Sara Matricardi

Memory impairment and Benign Epilepsy with centrotemporal spike (BECTS): A growing suspicion

Benign Epilepsy with centrotemporal spikes (BECTS) is considered a benign type of epilepsy; nevertheless a significant number of children present clear and heterogeneous cognitive deficits such as memory disturbances. Thus far, evidence about memory impairment has been less than conclusive. To clarify the quality of memory functioning in BECTS children, an analysis of existing findings has been conducted trying to identify the type of memory deficits and their underlying factors. Short- and long-term declarative memory are impaired in BECTS children, with both verbal and non-verbal material; co-occurrence of attentional, linguistic and behavioral disturbances is reported. In children with continuous spikes and waves during the slow-wave sleep pattern the normal downscaling of slow-wave activity is absent, disrupting plastic brain processes of sleep-related memory consolidation. In BECTS children, NREM sleep interictal epileptiform discharges (IED) may interfere in the dialogue between temporal and frontal cortex, causing declarative memory deficits: the role of NREM sleep IED acquires a special importance, leading to methodological guidance and suggesting aims for future researches in the field of childhood neuroscience.

Neuropsychological impairment in children with Rolandic epilepsy and in their siblings

To assess and characterize a possible neurocognitive endophenotype associated with Rolandic epilepsy (RE), a clinical study was carried out to evaluate the neuropsychological profile of children with RE at onset and of their healthy siblings. Seventeen subjects were recruited (10 boys and 7 girls): nine patients affected by RE and eight siblings who underwent clinical and neuropsychological evaluations. All patients and only two siblings showed centrotemporal spikes on the electroencephalographic recording. Eighteen age- and sex-matched healthy children were assessed as controls. A significant impairment was found in language domain, attentional functioning, and short- and long-term verbal memory in both patients and siblings. A positive correlation between verbal comprehension and working memory scores was found in both groups. A similar neuropsychological profile of RE, which affected patients and their siblings with impairment in the same developing areas, supports the hypothesis of a specific neurocognitive phenotype in RE.

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non‐specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs.

Transition into adulthood: Tuberous sclerosis complex, Sturge-Weber syndrome, and Rasmussen encephalitis

Children with tuberous sclerosis complex, Sturge‐Weber syndrome, and Rasmussen encephalitis all have complex but differing needs in the process of transition/transfer to adult care. All three may be associated with long‐term normal intelligence or a varying degree of intellectual disability. In tuberous sclerosis complex, the emphasis of care in adulthood shifts from seizure control and developmental issues to renal and psychiatric disease and other issues. In Sturge‐Weber syndrome, the emphasis shifts from seizure control and rehabilitation to management of disability and migraine. In Rasmussen encephalitis, transition may be particularly complex for those with adolescent onset. Those successfully operated on for childhood onset have a static problem and the potential to do well in life.

Neuropsychological impairment in childhood absence epilepsy: Review of the literature

AIM Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence seizures in school age children. Although it is commonly considered to have a good prognosis, with a good response to antiepileptic drugs, recent studies questioned this traditional view of a “benign” disorder, in particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological involvement in patients affected by CAE. METHODS A literature search was carried out in PubMeds and Medlines databases for all relevant studies published between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specific review articles, systematic reviews, textbooks and case reports were examined for any further publications. RESULTS In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions have been reported to be mildly impaired. Data regarding memory are still conflicting. DISCUSSION Given the neuropsychological deficits in many CAE patients which significantly affect their quality of life, CAE should not be considered entirely “benign”. An early identification of neuropsychological dysfunction in CAE children is essential for appropriate treatment.

