Idiopathic focal epilepsies: the "lost tribe".

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term "benign" is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence-free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the "unknown cause" classification and strongly suggest a genetic aetiology. The IFE are strongly age-related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age-related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of "Luke's Idiopathic Focal Epilepsy Project" to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.

Management of epilepsy in resource-limited settings.

Epilepsy is one of the most common and widespread neurological disorders affecting over 65 million people worldwide. Although estimates vary considerably, the annual incidence is considered to be almost 50 per 100,000 and prevalence around 700 per 100,000. It is thought, however, that more people are affected in low- and middle-income countries where resources to improve the care for people with epilepsy are limited. Of all people with epilepsy, around 80% live in resource-limited countries and up to 90% of these patients receive no treatment at all. National epilepsy programs to organize comprehensive care and cover educational, economic, and research aspects are necessary. A referral network will enable local healthcare workers to consult patients with more complex diseases and may ensure routine availability of inexpensive AEDs. Adequately identifying people with epilepsy and delivering cost-effective care in resource-limited countries is an important challenge for epileptologists and healthcare policy makers alike. Here we give an overview of the present situation and review the needs and the efforts currently being made in the field.

Congenital hemiparesis, unilateral polymicrogyria and epilepsy with or without status epilepticus during sleep: a study of 66 patients with long-term follow-up.

AIM: We retrospectively analysed the electroclinical features, treatment, and outcome in patients with unilateral polymicrogyria (PMG), focussing on epileptic syndrome with or without encephalopathy, with status epilepticus during sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) syndrome. METHODS: From June 1990 to December 2012, 39 males and 27 females, aged 5-26 years, were studied. We did not include patients with bilateral PMG or cases with unilateral PMG associated with other cerebral lesions. The mean follow-up period was 12 years (range: 3-22 years). RESULTS: Mean age at epilepsy onset was 6.5 years. Focal motor seizures occurred in all cases and 25 had secondary generalised seizures. Six patients also had complex focal seizures. Interictal EEG recordings showed focal spikes in all cases. For 43 of 53 patients with epilepsy, aged 2-9.5 years, the electroclinical features changed. An increase in frequency of focal motor seizures was reported in 20 patients, negative myoclonus occurred in 32 patients, atypical absences in 25 patients, and positive myoclonus in 19 patients. All patients had a continuous symmetric or asymmetric pattern of spike-wave activity during slow-wave sleep. CONCLUSION: For patients presenting with congenital hemiparesis, negative or positive myoclonus, and absences and focal motor seizures with ESES/CSWS, unilateral PMG should be considered. Brain MRI is mandatory to confirm this cortical malformation. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. For refractory cases, high-dose steroids were administered and surgery was performed in two patients. Outcome was relatively benign.

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.

Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10(-18), Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.

[Differential diagnoses of West syndrome]. / Diagnósticos diferenciales del síndrome de West.

This study describes the clinical and electroencephalographic characteristics of epileptic spasms, and more especially those that occur during the first two years of life (infantile spasms). West syndrome has been clearly defined as the association between infantile spasms with an electroencephalographic pattern of hypsarrhythmia. Although intellectual deficit appears in almost all cases in which infantile spasms are not controlled with medication, this is a developmental aspect of the condition and not a manifestation that must necessarily be present in order to define the syndrome. The analysis of the interictal and ictal electroencephalogram readings, together with the clinical characteristics of the spasms and the neurological examination of patients, provides some orientation as regards the causations. Despite the spectrum that the title of this work focuses on, the study does not cover the treatment of early infants with West syndrome. Emphasis is placed on the differential diagnoses of West syndrome with other epileptic syndromes that manifest in the first two years of life, and more especially with a series of abnormal non-epileptic motor phenomena that occur in early infants. All these last non-epileptic disorders are displayed in a table, but benign myoclonus of early infancy or Fejerman syndrome is given as a paradigmatic example for the differential diagnosis. The primordial aim is to prevent neurologically healthy early infants from receiving antiepileptic drugs and even adrenocorticotropic hormone or corticoids due to a mistaken diagnosis.

