Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy.

OBJECTIVE: To conduct an open-label, add-on trial on safety and efficacy of levetiracetam in severe myoclonic epilepsy of infancy (SMEI). PATIENTS AND METHODS: SMEI patients were recruited from different centers according to the following criteria: age > or =3 years; at least four tonic-clonic seizures/month during the last 8 weeks; previous use of at least two drugs. Levetiracetam was orally administrated at starting dose of approximately 10 mg/kg/day up to 50 to 60 mg/kg/day in two doses. Treatment period included a 5- to 6-week up-titration phase and a 12-week evaluation phase. Efficacy variables were responder rate by seizure type and reduction of the mean number per week of each seizure type. Analysis was performed using Fisher exact and Wilcoxon tests. RESULTS: Twenty-eight patients (mean age: 9.4 +/- 5.6 years) entered the study. Sixteen (57.1%) showed SCN1A mutations. Mean number of concomitant drugs was 2.5. Mean levetiracetam dose achieved was 2,016 mg/day. Twenty-three (82.1%) completed the trial. Responders were 64.2% for tonic-clonic, 60% for myoclonic, 60% for focal, and 44.4% for absence seizures. Number per week of tonic-clonic (median: 3 vs 1; p = 0.0001), myoclonic (median: 21 vs 3; p = 0.002), and focal seizures (median: 7.5 vs 3; p = 0.031) was significantly decreased compared to baseline. Levetiracetam effect was not related to age at onset and duration of epilepsy, genetic status, and concomitant therapy. Levetiracetam was well tolerated by subjects who completed the study. To date, follow-up ranges 6 to 36 months (mean, 16.2 +/- 13.4). CONCLUSION: Levetiracetam add-on is effective and well tolerated in severe myoclonic epilepsy of infancy. Placebo-controlled studies should confirm these findings.

'Benign focal epilepsy in infancy with vertex spikes and waves during sleep'. Delineation of the syndrome and recalling as 'benign infantile focal epilepsy with midline spikes and waves during sleep' (BIMSE).

PURPOSE: To better delineate the electroclinical features of infants who presented with focal seizures and typical midline sleep EEG abnormalities with a benign outcome. We discuss the significance of the typical EEG marker in non-epileptic patients. METHODS: Patients were selected from a group of epileptic subjects with seizure onset less than 3 years we observed from 1st November 1990 and 31st December 2003. Inclusion criteria were the presence of typical sleep EEG marker and focal seizures with benign outcome. Cases with less than 18 month follow-up period were excluded from this study. RESULTS: There were 19 patients (12 males, 7 females). Pre-, peri- and post-natal personal history was negative in all patients. Psychomotor development was normal, both before and after seizure onset. Neuroradiological investigations gave normal results. Seizure manifestations were typical, characterized by cyanosis, staring and rare lateralizing signs, of short duration. Age at onset was comprised between 4 and 30 months. The typical EEG marker, a spike followed by a bell-shaped slow-wave, localized in the midline regions, was present in all subjects only during sleep. All had a favorable outcome and the overwhelming majority of the patients were not treated. CONCLUSIONS: Our patients have an homogeneous electroclinical picture to constitute a new epileptic syndrome not included in the ILAE classification. We propose to call it 'benign focal epilepsy in infancy with midline spikes and waves during sleep' (BIMSE).

Efficacy of levetiracetam in pharmacoresistant continuous spikes and waves during slow sleep.

OBJECTIVE: To evaluate the efficacy of levetiracetam (LEV) in continuous spikes and waves during slow sleep (CSWS). Despite first description dates back to 1971, no agreement exists about CSWS treatment. The condition is rare and controlled clinical trials are very difficult to perform, so the reports about efficacy of different drugs are anecdotal. PATIENTS AND METHODS: We introduced LEV in three children affected by symptomatic focal epilepsy and pharmacoresistant CSWS and evaluated clinical, neuropsychological and electroencephalographic outcome. RESULTS: Two cases responded completely, one case showed only a mild reduction of spikes and waves during slow sleep. CONCLUSION: Even if our report is anecdotal, LEV expands the spectrum of antiepileptic drugs that can be used for the treatment of CSWS. LEV efficacy should be confirmed in larger series.

A clinical spectrum of the myoclonic manifestations associated with typical absences in childhood absence epilepsy. A video-polygraphic study.

