Faculty Bibliography
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563
Operationale Klassifikation der Anfallsformen durch die Internationale Liga gegen Epilepsie: Positionspapier der ILAE-Klassifikations- und Terminologiekommission
The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of this revision is to recognize that some seizure types can have either a focal or generalized onset, to enable a classification when the onset is unobserved, to include some missing seizure types and to implement a more transparent and understandable nomenclature. Because current knowledge is insufficient to form a scientifically based classification, the 2017 classification is operational (practical) and based on the 1981 classification with the amendments from 2010. The changes include the following: (1) "partial" becomes "focal"; (2) awareness (disturbance of consciousness) is used as a classification criterion of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic and secondarily generalized are eliminated, (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional, (5) epileptic spasms as well as atonic, clonic, myoclonic and tonic seizures can have a focal or generalized onset, (6) focal (seizure with progression) to (a) bilateral tonic-clonic seizure replaces secondarily generalized seizure, (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic seizures and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change but enables greater flexibility and transparency in naming seizure types.
EMBASE:624862024
ISSN: 1610-0646
CID: 3514702
Common data elements (CDEs) for preclinical epilepsy research: Introduction to CDEs and description of core CDEs. A TASK3 report of the ILAE/AES joint translational task force
Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.
PMID: 30450483
ISSN: 2470-9239
CID: 3479282
Preclinical common data elements (CDEs) for epilepsy: A joint ILAE/AES and NINDS translational initiative
PMCID:6210037
PMID: 30450482
ISSN: 2470-9239
CID: 3479272
Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age
OBJECTIVE:To determine how early lamotrigine clearance (LTG-CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG-CL/F to estradiol concentrations and gestational week. METHODS:This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed-effects modeling approach was used to describe the relationship between LTG-CL/F and gestational week and between LTG-CL/F and estradiol. Akaike information criterion (AIC) compared goodness of fit between final models and a generalized estimating equation to compare differences between low and high percentage LTG-CL/F change groups (p < 0.05). RESULTS:Twenty-five pregnancies (22 participants) were available. Increases in LTG-CL/F were present at 5 weeks gestational age. Both estradiol and gestational week were highly correlated with LTG-CL/F changes; LTG-CL/F increased at the rate of 0.115l/h for every gestational week and 0.844l/h for every 1ng/ml of estradiol, with women in the high LTG-CL/F percentage change group changing at a faster rate (p < 0.001). Models using gestational week performed better than models using estradiol. INTERPRETATION/CONCLUSIONS:Gestational week was a better predictor of changes in LTG-CL/F than estradiol concentration and may reflect additional factors, although neither was robust enough to use clinically due to substantial interpatient variability. Changes in LTG-CL/F begin as early as the 5th gestational week, often before women know they are pregnant, emphasizing the importance of planning and early detection of pregnancy and consideration of early implementation of therapeutic drug monitoring. Ann Neurol 2018;84:556-563.
PMID: 30168175
ISSN: 1531-8249
CID: 3387002
Migraine comorbidity and cognitive performance in patients with focal epilepsy [Meeting Abstract]
ISI:000452730900208
ISSN: 1129-2369
CID: 3587662
Fertility and Birth Outcomes in Women With Epilepsy Seeking Pregnancy
Importance/UNASSIGNED:Prior studies report lower birth rates for women with epilepsy (WWE) but have been unable to differentiate between biological and social contributions. To our knowledge, we do not have data to inform WWE seeking pregnancy if their likelihood of achieving pregnancy is biologically reduced compared with their peers. Objective/UNASSIGNED:To determine if WWE without a prior diagnosis of infertility or related disorders are as likely to achieve pregnancy within 12 months as their peers without epilepsy. Design, Setting, and Participants/UNASSIGNED:The Women With Epilepsy: Pregnancy Outcomes and Deliveries study is an observational cohort study comparing fertility in WWE with fertility in control women (CW) without epilepsy. Participants were enrolled at 4 academic medical centers and observed up to 21 months from November 2010 to May 2015. Women seeking pregnancy aged 18 to 40 years were enrolled within 6 months of discontinuing contraception. Exclusion criteria included tobacco use and a prior diagnosis of infertility or disorders that lower fertility. Eighteen WWE and 47 CW declined the study, and 40 WWE and 170 CW did not meet study criteria. The Women With Epilepsy: Pregnancy Outcomes and Deliveries electronic diary app was used to capture data on medications, seizures, sexual activity, and menses. Data were analyzed from November 2015 to June 2017. Main Outcomes and Measures/UNASSIGNED:The primary outcome was proportion of women who achieved pregnancy within 12 months after enrollment. Secondary outcomes were time to pregnancy using a proportional hazard model, pregnancy outcomes, sexual activity, ovulatory rates, and analysis of epilepsy factors in WWE. All outcomes were planned prior to data collection except for time to pregnancy. Results/UNASSIGNED:Of the 197 women included in the study, 142 (72.1%) were white, and the mean (SD) age was 31.9 (3.5) years among the 89 WWE and 31.1 (4.2) among the 108 CW. Among 89 WWE, 54 (60.7%) achieved pregnancy vs 65 (60.2%) among 108 CW. Median time to pregnancy was no different between the groups after controlling for key covariates (WWE: median, 6.0 months; 95% CI, 3.8-10.1; CW: median, 9.0 months; 95% CI, 6.5-11.2; P = .30). Sexual activity and ovulatory rates were similar in WWE and CW. Forty-four of 54 pregnancies (81.5%) in WWE and 53 of 65 pregnancies (81.5%) in CW resulted in live births. No epilepsy factors were significant. Conclusions and Relevance/UNASSIGNED:Women with epilepsy seeking pregnancy without prior known infertility or related disorders have similar likelihood of achieving pregnancy, time to pregnancy, and live birth rates compared with their peers without epilepsy.
PMID: 29710218
ISSN: 2168-6157
CID: 3246972
Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society
OBJECTIVE:To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS:The 2004 AAN criteria were used to systematically review literature (January 2003-November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS:Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. RECOMMENDATIONS/CONCLUSIONS:Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect-related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.
PMID: 29898971
ISSN: 1526-632x
CID: 3155242
Influences of temporal lobe epilepsy and temporal lobe resection on olfaction
Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.
PMCID:6239967
PMID: 29767353
ISSN: 1432-1459
CID: 4085052
Analysis of shared heritability in common disorders of the brain
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
PMCID:6097237
PMID: 29930110
ISSN: 1095-9203
CID: 3157462
Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology
Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect-related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.
PMID: 30254527
ISSN: 1535-7597
CID: 3315752
