Epidermal nevus syndrome (ENS) is an inclusive term for a heterogeneous group of congenital disorders characterized by the presence of epidermal nevi associated with systemic involvement. These disorders, as are all primary neurocutaneous syndromes, are neurocristopathies. The epidermal nevi that follow the lines of Blaschko and most systemic anomalies in skeletal, ocular, cardiovascular, endocrine, and orodental tissues, as well as lipomas, are due to defective neural crest. The most important and frequent anomaly in the brain in all forms of epidermal nevus syndromes (ENSs) is hemimegalencephaly (HME). This malformation often is not recognized, despite being the principal cause of neurological manifestations in ENSs. They consist mainly of epilepsy and developmental delay or intellectual disability. The onset of epilepsy in ENS usually is in early infancy, often as infantile spasms. Several syndromic forms have been delineated. I propose the term "Heide's syndrome" for those distinctive cases with the typical triad of hemifacial epidermal nevus, ipsilateral facial lipoma, and hemimegalencephaly. Most ENSs are sporadic. The mechanism is thought to be genetic mosaicism with a lethal autosomal dominant gene. Specific genetic mutations (PTEN, FGFR3, PIK3CA, and AKT1) have been documented in some patients. The large number of contributors for over more than a century and a half to the description of these disorders precludes the use of new author eponyms.

To review the current literature on the efficacy and safety of low- versus high-dose adrenocorticotropic hormone (ACTH) regimens, low-dose ACTH regimens, and comparison of ACTH with oral corticosteroids or vigabatrin for the treatment of West syndrome.A literature search was performed using MEDLINE, PubMed, and Inter national Pharmaceutical Abstracts (1975-November 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: infantile spasms, West syndrome, adrenocorticotropic hormone, corticotropin, symptomatic West syndrome, cryptogenic West syndrome, pediatric, children, infant, adolescent, and neonate.Studies included in this article evaluated low-dose versus high-dose ACTH, low-dose ACTH, and ACTH compared with vigabatrin and oral corticosteroids. Data reporting the efficacy and adverse effects of ACTH, vigabatrin, and oral corticosteroids were extracted from each publication. Only English-language publications were included. We initially reviewed 20 studies, and 14 were included: 5 prospective randomized clinical trials and 9 chart reviews.West syndrome is an age-specific epileptic disorder that occurs in infancy and early childhood. It is characterized by the triad of infantile spasms, neurodevelopmental regression or delay, and hypsarrhythmia on electroencephalogram (EEG). The efficacy and adverse events of ACTH with different dosage regimens were reviewed and analyzed. ACTH compared with vigabatrin and oral corticosteroids was also evaluated. Based on this review, low-dose ACTH is probably as effective as high-dose ACTH. Compared with other agents, ACTH is suggested to be more effective than oral corticosteroids, and compared with vigabatrin, it has improved outcomes in the cessation of spasms. However, studies evaluating the efficacy of ACTH are limited by small sample size, inconsistent dosage regimens, and the use of synthetic or natural ACTH products. Serious adverse events, including intracranial hemorrhage, brain atrophy, Cushing syndrome, infection, weight gain, and hypertension, may deter the use of ACTH. Short-term therapy is recommended to reduce the risk of adverse effects.The current literature suggests that short-term, low-dose ACTH should be considered first-line treatment of infantile spasms.

Glucose transporter type 1 (GLUT-1) deficiency is a rare cause of preventable intellectual disability. Intellectual disability is due to refractory seizures in infancy and reduced supply of glucose to the brain. The authors report a third born male child of consanguineous parentage who presented with infantile spasms. Initially, he had refractory convulsions of focal, generalised, and myoclonic jerks, not responding to multiple anticonvulsants. He also had choreoathetoid movements. On examination he had microcephaly. MRI of brain was normal and EEG showing diffuse slowing. CSF glucose was low compared to blood glucose, with normal lactate and without any cells, hence diagnosed as Glucose transporter-1 deficiency and started on ketogenic diet. With ketogenic diet, child was seizure free, anticonvulsants decreased to 2 from 5, and improvements in development were noted.

Migrating partial seizures of infancy, also known as epilepsy of infancy with migrating focal seizures, is a rare early infantile epileptic encephalopathy with poor prognosis, presenting with focal seizures in the first year of life. A national surveillance study was undertaken in conjunction with the British Paediatric Neurology Surveillance Unit to further define the clinical, pathological and molecular genetic features of this disorder. Fourteen children with migrating partial seizures of infancy were reported during the 2 year study period (estimated prevalence 0.11 per 100 000 children). The study has revealed that migrating partial seizures of infancy is associated with an expanded spectrum of clinical features (including severe gut dysmotility and a movement disorder) and electrographic features including hypsarrhythmia (associated with infantile spasms) and burst suppression. We also report novel brain imaging findings including delayed myelination with white matter hyperintensity on brain magnetic resonance imaging in one-third of the cohort, and decreased N-acetyl aspartate on magnetic resonance spectroscopy. Putaminal atrophy (on both magnetic resonance imaging and at post-mortem) was evident in one patient. Additional neuropathological findings included bilateral hippocampal gliosis and neuronal loss in two patients who had post-mortem examinations. Within this cohort, we identified two patients with mutations in the newly discovered KCNT1 gene. Comparative genomic hybridization array, SCN1A testing and genetic testing for other currently known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was non-informative for the rest of the cohort.

