Epilepsy & Behavior

From 1000 studies published in 2007 on all aspects of autism, those that reached clear conclusions or included quantitative data were selected for this review. Possible etiologies include elemental metals, especially the inconsistent evidence regarding mercury from the vaccine preservative thimerosal, not used after 2001, and chromosomes and genes with the conclusion that autism has a complex genetic architecture. Also, various parental conditions are considered, as are many different abnormalities in the central nervous system, especially underconnectivity within the cortex. Furthermore, deficiencies in mirror neurons have been proposed, leading to the "theory of mind" explanation that autistic children tend to disregard others. In addition, various global deficiencies, like an increase in inhibitory synaptic transmission, are proposed. Characteristics of these children include selective (inward) attention; underresponsiveness; stereotyped repetitive motor behavior; increased head size, weight, and height; various cognitive and communicative disorders; and also epilepsy. Therapy has emphasized risperidone, but some atypical antipsychotic medications have been helpful, as have robotic aids, massage, hyperbaric oxygen, and music. Nearly every conceivable problem that a child could have can be observed in these unfortunate children.

We performed positron emission tomography using [carbonyl-(11)C]WAY-100635, a serotonin 1A (5-HT(1A)) receptor antagonist, in 13 patients with temporal lobe epilepsy (TLE) and in 13 controls. 5-HT(1A) receptor distribution mapping allowed correct lateralization of the epileptogenic temporal lobe in all patients. 5-HT(1A) receptor binding potential (BP(ND)) was significantly reduced in almost all temporal regions of the epileptogenic lobe. Compared with controls, the patients had significantly decreased BP(ND) values in the hippocampus, parahippocampal gyrus, and amygdala. The asymmetry index (AI), which characterizes the interhemispheric asymmetry in BP(ND), was significantly higher in patients than in controls in most regions. Depression scores were not significantly correlated with BP(ND) or AI values. Our data provide further evidence of functional changes in the serotonergic system in TLE. Molecular imaging of the 5-HT(1A) receptor may help to define the in vivo neurochemistry of TLE, and may provide a valuable tool in the noninvasive presurgical assessment of patients with medically refractory TLE.

This article is part of a Special 15th AnniversaryIssue. Copyright © 2014. Published by Elsevier Inc.

Knowledge about long-term psychosocial outcome of temporal lobe resection (TLR) for epilepsy is limited. The aims of this study were to describe vocational outcome 10years after TLR and to analyze the effect on the vocational situation by seizures, laterality of resection, verbal memory, and mood. Fifty-one patients were prospectively followed 10years after TLR. Psychosocial and neuropsychological data were ascertained at baseline and 10years after surgery and at corresponding time points for 23 controls. Fewer patients worked 10years post-operatively compared with controls (TLR patients: 61% and controls: 96%). However, seizure-free patients were more likely to retain employment (71%) than patients who had seizures (41%). The odds of working full-time were 9.5 times higher for patients with seizure freedom than for those with continuing seizures. There were no associations between working at 10years and side of resection or mood, and impairment of verbal memory did not have an influence on vocational outcome.

Neural mechanisms underlying the onset and maintenance of epileptic seizures involve alterations in inhibitory and/or excitatory neurotransmitter pathways. Thus, the prospecting of novel molecules from natural products that target both inhibition and excitation systems has deserved interest in the rational design of new anticonvulsants. We isolated the alkaloids (+)-erythravine and (+)-11-α-hydroxy-erythravine from the flowers of Erythrina mulungu and evaluated the action of these compounds against chemically induced seizures in rats. Our results showed that the administration of different doses of (+)-erythravine inhibited seizures evoked by bicuculline, pentylenetetrazole, and kainic acid at maximum of 80, 100, and 100%, respectively, whereas different doses of (+)-11-α-hydroxy-erythravine inhibited seizures at a maximum of 100% when induced by bicuculline, NMDA, and kainic acid, and, to a lesser extent, PTZ (60%). The analysis of mean latency to seizure onset of nonprotected animals, for specific doses of alkaloids, showed that (+)-erythravine increased latencies to seizures induced by bicuculline. Although (+)-erythravine exhibited very weak anticonvulsant action against seizures induced by NMDA, this alkaloid increased the latency in this assay. The increase in latency to onset of seizures promoted by (+)-11-α-hydroxy-erythravine reached a maximum of threefold in the bicuculline test. All animals were protected against death when treated with different doses of (+)-11-α-hydroxy-erythravine in the tests using the four chemical convulsants. Identical results were obtained when using (+)-erythravine in the tests of bicuculline, NMDA, and PTZ, and, to a lesser extent, kainic acid. Therefore, these data validate the anticonvulsant properties of the tested alkaloids, which is of relevance in consideration of the ethnopharmacological/biotechnological potential of E. mulungu.

Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common surgically remediable epileptic syndrome, has been associated with a cellular prion protein (PrPc) gene (Prnp) variant allele at codon 171. The polymorphism consisting of a methionine-for-valine substitution at codon 129 has been associated with early cognitive deterioration in elderly people and patients with Down syndrome. The same variant allele in homozygosis (V129V) has been associated to a lower long-term memory in healthy humans. PrPc mediates several processes related to neuroplasticity, and its role in cognitive processes remains unknown. In this study, we evaluated the genetic contribution of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive performance, measured with 19 neuropsychological tests, of patients with refractory MTLE-HS with the normal Prnp genotypes was compared with that of patients with the variant alleles at codons 129 and 171. With the effects of clinical, demographic, electrophysiological, and neuroimaging variable interactions controlled by multiple linear regression analysis and adjustment for multiple test comparisons, the presence of Prnp variant alleles was found not to be significantly associated to cognitive performance of patients with MTLE-HS. The presence of variant alleles at codons 129 and 171 is not associated to cognitive performance of patients with refractory MTLE-HS.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

The aim of this study was to investigate the association between carbamazepine (CBZ)-induced cutaneous adverse drug reactions (cADRs) and the HLA-B*1502 allele among patients from central China. Eight patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), 28 with mild maculopapular eruptions (MPEs), 50 CBZ-tolerant controls, and 71 healthy volunteers were recruited. HLA genotyping was performed using the polymerase chain reaction sequence-based typing (SBT) method. As a result, the HLA-B*1502 allele was observed at the following rates: (1) 100% (8/8) among those with CBZ-induced SJS/TEN, (2) 10.7% (3/28) among those with CBZ-induced MPEs; (3) 8.0% (4/50) among CBZ-tolerant controls; (4) 8.5% (6/71) among healthy volunteers. The eight patients with SJS/TEN positive for the HLA-B*1502 allele had an odds ratio (OR) of 184 compared with CBZ-tolerant controls. There was no significant difference in frequency between patients with MPEs and CBZ-tolerant controls (P>0.05). Thus, CBZ-induced SJS/TEN, but not MPEs, is strongly associated with HLA-B*1502. Testing for HLA-B*1502 should be recommended for patients from central China prior to initial CBZ treatment.

Previous studies have reported that patients with phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (PHT-induced SJS/TEN) were positive for HLA-B*1502. We genotyped two patients with PHT-induced SJS using both polymerase chain reaction with sequence-specific primers and sequencing. The results revealed that one patient from Henan Province had HLA-B*1501/B*5401, and the other patient from Guangdong Province had HLA-B*1502/B*4601. When this information was combined with the results from Taiwan and Hong Kong, a significant difference was observed in the presence of HLA-B*1502 between PHT-SJS and PHT-tolerant populations (35% vs 8%, P=0.001, OR=6.08, 95% CI=2.183-16.946). Additional studies in large samples are required to confirm the association between HLA-B*1502 and PHT-induced SJS/TEN.

This article is part of a Special 15th Anniversary Issue. Copyright © 2014 Elsevier Inc. All rights reserved.

This article is part of a Special 15th Anniversary Issue. Copyright © 2014. Published by Elsevier Inc.

