Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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23384
Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study
BACKGROUND:The relationship between COVID-19 and epilepsy is uncertain. We studied the potential association between COVID-19 and seizures or epilepsy in the six months after infection. METHODS:We applied validated methods to an electronic health records network (TriNetX Analytics) of 81 million people. We closely matched people with COVID-19 infections to those with influenza. In each cohort, we measured the incidence and hazard ratios (HRs) of seizures and of epilepsy. We stratified data by age and by whether the person was hospitalized during the acute infection. We then explored time-varying HRs to assess temporal patterns of seizure or epilepsy diagnoses. RESULTS:We analyzed 860,934 electronic health records. After matching, this yielded two cohorts each of 152,754 patients. COVID-19 was associated with an increased risk of seizures and epilepsy compared to influenza. The incidence of seizures within 6 months of COVID-19 was 0.81% (95% CI, 0.75-0.88; HR compared to influenza 1.55 (1.39-1.74)). The incidence of epilepsy was 0.30% (0.26-0.34; HR compared to influenza 1.87 (1.54-2.28)). The HR of epilepsy after COVID-19 compared to influenza was greater in people who had not been hospitalized and in individuals aged under 16 years. The time of peak HR after infection differed by age and hospitalization status. CONCLUSIONS:The incidence of new seizures or epilepsy diagnoses in the six months following COVID-19 was low overall, but higher than in matched patients with influenza. This difference was more marked in people who were not hospitalized, highlighting the risk of epilepsy and seizures even in those with less severe infection. Children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations. That the varying time of peak risk related to hospitalization and age may provide clues as to the underlying mechanisms of COVID-associated seizures and epilepsy.
PMID: 36384658
ISSN: 1526-632x
CID: 5384832
Screening for PTSD and TBI in Veterans using Routine Clinical Laboratory Blood Tests
Post-traumatic stress disorder (PTSD) is a mental disorder diagnosed by clinical interviews, self-report measures and neuropsychological testing. Traumatic brain injury (TBI) can have neuropsychiatric symptoms similar to PTSD. Diagnosing PTSD and TBI is challenging and more so for providers lacking specialized training facing time pressures in primary care and other general medical settings. Diagnosis relies heavily on patient self-report and patients frequently under-report or over-report their symptoms due to stigma or seeking compensation. We aimed to create objective diagnostic screening tests utilizing Clinical Laboratory Improvement Amendments (CLIA) blood tests available in most clinical settings. CLIA blood test results were ascertained in 475 male veterans with and without PTSD and TBI following warzone exposure in Iraq or Afghanistan. Using random forest (RF) methods, four classification models were derived to predict PTSD and TBI status. CLIA features were selected utilizing a stepwise forward variable selection RF procedure. The AUC, accuracy, sensitivity, and specificity were 0.730, 0.706, 0.659, and 0.715, respectively for differentiating PTSD and healthy controls (HC), 0.704, 0.677, 0.671, and 0.681 for TBI vs. HC, 0.739, 0.742, 0.635, and 0.766 for PTSD comorbid with TBI vs HC, and 0.726, 0.723, 0.636, and 0.747 for PTSD vs. TBI. Comorbid alcohol abuse, major depressive disorder, and BMI are not confounders in these RF models. Markers of glucose metabolism and inflammation are among the most significant CLIA features in our models. Routine CLIA blood tests have the potential for discriminating PTSD and TBI cases from healthy controls and from each other. These findings hold promise for the development of accessible and low-cost biomarker tests as screening measures for PTSD and TBI in primary care and specialty settings.
PMCID:9944218
PMID: 36810280
ISSN: 2158-3188
CID: 5448152
Silent findings: Examination of asymptomatic demyelination in a pediatric US cohort
BACKGROUND AND OBJECTIVES/OBJECTIVE:Limited data is available on children with evidence of silent central nervous system demyelination on MRI. We sought to characterize the population in a US cohort and identify predictors of clinical and radiologic outcomes. METHODS:We identified 56 patients such patients who presented with incidental MRI findings suspect for demyelination, enrolled through our US Network of Pediatric Multiple Sclerosis Centers, and conducted a retrospective review of 38 patients with MR images, and examined risk factors for development of first clinical event or new MRI activity. MRI were rated based on published MS and radiologically isolated syndrome (RIS) imaging diagnostic criteria. RESULTS:One-third had a clinical attack and ¾ developed new MRI activity over a mean follow-up time of 3.7 years. Individuals in our cohort shared similar demographics to those with clinically definite pediatric-onset MS. We show that sex, presence of infratentorial lesions, T1 hypointense lesions, juxtacortical lesion count, and callosal lesions were predictors of disease progression. Interestingly, the presence of T1 hypointense and infratentorial lesions typically associated with worse outcomes were instead predictive of delayed disease progression on imaging in subgroup analysis. Additionally, currently utilized diagnostic criteria (both McDonald 2017 and RIS criteria) did not provide statistically significant benefit in risk stratification. CONCLUSION/CONCLUSIONS:Our findings underscore the need for further study to determine if criteria currently used for pediatric patients with purely radiographic evidence of demyelination are sufficient.