TITLE: Diagnosticos diferenciales del sindrome de West.Se describen las caracteristicas clinicas y electroencefalograficas de los espasmos epilepticos, en especial de aquellos que ocurren durante los dos primeros años de vida (espasmos infantiles). Queda claramente definido que el sindrome de West constituye la asociacion de espasmos infantiles con un patron de hipsarritmia en el electroencefagrama. Si bien el deficit intelectual aparece en casi todos los casos cuyos espasmos infantiles no se controlan con la medicacion, se trata de un aspecto evolutivo de la condicion y no de una manifestacion obligatoriamente presente para definir el sindrome. El analisis de los electroencefalogramas interictales e ictales, junto con las caracteristicas clinicas de los espasmos y el examen neurologico de los pacientes permite una orientacion respecto a las etiologias. En funcion del espectro enfocado en el titulo de este trabajo, se ha omitido abarcar el tratamiento de los lactantes con sindrome de West. Se pone enfasis en los diagnosticos diferenciales del sindrome de West con otros sindromes epilepticos que se manifiestan en los dos primeros años de vida, y muy especialmente con una serie de fenomenos motores anormales no epilepticos en lactantes. En una tabla se incluyen todos estos ultimos trastornos no epilepticos, pero se detalla como paradigmatico para el diagnostico diferencial el sindrome de mioclonias benignas del lactante o sindrome de Fejerman. El objetivo primordial es evitar que lactantes neurologicamente sanos reciban medicaciones antiepilepticas e incluso hormona adrenocorticotropa o corticoides por error en el diagnostico.

Idiopathic focal epilepsies.

In this chapter we include a series of epilepsies with onset in pediatric age characterized by focal seizures, idiopathic etiology, normal psychomotor development, and a benign course related to the spontaneous remission of seizures without sequelae. These entities are age-dependent and seizures tend to disappear spontaneously. For these reasons often the drug treatment is not necessary. On the basis of genetic assessment idiopathic focal epilepsies can be divided into two groups: nonautosomal dominant and autosomal dominant. In the group of nonautosomal entities we include benign epilepsy with centro-temporal spikes, Panayiotopoulos syndrome, idiopathic childhood occipital epilepsy described by Gastaut, and benign idiopathic midline spikes epilepsy. Seizures are rare, sometimes prolonged, as autonomic status in Panayiotopoulos syndrome. A common feature is the presence of peculiar EEG interictal paroxysmal abnormalities. In the group with an autosomal dominant mode of inheritance we include benign familial infantile seizures and benign familial neonatal-infantile seizures. These entities are characterized by partial seizures in cluster, self-limited in a brief period during the first months of life. There are no typical interictal EEG abnormalities. In some families a mutation in SCN2A, the gene coding for the 2α subunit of the voltage-gated sodium channel, has been described.

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.

[Genetic etiologies associated with severe epilepsies in infancy]. / Etiologías genéticas asociadas con epilepsias graves del lactante.

This is an update on severe epilepsies in infancy that are associated with genetic etiologies, either chromosomal abnormalities or gene mutations. These severe epilepsies may present the clinical and electroencephalographic phenotype of the so called epileptic encephalopathies, although a significant number of cases do not comply with the criteria to be included among the already known categories, as classified by the International League Against Epilepsy. Several chromosomal abnormalities, with or without a characteristic physical phenotype, are associated with epileptic encephalopathies in infants. Many patients are affected by metabolic or structural cerebral diseases of genetic etiology, in which seizures are not the only manifestation. Inborn errors of metabolism, deficiencies in cerebral transporters, mitochondrial encephalopathies, several neuroectodermosis, and part of the brain malformations and disorders of cortical development are examples. Recognition of new gene mutations in infants with epileptic encephalopathies or other severe epilepsies whose brain imaging studies, neurometabolic screenings and conventional cariotypes are normal, is emphasized in this review. An algorhythm for diagnosis and treatment of neonatal seizures with no determined etiology is also included. Finally, the new molecular genetics techniques applied in the diagnostic approach of these conditions, such as Array Comparative Genomic Hybridization, the identification of copy number variations and the eventual sequencing of genes, are commented but not described. The concept for pediatricians and pediatric neurologists is that mutations in one gene may provoke different epileptic syndromes, whereas one epileptic syndrome may be provoked by mutations in different genes.

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES).

PURPOSE: In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add-on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs). METHODS: Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow-up of 1.5-16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day. KEY FINDINGS: Since add-on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add-on of sulthiame. Twenty-one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days. SIGNIFICANCE: We understand that sulthiame may be effective as add-on treatment in children with ESES syndrome.

[Assessment of attention deficit hyperactivity: SNAP-IV scale adapted to Argentina]. / Evaluación de déficit de atención con hiperactividad: la escala SNAP IV adaptada a la Argentina.

