Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke. We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection. METHODS:Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020. Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior. RESULTS:<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality. CONCLUSIONS:COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

Coronavirus disease 2019 (COVID-19) is a highly infectious pandemic caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It frequently presents with unremitting fever, hypoxemic respiratory failure, and systemic complications (e.g., gastrointestinal, renal, cardiac, and hepatic involvement), encephalopathy, and thrombotic events. The respiratory symptoms are similar to those accompanying other genetically related beta-coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). Hypoxemic respiratory symptoms can rapidly progress to Acute Respiratory Distress Syndrome (ARDS) and secondary hemophagocytic lymphohistiocytosis, leading to multi-organ system dysfunction syndrome. Severe cases are typically associated with aberrant and excessive inflammatory responses. These include significant systemic upregulation of cytokines, chemokines, and pro-inflammatory mediators, associated with increased acute-phase proteins (APPs) production such as hyperferritinemia and elevated C-reactive protein (CRP), as well as lymphocytopenia. The neurological complications of SARS-CoV-2 infection are high among those with severe and critical illnesses. This review highlights the central nervous system (CNS) complications associated with COVID-19 attributed to primary CNS involvement due to rare direct neuroinvasion and more commonly secondary CNS sequelae due to exuberant systemic innate-mediated hyper-inflammation. It also provides a theoretical integration of clinical and experimental data to elucidate the pathogenesis of these disorders. Specifically, how systemic hyper-inflammation provoked by maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate CNS innate immune signaling pathways, and induce para-infectious autoimmunity, potentially contributing to the CNS complications associated with SARS-CoV-2 infection. Direct viral infection of the brain parenchyma causing encephalitis, possibly with concurrent neurovascular endotheliitis and CNS renin angiotensin system (RAS) dysregulation, is also reviewed.

OBJECTIVE:To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS:We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS:We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE/CONCLUSIONS:Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

BACKGROUND AND PURPOSE/OBJECTIVE:In this study, we used power analysis to calculate required sample sizes to detect group-level changes in quantitative neuroanatomical estimates derived from MRI scans obtained from multiple imaging centers. Sample size estimates were derived from (i) standardized 3T image acquisition protocols and (ii) nonstandardized clinically acquired images obtained at both 1.5 and 3T as part of the multicenter Human Epilepsy Project. Sample size estimates were compared to assess the benefit of standardizing acquisition protocols. METHODS:Cortical thickness, hippocampal volume, and whole brain volume were estimated from whole brain T1-weighted MRI scans processed using Freesurfer v6.0. Sample sizes required to detect a range of effect sizes were calculated using (i) standard t-test based power analysis methods and (ii) a nonparametric bootstrap approach. RESULTS:A total of 32 participants were included in our analyses, aged 29.9 ± 12.62 years. Standard deviation estimates were lower for all quantitative neuroanatomical metrics when assessed using standardized protocols. Required sample sizes per group to detect a given effect size were markedly reduced when using standardized protocols, particularly for cortical thickness changes <.2 mm and hippocampal volume changes <10%. CONCLUSIONS:The use of standardized protocols yielded up to a five-fold reduction in required sample sizes to detect disease-related neuroanatomical changes, and is particularly beneficial for detecting subtle effects. Standardizing image acquisition protocols across scanners prior to commencing a study is a valuable approach to increase the statistical power of multicenter MRI studies.

Seizures are an infrequent and serious neurological complication of SARS-CoV-2 infection, with limited data describing the etiology and the clinical context in which these occur or the associated electrographic and imaging findings. This series details four cases of seizures occurring in patients with COVID-19 with distinct time points, underlying pathology, and proposed physiological mechanisms. An enhanced understanding of seizure manifestations in COVID-19 and their clinical course may allow for earlier detection and improved patient management.

OBJECTIVE:We recently detected a significant racial difference in our population with temporal lobe epilepsy (TLE) at the University of Alabama at Birmingham (UAB) seizure monitoring unit. We found that Black patients were more likely than their White counterparts to carry a TLE diagnosis. Using this same patient population, we focus on the patients with TLE to better describe the relationship between race and epidemiology in this population. METHODS:We analyzed the data from patients diagnosed with TLE admitted to the UAB seizure monitoring unit between January 2000 and December 2011. For patients with a video electroencephalography (EEG) confirmed diagnosis of TLE (n = 385), basic demographic information including race and magnetic resonance imaging (MRI) findings were collected. Descriptive statistics and multivariate logistic regression were used to explore the relationship between MRI findings, demographic data, and race. RESULTS:For Black patients with TLE, we found that they were more likely to be female (odds ratio [OR] = 1.91, 95% confidence interval [CI]: 1.14-3.19), have seizure onset in adulthood (OR = 2.39, 95% CI: 1.43-3.19), and have normal MRIs (OR = 1.69, 95% CI: 1.04-2.77) compared to White counterparts with TLE after adjusting for covariates. CONCLUSIONS:These data suggest that Black race (compared to White) is associated with higher expression of adult-onset MRI-negative TLE, an important subtype of epilepsy with unique implications for evaluation, treatment, and prognosis. If validated in other cohorts, the findings may explain the lower reported rates of epilepsy surgery utilization among Blacks. The racial differences in surgical utilization could be due to a greater prevalence of an epilepsy that is less amenable to surgical resection rather than to cultural differences or access to care.

