Natural History Of Epilepsy Research Articles

The natural history of epilepsy and nonepileptic seizures in Sturge–Weber syndrome: A retrospective case-note review

ObjectivePatients with Sturge–Weber Syndrome (SWS) experience varying degrees of neurological problems – including epilepsy, hemiparesis, learning disability (LD), and stroke-like episodes. While the range of clinical problems experienced by children with SWS is well recognized, the spectrum of clinical presentation and its treatment during adulthood has been relatively neglected in the literature to date. This study explored the natural history of epileptic and nonepileptic seizures into adulthood in patients with SWS, and their treatment, and investigated whether any clinical factors predict which symptoms a patient will experience during adulthood. MethodsA retrospective case-note review of a cohort of 26 adults with SWS at the National Hospital for Neurology and Neurosurgery (NHNN). Childhood data were also recorded, where available, to enable review of change/development of symptoms over time. ResultsThe course of epilepsy showed some improvement in adulthood – seventeen adults continued to have seizures, while six patients gained seizure freedom, and no one had adult-onset seizures. However, seizures did worsen for some patients. Although no factors reached statistical significance regarding predicting continued epilepsy in adulthood, being male, more severe LD, having required epilepsy surgery, and bilateral cortical involvement may be important. Nonepileptic seizures (NES) also began during adulthood for four patients. SignificanceBy adulthood, there is some degree of improvement in epilepsy overall; while NES may occur for the first time. While the majority of the results did not survive adjustments for multiple comparisons, some interesting trends appeared, which require further investigation in a multicenter national audit. Patients with more neurologically severe presentations during childhood may continue to experience seizures. Careful monitoring and screening are needed during adulthood, to detect changes and newly developing symptoms such as NES, and target treatment promptly.

Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study.

Argininosuccinate lyase (ASL) is integral to the urea cycle, which enables nitrogen wasting and biosynthesis of arginine, a precursor of nitric oxide. Inherited ASL deficiency causes argininosuccinic aciduria, the second most common urea cycle defect and an inherited model of systemic nitric oxide deficiency. Patients present with developmental delay, epilepsy, and movement disorder. Here we aim to characterize epilepsy, a common and neurodebilitating comorbidity in argininosuccinic aciduria. We conducted a retrospective study in seven tertiary metabolic centers in the UK, Italy, and Canada from 2020 to 2022, to assess the phenotype of epilepsy in argininosuccinic aciduria and correlate it with clinical, biochemical, radiological, and electroencephalographic data. Thirty-seven patients, 1-31 years of age, were included. Twenty-two patients (60%) presented with epilepsy. The median age at epilepsy onset was 24 months. Generalized tonic-clonic and focal seizures were most common in early-onset patients, whereas atypical absences were predominant in late-onset patients. Seventeen patients (77%) required antiseizure medications and six (27%) had pharmacoresistant epilepsy. Patients with epilepsy presented with a severe neurodebilitating disease with higher rates of speech delay (p = .04) and autism spectrum disorders (p = .01) and more frequent arginine supplementation (p = .01) compared to patients without epilepsy. Neonatal seizures were not associated with a higher risk of developing epilepsy. Biomarkers of ureagenesis did not differ between epileptic and non-epileptic patients. Epilepsy onset in early infancy (p = .05) and electroencephalographic background asymmetry (p = .0007) were significant predictors of partially controlled or refractory epilepsy. Epilepsy in argininosuccinic aciduria is frequent, polymorphic, and associated with more frequent neurodevelopmental comorbidities. We identified prognostic factors for pharmacoresistance in epilepsy. This study does not support defective ureagenesis as prominent in the pathophysiology of epilepsy but suggests a role of central dopamine deficiency. A role of arginine in epileptogenesis was not supported and warrants further studies to assess the potential arginine neurotoxicity in argininosuccinic aciduria.