OBJECTIVE: Assess the usefulness of the SNAP-IV scale as an instrument for detecting attention deficit hyperactivity disorder (ADHD) in Argentine children aged 4 to 14 years. METHODS: The SNAP-IV scale was adapted and administered to a group of 1 230 schoolchildren in the province of Buenos Aires, Argentina. The diagnosis was determined with the clinical control, based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The sensitivity and specificity, as well as the cut-off scores for the SNAP-IV scale in the population studied, were determined. RESULTS: The score on the SNAP-IV scale with the best correlation between sensitivity and specificity was established in order to determine the true positive cases that in fact had a clinical diagnosis. The cut-off scores obtained were: 1.66 (15/27 points) for the attention deficit subscale and 1.77 (16/27 points) for hyperactivity/impulsivity in the population studied. CONCLUSIONS: The SNAP-IV scale for detection of ADHD is considered to be valid in the population studied as long as the cut-off scores are modified to obtain the best sensitivity/specificity ratio based on the cultural and socioeconomic features of the population.

Evaluación de déficit de atención con hiperactividad: la escala SNAP IV adaptada a la Argentina / Assessment of attention deficit hyperactivity: SNAP-IV scale adapted to Argentina

OBJETIVO: Valorar la utilidad de la escala SNAP IV como instrumento de detección de trastorno por déficit de atención con hiperactividad (TDAH) en niños argentinos de 4 a 14 años de edad. MÉTODOS: Se adaptó y se administró la escala SNAP IV a un grupo de 1 230 escolares de la provincia de Buenos Aires, Argentina. Se determinó el diagnóstico con el control clínico de acuerdo a los criterios del Manual diagnóstico y estadístico de los trastornos mentales, 4.ª edición. Se determinaron la sensibilidad y especificidad así como los puntajes de corte para la escala SNAP IV en la población estudiada. RESULTADOS: Se estableció el puntaje en la escala SNAP IV que tuviera la mejor correlación entre sensibilidad y especificidad para determinar los casos verdaderos positivos que realmente tuvieran un diagnóstico clínico. Los puntajes de corte obtenidos fueron: un índice de 1,66 (15/27 puntos) para la subescala déficit de atención y de 1,77 (16/27 puntos) para hiperactividadimpulsividad en la población estudiada. CONCLUSIONES: La escala SNAP IV para detección de TDAH se considera válida en el caso de la población estudiada, siempre y cuando se modifiquen los puntajes de corte para obtener la mejor relación sensibilidad/especificidad, con base en las particularidades culturales y socioeconómicas de dicha población.

OBJECTIVE: Assess the usefulness of the SNAP-IV scale as an instrument for detecting attention deficit hyperactivity disorder (ADHD) in Argentine children aged 4 to 14 years. METHODS: The SNAP-IV scale was adapted and administered to a group of 1 230 schoolchildren in the province of Buenos Aires, Argentina. The diagnosis was determined with the clinical control, based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The sensitivity and specificity, as well as the cut-off scores for the SNAP-IV scale in the population studied, were determined. RESULTS: The score on the SNAP-IV scale with the best correlation between sensitivity and specificity was established in order to determine the true positive cases that in fact had a clinical diagnosis. The cut-off scores obtained were: 1.66 (15/27 points) for the attention deficit subscale and 1.77 (16/27 points) for hyperactivity/impulsivity in the population studied. CONCLUSIONS: The SNAP-IV scale for detection of ADHD is considered to be valid in the population studied as long as the cut-off scores are modified to obtain the best sensitivity/specificity ratio based on the cultural and socioeconomic features of the population.

Idiopathic childhood occipital epilepsy of Gastaut: a review and differentiation from migraine and other epilepsies.

The purpose of this review is to provide guidance for appropriate diagnosis and management of idiopathic childhood occipital epilepsy of Gastaut. The typical clinical features are visual seizures that typically consist of brief elementary visual hallucinations, which are mainly multicolored and circular. Ictal blindness and deviation of the eyes are also common symptoms. The seizures are usually frequent and diurnal. The electroencephalography is the only investigation with abnormal results, showing occipital spikes and often occipital paroxysms demonstrating fixation-off sensitivity. Brain magnetic resonance imaging is used to exclude symptomatic occipital epilepsy. Patients usually respond well to antiepileptic medication and about two-thirds remit by the age of 16 years. Idiopathic childhood occipital epilepsy of Gastaut is frequently misdiagnosed as migraine with visual aura, acephalgic, or basilar migraine. Differentiation from symptomatic occipital epilepsy, particularly when children are otherwise normal, can be difficult. Most children need prophylactic antiepileptic medication.

Benign infantile seizures with mild gastroenteritis: study of 22 patients.