OBJECTIVE:We investigate whether a rapid and novel automated MRI processing technique for assessing hippocampal volumetric integrity (HVI) can be used to identify hippocampal sclerosis (HS) in patients with mesial temporal lobe epilepsy (mTLE) and determine its performance relative to hippocampal volumetry (HV) and visual inspection. METHODS:We applied the HVI technique to T1-weighted brain images from healthy control (n = 35), mTLE (n = 29), non-HS temporal lobe epilepsy (TLE, n = 44), and extratemporal focal epilepsy (EXTLE, n = 25) subjects imaged using a standardized epilepsy research imaging protocol and on non-standardized clinically acquired images from mTLE subjects (n = 40) to investigate if the technique is translatable to clinical practice. Performance of HVI, HV, and visual inspection was assessed using receiver operating characteristic (ROC) analysis. RESULTS:mTLE patients from both research and clinical groups had significantly reduced ipsilateral HVI relative to controls (effect size: -0.053, 5.62%, p =  0.002 using a standardized research imaging protocol). For lateralizing mTLE, HVI had a sensitivity of 88% compared with a HV sensitivity of 92% when using specificity equal to 70%. CONCLUSIONS:The novel HVI approach can effectively detect HS in clinical populations, with an average image processing time of less than a minute. The fast processing speed suggests this technique could have utility as a quantitative tool to assist with imaging-based diagnosis and lateralization of HS in a clinical setting.

There are no functional imaging based biomarkers for pharmacological treatment response in temporal lobe epilepsy (TLE). In this study, we investigated whether there is an association between resting state functional brain connectivity (RsFC) and seizure control in TLE. We screened a large database containing resting state functional magnetic resonance imaging (Rs-fMRI) data from 286 epilepsy patients. Patient medical records were screened for seizure characterization, EEG reports for lateralization and location of seizure foci to establish uniformity of seizure localization within patient groups. Rs-fMRI data from patients with well-controlled left TLE, patients with treatment-resistant left TLE, and healthy controls were analyzed. Healthy controls and cTLE showed similar functional connectivity patterns, whereas trTLE exhibited a significant bilateral decrease in thalamo-hippocampal functional connectivity. This work is the first to demonstrate differences in neural network connectivity between well-controlled and treatment-resistant TLE. These differences are spatially highly focused and suggest sites for the etiology and possibly treatment of TLE. Altered thalamo-hippocampal RsFC thus is a potential new biomarker for TLE treatment resistance.

OBJECTIVE:The majority of the 65 million people worldwide with epilepsy live in low- and middle-income countries. Many of these countries have inadequate resources to serve the large patient population affected by epilepsy. Panama is a middle-income country that currently has only 2 facilities that can provide basic epilepsy services and no epilepsy surgery services. To address this need, a group of Panamanian physicians partnered with U.S. epilepsy health care providers to test a hybrid epilepsy surgery program, combining resources and expertise. METHODS:From 2011 to 2017, a multidisciplinary team of neurologists, neurosurgeons, and an electroencephalography (EEG) technician from the United States traveled to Panama 6 times and, in collaboration with the local team, performed surgical procedures for intractable epilepsy at the national children's hospital. Resective surgeries were performed with intraoperative electrocorticography and/or implantation of subdural and depth electrodes and extra-operative monitoring. Cost was calculated using Panama government data. RESULTS:Twenty-seven children with intractable epilepsy were surgically treated. Fifteen children are seizure-free (Engle class I), 11 children are Engel II, and one child is Engel III. No major morbidity or mortality occurred, with only one postoperative infection. The average cost of treatment was calculated at $9850 per patient. SIGNIFICANCE/CONCLUSIONS:This program is a model for creating a multinational and multi-institutional collaboration to provide surgical epilepsy treatment in a middle-income country without an adequate infrastructure. To be successful, this collaboration needed to address medical, technical, and cultural challenges. This partnership helps to alleviate some of the present need for surgical epilepsy services while laying the groundwork for the development of a future local independent epilepsy surgery program.