Epilepsy, electroclinical features, and long-term outcomes in Pitt-Hopkins syndrome due to pathogenic variants in the TCF4 gene.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by deletions/variants in the TCF4 gene. Seizures may be present in up to half of the patients, leading to a more severe disease burden. This study aims to analyse the electroclinical phenotype, treatment options, and long-term outcomes of epilepsy in PTHS. A multicentre observational cohort study was performed, and the electroclinical data of PTHS individuals affected by epileptic seizures were retrospectively reviewed and analysed. The series includes 21 patients (11 female) with a median age at seizure onset of 2years (range = 0.5-8). The median time of follow-up was 7.9years (range = 2-27). Both generalized and focal epilepsies were present at the same prevalence (42.8%), whereas a minority of patients presented developmental and epileptic encephalopathies (14.4%). At the long-term follow-up, 42.8% achieved seizure freedom, whereas 42.8% developed drug-resistant epilepsy (DRE). The age at seizure onset was found to be an independent predictor for seizure outcome; in this regard, patients having seizure onset after the age of 2years were more prone to achieve seizure freedom (odds ratio = 0.04, 95% confidence interval = 0.003-0.53; p=0.01). During evolution, seizures tended to settle down, and even in patients with DRE, seizures tended to persist at a lower frequency and appeared to be more easily manageable over time. This study provides new insight into the natural history of epilepsy in PTHS. Better characterization of epileptic phenotype and prompt tailored treatment improve overall management and quality of life.

Probabilistic Study of the Effect of Anti-Epileptic Drugs Under Uncertainty: Cost-Effectiveness Analysis

Epilepsy is one of the most ancient diseases. Despite the efforts of scientists and doctors to improve the quality of live of epileptic patients, the disease is still a mystery in many senses. Anti-epileptic drugs are fundamental to reduce epileptic seizures but it have some adverse effects, which influence the quality of life outcomes of the patients. In this paper, we study the effectiveness of anti-epileptic drugs taking into account the inherent uncertainty. We establish a model, which allows to represent the natural history of epilepsy, using Markov chains. After randomizing the mathematical model, we compute the first probability density function of the solution stochastic process applying the random variable transformation technique. We also take advantage of this method to determine the distribution of some key quantities in medical decision, such as the time until a certain proportion of the population remains in each state and the incremental cost-effectiveness ratio. The study is completed computing all these quantities using data available in the literature. In addition, regarding the incremental cost-effectiveness ratio, different third generation anti-epileptic treatments are compared with the Brivaracetam, a new third generation anti-epileptic drug.

Variations in the natural history of epilepsy and epilepsy subgroups (P1.239)

Variations in the natural history of epilepsy and epilepsy subgroups (P1.239)

The Natural History of Epilepsy in 163 Untreated Patients: Looking for "Oligoepilepsy".

The clinical evolution of untreated epilepsy has been rarely studied in developed countries, and the existence of a distinct syndrome characterized by rarely repeated seizures (oligoepilepsy) is debated. The aim of this study is to assess the natural history of 163 untreated patients with epilepsy in order to evaluate whether oligoepilepsy retains specific features. We retrospectively evaluated 7344 patients with ≥2 unprovoked seizures. Inclusion criteria: sufficient anamnestic/EEG data, disease duration ≥10 years, follow-up ≥3 years. Exclusion criteria: psychogenic seizures, natural history of disease <5 years. The 163 included subjects were divided into 2 groups according to seizure frequency: oligoepilepsy (≤1/year; 47 subjects) and controls (>1/year; 116 subjects). We also evaluated seizure frequency during the natural history. There were no differences between groups regarding duration of natural history, family history of epilepsy/febrile seizures, interictal EEG. Subjects with oligoepilepsy differed from controls in terms of sex (females 38% vs. 58%, p = 0.03) and drug resistance (6% vs 28%; p = 0.003). Juvenile myoclonic epilepsy was more frequent in controls (9.5% vs 0%, p = 0.04). Patients with oligoepilepsy, differently from controls, had stable seizure frequency. Oligoepilepsy represents a favourable evolution of different epileptic syndromes and keeps a stable seizure frequency over time.

Widespread changes in network activity allow non-invasive detection of mesial temporal lobe seizures.

