Optimizing Surgical Planning for Epilepsy Patients With Multimodal Neuroimaging and Neurophysiology Integration: A Case Study.

Current preoperative evaluation of epilepsy can be challenging because of the lack of a comprehensive view of the network's dysfunctions. To demonstrate the utility of our multimodal neurophysiology and neuroimaging integration approach in the presurgical evaluation, we present a proof-of-concept for using this approach in a patient with nonlesional frontal lobe epilepsy who underwent two resective surgeries to achieve seizure control. We conducted a post-hoc investigation using four neuroimaging and neurophysiology modalities: diffusion tensor imaging, resting-state functional MRI, and stereoelectroencephalography at rest and during seizures.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort.

Background And Objectives: To identify the prevalence of EEG abnormalities in patients with coronavirus disease 2019 (COVID-19) with neurologic changes, their associated neuroimaging abnormalities, and rates of mortality.

Methods: A retrospective case series of 192 adult COVID-19-positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications (ASMs), metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed.

Intracranial EEG Validation of Single-Channel Subgaleal EEG for Seizure Identification.

Purpose: A device that provides continuous, long-term, accurate seizure detection information to providers and patients could fundamentally alter epilepsy care. Subgaleal (SG) EEG is a promising modality that offers a minimally invasive, safe, and accurate means of long-term seizure monitoring.

Methods: Subgaleal EEG electrodes were placed, at or near the cranial vertex, simultaneously with intracranial EEG electrodes in 21 epilepsy patients undergoing intracranial EEG studies for up to 13 days.

Cerebrovascular Complications of COVID-19.

Background And Purpose: 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.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

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.

Racial differences in adult-onset MRI-negative temporal lobe epilepsy.

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.

Hippocampal volumetric integrity in mesial temporal lobe epilepsy: A fast novel method for analysis of structural MRI.

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.

The brain connectome as a personalized biomarker of seizure outcomes after temporal lobectomy.

Objective: We examined whether individual neuronal architecture obtained from the brain connectome can be used to estimate the surgical success of anterior temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE).

Methods: We retrospectively studied 35 consecutive patients with TLE who underwent ATL. The structural brain connectome was reconstructed from all patients using presurgical diffusion MRI.

Utility of magnetic resonance spectroscopic imaging for human epilepsy.

This review discusses the potential utility of broad based use of magnetic resonance (MR) spectroscopic imaging for human epilepsy and seizure localization. The clinical challenges are well known to the epilepsy community, intrinsic in the variability of location, volumetric size and network extent of epileptogenic tissue in individual patients. The technical challenges are also evident, with high performance requirements in multiple steps, including magnet homogeneity, detector performance, sequence design, speed of acquisition in addition to large territory spectral processing.

Quantitative assessment of corpus callosum morphology in periventricular nodular heterotopia.

We investigated systematic differences in corpus callosum morphology in periventricular nodular heterotopia (PVNH). Differences in corpus callosum mid-sagittal area and subregional area changes were measured using an automated software-based method. Heterotopic gray matter deposits were automatically labeled and compared with corpus callosum changes.

Neuroimaging the epileptogenic process.

Epilepsy is one of the most common chronic neurological conditions worldwide. Anti-epileptic drugs (AEDs) can suppress seizures, but do not affect the underlying epileptic state, and many epilepsy patients are unable to attain seizure control with AEDs. To cure or prevent epilepsy, disease-modifying interventions that inhibit or reverse the disease process of epileptogenesis must be developed.

Long-term behavioral, electrophysiological, and neurochemical monitoring of the safety of an experimental antiepileptic implant, the muscimol-delivering Subdural Pharmacotherapy Device in monkeys.

Object: The authors evaluated the extent to which the Subdural Pharmacotherapy Device (SPD), chronically implanted over the frontal cortex to perform periodic, localized muscimol-delivery/CSF removal cycles, affects overall behavior, motor performance, electroencephalography (EEG) activity, and blood and CSF neurochemistry in macaque monkeys.

Methods: Two monkeys were used to adjust methodology and 4 monkeys were subjected to comprehensive testing. Prior to surgery, the animals' behavior in a large test chamber was monitored, and the motor skills required to remove food pellets from food ports located on the walls of the chamber were determined.

A developmental and genetic classification for malformations of cortical development: update 2012.

Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported.

Autoradiographic evidence for the transmeningeal diffusion of muscimol into the neocortex in rats.

Electrophysiological and behavioral studies have demonstrated that muscimol administered through the cranial meninges can prevent focal neocortical seizures. It was proposed that transmeningeal muscimol delivery can be used for the treatment of intractable focal neocortical epilepsy. However, it has not been proved that muscimol administered via the transmeningeal route can penetrate into the neocortex.

An implantable triple-function device for local drug delivery, cerebrospinal fluid removal and EEG recording in the cranial subdural/subarachnoid space of primates.

Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts.

Bottom-of-sulcus dysplasia: imaging features.

Objective: Dysplasia at the bottom of a sulcus is a subtle but distinct malformation of cortical development relevant to epilepsy. The purpose of this study was to review the imaging features important to the clinical diagnosis of this lesion.

Materials And Methods: All cases recognized as typical bottom-of-sulcus dysplasia in our comprehensive epilepsy program over the period 2002-2007 were included in the study.

Periodic transmeningeal muscimol maintains its antiepileptic efficacy over three weeks without inducing tolerance, in rats.

Periodic transmeningeal administration of muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug.

Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area.

Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity.

Evolution and prospects for intracranial pharmacotherapy for refractory epilepsies: the subdural hybrid neuroprosthesis.

Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling.

Comparison of the antiepileptic properties of transmeningeally delivered muscimol, lidocaine, midazolam, pentobarbital and GABA, in rats.

This study compared the potencies of epidurally delivered muscimol, lidocaine, midazolam, pentobarbital and gamma-aminobutyric acid (GABA) to prevent focal neocortical seizures induced by locally applied acetylcholine (Ach), in rats (n=5). An epidural cup was chronically implanted over the right somatosensory cortex in each animal, with epidural EEG electrodes placed posterior to the edge of the cup. After recovery, either artificial cerebrospinal fluid (ACSF; control solution) or one of the five drugs was delivered into epidural cup, followed by Ach administration into the cup to induce seizures.

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: therapeutic implications.

Purpose: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity.

Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys.

Voltage-gated potassium channel antibody-mediated syndromes: a spectrum of clinical manifestations.

Immune-related neurologic disorders have long been recognized. A number of specific targets have been identified, including neurons, Purkinje cells, and pre- and postsynaptic receptors. Over the past decade, antibodies against voltage-gated potassium channels (VGKCs) have been reported in a number of neurologic syndromes, such as neuromyotonia, limbic encephalitis, and Morvan's syndrome.

The interactions between sleep and epilepsy.

The interactions between sleep and epilepsy have been recognized for centuries. The electroencephalogram and more recently the polysomnogram have helped us understand these interactions. Certain epilepsy syndromes are more common during sleep, and frequently a sleep disorder is misdiagnosed as epilepsy.