Faculty Bibliography

ABSTRACT/UNASSIGNED:A collection of instructional videos that illustrate a step by step approach to tele-neuro-ophthalmology and neuro-otology visits. These videos provide instruction for patient preparation for their video visit, patient and provider interface with an electronic medical record associated video platform, digital applications to assist with vision testing, and practical advice for detailed remote neuro-ophthalmologic and neuro-otologic examinations.

During the height of the pandemic in NYC (March-June 2020), the NYU Langone Health Lysosomal Storage Disorders (LSD) Program reached out to 183 patients to provide information on how to mitigate exposure to COVID19 and to ascertain who had been exposed and/or infected. 139 patients were successfully contacted. Recommendations on how to safely continue enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were provided. 135 of the 139 respondents during March 2020-June 2020 had Gaucher disease (GD). Twenty-six patients with GD endorsed 2 or more symptoms consistent with COVID19 infection and/or were confirmed to have COVID19 either through RT-PCR test for SARS-CoV-2 RNA or through antibodies to the virus. The remaining 4 who had suspected or confirmed COVID19 infection were patients with Fabry (2), Pompe (1), and Mucopolysaccharidosis Type IIIA (1). This case series describes the impact of COVID19 on 30 patients with LSDs with details of symptomatology, duration of illness, and treatment. Baseline demographics were collected including age, sex, genotype, current disease burden, LSD treatment history, biomarkers and co-morbidities. At time of infection, 21 patients were on ERT (20 GD, 1 PD), 3 on SRT for GD, and 6 were naive to therapy. There was only 1 hospitalization of a 55 year old woman with GD on ERT that resulted in ARDS who subsequently died due to SARS-CoV-2. Her co-morbidities included morbid obesity, COPD, hypertension and diabetes. Her GD burden was minimal. The rest of the affected patients had a mild to moderate COVID19 course. In conclusion, patients with LSDs experienced varied symptomatology and severity from COVID19 infection, ranging from asymptomatic to critically ill. Risk factors included baseline health status regardless of specific LSD, age, and associated co-morbidities. The sample is too small to make conclusions on specific impact of treatment status on COVID19 severity.-.
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PURPOSE/OBJECTIVE:The unified multiple system atrophy (MSA) rating scale (UMSARS) was developed almost 20 years ago as a clinical rating scale to capture multiple aspects of the disease. With its widespread use, the shortcomings of the UMSARS as a clinical outcome assessment (COA) have become increasingly apparent. We here summarize the shortcomings of the scale, confirm some of its limitations with data from the Natural History Study of the Synucleinopathies (NHSS), and suggest a framework to develop and validate an improved COA to be used in future clinical trials of disease-modifying drugs in patients with MSA. METHODS:Expert consensus assessment of the limitations of the UMSARS and recommendations for the development and validation of a novel COA for MSA. We used UMSARS data from the ongoing NHSS (ClinicalTrials.gov: NCT01799915) to showcase some of these limitations. RESULTS:The UMSARS in general, and specific items in particular, have limitations to detect change resulting in a ceiling effect. Some items have specific limitations including unclear anchoring descriptions, lack of correlation with disease severity, susceptibility to improve with symptomatic therapies (e.g., orthostatic hypotension, constipation, and bladder dysfunction), and redundancy, among others. CONCLUSIONS:Because of the limitations of the UMSARS, developing and validating an improved COA is a priority. The time is right for academic MSA clinicians together with industry, professional societies, and patient advocacy groups to develop and validate a new COA.

The visual field region where a stimulus evokes a neural response is called the receptive field (RF). Analytical tools combined with functional MRI can estimate the receptive field of the population of neurons within a voxel. Circular population RF (pRF) methods accurately specify the central position of the pRF and provide some information about the spatial extent (diameter) of the receptive field. A number of investigators developed methods to further estimate the shape of the pRF, for example whether the shape is more circular or elliptical. There is a report that there are many pRFs with highly elliptical pRFs in early visual cortex (V1-V3; Silson et al., 2018). Large aspect ratios (>2) are difficult to reconcile with the spatial scale of orientation columns or visual field map properties in early visual cortex. We started to replicate the experiments and found that the software used in the publication does not accurately estimate RF shape: it produces elliptical fits to circular ground-truth data. We analyzed an independent data set with a different software package that was validated over a specific range of measurement conditions, to show that in early visual cortex the aspect ratios are less than 2. Furthermore, current empirical and theoretical methods do not have enough precision to discriminate ellipses with aspect ratios of 1.5 from circles. Through simulation we identify methods for improving sensitivity that may estimate ellipses with smaller aspect ratios. The results we present are quantitatively consistent with prior assessments using other methodologies.SIGNIFICANCE STATEMENT:We evaluated whether the shape of many population receptive fields in early visual cortex is elliptical and differs substantially from circular. We evaluated two tools for estimating elliptical models of the pRF; one tool was valid over the measured compliance range. Using the validated tool, we found no evidence that confidently rejects circular fits to the pRF in visual field maps V1, V2 and V3. The new measurements and analyses are consistent with prior theoretical and experimental assessments in the literature.

