Antiepileptic Drug Initiation Research Articles

Antiepileptic Drug Titration and Related Health Care Resource Use and Costs.

Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs. To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance. Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review. Patients with epilepsy who were aged ≥ 18 years and had initiated an AED between January 1, 2014, and January 1, 2016, were followed for 6 months from AED initiation. Titration duration was the time from AED initiation to the beginning of treatment maintenance as determined by the physician. Outcomes were epilepsy-specific HRU (hospitalizations, emergency department visits, outpatient visits, physician referral, laboratory testing/diagnostic imaging, and phone calls) and related costs that occurred during the titration or maintenance treatment periods. Of 811 patients, 156, 128, 125, 120, 114, 107, and 61 initiated the following AEDs: levetiracetam, lamotrigine, lacosamide, valproate, topiramate, carbamazepine, and phenytoin, respectively. Most patients (619/803 [77.1%] with complete AED data) received monotherapy. Baseline characteristics were similar across AEDs (mean [SD] age, 36.6 [14.4] years; 59.0% male). Kaplan-Meier estimates of titration duration ranged from 3.3 weeks (phenytoin) to 8.1 weeks (lamotrigine). From titration to maintenance, the overall incidence of HRU per person-month decreased 54.5%-89.3% for each HRU measure except outpatient visits (24.6% decrease). Total epilepsy-related costs decreased from $80.48 to $42.77 per person-month, or 46.9% from titration to maintenance. AED titration periods had higher HRU rates and costs than AED maintenance, suggesting that use of AEDs with shorter titration requirements reduces health care costs, although disease severity may also factor into overall cost. UCB Pharma sponsored this study and reviewed the manuscript. Fishman and Kalilani are employees of UCB Pharma. Wild was an employee of UCB Pharma at the time this analysis was conducted. Song and Swallow are employees of Analysis Group, which received funding from UCB Pharma.

Efficacy, Duration and Timing of Withdrawal of Prophylactic Treatment with Antiepileptic Drugs in Neurosurgical Conditions

Seizure control is a critical component of care in many neurosurgical conditions. The development of seizures in patients without a previously identified seizure disorder occurs in a significant proportion of traumatic brain injury, subarachnoid hemorrhage, and brain tumor patients. In this literature review and synthesis, we will discuss the incidence of seizures in selected conditions, indications and evidence for the initiation of antiepileptic drugs (AEDs), suggested duration of usage for AEDs, and current AED guidelines by the American Academy of Neurology (AAN), Congress of Neurological Surgeons (CNS), American Academy of Neurological Surgeons (AANS) and international committees.

Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy.

To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11years) and adolescents (age = 12-18years) were examined separately. A total of 380 youths with new onset epilepsy (Mage =8.9±4.3years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M=25.08±26.36) compared to adolescents (M=12.36±17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection.

The Utility of Surveillance Electroencephalography to Guide Early Antiepileptic Drug Therapy in Infants With Tuberous Sclerosis Complex

BackgroundSeizures are a common early presentation in infants with tuberous sclerosis complex (TSC) and can be preceded by electrographic changes on electroencephalography (EEG) before clinical seizure onset. A limited number of studies have addressed the initial EEG findings in TSC and the outcome of early treatment with antiepileptic medication prior to clinical seizure onset. MethodsWe describe two infants with tuberous sclerosis complex whose surveillance EEG showed focal seizures that were not previously recognized by caregivers. We review previously reported patients with TSC with early EEG findings. Our patients were started on vigabatrin after the onset of focal seizures with the aim of preventing seizure recurrence, halting the possible progression to infantile spasms or focal seizures, and preventing neurodevelopmental decline. ResultsBoth patients remain seizure free and have reached appropriate developmental milestones. ConclusionsWe recommend early serial EEG monitoring once a diagnosis of TSC is suspected or confirmed in infants. Additional prospective studies are needed to assess the long-term outcome of early antiepileptic drug initiation as soon as electrographic seizure activity is detected.

