Do antiepileptic drugs or generalized tonic–clonic seizure frequency increase SUDEP risk? A combined analysis

Purpose: In an analysis of four case–control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic–clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. Methods: We combined data from the three case–control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case–control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. Key Findings: In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. Significance: Our findings—that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account—provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.     

Seizure outcome and its predictors after temporal lobe epilepsy surgery in patients with normal MRI

Purpose: To characterize seizure outcomes following temporal lobe epilepsy (TLE) surgery in patients with normal preoperative brain magnetic resonance imaging (MRI). Methods: We reviewed adult patients with pharmacoresistant epilepsy and normal MRI who underwent TLE surgery (1996–2009). Seizure outcomes were analyzed using survival and multivariate regression with Cox proportional hazard modeling. Two analyses were performed using two favorable outcome definitions: complete seizure freedom and Engel classification. Key Findings: Sixty‐four patients were analyzed (mean follow‐up 4.1 years; range 1–14.5 years). Most had a standard anterior temporal lobectomy (84%) and unremarkable pathology (45%). At 1 year, the chance of complete seizure freedom was 76% [95% confidence interval (CI) 71–81%] comparable to an 81% (95% CI 76–86%) chance of Engel score of 1. With longer follow‐up, a progressively broadening significant discrepancy between the two outcome measures was observed. The chance of complete seizure freedom was 66% (95% CI 61–71%) at 2 years, and 47% (95% CI 40–54%) at 7 years and beyond, whereas the respective chances of achieving an Engel 1 classification were 76% (95% CI 70–82%), and 69% (95% CI 63–75%) at similar time points. Seizure outcome as defined by either measure was worse in patients with higher baseline seizure frequency (adjusted risk‐ratio 2.7 when >12 seizures/month; p = 0.01) and with preoperative generalized tonic–clonic seizures (adjusted risk ratio 10.8; p = 0.0006). Memory measures declined with dominant hippocampus resections. Significance: A normal MRI should not prevent presurgical evaluations in patients with suspected TLE, as favorable long‐term postoperative seizure outcomes are possible. Proposed mechanisms of epileptogenicity and seizure recurrence in this group are discussed.     

Atypical childhood absence epilepsy with preceding or simultaneous generalized tonic clonic seizures

Objective

Although the current diagnostic criteria for childhood absence epilepsy (CAE) do not specifically exclude children with generalized tonic clonic seizures (GTCSs) occurring before or early in the course of the active absence seizures, some workers have suggested that they should be interpreted as doing so. The aim of this study was to compare the clinical features between children with typical CAE and those with atypical CAE with preceding or simultaneous episodes of GTCS (atypical CAE-GTCS).

Methods

A total of 11 patients with atypical CAE-GTCS and 30 with typical CAE were identified by using the current CAE criteria. Their clinical data, including age, sex, family history of epilepsy, personal history of febrile convulsions, onset ages of absences and GTCS, treatment, and outcome were statistically analyzed.

Results

The two groups had the same mean onset age of absences (6 years), and their seizure outcome was comparably favorable in terms of both absences and GTCS. There was no significant difference in other clinical data except for the onset age of GTCS between the groups.

Conclusion

These findings show the similarity in the main clinical features between the groups, suggesting that some patients with atypical CAE-GTCS may have a variant form of CAE with early onset of GTCS.     

Benign focal seizures of adolescence: a prospective study

PURPOSE: To characterize the clinical and EEG findings and evolution of the syndrome of benign focal seizures of adolescence (BFSA), as described by Loiseau et al. METHODS: A prospective study was performed in adolescents with normal clinical and neurologic examinations and normal neuroradiologic studies who had focal seizures that occurred isolated or in a cluster, with or without secondary generalization in the first 24 to 48 h after onset. None of the patients was treated with antiepileptic drugs (AEDs). RESULTS: Between January 1996 and January 2002, 15 patients with BFSA were enrolled in the study. Median age at onset of BFSA was 14 years. Thirteen patients had focal sensory or motor seizures. In two patients, the ictal manifestation was motion arrest associated with oral automatisms. Eight of them evolved to generalized tonic-clonic seizures. Thirteen patients had seizures only when awake, and the other two, both when awake and during sleep. Repeated interictal EEGs were normal, but in four of the patients who had seizures in a cluster, we were able to record an EEG within 8 h after seizure onset. Two of these four patients had focal seizures, and their waking EEG showed focal centroparietal theta activities. The other two patients had secondarily generalized seizures, and their waking EEG showed bilateral theta activities instead. Prognosis was excellent. CONCLUSIONS: BFSA is a well-defined seizure syndrome, recognizable by clinical and EEG features, as described by Loiseau et al. In teenagers with these electroclinical features with a normal neurologic examination and normal neuroradiologic findings, AEDs should be avoided.     

