Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study.

The Brain Injury and Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (BIMA), sponsored by the Department of Defense, is a randomized, double-blind, sham-controlled trial of hyperbaric oxygen (HBO2) in service members with persistent post-concussive symptoms following mild TBI, undergoing comprehensive assessments. The clinical EEG was assessed by neurologists for slow wave activity, ictal/interictal epileptiform abnormalities, and background periodic discharges. There is scant literature about EEG findings in this population, so we report baseline clinical EEG results and explore associations with other evaluations, including demographics, medication, neurological assessments, and clinical MRI outcomes. Seventy-one participants were enrolled: median age 32 years, 99% male, 49% comorbid PTSD, 28% with mTBI in the previous year, 32% blast injuries only, and 73% multiple injuries. All participants reported medication use (mean medications = 8, SD = 5). Slowing was present in 39%: generalized 37%, localized 8%, both 6%. No other abnormalities were identified. Slowing was not significantly associated with demographics, medication or neurological evaluation. Participants without EEG abnormalities paradoxically had significantly higher number of white matter hyperintensities as identified on MRI (p = 0.003). EEG slowing is present in more than one-third of participants in this study without evidence of associations with demographics, medications or neurological findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.

Diuretics and epilepsy: will the past and present meet?

Clinical studies from over half a century ago suggested efficacy of a variety of diuretics in focal and generalized epilepsies as well as in status epilepticus, but these findings have not been translated into modern epilepsy training or practice. Recent advances in our understanding of neuronal maturation and the pathophysiology of neonatal seizures provide fresh insight into the mechanisms by which diuretics might reduce susceptibility to seizures. In vitro and in vivo rodent studies and human epilepsy surgical cases have shown that specific diuretic agents targeting the cation-chloride cotransporters decrease neuronal synchrony and neuronal hyperexcitability. These agents are thought to convey their antiepileptic activity by either expanding the extracellular space or promoting a cellular chloride transport balance that reflects a more developmentally "mature," less excitable state. It may be time to reexamine whether diuretics could serve as adjunctive therapies in the treatment of refractory epilepsies.

Electrographic seizure monitoring with a novel, wireless, single-channel EEG sensor.

OBJECTIVE: Recording seizures using personal seizure diaries can be challenging during everyday life and many seizures are missed or mis-reported. People living with epilepsy could benefit by having a more accurate and objective wearable EEG system for counting seizures that can be used outside of the hospital. The objective of this study was to (1) determine which seizure types can be electrographically recorded from the scalp below the hairline, (2) determine epileptologists' ability to identify electrographic seizures from single-channels extracted from full-montage wired-EEG, and (3) determine epileptologists' ability to identify electrographic seizures from Epilog, a wireless single-channel EEG sensor. METHODS: Epilog sensors were worn concurrently during epilepsy monitoring unit (EMU) monitoring. During standard-of-care review, epileptologists were asked if the electrographic portion of the seizure was visible on single channels of wired electrodes at locations proximal to Epilog sensors, and if focal-onset, which electrode was closest to the focus. From these locations, single channels of EEG extracted from wired full-montage EEG and the proximal Epilog sensor were presented to 3 blinded epileptologists along with markers for when known seizures occurred (taken from the standard-of-care review). Control segments at inter-ictal times were included as control. The epileptologists were asked whether a seizure event was visible in the single channel EEG record at or near the marker. RESULTS: A total of 75 seizures were recorded from 22 of 40 adults that wore Epilog during their visit to the EMU. Epileptologists were able to visualize known seizure activity on at least one of the wired electrodes proximal to Epilog sensors for all seizure events. Epileptologists accurately identified seizures in 71% of Epilog recordings and 84% of single-channel wired recordings and were 92% accurate identifying seizures with Epilog when those seizures ended in a clinical convulsion compared to those that did not (>55%). CONCLUSIONS: Epileptologists are able to visualize seizure activity on single-channels of EEG at locations where Epilog sensors are easily placed on the scalp below hairline. Manual review of seizure annotations can be done quickly and accurately (>70% TP and >98% PPV) on single-channel EEG data. Reviewing single-channel EEG is more accurate than what has been reported in the literature on self-reporting seizures in seizure diaries, the current standard of care for seizure counting outside of the EMU. SIGNIFICANCE: Wearable EEG will be important for seizure monitoring outside of the hospital. Epileptologists can accurately identify seizures in single-channel EEG, better than patient self-reporting in diaries based on the literature. Automated or semi-automated seizure detection on single channels of EEG could be used in the future to objectively count seizures to complement the standard of care outside of the EMU without the overt burden upon epileptologist review.

Wearable Reduced-Channel EEG System for Remote Seizure Monitoring.

