Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing.

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM- remains to be elucidated.

Fenfluramine below the age of 2 years in Dravet syndrome: What about safety and efficacy?

Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. Infants with DS are especially vulnerable to the detrimental effects of prolonged and frequent seizures on development. Fenfluramine (FFA) is approved for the treatment of DS in patients aged 2 years and older. This study aims to evaluate the safety and efficacy of FFA in patients with DS younger than 2 years. We analyzed safety, tolerability, seizure, and neuropsychological outcome in a real-world setting. Developmental profile was investigated using Griffiths Mental Development Scales (GMDS). Five patients received FFA at a mean age of 14.9 months (9.6-18.6). Median follow-up was 13 months (interquartile range [IQR] = 12.9-24.4). All patients showed good tolerance to FFA. No significant variation of body mass index or echocardiographic issue was observed. Monthly median convulsive seizure frequency (MCSF) was 1.71 (IQR = 1.56-3.27) at the 6-month baseline period and .92 (IQR = .43-1.28) at last follow-up, with a median 54.43 (IQR = 40.91-60.83) percentage reduction in MCSF. Two of five patients had a performance improvement on GMDS subscales. Overall, the use of FFA below the age of 2 years in our small sample of patients was safe and represents a promising opportunity for seizure control and for protection of the neurodevelopmental outcome.

Extended Glasgow Outcome Scale to Evaluate the Functional Impairment of Patients With Subcortical Band Heterotopia: A Multicentric Cross-sectional Study.

BACKGROUND: Subcortical band heterotopia (SBH) is a rare malformation of the cortical development characterized by a heterotopic band of gray matter between cortex and ventricles. The clinical presentation typically includes intellectual disability and epilepsy. PURPOSE: To evaluate if the Extended Glasgow Outcome Scale-pediatric version (EGOS-ped) is a feasible tool for evaluating the functional disability of patients with (SBH). METHOD: Cross-sectional multicenter study of a cohort of 49 patients with SBH (female n = 30, 61%), recruited from 23 Italian centers. RESULTS: Thirty-nine of 49 (80%) cases showed high functional disability at EGOS-ped assessment. In the poor result subgroup (EGOS-ped >3) motor deficit, language impairment, and lower intelligence quotient were more frequent (P < 0.001, P = 0.02, and P = 0.01, respectively); the age at epilepsy onset was remarkably lower (P < 0.001); and the prevalence of epileptic encephalopathy (West syndrome or Lennox-Gastaut-like encephalopathy) was higher (P = 0.04). The thickness and the extension of the heterotopic band were associated with EGOS-ped score (P < 0.01 and P = 0.02). Pachygyria was found exclusively among patients with poor outcome (P < 0.01). CONCLUSIONS: The EGOS-ped proved to be a reliable tool for stratifying the functional disability of patients with SBH. According to this score, patients could be dichotomized: group 1 (80%) is characterized by a poor overall functionality with early epilepsy onset, thick heterotopic band, and pachygyria, whereas group 2 (20%) is characterized by a good overall functionality with later epilepsy onset and thinner heterotopic band.

Epilepsy in "Sunflower syndrome": electroclinical features, therapeutic response, and long-term follow-up.

BACKGROUND: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking. METHODS: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability. RESULTS: 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings. CONCLUSION: While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.

Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis.

BACKGROUND: Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4-15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy. AIM: To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA. METHODS: By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA. RESULTS: We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA. CONCLUSIONS: We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels. SIGNIFICANCE: A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.

Hemispheric surgery for severe epilepsy in early childhood: a case series.