PURPOSE: To analyze the electroclinical features, aetiology and outcome in patients with normal neurological examination and psychomotor development who presented seizures during a mild gastroenteritis (MG). PATIENTS AND METHODS: Evaluation of the clinical charts of 22 patients who were assessed in the Neurology Department, Hospital Nacional de Pediatría Prof. Dr. JP Garrahan between 1999 and 2007. RESULTS: Twelve patients were boys and 10 were girls, the age of onset ranged from 5 to 26 months, and the median age was 10 months. Rotavirus antigen test in stool was positive in 9 of 18 studied patients. The seizures were brief, focal with secondary generalization in 15 patients (68.5%), apparently generalized in 5 (22.5%) and focal in two (9%). Seven of the patients (35%) had more than one seizure in 24h. The interictal EEG was normal in all patients. Neuroradiological studies were performed in 19 patients with a normal result. No patient was put on long-term treatment with antiepileptic drugs. Four patients had subsequent mild gastroenteritis and two of them presented convulsions during the disease. After between 12 and 67 months of follow-up, all patients had normal psychomotor development and neurological examination. CONCLUSIONS: In this study we confirmed the association of benign infantile seizures (BIS) and MG with or without rotavirus. The identification of this entity allows avoiding unnecessary complementary studies and treatment with antiepileptic drugs.

Atypical rolandic epilepsy.

Typical benign rolandic epilepsy (BRE) is a frequent and well-delineated epileptic syndrome in childhood. Mild cognitive and behavioral difficulties are increasingly recognized in the course of BRE and should not be considered as atypical features. Atypical features are recognized on electroclinical grounds. These features, particularly early age at onset and frequent spikes or spike-wave discharges, seem to be risk factors for neuropsychological deficits but also for an atypical evolution of BRE. Atypical evolutions of BRE are defined by the appearance of severe neuropsychological impairments and continuous spike-and-waves during slow sleep (CSWSS). The clinical expressions of these situations correspond to the syndromes known as atypical benign focal epilepsy of childhood (ABFEC), status of BRE, Landau-Kleffner syndrome (LKS), and CSWSS syndrome, which may be part of a continuum related to BRE.

A study of 63 cases with eyelid myoclonia with or without absences: type of seizure or an epileptic syndrome?

PURPOSE: Eyelid myoclonia and absences (EMA) induced by eye closure associated with brief, fast, and generalized paroxysms of polyspikes and waves was considered as an epileptic syndrome and a type of seizure as well. We analyzed the electroclinical features and evolution of EMA, and tried to determine if it represents a well-defined epileptic syndrome or a non-specific condition associated to other epilepsies. METHODS: Between June 1994 and June 2005, 63 patients who met diagnostic criteria of EMA were enrolled in the study and have been followed up to the present time. RESULTS: Two main groups could be identified. The first group was divided into two subgroups. One subgroup of 28 patients presented EMA associated with infrequent generalized tonic-clonic seizures (GTCS), and the other 1 of 9 patients presented early-onset EMA refractory to antiepileptic drugs (AEDs), associated or not with GTCS and mental retardation. Four of them had self-induced seizures. The second group included 26 patients with EMA associated with GTCS and/or massive myoclonias, or GTCS induced by intermittent photic stimulation. All these patients had electroclinical features compatible with idiopathic generalized epilepsies. CONCLUSION: In the first group, EMA should be considered as a photosensitive idiopathic epileptic syndrome. A subgroup of early-onset of EMA refractory to AEDs, associated or not with GTCS and mental retardation should also be considered as a variant or a distinct photosensitive idiopathic epileptic syndrome. Finally, in the second group EMA may correspond to a type of seizures in idiopathic generalized epilepsies.

The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic features in 102 patients.

PURPOSE: To redefine benign myoclonus of early infancy (BMEI) through analysis of clinical and neurophysiologic features in 102 patients with the aim to widen the spectrum of the syndrome, including a number of different clinical expressions of transient nonepileptic paroxysmal movements occurring in normal infants. METHODS: We recruited patients from one center in Argentina and two in Italy, including infants with normal neurologic and psychomotor development presenting with brief paroxysmal abnormal movements. Children with motor phenomena occurring only during sleep were excluded. Patients with abnormal interictal or ictal electroencephalography (EEG) findings were also excluded. The follow-up ranged from 2-40 years. RESULTS: One hundred and two infants (60 male) met the inclusion criteria. Age at onset ranged from 1-12 months, with a median age of 6.2 months. The following nonepileptic paroxysmal motor phenomena were recognized: (1) myoclonus, (2) spasms and brief tonic contractions, (3) shuddering, (4) atonia or negative myoclonus, (5) more than one type of motor phenomenon. In the majority of cases the episodes occurred only while awake and repeated several times a day. In 45 (44.1%) of the 102 cases contractions appeared in clusters. CONCLUSIONS: Based on the analysis of clinical and EMG features in this large series of infants, we postulate that the spectrum of the syndrome is wider than initially suspected, and that the different transient motor manifestations and their correlation with different EMG patterns will allow recognition of this definitely benign condition comprising a variety of episodic motor phenomena in normal babies.

