Diagnosing and predicting refractory epilepsy

Over 30% of people with epilepsy will never achieve remission with antiepileptic drug (AED) therapy. These individuals are often severely disabled by their condition, have an unsatisfactory quality of life, and are at increased risk of sudden unexpected death. Early identification of refractory epilepsy would allow prompt referral to specialist services, where the diagnosis can be confirmed, seizures and syndromes classified, AED therapy optimized, and suitability for surgery assessed. Recent studies suggest that patients with symptomatic or cryptogenic epilepsy, those who experience multiple seizures before AED treatment initiation, and those with febrile convulsions, a family history of epilepsy, or psychiatric comorbidities are least likely to respond to drug therapy. Failure to achieve good seizure control with the first one or two AED monotherapies is usually sufficient to highlight the possibility of subsequent refractory epilepsy. For most of these individuals, combination therapy using AEDs with complementary modes of action is the recommended treatment approach.     

Outcomes from a nurse-led clinic for adolescents with epilepsy

PURPOSE: Epilepsy is the commonest serious neurological condition to affect adolescents. We established a nurse-led clinic for young people with suspected or diagnosed epilepsy. Outcomes in all patients referred during the first 4 years after its inception are reported. METHODS: A total of 301 adolescents were seen at the clinic during 1996-1999. Epilepsy was excluded in 135 (45%), including 5 receiving antiepileptic drug (AED) therapy. A single seizure occurred in 22 (7%) others. Seventy-six patients (25%) had treated epilepsy and 68 (23%) were newly diagnosed. RESULTS: More than 1 year's seizure freedom was achieved by 53% of patients, 76% with one AED, 16% with two and 3% with three. Four (5%) patients remained seizure free off medication. Sixteen (11%) were lost to follow-up. Outcome was better (P<0.05) for newly diagnosed (59% seizure free) than for treated (47% seizure free) epilepsy and for idiopathic generalised (60% seizure free) than for partial (46% seizure free) seizures (P<0.02). Magnetic resonance imaging of brain was obtained in 63 (85%) patients with localisation-related epilepsy. Findings were abnormal in 43%, including nine with cortical dysplasia, eight with mesial temporal sclerosis and two with gliomas. CONCLUSIONS: Epilepsy can be difficult to diagnose in adolescents. Outcomes were surprisingly poor suggesting the need for improved services for this patient population.     

Effect of dosage failed of first antiepileptic drug on subsequent outcome

Purpose: The recent definition of drug‐resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization’s defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom (no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25%, 50%, or 75% cutoffs for the DDD of each AED. Key Findings: Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure‐free at last follow‐up (p = 0.06 for 25% DDD, p < 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p < 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure‐free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at <75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08–2.37). Significance: Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug‐resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.     

Prognostic Significance of Failure of the Initial Antiepileptic Drug in Children with Absence Epilepsy

PURPOSE: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long-term remission of epilepsy. METHODS: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and long-term seizure control and remission of epilepsy was collected by patient questionnaire and chart review. RESULTS: Eighty-six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p = 0.07), and lower if generalized tonic-clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow-up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04). CONCLUSIONS: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy.     

Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience

PURPOSE: Although epilepsy surgery, especially temporal lobe epilepsy surgery, is well established to control seizures in patients remaining on antiepileptic drug (AED) treatment, less information is available about how many seizure-free surgical patients will relapse after discontinuation of AEDs under medical supervision. METHODS: A literature review yielded six retrospective clinical observations. RESULTS: After planned discontinuation of AEDs in patients rendered seizure free after epilepsy surgery, most often various forms of temporal lobe surgery, the mean percentage recurrence rate in adults in four studies was 33.8%[95% confidence interval (CI), 32.4-35.2%], with maximum follow-up ranging from 1 to 5 years. Seizure recurrence increased during the follow-up of 1 to 3 years and occurred within 3 years of AED discontinuation. In one study of children with temporal lobe epilepsy, the recurrence rate was 20%. More than 90% of adult patients with seizure recurrence regained seizure control with reinstitution of previous AED therapy. Seizure recurrence was unaffected by the duration of postoperative AED treatment; as a consequence, delaying discontinuation beyond 1 to 2 years of complete postoperative seizure control seems to have no added benefit. The occurrence of rare seizures or auras after surgery did not eliminate the possibility of eventual successful AED discontinuation. CONCLUSIONS: AED discontinuation is associated with a seizure recurrence in one in three patients rendered seizure free by epilepsy surgery. These results will be useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy?

