Wada memory performance predicts seizure outcome after epilepsy surgery in children

PURPOSE: Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children. METHODS: One hundred fifty-six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty-eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II-IV) at follow-up (mean follow-up interval, 2.3 years). RESULTS: Seizure-free children recalled 19.3% more Wada memory items after ipsilateral injection than did non-seizure-free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure-free children recalled 27.7% more items after ipsilateral injection than did non-seizure-free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01). CONCLUSIONS: Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.     

Early predictors of outcome in newly diagnosed epilepsy

Longitudinal studies of newly diagnosed epilepsy in children and adults have identified prognostic factors that allow early identification of patients whose seizures are likely to remain uncontrolled with antiepileptic medication. Results from outcome studies may be subject to bias, depending on the setting (community versus clinic), design (retrospective versus prospective) and characteristics of the patient cohort studied (age, types of epilepsy, specific comorbidities). Nevertheless, factors such as early response to medication, underlying aetiology, and number of seizures prior to initiation of treatment have consistently been found to be predictive of seizure outcomes. Other variables such as age, electroencephalographic findings and the presence or absence of psychiatric co-morbidities have been correlated with outcomes in some analyses. This review has examined studies of seizure outcomes in adults and children with newly diagnosed epilepsy identifying the risk factors that are associated with subsequent refractory epilepsy.     

Predictors of seizure outcome after temporal lobectomy for intractable epilepsy

OBJECTIVES: To assess predictors of outcome of temporal lobectomy for intractable epilepsy. MATERIAL AND METHODS: In 63 adult patients operated with anterior temporal lobectomy during 198892, we used logistic regression analysis to assess predictors of being seizure-free (Engel's class I) 2 years after surgery. As potential predictors, we included the following variables: gender, age at operation, age at onset of seizures, epilepsy duration, etiology, generalized vs not generalized seizures, seizure frequency, intelligence quotient, ictal electroencephalography, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), side of resection, and extent of the resection. RESULTS: About 44% of the surgery patients were seizure-free (Engel's class I) 2 years after surgery. In multivariate analysis (n = 55), MRI pathology defined as atrophy in the temporal lobe, angioma, tumor or mesial temporal sclerosis (odds ratio, OR 7.4, 95%CI: 1.7-32.9) and extent of the hippocampal resection (increase of 1 cm) (OR 2.2, 95%CI: 1.1-4.6) predicted being seizure-free. CONCLUSION: Focal pathology in preoperative MRI and the extent of the hippocampal resection were the only significant predictors of being seizure-free after 2 years.     

Predictors of psychiatric and seizure outcome following temporal lobe epilepsy surgery

Purpose: Neurosurgery is an effective therapy for selected individuals with medically refractory temporal lobe epilepsy (TLE). De novo psychopathology may complicate the postsurgical outcome. Our aims were to identify predictors of de novo psychiatric and seizure outcome following TLE surgery. Methods: Medical records of 280 patients who underwent TLE surgery were reviewed. Preoperative and postoperative psychiatric diagnoses were identified, in addition to information on seizure recurrence and neuropsychological status. Logistic regression analysis was used to identify predictors of having a de novo psychiatric diagnosis and remaining seizure‐free within 4 years following surgery. Key Findings: One hundred five patients (38%) had significant psychiatric problems within 4 years following TLE surgery. Fifty‐one patients (18%) developed de novo psychopathology; half of cases presented within 6 months and 90% of psychopathologies persisted 6 months or longer. A preoperative history of secondary generalized tonic–clonic seizure(s) (SGTCS) was an independent predictor of de novo psychopathology (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.14–6.59, p = 0.02). From patients with available seizure data, 49% (127 of 258) remained seizure‐free for 4 years after surgery. Patients with a history of SGTCS (OR 0.47, 95% CI 0.25–0.90, p = 0.02) and those with a preoperative psychiatric diagnosis (OR 0.53, 95% CI 0.28–0.98, p = 0.04) were significantly less likely to remain seizure‐free. Significance: De novo psychopathology is a significant complication of TLE surgery. Inclusion of neuropsychiatric assessments in the presurgical evaluation may lead to increase in the power of prognostic models used to predict the neurologic outcome of TLE surgery.     

Levetiracetam is as effective as carbamazepine in newly diagnosed epilepsy

Evaluation of: Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 6, 402-408 (2007). Despite the emergence of multiple antiepileptic drugs (AEDs) in the past decade, the task of choosing the right drug for monotherapy in patients with newly diagnosed epilepsy remains a precarious task. This is especially true when trying to choose a new AED over a more traditional agent. Much of this uncertainty stems from the fact that there are only a handful of studies that are able to demonstrate efficacy of a new drug over an older AED. While the newer drugs appear more favorable because of better tolerability, safety profiles and simple pharmacokinetics, many do not have an indication for monotherapy. Of course, this is further contingent upon the stringent limitations placed by regulatory bodies, such as the US FDA, who govern approval of AEDs for monotherapy. The current randomized study attempts to evaluate the efficacy of levetiracetam in monotherapy compared with controlled-release carbamazepine, a gold standard in patients with newly diagnosed epilepsy.     