Decades of experience with intracranial recordings in patients with epilepsy have demonstrated that seizures can occur in deep cortical regions such as the mesial temporal lobes without showing any obvious signs of seizure activity on scalp electroencephalogram. Predicated on the idea that these seizures are purely focal, currently, the only way to detect these 'scalp-negative seizures' is with intracranial recordings. However, intracranial recordings are only rarely performed in patients with epilepsy, and are almost never performed outside of the context of epilepsy. As such, little is known about scalp-negative seizures and their role in the natural history of epilepsy, their effect on cognitive function, and their association with other neurological diseases. Here, we developed a novel approach to non-invasively identify scalp-negative seizures arising from the mesial temporal lobe based on scalp electroencephalogram network connectivity measures. We identified 25 scalp-negative mesial temporal lobe seizures in 10 patients and obtained control records from an additional 13 patients, all of whom underwent recordings with foramen ovale electrodes and scalp electroencephalogram. Scalp data from these records were used to train a scalp-negative seizure detector, which consisted of a pair of logistic regression classifiers that used scalp electroencephalogram coherence properties as input features. On cross-validation performance, this detector correctly identified scalp-negative seizures in 40% of patients, and correctly identified the side of seizure onset for each seizure detected. In comparison, routine clinical interpretation of these scalp electroencephalograms failed to identify any of the scalp-negative seizures. Among the patients in whom the detector raised seizure alarms, 80% had scalp-negative mesial temporal lobe seizures. The detector had a false alarm rate of only 0.31 per day and a positive predictive value of 75%. Of the 13 control patients, false seizure alarms were raised in only one patient. The fact that our detector specifically recognizes focal mesial temporal lobe seizures based on scalp electroencephalogram coherence features, lends weight to the hypothesis that even focal seizures are a network phenomenon that involve widespread neural connectivity. Our scalp-negative seizure detector has clear clinical utility in patients with temporal lobe epilepsy, and its potential easily translates to other neurological disorders, such as Alzheimer's disease, in which occult mesial temporal lobe seizures are suspected to play a significant role. Importantly, our work establishes a novel approach of using computational approaches to non-invasively detect deep seizure activity, without the need for invasive intracranial recordings.

Treating Drug-resistant Epilepsy – Why are we Waiting?

Drug-resistant epilepsy (DRE) has been defined by the ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies as the failure of two appropriately chosen and tolerated anti-epileptic drugs (AEDs) (whether as monotherapy or in combination) to control seizures when used for an adequate period of time. The difference between the number of patients with DRE and the number of these patients who do not get access to adequate treatment is defined as the ‘treatment gap’, which is considered to be substantial. There are multiple possible causes that underlie the treatment gap in DRE: economic costs, natural history of epilepsy, deficiencies in health service provision, social stigma and other as yet unidentified causes. Factors affecting quality of life in DRE include depression and anxiety, raised risk of mortality and morbidity, increased healthcare utilisation and increased risk of adverse events with long- term use of AEDs, cognitive and memory impairment, seizure-related injuries, impaired ability to achieve educational and vocational goals, to drive, establish families and benefit from social relationships. Among the reasons for the greater risk of premature death are the raised risk of suicide in those patients with comorbid psychiatric disease and the increased incidence of sudden unexpected death among those with epilepsy. Managing epilepsy well involves more than just seizure reduction and when freedom from seizures cannot be achieved, addressing quality of life is likely to be more beneficial than interventions aimed at seizure reduction alone. Options exist for patients with DRE who are not candidates for epilepsy surgery, including dietary treatments, further attempts with AEDs and non-pharmacological interventions with devices. Further, non-invasive modalities are emerging, creating a more hopeful picture that the treatment gap for patients with DRE may be narrowed or even closed.

Corpus Callosotomy for Childhood-Onset Drug-Resistant Epilepsy Unresponsive to Vagus Nerve Stimulation