Purpose: To investigate the feasibility of antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) and to identify the predictors of post withdrawal seizure recurrence. Methods: We prospectively studied the seizure outcome of 310 consecutive patients, who were followed for a minimum of 5 years following ATL for medically refractory mesial temporal lobe epilepsy. In seizure‐free patients, we started AED tapering at 3 months in patients on duotherapy/polytherapy and at 1 year after ATL for those on monotherapy. We used Kaplan‐Meier survival curves to estimate the probability of seizure recurrence and complete AED discontinuation, and compared the attributes of recurred and nonrecurred groups of patients by univariate and multivariate logistic regression analyses. Key Findings: Immediately after ATL, 197 patients were on duotherapy and 101 were on monotherapy. We attempted AED withdrawal in 258 patients (83.2%). Sixty‐four patients (24.8%) had seizure recurrence while reducing AEDs. Of 26 patients who had seizure recurrence after complete AED withdrawal, 24 (92.3%) again became seizure‐free after restarting the AEDs. Absence of hippocampal sclerosis on pathologic examination and abnormal postoperative electroencephalogram (EEG) predicted seizure recurrence on multivariate analysis. At the end of follow‐up duration of 8.0 ± 2.0 years, 163 patients (52.6%) were AED free. The cumulative probability of achieving AED‐free status among patients in whom AED withdrawal was attempted, was 44% at fourth year, 65% at sixth year, 71% at eighth year, and 77% at 10th year after ATL. Significance: AED withdrawal can be safely attempted following successful ATL. Seizure recurrences are few and can be managed easily.     

Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy

PURPOSE: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. METHODS: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for >or=1 year during the follow-up period. RESULTS: Sixty-six (75%) patients achieved complete seizure freedom for >or=1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n=60), and in seven (12%) patients after discontinuation of AEDs (n=38). The seizure recurrence rate was not different between the immediate-and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free >or=1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. CONCLUSIONS: Our results suggest that seizure freedom without aura at >or=1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period.     

Prognosis after late relapse following epilepsy surgery

OBJECTIVES: To assess prognosis after late relapse in patients who are seizure free for the first 5 years after epilepsy surgery. METHODS: Patients who were seizure free for the first 5 years after resective epilepsy surgery were included. Date of first seizure recurrence, current seizure status, medication, age, and type of surgery were prospectively registered. Non-parametric statistics were used. RESULTS: One hundred and fifty-nine patients were studied. Thirty-two had at least one recurrent seizure. Time to event analysis showed an annual relapse rate of 4% between years 5 and 10 after surgery. At study termination, 143 of 159 patients (89.9%) were in terminal remission. For 30 patients with late relapse and at least 1-year follow-up thereafter, 53% were in terminal remission and 30% had experienced only rare or nocturnal seizures. Medication use was not associated either with likelihood of relapse or entering remission after relapse. CONCLUSIONS: Patients who are seizure free for the first 5 years after epilepsy surgery remain at risk for seizure recurrence. These relapses are often isolated events, and the long-term prognosis after relapse is often good. Relapse rates were similar in patients on and off AEDs, but the relation between AED taper and relapse is uncertain since patient groups may not be similar.     

Does early postoperative drug regimen impact seizure control in patients undergoing temporal lobe resections?

Objective

To evaluate the impact of postoperative antiepileptic drug (AED) load on seizure control in patients who underwent surgical treatment for pharmacoresistant mesiotemporal lobe epilepsy during the first two postoperative years.

Patients and methods

532 consecutive patients (48.7% males and 51.7% females) who underwent surgical treatment for mesiotemporal lobe epilepsy were retrospectively evaluated regarding effects of AED load on seizures control during the first 2 years following epilepsy surgery. We analyzed whether postoperative increases in postoperative AED load are associated with better seizure control in patients initially not seizure free, and if postoperative decreases in postoperative AED load would increase the risk for seizure persistence or recurrence. For statistical analyses, Fisher’s exact and Wilcoxon test were applied.