Childhood absence epilepsy and electroencephalographic focal abnormalities with or without clinical manifestations.

PURPOSE: We studied the electroclinical features and evolution in patients with childhood absence epilepsy (CAE) associated with electroencephalographic findings similar to those of benign focal epilepsies (BFE) with or without clinical manifestations compatible with these focal idiopathic syndromes. METHODS: Between June 1994 and June 2002, we found 203 (3.6%) patients with typical electroclinical features of CAE among 8285 children with epilepsy. From this population of 203, we found 30 cases (14.7%) that also showed focal abnormalities of BFE on the EEG. Seven of these 30 cases also had clinical manifestations of BFE that preceded the onset of the absences. RESULTS: There were 20 (66.5%) boys and 10 (33.5%) girls. Age at onset of absences ranged from 2 to 10.5 years, with a mean age of 5.5 years. Of 30, 7 had focal clinical seizures as well. Three of seven had seizures characteristic of Panayiotopoulos syndrome (PS), and the other four had seizures compatible with childhood occipital epilepsy (COE) of Gastaut. The focal seizures started between 3 and 7 years of age. In all patients seizures were under control within 2-24 months (mean: 11 months) after onset. The focal discharges disappeared in 26 patients at a mean age of 8 years (range 4-13 years), 1 year after the typical absences had disappeared. In four patients the focal paroxysms are still present. CONCLUSION: The association of two different idiopathic focal and generalized epilepsies in the same patient may be merely coincidental, but a close genetic relationship between both epileptic syndromes might be another hypothesis. Another explanation could be that our series of patients represent a subgroup of CAE.

Epileptic encephalopathy with continuous spikes and waves during sleep in children with shunted hydrocephalus: a study of nine cases.

PURPOSE: We present a series of nine patients with early-onset hydrocephalus who had seizures and continuous spikes and waves during slow sleep (CSWS) associated with neurocognitive and motor deterioration. METHODS: Six boys and three girls aged 9-16 years (mean 11.3 years) were studied. [Correction added after online publication 12-Apr-2008: Number of girls and boys has been updated.] All patients underwent clinical examinations, electroencephalographic evaluations, neuroradiological imaging and neuropsychological assessment at first examination. Antiepileptic drugs (AEDs) were given in all cases and changed according to clinical and EEG evolution. RESULTS: Onset of epilepsy occurred from age 8 to 60 months (mean 19.6 months and median 14 months) with focal seizures with or without secondary generalized tonic-clonic seizures. Between ages 6 and 13 years (mean 10.4 years and median 8 years), hyperkinesia, aggressiveness, and poor socialization appeared in all nine cases. Reduced attention span, deterioration of language, and temporospatial disorientation were found in three of them. Negative myoclonus was found in two patients. The EEG showed CSWS. Response to change in treatment was good in all patients. None of the patients had relapses, seven of them have remained seizure free, and two continued having sporadic focal motor seizures during 2-5 years (mean 3 years) of follow-up. CONCLUSION: In children with early-onset hydrocephalus, particularly with behavioral and language disturbances and/or motor deterioration, CSWS should be considered. Periodic EEG recordings during sleep should be done in these children. The early identification of this particular electroclinical picture is crucial to start adequate treatment to avoid progressive cognitive deterioration.

Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients.

We describe the electroclinical features, therapy, and long-term evolution of 17 patients with migrating focal seizures in infancy, and analyzed the charts of these patients seen between February 1985 and July 2005. Three different electroclinical patterns were recognized: (1) 8 cases with alternating simple focal motor seizures at onset. The ictal electroencephalography (EEG) pattern was characterized by recurrence of rhythmic focal spikes or rhythmic sharp activity in the Rolandic region; (2) 5 cases with complex focal seizures and progressive appearance of polymorphic delta- activity in 1 temporo-occipital region recurring independently; (3) 4 cases with focal complex seizures with motor manifestations. Ictal EEG showed flattening or fast activity in 1 frontotemporal region followed by unilateral fast poly-spikes in alternating clusters in both hemispheres. The focal seizures were refractory to antiepileptic drugs, and all patients except 3 had severe developmental delay. Migrating focal seizures in infancy is a newly defined and rare, but underrecognized, epileptic encephalopathy.