Physician distress when treatments fail. Survey on physician distress when treating persons with drug-resistant epilepsy and knowledge of neuropalliative care.

OBJECTIVE: Drug-resistant epilepsy can be difficult to cure and may pose emotional challenges for epilepsy providers. Neuropalliative care (NPC) can augment quality of life (QOL) in persons with neurological diseases and may add meaningful elements to the treatment repertoire of epilepsy specialists even if seizures continue. However, NPC has not been widely implemented in epilepsy. Our study aimed to determine whether physicians of persons with drug-resistant epilepsy (PWDRE) experience distress when faced with treatment failure (Engel class ≥ 2), either failure of medications-only (PWDREmo) or of both medications and surgery (procedures with curative intent (PWDREms)). Furthermore, we evaluated physician knowledge about and referrals to NPC following treatment failures to help improve patient QOL despite ongoing seizures. METHODS: An anonymous online survey was distributed to US epilepsy physicians through the American Epilepsy Society website and personal email to assess levels of distress experienced when caring for PWDREmo and PWDREms (7-point Likert scale ["1" = "no distress", "7" = "most distress ever felt"]), and knowledge and use of NPC. RESULTS: Eighty-two physicians completed the survey. Most experienced distress when epilepsy treatments failed: 59% felt moderate distress (≥4) with PWDREmo (median "4", mean 3.74, range 1-7), 90% suffered moderate to severe distress (5, 5.17, 1-7) with PWDREms. Distress over PWDREms was significantly greater than distress over PWDREmo (p < 0.0001). Forty-three percent reported confidence in their knowledge about NPC. Only 15% were likely to refer PWDREmo to NPC, while 44% would consider it for PWDREms. CONCLUSION: Among survey responders, physician distress was high when confronted with treatment failures, especially the failure of epilepsy surgery. Fewer than half of responders were likely to refer patients to NPC. Further research is necessary to determine extent, reasons, and effects of physician distress and whether improved understanding of and patient access to NPC would help alleviate physician distress when faced with treatment failures in PWDRE.

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.

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.

Would people living with epilepsy benefit from palliative care?

Palliative care (PC) is an approach to the care of persons living with serious illness and their families that focuses on improving quality of life and reducing suffering by addressing complex medical symptoms, psychosocial needs, spiritual well-being, and advance care planning. While PC has traditionally been associated with hospice care for persons with cancer, there is now recognition that PC is relevant to many noncancer diagnoses, including neurologic illness, and at multiple points along the illness journey, not just end of life. Despite the recent growth of the field of neuropalliative care there has been scant attention paid to the relevance of PC principles in epilepsy or the potential for PC approaches to improve outcomes for persons living with epilepsy and their families. We believe this has been a significant oversight and that PC may provide a useful framework for addressing the many sources of suffering facing persons living with epilepsy, for engaging patients and families in challenging conversations, and to focus efforts to improve models of care for this population. In this manuscript we review areas of significant unmet needs where a PC approach may improve patient and family-centered outcomes, including complex symptom management, goals of care, advance care planning, psychosocial support for patient and family and spiritual well-being. When relevant we highlight areas where epilepsy patients may have unique PC needs compared to other patient populations and conclude with suggestions for future research, clinical, and educational efforts.

Quantitative EEG Biomarkers for Mild Traumatic Brain Injury.

PURPOSE: The development of objective biomarkers for mild traumatic brain injury (mTBI) in the chronic period is an important clinical and research goal. Head trauma is known to affect the mechanisms that support the electrophysiological processing of information within and between brain regions, so methods like quantitative EEG may provide viable indices of brain dysfunction associated with even mTBI. METHODS: Resting-state, eyes-closed EEG data were obtained from 71 individuals with military-related mTBI and 82 normal comparison subjects without traumatic brain injury. All mTBI subjects were in the chronic period of injury (>5 months since the time of injury). Quantitative metrics included absolute and relative power in delta, theta, alpha, beta, high beta, and gamma bands, plus a measure of interhemispheric coherence in each band. Data were analyzed using univariate and multivariate methods, the latter coupled to machine learning strategies. RESULTS: Analyses revealed significant (P < 0.05) group level differences in global relative theta power (increased for mTBI patients), global relative alpha power (decreased for mTBI patients), and global beta-band interhemispheric coherence (decreased for mTBI patients). Single variables were limited in their ability to predict group membership (e.g., mTBI vs. control) for individual subjects, each with a predictive accuracy that was below 60%. In contrast, the combination of a multivariate approach with machine learning methods yielded a composite metric that provided an overall predictive accuracy of 75% for correct classification of individual subjects as coming from control versus mTBI groups. CONCLUSIONS: This study indicates that quantitative EEG methods may be useful in the identification, classification, and tracking of individual subjects with mTBI.