We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE), presenting with typical absence seizures associated with myoclonic manifestations of the face or neck. All patients underwent repeated and prolonged split-screen video-polygraphic EEG recordings. The polygraphic recordings and clinical correlations of the absence seizures were analysed. All patients presented with multi-quotidian, typical absence seizures. During the absences, the patients could show mild, rhythmic, myoclonic jerks involving facial areas (eyebrows, nostrils, perioral region, chin) or neck muscles (sternocleidomastoideus), with the same frequency as the spike-wave complexes. Polygraphic tracings demonstrated that the myoclonias were correlated to the spike component. Clinically, all patients showed a benign course, with complete seizure control under antiepileptic treatment. In the follow-up, 7 patients withdrew from treatment without relapse. We conclude that all our patients showed an electroclinical picture consistent with CAE. The occurrence of myoclonic manifestations of the face or neck associated with the absences did not influence the benign course of their disease. The electroclinical features observed in our group of patients differentiates our cases both from epilepsy with myoclonic absences and from absences with perioral myoclonia (with Video).

Benign partial epilepsies of adolescence: a report of 37 new cases.

PURPOSE: To delineate the electroclinical features of patients with partial seizures in adolescence with a benign outcome. METHODS: Patients were recruited in five different Italian epilepsy centers. Patients were selected among those with partial seizures between ages 11 and 17 years. We excluded benign childhood epilepsies, those with neurologic or mental deficits, and those with neuroradiologically documented lesions. We also excluded patients with less than 3 years' follow-up or who were still receiving antiepileptic therapy. RESULTS: There were 37 (22 male, 15 female) patients. Seizures started at the mean age of 14.5 years (range, 11-16.11). Two main electroclinical patterns emerged: 16 of 37 patients had somatomotor seizures frequently associated with focal theta discharges involving the centroparietal regions. Ten of 37 patients showed versive seizures and interictal spiking involving the posterior regions. A third group had clinical characteristics resembling the cases described by Loiseau. All had a favorable outcome. CONCLUSIONS: This relevant multicenter study further confirms the existence of benign partial epilepsies with onset during adolescence.

Benign partial epilepsy in infancy and early childhood with vertex spikes and waves during sleep: a new epileptic form.

International epilepsy classification includes different epileptic syndromes with favourable outcomes in paediatric age, both partial and generalised. This is true in childhood while no partial benign forms are accepted in infancy. In 1987, Watanabe first described a new entity and he defined it as 'benign complex partial epilepsies in infancy'. In 1992, Vigevano referred similar but familial cases whose seizures had secondary generalisation. Both these forms had no interictal EEG abnormalities neither awake nor during sleep. This article presents a survey of 12 cases of partial epilepsy with favourable outcome differing from Watanabe and Vigevano's cases, both for the presence of interictal EEG abnormalities only during sleep and for seizure picture. All our patients are neurologically and neuroradiologically normal. Psychomotor development is unremarkable. Age onset range is 13-30 months. All cases present characteristic spikes and waves during slow-sleep in vertex cerebral areas. Awake EEG is always normal, at follow-up too. Our cases have such homogeneous electroclinical features as to hypothesise a new partial idiopathic epileptic syndrome with favourable outcome in infancy and early childhood. We propose to define it as 'benign partial epilepsy in infancy and early childhood with vertex spikes and waves' (BVSE).

Intermittent falls and fecal incontinence as a manifestation of epileptic negative myoclonus in idiopathic partial epilepsy of childhood.

We report two children, suffering from idiopathic partial epilepsy, who started to present, in the same period of time, with epileptic negative myoclonus (ENM) in one lower limb and fecal incontinence (FI). Polygraphic recordings showed that ENM was associated with paroxysmal activities distributed over the vertex region. Both ENM and FI disappeared when ethosuximide treatment was started. We hypothesize that, in our patients, ENM in one lower limb and FI depended on a transitory impairment, caused by epileptic activity that altered the functionality of nearby cortical areas, located in fronto-mesial regions, involved in the control of the muscular tone of the lower limbs and of the pelvic floor muscles.

Effectiveness of a particular blue lens on photoparoxysmal response in photosensitive epileptic patients.

The aim of our work was to test a particular type of lens for photosensitivity control in photosensitive epileptic patients. Previous papers considered color and shade of dark to test lens efficacy. We added a new variable, namely lens material, to these well-known variables. We performed electroencephalography (EEG) and simultaneous video recordings in 83 epileptic patients to evaluate the effectiveness of these experimental blue lenses on photoparoxysmal response (PPR). In addition, we compared the lenses with four other types of commercially available lenses. We found that the experimental lens type was very effective for photosensitivity inhibition in epileptic subjects. Indeed, PPR disappeared in 64 of 83 patients (77%) and diminished in 16 (19%). All the other commercial lenses were less effective. We think that this particular lens type could be useful in managing photosensitive epileptic patients.

Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern?

