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Objective We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)-resistant vs ASM-responsive outcome for patients with idiopathic generalized epilepsy (IGE). Methods This was a case-control study of ASM-resistant cases and ASM-responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient. We then compared characteristics of cases vs controls using multivariable logistic regression to develop a predictive model of ASM-resistant IGE. Results We identified 118 ASM-resistant cases and 114 ASM-responsive controls with IGE. First, we confirmed our recent finding that catamenial epilepsy is associated with ASM-resistant IGE (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.32-10.41, for all study subjects) after covariate adjustment. Other independent factors seen with ASM resistance include certain seizure-type combinations (absence, myoclonic, and generalized tonic-clonic seizures [OR 7.06, 95% CI 2.55-20.96]; absence and generalized tonic-clonic seizures [OR 4.45, 95% CI 1.84-11.34]), as well as EEG markers of increased generalized spike-wave discharges (GSWs) in sleep (OR 3.43, 95% CI 1.12-11.36 for frequent and OR 7.21, 95% CI 1.50-54.07 for abundant discharges in sleep) and the presence of generalized polyspike trains (GPTs; OR 5.49, 95% CI 1.27-38.69). The discriminative ability of our final multivariable model, as measured by area under the receiver-operating characteristic curve, was 0.80. Significance Multiple clinical and EEG characteristics independently predict ASM resistance in IGE. To improve understanding of a patient's prognosis, clinicians could consider asking about specific seizure-type combinations and track whether they experience catamenial epilepsy. Obtaining prolonged EEG studies to record the burden of GSWs in sleep and assessing for the presence of GPTs may provide additional predictive value.

This article provides an overview of the pathogenesis and risk factors associated with antiepileptic drug (AED) hypersensitivity reactions, provides prescribing guidelines that may minimize the risk of antiepileptic induced rashes, and discusses treatment options for rashes. Articles indexed in PubMed, Science Citation, and Google Scholar (January 1946-March 2019) were systematic searched using the following key terms: hypersensitivity, rash, antiepileptic, epilepsy, cross-sensitivity, desensitization, patch testing and supplemented with our clinical experiences. Additional references were identified from a review of literature citations. AEDs are associated with cutaneous adverse reactions. Aromatic AEDs and higher titration rates are associated with increased risk of hypersensitivity reaction. Patient characteristics, underlying health conditions, and genetic variations may increase the likelihood of a hypersensitivity reaction. Once a hypersensitivity reaction occurs, the likelihood of cross sensitivity to another AED increases, especially among other aromatic AEDs. Withdrawal of the causal agent and initiation of a lower risk agent usually leads to resolution of symptoms. Desensitization protocols may be an option for patients whose seizures only respond to the AED causing the rash.

To investigate the performance of seizure detection methods and nursing staff response in our epilepsy monitoring unit (EMU).We retrospectively reviewed 38 EMU patient admissions over a 1-year period capturing 133 epileptic and non-epileptic seizures with associated video-EEG data. We recorded detailed seizure event characteristics for further analysis.Rates of seizure detection, alarm usage, and time to nursing response varied by seizure type. Patients self-activated the push button (PB) alarm for 31.1% of all seizures, but only 8.9% of focal impaired awareness (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS). In comparison, the Persyst automated seizure alarm reliably detected both electrographic seizures (76.2% of electrographic seizures) and FIAS/FBTCS (87.2% of FIAS/FBTCS), with a false positive alarm rate (FAR) of 0.14/hour, or every 7.3 h. 11.4% of all seizures went unrecognized by nursing staff, of which the majority (80.0%) were FIAS. The PB alarm was of higher yield for alerting nurses to focal aware seizures (FAS) and psychogenic non-epileptic seizures (PNES) versus FIAS and FBTCS (p 0.001). In contrast, nurses relied more on the automated Persyst software alarm to detect FIAS (p 0.001). Time to nursing response was no different following audible alarm onset for the PB compared to the Persyst alarms (p = 0.14).Automated seizure detection software plays an important role in our EMU in seizure recognition, particularly for alerting nurses to FIAS. More rigorous studies are needed to determine the best utilization of various monitoring techniques and to promote high quality standards and patient safety in the EMU.