Results

68.9, 64.0 and 59.1% of patients were completely seizure free (Engel Ia) at 3, 12 and 24 months after surgery, respectively. Patients in whom daily drug doses were increased did not have a higher rate of seizure freedom at any of the three follow-up periods. Of 16 patients achieving secondary seizure control at 12 months after surgery, only one did so with an increase in drug load in contrast to 15 patients who experienced a running down of seizures independent of drug load increases. Decreases in drug load did not significantly increase the risk for seizure recurrence. Of postoperatively seizure free patients at 3 months after surgery in whom AED were consequently reduced, 85% remained completely seizure free at 1 year and 76% at 1 year after surgery, respectively, as opposed to 86% each when AED was not reduced (differences n.s.). Mean daily drug load was significantly lower in seizure free patients at 12 and 24 months compared to patients with ongoing seizures.

Conclusion

In this large patient cohort stratified to the epilepsy syndrome neither did a postoperative reduction in drug load significantly increase the risk for seizure relapse nor did increases in drug dosages lead to improved seizure control. Mean drug load was on average lower in seizure free- than non-seizure free patients at 12 and 24 months of follow-up. Secondary seizure control after initial postoperative seizures in > 90% of cases occurred as a running down, independent of an AED increase. Thus, the effect of the surgical intervention rather than the postoperative drug regimen was the key determinant for seizure control. This finding supports a curative role of temporal lobe surgery rather than an effect rendering the majority of patients’ pharmacoresponsive with a critical role of the antiepileptic drug regime for seizure control.

     

First, do no harm: the risks of overtreating children with epilepsy

BACKGROUND: Although overtreatment with antiepileptic drugs contributes to the morbidity associated with epilepsy, many children still are overtreated. OBJECTIVE: To evaluate if the withdrawal of at least one antiepileptic drug (AED) in children with refractory epilepsy using polytherapy enable a better seizure control. METHOD: This was a prospective study. Children with refractory epilepsy using at least two AEDs were included. Once the patient, or guardian, agreed to participate in the study, one or more AED were slowly tapered off. The remaining AEDs dosages could be adjusted as needed, but a new AED could not be introduced. RESULTS: Fifteen patients were evaluated, three girls; ages ranging from 3 to 18 (mean=8.7 years). After at least one AED withdrawal, two (13.5%) patients became seizure free, seizures improved >50% in 5 (33.5%) patients, did not change in 5 (33.5%), and seizure frequency became worse in 3 (20%). Adverse events improved in 12 patients (80%). CONCLUSION: The withdrawal of at least one AED is a valuable option in the treatment of selected children with refractory epilepsy.     

Remission of Seizures in a Population-Based Adult Cohort with a Newly Diagnosed Unprovoked Epileptic Seizure

PURPOSE: To investigate the probability of achieving remission of seizures after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. METHODS: 107 patients aged 17 years or older with a newly diagnosed unprovoked epileptic seizure (index seizure) in 1985 through 1987 were followed up until the date of death or to the end of 1996. The proportion of cases during follow-up that attained a 1-year, 3-year, 5-year remission was calculated by actuarial analyses. Variables for stratification were age at diagnosis, seizure type, etiology, EEG, and the occurrence of seizures within 1 year of initiation of antiepileptic drug (AED) therapy. RESULTS: Cumulative 1-, 3- and 5-year remission rates were 68, 64, and 58%. There was no statistically significant difference regarding time points of achieving a 1-year remission after epilepsy diagnosis and the subsequent probability during follow-up of attaining a 5-year remission. Having seizures within 1 year after beginning with an AED was a statistically significant predictor of never achieving 1-year remission of seizures during follow-up (refractory seizures). Other stratified variables were not statistically significant predictors. CONCLUSIONS: Seizure prognosis for the majority of patients with newly diagnosed epilepsy is good. The time required after epilepsy diagnosis to achieve a 1-year remission of seizures does not affect the probability of additionally achieving a 5-year remission. Patients with refractory seizures can be identified within a few years from diagnosis of epilepsy. These patients must be targeted early for optimization of pharmacologic treatment, possible surgery, and psychosocial intervention.     

