Nathanel Zelnik

Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).

Purposes:  To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES).

Handedness in Patients With Developmental Coordination Disorder

Developmental coordination disorder affects 5% to 8% of the general population, and about 50% to 60% of these children have a comorbid attention-deficit disorder with hyperactivity and learning disorders. Left-handedness is relatively common among children with dyslexia, learning disabilities, and autism; however, its frequency in children with developmental coordination disorder is less clear. The present study investigated the distribution of hand dominance in 98 children (age range, 5.5-17 years) with developmental coordination disorder compared with their parents or siblings. Thirty children (30.6%) were left-handed and 13 (13.3%) were ambidextrous. The prevalence of left-handedness among their parents and siblings was similar to that of the general population. The results suggest that children with developmental coordination disorder, like children with learning disorders and deficit disorder with hyperactivity, present with higher frequency of left-hand dominance compared with the general population.

Benign childhood epilepsy with centrotemporal spikes: clinical characteristics and identification of patients at risk for multiple seizures.

This study aimed to characterize patients diagnosed as having benign childhood epilepsy with centrotemporal spikes and few seizures and compare them with patients with benign childhood epilepsy with centrotemporal spikes with multiple seizures. The medical files of 87 consecutive patients with benign childhood epilepsy with centrotemporal spikes were reviewed and data on gender, age at disease onset, duration of the disease, number of seizures, seizure semiology, and electroencephalographic and neuroimaging findings were analyzed. The mean age at disease onset was 8 years. The mean duration of the disease was 2 years. Eighteen percent of the patients had more than 20 seizures each, whereas 24% had 1 to 3 seizures each. The only predictor for a disease course with multiple seizures was an onset prior to 3 years of age. (J Child Neurol 2002;17:17-19).

Delayed Language Development Due to Infantile Thiamine Deficiency.

The aim of this study was to investigate the language development of 20 children who had been exposed to thiamine (vitamin B1) deficiency in infancy due to feeding with soy‐based formula that was accidentally deficient of thiamine. In this case–control study, 20 children (12 males, eight females; mean age 31.8mo [SD 4.1], range 24–39mo) who were fed thiamine‐deficient formula in infancy were compared with 20 children (12 males, eight females; mean age 32.2mo [SD 3.9], range 25–39mo) fed with other milk sources and matched for age, sex, and maternal education. Receptive and expressive language development was assessed with the Preschool Language Scale, 3rd edition. Other assessments included mental development (Bayley Scales of Infant Development, 2nd edition), evaluation for autistic spectrum disorders, and neurological examination. Motor development was compared by age at independent walking. The study and control groups differed significantly in the expressive communication (p<0.001) and auditory comprehension language subscales (p<0.001), the Mental Developmental Index score (p<0.001), and age at independent walking (p=0.001). A significant correlation was found between the receptive language score and age at independent walking, i.e. poorer language associated with later walking (r=–0.601, p=0.005). The conclusion was that thiamine deficiency in infancy could affect language development in childhood.

Differential stimulant response on attention in children with comorbid anxiety and oppositional defiant disorder

Attention-deficit hyperactivity disorder (ADHD) affects 3% to 7% of school-age children. Approximately 30% of the children with ADHD also have comorbid anxiety or oppositional defiant disorder. Methylphenidate is the drug of choice for the medical treatment of such cases. When compared with children with ADHD alone, children with comorbid anxiety or oppositional defiant disorder may show worsening of the global attention score in response to methylphenidate and not only a “reduced response,” as reported in previous studies. This study included 1122 children diagnosed as ADHD, of which 174 were diagnosed with comorbid anxiety and 141 with comorbid oppositional defiant disorder. All patients performed the Test of Variables of Attention before and after methylphenidate administration. A normal distribution (Gaussian distribution) of reaction to methylphenidate, as measured by the global ADHD score in children diagnosed as pure ADHD, was found. These findings were in contrast to children with ADHD and comorbid anxiety or oppositional defiant disorder who showed a bimodal distribution and hence represent a distinct population. In both groups with comorbid disorders, there was a larger subgroup in which significant worsening of global ADHD score occurred after methylphenidate administration (P < .05). Children with ADHD and comorbid anxiety or oppositional defiant disorder might represent clinically distinct populations in which inattention is secondary to those disorders; therefore, methylphenidate may be an inappropriate treatment for such children.

Attention-Deficit Hyperactivity Disorder in Children with Benign Epilepsy and Their Siblings

This prospective study explores the prevalence and characteristics of attention-deficit hyperactivity disorder in children with benign epilepsy, compared with its prevalence in their siblings. Among 40 patients with benign epilepsy, 28 (70%) were diagnosed with attention-deficit hyperactivity disorder: 19 with the inattentive type, one with the hyperactive type, and eight with the combined type. In the control group of 12 siblings, only two (16.7%) were diagnosed with attention-deficit hyperactivity disorder (P<0.03). A trend toward an increased risk for attentional difficulties was evident in children whose seizures were more resistant and required more than one antiepileptic drug for seizure control. Children with more epileptiform features in their electroencephalograms were also more subject to signs of attention deficit hyperactivity disorder. Larger scale studies are required to validate our findings.

