Risk factors for neonatal seizures: A case-control study in the province of Parma, Italy.

PURPOSE: The present study evaluated the risk factors for electroencephalographic (EEG)-confirmed seizures during the whole neonatal period in preterm and term neonates born in the province of Parma between January 2009 and December 2014. METHODS: We selected as cases the infants that presented EEG-confirmed neonatal seizures (NS). Two population controls for each case were matched by gestational age (GA), sex, hospital, and period of birth. Information on the mother, the pregnancy, the labor and delivery, and the neonates were taken from the Emilia-Romagna Certificate of Delivery Assistance database and from hospital charts and ICD-9-CM codes. RESULTS AND INTERPRETATION: In the 6-year period of this study, 22 patients were recorded with NS. The association between at least one pregnancy complication and at least one neonatal complication, a low Apgar score, the need for resuscitation at birth, intraventricular hemorrhages (IVH) grades II-IV for preterm, and acute perinatal asphyxia/hypoxic-ischemic encephalopathy (HIE) for term infants were all statistically significant among cases. Neonates presenting these risk factors are more prone to develop NS and have to be strictly monitored.

Características clínicas, electroencefalográficas, terapéuticas y recurrencia de la epilepsia en el lactante / Clinical, therapeutic, electroencephalographic characteristics and recurrence of epilepsy in nursing babies

Introducción: La epilepsia es motivo de consulta frecuente en los servicios de neuropediatría a nivel mundial, con incidencia máxima en el menor de un año, se asocia con retraso del neurodesarrollo y recurrencia de las crisis. Objetivo: Caracterizar a los lactantes con epilepsia según aspectos clínicos, electro-encefalográficos, terapéuticos y la recurrencia de las crisis epilépticas. Métodos: Estudio observacional, prospectivo y longitudinal en 50 lactantes con epilepsia ingresados en el Hospital William Soler: 2016 a 2018. Se analizaron variables demográficas, clínicas y paraclínicas, tratamiento y recurrencia a los seis meses de iniciado el tratamiento antiepiléptico. Resultados: El inicio de las crisis se presentó de 1 a 4 meses en 60 por ciento, con predominio del sexo masculino (60 por ciento). El 44 por ciento presentó retraso del neurodesarrollo global y 32 por ciento parálisis cerebral. Predominaron las crisis epilépticas generalizadas motoras espasmos epilépticos (32 por ciento); la epilepsia generalizada (60 por ciento), el síndrome epiléptico: el síndrome de West (32 por ciento) y de etiología: desconocida (48 por ciento). El trazado electroencefalográfico más frecuente fue el generalizado (26 por ciento) seguido de hisparritmia (24 por ciento) La vigabatrina y el fenobarbital fueron los antiepilépticos más utilizados al inicio del tratamiento (24 por ciento cada uno. La recurrencia fue alta (62 por ciento). Conclusiones: La epilepsia en el lactante es más frecuente en varones y de inicio precoz. El retraso del neurodesarrollo global constituyó un factor asociado a la recurrencia de las crisis epilépticas. La parálisis cerebral, los hallazgos en estudios de neuroimagen y la etiología estructural son factores clínicamente significativos para la recurrencia(AU)

Introduction: Epilepsy is a reason of frequent consultation in neuropediatrics services at the global level, with peak incidence in infants of less than one year old. This is associated with neurodevelopmental delay and seizures recurrence. Objective: To characterize infants with epilepsy according to clinical, electro-encephalographic, therapeutic aspects and the seizures recurrence. Methods: Observational, prospective and longitudinal study in 50 infants with epilepsy whom were admitted in William Soler Hospital from 2016 to 2018. There were analysed demographic, clinical and paraclinical variables, and the treatment and recurrence six months after the beginning of the antiepileptic treatment. Results: The beginning of the seizures was at 1 to 4 months in the 60 percent, with predominance of males (60 percent). 44 percent presented global neurodevelopmental delay and 32 percent cerebral palsy. Generalized motor epileptic seizures and epileptic spasms predominated (32 percent); generalized epilepsy (60 percent), epilepsy syndrome: West syndrome (32 percent); and of unknown etiology (48 percent). The most frequent electroencephalographic tracing was the generalized one (26 percent) followed by hypsarrhythmia (24 percent). Vigabatrin and phenobarbital were the most commonly antiepileptic drugs used at the beginning of treatment (24 percent) each. Recurrence was high (62 percent). Conclusions: Epilepsy in the infant is more common in males and of early-onset. The delay in the global neurodevelopment was a factor associated with the recurrence of seizures. Cerebral palsy, findings in neuroimaging studies and the structural etiology are clinically significant factors for recurrence(AU).

