Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy.

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy.

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PURPOSE: The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. METHODS: Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. RESULTS: Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). CONCLUSIONS: Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.

Paroxysmal non-epileptic events in infants and toddlers: A phenomenologic analysis.

AIM: The aim of this study was to analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEE) in infants and toddlers. METHODS: We studied all children aged ≤2 years who were diagnosed with PNEE based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: (i) motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing); (ii) oral/vocal (crying, vocalization, sighing); (iii) behavioral change (arrest of activity, staring); (iv) and autonomic (facial flushing, breath holding). RESULTS: Thirty-one of 81 (38.3%) infants and toddlers had 38 PNEE recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events, and autonomic in 8/38 events. Epileptic seizures and PNEE coexisted in four children (12.9%). Seventeen children (54.8%) had one or more risk factors suggestive of epilepsy. Twelve children (38.7%) had a normal neurologic examination, 10 (32.3%) had developmental delay, and eight (25.8%) had a family history of epilepsy or seizures. CONCLUSION: VEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that paroxysmal non-epileptic seizures may frequently coexist in young children with epilepsy.

Age-specific periictal electroclinical features of generalized tonic-clonic seizures and potential risk of sudden unexpected death in epilepsy (SUDEP).

Generalized tonic-clonic seizure (GTCS) is the commonest seizure type associated with sudden unexpected death in epilepsy (SUDEP). This study examined the semiological and electroencephalographic differences (EEG) in the GTCSs of adults as compared with those of children. The rationale lies on epidemiological observations that have noted a tenfold higher incidence of SUDEP in adults. We analyzed the video-EEG data of 105 GTCS events in 61 consecutive patients (12 children, 23 seizure events and 49 adults, 82 seizure events) recruited from the Epilepsy Monitoring Unit. Semiological, EEG, and 3-channel EKG features were studied. Periictal seizure phase durations were analyzed including tonic, clonic, total seizure, postictal EEG suppression (PGES), and recovery phases. Heart rate variability (HRV) measures including RMSSD (root mean square successive difference of RR intervals), SDNN (standard deviation of NN intervals), and SDSD (standard deviation of differences) were analyzed (including low frequency/high frequency power ratios) during preictal baseline and ictal and postictal phases. Generalized estimating equations (GEEs) were used to find associations between electroclinical features. Separate subgroup analyses were carried out on adult and pediatric age groups as well as medication groups (no antiepileptic medication cessation versus unchanged or reduced medication) during admission. Major differences were seen in adult and pediatric seizures with total seizure duration, tonic phase, PGES, and recovery phases being significantly shorter in children (p<0.01). Generalized estimating equation analysis, using tonic phase duration as the dependent variable, found age to correlate significantly (p<0.001), and this remained significant during subgroup analysis (adults and children) such that each 0.12-second increase in tonic phase duration correlated with a 1-second increase in PGES duration. Postictal EEG suppression durations were on average 28s shorter in children. With cessation of medication, total seizure duration was significantly increased by a mean value of 8s in children and 11s in adults (p<0.05). Tonic phase duration also significantly increased with medication cessation, and although PGES durations increased, this was not significant. Root mean square successive difference was negatively correlated with PGES duration (longer PGES durations were associated with decreased vagally mediated heart rate variability; p<0.05) but not with tonic phase duration. This study clearly points out identifiable electroclinical differences between adult and pediatric GTCSs that may be relevant in explaining lower SUDEP risk in children. The findings suggest that some prolonged seizure phases and prolonged PGES duration may be electroclinical markers of SUDEP risk and merit further study.

Sturge-Weber syndrome: clinical and radiological correlates in 86 patients.

BACKGROUNDS AND PURPOSE: To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge-Weber syndrome (SWS). METHODS: The study group consisted of 86 consecutive patients aged two months to 56 (mean 7.9 +/- 10.3) years with SWS and epilepsy. Clinical and MRI data were analyzed. RESULTS: Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement. Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension. Hemispheric and focal subgroups were clinically different. Patients with hemispheric SWS were younger at the age of epilepsy onset (p < 0.001) and age at MRI examination (p < 0.05). Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups. CONCLUSION: Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side. The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis. Patients with hemispheric form of SWS presented with earlier age of seizure onset. Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement). Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis.

