Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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22914
Visually sensitive seizures: An updated review by the Epilepsy Foundation
Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m2 at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.
PMID: 35132632
ISSN: 1528-1167
CID: 5167142
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092
Acute ischaemic stroke associated with SARS-CoV-2 infection in North America
BACKGROUND:To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS:Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS:A total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome. CONCLUSION/CONCLUSIONS:There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.
PMCID:8804309
PMID: 35078916
ISSN: 1468-330x
CID: 5154472
Anxiety, worry, and job satisfaction: effects of COVID-19 care on critical care anesthesiologists [Letter]
PMCID:8756752
PMID: 35025026
ISSN: 1496-8975
CID: 5118922
Observational study of medical marijuana as a treatment for treatment-resistant epilepsies
OBJECTIVES/OBJECTIVE:Medical cannabis formulations with cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are widely used to treat epilepsy. We studied the safety and efficacy of two formulations. METHODS:We prospectively observed 29 subjects (12 to 46 years old) with treatment-resistant epilepsies (11 Lennox-Gastaut syndrome; 15 with focal or multifocal epilepsy; three generalized epilepsy) were treated with medical cannabis (1THC:20CBD and/or 1THC:50CBD; maximum of 6 mg THC/day) for ≥24 weeks. The primary outcome was change in convulsive seizure frequency from the pre-treatment baseline to the stable optimal dose phase. RESULTS:There were no significant differences during treatment on stable maximal doses for convulsive seizure frequency, seizure duration, postictal duration, or use of rescue medications compared to baseline. No benefits were seen for behavioral disorders or sleep duration; there was a trend for more frequent bowel movements compared to baseline. Ten adverse events occurred in 6/29 patients, all were transient and most unrelated to study medication. No serious adverse events were related to study medication. INTERPRETATION/CONCLUSIONS:Our prospective observational study of two high-CBD/low-THC formulations found no evidence of efficacy in reducing seizures, seizure duration, postictal duration, or rescue medication use. Behavioral disorders or sleep duration was unchanged. Study medication was generally well tolerated. The doses of CBD used were lower than prior studies. Randomized trials with larger cohorts are needed, but we found no evidence of efficacy for two CBD:THC products in treating epilepsy, sleep, or behavior in our population.
PMID: 35267245
ISSN: 2328-9503
CID: 5182322
mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis
BACKGROUND:Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. OBJECTIVE:To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants. METHODS:Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976). RESULTS:The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression. CONCLUSIONS:Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.
PMID: 35040506
ISSN: 1531-8257
CID: 5131432
The ConTraSt database for analysing and comparing empirical studies of consciousness theories
Understanding how consciousness arises from neural activity remains one of the biggest challenges for neuroscience. Numerous theories have been proposed in recent years, each gaining independent empirical support. Currently, there is no comprehensive, quantitative and theory-neutral overview of the field that enables an evaluation of how theoretical frameworks interact with empirical research. We provide a bird's eye view of studies that interpreted their findings in light of at least one of four leading neuroscientific theories of consciousness (N = 412 experiments), asking how methodological choices of the researchers might affect the final conclusions. We found that supporting a specific theory can be predicted solely from methodological choices, irrespective of findings. Furthermore, most studies interpret their findings post hoc, rather than a priori testing critical predictions of the theories. Our results highlight challenges for the field and provide researchers with an open-access website ( https://ContrastDB.tau.ac.il ) to further analyse trends in the neuroscience of consciousness.
PMID: 35190711
ISSN: 2397-3374
CID: 5175042
Interaction Between Cerebellum and Cerebral Cortex, Evidence from Dynamic Causal Modeling
The interaction of the cerebellum with cerebral cortical dynamics is still poorly understood. In this paper, dynamical causal modeling is used to examine the interaction between cerebellum and cerebral cortex as indexed by MRI resting-state functional connectivity in three large-scale networks on healthy young adults (N = 200; Human Connectome Project dataset). These networks correspond roughly to default mode, task positive, and motor as determined by prior cerebellar functional gradient analyses. We find uniform interactions within all considered networks from cerebellum to cerebral cortex, providing support for the notion of a universal cerebellar transform. Our results provide a foundation for future analyses to quantify and further investigate whether this is a property that is unique to the interactions from cerebellum to cerebral cortex.
PMID: 34146220
ISSN: 1473-4230
CID: 5454372
Journal of stroke & cerebrovascular diseases. 2022:31(6).DOI: 10.1016/j.jstrokecerebrovasdis.2022.106450
Tachycardia is associated with mortality and functional outcome after thrombectomy for acute ischemic stroke
BACKGROUND:The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS:We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS:Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS:Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.
PMID: 35367848
ISSN: 1532-8511
CID: 5192412
A pilot randomized controlled clinical trial of Transcranial Alternating Current Stimulation in patients with multifocal pharmaco-resistant epilepsy
Transcranial Alternating Current Stimulation (tACS) is a promising noninvasive electrical stimulation therapy for neuropsychiatric diseases. Invasive neuromodulation using alternating current has been efficacious for drug-resistant epilepsy, but it is associated with surgical and medical complications. We aimed to explore the safeness and effectivity on seizure frequency reduction of two tACS protocols against placebo in patients with multifocal refractory epilepsy. This was a randomized, double-blinded, placebo-controlled clinical trial with 3-arm parallel-group (placebo, 30 min/2 mA daily sessions for 3 days [tACS-30], and 60 min/2 mA weekday sessions [tACS-60]). The main outcome was considered a change in reducing seizure frequency at 2 months after the intervention. Secondary outcomes were the apparition of any adverse effects during follow-up. At the second month, we observed a nonsignificant reduction in the seizure frequency in the placebo (7.3 ± 40.4%, p > 0.05) and the tACS-60 (26 ± 37.7%, p > 0.05). While the tACS-30 group showed a nonsignificant increase in seizure frequency (63.6 ± 155.3%, p > 0.05). No changes were statistically different from the placebo group. Otherwise, participants experienced only minor adverse events - the most common being an initial local transient tingling sensation (21%). This pilot study of tACS raises no severe safety issues, but provides negligible evidence for efficacy using this brief treatment protocol. Therefore, more studies are warranted testing different parameters to further verify the safety and effectivity of tACS in multifocal epilepsy.
PMID: 35366528
ISSN: 1525-5069
CID: 5201492