Postictal breathing pattern distinguishes epileptic from nonepileptic convulsive seizures

PURPOSE: To examine postictal breathing pattern in generalized convulsive nonepileptic seizures (GCNES) and generalized tonic-clonic seizures (GTCS) and evaluate this feature as a discriminating sign. METHODS: We reviewed the postictal breathing pattern seizures in 23 generalized tonic-clonic seizures in 15 consecutive patients with epilepsy and 24 convulsive nonepileptic seizures in 16 consecutive patients with pure psychogenic seizures. We also analyzed 21 frontal lobe hypermotor seizures (FLHS) in 9 patients with frontal lobe epilepsy. RESULTS: The breathing after GTCS was deep with prolonged inspiratory and expiratory phases, regular, and loud (except for two short seizures). The breathing after GCNES was characterized by increased respiratory rate or hyperpnea with short inspiratory and expiratory phases, as can be noted after exercise. The breathing was often irregular, with brief pauses. The altered breathing lasted longer after GTCS. The two groups differed significantly in loudness of postictal respiration, postictal snoring (only with GTCS), respiratory rate (faster for the GCNES group), and duration of altered breathing (longer after GTCS) (p < 0.00001 for all features). FLHS shared postictal breathing features of GCNES, but had other distinguishing features. CONCLUSIONS: The postictal breathing pattern can help differentiate generalized tonic-clonic seizures from nonepileptic psychogenic seizures with generalized motor activity and may be helpful to the practitioner obtaining a seizure history in the clinic setting or witnessing a seizure.     

Imaging onset and propagation of ECT-induced seizures

PURPOSE: Regions of seizure onset and propagation in human generalized tonic-clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)-induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions. METHODS: ECT stimulation induces a typical generalized tonic-clonic seizure, resembling spontaneous generalized seizures in both clinical and electroencephalogram (EEG) manifestations. Patients were divided into two groups based on timing of ictal (during seizure) SPECT tracer injections: 0 s after ECT stimulation (early group), and 30 s after ECT (late group). Statistical parametric mapping (SPM) was used to determine regions of significant CBF changes between ictal and interictal scans on a voxel-by-voxel basis. RESULTS: In the early injection group, we saw increases near the regions of the bitemporal stimulating electrodes as well as some thalamic and basal ganglia activation. With late injections, we observed increases mainly in the parietal and occipital lobes, regions that were quiescent 30 s prior. Significant decreases occurred only at the later injection time, and these were localized to the bilateral cingulate gyrus and left dorsolateral frontal cortex. CONCLUSIONS: Activations in distinct regions at the two time points, as well as sparing of intermediary brain structures, suggest that ECT-induced seizures propagate from the site of initiation to other specific brain regions. Further work will be needed to determine if this propagation occurs through cortical-cortical or cortico-thalamo-cortical networks. A better understanding of seizure propagation mechanisms may lead to improved treatments aimed at preventing seizure generalization.     

Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study

PURPOSE: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new-onset seizures. METHODS: Subjects were 224 children with new-onset seizures (aged 4-14 years) and 159 siblings (4-18 years). Caregiver's ratings of the behavior were collected 4 times: at baseline, and at 6, 12, and 24 months. During the 2-year period, 163 (73%) children had at least one additional seizure, and 61 (27%) had none. Data were analyzed by using repeated measures analysis of variance both with and without covariates [site, age, gender, race, caregiver education (years), and seizure medications]. RESULTS: On average, children had higher CBCL Total and Internalizing Behavior Problems scores across all times when experiencing recurrent seizures than when not experiencing recurrent seizures (Total Problems, p = 0.041, controlling for demographics and seizure medications). Siblings had significantly lower Total and Internalizing Problems scores than both children experiencing (Total Problems adjusting for covariates, p = 0.0001) and not experiencing recurrent seizures (p = 0.0004). Externalizing Problems scores were not significantly different among children with recurring seizures, children without recurring seizures, and siblings. CONCLUSIONS: Recurrent seizures significantly predicted behavior problems very early in the course of a seizure condition, even when key child, demographic, and seizure variables were controlled. Explanations for these findings include the possibilities that both seizures and behavior problems are caused by an underlying neurological disorder, that seizures per se disrupt behavior, or that children have negative psychological responses to seizure activity.     