Risk factors for epilepsy in children with cerebral palsy

The purpose of the study was to identify predictive risk factors for epilepsy among children with cerebral palsy. We conducted a retrospective study of the clinical characteristics of children with cerebral palsy and epilepsy in comparison to those of children with cerebral palsy without epilepsy. The examined parameters included: the prevalence and the age of onset of the seizures, the clinical subgroup of cerebral palsy and subtype of epileptic seizures. We looked for possible risk factors including the presence of neonatal seizures, the imaging findings, the gestational age at delivery, the adjusted birth weight, the mode of delivery, the Apgar scores, and the head size as well as the presence of consanguinity. Epilepsy occurred in 33% of the studied children. Almost 50% of the epileptic children had their first seizure within the first 12 months of life. Neonatal seizures were strong predictors for epilepsy (p<0.001). Presence of at least one abnormal structural finding (particularly brain atrophy) was also a significant predictor of epilepsy (p<0.003). Low Apgar score at 5 min after birth and birth at term were also found more frequently among patients with epilepsy, although when adjusted with other risk factors, Apgar score did not reach statistical significance. The mode of delivery, head circumference, adjusted birth weight, gender and ethnic group, consanguineous marriage and prematurity were not found to be risk factors for the occurrence of epilepsy in these children.

Clinical Characteristics and Muscle Pathology in Myopathic Mitochondrial DNA Depletion

Four nonrelated children with myopathic mitochondrial DNA depletion are described. Two of them initially had normal motor development and two had mild motor delay. Motor arrest and regression started at age 6 to 21 months. All four had mitochondrial DNA:nuclear DNA ratios reduced to 16 to 22% of the control mean and mutations in their mitochondrial thymidine kinase 2. Muscle pathology was genotype related: homozygosity for a missense mutation at position 181 was associated with severe myopathic changes, including marked variation in muscle fiber size, myofiber necrosis, regeneration, and interstitial fibrosis, whereas homozygosity for a missense mutation at position 90 was associated with essentially normal muscle histology. No ragged red fibers were detected in any study child. Mitochondrial DNA depletion should be considered in children with myopathy, worsening hypotonia, motor regression, and death during infancy or early childhood. The severity of pathologic findings on muscle biopsy is variable and may correlate with specific mutations and thymidine kinase 2 protein residual activity. (J Child Neurol 2002;17:499-504).

Childhood epilepsy with occipital paroxysms : Difficulties in distinct segregation into either the early-onset or late-onset epilepsy subtypes

The Commission on Classification and Terminology of the International League Against Epilepsy Childhood rigidly segregated epilepsy with occipital paroxysms into 2 separate syndromes with different predominant seizure types: early-onset seizure susceptibility type consisting of prolonged infrequent, nocturnal autonomic seizures and accompanied by eye deviation and ictal vomiting and late onset with short diurnal frequent seizures and visual ictal manifestations along with throbbing headaches. Epileptic clinical manifestations and electroencephalographic data were analyzed in 28 patients with suspected occipital lobe epilepsy in an attempt to segregate them into either the early or late forms according to the International League Against Epilepsy classification. Electroencephalography in 25 children demonstrated occipital epileptiform paroxysms compatible with the suspected epileptic syndrome. Only 14 (50%) children complied with the rigid criteria of either early-onset or late-onset presentations. The other 14 (50%) children presented with mixed diverse epileptic phenomena such as short-lived seizures in infancy or prolonged seizures during childhood, not complying with either rigid syndrome (ie, short-lived epileptic blindness at an early age or vomiting during later childhood). Despite present attempts to rigidly segregate childhood epilepsy with occipital paroxysms into 2 distinct epileptic syndromes, a high percentage of children still present with various mixed clinical phenomena. Therefore, clinicians should be aware of possible unique and unusual presentations of occipital lobe epilepsy at various ages.

Carbamazepine versus Sulthiame in Treating Benign Childhood Epilepsy With Centrotemporal Spikes

We compared the therapeutic efficacy of carbamazepine versus sulthiame in patients with benign childhood epilepsy with centrotemporal spikes. Drug efficacy was evaluated only in those patients who initiated treatment with any drug after at least three seizures. Thirty-eight patients who received carbamazepine and 18 patients who received sulthiame were included in the analysis. Cessation of seizures was observed in 73.6% of the former and in 66.7% of the latter (P = not significant). Five of eight patients who were switched to sulthiame after failing carbamazepine became seizure free, whereas none of the three patients who failed sulthiame became seizure free after being switched to carbamazepine. The rate of drug discontinuation owing to adverse reaction was 15% in carbamazepine and 14.3% in sulthiame. Normalization of interictal epileptiform activity on electroencephalography was seen more often following treatment with sulthiame (71%) than with carbamazepine (42%) (P = not significant). No significant differences between these two medications were found in the treatment of benign childhood epilepsy with centrotemporal spikes in this small patient sample. (J Child Neurol 2002;17:913—915).