We reviewed the incidence of aspiration pneumonia secondary to seizures in three populations of patients with chronic epilepsy: 733 outpatients seen in an Epilepsy Foundation clinic; 806 adult patients admitted to two university video telemetry units; and 95 institutionalized, profoundly retarded adult patients with chronic epilepsy. Two of the 733 adults who had seizures in the outpatient setting and 2 of the 806 patients who had one or more epileptic seizures in the telemetry units developed aspiration pneumonia. In the 95 institutionalized patients, there were 17 instances of aspiration pneumonia after a generalized seizure and 32 instances of aspiration unrelated to seizures over a 12-month period. Our findings suggest that aspiration pneumonia is not a common complication of seizures in otherwise healthy adults. The increased incidence of aspiration in developmentally delayed individuals seems to derive from a combination of factors. Increased oral secretions, impaired swallowing mechanisms, and difficulty in attaining adequate patient positioning significantly increased the risk of aspiration.

Testosterone (T), the principal androgen secreted by the testes, can have antiseizure effects. Some of these effects may be mediated by T's metabolites. T is metabolized to 3alpha-androstanediol (3alpha-diol). T, but not 3alpha-diol, binds androgen receptor. We investigated effects of 3alpha-diol (1 mg/kg, SC) and/or an androgen receptor blocker (flutamide 10 mg, SC), 1 hour prior to administration of pentylenetetrazol (85 mg/kg, IP). Juvenile male rats administered 3alpha-diol had less seizure activity than those administered vehicle. Flutamide had no effects. T is aromatized to 17beta-estradiol (E(2)), which, like 3alpha-diol, acts at estrogen receptors (ERs). Selective estrogen receptor modulators that favor ERalpha (propyl pyrazole triol, 17alpha-E(2)) or ERbeta (diarylpropionitrile, coumestrol, 3alpha-diol), or both (17beta-E(2)), were administered (0.1 mg/kg, SC) to juvenile male rats 1 hour before pentylenetetrazol. Estrogens with activity at ERbeta, but not those selective for ERalpha, produced antiseizure effects. Actions at ERbeta may underlie some antiseizure effects of T's metabolites.

We report a five-year-old girl presenting with dysphagia, dysarthria, drooling, and generalized tonic convulsions in whom the final diagnosis was acquired epileptiform opercular syndrome. Levetiracetam monotherapy at a dosage of 40mg/kg/day improved the clinical findings, and seizures were controlled at the end of the first month of treatment. Six months after the initial diagnosis, she presented with speech deterioration and dysarthria. At this time, although sleep and awake electroencephalography (EEG) were normal, FDG-PET showed hypometabolic and hypermetabolic regions in the anterior/inferior and anterior regions of the right frontal lobe, respectively. By increasing before levetiracetam dosage to 50mg/kg/day, the clinical findings resolved and the patient is still seizure free. Acquired epileptiform opercular syndrome is a rare epileptic disorder in which the seizures are resistant to conventional antiepileptic drugs. Levetiracetam may be an effective antiepileptic drug in controlling seizures and other clinical findings in acquired opercular epileptiform syndrome. Hypometabolic and hypermetabolic regions in FDG-PET study may be due to ongoing seizure activity or impaired glucose metabolism in this disorder.

The goals of this work were (1) to determine the effect of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, and EEG on the decision to perform temporal lobe epilepsy (TLE) surgery, and (2) to determine if FDG-PET, MRI, or EEG predicts surgical outcome. All PET scans ordered (2000-2010) for epilepsy or seizures were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, κ statistics, univariate analysis, and logistic regression. Of the 186 patients who underwent FDG-PET, 124 had TLE, 50 were surgical candidates, and 34 had surgery with post-operative follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (P<0.001) with odds ratios of 42.8, 20.4, and 6.3, respectively. FDG-PET was the only significant predictor of postoperative outcome (P<0.01). MRI showed a trend toward having the most influence on surgical candidacy, but only FDG-PET predicted surgical outcome.