The First-Time Seizure Emergency Department Electroencephalogram Study

Seizures account for 1.2% of all emergency department (ED) visits, with 24% of those representing first-time seizures. Our primary goal is to determine whether obtaining an electroencephalogram (EEG) in the ED after a first-time seizure can identify individuals appropriate for initiation of anticonvulsant therapy on ED discharge. Our secondary goals are to determine the association of historical and clinical seizure features with epileptic EEGs and to determine the interobserver agreement for the EEG interpretation. We conducted a prospective study including patients older than 17 years with either a first-time seizure or previous seizures without a previous EEG, all of whom were candidates for discharge home from the ED without antiepileptic drug treatment. We based seizure diagnosis on provider impression. We excluded patients with laboratory studies or neuroimaging deemed to be the seizure cause. EEG technicians performed a 30-minute EEG in the ED, which was immediately remotely interpreted by an epileptologist, who made a recommendation on antiepileptic drug initiation. We categorized EEGs as normal, abnormal but not epileptic, or epileptic. In accordance with duplicate EEG interpretation by a second, blinded epileptologist, we calculated interrater agreement for EEG interpretation and antiepileptic drug initiation. As a secondary analysis, according to questionnaires completed by patients and seizure observers, we explored the association of aura, focal symptoms, provocation, or historical risk factors with epilepsy. We enrolled 73 patients, 71 of whom had an EEG performed. All EEGs were performed within 11 hours of seizure, with an average of 3.85 hours. Twenty-four percent of patients (95% confidence interval 15% to 36%) received a diagnosis of epilepsy, and all began receiving antiepileptic drug therapy from the ED. Our final study sample size afforded only an exploratory analysis about an association between aura, focal onset, provocation, or historical risk factors with an epilepsy diagnosis. Weighted κ agreement for EEG interpretation was 0.69 (95% confidence interval 0.55 to 0.82). Of the 34 patients who followed up with an epileptologist, 9 had received a diagnosis of epilepsy in the ED, and none had antiepileptic drug medication stopped at initial follow-up. ED EEG performance in adults with first-time seizures results in a substantial yield of an epilepsy diagnosis and immediate initiation of antiepileptic drug treatment. A larger study is required to determine whether historical and clinical seizure features are associated with an ED epilepsy diagnosis.

P.028 Incidence and management of seizures and epilepsy after ischemic stroke: a systematic review

Background: Seizures and epilepsy are well-recognized complications after stroke. However, the reported incidence varies and so does their management. Methods: We conducted a systematic review and sought observational studies that reported incidence of seizures and/or epilepsy following arterial ischemic stroke in adults, and those that reported the management of epilepsy, specifically the use of EEG to determine the diagnosis, timing of initiation of anti-epileptic drug (AED), and the treatment response to AEDs. We systematically searched in Medline including Pre-Medline and EMBASE databases from their inception to October 1, 2015. First the titles and then the articles were reviewed and rated by two independent reviewers, and disagreements were resolved by consultation with a third reviewer. A pre-set data abstraction form was used for extracting the information of interest. Results: A total of 11,815 titles were found from the initial search strategy across all databases following de-duplication. Of these 130 studies are included for full text review. The adjudication process is underway and the reviewers are sifting through these studies to select the studies that will be included in the final review. Conclusions: Understanding incidence and management of post-stroke epilepsy is important to improve the quality of life of stroke survivors.

Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics.

Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.

Poor treatment outcomes and associated factors among epileptic patients at Ambo Hospital, Ethiopia

Abstract Approximately one third of patients with epilepsy continue to experience seizure despite the prescription of appropriate doses of anti-epileptic drugs. The objective of this study was to assess treatment outcomes and associated factors for poor treatment outcomes among patients taking anti-epileptic drugs at Ambo Hospital, West Shewa, Ethiopia. A hospital based cross–sectional study was conducted. Verbal consent from participants was taken before interview. Fifty-nine patients (44.7%) had poor seizure control. The most common seizure triggering factors were emotional stress (97.4%), sleep deprivation (78.1%), missing meal (29.8%)and missing medication (21.9%). Seventy one patients (53.8%) were non-adherent to medication. Therefore there is significant association between level of adherence (P=0.001), number of seizure attacks before anti-epileptic drugs initiation (p=0.028), electroencephalogram(neurologic abnormality) (p=0.04) and age at onset of seizure (diagnosis) (p=0.026). Poor treatment outcomes among epileptic patients is associated with level of adherence, number of seizure attacks before anti-epileptic drugs initiations, electroencephalogram(neurologic abnormality) and age at onset of seizure (diagnosis). The most common seizure triggering factors were emotional distress, sleep deprivation, missing meal, missing medication and noise. Strict medication adherence evaluation and enhancement through continues health education, close follow up with multidisciplinary approach are fundamental to the successful management of epileptic patients.

