Naymee Velez-Ruiz

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.

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.

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.

Utility of foramen ovale electrodes in mesial temporal lobe epilepsy.

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).

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.

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.

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.

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.

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.