[Frequency, semiology and prognosis of benign infantile epilepsy]. / Frecuencia, semiologia y pronostico de la epilepsia infantil benigna.

INTRODUCTION: Benign infantile epilepsy is an epileptic syndrome of infancy. Until now, only a small number of case-series have been published. AIM: To study the frequency, semiology and prognosis of benign infantile epilepsy. PATIENTS AND METHODS: The 827 patients with one or more epileptic seizures seen at our hospital between 1 June 1994 and 1 March 2011 were included and prospectively followed. A diagnosis of benign infantile epilepsy was made in patients that fulfilled the following criteria at six month of evolution: one or more focal and/or generalised seizures, onset before 24 months, no neurological deficit and normal neuroimaging and interictal EEG. RESULTS: 77 cases (9%) met the diagnostic criteria. Semiology of the seizures was similar to that of other focal seizures in children under 24 months. 25% of the patients remained as isolated seizures. Among those with two or more seizures, the probability of achieving a 3 year initial remission without antiepileptic treatment was 86%. In the subgroup of patients with focal seizures without family history the probability was 74% and in five cases a global developmental delay/intellectual disability was detected thereafter. CONCLUSIONS: Benign infantile epilepsy is a frequent epileptic syndrome. Semiology of seizures is not useful to characterize the syndrome. A diagnosis of benign infantile epilepsy at six month of evolution implies a reasonably good prognosis, but possibly not as good as for other self-limited epilepsies of infancy.

TITLE: Frecuencia, semiologia y pronostico de la epilepsia infantil benigna.Introduccion. La epilepsia infantil benigna es un sindrome epileptico sobre el que hasta ahora se ha publicado tan solo un pequeño numero de series de casos. Objetivo. Estudiar la frecuencia, semiologia y pronostico de la epilepsia infantil benigna. Pacientes y metodos. Los 827 pacientes con una o mas crisis epilepticas no provocadas que consultaron en nuestro hospital entre el 1 de junio de 1994 y el 1 de marzo de 2011 fueron incluidos y seguidos prospectivamente. Se diagnosticaron de epilepsia infantil benigna los pacientes que cumplieron los siguientes criterios a los seis meses de evolucion: una o mas crisis focales o generalizadas, inicio antes de los 24 meses, ausencia de deficits neurologicos y electroencefalograma y neuroimagen normales. Resultados. Cumplieron los criterios diagnosticos 77 casos (9%). La semiologia de las crisis fue similar a la de otras crisis focales en niños menores de 24 meses. Un 25% de los pacientes permanecio como con crisis aisladas. Entre los de dos o mas crisis epilepticas, la probabilidad de alcanzar una remision inicial de tres años sin tratamiento antiepileptico fue del 86%. En el subgrupo de pacientes con crisis focales sin antecedentes familiares, la probabilidad fue del 74%, y en cinco casos se detecto posteriormente un retraso psicomotor o discapacidad intelectual. Conclusiones. La epilepsia infantil benigna es un sindrome epileptico frecuente. La semiologia de las crisis no es util para caracterizar el sindrome. El diagnostico de epilepsia infantil benigna a los seis meses de evolucion implica un pronostico razonablemente bueno, pero posiblemente no tanto como el de otras epilepsias autolimitadas de la infancia.