This article describes the diary of a man from 19th-century England (1829-1834) that documents the onset and course of his wife's epilepsy after a stroke. Her stroke produced aphasia and right hemiparesis, but her epilepsy was the diary's focus and caused the greatest concern. The diary documents the history of her epilepsy in detail. In addition to tonic-clonic seizures, she experienced frequent bouts of status epilepticus and complex partial seizures. The diary contains some of the earliest recorded descriptions of status epilepticus and its aftermath of delirium, mood disorder, and hysteria. It also offers some of the earliest and most detailed accounts of complex partial seizures. Bleeding by cupping was the only symptomatic or prophylactic treatment recorded. These aspects of the diary are presented, as are the historical perspectives on epilepsy, including early beliefs and stigmas, therapeutic remedies, and early European views of epilepsy.

To coincide with the bicentenary of the birth of Charles Dickens (1812-1870), accounts of epilepsy found in his novels and journalism have been collated and analyzed. From these, it may be inferred that Dickens was clearly aware of the difference between epilepsy and syncope and recognized different types of epilepsy and that seizures could be fatal. Speculations that Dickens himself suffered from epilepsy are not corroborated. Dickens's novelistic construction of epilepsy as a marker of criminality, as in the characters of Monks in Oliver Twist and Bradley Headstone in Our Mutual Friend, and perhaps of mental abnormality, was in keeping with conventional contemporary views of epilepsy, but his journalistic descriptions of individuals with epilepsy confined in the workhouse system indicate an awareness of the inadequacy of their care.

Machado de Assis (1839-1908)-novelist, short story writer, essayist, and poet-is a fascinating personality. Had he written in French, English, German, or Italian, he would have achieved universal fame and would be in the same company as Balzac, Tolstoy, Dickens, and Dostoevsky. This article discusses stigma in epilepsy through Machado de Assis' life, literary work, and letters to other Brazilian writers. Founder of the Brazilian Academy of Letters, Machado offers an insoluble enigma to psychologists and essayists. Born in stark poverty, feeble, and ugly, he had to fight the taint of epilepsy. The documentation of epilepsy in Machado de Assis' texts and letters and the testimony of his contemporaries is unique, allowing the comprehension of scientific concepts and stigma related to epilepsy in the 19th century, when the positivist ideas of the Italian neuropsychiatrist Cesare Lombroso (1835-1909) permeated nascent Brazilian neuropsychiatry. Much of the stigma associated with epilepsy we witness today emerged from these concepts. Even today in Brazil, when barbaric crimes are committed, headlines in newspapers produced by forensic psychiatrists often attribute the conduct of the criminal to epileptic behavior.

Bilateral temporal lobe hypometabolism (BTH) on (18)F-FDG PET brain scan is frequently seen in unilateral medial temporal lobe epilepsy (mTLE). This study aimed to identify the factors that influence BTH in patients with mTLE in order to minimize the significant factor(s) prior to performing a FDG-PET brain scan. Forty patients with unilateral mTLE who underwent (18)F-FDG PET scan for presurgical epilepsy workup were included. Bilateral temporal lobe hypometabolism of the anterior and medial parts of the temporal lobe was identified by a semiquantitative visual scale. Lateralization of TLE was identified by either intracranial EEG (22/40 cases) and/or improvement of seizure 2years after temporal lobectomy (37/40 cases). The factors analyzed included basic demographic characteristics (age, sex, occupation, years of education, and handedness), history related to seizure (age at epilepsy onset and epilepsy duration, history of febrile seizure and head injury, frequency of seizure with impaired cognition in the last 3months, presence of secondarily generalized tonic-clonic seizure, automatism side, presence of postictal confusion, and side of MRI temporal abnormality), information during video-EEG monitoring (clinical lateralization, interictal scalp EEG lateralization (interictal epileptiform discharge), and ictal scalp EEG lateralization), and information during the FDG-PET study (duration from the last seizure (≤2days or >2days), last seizure type, and the presence of slow waves or sharp waves during the FDG uptake period). Significant factors related to BTH were analyzed using multivariate analysis. Only the ≤2-day duration from the last seizure to the PET scan shows a significant effect (p=0.021) on BTH finding with 15 times greater incidence compared to a duration >2days. Bilateral temporal lobe hypometabolism, which causes conflict in lateralizing the epileptogenic zone in temporal lobe epilepsy, can be avoided by performing PET scan more than 2days after the last seizure.