Factors affecting epilepsy treatment outcomes in Nigeria.

Epilepsy is a complex chronic illness with variable treatment outcomes determined by factors specific to each affected person. We investigated prognostic factors for epileptic seizure outcome after 2 years of anti-epileptic drug (AED) monotherapy. Two hundred and thirty-four AED naïve epilepsy patients were started on AED monotherapy and monitored for 2 years for seizure control. Patients on AED polytherapy were excluded. Prognostic factors investigated were socio-demographics characteristics, age of onset of epilepsy, etiology and precipitants of seizures, presenting seizure types, duration of epilepsy before initiation of AED, family support for treatment, compliance to AED, and clinic attendance. Patients were 160 (68.4%) males and 74 (31.6%) females, with mean ages of 26.2 ± 10.4 and 30.7 ± 16.0 years, respectively. Mean age of onset of epilepsy was 19.0 ± 15.0 years. None of the patients was treated with AED for first seizures, although 75% received traditional and spiritual therapy. Majority were single and of low socioeconomic background, and treatment was funded mainly by parents/guardians. About 88% presented with partial seizures, and carbamazepine was the commonest AED used followed by phenytoin sodium. At the end of 2 years of AED, 147 (63%) achieved complete seizure control, and significant prognostic factors were female sex, age older than 20 years at presentation, secondary and tertiary education attainment, being employed, family support, regular clinic attendance, AED compliance, and generalized epilepsy. Patients with epilepsy are more likely to achieve complete seizure control when they are older, educated, and employed or supported by family members to buy their AEDs and attend clinics regularly.

An Examination of 1-Year Adherence and Persistence Rates to Antiepileptic Medication in Children With Newly Diagnosed Epilepsy

The primary aim of the current study was to use new methods to examine 1-year quality of medication dosing (adherence) and continuation with medication treatment (persistence) rates to antiepileptic drugs (AEDs) in children with newly diagnosed epilepsy. Medication-taking behaviors of AEDs were assessed using electronic monitors for 117 children with newly diagnosed epilepsy for the first year after diagnosis. Approximately 15% of participants were categorized as nonpersistent (i.e., failed to take medication for >15 consecutive days) 6 months after AED initiation, which increased to 26.6% of participants at 1 year. The majority of medication dosing events took place within a +/-2-hr interval as recommended. The group with lower socioeconomic status demonstrated more nonpersistence over time. Examining adherence and persistence in medication taking behaviors may yield different types of data for clinical and research purposes.

Emergency management of febrile status epilepticus: results of the FEBSTAT study.

Treatment of seizures varies by region, with no standard emergency treatment protocol. Febrile status epilepticus (FSE) is often a child's first seizure; therefore, families are rarely educated about emergency treatment. From 2002 to 2010, 199 subjects, age 1month to 6years, were recruited as part of a prospective, multicenter study of consequences of FSE, which was defined as a febrile seizure or series of seizures lasting >30min. The patients' charts were reviewed. No standardized treatment protocol was implemented for this observational study. One hundred seventy-nine children received at least one antiepileptic drug (AED) to terminate FSE, and more than one AED was required in 140 patients (70%). Median time from the seizure onset to first AED by emergency medical services (EMS) or emergency department (ED) was 30min. Mean seizure duration was 81min for subjects given medication prior to ED and 95min for those who did not (p=0.1). Median time from the first dose of AED to end of seizure was 38min. Initial dose of lorazepam or diazepam was suboptimal in 32 (19%) of 166 patients. Ninety-five subjects (48%) received respiratory support by EMS or ED. Median seizure duration for the respiratory support group was 83min; for the nonrespiratory support group the duration was 58min (p-value<0.001). Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration. FSE rarely stops spontaneously, is fairly resistant to medications, and even with treatment persists for a significant period of time. The total seizure duration is composed of two separate factors, the time from seizure onset to AED initiation and the time from first AED to seizure termination. Earlier onset of treatment results in shorter total seizure duration. A standard prehospital treatment protocol should be used nationwide and education of EMS responders is necessary.