Frecuencia, semiología y pronóstico de la epilepsia infantil benigna / Frequency, semiology and prognosis of benign infantile epilepsy

Introducción. La epilepsia infantil benigna es un síndrome epiléptico sobre el que hasta ahora se ha publicado tan sólo un pequeño número de series de casos. Objetivo. Estudiar la frecuencia, semiología y pronóstico de la epilepsia infantil benigna. Pacientes y métodos. Los 827 pacientes con una o más crisis epilépticas no provocadas que consultaron en nuestro hospital entre el 1 de junio de 1994 y el 1 de marzo de 2011 fueron incluidos y seguidos prospectivamente. Se diagnosticaron de epilepsia infantil benigna los pacientes que cumplieron los siguientes criterios a los seis meses de evolución: una o más crisis focales o generalizadas, inicio antes de los 24 meses, ausencia de déficits neurológicos y electroencefalograma y neuroimagen normales. Resultados. Cumplieron los criterios diagnósticos 77 casos (9%). La semiología de las crisis fue similar a la de otras crisis focales en niños menores de 24 meses. Un 25% de los pacientes permaneció como con crisis aisladas. Entre los de dos o más crisis epilépticas, la probabilidad de alcanzar una remisión inicial de tres años sin tratamiento antiepiléptico fue del 86%. En el subgrupo de pacientes con crisis focales sin antecedentes familiares, la probabilidad fue del 74%, y en cinco casos se detectó posteriormente un retraso psicomotor o discapacidad intelectual. Conclusiones. La epilepsia infantil benigna es un síndrome epiléptico frecuente. La semiología de las crisis no es útil para caracterizar el síndrome. El diagnóstico de epilepsia infantil benigna a los seis meses de evolución implica un pronóstico razonablemente bueno, pero posiblemente no tanto como el de otras epilepsias autolimitadas de la infancia

Introduction. Benign infantile epilepsy is an epileptic syndrome of infancy. Until now, only a small number of case-series have been published. Aim. To study the frequency, semiology and prognosis of benign infantile epilepsy. Patients and methods. The 827 patients with one or more epileptic seizures seen at our hospital between 1 June 1994 and 1 March 2011 were included and prospectively followed. A diagnosis of benign infantile epilepsy was made in patients that fulfilled the following criteria at six month of evolution: one or more focal and/or generalised seizures, onset before 24 months, no neurological deficit and normal neuroimaging and interictal EEG. Results. 77 cases (9%) met the diagnostic criteria. Semiology of the seizures was similar to that of other focal seizures in children under 24 months. 25% of the patients remained as isolated seizures. Among those with two or more seizures, the probability of achieving a 3 year initial remission without antiepileptic treatment was 86%. In the subgroup of patients with focal seizures without family history the probability was 74% and in five cases a global developmental delay/intellectual disability was detected thereafter. Conclusions. Benign infantile epilepsy is a frequent epileptic syndrome. Semiology of seizures is not useful to characterize the syndrome. A diagnosis of benign infantile epilepsy at six month of evolution implies a reasonably good prognosis, but possibly not as good as for other self-limited epilepsies of infancy

Neonatal seizures-part 2: Aetiology of acute symptomatic seizures, treatments and the neonatal epilepsy syndromes.

Most neonatal epileptic seizures are provoked by an underlying condition or problem-'acute symptomatic seizures'. However, a few neonatal epilepsy syndromes exist, and these are defined by the constellation of seizure types, EEG findings and family history seen. Making an accurate diagnosis of an epilepsy syndrome can help direct investigations, treatment options and provide prognostic information. This article discusses the investigative approach and treatments for neonatal epileptic seizures, including the neonatal epilepsy syndromes.

Atypical course in individuals from Spanish families with benign familial infantile seizures and mutations in the PRRT2 gene.

A benign prognosis has been claimed in benign familial infantile seizures (BFIS). However, few studies have assessed the long-term evolution of these patients. The objective of this study is to describe atypical courses and presentations in BFIS families with mutations in PRRT2 gene. We studied clinically affected individuals from five BFIS Spanish families. We found mutations in PRRT2 in all 5 families. A non-BFIS phenotype or an atypical BFIS course was found in 9/25 (36%) patients harbouring a PRRT2 mutation. Atypical features included neonatal onset, mild hemiparesis, learning difficulties or mental retardation, and recurrent seizures during adulthood. We also report a novel PRRT2 mutation (c.121_122delGT). In BFIS families an atypical phenotype was present in a high percentage of the patients. These findings expand the clinical spectrum of PRRT2 mutations including non-benign epileptic phenotypes.