The use of lamotrigine monotherapy in children with newly diagnosed partial epilepsy

Lamotrigine (Lamictal, Glaxo Wellcome) is a drug which is used as add-on therapy in patients with refractory epilepsy. Several previous studies have demonstrated the efficacy of lamotrigine monotherapy, but only few have been done in pediatric patients. The aim of our study was the assessment of efficacy and tolerability of lamotrigine monotherapy in children with newly diagnosed partial epilepsy. Lamictal was used in 19 children (11 boys and 8 girls), aged 3-16 years. 17 patients demonstrated complex partial seizures (with or without secondarily generalisation), 2 children had simplex partial seizures. Symptomatic epilepsy was diagnosed in 10 patients and cryptogenic epilepsy in 9 cases. The drug was administered at the dose of 3.87 +/- 1.02 mg/kg/day during 24 weeks. Three children withdrew from the study because of adverse events: one patient developed rash, two ones seizure exacerbation. Lamictal produced of at least 50% reduction in seizure frequency in 12 (63.15%) children, included 10 seizure-free patients. One third patients experienced EEG improvement. The most common adverse effects were gastrointestinal and sleep disturbances, infections, dizziness, all of them were mild and transient and observed more often in children under 12 years of age. Lamotrigine monotherapy is effective and safe for treatment of newly diagnosed cryptogenic and symptomatic epilepsy with partial seizures but further studies are necessary specially in young children.     

Absence of simple partial seizure in temporal lobe epilepsy: its diagnostic and prognostic significance

The diagnostic and prognostic significance of the absence of simple partial seizures (SPS) immediately preceding complex partial seizures (CPS) was examined in patients with temporal lobe epilepsy. The status of self-reported SPS in 193 patients with temporal lobe epilepsy who had surgical therapy more than 2 years ago was reviewed. Before surgery, 37 patients never experienced SPS before CPS (Group A), 156 patients either always or occasionally had SPS before CPS (Group B). The frequency of mesial temporal sclerosis (MTS) was lower and the age at onset of epilepsy was higher in Group A. The seizure focus was in the language-dominant temporal lobe in 73% of the cases in Group A, compared with 40% in Group B. The surgical outcome did not differ between the two groups. The findings suggest that temporal lobe seizures without preceding SPS tend to originate in the language-dominant temporal lobe that contains a pathologic etiology other than MTS, especially in the lateral temporal lobe. The surgical outcome in patients without SPS is similar to that in patients with SPS.     

Predictors of epilepsy surgery outcome: a meta-analysis

The potential efficacy of temporal and extratemporal resection in patients with partial epilepsy uncontrolled by anti-epileptic drugs is undisputed. However, there are still uncertainties about which patients will benefit most. A systematic review of the available literature has been undertaken by four pairs of reviewers to assess the overall outcome of epilepsy surgery and to identify factors better correlated to seizure outcome. A Medline search for studies on epilepsy surgery published since 1984 was performed. Studies were included if they had a well-defined population and design, a sample size of at least 30 patients, an MRI performed in least 90% of cases, an expected duration of follow-up of at least one year, and a post-operative outcome measured as seizure remission. A good outcome was considered as seizure control or seizure-free status for at least one year or Engel class I. Based on the review of 47 articles meeting all the eligibility criteria, febrile seizures (odds ratio, OR, 0.48; 95% confidence interval, CI, 0.27-0.83), mesial temporal sclerosis (OR 0.47; 95% CI 0.35-0.64), tumors (OR 0.58; 95% CI 0.42-0.80), abnormal MRI (OR 0.44; 95% CI 0.29-0.65), EEG/MRI concordance (OR 0.52; 95% CI 0.32-0.83), and extensive surgical resection (OR 0.24; 95% CI 0.16-0.36) were the strongest prognostic indicators of seizure remission (positive predictors); by contrast, post-operative discharges (OR 2.41; 95% CI 1.37-4.27) and intracranial monitoring (OR 2.72; 95% CI 1.60-4.60) predicted an unfavorable prognosis (negative predictors). Firm conclusions cannot be drawn for extent of resection, EEG/MRI concordance and post-operative discharges for the heterogeneity of study results. Neuromigrational defects, CNS infections, vascular lesions, interictal spikes, and side of resection did not affect the chance of seizure remission after surgery. Despite a number of limitations, the results of the review provide some insight into the selection of the best surgical candidates in clinical practice but raise concerns on the quality of published reports, and may serve as the basis for the identification of better standards to assess surgical outcome in observational studies.     