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.

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.

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.

Pre-admission clinical factors affect length of stay in the epilepsy monitoring unit.

OBJECTIVE: Video-EEG monitoring in the epilepsy monitoring unit (EMU) is a limited clinical resource. Knowledge of the predicting factors for length of stay (LOS) in the EMU may allow providers to more efficiently utilize EMU bed space. METHODS: The records for all consecutive admissions to the EMU at the University of Colorado Hospital between December 1, 2010 and May 31, 2011 (n = 142) were retrospectively reviewed. RESULTS: Univariate analyses focusing on variables known prior to admission showed that EMU LOS (in hours) was not significantly correlated with patient age, number of event types, or number of antiepileptic drugs at admission. Patients who were admitted to the EMU for event characterization had statistically significantly shorter average LOS than patients who had been admitted as a part of a presurgical evaluation. Patients who reported < = 1 seizure per week had a statistically significantly higher average LOS than patients who reported >= 1 seizure per day. These variables were also significantly predictive of total LOS (p < 0.0001 and p = 0.03, respectively) in multivariate analysis. SIGNIFICANCE: Pre-admission clinical variables may predict EMU LOS. These factors could be used at the administrative level for maximum EMU resource utilization.

Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS: Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS: 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION: SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING: Commission of European Affairs of the International League Against Epilepsy.

Disrobing associated with epileptic seizures and forensic implications.

Little is known about the clinical aspects and medico-legal consequences of disrobing in the context of epileptic seizures. Seizure-related disrobing may occur either as an ictal automatism or during the postictal period. Some patients may experience a seizure while already in the unclothed state, engage in ictal wandering, and thereby appear in public in the nude. Two cases involving disrobing associated with seizures captured via video-monitored electroencephalography are offered. An additional case reveals the legal consequences endured by one patient who experienced a nocturnal seizure and began wandering in an unclothed state. Collectively, these cases illustrate the medical reality of seizure-related disrobing and the related adverse effects on patients' quality of life. Disrobing associated with epileptic seizures carries the potential for serious legal consequences if not properly identified as an ictal phenomenon.

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.

Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two deaths in video-EEG-monitored patients.

Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in patients with epilepsy, with cardiorespiratory dysfunction and a primary cessation of cerebral function proposed as causes. We report two cases of SUDEP in patients with intractable temporal lobe epilepsy undergoing video-EEG (electroencephalography) telemetry at two centers. Both had secondarily generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes in these two patients are reported herein. Ictal/postictal hypoventilation may contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure of recovery of cortical function and eventual cardiac failure.

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.

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.

Topiramate in older patients with partial-onset seizures: a pilot double-blind, dose-comparison study.

PURPOSE: Pharmacokinetics of antiepileptic drugs (AEDs) can be altered by age-related changes in physiology, thereby altering clinical effects, especially tolerability, in older adults. We compared two dosages of topiramate (TPM) in a pilot study of patients >or=60 years of age with partial-onset seizures. METHODS: In this 24-week, double-blind, randomized, parallel-group study, patients with one or more seizures in previous 6 months were randomized to treatment with 50 or 200 mg/day TPM. TPM was initiated as monotherapy or added to one AED and titrated by 25 mg/day per week to target or maximum tolerated dose as the concomitant AED, if any, was withdrawn. RESULTS: Thirty-eight patients were randomized to the 50 mg/day TPM (mean age, 68 years) and 39-200 mg/day TPM (69 years). Seizure control was similar with the two dosages when TPM could be used as monotherapy, whereas 200 mg TPM was more effective than 50 mg in patients requiring adjunctive therapy. The overall incidence of adverse events was similar for the two dosages--66% with 50 mg and 62% with 200 mg TPM. Most common adverse events were somnolence (TPM 50, 13%; TPM 200, 8%), dizziness (13% vs. 8%), and headache (13% vs. 5%). Of 10 (13%) patients reporting a cognitive-related adverse event, six patients were assigned to the 50-mg group. A total of 14 patients (18%; seven in each group) discontinued TPM due to adverse events. CONCLUSIONS: This pilot study supports the practice of using low-to-moderate dosages of AEDs in older adults.

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.