The purpose of this study was to reveal the major views of the early scientific period (18th and 19th centuries) on epilepsy as both a disease and a symptom. The shaping of thought about illness and medicine as a science, which began in the Renaissance and progressed into the Enlightenment, intensified during the 18th and 19th centuries. During this period of increasingly methodical investigation, researchers undertook a thorough study of epilepsy. Renowned doctors of this period from the Dutch and German medical schools, the "golden era" of French medicine, and British medicine, including, of course, John Hughlings Jackson, all left their mark in this era of epilepsy research. Epidemiological studies using large patient data sets were conducted for the first time, as was systematic research on the pathophysiological, pathological, neurological, and psychiatric aspects of the disease.

The purpose of our study was to determine whether a single administration of anticonvulsant doses of two ligands of benzodiazepine receptors, clonazepam and Ro 19-8022, leads to development of rebound phenomena in immature 12-day-old rats. Three tests were used: pentylenetetrazole (PTZ)-induced seizures, isolation-induced ultrasonic vocalizations, and motor performance. Susceptibility to the convulsant effects of PTZ decreased 24 hours, but increased 48 hours, after clonazepam administration. Ultrasonic vocalizations were completely suppressed 30 minutes and 3 hours after clonazepam; a moderate inhibitory effect persisted even at 48 hours. Motor abilities were slightly compromised up to 3 hours. Similar effects of Ro 19-8022 on PTZ-induced seizures and ultrasonic vocalizations were observed 24 and 48 hours after administration; motor performance was not affected. Rebound proconvulsant effects followed different time courses after administration of the two benzodiazepine receptor ligands in developing animals. Anxiolytic-like effects of these drugs were still present at the time when animals exhibited rebound proconvulsant effects.

The author Margiad Evans (1909-1958), a celebrated Anglo-Welsh writer of the 1930s and 1940s, developed epilepsy in 1950, and subsequently wrote accounts of her experiences of seizures, their diagnosis, and their management. These documents are among the first patient accounts of epilepsy, and remain of value today, not least because they prefigure ongoing problems in epilepsy management such as pregnancy and the adverse effects of antiepileptic drugs. They also give some insights into the consequences of epilepsy for a creative writer.

The aim of the work described here was to characterize quality of life (QOL) and its determinants in a large cohort of adult patients with epilepsy. Validated measures reflecting disease severity and psychosocial functioning were electronically collected on all outpatients seen during 2009. Multivariate regression adjusting for repeated measures identified determinants of QOL, as defined by the Quality of Life in Epilepsy Questionnaire-10 (QOLIE-10). Seven thousand seven hundred eighty-four visits from patients with epilepsy were identified. The questionnaire completion rate was 77%, yielding 5960 records corresponding to 1931 individual patients for analysis. Following multivariate modeling, the two most clinically significant QOL predictors were seizure severity (mean QOLIE-10 score=28.8 if LSSS>40 vs 19.2 otherwise) and depression (mean QOLIE-10 score=31.7 if PHQ-9≥10 vs 19.3 otherwise). Optimizing quality of life in patients with epilepsy requires an approach that extends beyond controlling seizures. Collection of validated health status measures improving patient management is possible within the setting of routine clinical care.

Norman Geschwind catalyzed academic interest in the study of interictal behavioral changes in temporal lobe epilepsy. His contributions to this area comprise a series of 11 articles, chapters, editorials, and commentaries published between 1973 and 1984. This article summarizes, both chronologically and by behavioral topic, Geschwind's contributions and opinions on behavioral changes in temporal lobe epilepsy. A previously unpublished lecture (see article in this issue), "Personality Change in Temporal Lobe Epilepsy," from his course at Harvard Medical School on The Neurology of Behavior (1974), is also quoted to further illustrate his views on specific features of this syndrome. Notably, many of Geschwind's observations and formulations regarding this topic were highly developed in 1974, reflecting his long-standing interest in behavioral changes in epilepsy. Geschwind and his collaborators viewed temporal lobe epilepsy as an important model of behavioral change resulting from a stimulating lesion in the limbic system. This neurobiology accounted for the overarching increased interictal emotionality that underlay the increased religious interests, hypergraphia, increased aggression, increased moral and philosophical concerns, viscosity, and seriousness (lack of humor). Hyposexuality was the exception, although it was consistent with a discharging lesion altering this emotion-driven behavior. Geschwind provided a series of arguments to support the existence of this limbic syndrome and explain why alternative views (e.g., destructive lesion, psychological factors) and arguments against the syndrome's existence are inconsistent with the data.