PurposeCorpus callosotomy and vagus nerve stimulation are common palliative options for people with drug-resistant epilepsy when resective epilepsy surgery is not feasible. Because most of the published corpus callosotomy experience comes from a period before vagus nerve stimulation was approved and widely used, there is a paucity of data about efficacy of corpus callosotomy in patients with inadequate response to vagus nerve stimulation. MethodsWe report seven patients who had complete corpus callosotomy after an inadequate response to vagus nerve stimulation. At the time of surgery, these patients had failed a median of six antiseizure medications, three patients also had failed a trial of ketogenic diet, and all the patients had a vagus nerve stimulation implanted for a mean duration of 2.5 years with maximal tolerated settings. ResultsThere was a decrease in total daily seizure frequency of 34.7% (±94.7; median, 71.4%; interquartile range, 55.3) after corpus callosotomy at a mean follow-up of 2.6 years (±1.4). One patient achieved complete seizure freedom and five patients had ≥50% reduction in seizure frequency. Six patients continued to have partial-onset seizures though the frequency was decreased. Drop attacks and tonic seizures stopped in all the patients. ConclusionSeizure outcomes after corpus callosotomy in our series are most likely a result of complex dynamic interaction between the natural history of epilepsy, the effect of the surgery, ongoing vagus nerve stimulation modulation, and modification in antiseizure drugs. Our study supports the clinical decision to try corpus callosotomy in patients having nonlateralizing drug-resistant epilepsy with inadequate response to vagus nerve stimulation.

The puzzle(s) of pharmacoresistant epilepsy

Despite the availability of >25 antiepileptic drugs, 30% of people with epilepsy do not respond to conventional agents, exhibiting pharmacoresistance (PR)--a high percentage that has not changed significantly in decades. This is not surprising given that all current pharmaceutical agents merely reduce the incidence of seizures ("antiictogenic"); they do not interfere with the natural history of epilepsy and are therefore not antiepileptogenic. The two prevailing hypotheses of pharmacoresistance, the target hypothesis and the transporter hypothesis, can only partially explain the complexity and the diversity of PR. It is a neuropharmacologic priority that we change our approach to understanding PR. Herein we suggest the need to regard PR as a complex puzzle in which the target and transporter hypotheses represent a very small piece of the whole. Indeed, we do not even know if this piece of the whole is epiphenomenal or neurobiologically causal. To grasp the whole, we need to constantly gather information (look around for other pieces) from other perspectives and insights coming from clinical, epidemiologic, neuroradiologic, genetic, and other data. A recent research workshop on PR, the 2nd Halifax International Epilepsy Conference & Retreat, chose this eclectic and all-encompassing approach. The participants were fully aware that their diverse contributions represent only still-fragmented pieces of this frustrating but clinically important puzzle.

The natural history of epilepsy in tuberous sclerosis complex

Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease. A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox-Gastaut syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment, and genetic mutation. Two hundred ninety-one patients were included. Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure; 54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset in the first year of life; and 12.1% of adults without a seizure history developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and 33.5% achieved epilepsy remission; 37.5% of these patients achieved medication freedom. IS was a risk factor for refractory epilepsy (p<0.0001) and LGS (p<0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy each correlated with poor cognitive outcome (p<0.0001). Epilepsy remission correlated with better cognitive outcome (p<0.0001). TSC2 was a risk factor for IS and epilepsy; patients without an identified mutation were more likely to achieve remission. Most patients with TSC develop epilepsy and most develop multiple seizure types. Onset typically occurs in the first year of life; however, adults remain at risk. Although refractory epilepsy is common, many patients achieve seizure control. Many features of seizure history are predictive of cognitive and epilepsy outcome.

The Natural History of Epilepsy: Spontaneous Remission and Mortality

Natural History and Mortality of Chronic Epilepsy in an Untreated Population of Rural Bolivia: A Follow-Up after 10 years. Nicoletti A, Sofia V, Vitale G, Bonelli SI, Bejarano V, Bartalesi F, Tran DS, Preux PM, Zappia M, Bartoloni A. Epilepsia 2009;50(10):2199–2206. PURPOSE: To evaluate the natural history and mortality of chronic epilepsy in an untreated prevalence cohort of people with epilepsy (PWE) in a rural area of Bolivia. METHODS: During 1994–1996 we carried out an epidemiologic survey in a sample of 9,995 subjects in the Cordillera province. At the end of the survey we identified 130 PWE, of whom 118 were classified as having “active epilepsy.” We revisited this cohort 10 years after the prevalence survey. RESULTS: We were able to trace 103 (87.3%) of the 118 PWE previously identified. Ten of the 103 subjects died during the follow-up period. Of the 93 PWE still alive, adequate information on the occurrence of seizures was available for 71 subjects, of whom 31 (43.7%) were seizure-free for more than 5 years; only 3 of these 31 subjects have taken an antiepileptic drug (AED) for more than 1 year. Generalized seizures were associated with a better prognosis. Mortality rate in our prevalent cohort was 10.0/1,000 person-year at risk [95% confidence interval (CI) 5.5–18.3], without a significant increased risk respect to the general population [standardized mortality rate (SMR) 1.34; 95% CI 0.68–2.39]; a significant increased risk of death was found for patients with remote symptomatic epilepsy (SMR 3.0; 95% CI 1.2–6.3) but not with idiopathic epilepsy. Three of the 10 subjects died of causes possibly related to epilepsy. DISCUSSION: Our data suggest that spontaneous remission of epilepsy occurs in a substantial proportion of untreated patients affected by chronic epilepsy; concerning mortality, we found a three-fold increased mortality in patients with remote symptomatic epilepsy.

