Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.

OBJECTIVE: Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. METHODS: Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. RESULTS: Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). SIGNIFICANCE: LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.

Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy.

OBJECTIVE: We analyzed current prescribing patterns for antiepileptic drugs (AEDs) in pregnant women with epilepsy (PWWE) at 20 USA tertiary epilepsy centers. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women from December 2012 to January 2016. Inclusion criteria for PWWE included ages 14-45 years and up to 20 weeks gestational age. Exclusion criteria included history of psychogenic nonepileptic spells, expected intelligence quotient (IQ) <70, other major medical illness, progressive cerebral disease, and switching AEDs in pregnancy prior to enrollment. RESULTS: Three hundred fifty-one PWWE were enrolled in the MONEAD study, which included 259 (73.8%) on monotherapy, 77 (21.9%) on polytherapy, and 15 (4.3%) on no AEDs. The most common AED monotherapy regimens were lamotrigine (42.1% of monotherapies), levetiracetam (37.5%), carbamazepine (5.4%), zonisamide (5.0%), oxcarbazepine (4.6%), and topiramate (3.1%). All other individual monotherapies were each <1%. The most common AED polytherapy combination was lamotrigine + levetiracetam (42.9% of polytherapies), followed by lacosamide + levetiracetam (6.5%), lamotrigine + zonisamide (5.2%), and all other remaining combinations (each <4%); only 5.2% of polytherapy subjects were on ≥3 AEDs (1.1% of total PWWE). Only four subjects (1.1%) were on valproate (1 monotherapy, 3 polytherapy). CONCLUSIONS: The distribution of AED use likely reflects current prescribing patterns for PWWE cared for in USA tertiary epilepsy centers. This distribution has changed markedly since the turn of the century, but changes in the general population remain uncertain.

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile.

Utility of foramen ovale electrodes in mesial temporal lobe epilepsy.

OBJECTIVES: To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE). METHODS: We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision. RESULTS: Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months). SIGNIFICANCE: More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation.

Neuroimaging in the evaluation of epilepsy.

Neuroimaging has provided extraordinary insight into the pathologic substrate of epilepsy. The excellent spatial resolution and soft tissue contrast of magnetic resonance imaging (MRI) allows identification of a substantial number of pathologies including hippocampal sclerosis, malformations of cortical development, low grade tumors, and vascular abnormalities, among others. Complementary imaging modalities such as positron emission tomography, single photon emission computed tomography, and magnetoencephalography can be diagnostically helpful as well. Identification of a pathologic substrate is particularly important in patients with medically refractory epilepsy who are undergoing evaluation for surgery, and essential in determining the likelihood of seizure freedom after surgical intervention. This article reviews current and emerging neuroimaging techniques in the field of epilepsy.

Foramen ovale electrodes in the evaluation of epilepsy surgery: conventional and unconventional uses.

Foramen ovale (FO) electrodes have been used in the evaluation of epilepsy surgery for more than 25 years. Their traditional application was in patients with mesial temporal lobe epilepsy. Due in part to advances in neuroimaging, their use has declined. We describe our cumulative experience with FO electrodes and use examples to illustrate a range of indications for FO recordings that extend beyond their conventional utility for mesial temporal lobe cases. We also summarize the pros and cons of FO electrodes implantation and attempt to reestablish their utility in presurgical evaluation.

Neuromodulation in Drug Resistant Epilepsy.

Epilepsy affects approximately 70 million people worldwide, and it is a significant contributor to the global burden of neurological disorders. Despite the advent of new AEDs, drug resistant-epilepsy continues to affect 30-40% of PWE. Once identified as having drug-resistant epilepsy, these patients should be referred to a comprehensive epilepsy center for evaluation to establish if they are candidates for potential curative surgeries. Unfortunately, a large proportion of patients with drug-resistant epilepsy are poor surgical candidates due to a seizure focus located in eloquent cortex, multifocal epilepsy or inability to identify the zone of ictal onset. An alternative treatment modality for these patients is neuromodulation. Here we present the evidence, indications and safety considerations for the neuromodulation therapies in vagal nerve stimulation (VNS), responsive neurostimulation (RNS), or deep brain stimulation (DBS).