Epitel has developed Epilog, a miniature, wireless, wearable electroencephalography (EEG) sensor. Four Epilog sensors are combined as part of Epitel's Remote EEG Monitoring platform (REMI) to create 10 channels of EEG for remote patient monitoring. REMI is designed to provide comprehensive spatial EEG recordings that can be administered by non-specialized medical personnel in any medical center. The purpose of this study was to determine how accurate epileptologists are at remotely reviewing Epilog sensor EEG in the 10-channel "REMI montage," with and without seizure detection support software. Three board certified epileptologists reviewed the REMI montage from 20 subjects who wore four Epilog sensors for up to 5 days alongside traditional video-EEG in the EMU, 10 of whom experienced a total of 24 focal-onset electrographic seizures and 10 of whom experienced no seizures or epileptiform activity. Epileptologists randomly reviewed the same datasets with and without clinical decision support annotations from an automated seizure detection algorithm tuned to be highly sensitive. Blinded consensus review of unannotated Epilog EEG in the REMI montage detected people who were experiencing electrographic seizure activity with 90% sensitivity and 90% specificity. Consensus detection of individual focal onset seizures resulted in a mean sensitivity of 61%, precision of 80%, and false detection rate (FDR) of 0.002 false positives per hour (FP/h) of data. With algorithm seizure detection annotations, the consensus review mean sensitivity improved to 68% with a slight increase in FDR (0.005 FP/h). As seizure detection software, the automated algorithm detected people who were experiencing electrographic seizure activity with 100% sensitivity and 70% specificity, and detected individual focal onset seizures with a mean sensitivity of 90% and mean false alarm rate of 0.087 FP/h. This is the first study showing epileptologists' ability to blindly review EEG from four Epilog sensors in the REMI montage, and the results demonstrate the clinical potential to accurately identify patients experiencing electrographic seizures. Additionally, the automated algorithm shows promise as clinical decision support software to detect discrete electrographic seizures in individual records as accurately as FDA-cleared predicates.

End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: a case series of six patients.

OBJECTIVE: Specific psychological withdrawal symptoms following the cessation of treatment with many drugs that affect the central nervous system, including anxiolytics and antidepressants, have been well documented. Studies have investigated withdrawal symptoms associated with some of the older antiepileptic drugs, but the potential for withdrawal symptoms associated with newer antiepileptic drugs, including lamotrigine, has not yet been investigated. METHODS: Using a retrospective chart review, we identified six patients with epilepsy who reported transient emergent psychological symptoms during stable, chronic lamotrigine monotherapy. RESULTS: These symptoms included anxiety, emotional lability, and irritability. In each case, the symptoms resulted in marked subjective distress and reliably occurred in the 1-2h before the patients were due to take their next dose of medication. CONCLUSIONS: Lamotrigine withdrawal symptoms exist and can occur as an end-of-dose phenomenon, even in patients on stable medication doses. End-of-dose withdrawal from lamotrigine is a clinically significant adverse effect that can hamper successful treatment with this medication.

Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. METHODS: Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus. RESULTS: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16-0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Practice Guideline Summary: Sudden Unexpected Death in Epilepsy Incidence Rates and Risk Factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. METHODS: Systematic review of evidence; modified Grading Recommendations Assessment, Development and Evaluation process for developing conclusions; recommendations developed by consensus. RESULTS: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% CI 0.16-0.31) (high confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Treatment strategies in Landau-Kleffner syndrome and paraictal psychiatric and cognitive disturbances.

Psychiatric and cognitive disturbances of the peri-ictal period (i.e., the seizure prodrome and the postictal period) can be considered paraictal disturbances, as they are directly related to the ictal event. There are also certain interictal psychiatric and cognitive disturbances that become apparent concomitantly with the onset of a seizure disorder and remit and/or significantly improve upon its remission. Such disorders also fall under the classification paraictal disorders, and are exemplified by Landau-Kleffner syndrome (LKS), a disorder in which language and psychiatric disturbances begin with the onset of epileptic activity and improve upon its disappearance. In this article, we review the treatment of paraictal cognitive and psychiatric disorders presenting as preictal and postictal psychiatric disturbances and LKS.

Insulation discontinuity in a vagus nerve stimulator lead: a treatable cause of intolerable stimulation-related symptoms.

Discontinuity in the silicone insulation over an electrode of a left vagus nerve stimulator (VNS) allowed the aberrant leak of current to the phrenic nerve and other structures. This resulted in ipsilateral diaphragmatic dysfunction, inability to vocalize, and severe radiating pain into the jaw and upper incisor for the duration of each stimulation. The device was explanted and a new device was implanted. All stimulation-related symptoms ceased immediately. A similar discontinuity in the silicone insulation is the likely explanation for several prior reports of poorly understood pains and phrenic nerve stimulation in patients with VNSs. The findings and analysis of this case establish a rationale for consideration of replacement of the VNS lead in all similarly symptomatic patients.