Epilepsy in children with periventricular leukomalacia.

OBJECTIVE: We aimed to analyze the development of epilepsy in a patient group with periventricular leukomalacia followed at a tertiary pediatric neurology center. PATIENTS AND METHODS: The study included 108 children aged between 2 and 8 years with radiologically proven periventricular leukomalacia who had been regularly observed at the Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Neurology outpatient clinic between January 2006 and December 2011. RESULTS: Neonatal seizures were reported in 22 patients (20.3%), 14 of whom developed epilepsy. A significant correlation was found between neonatal seizures and prematurity and newborn asphyxia (p=0.013 and p=0.010, respectively). Epilepsy developed in 35 patients (32.4%), history of neonatal seizures and more severe loss of white matter, periventricular hyperintensity and corpus callosum involvement were found to be correlated with epilepsy (p=0.001, p=0.004, p=0.016, and p=0.004, respectively). The most common seizure pattern observed was generalized tonic clonic seizures (n=13) and complex partial seizures (n=11). Those with focal EEG findings had a significantly better neurodevelopmental and cognitive level than those with multifocal/generalized EEG findings (p=0.024). Seizures continued with varying frequency in 14 epileptic patients (40%) despite antiepileptic treatment. CONCLUSION: Almost a third of patients with periventricular leukomalacia develop epilepsy that can be intractable in substantial part. Neonatal seizures and severe MRI findings are important clues that can indicate the development of epilepsy in these patients.

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

OBJECTIVE: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. METHODS: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. RESULTS: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. CONCLUSIONS: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

Benign convulsions in newborns and infants: occurrence, clinical course and prognosis.

BACKGROUND: During early development severe epilepsies may appear, some with well established occurrence. Benign non-epileptic and epileptic paroxysmal syndromes with excellent prognosis occur in the same period. There are no exact data on their occurrence. AIM: We have reviewed medical histories of children with benign non-epileptic or benign epileptic events: benign myoclonus of early infancy, benign neonatal sleep myoclonus, benign sleep myoclonus in infancy, benign partial epilepsy in infancy (BPEI) and benign infantile familial convulsions (BIFC) were established. The occurrence, clinical characteristics and prognosis of these syndromes were evaluated. METHODS: Inclusion criteria were met in 31 children. Research included retrospective analysis of clinical characteristics, laboratory values, neuroimaging and neurophysiological assessments, followed by evaluation of psychosocial development with the use of the Strengths and Difficulties Questionnaire (SDQ), fulfilled by parents. RESULTS: In our group the incidence of benign non-epileptic convulsions was 6.69 per 10 000 live births and the incidence of benign epileptic convulsions was 1.35 per 10 000. Male/female ratio in the group of children with non-epileptic events was 2.1:1. Among non-epileptic group 5 out of 23 children and among epileptic group 3 out of 8 children had minimal, mild or moderate abnormalities at neurological assessment at the time of the first clinical examination. Nonspecific changes in laboratory values were seen in 6 out of 23 in the non-epileptic and in 1 out of 8 children in the epileptic group. Neurophysiological assessments showed subtle changes in 4/23 in the non-epileptic and 6/8 in the epileptic group. Neuroimaging was not optimal in 5/23 with non-epileptic and 3/8 with epileptic events. Analysis of SDQ did not show significant deviations in psyhosocial development. Statistically significant deviation was observed only in relations with peers (p = 0.009). CONCLUSIONS: Benign neonatal and infantile convulsions are more frequent than severe epilepsies of the same age period. Results show higher proportion of males with benign non-epileptic conditions. No deviations in further development was found. Laboratory values, neuroimaging and neurophysiological assessments were normal or nonspecifically changed.

Isolated neonatal seizures: when to suspect inborn errors of metabolism.

Neonatal seizures are common, and often comprise the first clinical indicator of central nervous system dysfunction. Although most neonatal seizures are secondary to processes such as hypoxic-ischemic injury, infection, or cortical malformations (which are readily identifiable through routine testing and imaging), seizures secondary to inborn errors of metabolism can be much more difficult to diagnose, and thus a high index of suspicion is required. The early diagnosis of inborn errors of metabolism is crucial, considering that many can receive effective treatment (e.g., dietary supplementation or restriction) with favorable long-term outcomes. This review emphasizes the importance of considering inborn errors of metabolism in the differential diagnosis of neonatal seizures, discusses red flags for inborn errors of metabolism as a cause of neonatal seizures, and provides an overview of diagnoses and treatments of inborn errors of metabolism most commonly associated with neonatal seizures.