Reducing versus stopping antiepileptic medications after temporal lobe surgery.

ObjectiveTo study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery.MethodsWe reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using Cox-proportional hazard modeling and adjusted for, while comparing longitudinal seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped.ResultsA total of 609 patients (86% adults) were analyzed. Follow-up ranged from 0.5 to 16.7 years. Most (64%) had hippocampal sclerosis. Overall, 229 patients had remained on their same baseline AEDs, while 380 patients stopped (127 cases) or reduced (253 cases) their AEDs. Mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) compared to those seizure-free at last follow-up (1.44 years; P-value 0.03). Whether AEDs were withdrawn 12 or 24 months after surgery, there was a 10–25% higher risk of breakthrough seizures within the subsequent 2 years. However, 70% of patients with seizure recurrence after AED discontinuation reachieved remission, as opposed to 50% of those whose seizures recurred while reducing AEDs (P = 0.0001). Long-term remission rates were similar in both AED discontinuation and “unchanged” groups (82% remission for AEDs withdrawn after 1 year and 90% for AEDs withdrawn after 2 years), while only 65% of patients whose recurrences started during AED reduction achieved a 2-year remission by last follow-up.InterpretationAED withdrawal increases the short-term risk of breakthrough seizures after TLE surgery, and may alter the long-term disease course in some patients.

Antiepileptic drug nonadherence in children with epilepsy

Currently, no cure is available for many children with epilepsy, and the most frequently used treatment for seizures is antiepileptic drug (AED) therapy. Since 20% to 30% of children with epilepsy experience seizures that are not completely controlled with treatment,1 it is imperative that these children achieve and maintain adherence to prescribed treatment to have the best possible health outcomes. Studies have consistently shown that nonadherence is related to increased health care utilization.2 However, adherence rates in children with epilepsy, even within the first month of AED initiation, are not ideal.3 Modi et al.4 previously found that 58% of children with newly diagnosed epilepsy exhibited nonadherence over the first 6 months of AED therapy, and they identified 4 nonadherent trajectories: severe early, severe delayed, moderate, and mild, in addition to a near-perfect trajectory.

Suicide Attempts in Patients With Bipolar Disorder Tend to Precede, Not Follow, Initiation of Antiepileptic Drugs

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.To the Editor: In 2008, the US Food and Drug Administration (FDA) issued an alert stating that antiepileptic drugs (AEDs) can increase suicidal thoughts and behaviors. However, subsequent studies found conflicting evidence regarding the relationship between antiepileptic drugs and suicidal behavior. Furthermore, the American Epilepsy Society and others have cautioned against the unintended consequences of putting warnings on safe drugs.

Enzyme induction with antiepileptic drugs: Cause for concern?

Several commonly prescribed antiepileptic drugs (AEDs)-including phenobarbital, phenytoin, and carbamazepine-stimulate the synthesis of a broad range of monooxygenase and conjugating enzymes. These agents are well known to reduce the duration and action of many lipid- and non-lipid-soluble drugs, including anticoagulants, cytotoxics, analgesics, antiretrovirals, glucocorticoids, statins, antihypertensives, oral contraceptives, psychoactive drugs, immunosuppressants, and of course, other AEDs. This process, therefore, may be associated with a number of clinical problems including higher cancer mortality, progressive AIDS, transplant rejection, and unwanted pregnancy. Withdrawal of enzyme-inducing AEDs will increase the concentration of induced drugs, bringing with it substantial risk of toxicity if doses are not concomitantly reduced. Yet the potential widespread adverse health consequences of these interactions, both with AED initiation and withdrawal, remain largely underappreciated. Furthermore, induction also affects enzymes involved in endogenous metabolic pathways, and can alter bone biochemistry, gonadal steroids, and lipid markers. Therefore, enzyme-inducing AEDs may contribute to the development of a number of comorbidities, including osteoporosis, sexual dysfunction, and vascular disease. This process continues as long as the patient takes the inducer. Modern AEDs that do not possess this property have similar efficacy for the common epilepsies. Accordingly, perhaps consideration should be given to starting treatment with, or even switching patients to, non-enzyme-inducing AEDs.