Gaucher disease: successful treatment of myoclonic status epilepticus with levetiracetam.

We present the first reported case of a rapid clinical and electroencephalographic response to intravenous levetiracetam infusion of myoclonic status epilepticus in a patient with progressive myoclonus epilepsy due to Gaucher disease. Under continuous video-EEG monitoring, the clinical myoclonic status and the electrographic ictal discharges resolved within 10 minutes after the infusion was initiated. The patient tolerated the treatment well without any reported side effects. This case suggests that levetiracetam may be a safe, effective, and well tolerated intravenous drug in patients with metabolic myoclonic status epilepticus such as Gaucher disease.

Sublobar dysplasia--A clinicopathologic report after successful epilepsy surgery.

We report the clinical presentation, neuroradiologic characteristics, and detailed histopathologic findings in a unique case of drug-resistant focal epilepsy due to sublobar dysplasia (SLD), treated successfully by resection of the malformed cortex. Histopathology with leptomeningeal and subcortical heterotopia, disturbance of cortical lamination and marked cortical and subcortical astrocytosis, but absence of balloon cells, points to a disorder of neuronal migration and organization rather than proliferation in SLD. The additional presence of a lateral proboscis and meningocele in our case as well as further associated callosal and cerebellar anomalies may suggest an etiologic unknown damage of pathways controlling the embryogenesis of craniofacial field processes.

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy.

Reports of decreased serum 25-hydroxyvitamin D (25-OHD) and altered bone metabolism associated with antiepileptic drug (AED) treatment are inconsistent and predominantly restricted to adults. In this cross-sectional observational study, the aim was to evaluate the influence of AED treatment on vitamin D status and markers of bone turnover in children with epilepsy. In 38 children taking AEDs and 44 healthy control subjects, blood samples were collected to determine the levels of serum 25-OHD, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), bone alkaline phosphatase (BAP), osteocalcin (OC) and C terminal telopeptide of type I collagen (ICTP). More than 75% of the patients were vitamin D deficient (serum 25-OHD<20 ng/mL) and 21% of the patients had an insufficient vitamin D status (serum 25-OHD=20-30 ng/mL). In the patients, the serum levels of OC (p = 0.002) and BAP (p < 0.001) were significantly increased, but ICTP (p = 0.002) concentrations were significantly decreased compared with the control group. When patients where divided into two groups according to their medication (mono- or polytherapy), significantly lower 25-OHD (p = 0.038) and ICTP (p = 0.005) levels and elevated BAP (p = 0.023) concentrations were found in patients under polytherapy. An association between 25-OHD and the measured bone markers could not be determined. Our results indicate that the prevalence of vitamin D deficiency in epilepsy patients under AED treatment is high, especially under polytherapy, and alteration markers of bone formation and resorption suggests an accelerated skeletal turnover. The routine monitoring of serum 25-OHD and vitamin D supplementation on an individual basis should be considered.

Angiocentric glioma: report of clinico-pathologic and genetic findings in 8 cases.

Angiocentric glioma has recently been described as a novel epilepsy associated tumor with distinct clinico-pathologic features. We report the clinical and pathologic findings in 8 additional cases of this rare tumor type and extend its characterization by genomic profiling. Almost all patients had a history of long-standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery was performed at 6 to 70 years. Histologically, the tumors were characterized by diffuse growth and prominent perivascular tumor cell arrangements with features of astrocytic/ependymal differentiation, but lacking neoplastic neuronal features. Necrosis and vascular proliferation were not observed and mitoses were sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%. Immunohistochemically, all cases stained positively for glial fibrillary acidic protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances by chromosomal comparative genomic hybridization revealed loss of chromosomal bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high-resolution screen by array-comparative genomic hybridization identified a copy number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are seizure free and without evidence of tumor recurrence at follow-up times ranging from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that angiocentric glioma is a novel glial tumor entity of low-grade malignancy.

Epilepsy surgery in an 8-year-old boy with intractable seizures.