Enhancement of GABA A -current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy

Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABA(A) receptors. In particular, the use-dependent decrease (run-down) of the currents (I(GABA)) evoked by the repetitive activation of GABA(A) receptors is markedly enhanced in hippocampal and cortical neurons of TLE patients. Understanding the role of I(GABA) run-down in the disease, and its mechanisms, may allow development of medical alternatives to surgical resection, but such mechanistic insights are difficult to pursue in surgical human tissue. Therefore, we have used an animal model (pilocarpine-treated rats) to identify when and where the increase in I(GABA) run-down occurs in the natural history of epilepsy. We found: (i) that the increased run-down occurs in the hippocampus at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made), and then extends to the neocortex and remains constant in the course of the disease; (ii) that the phenomenon is strictly correlated with the occurrence of spontaneous seizures, because it is not observed in animals that do not become epileptic. Furthermore, initial exploration of the molecular mechanism disclosed a relative increase in alpha4-, relative to alpha1-containing GABA(A) receptors, occurring at the same time when the increased run-down appears, suggesting that alterations in the molecular composition of the GABA receptors may be responsible for the occurrence of the increased run-down. These observations disclose research opportunities in the field of epileptogenesis that may lead to a better understanding of the mechanism whereby a previously normal tissue becomes epileptic.

The natural history of epilepsy in the era of new antiepileptic drugs and surgical treatment.

To review the factors influencing prognosis of epilepsy in this era of antiepileptic drugs and surgical treatment. Systematic review of peer-reviewed literature. The prognosis depends on many factors; aetiology, age of onset, number of seizures at onset, the natural history of the condition, and the influence of treatment. However, between 70 and 80% of people developing epilepsy will go into long-term remission, usually within the first 5 years. Prognosis in epilepsy is the prospect of attaining complete seizure freedom once a pattern of recurrent epileptic seizures has been established. Well-designed prospective cohort studies using standard outcome measures need to be conducted, especially in non-Western cultures.

Neurological complications of pregnancy

Epilepsy is the second most common neurological disorder, affecting 0.3 to 0.6% of the population. A number of studies evaluated the effect of pregnancy on seizure frequency in epileptic women. According to Schmidt, 1982 Schmidt, D., 1982. The effect of pregnancy on the natural history of epilepsy:review of the literature. In: Janz, D., Dam, M., Richens, A., Bossi, L., Helge, H., Schmidt, D. (Eds.), Epilepsy, pregnancy and the child. Raven Press, New York, pp. 3–14. The author compiled the results of 27 studies. Of the 2165 patients included in these studies, 24% experienced an increase in seizure frequency, 22% experienced a decrease in seizure frequency, and 53% experienced no change in seizure frequency. Google Scholar 50–65% of patients experience no change in seizure frequency, 20–25% experience an increase in seizure frequency, and 20–25% experience a decrease in seizure frequency. This variability of seizure frequency in pregnancy does not differ significantly from what is known of fluctuations in non-pregnant patients. Nevertheless, frequency of seizures in some patients may increase during pregnancy with serious consequences for mother and offspring.

Antiepileptic drugs in pediatric practice.