The characteristics and related influencing factors of ambulatory EEGs in patients seizure-free for 3–5 years

Epileptic patients have a higher relapse risk when EEGs before the initiation of anti-epileptic drug (AED) withdrawal show epileptiform activity. The purpose of this study is to assess the characteristics of ambulatory EEGs before the decision to withdraw AEDs and to clarify potential influencing factors for abnormal EEGs. 214 epileptic patients were included in the study. These patients were seizure-free for 3-5 years on AED medication. Ambulatory 24-h EEGs were performed before the decision to withdraw AEDs. The demographical data and clinical information of the patients were used for the analysis of influencing factors for EEG findings. Ambulatory EEGs showed abnormalities in 41.1% of the patients (88/214). Of 88 patients with abnormal EEGs, 43 had unequivocal epileptic discharges; and 45 only had nonspecific EEG abnormalities. In our analysis, the potential factors for abnormal EEGs included female, delayed therapy, longer duration of intractability/treatment response time and medications failed. In many patients ambulatory EEGs remain abnormal even after seizure-free for 3-5 years; and many factors influenced the characteristics of the EEGs. The findings can assist in establishment of therapeutic principles.

Cerebral infarction following a seizure in a patient with subarachnoid hemorrhage complicated by delayed cerebral ischemia

Seizures are a recognized complication of subarachnoid hemorrhage (SAH). They can increase the cerebral metabolic demands and lead to cardiopulmonary compromise. This could be detrimental in the setting of delayed cerebral ischemia (DCI), when the brain tissue is vulnerable to further reductions in oxygen delivery or increases in demand. An association between seizures and worsening ischemia could influence the decision to use antiepileptic drug (AED) prophylaxis in patients with vasospasm. A 64-year-old woman developed confusion, aphasia and right hemiparesis on day 7 after aneurysmal SAH. Angiography confirmed severe anterior circulation vasospasm. She initially responded to hypertensive therapy with almost complete resolution of her ischemic neurological deficits. However, on day 10, she had a single generalized seizure and required intubation for airway protection. Her blood pressure dropped with AED initiation, necessitating an increase in the previously stable dose of vasopressors. She developed aphasia and worsening hemiparesis that did not resolve despite hemodynamic augmentation. Subsequent head computed tomographies revealed new infarction in the left anterior cerebral artery territory not present previously. She had received prophylactic phenytoin for only 3 days, as per our SAH protocol. AED prophylaxis is typically used early after SAH when the risk is high and a seizure may precipitate aneurysmal rebleeding. This case illustrates how a later seizure in the setting of vasospasm can lead to decompensation of DCI, with potential for irreversible infarction. Therefore, patients with vasospasm may benefit from extended durations of prophylaxis to prevent such complications.

Hypersensitivity syndrome reactions to antiepileptic drugs, clinical characteristic and association with HLA-B*1502

To investigate the cutaneous adverse reactions to antiepileptic drugs (AEDs), clinical characteristic and the association with HLA-B*1502. A retrospective analysis of four cases of antiepileptic drug hypersensitive syndrome (AHS) were performed on the basis of clinical data, cutaneous adverse reactions to carbamazepine (CBZ) (n = 2) including Stevens-Johnson syndrome (SJS) (n = 1) and hypersensitivity syndrome (HSS) (n = 1); phenobarbital-induced HSS (n = 1) and oxcarbazepine (OXC)-induced HSS (n = 1). All patients received the examinations of polymerase chain reaction (PCR) with sequence specific primers to analyze HLA-B*1502. Two healthy subjects had no history of using antiepileptic drugs as the control. All patients had manifestations of fever, eruption, mucosal involvement and visceral injury. Two cases were diagnosed as Stevens-Johnson syndrome associated with apparent bullae formation. Genotype positive for HLA-B*1502 was association with 2 patients with CBZ/OXC-induced SJS while the other 1 case of CBZ and 1 case of phenobarbital-induced HSS were genotype non-HLA-B*1502. AHS usually occurs within 1 to 2 weeks after initiation of AEDs therapy. The typical presentations are fever, eruption and internal organ involvements, etc. The epileptic patients with CBZ/OXC-induced SJS are related with HLA-B*1502 genotype. But it is not found in HSS patients.