PMID: 36871372
ISSN: 2211-0356
CID: 5432502
Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases
PURPOSE:Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response. EXPERIMENTAL DESIGN:We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival. RESULTS:The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05). CONCLUSIONS:In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
PMCID:9957915
PMID: 36449664
ISSN: 1557-3265
CID: 5770452
Trends in concussion mechanism of injury during the COVID-19 pandemic
OBJECTIVE:The primary objective was to determine the effect of the COVID-19 pandemic on volume, demographics, and mechanisms of injury (MOI) for patients seen at an urban multidisciplinary concussion center. During the first phase of the pandemic in the United States, stay-at-home orders led to decreased group activities and required cancellation of outpatient appointments or initiation of telemedicine visits. METHODS:This study was a retrospective chart review of 3500 patient electronic medical records (EMR). Patients aged 1-99 years were eligible if they had been seen at New York University Langone Health Concussion Center during March 1-December 31, 2019 (control/pre-pandemic period) or during the same period in 2020 (pandemic period). Injury date, appointment date, age, sex, and MOI were captured; statistical analyses were performed using Stata17 (StataCorp, College Station, TX). RESULTS:There were 48% fewer visits during the COVID-19 pandemic period compared to the 2019 control period. There was a decreased proportion of pediatric patients (15% control, 6% pandemic; p = 0.007, chi-square test). Fewer concussions were related to team sports (21% control, 5% pandemic; p < 0.001), and a greater proportion were caused by bicycle accidents (4% control, 8% pandemic; p = 0.037) and assault/domestic violence (3% control, 9% pandemic; p < 0.001). CONCLUSION/CONCLUSIONS:The relative proportions of concussion MOI, age distributions, and visit volumes were significantly associated with pre-pandemic vs. pandemic periods, suggesting that COVID-19 changed concussion epidemiology during the pandemic period. This study demonstrates how epidemiologic data may inform future resource allocation during public health emergencies.
PMCID:9797225
PMID: 36608628
ISSN: 1878-5883
CID: 5410162
Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data
Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo. These particles could have been produced during the post-inflationary epoch and match the relic abundance of dark matter inferred today. The nonobservation of the signatures searched for allows us to derive a bound on the reduced coupling constant of gauge interactions in the dark sector: α_{X}≲0.09, for 10^{9}≲M_{X}/GeV<10^{19}. Conversely, we obtain that, for instance, a reduced coupling constant α_{X}=0.09 excludes masses M_{X}≳3×10^{13} GeV. In the context of dark matter production from gravitational interactions alone, we illustrate how these bounds are complementary to those obtained on the Hubble rate at the end of inflation from the nonobservation of tensor modes in the cosmological microwave background.
PMID: 36827568
ISSN: 1079-7114
CID: 5911432
Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC)
Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants"™ response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.
SCOPUS:85148608165
ISSN: 2296-858x
CID: 5445692
Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation
Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.
PMCID:9973654
PMID: 36695309
ISSN: 2047-9980
CID: 5857802
Author Correction: Dysautonomia and REM sleep behavior disorder contributions to progression of Parkinson's disease phenotypes
PMID: 36739278
ISSN: 2373-8057
CID: 5449162
Evaluating sleep in covert encephalopathy with wearable technology: results from the WATCHES study
BACKGROUND AND AIMS:Covert HE (CHE) is a common early stage of HE associated with poor outcomes. Available neuropsychiatric diagnostic testing is underutilized and has significant clinical limitations. Sleep deterioration is consistently associated with CHE and HE; however, objective data is sparse and it has not been studied longitudinally. We longitudinally study and describe an association of sleep metrics with CHE as detected by a commercial wearable technology. METHODS:We monitored sleep for 6 months using a commercial fitness tracker in 25 participants with cirrhosis, hypothesizing that CHE as diagnosed by psychometric testing would be associated with significant reductions in sleep quality, especially restorative sleep (deep sleep + rapid eye movement). Mixed-effects modeling was performed to evaluate sleep factors associated with CHE and developed and internally validated a score based on these sleep metrics for associated CHE. RESULTS:Across 2862 nights with 66.3% study adherence, we found that those with CHE had consistently worse sleep, including an average of 1 hour less of nightly restorative sleep, driven primarily by reductions in rapid eye movement. A model including albumin, bilirubin, rapid eye movement, sleep disturbances, and sleep consistency showed good discrimination (area under the receiver operating curve=0.79) for CHE status with a sensitivity of 76% and specificity of 69%. CONCLUSIONS:Our large longitudinal study of sleep in cirrhosis suggests that sleep derangements in CHE can be detected using wearable technology. Given the known importance of sleep to overall health and CHE/HE to prognosis in cirrhosis, the ability to associate dynamic sleep metrics with CHE may in the future help with the detection and passive monitoring as factors that precipitate decompensation of cirrhosis become better understood and mobile health data validation and integration improves.
PMID: 36724117
ISSN: 2471-254x
CID: 5923592
