Faculty Bibliography

OBJECTIVE:To investigate differences between flail limb syndrome (FLS) and amyotrophic lateral sclerosis (ALS). DESIGN/METHODS:Retrospective chart review identified 16 cases of ALS and 16 of FLS. Revised ALS Functional Rating Scale (ALSFRS-R), compound muscle action potential (CMAP) amplitudes, and rate of loss of vital capacity (ΔVC) were compared. RESULTS:Comparing ALS and FLS patients, ΔVC was 5.26% ± 0.33% vs. 0.54% ± 0.06%, respectively (p<0.05). No patient in FLS group had a ΔVC more that 0.65% per month. No patient in ALS group had a ΔVC less than 4.6% per month. Average ulnar nerve CMAP amplitudes were significantly lower in FLS (p<0.05). No significant difference was observed in rate of ALSFRS-R decline or average peroneal, tibial, and median nerve CMAP amplitudes. CONCLUSION/CONCLUSIONS:In FLS, an average monthly decrease in VC exceeding 0.65% may suggest a spread of motor neuron loss to higher cervical anterior horn areas and raise the possibility of progression to ALS. Larger prospective studies are needed to investigate the rate of VC decline in FLS and limb-onset ALS and to establish whether a cut-off score combining ΔVC and CMAP amplitude mainly of the ulnar nerve might predict progression of FLS to ALS, the knowledge of which can facilitate appropriate patient counseling.

Objective: Test the null hypothesis that Level III support measures do not differ between Chinese and Caucasian nulliparous women with normal support.
Method(s): Pelvic floor 3D MRIs at rest were analyzed (Image J, 3D slicer v. 4.10.1) from Chinese and Caucasian nulliparous women with no prolapse at/below the hymen. Urogenital hiatus (UGH), levator hiatus (LH), and levator bowl volume (LBV) were measured and levator plate (LP) was traced (Figure 1A-D). Perineal body (PB) location was measured relative to Pelvic Inclination Correction System (PICS) line, 34degree below the SCIPP line. Muscle fiber directions were traced for the pubococcygeus (PCM), puborectalis (PR), and external anal sphincter muscles (EAS) in parasagittal slides (Figure1E-F). LP shape was analyzed using principal component analysis (PCA) (Figure 2C-D). Student's t-test was used to compare measurements between groups.
Result(s): Eleven Chinese and 10 Caucasian women were included with average ages of 28+/-3 and 23+/-2 years, respectively (P<.001). BMI was lower in Chinese women (21.5+/-2.5kg/m2 vs 25.6+/-5.6kg/m2, P=.04) and height was similar (1.63 +/-0.06m vs 1.65+/-0.12m, P=.56). Chinese women had 18% smaller UGH, 10% smaller LH and 33% smaller LBV compared to Caucasian women at rest (Figure 2A). PB position was higher in Chinese versus Caucasian women (-2mm vs-12mm, P<.001). PCM fiber direction was more horizontal in Chinese women compared to Caucasian women (16+/-12degree vs 25+/-5degree, P=.047), while the direction of PR (-21+/-5degree vs-20+/-5degree, P=.91) and EAS (-49+/-9degree vs-51 +/-10degree, P=.80) are similar (Figure 2B). PCA showed the LP is significantly more horizontal in Chinese than Caucasian women (PC1 score for Chinese-6.5 vs Caucasian 7.1, P=.020).
Conclusion(s): We reject our null hypothesis. In nulliparas with normal support, Chinese women have a smaller hiatus size and LBV than Caucasian women and their PCM fiber direction and LP shape are oriented more horizontally. Comment: This analysis is consistent with the hypothesis that PCM fiber direction varies with LP shape and bowl volume. These baseline differences in anatomy may influence birth injury, mechanism of prolapse, and treatment outcomes

OBJECTIVE:People with Multiple Sclerosis (pwMS) often exhibit generalized weakness that affects several activities of daily life, particularly those relying on balance and gait. While it is known that such a symptom has a strong impact on mobility, to what extent muscular strength is linked with functional mobility in men and women with MS remains mostly unexplored. The aim of this study is to assess the existence of possible sex-related differences in functional mobility in pwMS, also considering the muscular strength capacity. METHODS:Functional mobility and hand-grip strength (HGS) were assessed in 49 pwMS with mild-moderate disability using instrumental Timed-up-and-go (TUG) test carried out using an inertial sensor and digital dynamometry. We investigated the existence of sex-related differences in the duration of each TUG sub-phase and their correlation with the HGS. RESULTS:No sex-related differences in TUG performance (either in terms of overall or sub-phase time) were found. Similar large negative correlations were found in men and women with MS between HGS and overall TUG and walking phase duration. However, changes in strength have a more marked impact in women as indicated by the different slope of the HGS-TUG time relationship., In women, HGS also appears significantly correlated with all TUG sub-phases, while in men this occurs only for overall TUG and walking time. CONCLUSIONS:Rehabilitation and training programs for pwMS should take into account the peculiar features associated with the interaction between strength and mobility specific for each individual's sex to optimize their effectiveness.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.