PURPOSE: We reviewed the electroclinical pictures and clinical characteristics of 32 patients with continuous spike-and-wave activity during slow sleep (CSWS) to ascertain to what extent this electroencephalogram (EEG) pattern is associated with the age-related CSWS syndrome as defined by the International League Against Epilepsy (ILAE) International Classification or with different clinical settings. METHODS: We reviewed clinical and EEG characteristics of 32 CSWS patients. RESULTS: In all patients, detection of CSWS coincided with a worsening of neurologic status. Ten (34%) patients had the typical features of CSWS syndrome, four were classified as having Landau-Kleffner syndrome, and three had acquired opercular syndromes. The remaining 15 patients, all with symptomatic epilepsy, had CSWS, which lasted for variable periods and might be related to inappropriate drug choice. Three patients of this group had unilateral CSWS and exhibited worsening of spontaneous movements in the hemibody contralateral to CSWS activity lasting for a few hours after awakening. CONCLUSIONS: Our data show that a number of factors can intervene in the genesis of CSWS, which may explain the variability of the associated clinical conditions. In view of this etiologic heterogeneity, it is not possible to classify all the patients with CSWS as having the CSWS syndrome. Therefore, the CSWS syndrome should be considered a category embracing a limited group of patients, whereas the EEG pattern of CSWS is seen commonly in various clinical conditions.

Ethosuximide is effective in the treatment of epileptic negative myoclonus in childhood partial epilepsy.

The aim of our study was to evaluate the effectiveness of ethosuximide in the treatment of epileptic negative myoclonus, a motor disorder that can occur in childhood partial epilepsy. We introduced ethosuximide in nine patients with partial epilepsy of varying etiology (idiopathic, cryptogenic, symptomatic) who presented with epileptic negative myoclonus. The drug was added to the patients' preexisting antiepileptic drugs, which were maintained unchanged for the following 6 months. Epileptic negative myoclonus disappeared in all patients 15 to 30 days after ethosuximide was started. Plasma ethosuximide levels ranged from 55 to 89 micrograms/mL. The clinical response was not influenced by the patients' preexisting treatment or by the etiology of the epilepsy. No side effects were observed, and none of the patients presented a recurrence of epileptic negative myoclonus during follow-up. Furthermore, in five patients we observed the disappearance of partial seizures; in the remaining patients seizures were reduced by more than 75%. Electroencephalograms showed a decrement or disappearance of focal paroxysmal abnormalities. Our results suggest that ethosuximide is effective in the treatment of epileptic negative myoclonus and that it should be considered as a first-choice drug in the treatment of this motor disorder.

Can protrusion of the tongue stop seizures in Rolandic epilepsy?

We report the case of a child with benign partial epilepsy with centro-temporal spikes (BECT) in whom protrusion of the tongue stopped the interictal abnormalities, and describe the polygraphic EEG recording of a seizure which terminated upon voluntary protrusion of the tongue. We mention the close link between the post-central (somatosensory) cortex and pre-central (motor) cortex, and how the primary sensory area has direct access to the motor cortex. We also examine how a tactile stimulus may provoke the inhibition of an epileptic discharge.

Continuous spikes and waves during sleep in children with shunted hydrocephalus.

Focal epileptiform abnormalities in awake children submitted to ventricular shunting are well described in the literature, but there are few reports about EEG patterns during sleep. We studied 20 children affected by hydrocephalus of various aetiology and submitted to shunting during the first year of life. We found focal abnormalities in all the children and in 95% of cases they were on the same side as the shunt; in 65% of cases they had an amplitude of 300 mV or more. During sleep there was activation of abnormalities in all subjects, and in 33% we found continuous spikes and waves during slow sleep (CSWS). We discuss the aetiology of CSWS and its possible role in causing the neuropsychological disturbances of our patients.

Perinatal factors and 2-year minor neurodevelopmental impairment in low birth weight infants.

Perinatal factors were investigated in 53 low birth weight infants with minor neurodevelopmental dysfunction at 2-year follow-up and in 106 consecutive controls matched for gestational age and birth weight (within 100-gram intervals). The obstetrical history, as evaluated by the obstetrical optimality score, was significantly worse in the cases than in controls (obstetrical optimality score = 50.9 +/- 5.9 vs. 53.2 +/- 6.9, p = 0.019 by Mann-Whitney test). Multiple conditional logistic regression analysis showed that after adjustment for socioeconomic status and education of the mother, a low number (< 3) of prenatal visits, and a third trimester hemorrhage were the only antenatal factors significantly associated with an increased risk of minor infant neurodevelopmental impairment. Neonatal acidosis (pH < 7.2 in the first 24 h of life) and male gender were additional significant perinatal risk factors. Only a few antenatal and perinatal factors are correlated with subsequent minor neurodevelopmental impairment in low birth weight infants.