Response to sequential treatment schedules in childhood epilepsy: Risk for development of refractory epilepsy

PurposeTo investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood.MethodsAll children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. “Seizure control” was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and “refractory epilepsy” as failure of >2 drugs plus >1 seizure/month for ≥18 months.Results343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving “seizure control” was 70% and 86% at 5 and 10 years. 59% of patients were “controlled” with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally “controlled” with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years.ConclusionAfter failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy.     

Levetiracetam in clinical use—a prospective observational study

This prospective observational study explored the efficacy and tolerability of levetiracetam (LEV) in a prospective series of 200 patients with refractory epilepsy attending a single epilepsy service. Patients were started on adjunctive LEV using one of two titration schedules (slow and fast) and patients were studied for at least 6 months after commencing LEV. Fifty-three patients had severe learning disabilities. 14.3% became seizure free, 57.7% showed >50% reduction, 15.4% showed seizure increase. Patients with learning disability showed less positive but still very worthwhile results. A highly significant improvement in clinical outcomes overall is shown (P<0.0001). 56.6% showed no adverse effects, 27.4% showed minor adverse effects, 16% were withdrawn. The most common adverse effect causing drug withdrawal was seizure exacerbation (12%) which was much commoner in primary generalised epilepsies (P=0.00035). LEV appears to be an effective and well-tolerated anti-epileptic drug in drug resistant partial epilepsies.     

Limitations in the Medical Treatment of Cryptogenic or Symptomatic Localization-Related Epilepsies of Childhood Onset

Summary: We retrospectively examined 169 patients who had cryptogenic or symptomatic localization-related epilepsies (LRE) and were followed-up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.     

Predictors for long-term seizure outcome in juvenile myoclonic epilepsy: 25-63 years of follow-up

Purpose: The long‐term seizure outcome of juvenile myoclonic epilepsy (JME) is still controversial; the value of factors that are potentially predictive for seizure outcome remains unclear. The aim of this study was both to investigate the long‐term seizure outcome in patients with JME after a follow‐up of at least 25 years and to identify factors that are predictive for the seizure outcome. Methods: Data from 31 patients (19 women) with JME were studied. All of them had a follow‐up of at least 25 years (mean 39.1 years) and were reevaluated with a review of their medical records and direct telephone or face‐to‐face interview. Key Findings: Of 31 patients 21 (67.7%) became seizure‐free; in six of them (28.6%) antiepileptic drug (AED) treatment was discontinued due to seizure freedom. The occurrence of generalized tonic–clonic seizures (GTCS) preceded by bilateral myoclonic seizures (BMS) (p = 0.03), a long duration of epilepsy with unsuccessful treatment (p = 0.022), and AED polytherapy (p = 0.023) were identified as significant predictors for a poor long‐term seizure outcome, whereas complete remission of GTCS under AED significantly increased the chance for complete seizure freedom (p = 0.012). The occurrence of photoparoxysmal responses significantly increases the risk of seizure recurrence after AED discontinuation (p = 0.05). Significance: This study shows conclusively that JME is a heterogeneous epilepsy syndrome. Life‐long AED treatment is not necessarily required to maintain seizure freedom. Several long‐term outcome predictors that can potentially increase the ability of clinicians and their confidence to recommend different treatment options to patients with JME were identified.     

Systematic Testing of Medical Intractability for Carbamazepine, Phenytoin, and Phenobarbital or Primidone in Monotherapy for Patients Considered for Epilepsy Surgery

Summary: Purpose: To assess medical intractability in patients considered for restrictive epilepsy surgery.
Methods: Seventy-four patients received single drug treatment with carbamazepine (CBZ), phenytoin (PHT), and either phenobarbital (PB) or primidone (PRM). Medical intractability was established if seizure control was not obtained despite maximum tolerable doses of the drug. In all, 120 single drug treatments were administered with the drugs that has not been administered at maximal doses in monotherapy before the study.
Results: Complete seizure control was not achieved in any patient. However, 7 patients (9.5%) had significant seizure reduction of at least 80%. In 4 patients, only the third antiepileptic drug (AED) proved effective.
Conclusion: The poor result of AED monotherapy in our patients may be attributed to the patients'long-standing chronic epilepsies and high seizure frequencies. Our findings suggest that despite the failure of one or two major AEDs in controlling seizures completely, further single drug treatment may still improve the quality of life in some patients who are candidates for epilepsy surgery.     