This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage-gated sodium channels (protein name: Nav 1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI because genetic confirmation of the clinical diagnosis may allow optimization of antiepileptic therapy with the potential to improve seizure control and developmental outcome. In addition, a molecular diagnosis may prevent the need for unnecessary investigations, as well as inform genetic counseling. (2) SCN1A testing should be considered in people with possible DS where the typical initial presentation is of a developmentally normal infant presenting with recurrent, febrile or afebrile prolonged, hemiclonic seizures or generalized status epilepticus. After age 2, the clinical diagnosis of DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA sequencing of the coding regions and analyses to detect genomic rearrangements within the relevant chromosomal region: 2q24. Interpretation of the test results must always be done in the context of the electroclinical syndrome and often requires the assistance of a medical geneticist, since many genomic variations are possible and it is essential to differentiate benign polymorphisms from pathogenic mutations. (2) Missense variants may have no apparent effect on the phenotype (benign polymorphisms) or may represent mutations underlying DS, MPSI, GEFS+, and related syndromes and can provide a challenge in interpretation. (3) Conventional methods do not detect variations in introns or promoter or regulatory regions; therefore, a negative test does not exclude a pathogenic role of SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A may be involved. Obtaining written informed consent and genetic counseling should be considered prior to molecular testing, depending on the clinical situation and local regulations.

Infantile spasms constitute a severe epileptic encephalopathy of infancy with poor long-term developmental outcome. Many diverse etiologies have been associated with infantile spasms, but the pathophysiological process is still not fully understood. We describe 2 cases of previously healthy 1- and 3-month-old infants who suffered a nonaccidental head injury with extensive cerebral lesions. Both presented with acute focal seizures rapidly controlled with phenobarbital. Nevertheless, they developed infantile spasms after a latency period of 3-4 months. Spasms were rapidly controlled with vigabatrin. Both children manifested with developmental delay, either exacerbated (case 1) or elicited (case 2) by infantile spasms. Our report highlights nonaccidental head injury as a risk factor for developing infantile spasms following a seizure-free latency period. A better understanding of the pathophysiology linking accidental brain trauma with infantile spasms could lead to more effective neuroprotective strategies. In the meantime, increased awareness and follow-up are warranted.

To compare the effectiveness of 2 novel antiepileptic drugs, topiramate and levetiracetam, as a second line treatment for infantile spasm when oral steroids fail.Forty infants under 2 years with clinically- and EEG-proven infantile spasms that did not respond to prednisone (2mg/kg/day in 2 divided doses) were recruited and randomized into 2 groups. They were randomly assigned to either topiramate (group 1; 1mg/kg/day for 3 days then increased by 1mg/kg/day every third day up to 6mg/kg/day) or levetiracetam (group 2; 10mg/kg/day for 5 days and then increased by 10mg/kg/day every 5 days up to 60mg/kg/day). The study was conducted in the Pediatric Neurology Department at the National Neuroscience Institute of King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia between January 2008 and December 2010.Of the 20 patients included in the final data analysis, 11 (55%) were administered topiramate and 9 (45%) levetiracetam. Eighteen patients did not respond to the first drug, and subsequently to the other drug when crossed-over. Two patients with infantile spasm responded to either one drug without crossover. Their EEGs improved with time.The present study demonstrated the ineffectiveness of topiramate and levetiracetam suggesting current treatment modalities are grossly inadequate underscoring the urgent need for more research efforts to overcome current deficiencies. Two patients with cryptogenic infantile spasm responded to treatment suggesting the potential for treatment of such patients with these 2 drugs, and merits further multicenter investigation.

Early-onset epileptic encephalopathies (EOEEs) are characterised by epileptic seizures beginning in the first months of life, abnormal background EEG activity, and are associated with severe developmental delay and poor prognosis. Mutations and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also known as "early infantile epileptic encephalopathy". We report an infant affected by EOEE with a 9q34.11 deletion that encompassed the genes STXBP1 and SPTAN1. The infant presented with neonatal encephalopathy without epileptic seizures and an EEG pattern varying from highly discontinuous to suppression-burst. This was followed by West syndrome at 2 months with atypical hypsarrhythmia and spasms, easily controlled by therapy. Our findings suggest that molecular analysis of STXBP1 should be considered for newborns affected by neonatal encephalopathy associated with a peculiar EEG pattern, even in the absence of neonatal epileptic seizures.

PURPOSE:

The semiology of infantile seizures often shows different characteristics from that of adults. We performed this study to describe clinical and ictal characteristics of infantile seizures at less than two years of age.

METHODS:

A retrospective study was done for infants with epilepsy (ages: 1-24months) who underwent long-term video electroencephalography (EEG) monitoring at Samsung medical center between November 1994 and February 2012. We analyzed the clinical and ictal characteristics of the 56 cases from 51 patients.

RESULTS:

In 69% of the patients, the seizure onset was before six months of age and the etiology was symptomatic in one third of the patients. Twelve seizure types were identified; spasms (24%), unilateral motor seizures (18%), and generalized tonic seizures (15%) were the three frequent types of seizure. All partial seizures were well correlated with the partial-onset ictal EEG, however 19.4% (7/36) of clinically generalized seizures revealed partial-onset ictal EEG. About one-thirds (4/11) of generalized tonic seizures had its ictal onset on unilateral or bilateral frontal areas and two out of seven generalized myoclonic seizures showed unilateral frontal rhythmic activities. Hypomotor seizures mainly arose from the temporal areas and hypermotor seizures from the frontal regions.

CONCLUSIONS:

Even though most of the seizure semiology of infants is well correlated with ictal EEG, some of the generalized tonic seizures or myoclonic seizures revealed partial-onset ictal EEG suggesting localized epileptic focus. Accurate definition of seizures via video EEG monitoring is necessary for proper management of seizures in infancy, especially in some clinically generalized seizures.