Cognitive outcomes following laser interstitial therapy for mesiotemporal epilepsies.

OBJECTIVE: To provide a review of cognitive outcomes across a full neuropsychological profile in patients who underwent laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). METHODS: We examined cognitive outcomes following LiTT for mTLE by reviewing a consecutive series of 26 patients who underwent dominant or nondominant hemisphere procedures. Each patient's pre- and postsurgical performance was examined for clinically significant change (>1SD improvement or decline on standardized scores), with a neuropsychologic battery that included measures of language, memory, executive functioning, and processing speed. RESULTS: Presurgical performance was largely consistent with previous research, where patients suffering from dominant hemisphere epilepsies demonstrated deficits in verbal learning and memory, whereas patients with nondominant hemisphere scored lower on visually mediated tests. Case-by-case review comparing presurgical to postsurgical scores revealed clinically significant improvement in both dominant and nondominant patients in learning and memory and other aspects of cognition such as processing speed and executive functioning. Of the few patients who did experience clinically significant decline following LiTT, a greater proportion had undergone dominant hemisphere procedures. CONCLUSIONS: Compared with the outcome literature of dominant open anterior temporal lobectomies (ATLs), where postsurgical decline has been documented in up to 40%-60% of cases, our LiTT case series exhibited a much lower incidence of postoperative language or verbal memory decline. Moreover, promising rates of postoperative improvements were also observed across multiple cognitive domains. Future studies exploring cognitive outcomes following LiTT should include comprehensive neuropsychological findings, rather than only select domains, as clinically significant change can occur in areas other than those typically associated with mesiotemporal structures.

Is Spontaneity Overrated? The Value of Cortical Stimulation-Induced Seizures.

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Cutting the Losses of Pregnant Women With Epilepsy.

Association of Unintended Pregnancy With Spontaneous Fetal Loss in Women With Epilepsy: Findings of the Epilepsy Birth Control RegistryHerzog AG, Mandle HB, MacEachern DB. JAMA Neurol. 2018. doi:10.1001/jamaneurol.2018.3089. [Epub ahead of print] PMID: 30326007. IMPORTANCE: If unintended pregnancy is common among women with epilepsy and is associated with increased risk of spontaneous fetal loss (SFL), it is important to develop guidelines for safe and effective contraception for this community. OBJECTIVE: To assess whether planned pregnancy is a determinant of SFL in women with epilepsy. DESIGN, SETTING, AND PARTICIPANTS: The Epilepsy Birth Control Registry conducted this web-based, retrospective survey between 2010 and 2014. It gathered demographic, epilepsy, antiepileptic drug (AED), contraceptive, and reproductive data from 1144 women with epilepsy in the community between ages 18 and 47 years. Data were analyzed between March 2018 and May 2018. Main outcomes and measures The primary outcome was the risk ratio (RR) with 95% confidence intervals (CIs) for SFL in unplanned versus planned pregnancies. The secondary outcome was the identification of some potentially modifiable variables (maternal age, pregnancy spacing, and AED category) of SFL versus live birth using binary logistic regression. RESULTS: The participants were proportionally younger (mean [standard deviation] age, 28.5 [6.8] years), and 39.8% had household incomes of $25 000 or less. Minority women represented only 8.7% of the participants. There were 530 (66.8%) of 794 unplanned pregnancies and 264 (33.2%) of 794 planned pregnancies. The risk of SFL in 653 unaborted pregnancies in women with epilepsy was greater for unplanned (n = 137 of 391; 35.0%) than planned (n = 43 of 262; 16.4%) pregnancies (RR: 2.14; 95% CI: 1.59-2.90; P < .001). Regression analysis found that the risk of SFL was greater when planning was entered alone (odds ratio [OR], 2.75; 95% CI: 1.87-4.05; P < .001) and more so when adjusted for maternal age, interpregnancy interval, and AED category (OR: 3.57; 95% CI: 1.54-8.78; P = .003). Interpregnancy interval (OR: 2.878; 95% CI: 1.8094-4.5801; P = .008) and maternal age (OR: 0.957; 95% CI: 0.928-0.986 for each year from 18 to 47 years; P = .02), but not AED category, were also associated. The risk was greater when interpregnancy interval was less than 1 year (n = 56 of 122; 45.9%) versus greater than 1 year (n = 56 of 246; 22.8%; RR: 2.02; 95% CI: 1.49-2.72; P < .001). Relative to the younger than 18 years cohort (n = 15 of 29; 51.7%), the risks were lower for the intermediate older cohort aged 18 to 27 years (n = 118 of 400; 29.5%; RR: 0.57; 95% CI: 0.39-0.84; P < .004) and the cohort aged 28 to 37 years (n = 44 of 212; 20.8%; RR: 0.40; 95% CI: 0.26-0.62; P < .001) but not significantly different for the small number of participants in the aged 38 to 47 years cohort (n = 3 of 12; 25.0%). No individual AED category's SFL frequency differed significantly from the no AED category. CONCLUSIONS AND RELEVANCE: The Epilepsy Birth Control Registry retrospective survey finding that unplanned pregnancy in women with epilepsy may double the risk of SFL warrants prospective investigation with outcome verification.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Mesial Temporal Epilepsy: A Case Series Analysis of Outcomes and Complications at 2-Year Follow-Up.

