Pharmacological outcomes in people with mental retardation and epilepsy

The aim of this study was to examine prospective outcomes in mentally retarded people with epilepsy seen for the first time during 1998 until the end of 2001. Two hundred and fourteen patients (120 men, 94 women, aged 11-70 years [median 34 years]) were referred over this 4-year period. Median duration of follow-up was 18 months (range, 13-36 months). Seventeen (8%) had nonepileptic attacks only, 10 of whom were being treated with antiepileptic drugs (AEDs). The remaining 197 (92%) patients had epilepsy, the majority (n=151, 77%) presenting with focal seizures. A total of 22 patients were started on AED treatment, with seizure freedom for at least a year being achieved in 10 (45%). AED manipulation was undertaken in a further 136 patients, resulting in 59 (43%) becoming seizure-free. No relationship was found between extent of mental retardation and seizure control. There was no deterioration in mean caregiver scores rating sleep, appetite, alertness, and behavior. These findings suggest that AED therapy can result in seizure freedom in more than 40% of mentally retarded people with epilepsy without producing unacceptable toxicity.     

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.     

Prognosis of epilepsy withdrawn from antiepileptic drugs

Abstract Antiepileptic drugs (AED) were discontinued in 55 epileptics who had been free from seizures treated with AED, in accordance with the following criteria and procedures. (i) A reduction in AED commences when patients have been free from seizures for at least 2 years and epileptic discharges have also disappeared in repeated electroencephalogram (EEG) recordings during that period. (ii) AED are gradually reduced if no relapse is seen in clinical seizures and epileptic discharges in EEG. (iii) As a rule at least 2 years are required as the interval from the onset of a reduction to the withdrawal of AED. Forty-three patients were followed up by a questionnaire and/or by telephone and the follow-up period from the withdrawal of AED to the survey ranged from 0.9 to 8.8 years; in 38 patients (88.4%) the period was longer than 2 years. No relapse of seizures was found in any of the 43 patients. The severity of epilepsy judged by the total number and frequency of seizures, the presence of neuropsychiatric complications, the combination of different types of seizures, and the duration of epilepsy from the seizure onset to the last seizure appeared not to be risk factors for the recurrence of seizure. Normal EEG was, however, considered to be an important prerequisite for a good prognosis.     

Intermittent symptoms in neurocysticercosis: could they be epileptic?

OBJECTIVES: Some patients with neurocysticercosis (NCC) develop perilesional gliosis during the course of healing and carry poor prognosis for the seizure control. We evaluated the clinical status of these patients during complete control of their original seizures on anti-epileptic drugs (AED). MATERIAL AND METHODS: We studied 172 patients with solitary NCC, 45 with perilesional gliosis as visible on magnetization transfer spin echo (MTSE) magnetic resonance imaging and 127 without gliosis, for any abnormal symptom during the course of their "seizure-free" period. All of them received optimum doses of AED to control the original seizures. RESULTS: Patients with gliosis had high incidence of abnormal symptoms with or without corresponding abnormalities on surface electroencephalogram (EEG). These symptoms disappeared on increasing the dose or adding a new AED. The symptoms, which were transient episodic in nature, included heaviness, dystonic posturing, weightlessness, numbness and alien limb phenomenon on the side of the body contralateral to cerebral lesion, and headache. CONCLUSION: Patients with NCC who develop perilesional gliosis during the process of healing tend to suffer from disturbing intermittent symptoms during their apparent control of seizures. The symptoms are controllable with increased dosage of previously prescribed or addition of another AED. As these symptoms could possibly be epileptic in nature, their identification and treatment may have a bearing on long-term seizure control after stopping AED therapy.     

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.     

Remission of Seizures and Predictors of Intractability in Long-Term Follow-Up

In an incidence cohort, remission and relapse rates and determinants were studied in 178 patients followed long-term. A comparative study of predictive factors was performed in 40 patients with histories of antiepileptic (AED)-drug-refractory epileptic seizures in the last 10 years of follow-up and compared with the other 138 cohort subjects. The two groups were cross-tabulated with 353 variables of family history, obstetric, developmental and seizure histories, and current medical and social status. Multivariate analyses were applied for control of confounding. Defined or probable remote symptomatic etiology of seizures, abnormal neurologic development/ status, high initial seizure frequency, occurrence of status epilepticus, and poor short-term effects of AED therapy were significantly associated with long-term AED refractoriness. On logistic regression analyses, poor short-term outcome of AED therapy [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2–10.4], occurrence of status epilepticus (OR 11.4; 95% CI 3.2–41.0), high initial seizure frequency (OR 4.6; 95% CI 1.1–19.3), and remote symptomatic seizure etiology (OR 2.9; 95% CI 1.1–8.2) remained the only independent predictors of seizure intractability. These factors enable early assessment of need for epilepsy surgery.     

Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex

BACKGROUND: Epilepsy is a common neurologic complication of tuberous sclerosis complex (TSC) and it is often refractory to treatment. Therefore, treating physicians are often reluctant to discontinue antiepileptic drugs (AEDs) in individuals with TSC who have attained seizure remission. To our knowledge, seizure remission and AED discontinuation in children with TSC has not been studied. OBJECTIVE: To characterize seizure remission and AED discontinuation in children with TSC. METHODS: Retrospective medical record and neuroimaging analysis of 15 children with TSC and epilepsy who had seizure remission, with a subsequent trial of discontinuation of AED treatment. RESULTS: The seizure remission rate for the group of patients with TSC and epilepsy was 14.2%. From the group of 15 patients who had a remission, the absolute relapse rate was 26.7% after a mean follow-up of 5 years 7 months. Patients with sustained remission were more likely to have normal intelligence and only a few cortical or subcortical lesions on neuroimaging. CONCLUSIONS: The proportion of children with TSC and epilepsy who achieve seizure remission is small. Nevertheless, some do attain seizure remission, and AEDs may be successfully discontinued. Mild cerebral involvement is a general clinical marker for seizure remission. The relapse rate in those who have undergone a trial of discontinuation of AED therapy is comparable with the rate in the general pediatric population with epilepsy.     

Association between antiepileptic drug dose and long-term response in patients with refractory epilepsy

Seizures in patients with medically refractory epilepsy remain a substantial clinical challenge, not least because of the dearth of evidence-based guidelines as to which antiepileptic drug (AED) regimens are the most effective, and what doses of these drugs to employ. We sought to determine whether there were regions in the dosage range of commonly used AEDs that were associated with superior efficacy in patients with refractory epilepsy. We retrospectively analyzed treatment records from 164 institutionalized, developmentally disabled patients with refractory epilepsy, averaging 17 years of followup per patient. We determined the change in seizure frequency in within-patient comparisons during treatment with the most commonly used combinations of 12 AEDs, and then analyzed the response to treatment by quartile of the dose range for monotherapy with carbamazepine (CBZ), lamotrigine (LTG), valproate (VPA), or phenytoin (PHT), and the combination LTG/VPA. We found that of the 26 most frequently used AED regimens, only LTG/VPA yielded superior efficacy, similar to an earlier study. For the monotherapies, patients who were treated in the lowest quartile of the dose range had significantly better long-term reduction in seizure frequency compared to those treated in the 2nd and 3rd quartiles of the dose range. Patients with paired exposures to CBZ in both the lowest quartile and a higher quartile of dose range experienced an increase in seizure frequency at higher doses, while patients treated with LTG/VPA showed improved response with escalation of LTG dosage. We conclude that in this population of patients with refractory epilepsy, LTG/VPA was the most effective AED combination. The best response to AEDs used in monotherapy was observed at low dosage. This suggests that routine exposure to maximally tolerated AED doses may not be necessary to identify those patients with drug-resistant seizures who will have a beneficial response to therapy. Rather, responders to a given AED regimen may be identified with exposure to low AED doses, with careful evaluation of the response to subsequent titration to identify non-responders or those with exacerbation of seizure frequency at higher doses.     

How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy?

It is well recognized that two-thirds of patients with drug-resistant temporal lobe epilepsy will be free of disabling seizures with continued medical treatment after temporal resection. Seizure recurrence has been noted during a five-year follow-up in approximately one-third of these seizure-free patients mostly but not exclusively following planned complete discontinuation of antiepileptic drugs (AEDs). This leaves one-third of patients without disabling seizures and without AEDs several years after surgery. Despite improvements in seizure frequency or severity, seizures persist in another third of patients undergoing surgery. Although cure (five years without any seizures and off AEDs) is the ultimate aim of epilepsy surgery, the percentage of patients cured by surgery cannot be well defined at the moment. We need a long-term randomized controlled trial on AED discontinuation in seizure-free patients followed by long-term open extension to determine if only one in three adult patients with drug-resistant temporal lobe epilepsy is cured by surgical intervention.     

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.