Psychological trajectories in the year after a newly diagnosed seizure

Purpose: Underdiagnosed depression and anxiety are well‐recognized issues in chronic epilepsy, but the evolution of these symptoms after diagnosis is not well understood. We aimed to identify mood trajectories after a first seizure, and to examine factors impacting these trajectories. Methods: Seventy‐four patients were evaluated at 1, 3, and 12 months with (1) the Hospital Anxiety and Depression Scale, and (2) a semistructured interview assessing patients’ initial psychological reaction to the seizure at 1 month (limited vs. pervasive loss of control). The SAS Institute’s TRAJ data modelling procedure was employed to delineate trajectories. Key Findings: Two depression and three anxiety trajectories were identified, with significant overlap. The majority of patients (～74%) followed a trajectory with low depression throughout the study, and either low or moderate anxiety. A minority followed trajectories with high depression and anxiety from diagnosis (～16%). Patients with high levels of distress were adversely affected by seizure recurrence and antiepileptic drugs (AEDs), whereas those with low levels were not. Trajectories were predicted by the patient’s sense of loss of control early after diagnosis and were weakly related to demographic and medical variables (age, gender, education, relationship status, psychiatric history, and prior epileptic events). Significance: Methods that account for heterogeneity in patient responses are critical for developing a clinically relevant understanding of adjustment after a newly diagnosed seizure. Most patients appear to be resilient in the face of early seizures, whereas those at risk of longer‐term psychological difficulties may be evident from diagnosis. Early screening for depression and anxiety is warranted.     

A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy.

Monotherapy with lamotrigine or carbamazepine was evaluated in a multicentre open trial of patients aged 2 years and above with newly diagnosed partial epilepsy. A total of 417 patients were randomised to treatment with lamotrigine, while 201 patients received carbamazepine. Following a dose escalation period of 6 weeks, maintenance therapy (Weeks 7-24) was adjusted according to response. Efficacy was similar with both treatments (65% with lamotrigine, 73% with carbamazepine, P=0.085). Efficacy was assessed by the proportion of patients seizure free during the last 16 weeks of treatment; all subjects who remained in the study for at least 18 weeks after the week 4 visit were included in the analysis. More patients receiving lamotrigine completed the study (81%), compared with those receiving carbamazepine (77%). This difference was primarily due to discontinuation as a result of adverse events, reported by 34 (8%) of those treated with lamotrigine but 26 (13%) of those treated with carbamazepine. The proportion of patients who experienced adverse events in the lamotrigine group was lower (218 patients, 52%) compared with the carbamazepine group (120 patients, 60%). The proportion of patients with adverse events considered to be drug related was lower in the lamotrigine group (132 patients, 32%) compared with the carbamazepine group (83 patients, 41%). Somnolence was the only adverse event reported at an incidence of greater than 5% and where there was a difference of 5% or more between treatment groups (4% lamotrigine, 11% carbamazepine patients). The small subsets of elderly patients (aged 65 years or over) and paediatric patients (aged 2-12 years) also showed better tolerability to lamotrigine than to carbamazepine. In conclusion, monotherapy with lamotrigine is as effective as carbamazepine in patients with newly diagnosed partial epilepsy. Patients were able to tolerate lamotrigine better than carbamazepine, so more patients receiving lamotrigine were able to remain on therapy.     

Proton magnetic resonance spectroscopic imaging studies in patients with newly diagnosed partial epilepsy

PURPOSE: To assess whether the N-acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr. PATIENTS AND METHODS: Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow-up 1H-MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging. RESULTS: Initial 1H-MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow-up 1H-MRSI were seizure-free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H-MRSI examination and follow-up 1H-MRSIs showed no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free patients. CONCLUSIONS: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure-free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.     

The development of a seizure severity scale as an outcome measure in epilepsy

In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post-ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid.     

Status epilepticus in children with newly diagnosed epilepsy.

Status epilepticus (SE) constitutes a neurological emergency and may be of prognostic value in individuals with epilepsy. Little is known about the associations between other prognostic factors in epilepsy and the occurrence of SE. The following study examines associations between clinical characteristics of children with newly diagnosed epilepsy and the occurrence of SE when epilepsy is first diagnosed. Children were recruited prospectively from the practices of physicians throughout Connecticut. Information was collected via standardized interviews with parents and review of pertinent records. Analyses were performed for any SE, unprovoked SE only, and previous provoked SE. Of 613 children, 56 (9.1%) had one or more episodes of SE by the time the diagnosis of epilepsy was established. Factors correlated with SE during an unprovoked seizure were partial seizures and previous craniotomy. For SE during a provoked seizure, correlates were primarily young age at onset of epilepsy and nonidiopathic epilepsy syndrome. To date, subsequent SE has occurred in 4.3% of children without and in 19.6% of those with SE at diagnosis. By the time epilepsy is first diagnosed in children, SE has already occurred in a substantial minority. It is correlated with specific clinical characteristics in the children, which differ depending on whether the SE was provoked or unprovoked. SE has a high risk of recurring.     

