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.

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.

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.

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.

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.

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.

Dravet syndrome: a study of 53 patients.

OBJECTIVE: We analyzed the electroclinical features, treatment and evolution of patients with Dravet syndrome (DS). MATERIAL AND METHODS: We evaluated the clinical records of 53 patients that met the diagnostic criteria of DS according to the ILAE classification of 1989 seen at our center between February 1990 and December 2004. RESULTS: Thirty-four male and 19 female patients met the diagnostic criteria of DS. Mean time of follow-up was 10 years. The mean age at onset was 6 months and in all patients the seizures were associated with febrile illness. Myoclonias were found in 39 children. These seizures appeared between the ages of 1 and 5.5 years, with an average of 1 year and 5 months. The seizures were difficult to control with AEDs. All patients presented some degree of mental delay. At the age of 6 years, one of the children in our series presented kinesigenic paroxysmal dyskinesias. Twenty patients were placed on the ketogenic diet (KD). Two did not tolerate the KD and the diet was ineffective in five cases. The other 13 showed different degrees of control of seizures. CONCLUSION: The present study confirms the severity and intractability of the seizures and the difficulties to make an early diagnosis in DS. The onset of febrile seizures or seizures related to infectious disease or vaccination, focal or generalized, prolonged in time and during the first year of life, is especially suggestive of DS. The final diagnosis is usually made after 2 or 3 years when the electroclinical picture is complete, but earlier diagnosis is desirable. Myoclonias are the most representative type of non-febrile seizures in this syndrome but are not always present. Cognitive development is poor in all patients. Treatment with the KD should be considered early. A ion-channel disorder could explain the association between DS and paroxysmal diskinesias, as seen in one of our patients.

Ketogenic diet in patients with myoclonic-astatic epilepsy.

For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment. Objective. In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic-astatic epilepsy. Material and methods. Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic-astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months. Results. The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure-free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting). Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic-astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic-astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.

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.

Late-onset, "Gastaut type", childhood occipital epilepsy: an unusual evolution.

We report on two girls and one boy with clinical and electroencephalographic features of late-onset childhood epilepsy with occipital paroxysms of the "Gastaut type", showing an unusual evolution. Neurological examination and brain imaging were normal in all three. At the age of 7.5 years, eight years and ten years respectively, the three children presented with episodes of visual symptoms when awake, and in one of them, the seizures were occasionally followed by oculocephalic deviation. The interictal EEG showed bilateral occipital spike-wave activated by eye closing. In two patients, the occipital seizures had been immediately followed by typical absences, since onset; in the other patient, five months after onset. The ictal EEG showed irregular bilateral occipital spike-wave discharges during the visual symptoms, followed by generalized spike-wave activity during the typical absences. The typical absences were activated by hyperventilation; the EEG did not show continuous spikes and waves during slow sleep. These three patients, with typical electroclinical features of "Gastaut type", childhood occipital epilepsy, demonstrated an evolution which, to our knowledge, has not been previously described. We investigated whether this unusual, age-dependent evolution was due to secondary bilateral synchrony or if these electroclinical features represent two types of idiopathic epileptic syndromes in the same patients.

Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the CNS. Few pediatric series have been published, with retrospective and short-term follow-up studies. OBJECTIVES: To describe a cohort of pediatric patients with ADEM and to determine whether clinical and neuroimaging findings predict outcome. METHODS: A prospective study was conducted between March 1988 and July 2000 on 84 consecutive children with ADEM at the National Pediatric Hospital "Dr. J. P. Garrahan." RESULTS: Mean age at onset was 5.3 +/- 3.9 years, with a significant male predominance. Sixty-two patients (74%) had a preceding viral illness or vaccination. Acute hemiparesis (76%), unilateral or bilateral long tract signs (85%), and changes in mental state (69%) were the most prominent presenting features. Four MRI groups were identified: ADEM with small lesions (62%), with large lesions (24%), with additional bithalamic involvement (12%), and acute hemorrhagic encephalomyelitis (2%). Of the 54 children whose CSF samples were analyzed, none showed intrathecal oligoclonal bands. The use of high-dose corticosteroid treatment, particularly IV methylprednisolone, was associated with good recovery and resolution of MRI lesions. After a mean follow-up of 6.6 +/- 3.8 years, 90% of children showed a monophasic course, and 10% a biphasic disease. Eighty-nine percent of patients show at present Expanded Disability Status Scale scores of 0 to 2.5. Eleven percent have disability scores of 3 to 6.5. CONCLUSIONS: Childhood acute disseminated encephalomyelitis is a benign condition, affecting boys more frequently. No association was found between MRI groups and disability. Disability was related to optic nerve involvement at presentation. Even in relapsing cases, the distinction between acute disseminated encephalomyelitis and MS was possible on the basis of long-term clinical and neuroimaging follow-up and the absence of oligoclonal bands in CSF.

Epilepsy, occipital calcifications, and oligosymptomatic celiac disease in childhood.