Intractable Epilepsy: Relapsing, Remitting, or Progressive?

Seizure Remission and Relapse in Adults with Intractable Epilepsy: A Cohort Study. Choi H, Heiman G, Pandis D, Cantero J, Resor SR, Gilliam FG, Hauser WA. Epilepsia 2008;49(8):1440–1445. PURPOSE: To investigate the cumulative probabilities of ≥12 month seizure remission and seizure relapse following remission, and to test the associations of clinical characteristics with these two study end points in a prevalence cohort of intractable adult epilepsy patients during medical management. METHODS: A retrospective cohort study of intractable epilepsy patients seen in 2001 at a single center was conducted. Kaplan–Meier analysis was used to estimate the cumulative probabilities of seizure remission and subsequent seizure relapse. Cox proportional hazards models were used to estimate the association ( 1 ) between clinical factors and ≥12 month seizure remission and ( 2 ) between clinical factors and seizure relapse following remission. RESULTS: One hundred eighty-seven subjects met the eligibility criteria for intractable epilepsy. The estimate of probability of remission was about 4% per year. Seizure remission was temporary for some individuals, as 5 out of 20 subjects with remission ultimately relapsed. No clinical factors predicted the likelihood of achieving ≥12 month seizure remission or subsequent seizure relapse. DISCUSSION: Some people with intractable epilepsy achieve ≥12 month seizure remission during medical treatment. Remission, however, is only temporary for some individuals. We were unable to identify clear predictors for remission. Quantifying the Response to Antiepileptic Drugs: Effect of Past Treatment History. Schiller Y, Najjar Y. Neurology 2008;70(1):54–65. OBJECTIVE: To quantify the response to treatment with antiepileptic drugs (AEDs) as a function of the past treatment history and identify additional prognostic factors for predicting the response to newly administered AED treatments. METHODS: A cohort of 478 consecutive patients who received newly administered AED treatments between January 1999 and December 2004 and were followed prospectively for 1.5 to 7.5 years in a single epilepsy clinic. RESULTS: The response to newly administered AED treatments was highly dependent on the past treatment history. The seizure-free rates decreased from 61.8% for the first AED to 41.7%, 16.6%, and 0% after one, two to five, and six to seven past AEDs proved inefficient. This response curve corresponded to a mono-exponential function with a maximal response of 61.8% and half-decay constant of 1.5 AEDs. Likewise the response curve describing a greater than 50% reduction in seizure frequency corresponded to a mono-exponential function with a maximal response of 85.3% and half-decay constant of two AEDs. Three additional independent prognostic factors for predicting the response to AEDs were identified: type of epilepsy, duration of epilepsy, and number of seizures in the 3 months prior to AED initiation. CONCLUSION: Drug resistance is a graded process that follows a mono-exponential course with a half-decay constant of 1.5 to two antiepileptic drugs (AEDs). Although relative drug-resistant epilepsy can be diagnosed after failure of two past AEDs, absolute drug resistance requires failure of six AEDs, as a significant minority of patients (16.6%) is rendered seizure-free by addition of newly administered AEDs even after failure of two to five past antiepileptic drugs.

ANTIEPILEPTIC DRUG THERAPY

We are fortunate to practice in an era in which multiple antiepileptic drug (AED) options are available for use in the treatment of epilepsy and seizures. However, clinical decisions regarding when AED therapy should be initiated and when discontinuation can be considered remain complex. It is known that not every patient presenting with a seizure will suffer a recurrence, and some will do well without treatment. It is also known that a certain proportion of patients with a past history of seizures will enter remission, in which case AEDs can be discontinued. In this chapter, the subjects of AED initiation and discontinuation will be reviewed.