Outcomes in newly diagnosed localization-related epilepsies.

A total of 558 patients with a range of localization-related epilepsy syndromes starting treatment in a single centre were followed over a period of up to 20 years. Overall, 343 (62%) patients became seizure free for 12 months or more (responders), 92% of whom (57% of total population) remained in remission until the end of follow-up. Only 27 (5%) responders relapsed and subsequently developed refractory epilepsy. The remaining 215 (38%) patients never became seizure free for any 12-month period. There were no significant differences in outcome between cryptogenic (56% remission) and symptomatic (57% remission) epilepsies. Patients with underlying cortical atrophy (71% remission; p<0.05) or cerebrovascular disease (70% remission; p<0.01) did better, while those with traumatic brain injury (35% remission; p<0.001) did worse than the remainder of the symptomatic group. Remission rates in patients with cortical dysplasias (60%), hippocampal atrophy (50%) and primary brain tumors (52%) appeared no different from those with other symptomatic epilepsies. Overall, 20-40% patients with each epilepsy syndrome reported no further seizures after starting AED treatment including 21% with hippocampal atrophy and 33% with cortical dysplasia. More than 50% of patients developing localization-related epilepsy during adolescence or in adulthood had a good outcome. Prognosis in those with underlying hippocampal atrophy or cortical dysplasia was not always bad.     

Response to first drug trial predicts outcome in childhood temporal lobe epilepsy.

OBJECTIVE: To construct a clinical prediction model for the early identification of children destined to develop refractory temporal lobe epilepsy (TLE) 2 years after epilepsy onset. METHODS: Patients with TLE between 1 and 18 years old seen in the Division of Neurology at Children's Hospital of Philadelphia during 1999 were identified through billing records and chart review. Data were abstracted independently on 5 candidate predictor variables for refractory TLE and on seizure frequency outcome at 2 years after epilepsy onset. RESULTS: One hundred twenty patients met inclusion criteria and had at least 2 years of follow-up. Forty-five of 120 patients (37.5%) had refractory TLE at 2 years after onset, and 75 of 120 (62.5%) were seizure free. Three significant predictors of refractory TLE were found on bivariate analysis: an early risk factor for epilepsy (risk ratio = 3.5 [95% CI 2.2, 5.6]), temporal lobe abnormality on MRI scan (2.9 [95% CI 1.9, 4.6]), and failure of the first antiepileptic drug (AED) trial (16.5 [95% CI 6.3, 43.9]). Logistic regression indicated that the best model to predict refractory TLE contained only the variable "failure of first AED trial," with a positive predictive value of 0.89 (95% CI 0.76, 0.96) and negative predictive value of 0.95 (95% CI 0.87, 0.99) to predict "refractory TLE" at 2 years. CONCLUSIONS: Failure of first AED trial accurately predicts refractory TLE at 2 years after onset, based on retrospective cohort data in children. If verified prospectively and with longer follow-up, this finding should support earlier consideration of surgical options.     

Factors related to successful antiepileptic drug withdrawal after anterior temporal lobectomy for medial temporal lobe epilepsy.

OBJECTIVE: To assess the rate of successful antiepileptic drug (AED) discontinuation, prognostic factors and proper time of AED withdrawal after surgery for medial temporal lobe epilepsy (MTLE). METHODS: We reviewed 171 consecutive patients who underwent resective surgery for MTLE. All patients were followed up for more than two postoperative years. AEDs were slowly tapered with an individualized schedule for each patient. Outcome status was determined from medical records and telephone interviews. RESULTS: 41.2% of patients experienced no seizure recurrence. 34.5% discontinued medication without seizure recurrence for more than 2 years at final assessment. Multivariate analysis revealed that an age greater than 30 years at surgery and postoperative AED reduction before 10 months increased the risk of recurrence [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1-3.9 and HR 2.5, CI 1.1-5.8]. CONCLUSIONS: Resective surgery for MTLE brings seizure remission without AED to one-third of patients. Postoperative AED tapering is recommended after at least 10 months. Younger age at surgery is a good predictive factor of remission after MTLE surgery.     

Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring

PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.