Several factors characterize the current medical treatment of epilepsy during childhood. Children do not present the same types of seizures or epilepsies as adults, and certain epilepsy syndromes are seen only during childhood. Accordingly, the choice of antiepileptic drugs (AEDs) may differ in children. In addition, certain medical therapies, such as ACTH or pyridoxine, are used only in children. It is also common practice to prescribe AEDs in children for indications that are "off-label," such as the treatment of partial-onset seizures with carbamazepine before the age of 6 years. The natural history of epilepsy and the risk for seizure recurrence may be different in the pediatric age range, and this may influence the decision to institute chronic prophylactic therapy in children. Similar considerations may apply to the decision to discontinue AED therapy. The pharmacokinetics of several AEDs are age-dependent, and dosages are more variable among patients. The adverse effects of AEDs may be age-dependent, and the pattern of exacerbation of certain seizures by AEDs may be different in children. In addition, several new AEDs are now available, or are about to be released, and the preferential sequence of AEDs of choice in children with epilepsy will need to be reassessed as experience grows and as the results of comparative studies become available.

Epilepsy and primary cerebral tumours

Although the association of epilepsy with cerebral tumours is well recognized, the reported incidence of seizures and relationship to tumour pathology varies significantly. This study assessed retrospectively the incidence of seizures, relationship to tumour pathology, natural history of epilepsy and prognostic significance of presentation with a seizure in 120 consecutive adults with histologically proven primary cerebral hemisphere tumours including meningiomas. 52% had a seizure and most were at presentation. Seizures were more common with anaplastic astrocytoma (AA) (18 23 ) than glioblastoma multiforme (21 56 ) (p = 0.001) and seizure occurrence was associated with cortical invasion. 52% of meningioma patients had a seizure. Seizures recurred in 34%, more frequently with glioma (19 of 46) than meningioma (1 of 15) (p < 0.05). Patients with AA presenting with a seizure had a longer survival (28 months) than patients without seizure (8 months) (p = 0.05 one sided). In conclusion, seizures are a common complication of cerebral tumours, usually at presentation and correlate with tumour pathology. A seizure at presentation in AA correlates with longer survival.

The Effect of Pregnancy on the Epilepsies: A Study of 37 Pregnancies

Background: Although studies have assessed the effect of pregnancy on epilepsy, usually the types of epilepsy are not differentiated and most have not included a control group, despite the natural history of epilepsy including fluctuations in seizure frequency. Aims: To assess the effect of pregnancy on seizure frequency and compare this with changes in seizure frequency in non-pregnant patients. In addition, the relationship between seizure frequency during pregnancy and epilepsy type, seizure frequency prior to pregnancy and duration of epilepsy will be assessed. Methods: Seizure frequency was assessed retrospectively in 37 pregnancies from 24 women by comparing the seizure number for the nine-month period prior to pregnancy with the number during the pregnancy. An increase in frequency was defined as a 50% or greater increase in the number of seizures. Twenty-four non-pregnant women, matched for age and epilepsy type, were included to assess fluctuations in control. Results: In 41% of pregnant women, there was an increase in seizure frequency, in 51% no change and in 8% improvement. In the control group, 24% had an increase, 65% no change and 11% improvement. There was no correlation between seizure frequency during pregnancy and epilepsy type and seizure frequency prior to pregnancy, but those with longer duration of epilepsy were more likely to deteriorate (p < 0.05). Alterations in anticonvulsants to reduce the risk of teratogenicity was a common identifiable cause of deterioration in control. Conclusions: Significant random fluctuations in epileptic control occur, but pregnancy may have a deleterious effect on epilepsy, particularly when appropriate therapy is withdrawn to reduce teratogenicity.

Epilepsy and pregnancy.

The management of the pregnant epileptic requires close cooperation between the neurologist and obstetrician. To prevent complications, knowledge is required about the natural history of epilepsy during pregnancy, the possible teratogenic effects of antiepileptic drugs, and changes in their absorption, biotransformation, and excretion. Close plasma antiepileptic drug monitoring is required because of the change in the handling of antiepileptic drugs during pregnancy. The treatment of status epilepticus with intravenous phenytoin is effective. Drug interactions which may lead to toxic plasma levels of some drugs and subtherapeutic plasma levels of others should be anticipated. The risk of problems resulting from antiepileptic drug therapy during pregnancy appears to be minor, provided that proper medical supervision is available. Newer antiepileptic drugs should not be administered to the pregnant epileptic until their safety in pregnancy is fully established.