[Familial and non-familial benign infantile seizures: A homogeneous entity?]. / Convulsions infantiles bénignes familiales et non familiales : une entité homogène ?

Among the epileptic syndromes occurring during infancy, which are mostly non-idiopathic and associated with a poor prognosis, benign infantile convulsions are characterized by a favourable evolution. This work aims to analyse and compare the clinical, EEG and outcome characteristics of familial benign infantile convulsions (FBIC) and non-familial benign infantile convulsions (NFBIC). This is a retrospective study, conducted between 1988 and 2008, in 40 infants who presented benign infantile seizures during the two first years of life. All of them had no personal history, normal psychomotor development, normal neurological examinations, no abnormalities on biological and radiological investigations and a favourable outcome. In 14 cases, there was a familial history of familial benign infantile convulsions. However, among the 26 cases with non-familial benign infantile convulsions, 11 children had a familial history of other epileptic syndrome. That may suggest a genetic familial susceptibility. In the two groups, the clinical features and the electroencephalography were similar. The seizures had short duration and occurred most often in clusters. Twenty-nine children had secondarily generalized partial seizures and 11 infants had generalized seizures but a focal onset cannot be excluded. The antiepileptic drugs allowed rapid resolution of seizures. One child necessitated a prolonged antiepileptic treatment. In the other cases, seizures cured in the first year without recurrence of seizures after treatment discontinuation. The evolution was characterised in five children by a later occurrence of dystonia. This subgroup was described as infantile convulsion and choreoathetosis syndrome (ICCA). Benign infantile convulsions are probably an underestimated epileptic syndrome. The diagnosis is relatively easy in the familial forms with dominant autosomal transmission. In contrast, in sporadic forms, the diagnosis can be confirmed only by the evolution. The good prognosis must be tempered by the subsequent onset of dystonia consisted in the ICCA syndrome and justifies a prolonged follow-up.

Neonatal seizures and long QT syndrome: a cardiocerebral channelopathy?

We identified a patient with electrophysiologically verified neonatal long QT syndrome (LQTS) and neonatal seizures in the presence of a controlled cardiac rhythm. To find a cause for this unusual combination of phenotypes, we tested the patient for mutations in seven ion channel genes associated with either LQTS or benign familial neonatal seizures (BFNS). Comparative genome hybridization (CGH) was done to exclude the possibility of a contiguous gene syndrome. No mutations were found in the genes (KCNQ2, KCNQ3) associated with BFNS, and CGH was negative. A previously described mutation and a known rare variant were found in the LQTS-associated genes SCN5A and KCNE2. Both are expressed in the brain, and although mutations have not been associated with epilepsy, we propose a pathophysiologic mechanism by which the combination of molecular changes may cause seizures.

Treatment of pediatric epilepsy: European expert opinion, 2007.

BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and approximately 650 treatment options) was sent to 57 European physicians specializing in pediatric epilepsy, 42 (74%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures. For initial monotherapy for complex partial seizures, carbamazepine and oxcarbazepine were treatments of choice, with valproate also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice. As initial therapy for infantile spasms that are symptomatic in etiology, vigabatrin was also treatment of choice, with adrenocorticotropic hormone (ACTH) and prednisone other first-line options. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. Valproate was treatment of choice as preventive therapy for febrile seizures. For benign childhood epilepsy with centro-temporal spikes, valproate was treatment of choice. For childhood and juvenile absence epilepsy, valproate was treatment of choice, with lamotrigine another first-line option (ethosuximide was another first-line option for childhood absence epilepsy). For juvenile myoclonic epilepsy in adolescent males, valproate was treatment of choice, with lamotrigine another first-line option; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with valproate another firstline option. As initial therapy for neonatal status epilepticus, intravenous (IV) phenobarbital was treatment of choice. As initial therapy for all types of pediatric status epilepticus, IV diazepam was treatment of choice. For generalized tonic-clonic status epilepticus, rectal diazepam and IV lorazepam were also treatments of choice; for complex partial status epilepticus, IV lorazepam was another first-line option. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