Hemispheric surgery is an effective and cost-effective option for hemispheric epilepsy. Data specifically focusing on very early infancy are scant. In our study, we report the results of hemispheric surgery in children under three years of age, along with clinical, neuroradiological and EEG features, from two Italian epilepsy surgery centres. After reviewing our epilepsy surgery databases (2008-2018), we identified 14 patients (seven males) submitted to hemispheric surgery, under three years (range: 2-29 months), with a follow-up of at least 12 months. No deaths occurred, and surgical complications were observed in 3/17 procedures. At final follow-up visit (mean: 30.8 months; range: 12-90), 10/14 patients (71.4%) achieved Engel Class I (eight Class 1A, one Class 1B, and one Class 1C). Antiepileptic drugs were completely discontinued in three and reduced in eight, thus a significant decrease in drug regimen after surgery was achieved in 11/14 patients (78.6%). Before surgery, severe developmental delay was present in 10 patients, moderate in two and mild in two. At the last follow-up visit, the degree of developmental delay changed from severe to moderate in five patients, remained unchanged in six cases (four severe and two moderate), and changed from mild to moderate in two following surgery. In many cases, hemispheric surgery in children under three years is effective in achieving seizure freedom or reducing seizure frequency, with the possibility of simplifying complex drug regimens. Moreover, it appears to be a safe and well tolerated procedure, leading to improvement in cognition and posture.

CACNA1A-Linked Hemiplegic Migraine in GLUT 1 Deficiency Syndrome: A Case Report.

Background: Glucose-transporter-1 deficiency syndrome (GLUT1-DS), due to SLC2A1 gene mutation, is characterized by early-onset seizures, which are often drug-resistant, developmental delay, and hypotonia. Hemiplegic migraine (HM) is a rare form of migraine, defined by headache associated with transient hemiplegia, and can be caused by mutations in either CACNA1A, ATP1A2, or SCN1A. Paroxysmal movements, other transient neurological disorders, or hemiplegic events can occur in GLUT1-DS patients with a mild phenotype. Case: We report on a girl with GLUT1-DS, due to SLC2A1 mutation, with a mild phenotype. In early childhood, she developed epilepsy and mild cognitive impairment, balance disorders, and clumsiness. At the age of 9, the patient reported a first hemiplegic episode, which regressed spontaneously. Over the next 3 years, two similar episodes occurred, accompanied by headache. Therefore, in the hypothesis of HM, genetic testing was performed and CACNA1A mutation was identified. The treatment with Lamotrigine avoided the recurrence of HM episodes. Discussion: To our knowledge, among the several cases of GLUT1-DS with HM symptoms described in the literature, genetic testing was only performed in two of them, which eventually proved to be negative. In all other cases, no other genes except for SLC2A1 were examined. Consequently, our patient would be the first description of GLUT1-DS with HM due to CACNA1A mutation. We would emphasize the importance of performing specific genetic testing in patients with GLUT1-DS with symptoms evocative of HM, which may allow clinicians to use specific pharmacotherapy.

Anti-GAD epileptic encephalopathy in a toddler with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a progressive facial hemiatrophy often associated with severe epilepsy. Although an immune-mediated vasculitic pathogenesis is widely assumed, no CNS-specific autoantibody has been described so far. A 2-year-old boy was admitted for a status epilepticus preceded by fever, restlessness, insomnia, and left facial rash. Cerebrospinal fluid was positive for glutamic acid decarboxylase (GAD)-antibodies. Brain MRI revealed FLAIR hyperintensities on left mediotemporal areas. He was successfully treated with intravenous methylprednisolone. One month later, seizures and facial rash reappeared and steroids were satisfactorily repeated. However, left hemifacial rash reappeared 5 months later, slowly followed by sclerotic skin lesions on frontal scalp and hemifacial sub-atrophy, leading to a diagnosis of PRS. Three years later, and despite chronic immunosuppression, new MRI lesions on left white matter are seen and left hemifacial atrophy has progressed. For the first time, we describe GAD autoantibodies in a PRS patient with epileptic encephalopathy. Epileptic syndromes with GAD autoantibodies are frequently described though with a questionable pathogenic significance. Given the clinical and MRI similarities of PRS with both Morphea and Rasmussen's encephalitis, we suggest that, in our patient, the initial facial skin vasculitis spread into CNS vessels through perforating arteries, inducing neuronal MHC-class I presentation of GAD epitopes, ultimately causing CD8-mediated neuronal cytotoxicity and the epileptic encephalopathy. GAD autoantibodies might represent the missing pathophysiological link between PRS and neuropsychiatric manifestations.

Early clinical and EEG findings associated with the outcome in childhood absence epilepsy.