BACKGROUND: Laser interstitial thermal therapy (LITT) presents an important new minimally invasive tool in the management of drug-resistant mesial temporal epilepsy (MTE). However, because of its relative novelty, not much is known about long-term seizure freedom rates. The objective of this study was to evaluate the postsurgical seizure outcome following LITT after a minimum follow-up period of 2 years. METHODS: Medical records of all patients who underwent LITT for MTE from 2013 to 2018 at our comprehensive epilepsy center under a single surgeon were retrospectively reviewed. Data related to demographics, presurgical evaluations, and seizure outcome were compared between seizure-free (SF) and non-seizure-free (NSF) patients. RESULTS: In all, 26 patients were identified with at least 2 years of follow-up. Mean age was 43.8 years ± 11.6 years, and 46.2% were female. After a mean follow-up time of 42.9 months (range, 24.3-58.8 months), 61.5% (16/26) were free of disabling seizures, and 26.9% (7/26) had only rare disabling seizures. Whereas seizure-freedom rates between patients with and without mesial temporal sclerosis (MTS) were not statistically different (68% vs. 43%, P = 0.23), NSF patients without MTS had a shorter median time to first seizure than did NSF patients with MTS (0.55 month vs. 10 months, log-rank test P = 0.007). Postoperative complications occurred in 2 patients (7.7%), consisting of 1 permanent and 1 transient homonymous hemianopia. CONCLUSIONS: LITT appears to be a safe and effective initial surgical option for treatment-resistant MTE. Among patients who have seizures after treatment, those without MTS appear to have seizures earlier than those with MTS.

Issues for Women with Epilepsy.

Epilepsy and antiepileptic drugs affect the menstrual cycle, aspects of contraception, reproductive health, pregnancy, and menopause through alteration of sex steroid hormone pathways. Sex steroid hormones often have an effect on seizure frequency and may alter the level of some antiepileptic drugs. Approximately one-third of women experience an increase in perimenstrual and/or periovulatory seizure frequency. Some women experience an increase in seizure frequency during pregnancy. Balancing maternal seizure control and the risk of congenital malformations associated with fetal antiepileptic drug exposure may be challenging. Some antiepileptic drugs are associated with cognitive and behavioral teratogenesis and should be avoided if possible during pregnancy.

New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel.

Ezogabine, clobazam, and perampanel are among the newest antiseizure drugs approved by the Food and Drug Administration between 2011 and 2012. Ezogabine and perampanel are approved for adjunctive treatment of partial epilepsy. Perampanel is also approved for adjunctive treatment of primary generalized tonic-clonic seizures. Ezogabine and perampanel have novel mechanisms of action. Ezogabine binds to voltage-gated potassium channels and increases the M-current thereby causing membrane hyperpolarization. Perampanel is a selective, non-competitive 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist, which reduces neuronal excitation. Clobazam has been used worldwide since the 1970s and is approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. Clobazam is the only 1,5-benzodiazepine currently in clinical use, which is less sedating than the commonly used 1,4-benzodiazepines. Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated efficacy and good tolerability of these 3 new antiepileptic drugs. These drugs represent a welcome addition to the armamentarium of practitioners, but it remains to be seen how they will affect the landscape of pharmacoresistant epilepsy.