Estudio epidemiológico, clínico y evolutivo de 37 pacientes con epilepsia occipital benigna infantil de comienzo precoz / An epidemiological, clinical and developmental study of 37 patients with early-onset benign occipital epilepsy of childhood

Objetivo. Analizar las características epidemiológicas, clínicas y evolutivas de la epilepsia occipital benigna infantil de comienzo precoz para facilitar su sospecha diagnóstica en la práctica clínica diaria. Pacientes y métodos. Se han revisado 37 historias clínicas de pacientes con epilepsia occipital benigna infantil de comienzo precoz, recogiéndose características epidemiológicas y clínicas, exploraciones complementarias y datos evolutivos. Los criterios diagnósticos aplicados fueron los de la ILAE (International League Against Epilepsy). Resultados. La edad media al diagnóstico era de 5,4 años. El 64,9% fueron diagnosticados en edad preescolar, con mayor prevalencia del sexo femenino (67,6%). El número medio de crisis por paciente era de 3,3, y se caracterizaban preferentemente por alteración de la conciencia (90,3%), vómitos (70,1%), desviación ocular y/o cefálica (30,6%), y crisis motoras generalizadas (32,8%) o parciales (11,2%). El 67,2% de las crisis fueron durante el sueño. En 28 casos (75,7%) se objetivaron paroxismos occipitales que coexistían con paroxismos generalizados y/o multifocales. El 71,3% de las recurrencias se dieron en los primeros 6 meses, y a partir de los 2 años el 82,9% de los pacientes no tuvieron crisis, no encontrándose diferencias evolutivas entre pacientes tratados y no tratados. Se registró un paciente con evolución atípica. Conclusiones. La epilepsia occipital benigna infantil de aparición precoz es relativamente frecuente en la edad pediátrica, especialmente en edad preescolar. Aunque su secuencia semiológica es bastante característica, su inespecificidad clínica y neurofisiológica dificulta la sospecha diagnóstica. Su pronóstico es excelente; sin embargo, dado que podrían cursar de forma atípica, sería prioritario un riguroso control evolutivo de estos pacientes (AU)

Aim. To analyse the epidemiological, clinical and developmental characteristics of early-onset benign occipital epilepsy of childhood in order to facilitate its diagnostic suspicion in daily clinical practice. Patients and methods. The medical records of 37 patients with early-onset benign occipital epilepsy of childhood were reviewed in order to collect epidemiological and clinical features, results of complementary examinations and developmental data. The diagnostic criteria applied were those of the ILAE (International League Against Epilepsy). Results. The mean age at diagnosis was 5.4 years. In all, 64.9% were diagnosed at a pre-school age, with a greater prevalence of females (67.6%). The mean number of seizures per patient was 3.3 and they were mainly characterised by impaired consciousness (90.3%), vomiting (70.1%), eye deviation and/or headaches (30.6%), and generalised (32.8%) or partial (11.2%) motor crises. Seizures occurred during sleep in 67.2% of cases. In 28 cases (75.7%) occipital paroxysms were observed that coexisted with generalised and/or multifocal paroxysms. Of all recurrences, 71.3% occurred during the first 6 months, and from 2 years onwards 82.9% of the patients had no seizures; no developmental differences were found between treated and non-treated patients. One patient with an atypical development was recorded. Conclusions. Early-onset benign occipital epilepsy of childhood is relatively frequent at the paediatric age, especially in the pre-school years. Although its semiological sequence is quite characteristic, the fact that it lacks clinical and neurological specificity makes diagnostic suspicion more difficult. Its prognosis is especially favourable; however, since their progress may develop in an atypical manner, a rigorous developmental control of these patients would be of the highest priority (AU)

SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum.