Refractory Absence Epilepsy and Glut1 Deficiency Syndrome: A New Case Report and Literature Review

We report a 12-year-old female patient with a mild phenotype of glucose transporter type 1 deficiency syndrome (Glut1D). The clinical picture was characterized by refractory absence epilepsy, migraine, and learning disabilities. Absence seizures appeared at the age of 4 years, and electroencephalogram (EEG) showed irregular discharges of diffuse epileptic abnormalities. During the follow-up, seizures became drug resistant, cognitive evaluation revealed learning difficulties, and the patient complained migraine episodes. The evidence of seizure worsening before meals and the drug resistance suggested a Glut1D. Molecular analysis of SLC2A1 gene showed the presence of a pathogenic de novo mutation of the gene in heterozygosity (p.Ala275Thr, c.823G > A). Our case and the review of literature data on patients with Glut1D and absences provide a combination of clinical and EEG keys that should prompt the genetic analysis. The Glut1D should be suspected when absence seizures are associated with at least one among: irregular ictal EEG discharges, mild mental retardation, migraine, microcephaly, drug resistance, and worsening during fasting. An early diagnosis allows to establish one of the available ketogenic regimens which could modify the natural history of this treatable condition.

Hemispherotomy in Rasmussen encephalitis: Long-term outcome in an Italian series of 16 patients

Surgical disconnection of the affected hemisphere is considered the treatment of choice for Rasmussen encephalitis (RE), however few data on long-term outcomes after disconnective surgery are available. We report on long-term seizure, cognitive and motor outcomes after disconnective surgery in 16 (8 M, 8 F) RE patients. Pre- and post-operative evaluations included long-term video-EEG monitoring, MRI, assessment of motor function, and cognitive evaluation. Hemispherotomy, by various techniques was used to obtain functional disconnection of the affected hemisphere. The patients, of median current age 23.5 years, range 12-33, were operated on between 1993 and 2009. Median age at disease onset was 5.8 years (range 3-11.4). Median time from seizure onset to surgery was 3.8 years, range 8 months to 21 years. Post-surgical follow-up was a median of 9.5 years, range 3-20. At surgery all patients were receiving two or more antiepileptic drugs (AEDs). All but three patients were seizure-free at latest follow-up. AEDs had been stopped in ten patients; in the remaining six AEDs were markedly reduced. Postural control improved in all patients. Gain in cognitive functioning was significantly (p=0.002) related to disease duration. The long-term outcomes, in terms of seizure control, motor improvement, and cognitive improvement provide important support for disconnective surgery as first choice treatment for RE.

Rufinamide for the treatment of refractory epilepsy secondary to neuronal migration disorders

OBJECTIVE To evaluate the efficacy and tolerability of add-on rufinamide in children with refractory epilepsy symptomatic of neuronal migration disorders. MATERIALS AND METHODS We recruited 69 patients in a prospective, open-label, add-on treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care according to the following criteria: age 3 or above; focal or generalized seizures refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination, secondary to neuronal migration disorders; two or more seizures per month in the last 6 months; use of another AED, but no more than three, at baseline. Informed consent from parents and/or caregivers was obtained at the time of enrollment. RESULTS We enrolled 69 patients with a mean age of 15 years (range 3-43). Forty-three patients (62%) had a 50-99% seizure reduction, and two (3%) became seizure-free. Seizure frequency was unchanged in 18 (26%) and worsened in 6 (8.7%). Twenty-nine patients (42%) reported adverse side effects, whilst taking rufinamide. Irritability was the most common side effect (11 patients), followed by decreased appetite (10), mood shift (6), vomiting (5), drowsiness (4), and decreased attention (2). Blood levels of concomitant anticonvulsive drugs were transiently abnormal in 5 patients. CONCLUSION In our population of severely refractory epilepsy due to neuronal migration disorders, rufinamide appeared to be effective and generally well tolerated.

Reflex myoclonic epilepsy in infancy: A multicenter clinical study

PURPOSE To describe the clinical and electroencephalographic (EEG) features of reflex myoclonic epilepsy in infancy (RMEI) and long-term cognitive outcome. METHODS We enrolled 31 children from 16 neuropediatric centres in Italy, who underwent clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests. RESULTS The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Spontaneous attacks were reported in 32.2% of the cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity. Patients were re-evaluated after a period of 7.2 ± 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children. CONCLUSIONS RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children.

Perisylvian, including insular, childhood epilepsy: Presurgical workup and surgical outcome

To report the presurgical workup, surgical procedures, and outcomes in a series of pediatric patients with drug‐resistant epilepsy involving the perisylvian/insular regions.