Testing for minimal consciousness in complex partial and generalized tonic–clonic seizures

Impaired consciousness in epilepsy has a major negative impact on quality of life. Prior work suggests that complex partial seizures (CPS) and generalized tonic–clonic seizures (GTCS), which both cause loss of consciousness, affect similar frontoparietal networks. Milder involvement in CPS than in GTCS may spare some simple behavioral responses, resembling the minimally conscious state. However, this difference in responses has not been rigorously tested previously. During video–electroencephalography (EEG) monitoring, we administered a standardized prospective testing battery including responses to questions and commands, as well as tests for reaching/grasping a ball and visual tracking in 27 CPS (in 14 patients) and 7 GTCS (in six patients). Behavioral results were analyzed in the ictal and postictal periods based on video review. During both CPS and GTCS, patients were unable to respond to questions or commands. However, during CPS, patients often retained minimally conscious ball grasping and visual tracking responses. Patients were able to successfully grasp a ball in 60% or to visually track in 58% of CPS, and could carry out both activities in 52% of CPS. In contrast, during GTCS, preserved ball grasp (10%), visual tracking (11%), or both (7%), were all significantly less than in CPS. Postictal ball grasping and visual tracking were also somewhat better following CPS than GTCS. These findings suggest that impaired consciousness in CPS is more similar to minimally conscious state than to coma. Further work may elucidate the specific brain networks underlying relatively spared functions in CPS, ultimately leading to improved treatments aimed at preventing impaired consciousness.     

Decreased cerebrospinal fluid hypocretin-1 (orexin A) in patients after repetitive generalized tonic–clonic seizures

The effects of seizures on the hypocretin/orexin system have not yet been investigated in epileptic patients. The present study aimed to assay hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized tonic–clonic (GTC) seizures. Study groups consisted of 21 patients after GTC seizures and 19 controls. Diagnostic lumbar puncture was performed in control and epileptic patients within 48 h after the GTC seizures. Hypocretin-1 levels were measured in unextracted CSF samples, using a standardized commercial radioimmunoassay. There was a significant overall difference in median CSF hypocretin-1 concentrations between controls and patients with GTC patients (p < 0.001). The lowest concentrations were noted in a subgroup of patients with repetitive GTC seizures (RS) compared to those with a single GTC seizure (SS) (p > 0.05) or controls (p < 0.001). The current results suggest that the hypocretin-1 system deficiency contributes to the complex pathophysiology of repetitive GTC seizures and status epilepticus (SE) and could be associated with typical somnolence after seizure attacks.     

Efficacy and safety of perampanel in generalized and focal to bilateral tonic‐clonic seizures: A comparative study of Asian and non‐Asian populations

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures and generalized tonic‐clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non‐Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4‐6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: ?30.32%, P = 0.0017; ?30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non‐Asian population (?35.07%, P = 0.0001; ?37.78%, P < 0.0001; ?34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, ?37.37%, P = 0.0139; non‐Asian, ?27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non‐Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non‐Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment‐related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.     

Consciousness as a useful concept in epilepsy classification

Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front‐and‐center in our discussions.     

Divalproex extended-release versus the original divalproex tablet: results of a randomized,crossover study of well-controlled epileptic patients with primary generalized seizures

Purpose: To compare the safety and efficacy of two formulations of divalproex, extended-release divalproex versus the original divalproex tablet, in adolescent and adult patients with epilepsy. Methods: Eligible patients were between the ages of 12 and 65 years with primary generalized epilepsy, which was controlled over the month prior to study enrollment with divalproex or valproic acid 1000 mg to 2000 mg/day. The patients were well-controlled; 39 of 43 (91%) had no seizures in the previous year. Patients were randomized to receive 84 days of either divalproex two times a day (b.i.d.)/three times a day (t.i.d.) or extended-release divalproex qd and then (crossed over to) 84 days of the comparator formulation. During the two treatment periods, patients received the same daily dose equivalent of divalproex as was taken during the month prior to study entry. The clinical status of patients was evaluated at a screening visit and at four subsequent visits conducted every 42 days. Results: There was no statistically significant difference between the formulation groups for seizure control rate (95% [41/43] for divalproex and 93% [40/43] for extended-release divalproex). Likewise, the formulation groups were similar based on the incidence of treatment-related adverse events. The most frequently reported (≤11.4% for either formulation) treatment-related adverse events were asthenia, tremor, nausea, and dizziness. Conclusions: Extended-release divalproex was similar to divalproex for the treatment of well-controlled, primary generalized epilepsy in terms of overall safety and efficacy parameters.     