Mutations of the sodium channel subunit gene SCN2A have been described in families with benign familial neonatal-infantile seizure (BFNIS). We describe two large families with BFNIS and novel SCN2A mutations. The families had 12 and 9 affected individuals, respectively, with phenotypes consistent with BFNIS. Two mutations were discovered in SCN2A (E430Q; I1596S). Both families had individuals with neonatal onset but the typical age of onset was in the early infantile period (mean 3.0 months). One mutation positive individual, with an otherwise typical clinical pattern, had seizures beginning at 13 months. Two individuals with SCN2A mutations were identified with seizures in later life. In each family a single individual with infantile seizures was mutation negative and thus represented phenocopies. This study extends the age range of presentation of BFNIS, confirms that neonatal and early infantile onsets are characteristic, and emphasizes the role of molecular diagnosis to confirm the etiology.

Early pattern of epilepsy in the ring chromosome 20 syndrome.

PURPOSE: The characteristics of epilepsy in ring chromosome 20 have been reported in adolescents and adults. The mode of onset most often remains imprecise. To clarify this onset period, we studied the early-onset features in our personal series and in the reported pediatric cases. METHODS: Our series comprises one child with an onset of epilepsy in the neonatal period and five others with an onset before age 8 years. The cases in the literature with an epilepsy onset before 8 years also were reviewed. RESULTS: Seizures in the neonatal period were described as motor seizures. Our personal patient with a neonatal onset had severe psychomotor delay. In both infancy and early childhood, the EEG showed no interictal frontal localization of the anomalies, and no long-lasting seizure was recorded. Seizures with terror and hallucinations usually appeared from about age 4 years. It is not before the age of 8 years that the usual interictal EEG pattern appeared of rhythmic theta slow-waves activity with spikes predominating in frontal areas described in adolescence and adulthood. The interictal EEG showed 1- to 2-Hz delta slow waves and spike-and-waves predominating in frontal areas, but no physiologic activity. CONCLUSIONS: In ring 20 chromosome, specific epilepsy features are lacking in the neonate, but the whole phenotype shows a more severe expression in terms of mental delay. The characteristic frontal EEG pattern and ictal terror do not appear before age 4 to 5 years.

Neonatal epilepsy syndromes and GEFS+: mechanistic considerations.

Genetic analyses of familial epilepsies over the past decade have identified mutations in several different ion channel genes that result in neonatal or early-onset seizure disorders, including benign familial neonatal convulsions (BFNC), generalized epilepsy with febrile seizures plus (GEFS+), and severe myoclonic epilepsy of infancy (SMEI). These genes encode voltage-gated Na+ channel subunits (SCN1A, SCN2A, SCN1B), voltage-gated K+ channel subunits (KCNQ2, KCNQ3), and a ligand-gated neurotransmitter receptor subunit (GABRG2). While the opportunity to genotype patients for mutations in these genes can have an immediate and significant impact on our ability to diagnose and provide genetic counseling to patients, the ultimate goal is to use this molecular knowledge to develop effective treatments and cures for each disorder. This will necessitate elucidation of the molecular, cellular, and network mechanisms that translate ion channel defects into specific epilepsy phenotypes. The functional analysis of epileptogenic channel mutations in vitro and in vivo has already provided a vast amount of raw biophysical data, but attempts to interpret these data to explain clinical phenotypes so far appear to raise as many questions as they answer. Nevertheless, patterns are beginning to emerge from these early studies that will help define the full scope of the challenges ahead while simultaneously providing the foundation of future efforts to overcome them. Here, I discuss some of the potential mechanisms that have been uncovered recently linking mutant ion channel genes to neonatal epilepsy syndromes and GEFS+.

Pediatric epilepsy -- an Indian perspective.

Prevalence studies from India suggest that epilepsy prevalence is similar to developed nations. Neurocysticercosis (NCC) predominates as an etiology. A large treatment gap is still a public health problem. Benign epilepsies and West syndrome appear to be underrepresented in studies on classification of seizures/syndromes. Febrile seizures prevalence in India is similar to other countries and appear to be as benign. Risk factors of intractable epilepsy (IE) in Indian studies include early age of onset, neurodevelopmental abnormalities and certain seizure types. Perinatal injuries underlie many IE. Many IE are not truly intractable and respond to simple therapeutic measures. The ketogenic diet and surgery are other methods now being used in Indian centers. Neurocysticercosis and neonatal hypoglycemic brain injury, two widely prevalent etiologies are reviewed in detail.