Implantable neural stimulators represent an advanced treatment adjunct to medication for pharmacoresistant epilepsy and alternative for patients that are not good candidates for resective surgery. Three treatment modalities are currently FDA-approved: vagus nerve stimulation, responsive neurostimulation, and deep brain stimulation. These devices were originally trialed in very similar patient populations with focal epilepsy, but head-to-head comparison trials have not been performed. As such, device selection may be challenging due to large overlaps in clinical indications and efficacy. Here we will review the data reported in the original pivotal clinical trials as well as long-term experience with these technologies. We will highlight differences in their features and mechanisms of action which may help optimize device selection on a case-by-case basis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-019-00727-2) contains supplementary material, which is available to authorized users.

Simple Summary Current estimates by GLOBOCAN now incorporate NPC as a malignancy discrete from other head and neck malignancies among the 36 disease locales assessed. Based on the latest report, the global cancer burden is estimated to have risen to 19.3 million new cases, and 9.6 million malignancies were recorded in 2020 throughout the world. The study has clinical implications and could improve treatment decision-making and post-treatment care. The study could also motivate future clinical research and development in the arena of NPC prognostic biomarkers.ve men and one in every six women develops cancer during their lifetime, and one out of eight men and one in every 11 women progresses to chronic stage. The study has clinical implications and could improve treatment decision-making and post-treatment care. The study could also motivate future clinical research and development in the arena of NPC prognostic biomarkers. Abstract Background: Nasopharyngeal carcinoma (NPC), a relatively uncommon malignancy in the Western world, is highly prevalent in Southeast Asia where the treatment outcomes are poor. Despite recent improvements in diagnosis and treatment locoregional control, distant metastasis and chemoresistance continue to be a significant cause of mortality. Identification of a reliable and comprehensive prognostic biomarker is highly desirable. The potential relevance of microRNAs (miRNAs) as prognostic markers in NPC is assessed in this systematic review and meta-analysis. Methods: A systematic review was performed using the PubMed and Science Direct databases. The search was limited to search results between 2018 and 2020 with the keywords and search strings developed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The recovered articles were carefully screened based on the selection criteria. In the meta-analysis study, high and low expression levels of miRNAs were measured using the hazard ratio (HR) and 95 percent confidence interval (CI) for patients’ survival outcomes. Egger’s bias indicator test and funnel plot symmetry were used to assess the risk of bias. Results: Amongst the 25 studies, 13 fulfilled the conditions of inclusion in this meta-analysis. The researchers further delved into the 21 miRNA expression levels from 3015 NPC patients to ascertain a link between miRNA’s predictive role and survival outcomes. The majority of the articles retrieved during this study were from China, with two studies from Canada and Malaysia. The overall pooled effect size estimation (HR) for dysregulated miRNAs was 1.590 (95% CI: 1.253–2.017), displaying that miRNA marker expression increased the risk of mortality in NPC patients by 59%. Conclusions: This meta-analysis is novel and looks at the prognostic significance of miRNAs as biomarkers in NPC patients using a continuous version pooled meta-analysis. Although our findings are ambiguous, they do show that greater miRNA expression in NPC may be associated with a lower overall survival rate. To acquire clear conclusions, more prospective studies with large cohorts are required to determine the clinical utility of miRNAs as prognostic biomarkers.

Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019. We applied prespecified queries for admissions coded as follows: 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.

Objective Obstructive sleep apnea (OSA) is common in patients with epilepsy (PWE), and treatment may improve seizure control. However, OSA is often undiagnosed in PWE, and understanding of the risk profile for OSA is important. In this study, we sought to determine if OSA risk is similar in patients with generalized versus focal epilepsy. Methods We recruited 115 patients presenting to the Rutgers-Robert Wood Johnson Epilepsy Clinic with focal or generalized epilepsy. Obstructive sleep apnea risk was assessed using the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Demographic and clinical information was gathered from the electronic medical record. Unadjusted and adjusted analyses were carried out to assess differences in the SA-SDQ between patients with generalized versus focal epilepsy. Further analyses were done to assess the relationship between seizure frequency, epilepsy type, and the SA-SDQ. Results Unadjusted mean SA-SDQ scores, as well as scores high enough to represent likely OSA, were similar in patients with generalized versus focal epilepsy. However, in adjusted analyses, patients with generalized epilepsy had a significantly higher mean SA-SDQ score. Older age, higher body mass index (BMI), and a history of hypertension (HTN) were also associated with higher SA-SDQ scores. Sleep Apnea Scale of the Sleep Disorders Questionnaire scores were not significantly affected by the presence of a seizure within the prior one month or six months. Average ESS scores and the percentage of scores consistent with an abnormal degree of sleepiness were statistically similar in patients with generalized versus focal epilepsy. Significance Our study suggests that patients with generalized epilepsy have a higher risk of OSA. Further studies measuring OSA directly as well as assessing potential benefits of treatment are needed.

Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016–2019. We applied prespecified queries for admissions coded as follows: 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis., Highlights • Code-based queries identify elective EMU admissions from a hospital billing dataset • Inclusion of diagnoses required by payers for EMU admission increased accuracy • Use of these queries may facilitate monitoring of EMU utilization in large cohorts.

Lacosamide (LCM) is a novel antiepileptic drug (AED) approved by the FDA for adjunctive treatment of partial epilepsy with and without secondary generalization. Lacosamide dose-dependent dysrhythmias (PR-interval prolongation, AV block, and atrial fibrillation/flutter) have been reported. This case represents the first instance of LCM-induced atrial fibrillation following a low loading dose (200mg). Risk factors for atrial fibrillation are addressed and discussed in the context of this case. Full cardiac history is recommended prior to patients being initiated on LCM. Cardiac monitoring may be required for at-risk patients on LCM. Clinicians need to be cognizant of this potential adverse effect.

Standardized research terminology critical to the establishment of a multicenter intensive care unit (ICU) electroencephalogram (EEG) database was originally proposed in 2005 and has been modified many times since. However, interrater agreement (IRA) of the revised terminology has not been investigated.After a brief tutorial, investigators of ICU EEG research centers (n = 16) took an 82-question EEG certification test comprising 10-second EEG samples, which assessed the use of main term 1 (pattern location), main term 2 (pattern type), and modifiers from the most recently revised terminology.Kappa values for main terms 1 and 2 were 0.87 and 0.92, respectively. Agreement was 93% for determination of amplitude and 80% for determination of frequency. Kappa values for each of the "plus" modifiers (fast, rhythmic, and sharp/spike activity) were 0.54, 0.62, and 0.16 respectively.Main terms 1 and 2 have high IRA and are reasonable for use in multicenter research. There is a suggestion that assessment of amplitude has good reliability, while assessment of frequency may have less reliability. The fast and rhythmic "plus" modifiers have moderate IRA, while sharp/spike modifier has only slight IRA implying that further refinement and assessment of terminology modifiers may be necessary.

Therapeutic hypothermia is being utilized as a neuro-protective strategy in neonates, children, and adults. The most common indications are hypoxic ischemic encephalopathy in neonates and post cardiac arrest in adults. Electroencephalographic monitoring use is increasing in critical care units, and is sometimes a component of therapeutic hypothermia clinical pathways. Monitoring may detect non-convulsive seizures or non-convulsive status epilepticus, and it may provide prognostic information. We review data regarding indications for therapeutic hypothermia and electroencephalographic monitoring in neonatal, pediatric, and adult critical care units, and discuss technical aspects related to such monitoring.

Blocking the development of epilepsy (epileptogenesis) is a fundamental research area with the potential to provide large benefits to patients by avoiding the medical and social consequences that occur with epilepsy and lifelong therapy. Human clinical trials attempting to prevent epilepsy (antiepileptogenesis) have been few and universally unsuccessful to date. In this article, we review data about possible pathophysiological mechanisms underlying epileptogenesis, discuss potential interventions, and summarize prior antiepileptogenesis trials. Elements of ideal trials designs for successful antiepileptogenic intervention are suggested.

Brain tissue oxygen (PbtO(2)) monitors are utilized in a threshold-based fashion, triggering actions based on the presumption of tissue compromise when PbtO(2) is less than 20 mmHg. Some early published practice guidelines suggest that seizure is a potential culprit when PbtO(2) crosses this threshold; evidence for this is not well defined.Data were collected manually as part of a prospective observational database. PbtO(2) monitors and continuous electroencephalogram (cEEG) were placed by clinical protocol in aneurysmal subarachnoid hemorrhage (aSAH) or traumatic brain injury (TBI) patients with a Glasgow Coma Scale (GCS) ≤ 8. Eight patients with discrete seizures during an overlapping monitored period were identified. Probability of seizure when PbtO(2) value was20 mmHg (and the inverse) were calculated.There were 343 distinct seizure episodes and 1797 PbtO(2) measurements. 8.9% of seizures were followed by a PbtO(2) value below 20 mmHg. Of all observed low PbtO(2) values, 3.8% were associated with seizure. Seizure length did not influence PbtO(2). Two patients with the highest number of seizures developed low PbtO(2) values post-seizure.Seizures were neither associated with a PbtO(2) value of20 mmHg nor associated with a drop in PbtO(2) value across a clinically significant threshold. However, we cannot rule out the existence of any relationship between PbtO(2) and seizure with this limited data set. Prospective research using electronically recorded data is required to more effectively examine the relationship between PbtO(2) and seizure.