The association of epilepsy, occipital calcifications, and celiac disease has been recognized as a distinct syndrome. The objective of this study was to present the clinical, electrophysiologic, and neuroradiologic features in a series of patients with this syndrome. Thirty-two patients with the constellation of epilepsy, occipital calcifications, and celiac disease were identified in our epilepsy clinic. The mean age was 11 years and the mean length of follow-up was 7.4 years. The 1990 criteria of the European Society of Pediatric Gastroenterology and Nutrition were used to diagnose celiac disease. The Kruskal-Wallis statistics test was employed with a signficance of P < .05. Thirty-one patients had partial seizures, 21 of them with symptoms related to the occipital lobe. In most patients, the epilepsy was controlled or the seizures were sporadic. Three developed severe epilepsy. Occipital calcifications were present in all cases. Computed tomography in 7 patients showed hypodense areas in the white matter around calcifications, which decreased or disappeared after a period of gluten-free diet in 3 patients. A favorable outcome of epilepsy was detected in patients with the earliest dietary therapy. This study presents the largest series of children with this syndrome outside Italy. White-matter hypodensities surrounding calcifications are rarely reported. A prompt diagnosis of celiac disease might improve the evolution of the epilepsy and may improve cognitive status.

Benign familial infantile seizures: further delineation of the syndrome.

Benign familial infantile seizures are an autosomal dominant epilepsy disorder that is characterized by convulsions, with onset at age 3 to 12 months and a favorable outcome. Benign familial infantile seizures have been linked to chromosome 19q whereas infantile convulsions and choreoathetosis syndrome, in which benign familial infantile seizure is associated with paroxysmal choreoathetosis, has been linked to chromosome 16p 12-q12. Many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 infantile convulsions and choreoathetosis syndrome region. Moreover, in one large pedigree with paroxysmal kinesiogenic dyskinesias only, the syndrome has also been linked to the same genomic area. Families with pure benign familial infantile seizures may be linked to chromosome 16 as well. In this study, we present a series of 19 families and 24 otherwise healthy infants with benign familial infantile seizures. Two of these families include members affected with benign familial infantile seizures and paroxysmal choreoathetosis. We included patients with normal neurologic examinations, who started having simple partial seizures, complex partial seizures, or apparently generalized seizures without recognized etiology between 2 months and 2 years of age. Neurologic studies were normal, but in all patients, there was a history of similar seizures and age at onset in either the father or the mother. Twenty-four patients (14 girls and 10 boys) were evaluated at our hospital between February 1990 and February 2001. Age at onset, sex, family history of epilepsy and/or paroxysmal dyskinesias, neurologic examination, semiology, distribution, and frequency and duration of seizures were evaluated. Electroencephalographic (EEG) and neuroradiologic studies were also performed. Seizures began between 3 and 22 months of life, with a median age of 5 1/2 months. Nine patients (37.5%) had only apparently generalized seizures, 5 patients (20.8%) had only partial seizures, and 10 patients had both partial and apparently generalized seizures (41.6%). Seizures were invariably brief, occurred during the waking state (100%), and presented mainly in clusters in 12 patients (50%). Interictal EEG was normal in 23 patients (95.8%). Sixteen patients (66.6%) had a confirmed history of convulsions in family members other than parents. Twenty-two patients became seizure free after 30 months of life. Two brothers in the same family had brief paroxysmal episodes of choreoathetosis in the hemibody triggered by stress while awake at 15 and 17 years old, respectively. One of them had paroxysmal choreoathetosis only, and the other was associated with benign familial infantile seizures. One father had brief spontaneous episodes of paroxysmal choreoathetosis when awake at age 18 years. All of them had a good response to antiepilepsy drugs, and neurologic examination and EEG and neuroradiologic studies were normal. Benign familial infantile seizure is a genetic epilepsy syndrome with autosomal dominant inheritance. It may be associated with paroxysmal choreoathetosis (infantile convulsions and choreoathetosis syndrome), which has been linked to the chromosome 16 infantile convulsions and choreoathetosis syndrome region. Patients in families with infantile convulsions and choreoathetosis syndrome could display either benign familial infantile seizures or paroxysmal choreoathetosis or both. It is likely that the disease in families with pure benign familial infantile seizures may be linked to the infantile convulsions and choreoathetosis region as well. We cannot exclude the possibility that the youngest patients may develop choreoathetosis or other dyskinesias later in life.

Unilateral closed-lip schizencephaly and epilepsy: a comparison with cases of unilateral polymicrogyria.