CASE: Mark is an 8-year-old boy with a history of intractable epilepsy. Mark's seizures started when he was five years old, lasting less than a minute, with 7-10 episodes occurring in succession. Daytime seizures were described by his parents a "staring events where he does not respond, he will pick at clothes and speak gibberish." He was often disorientated for the remainder of the day. Nighttime seizures were described as "sitting up straight in bed, staring at the ceiling, and being unresponsive." An increase in his seizure frequency after multiple anticonvulsant medications prompted a surgical evaluation. A magnetic resonance (MR) brain scan indicated mild encephalomacia in the left hemisphere. A video electroencephalogram (EEG) demonstrated that the seizures initiated from the left hemisphere in association with multiple subclinical seizures. A PET scan showed decreased uptake in the left frontal lobe compared to the right. At 7 years of age Mark underwent a left frontal temporal-parietal resection. He had a post-surgical infection, but no other medical sequelae. After surgery, there was a significant decrease in seizures with only one seizure in the 2 month post operative period. Mark had neuropsychological testing prior to and following surgery. Pre-surgical results indicated that his IQ was within the low-average range. Visual-perceptual abilities, motor tasks and attention domains indicated difficulties. Post-surgical neuropsychological evaluation revealed a positive outcome. IQ remained in the low average range and there was a mild improvement in visual-perceptual/visual-constructional areas. Academic skills were unchanged with the exception of a slight decline in reading ability. Attention scores improved although redirection was required to sustain his attention during tasks. An increase in non-compliant behavior and emotional liability was noted by his parents.At the time of referral, when Mark was 8-years 3-months old, parental concerns included inattention, anger and emotional lability. The referral question posed was: "Does Mark's inattention represent an attention deficit/hyperactivity disorder, anxiety, or other psychological problems and what is the relationship of his current behaviors to his epilepsy?"

Tailored disconnection based on presurgical evidence in catastrophic epilepsy: report of 2 cases.

Catastrophic epilepsy in infants, often due to extensive cortical dysplasia, has devastating consequences with respect to brain development. Conventional lobar, multilobar, or hemispheric resection in these infants is challenging, carrying an increased operative risk compared with that in older children. Removing a larger tissue volume versus removing or disconnecting the epileptogenic region does not always guarantee better seizure outcome. The authors describe 2 infants with catastrophic epilepsy who benefited from individually tailored disconnections based on a hypothesized epileptogenic zone following intensive presurgical evaluation. Two infants with catastrophic epilepsy and epileptic spasms underwent leukotomies between 3 and 12 months of age. They were followed up postoperatively for 19-36 months. Both patients had 90%-100% seizure reduction and a significantly improved neurodevelopmental outcome without postoperative complication. Cortical malformation was seen in both patients. Modifications of established surgical disconnection techniques, tailored to each patient's specific epileptogenic zone, optimized seizure and neurodevelopmental outcomes while minimizing the risks associated with more extensive resections.

Ictal pallor is associated with left temporal seizure onset zone in children.

PURPOSE: To describe the frequency, localizing and lateralizing value of ictal pallor (IP) in children with focal epilepsy. METHODS: A retrospective review of medical charts and 514 archived seizures from 100 children < or =12 years old was performed. All patients had a history of therapy-resistant partial epilepsy and a seizure-free postoperative outcome. The presence and attributes of IP were analyzed. RESULTS: No IP was detected by reviewing the archived seizures. According to medical charts, IP was reported in 11/100 children (six girls) aged 14 months to 12 (mean 5.5+/-4.1) years. Ten of them had temporal lobe epilepsy (p=0.046) - including nine temporo-medial and one temporo-lateral cases - while only one child had an extratemporal (parietal lobe) seizure onset zone. All but one children had left-sided operation (p=0.01). Presence of IP had a positive predictive value of 91% for both lateralizing (left) and localizing (temporal lobe) the seizure onset zone. History of IP was neither age-, epilepsy onset-, nor gender-related. CONCLUSIONS: Ictal pallor is a frequently reported autonomic symptom during childhood focal seizures but difficult to assess purely by video-monitoring. It has a high predictive value to localize the seizure onset zone to the left temporal region already in very young patients.

Genital automatisms in childhood partial seizures.