Efficacy,tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new‐onset epilepsy: A randomized double‐blind clinical trial

Purpose: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new‐onset epilepsy. Methods: Randomized, double‐blind, 28‐day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new‐onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. Results: At day 28, the estimated seizure‐free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment‐related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). Conclusion: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new‐onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new‐onset epilepsy requiring rapid treatment initiation.     

Development of a validated clinical case definition of generalized tonic-clonic seizures for use by community-based health care providers

PURPOSE: To develop and test a clinical case definition for identification of generalized tonic-clonic seizures (GTCSs) by community-based health care providers. METHODS: To identify symptoms that can help identify GTCSs, patients with history of a jerky movements or rigidity in any part of the body ever in life were recruited from three sites: the community, secondary care hospital, and tertiary care hospital. These patients were administered a 14-item structured interview schedule focusing on the circumstances surrounding the seizure. Subsequently, a neurologist examined each patient and, based on available investigations, classified them as GTCS or non-GTCS cases. A logistic regression analysis was performed to select symptoms that were to be used for case definition of GTCSs. Validity parameters for the case definition at different cutoff points were calculated in another set of subjects. RESULTS: In total, 339 patients were enrolled in the first phase of the study. The tertiary care hospital contributed the maximal number of GTCS cases, whereas cases of non-GTCS were mainly from the community. At the end of phase I, the questionnaire was shortened from 14 to eight questions based on statistical association and clinical judgment. After phase II, which was conducted among 170 subjects, three variables were found to be significantly related to the presence of GTCSs by logistic regression: absence of stress (13.1; 4.1-41.3), presence of frothing (13.7; 4.0-47.3), and occurrence in sleep (8.3; 2.0-34.9). As a case definition using only three variables did not provide sufficient specificity, three more variables were added based on univariate analysis of the data (incontinence during the episode and unconsciousness) and review of literature (injury during episode). A case definition consisting of giving one point to an affirmative answer for each of the six questions was tested. At a cutoff point of four, sensitivity was 56.9 (47.4-66.0) and specificity, 96.3 (86.2-99.4). Among the 197 GTCS and 26 new non-GTCS patients recruited from hospitals from select SEAR Member Countries, in phase III, the sensitivity of this clinical case definition was 72% and specificity, 100%. A stratified analysis by gender in all the three phases did not show any differences between the sexes. CONCLUSIONS: Based on these criteria, we recommend that all patients with a history of two or more episodes of jerking or rigidity of limbs, having a score of > or =4 in the case definition, be identified as having GTCSs and started on antiepileptic medications. This clinical case definition can be very useful for community-based health care providers to identify and manage cases of GTCSs in the community. This should play a major role in the reduction of treatment gap for epilepsy in developing countries.     

Lateralizing value of asymmetric tonic limb posturing observed in secondarily generalized tonic-clonic seizures

PURPOSE: A striking asymmetry of limb posture occurs during secondarily generalized tonic-clonic (GTC) seizures wherein one elbow is extended while the other is flexed during the tonic phase of the GTC seizure. We have named this phenomenon asymmetric tonic limb posturing (ATLP) or the "Figure 4 Sign." METHODS: Fifty-nine secondarily GTC seizures from 31 patients with partial epilepsy who underwent successful epilepsy surgery were analyzed, in addition to another group of 64 GTC and generalized clonic seizures from 26 patients collected prospectively over a 7-month period. Three observers reviewed these seizures blinded to the side of ictal EEG onset and other clinical data. RESULTS: The extended elbow was contralateral to the side of ictal onset in 35 of 39 patients who had ATLP during their seizures. The kappa index, a measure of interobserver agreement, was calculated, and ATLP was found to have very good agreement between observers. CONCLUSIONS: In secondarily generalized tonic-clonic seizures, ATLP (Figure 4 Sign) may sometimes be only available lateralizing sign.     

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study

Purpose: To evaluate the long‐term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE). Methods: This phase III, open‐label, long‐term, follow‐up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic–clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000–4,000 mg/day; 20–80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention‐to‐treat (ITT) population, N = 217] and subpopulations with tonic–clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline. Key Findings: One hundred twenty‐five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1–Q3) exposure to LEV was 2.1 (1.5–2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or ≥2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of ≥6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of ≥6 months from tonic–clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment‐emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%). Significance: Adjunctive LEV (range 1,000–4,000 mg/day) demonstrated efficacy as a long‐term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated.     

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures

OBJECTIVES: The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. PATIENTS AND METHODS: Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. RESULTS: Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. CONCLUSIONS: There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.