We compared the electroclinical features and evolution of patients with two different types of abnormal cortical organization: unilateral closed-lip schizencephaly (SCHZ) and unilateral polymicrogyria (PMG). Between February 1990 and June 2002, 51 children with either unilateral PMG or closed-lip SCHZ were selected through neuroradiological analysis for investigation at our service. We evaluated the frequency of epilepsy, electroclinical features and evolution. The mean time of follow-up was 7 years (range 1-12 years). All patients underwent neurological examination, computed tomography scan and magnetic resonance imaging, serial electroencephalographic (EEG) recordings and neuropsychological assessment. Thirty-six of the 51 patients had unilateral PMG. All patients had hemiparesis with mild spasticity. Mental retardation was mild in 20 and moderate in 14. In two patients IQ was normal. Partial motor seizures were recorded in 28 patients, with secondary generalization in 20. The median age at onset of seizures was 2 years (range 4 months-7 years). Interictal EEGs showed unilateral spikes in all patients. In 21 patients epilepsy worsened between the ages of 4 and 8 (mean 5.6 years) with frequent atonic seizures, atypical absences, epileptic negative myoclonus and gait difficulties. EEGs showed continuous spike-wave activity or bilateral high-frequency spike discharges during slow-wave sleep. Frequent relapses of atonic and myoclonic seizures were seen in nine patients. At present, 16 patients are seizure-free. Fifteen patients with unilateral SCHZ were included in the study. Focal motor seizures were registered in seven cases, in three of them with secondary generalization. The median age at onset of epilepsy was 2.5 years (range 1-4 years). Interictal EEGs showed unilateral spikes in these seven cases. All patients except one presented mild spastic hemiparesis. Mental retardation was mild in ten children, moderate in two and IQ was normal in three. Although the underlying mechanisms leading to PMG and SCHZ are probably similar, the electroclinical phenomenon of secondary bilateral synchrony with frequent negative myoclonus was not present in our cases with unilateral closed-lip SCHZ.

Bilateral posterior agyria-pachygyria and epilepsy.

We analyzed the electroclinical findings in two patients with bilateral posterior agyria-pachygyria. Both patients presented with mental retardation, mild motor deficit and epilepsy. The electroclinical findings were characterized by frequent tonic or atonic generalized seizures with occasionally simple or complex partial seizures. Interictal electroencephalography (EEG) showed occipital spikes and diffuse polyspike-wave paroxysms predominantly in the posterior region. Ictal EEG showed diffuse 10-11 Hz activity. Cerebral magnetic resonance imagings (MRIs) showed thickened cortex in the parieto-occipital lobes, bilaterally and symmetrically. The volume of underlying white matter appeared reduced, and the overlying subarachnoid spaces were enlarged. The occipital horns were dilated. These findings were compatible with agyria-pachygyria of the posterior portions of the brain. In conclusion, in patients with mental retardation, mild motor deficit and epilepsy characterized by tonic or atonic generalized seizures, interictal EEG with diffuse polyspike-wave paroxysms predominantly in posterior region, posterior focal epileptilorm abnormalities and ictal diffuse 10-11 Hz activity, bilateral parieto-occipital agyria-pachygyria should be considered as a possible etiology. Magnetic resonance image is the best neuroradiological study to identify this disorder of cortical development.

Idiopathic occipital and absence epilepsies appearing in the same children.

Our aim is to report the association between idiopathic occipital epilepsy and childhood absence epilepsy in the same children. Six children met the diagnostic criteria for both idiopathic occipital epilepsy and childhood absence epilepsy, five patients with idiopathic occipital epilepsy Gastaut type and another with Panayiotopoulos type. All patients were monitored for 2 to 10 years with repeated electroencephalograms when awake and during sleep. Age at onset of seizures ranged from 4.6 to 8 years. Five patients had focal sensory visual seizures, all with migraine-like episodes. One patient presented ictal vomiting followed by oculocephalic deviation. All patients presented typical absences, with onset at least 1 year after having had idiopathic occipital epilepsy Gastaut type in three patients. In the other two patients with idiopathic occipital epilepsy Gastaut type and the patient with idiopathic occipital epilepsy Panayiotopoulos type, both types of epilepsy appeared at the same time. The electroencephalograms documented occipital paroxysms in all cases, with positive reactivity to the eye closure in five patients. All children presented spike-wave discharges at 3 cycles per second activated by hyperventilation. More genetic information would be necessary to demonstrate either a close genetic relationship between these syndromes or common markers with variable phenotypes.

Symptomatic occipital lobe epilepsy following neonatal hypoglycemia.

This study reports on the clinical, electrophysiologic, and neuroradiologic aspects of patients with epilepsy secondary to neonatal hypoglycemia. Fifteen patients with epilepsy and/or posterior cerebral lesions, and neonatal hypoglycemia were studied in the epilepsy clinic between February 1990 and March 2003. The mean age was 12 years. The different types of neonatal hypoglycemia were as follows: four patients had transitional-adaptive, seven classic transient, two secondary-associated, and two severe recurrent hypoglycemia. As to epilepsy, we recognized a larger group of 12 patients characterized by focal seizures and posterior abnormalities on the electroencephalogram, the majority of whom had a good outcome, and a second group of two patients presenting electroclinical features of encephalopathy with refractory seizures. All patients except two manifested parieto-occipital lesions on neuroradiologic images. Neurologic examination was normal in one patient. Six patients had microcephaly; eight manifested visual disturbances. Fourteen patients were mentally retarded. One had a pervasive developmental disorder. This study indicates neonatal hypoglycemia may cause posterior cerebral lesions, abnormal findings at neurologic examination, and symptomatic epilepsy, most frequently occipital lobe epilepsy, usually with a good prognosis, and occasionally epileptic encephalopathy with refractory seizures. MRI studies are essential to define the characteristics of cerebral lesions after neonatal hypoglycemia.