PURPOSE: To describe frequency and electroclinical characteristics as well as localizing and lateralizing value of childhood periictal genital automatisms (GAs). METHODS: Five-hundred-forty-one videotaped seizures of 109 consecutive patients <12 years with refractory partial epilepsy and postoperatively seizure-free outcome were analyzed. Genital automatisms (scratching, fondling or grabbing of the genitals) were monitored by two independent investigators. RESULTS: Eight (four temporal, four extratemporal) patients (7%) showed GA at least once during 20 (3.7%) seizures. Age of patients with GA was between 4.5 and 11.9 (mean 9.5+/-2.4) years and was significantly higher than the age of children without GA (p=0.006). Boys showed GAs more frequently than girls (p=0.026). Genital automatisms appeared both ictally and postictally with a mean duration of 51s. They were unilateral (completed by one hand) in 18/20 seizures and were done by the hand ipsilateral to the seizure onset zone in 16/18 cases (p=0.001). Although consciousness was preserved during GA in 3/8 patients, neither periictal urinary urge nor penile erection was associated with it. CONCLUSIONS: Periictal GAs appear in school-age patients with a similar frequency to that in adults but almost lack in preschool children. Although the presence of childhood GA has neither localizing nor lateralizing value per se, the hand used for GA is more frequently ipsilateral to the seizure onset zone. The mechanisms for childhood GAs are not clear but probably different from those of adults.

Levetiracetam in children with refractory epilepsy: a multicenter open label study in Germany.

PURPOSE: To evaluate the efficacy and tolerability of Levetiracetam (LEV) in a large pediatric cohort with drug-resistant epilepsy from a prospective multicenter observational study. METHODS: We report the results of a multicenter observational survey of a cohort of 285 pediatric patients (mean: 9.9 years, range: 0; 6-17; 11) with refractory generalized and focal epilepsy who received Levetiracetam as an add-on open label treatment trial. The average duration of epilepsy was 6.0 years and the patients were treated with a mean of 7.0 antiepileptic drugs (AED) before LEV was introduced. RESULTS: No serious persistent adverse events were reported. Reversible colitis and an apnoea syndrome in a child with phosphorylase-A-kinase-deficiency were noted. Mild to moderate side effects were reported in 128 patients (44.9%), consisting most frequently of somnolence (23.9%), general behavioral changes (15.4%), aggression (10.5%) and sleep disturbances (3.2%). In 209 patients, efficacy was analyzed over a treatment period of at least 12 weeks compared to a baseline of 2 weeks. Thirteen patients (6.2%) became seizure free, 39 (18.7%) responded with a seizure reduction of more than 50% following introduction of LEV. No response to LEV was reported in 65.1% (n=136). A decrease of initial treatment effect was seen in 37 patients (17.8%) while in 6.7% the seizure frequency doubled to the baseline (n=14). In seven patients (3.3%), the effect of LEV on seizure frequency could not be evaluated. A positive psychotropic effect was observed in 18 patients (8.6%). Mental retardation was associated with poor response and associated with more side effects and earlier discontinuation of LEV therapy. CONCLUSION: LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

A semiological classification of status epilepticus.

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Familial subacute sclerosing panencephalitis in two siblings.

Subacute sclerosing panencephalitis is a form of chronic persistent measles encephalitis in childhood which rarely manifests after wild virus infection. One previous case of familial subacute sclerosing panencephalitis in two siblings and a number of reports of subacute sclerosing panencephalitis in one member of monozygous twins have been reported in the literature. This report describes a second sibling set who both contracted subacute sclerosing panencephalitis after concurrent sporadic measles infection. Two nonimmunized brothers developed neuropsychological decline and progressive myoclonic and complex partial seizures after earlier measles infection. Stereotyped periodic 5- to 8-second complexes in the electroencephalogram suggested the diagnosis of subacute sclerosing panencephalitis, subsequently confirmed by intrathecal and serum measles-specific immunoglobulin G synthesis and the presence of rubeola nucleocapsid protein and ribonucleic acid in the biopsied brain. The viral genome has not been further subtyped in either patient at this point. Although a rare event, subacute sclerosing panencephalitis cases involving familial and singular monozygous twins may shed light on a variety of host susceptibility factors and specific viral genotype features predisposing to this disease.

Pseudostatus epilepticus in childhood.