Neurodevelopmental effects of fetal antiepileptic drug exposure.

Many studies investigating cognitive outcomes in children of women with epilepsy report an increased risk of mental impairment. Verbal scores on neuropsychometric measures may be selectively more involved. While a variety of factors contribute to the cognitive problems of children of women with epilepsy, antiepileptic drugs (AEDs) appear to play a major role. The mechanisms by which AEDs affect neurodevelopmental outcomes remain poorly defined. Animal models suggest that AED-induced apoptosis, altered neurotransmitter environment, and impaired synaptogenesis are some of the mechanisms responsible for cognitive and behavioral teratogenesis. AEDs that are known to induce apoptosis, such as valproate, appear to affect children's neurodevelopment in a more severe fashion. Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains, and these appear to persist at least until the age of 6. Some studies have shown neurodevelopmental deficiencies associated with the use of phenobarbital and possibly phenytoin. So far, most of the investigations available suggest that fetal exposures to lamotrigine or levetiracetam are safer with regard to cognition when compared with other AEDs. Studies on carbamazepine show contradictory results, but most information available suggests that major poor cognitive outcomes should not be attributed to this medication. Overall, children exposed to polytherapy prenatally appear to have worse cognitive and behavioral outcomes compared with children exposed to monotherapy, and with the unexposed. There is an increase risk of neurodevelopmental deficits when polytherapy involves the use of valproate versus other agents.

Defining the role of the academic neurohospitalist in residency education.

OBJECTIVE: We sought to better understand the potential impact of the burgeoning neurohospitalist model of inpatient care on education of neurology residents and to better define possible roles for "neurohospitalists" in residency education. METHOD: We designed a brief qualitative open-ended survey directed toward academic leaders in neurology and distributed it by e-mail to every academic neurology department in the United States and Canada. RESULTS: Of 83 respondents, 36 (43%) had an active neurohospitalist program and only 10% felt certain they would not have 1 within the next 5 years. All respondents expected to have residents continue to be involved with inpatient care. The main perceived advantage for resident education associated with neurohospitalists was inpatient care expertise, and the main expected disadvantage was decreased exposure to subspecialty attendings. The majority anticipated positive impact on all Accreditation Council for Graduate Medical Education core competencies predominantly based on neurohospitalists' expertise in the inpatient setting. CONCLUSION: The majority of academic neurology departments are expected to have a neurohospitalist program within the next 5 years. There are several perceived advantages and disadvantages to such a program for education of neurology residents. In general, the impact of these programs is expected to improve resident education. Regardless of expectations, neurohospitalists will likely play a prominent role in the education of the next generation of neurologists.

A quick and reliable EEG montage for the detection of seizures in the critical care setting.

Obtaining an emergent EEG for the diagnosis of nonconvulsive status epilepticus and conconvulsive seizures in the intensive care unit raises logistic problems in most hospitals. Previous studies have looked into the hairline EEG for a broader population than the critically ill, with controversial conclusions. The authors created a montage sufficiently simple to be performed and interpreted by residents and rapidly achievable to meet the time constraints of a busy on-call schedule. Seven electrodes (Fp1, Fp2, T3, T4, O1, O2, and Cz), easily applied without the need for tape measure by using only anatomic landmarks (pupils, ears, vertex, and inion), were used to configure three different montages: double diamond, circumferential, and Cz referential. EEG records obtained with the full 10-20 system in critically ill patients were reformatted into these montages and reviewed retrospectively independently by neurology attending physicians with expertise in EEG interpretation and senior neurology residents. A comparison was done with the previously studied hairline EEG. The average sensitivity of the study montage for seizure detection was 92.5%, whereas the average specificity was 93.5%. These results suggest that the seven-electrode montage could potentially be a quick and reliable EEG montage for the detection of seizures in the intensive care unit, when technical support is not available. Further prospective studies are required to validate these promising results in a larger population sample.