Background: There has been a rapid expansion in the number of research papers published on clinical epilepsy topics and the number of journals in the medical field. In this expanding publishing environment, the question arises as to how much of the published medical literature has 'enduring value' in terms of advancing knowledge in any significant way. Methods: We developed a methodology to assess the enduring value of papers published in the field of clinical epilepsy and established its internal validity. We studied 300 research papers published in 1981, 1991, and 2001 (100 in each year) and assessed their enduring value in four domains: citations in the last year, citations in the last 10years, citations in the standard epilepsy textbook, and a subjective assessment by an experienced epileptologist. Results: Of the 300 papers, 214 (71%) were categorized as having 'no enduring value', and only 11 (4%) were identified as having 'high enduring value'. The 'high enduring value' papers could generally be identified immediately on publication, by high initial citation values, and were also more likely to be published in journals with a high impact factor. The commonest characteristics of a paper with no enduring value were that they reported research that was inherently unimportant (55.6%), not novel (38.8%), or had significant methodological flaws (22.0%). Conclusions: Although there are other reasons for publishing papers, the fact that the great majority of published papers lack enduring value in terms of advancing knowledge should be a concern to the medical and scientific community.

Patients with epilepsy are known to have comorbid affective disorders and a higher risk for suicide compared with the general population. Epilepsy, depression, and suicidal behavior have been shown to have common pathogenic mechanisms in their etiology. We evaluated the association between epilepsy, suicidal behavior, and depression by using the comprehensive database of all suicides (n=1877) committed in northern Finland during the years 1988-2002 with information on all hospital-treated somatic and psychiatric disorders. Hospital-treated epilepsy occurred in 1.3% of the victims. Compared with other suicide victims, those with epilepsy were more often female, were older, and had significantly more often suffered from depression. Epilepsy was first diagnosed 8.8 (3.9-11.6) years before suicide, and depression, about 1 year after epilepsy diagnosis. Interictal depression among patients with chronic epilepsy is often classified as atypical or chronic depression, or it can mimic a dysthymic disorder. Therefore, diagnosis and treatment of depression among patients with epilepsy constitute a great challenge in clinical practice.

Epilepsy-related employment prevalence and retirement incidence were investigated in the German working population from 1994 to 2009. The overall mean prevalence of employment of people with epilepsy was 5.1±0.2 per 1000 workers. The employment rate among people with epilepsy increased from 63.5% in 1994 to 65.9% in 2000 (0.4% annually) and then more steeply from 66.8% in 2001 to 76.9% in 2009 (1.4% annually). A prominent increase in rate of employment of people with epilepsy since 2001 was temporarily associated with approval of leviteracetam in 2000 (P<0.001, OR=8.3, CI=6.45-10.12). The overall mean employment rate of people with epilepsy was lower than that of the general population (68.5% vs 90.1%, P<0.001). The overall mean incidence of epilepsy-related retirement (RI) during the study was 4.6±1.6/1000, similar to the RI for people with other illnesses (5.1±0.8/1000), and the risk of retiring because of epilepsy was not higher than that for other illnesses over the entire study period (P=0.52, OR=1.11, CI=0.86-1.43). The RI among workers with epilepsy, however, sharply declined from 8.3/1000 in 1994 to 2.9/1000 in 2000 (-65%, < 0.001), followed by a slight increase and stabilization at 3.9/1000 workers between 2001 and 2009. The decline in RI among people with epilepsy was temporarily associated with legislation of the Law on Support of Employment in 1996 (P=0.032, OR=2.15, CI=1.17-2.89) and approval of lamotrigine in 1993 (P=0.024, OR=2.64, CI=2.17-3.88). These patterns suggest that drug treatment and legislative laws may have led to increased employment and reduced retirement rates for people with epilepsy.