Background/UNASSIGNED:There remains no consensus on the optimal primary intervention for subdural hematoma (SDH). Although historically favored, craniotomy carries substantial morbidity and incurs significant costs. Contrastingly, the subdural evacuating port system (SEPS) is a minimally invasive bedside procedure. We assessed the benefits of SEPS over traditional craniotomy for SDH evacuation. Methods/UNASSIGNED:A single-center retrospective cohort study of SDH patients receiving craniotomy or SEPS between 2012 and 2017 was performed. Information regarding demographics, medical history, presentation, surgical outcomes, cost, and complications was collected. Pre- and postoperative hematoma volumes were calculated using 3D image segmentation using Vitrea software. Multivariate regression models were employed to assess the influence of intervention choice. Results/UNASSIGNED:= 1.000). Conclusion/UNASSIGNED:In this retrospective cohort, SEPS was noninferior to craniotomy at reducing SDH hematoma volume. The SEPS procedure was also associated with decreased length of stay hospitalization costs, and postoperative seizures and demonstrated a comparable recurrence rate to craniotomy for chronic SDH in particular.

Background/UNASSIGNED:In the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life. Objectives/UNASSIGNED:In light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019. Methods/UNASSIGNED:We included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria. Results/UNASSIGNED:We discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected. Conclusions/UNASSIGNED:This systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA.

OBJECTIVES/OBJECTIVE:Guidelines recommend to initiate anticoagulation within 4-14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation such as infarct size, hemorrhagic transformation, or high risk features on echocardiography. METHODS:We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and outcomes were recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. RESULTS:Among 2084 patients, 1289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the three groups: 0-3 days [10.3% (64/617)], 4-14 days [(9.7%) 52/535)], >14 days [10.2% (14/137), p=0.933]. In adjusted models, patients started on anticoagulation between 4-14 days did not have a lower rate of sICH (vs. 0-3 days) (OR 1.49 95% CI 0.50 - 4.43) neither did they have a lower rate of recurrent ischemic events (vs. > 14 days) (OR 0.76 95% CI 0.36 - 1.62, p = 0.482). INTERPRETATION/CONCLUSIONS:In this multicenter real world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. This article is protected by copyright. All rights reserved.

Background: Inadequate norepinephrine (NE) release in neurogenic orthostatic hypotension (nOH) causes blood pressure to fall on standing and debilitating symptoms of cerebral hypoperfusion. Ampreloxetine, a novel, long-acting NE reuptake inhibitor, potentiates the effects of endogenous NE, and may improve symptoms of nOH. The objective of the study was to explore the durability of effect and safety of once-daily oral ampreloxetine for the symptomatic treatment of nOH in subjects with synucleinopathies.
Method(s): In an open-label, phase 2, exploratory, multicenter study, subjects received open-label ampreloxetine (3-20 mg) once-daily for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint), OHSA and Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and Patient Global Impression of Severity (PGI-S).
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Week 4, mean (SD) improvement on OHSA#1 was -3.8 (3.1) points; approximately 77% of subjects reported >=1-point improvement (minimal clinically important difference). At Week 20, mean improvement was -3.1 (3.0) points; approximately 86% reported >=1-point improvement. Symptom improvement was observed as early as Week 1 and was sustained throughout the study. Deterioration to baseline symptom severity was after ampreloxetine withdrawal. Similar trends were seen in OHSA and OHDAS composite scores, and PGI-S. Most common adverse events were urinary tract infection (24%), hypertension (19%), and headache (14%), with no study-drug related serious adverse events.
Conclusion(s): Ampreloxetine showed durable symptom improvement in symptomatic subjects with nOH over 20 weeks, with return to baseline symptom severity after ampreloxetine withdrawal. Ampreloxetine was well tolerated with a favorable safety profile. These encouraging open-label findings are being evaluated further in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH and synucleinopathies.
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The RNS System is not approved in patients under 18, although a critical need for novel treatment modalities in this vulnerable population persist. We present two pediatric patients with drug-resistant epilepsy secondary to Lennox-Gastaut Syndrome (LGS) and autism spectrum disorder (ASD) treated with the RNS System. Both patients have experienced 75-99% clinical seizure reductions in >1 year of follow-up. We illustrate that children with diffuse onset, multifocal epilepsy, including frontal and thalamic circuits thought to exist in the generation of LGS seizures, can be treated with responsive neurostimulation safely and effectively, targeting thalamic networks, and avoiding palliative disconnections and resections.

PURPOSE/OBJECTIVE:Surgical planning for people with drug resistant non-lesional focal epilepsy can be challenging. Prior studies focus on cases that are only MRI-negative or MRI-negative with PET-positive imaging, but little is known about outcomes in patients with non-lesional findings on both MRI and PET imaging. In this study, we investigate 5-year surgical outcomes in patients who underwent epilepsy surgery for drug resistant MRI/PET-negative focal epilepsy. METHODS:We collected clinical and testing data on 131 consecutive patients with drug resistant non-lesional epilepsy who were presented at a multidisciplinary epilepsy surgery conference at the New York University Comprehensive Epilepsy Center between 2010 and 2014, and identified those who underwent epilepsy surgery in order to review 5-year surgical outcomes. RESULTS:There were 103 with non-lesional MRI studies, and of these, 22 had corresponding non-lesional PET imaging. 14 MRI/PET-negative patients pursued a surgical treatment option and 9 underwent resections after intracranial EEG. At 5 years, 77.8 % of patients had favorable (ILAE class 1 and 2) outcomes. Most (77.8 %) had focal cortical dysplasia type Ia (FCDIa) on pathology. CONCLUSION/CONCLUSIONS:These findings suggest that with careful planning and patient selection, surgery for patients with drug resistant MRI/PET-negative focal epilepsy can be successful.