OBJECTIVES: The objective of this study was to investigate several clinical electroencephalogram (EEG) findings possibly predicting the early response to antiepileptic drugs (AEDs) and the late outcome in children with clinical EEG features fitting the syndromic diagnosis of childhood absence epilepsy (CAE). METHODS: In 117 untreated patients with typical absences, we analyzed clinical EEG features, and resting EEG activity using partial directed coherence to calculate out- and inflow of cortical oscillations in different regions of interest. RESULTS: Absences began before 4 years in 12.0%, at 4-9.5 years in 71.8%, and at 10-13 years in 16.2% of the cases. Valproate was started in 91 patients and ethosuximide in 27. With one of AEDs, 77.8% reached seizure control, while the remaining patients needed to switch to the alternative AED. Only 5.9% patients remained drug-resistant. Absences with simple automatisms were the only feature associated with a lack of response to the first AED. Connectivity analysis of resting EEGs showed increased frontal outflow in patients compared with controls, which was significantly greater in the nonresponders to the first AED than in responders. Among the 91 patients followed for 61.2 ±â€¯31.7 months, 14.2% relapsed after a seizure-free period, without differences between the responders to the first or second AED. CONCLUSIONS: The assessment of electroclinical features provided only minimal prognostic indices. The enhanced outflow of frontal oscillations suggests a circuitry dysfunction significantly greater in the nonresponder to the early treatment. Seizure relapses were rare and comparable in patients who reached seizure freedom with first or second AED, indicating that the resistance to one AED does not influence the outcome.

VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.

BACKGROUND: Mitochondrial respiratory chain consists of five complexes encoded by nuclear and mitochondrial genomes. Mitochondrial aminoacyl-tRNA synthetases are key enzymes in the synthesis of such complexes. Bi-allelic variants of VARS2, a nuclear gene encoding for valyl-tRNA (Val-tRNA) synthetase, are associated to several forms of mitochondrial encephalopathies or cardiomyoencephalopathies. Among these, the rare homozygous c.1100C > T (p.Thr367Ile) mutation variably presents with progressive developmental delay, axial hypotonia, limbs spasticity, drug-resistant epilepsy leading, in some cases, to premature death. Yet only six cases, of which three are siblings, harbouring this homozygous mutation have been described worldwide. CASE PRESENTATION: Hereby, we report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes. Standard genetic tests were normal, as well as metabolic investigations. Brain MRI showed unspecific progressive abnormalities, such as corpus callosum hypoplasia (patient A) and cerebellar atrophy (patient A and B). Diagnosis was reached by adopting massive parallel next generation sequencing. Notably clinical phenotype of the first patient appears to be milder compared to previous known cases. The second patient eventually developed refractory epilepsy and currently presents with severe global impairment. Because no specific treatment is available as yet, both patients are treated with supporting antioxidant compounds along with symptomatic therapies. CONCLUSIONS: Given the paucity of clinical data about this very rare mitochondrial encephalopathy, our report might contribute to broaden the phenotypic spectrum of the disorder. Moreover, noteworthy, three out of five pedigrees so far described belong to the Northern Sardinia ethnicity.

Symptoms of anxiety and depression and family's quality of life in children and adolescents with epilepsy.

INTRODUCTION: We studied children and adolescents with epilepsy (CAWE) and their families to evaluate symptoms of anxiety and depression, quality of life (QoL), and their correlations with epilepsy characteristics. MATERIAL AND METHODS: The study included 326 (52.5% females) 8 to 18years old CAWE. Anxiety and depression were assessed with the "Self-administered psychiatric scales for children and adolescents" (SAFA), and family's QoL with the parents' report "Impact of Epilepsy on QoL" (IEQoL). RESULTS: The CAWE exhibiting abnormal (T≥70) scores were 8.0% in the anxiety scale, 9.2% in the depression scale, and 4.6% in both scales. Social anxiety was the predominant anxiety symptom, while irritable mood and desperation were the most frequent symptoms of depression. Depressive symptoms were associated with parents' complaint of higher worries about the child's condition and future and lower well-being of the family. Severity and duration of the epilepsy and polypharmacy were independent from abnormal scores of anxiety and depression, but were associated with parents' worries about the child's condition and family's well-being. CONCLUSIONS: Anxiety and depression in CAWE are independent from the characteristics of the disease but are correlated to the lower well-being of the family. A search of these emotional problems is recommended for better care of the patients and their families.

