Margherita Santucci

EEG features and epilepsy in patients with autism

Epileptic seizures are frequently reported (4-32%) in autism. These values are higher than in the normal population of children and adolescents (0.5%). In the literature there is no uniform description of epilepsy in autism. We examined 106 patients with autistic disorder divided into three groups on the basis of presence or absence of EEG paroxysmal abnormalities (PA) and / or epilepsy including febrile convulsions (FG). Our patients presented an autistic syndrome unrelated to clear congenital or acquired encephalopathy. The prevalence of epilepsy and EEG PA was 23.6% and 18.9%, respectively. Significant differences between the three groups appeared for (i) familial antecedents for epilepsy / FC and neurologic and psychiatric diseases (P < 0.004), (ii) a different proportion between the three groups for mental retardation (P < 0.03), (iii) and EEG fast activity (P < 0.04). Our patients showed several types of epilepsy, including idiopathic forms with seizure onset after the age of 10 in 45% of cases. Seizures were mainly partial, not frequent and controllable by anti-epileptic drugs. PA were mostly focal and multifocal and in 45% of cases were typical of benign childhood partial epilepsy with centro-temporal spikes. The higher incidence of epilepsy and EEG PA is apparently not related to organic pre-, peri- and postnatal antecedents or cerebral lesions. On the contrary, genetic factors responsible for autism and epilepsy seem important in the genesis of these two disorders.

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus.

Background and Objective: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. Methods: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. Results: ESES and drop attack seizures appeared between the ages of 2 and 5 years(mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. Conclusions: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.

Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders

The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal abnormalities (PA) are frequently recorded in patients with autism, although the influence of epilepsy and/or EEG PA on the autistic regression has not been clarified yet. We examine a large sample of 345 inpatients with autism, divided into three groups: (1) patients without epilepsy and EEG PA; (2) patients with EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions. The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that reported in the general population. The significant differences among the three groups concerned autistic regression (comparison between groups 1 and 2, p<0.05; comparison between groups 1 and 3, p<0.01), cerebral lesions (comparison between groups 1 and 2, p<0.05; between groups 1 and 3, p<0.001), and symptomatic autism (comparison between groups 1 and 2 as much as comparison between groups 1 and 3, p<0.001), which were prevalent in groups 2 and 3; while severe/profound mental retardation was more frequent in group 3 compared to group 1 (p<0.01). Focal epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group with epilepsy. EEG PA were mainly localized in temporal and central areas (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep. Seizures and EEG PA were not related to autistic regression. EEG PA occurred mainly in childhood, while epilepsy tended to occur (p<0.001) as age increased. The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15 years with no difference between idiopathic and symptomatic cases. In 58.5% of subjects aged > or = 20 years, epilepsy including febrile seizures occurred at some point of their lives, while cases with only EEG PA were less frequent (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified and investigated. In autism, seizures and EEG PA could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions.

Early‐onset Absence Epilepsy and Paroxysmal Dyskinesia

Summary:  Purpose: To report on the association of childhood absence epilepsy and paroxysmal dyskinesia (PD).

Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy.

Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy.

Mutations in the mTOR pathway regulators NPRL2 and NPRL3 cause focal epilepsy

Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy.

Prognostic factors in patients with mesial temporal lobe epilepsy

Purpose:  To disclose clinical, electrophysiologic, and neuroradiologic factors correlated to prognosis in patients with mesial temporal lobe epilepsy (MTLE).

Familial Occurrence of Febrile Seizures and Epilepsy in Severe Myoclonic Epilepsy of Infancy (SMEI) Patients with SCN1A Mutations

Summary:  Purpose: The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25–70% of the patients having a family history of febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder.

Seizure worsening caused by decreased serum valproate during meropenem therapy.

Serum concentrations of valproate were reduced and seizures were exacerbated by concomitant meropenem therapy in a child with a neurodegenerative disorder and epilepsy. In this patient, a rapid decline of valproate serum concentrations was observed on two occasions with meropenem antibiotic therapy. This event was the most likely cause of observed seizure exacerbation. Meropenem should be used with caution in patients treated with valproate owing to the drastic lowering of serum valproate concentration and the consequent risk of seizure worsening. (J Child Neurol 2005;20:456—457).

Epilepsy in patients with pervasive developmental disorder not otherwise specified.

Data on epilepsy in pervasive developmental disorder not otherwise specified are few and scanty. Seventy-seven patients with pervasive developmental disorder not otherwise specified were compared with 77 with autistic disorder, matched for age and sex. The 2 groups were divided into 3 subgroups each: A, without electroencephalography (EEG) paroxysmal abnormalities or epilepsy; B, with EEG paroxysmal abnormalities without epilepsy; and C, with epilepsy. Mild mental retardation (P < .01), pathological neurological examination (P < .05), cerebral lesions (P < .01), abnormal EEG background activity (P < .001), and associated genetic pathologies (P < .01) were more common in pervasive developmental disorder not otherwise specified. Familial antecedents for epilepsy prevailed in subgroup C (P < .01). Epilepsy occurred in 35.1% of patients with pervasive developmental disorder not otherwise specified, with no statistically significant difference compared with autistic disorder. The mean age of seizure onset was earlier (2 years 8 months) in pervasive developmental disorder not otherwise specified (P < .000). Seizure outcome was better in autistic disorder. Genetic diseases and cerebral lesions should be investigated in pervasive developmental disorder not otherwise specified to clarify the etiological and clinical features.