A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure.

The aim of this study was to compare the effect of treatment with lamotrigine (LTG) or carbamazepine (CBZ) on health-related quality of life (HRQOL) and to demonstrate the use of the SEALS Inventory as a comparative tool in clinical trials. Two hundred and sixty patients with newly diagnosed epilepsy were randomized to 48 weeks of treatment with LTG (n = 131) or CBZ (n = 129). HRQOL was measured at baseline and weeks 4, 12, 24, and 48 using the modified Side Effect and Life Satisfaction (SEALS) Inventory-a 38-item questionnaire divided into five subscales: Worry, Temper, Cognition, Dysphoria, and Tiredness. Overall, SEALS scores in the LTG group decreased (improved) significantly from baseline (P = 0.001). The LTG group had improvement in all five subscales over the 48 weeks of the study. CBZ patients had significantly worse SEALS scores than LTG patients at week 4 (P < 0.038). There was no significant change (positive or negative) in subsequent SEALS assessments. Analysis of SEALS data by subscale showed that the the CBZ group experienced more cognitive side-effects in general and more general changes in energy levels and affect during the first 4 weeks of treatment. These changes may help explain the difference in study completion rate: LTG 65%, CBZ 51% (P = 0.018). LTG offers the patient with newly diagnosed epilepsy significant benefits of greater tolerability and better health-related quality of life compared with CBZ. The SEALS Inventory is an effective tool for use in clinical trials of AEDs; it was a better predictor of trial completion than seizure counts, and used as a covariate enabled better detection of treatment effects. In general practice, the use of the SEALS Inventory to assess HRQOL has the potential to improve quality of care for people with epilepsy.     

Seizure recurrence in adults after a newly diagnosed unprovoked epileptic seizure

PURPOSE: To investigate the risk of seizure recurrence after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. MATERIAL AND METHODS: A total of 107 patients aged >or=17 years with a newly diagnosed unprovoked epileptic seizure (index seizure) were prospectively identified for the period 1985-87. Patients were followed until the date of death or to the end of 1996 with a median follow-up of 10.3 years for surviving cases. Overall cumulative recurrence rates and possible influencing variables were calculated. RESULTS: At 750 days after the index seizure the recurrence was 58%, and after that no events occurred. Recurrence risk was significantly higher when index seizure was remote symptomatic or preceded by two or more seizures. No other study variable predicted seizure recurrence. CONCLUSION: Etiology and the occurrence of seizures before the index seizure after a newly diagnosed unprovoked epileptic seizure predict seizure recurrence. Thus, particular consideration should be given to these factors in the decision of whether or not to initiate antiepileptic treatment.     

Oxcarbazepine reduces seizure frequency in a high proportion of patients with both newly diagnosed and refractory partial seizures in clinical practice.

The antiepileptic efficacy and tolerability of oxcarbazepine, used both as monotherapy and adjunctive therapy, were observed for 1 year in 202 adult patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy in clinical practice in Italy. At first observation, the seizure free rate was 72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom oxcarbazepine replaced another monotherapy and 10.3% in patients given oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the duration of treatment (p < 0.0001). In the 160 completers the seizure free rate was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients reported adverse effects, mainly sedation and sleepiness; 5% discontinued oxcarbazepine because of adverse events. OXC is an effective and well-tolerated antiepileptic agent for the long-term treatment of partial epilepsy in adults.     

The choice of antiepileptic drugs in newly diagnosed epilepsy: a national French survey.

The choice of an antiepileptic drug (AED) in patients with epilepsy is mainly based on efficacy and safety of each drug. However, these criteria of drug selection should be further evaluated according to the epileptic syndromes, and adjusted to the sex and age of the patient. Unfortunately, very few studies have been conducted based on these latter criteria. We conducted a survey on the management of epilepsy treatment in adults. This survey was undertaken in France, and led to the establishment of a French consensus on antiepileptic drug treatment in adult patients with newly diagnosed epilepsy. Patients were grouped into 18 categories according to the epileptic syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy and unclassified epilepsy), and to the patient's gender and age. Our survey suggests that there is a consensus among French epileptologists for the choice of AEDs, mainly based on the epilepsy syndrome. Gender also plays a crucial role. Sodium valproate and lamotrigine are the two drugs of choice for generalized epilepsies, as well as for undetermined epilepsies. Lamotrigine is often prefered for women of childbearing age. First line AEDs in partial epilepsy are carbamazepine (particularly for men), lamotrigine (particularly for women), and gabapentin (in the elderly). In cases of failure and/or intolerance to one of these AED, the principal alternatives are oxcarbazepine, sodium valproate and topiramate.