Pseudostatus epilepticus in childhood has not been well reported in the literature. We describe the clinical presentation and management of a 9-year-old child with well-controlled epilepsy who presented in a prolonged period of pseudoseizures. Intensive care management over a number of weeks with multiple high-dose antiepileptic drugs, anesthesia, and ventilation at a tertiary care pediatric center was performed before the diagnosis of pseudostatus epilepticus was made. Initiation of family counseling and behavior therapy after diagnosis of the nonepileptic nature of the protracted paroxysmal events with video telemetry in our pediatric epilepsy unit was followed by remission. The patient reported herein illustrates the risks of iatrogenic morbidity that may result from a delay in the diagnosis of pseudoseizures and pseudostatus epilepticus in childhood.

Epilepsy surgery in bilateral Sturge-Weber syndrome.

Two infants with severe drug refractory focal epilepsy caused by Sturge-Weber syndrome and extensive cerebral leptomeningeal angiomatosis were referred for preoperative video-electroencephalographic evaluation. Brain imaging with computed tomography and gadolinium-enhanced magnetic resonance imaging demonstrated bilateral disease in both children with a predominance of involvement of one hemisphere. Clinical examination and neurophysiology with ictal video recording demonstrated epileptogenesis from one hemisphere. Successful surgical treatment with functional hemispherectomy was followed by good long-term seizure control in both patients. The dramatic seizure control was accompanied by markedly improved quality of life for the family and children. These cases indicate that the spectrum of children that may benefit from epilepsy surgery should not be viewed too restrictively, and subsets of children with localization related epilepsy caused by extensive lesions may be resective surgical candidates with a good seizure outcome prognosis.

Levetiracetam vs. sulthiame in benign epilepsy with centrotemporal spikes in childhood: a double-blinded, randomized, controlled trial (German HEAD Study).

OBJECTIVE: To show non-inferiority of levetiracetam to sulthiame with respect to efficacy, tolerability and safety in benign epilepsy with centrotemporal spikes in a prospective, double-blinded randomized controlled trial. METHODS: A sample size of 60 subjects (treatment group) was calculated to show reliable statistical results for non-inferiority. A total of 44 patients could be randomly allocated to either (LEV or STM) treatment group. Explorative data analysis was performed to investigate differences in the number of treatment failure events (occurrence of a seizure during the observation period of 6 months) and total dropouts. In addition, information of the occurrence of adverse events was collected. RESULTS: 43 patients were analyzed. One patient had to be excluded due to protocol violation. Treatment failure events occurred in four patients (19.0%) in the LEV treatment group and in two patients (9.1%) in the STM treatment group, respectively, (p = 0.412). The number of dropouts due to adverse reactions was five in the LEV treatment group and one in STM treatment group (23.8% vs. 4.5%, respectively, p = 0.095). Severe adverse events occurred in patients treated with LEV (n = 2, 9.5%). The total number of dropouts due to either seizure recurrence or adverse events was significantly higher in the LEV group (n = 9, 42.9%) compared to the STM group (n = 3, 13.6%, p = 0.03). INTERPRETATION: The study results concerning non-inferiority were not conclusive, as the calculated sample size was not reached to support sufficient statistical power due to limited recruitment in a 26 months period. The rates of seizure free patients were [relatively] high in both groups. However, the results indicate that termination of drug treatment due to seizure recurrence or adverse events occurred more frequently in the LEV group compared to STM. Behavioral disturbances were the most common adverse event causing study termination.

Epilepsy surgery outcome in coexisting symptomatic refractory focal epilepsy and benign focal epilepsy of childhood.

Epilepsy surgery may successfully treat refractory symptomatic focal epilepsy in patients with coexisting benign focal epileptiform discharges. Reported here is the outcome after resective epilepsy surgery in three children with pharmacoresistant lesional focal epilepsy in whom seizures of benign focal epilepsy of childhood had been recorded. Two patients had left temporal epilepsy due to a malformation of cortical development; one of these had dual pathology, with additional ipsilateral hippocampal sclerosis. One child had catastrophic left hemispheric epilepsy due to left hemimegalencephaly. Frequent, habitual seizures of symptomatic epilepsy resolved after surgery (follow-up duration, 32-55 months); however, rare benign focal seizures of childhood have continued. These cases demonstrate that lesional pharmacoresistant focal epilepsy can be successfully treated with resective epilepsy surgery even when coexisting with benign focal epilepsy of childhood. During postoperative follow-up, careful documentation of breakthrough seizures due to benign focal epilepsy of childhood is important, so that these patients are not labeled as surgical failures.