OBJECTIVE:To study the efficacy of middle meningeal artery (MMA) embolization for the treatment of chronic subdural hematoma (SDH) and characterize its post-embolization volumetric resolution. METHODS:Ten patients diagnosed with 13 cSDH underwent MMA embolization. SDH volumes were measured from time of initial discovery on imaging to pre-operative, post-operative, short-term and long-term follow-up. Time between procedure to obliteration was also measured. Volumetric analysis was done using the coniglobus formula, and recurrence rate as well as resolution timeline was defined using best-fit models. RESULTS:Out of 10 patients, five were recurrent lesions, three were bilateral and seven unilateral cSDH. Average and median pre-operative volumes were 105.3 cc and 97.4 cc, respectively. Embolization on average was performed 21 days after discovery. Sixty percent of patients had concurrent antiplatelets or anticoagulation use. Forty percent underwent embolization treatment as the primary therapy. Recurrence was not seen in any patients treated with embolization. There were no peri- or post-operative complications. Five patients experienced complete or near-complete obliteration, while those with partial resolution showed a composite average of 75% volumetric reduction in 45 days. Post-embolization, the volumetric resolution followed an exponential decay curve over time and was independent of initial volume. CONCLUSION/CONCLUSIONS:MMA embolization contributed to a marked reduction in SDH volume post-operatively and can be used as a curative therapy for primary or recurrent chronic SDH.

OBJECTIVE:To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. METHODS:We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. RESULTS:Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. CONCLUSION/CONCLUSIONS:Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

BACKGROUND AND PURPOSE/OBJECTIVE:Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients. METHODS:This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS. RESULTS:One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244). CONCLUSION/CONCLUSIONS:In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.

BACKGROUND:Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS:In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS:Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS:aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

OBJECTIVE:The electroencephalographic (EEG) terms "brief potentially ictal rhythmic discharges" (BIRDs) and "paroxysmal fast activity" (PFA) are considered distinct entities; however, their definitions overlap, and they may have similar clinical significance. We investigated their clinical significance and their association with seizures and the seizure onset zone (SOZ). METHODS:We retrospectively identified an adult cohort (July 2015 to March 2018) whose long-term (>12 h) EEGs in any setting reported BIRDs (>4 Hz, lasting .5-10 s) and/or PFA. Different frequency cutoffs for PFA (>13 Hz or ≥8 Hz) were tested to compare their clinical significance. Patient demographics, clinical history, and EEG features were recorded. RESULTS:We identified 94 patients with BIRDs/PFA out of 3520 patients (3%); 36 were critically ill (12 with epilepsy), and 58 were noncritically ill (all with epilepsy). The frequency of BIRDs/PFA was largely dependent on EEG background: it tended to be slower (theta) in the absence of a posterior dominant rhythm or in the presence of continuous focal slowing in the same region (p = .01). Sixty-two of 94 patients (66%; 32/36 [89%] critically ill, 30/58 [52%] noncritically ill) had electrographic seizures during the recording. The scalp EEG SOZ colocalized with BIRDs/PFA in all cases. BIRDs with faster frequency (also qualifying as PFA by definition) had similar seizure risk to that of slower BIRDs (62%-71%), regardless of frequency cutoff used to define PFA. In addition, 30 of 30 (100%) patients with evolving BIRDs/PFA (which lasted a median of 6 s, range = 2-9.5 s) had electrographic seizures (>10 s), compared to 32 of 64 (50%) with nonevolving BIRDs (median = 1 s, range = .5-3.5 s; p < .01). SIGNIFICANCE/CONCLUSIONS:A high proportion of patients with BIRDs/PFA had seizures on EEG, regardless of their frequency (i.e., whether they also qualified as PFA), and their location colocalized with scalp SOZ in all cases. BIRDs appear to be a scalp EEG biomarker of uncontrolled seizure activity and a reliable localizing sign of the SOZ.

Motor function depends on neural dynamics spanning multiple spatiotemporal scales of population activity, from spiking of neurons to larger-scale local field potentials (LFP). How multiple scales of low-dimensional population dynamics are related in control of movements remains unknown. Multiscale neural dynamics are especially important to study in naturalistic reach-and-grasp movements, which are relatively under-explored. We learn novel multiscale dynamical models for spike-LFP network activity in monkeys performing naturalistic reach-and-grasps. We show low-dimensional dynamics of spiking and LFP activity exhibited several principal modes, each with a unique decay-frequency characteristic. One principal mode dominantly predicted movements. Despite distinct principal modes existing at the two scales, this predictive mode was multiscale and shared between scales, and was shared across sessions and monkeys, yet did not simply replicate behavioral modes. Further, this multiscale mode's decay-frequency explained behavior. We propose that multiscale, low-dimensional motor cortical state dynamics reflect the neural control of naturalistic reach-and-grasp behaviors.