewed charts of patients with clinical features of CTS and at least 1 median nerve conduction parameter showing slowing across the wrist. Patients were divided into those with and without PCP. Radiculopathy was defined electrophysiologically. We assessed group differences in the frequency of radiculopathy and how radiculopathy frequency varied with median nerve entrapment severity. RESULTS: Of 108 patients meeting criteria, 56 had PCP and 52 did not. Eight of 56 patients with PCP and 4 of 52 without pain had cervical radiculopathy (P = 0.36). There was no difference in the frequency of radiculopathy related to the severity of median nerve entrapment (P = 0.64). DISCUSSION: In patients with CTS, PCP is not associated with cervical radiculopathy. Cervical radiculopathy is not more frequent in more severe CTS.

Incidence of meningeal enhancement on brain MRI secondary to lumbar puncture.

BACKGROUND: Concern for reactive meningeal enhancement after lumbar puncture (LP) is a common reason for performing brain MRI prior to LP. We sought to determine actual incidence of unexplained meningeal enhancement after LP. METHODS: We collected results from all contrasted brain MRIs in patients admitted to adult neurology at a New York City hospital over a 3-year period. We used electronic medical records to determine whether an LP had been done within 30 days prior to brain MRI. The control group comprised those brain MRIs not preceded by an LP within 30 days prior to imaging. Number of cases of unexplained meningeal enhancement was compared between groups using a Fisher exact test. We recorded variables such as number of LP attempts, needle size, amount of fluid removed, and days from LP to brain MRI. RESULTS: From 2011 to 2013, there were 77 cases of LP prior to brain MRI and 707 controls (n = 784). Of the cases, 3 had meningeal enhancement, 1 (1.2%) of which was unexplained. Of the 707 controls, 36 had enhancement, and none was unexplained. The p value comparing unexplained enhancement in the cases vs controls was 0.098. CONCLUSIONS: Iatrogenic meningeal enhancement from prior LP that is not attributable to traumatic LP or intracranial hypotension is rare and not more common than in cases without a prior LP. Results suggest that the practice of delaying LP until after brain MRI might not be supported in cases where LP is necessary.

Isolated Hyperreligiosity in a Patient with Temporal Lobe Epilepsy.

A 40-year-old man with history of temporal lobe epilepsy presented to the emergency department with hyperreligiosity after medication noncompliance. After medications were resumed, he returned to baseline. Many famous prophets are believed to have suffered epilepsy. Waxman and Geschwind described a group of traits in patients with temporal lobe epilepsy consisting of hyperreligiosity, hypergraphia, altered sexual behavior, aggressiveness, preoccupation with details, and circumstantiality. The incidence of religious experiences ranges from 0.3 to 3.1 percent in patients with epilepsy. Religious experiences can be ictal, interictal, or postictal. Treatment is aimed at the underlying seizure etiology.

Comparison of Stroke Codes in the Emergency Room and Inpatient Setting.

BACKGROUND: Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator (t-PA) is indicated within 3-4.5 hours of symptom onset and endovascular intervention within 6 hours. Time to treatment may depend on the patient's location. This study seeks to determine whether there is a difference in the timing of key aspects of stroke codes between the emergency room and the inpatient setting. METHODS: Stroke codes ending in t-PA administration or endovascular intervention between 2010 and 2013 were included. Emergency room stroke codes were compared with those in the inpatient setting. Data were obtained from the Yarmon Stroke Center log. The variables were time to neurological evaluation, time to computed tomography (CT) scan, time to t-PA administration, time from CT scan to t-PA, and time to endovascular intervention. The variables were compared using the t test. RESULTS: One hundred twenty-two stroke codes were included (106 from emergency room and 16 from inpatient setting). There was no difference in the time to neurological evaluation (P = .19). The time to CT scan and to t-PA administration was significantly increased in the inpatient group (P ≤ .001 and P = .01, respectively). There was no difference in the time from CT scan to t-PA (P = .09) and in the time to endovascular intervention (P = .21). CONCLUSIONS: Our results show that in the inpatient setting, there was a significant delay in the time to CT scan and to t-PA administration and that the source of the delay is the time to CT scan.

Neuroinvasive cryptococcosis in an immunocompetent patient with a negative spinal fluid cryptococcus antigen.

58-year-old man presented with headache, nausea, vomiting, and gait disturbance. Brain MRI showed meningeal enhancement and herniation. Serum Cryptococcus antigen was positive but spinal fluid antigen and cultures were negative. A cerebellar biopsy revealed nonencapsulated Cryptococcus. He completed antifungal therapy. Serum Cryptococcus antigen titer decreased. He had a full neurological recovery.

[Gollop-Wolfgang complex and cloacal exstrophy, a strange association]. / Complejo de Gollop-Wolfgang y extrofia cloacal, una rara asociación.

Cloacal exstrophy and Gollop-Wolfgang complex are very rare pathologies and their association has been reported in only one patient. We present a case of a newborn of indeterminate sex with anomalies of the lower limbs, and an anterior abdominal wall defect. External genitalia were not observed, ectrodactyly of lower limbs, omphalocele, lipomeningocele and imperforate anus were detected. During the diagnostic and therapeutic surgery other anomalies were found, such as vesical exstrophy, cecal fistula, uterine duplication, vaginal agenesis, urethral agenesis, ectopic ureters, stenosis of the left ureter, biphid clitoris and patent urachus. The abdominal ecography showed ectopic right lower quadrant localization of right kidney. Radiographic images of lower limbs showed bifurcation of left femur and absent tibia in both limbs. Due to the findings a diagnosis of cloacal exstrophy and Gollop- Wolfgang complex was made. The patient developed sepsis, liver failure, metabolic acidosis and hyponatremia, she died at seven weeks of age.

Complejo de Gollop-Wolfgang y extrofia cloacal, una rara asociación / Gollop-Wolfgang complex and cloacal exstrophy, a strange association

La extrofia cloacal y el complejo de Gollop-Wolfgang son patologías muy raras y su asociación ha sido comunicada en un solo paciente. Presentamos el caso de un neonato, de sexo indeterminado, con anormalidades de miembros inferiores y defecto en la pared abdominopélvica anterior. No se observan genitales, presenta ectrodactilia en miembros inferiores, onfalocele, lipomeningocele y ano imperforado. Se realiza cirugía diagnóstica y terapéutica que revela extrofia vesical, fístula cecal, útero doble, agenesia de vagina, agenesia de uretra, uréteres mal implantados, estenosis de uréter izquierdo, clítoris bífido y uraco persistente. La ecografía abdominal mostró riñón derecho ectópico en fosa ilíaca derecha. Radiografías de los miembros inferiores mostraron bifurcación del fémur izquierdo y ausencia de tibia en ambos miembros. Debido a los hallazgos se llega al diagnóstico de extrofia cloacal y complejo de Gollop-Wolfgang. La paciente presentó sepsis, insuficiencia hepática, acidosis metabólica e hiponatremia; falleció a las siete semanas de edad.