Levetiracetam (LEV) is a novel antiepileptic drug (AED) approved for the adjunctive treatment of generalized and partial seizures. LEV has no clinically significant drug interactions and has limited adverse effects. The psychiatric adverse effects of LEV include de novo psychosis, affective disorder, and aggression. LEV-induced suicidal behavior has been reported infrequently with a past history of affective disorders. The authors report an apparent dose/concentration-dependent LEV-induced de novo major depression with near fatal suicide attempt in a patient without prior history of affective disorder. Psychiatric evaluation with emphasis on historic/current affective disorders, impulsive–aggressive behaviors, and assessment of risk factors for suicidal behaviors is indicated in treating patients with epilepsy with LEV. Clinicians should consider therapeutic drug monitoring to optimize therapeutic LEV treatment.

Purpose Anterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. Methods MEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6–12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. Results 350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. Conclusions This decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

Topiramate (TPM) is effective for multiple seizure types and epilepsy syndromes in children and adults. Topiramate has adverse effects (including cognitive, depression, renal stones), but many of these are low incidence when started at a low dose and slowly titrated to 100 to 200 mg/day. Also, TPM has proven benefit for migraine, obesity, eating disorders, and alcohol use disorders, which can be comorbid in patients with epilepsy and may also be effective in subpopulations within specific psychiatric diagnoses. Recently approved extended-release formulations of TPM (Trokendi and Qudexy in the United States) have reliable data supporting their safety and efficacy for patients with epilepsy. They have potential for more rapid titration within 1 month to 200 mg/day and have better patient retention than TPM immediate-release, but there are no robust double-blind randomized controlled trials comparing the different formulations. We expect the once per day extended-release formulations to improve medication adherence compared with the twice per day formulations. This has significant potential to improve outcomes in epilepsy and the other TPM-responsive disorders.

Surgical resection for well-selected patients with refractory epilepsy provides seizure freedom approximately two-thirds of the time. Despite this, many good candidates for surgery, after a presurgical workup, ultimately do not consent to a procedure. The reasons why patients decline potentially effective surgery are not completely understood. We explored the socio cultural, medical, personal, and psychological differences between candidates who chose (n = 23) and those who declined surgical intervention (n = 9). We created a novel questionnaire addressing a range of possible factors important in patient decision making. We found that patients who declined surgery were less bothered by their epilepsy (despite comparable severity), more anxious about surgery, and less likely to listen to their doctors (and others) and had more comorbid psychiatric disease. Patients who chose surgery were more embarrassed by their seizures, more interested in being “seizure-free”, and less anxious about specific aspects of surgery. Patient attitudes, beliefs, and anxiety serve as barriers to ideal care. These results can provide opportunities for education, treatment, and intervention. Additionally, patients who fit a profile of someone who is likely to defer surgery may not be appropriate for risky and expensive presurgical testing.

Many patients with epilepsy are on lifelong therapy with antiepileptic drugs (AEDs), and AEDs are used for other conditions such as mood stabilization and headache prophylaxis. These drugs have high potential for clinically significant interaction with nonepilepsy drugs. Interactions occur largely through altered pharmacokinetics. One drug may increase the hepatic clearance of another, leading to attenuated efficacy of the affected drug. Alternatively, inhibition of liver metabolism by one drug can cause acute toxicity by reducing clearance of another drug. To identify potential drug interactions before they lead to toxicity or therapy failure, the treating clinician should combine knowledge of the patient’s overall history with a general knowledge of comorbid conditions in which significant interactions involving AEDs are most likely to occur. Treatments susceptible to interactions include anticoagulants, antiarrhythmics, antibiotics, antiretroviral drugs, immunosuppressives, antineoplastics, and contraceptives. Therefore, it is important to obtain periodically a thorough history of medical problems, use of medications or herbal remedies, and adverse effects of medications. Physicians managing epilepsy patients should also strive to avoid potential drug interactions by favoring low-interaction AEDs in patients taking many other types of drugs. There is quite a large degree of patient heterogeneity in the extent of any given interaction between an AED and another drug. Indeed, some groups of patients may have different susceptibilities to such interactions because of genetic and environmental influences on drug metabolism. Effective treatment with AEDs should include attention to drug interactions.