Follow-up study of idiopathic generalized epilepsy with associated absence seizure and myoclonic epilepsy of infancy.

We evaluated the long-term prognosis of patients featuring the association of absences and myoclonic epilepsy of infancy. Our cohort consisted of 10 male subjects with mean age at seizure onset of 29 months. Follow-up data included seizure outcome and EEG findings. All individuals received antiepileptic drugs (AEDs) as monotherapy (6 patients) or polytherapy (4 patients) for a mean period of 24 months. Over a 30-60 month evaluation period (mean: 43 months), all patients were seizure-free. Follow-up data after withdrawal of antiepileptic therapy were obtained for a mean period of 22 months. None of the children did develop other age-related epileptic syndrome after AEDs discontinuation. Furthermore, follow-up EEG data after drugs withdrawal were normal and none of the patients showed cognitive impairment. In conclusion, we confirm that absence seizures may occur in association with myoclonic epilepsy of infancy. This condition shows excellent prognosis with either favourable neurologic development and seizure outcome in these children.

Epilepsy in fragile-X-syndrome mimicking panayiotopoulos syndrome: Description of three patients.

Fragile-X-syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10-20% of individuals with Fragile-X-syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. We describe the clinical features, EEG findings and evolution in three patients affected by Fragile-X-syndrome and epilepsy mimicking Panayiotopoulos syndrome. Age at seizure onset was between 4 and about 7 years. Seizures pattern comprised a constellation of autonomic symptoms with unilateral deviation of the eyes and ictal syncope. Duration of the seizures could be brief or lengthy. Interictal EEGs revealed functional multifocal abnormalities. The evolution was benign in all patients with seizures remission before the age of 14. This observation expands the spectrum of benign epileptic phenotypes present in Fragile-X-syndrome and may be quite helpful in guiding anticonvulsant management and counseling families as to expectations regarding seizure remission.

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

Symptomatic and presumed symptomatic focal epilepsies in childhood: An observational, prospective multicentre study.

OBJECTIVE: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance. METHODS: In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses. RESULTS: Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy. SIGNIFICANCE: In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.

The perceived burden of epilepsy: Impact on the quality of life of children and adolescents and their families.

PURPOSE: The assessment of the quality of life (QoL) is relevant for a comprehensive treatment of patients with epilepsy. In children and adolescents, an impact of epilepsy on the QoL of the entire family is expected. METHODS: We asked 293 parents of children and adolescents with epilepsy, included in an observational study on treatment satisfaction, to evaluate the impact of the disease on several aspects of the QoL of the whole family using a specifically organized questionnaire (IEQoL). RESULTS: The degree of parents' concerns about epilepsy and the severity of the disease correlated with a deterioration of QoL in both the children and the family. This involved all aspects of QoL (conflicts within the family, job, leisure activities, peer relationship, economy) although to a different degree. Parents frequently admitted increased apprehensiveness, even when not justified by the low severity of the disease. There was general agreement between parents and their adolescent children, although in a few cases adolescents overrated their school and daily performance in respect to the parents, suggesting a tendency to overlook their problems. CONCLUSION: Epilepsy impairs all aspects of QoL, although at different degree, both in children/adolescents and in their families. Parental apprehensiveness appears to have a role on this, and it may not reflect the severity of the disease.

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.

Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.

An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program.

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.

Long-term follow-up in children with benign convulsions associated with gastroenteritis.

BACKGROUND: The outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations. AIM: To assess the long-term neurological outcome of a large sample of children presenting with CwG. METHODS: We reviewed clinical features of 81 subjects presenting with CwG (1994-2010) from three different Italian centers with a follow-up period of at least 3 years. RESULTS: Follow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7%). Fourteen children (17.3%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7%), and a transient photosensitivity in one (1.2%). No recurrence of CwG was observed. Three patients (3.7%) presented with a febrile seizure and two (2.5%) with an unprovoked seizure, but none developed epilepsy. CONCLUSIONS: The long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.