Jacqueline R. Farwell

Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence.

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.

Neuropsychological Abilities of Children with Epilepsy

Summary: One hundred eighteen epileptic children, aged 6–15 years, underwent detailed neuropsychological testing including the Wechsler Intelligence Scale for Children‐Revised and the age‐appropriate Halstead‐Reitan battery. Eight had classical absence seizures only, eight had classic absence seizures and generalized tonic‐clonic seizures, 30 had generalized tonic‐clonic seizures only, 31 had partial seizures only, 20 had partial seizures and generalized seizures, 15 had atypical absence seizures, and five had minor motor seizures. A control group of 100 children without seizures, matched to the general population for intelligence and matched to the seizure cases for age, underwent identical testing. The Wechsler full‐scale intelligence quotient (FSIQ) of cases was significantly (p = 0.01) lower than that of controls and was related to seizure type. Children with minor motor or atypical absence seizures had the lowest average FSIQ (70 and 74, respectively). All seizure types were associated with below‐control intelligence except classic absence only. Intelligence was also correlated with degree of seizure control. A highly significant inverse correlation between years with seizures and intelligence was found (p < 0.0001). A rating of neuropsychological impairment, derived from all measures of brain function, was assigned to each child. Epileptic children had significantly more impairment than controls (p < 0.0001). Children with seizures had been placed in special education or had repeated a grade in school almost twice as frequently as controls (p < 0.001). Even though often placed in a class of younger children, their academic achievement was behind grade placement more often than in controls. Children with seizures differed significantly from controls in making more errors on language‐related tasks.

Late Cognitive Effects of Early Treatment with Phenobarbital

We previously reported that IQ, was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n=217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p=0.007). There was a nonsignificant mean difference of 3.71 IQ, points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p=0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures. Clin Pediatr. 1999;38:387-394

Cancer in Relatives of Children with Central-Nervous-System Neoplasms

We compared the occurrence of cancer in parents, siblings, and offspring of 643 patients who had central-nervous-system tumors in childhood (cases), as recorded in the Connecticut Tumor Registry, with the occurrence in parents, siblings, and offspring of 360 controls selected according to birth certificate and matched for sex, birth date, and birthplace. Overall cancer incidence was comparable in the two groups. However, 11 nervous-system tumors occurred in relatives of cases, whereas none occurred in relatives of controls (P = 0.0005). Nine relatives of cases but no relatives of controls had cancer of the hematopoietic-lymphatic system (P = 0.003). Nine siblings of cases but only one sibling of a control had cancer as children. Medulloblastoma and glioblastoma multiforme were overrepresented in the group of children whose relatives had central-nervous-system tumors. We compared the actual number of cancers of the central nervous system or hematopoietic-lymphatic system in relatives of cases with the number expected on the basis of known incidence rates and found a fivefold excess. We conclude that the occurrence of a brain tumor in a child is a marker for an increased likelihood of central-nervous-system tumors, leukemia, and childhood tumors in the family.

Stiripentol in Atypical Absence Seizures in Children: An Open Trial

Summary: Stiripentol (STP) was added to the antiepileptic drug (AED) regimen of 10 patients with uncontrolled atypical absence seizures (more than one seizure a day). Seven boys and three girls aged 6–16 years participated in the study. Concomitant AEDs included various combinations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). Parents counted daily seizures over a 4‐week baseline period before institution of STP, and in a 20‐week period during STP therapy. To compensate for drug interactions, doses of other AEDs were adjusted during STP administration to keep serum levels close to levels of the baseline period. Maintenance doses of STP were 1,000–3,000 mg/day, giving serum levels of 4–22 μg/mL. All patients experienced a decrease in atypical absence seizures. Average decrease was 70% (range 5–95%). Side effects experienced by some patients were dose related and included anorexia, nausea, vomiting, and lethargy. In only 1 patient did an adverse effect (vomiting) require discontinuation of STP. We conclude that STP shows promise in treatment of atypical absence seizures in children, and further trials are warranted.

An Objective Method for the Assessment of Psychosocial Problems in Adolescents with Epilepsy

Summary: Psychosocial problems in adolescents with epilepsy have béen of concern for many years, but have béen difficult to assess. This article presents the multi‐center development of the Adolescent Psychosocial Seizure Inventory (APSI), an empirically based self‐report test patterned after the Washington Psychosocial Seizure Inventory, which is used to evaluate psychosocial problems in adults. After pilot work, 120 adolescents with epilepsy from five centers in North America took the APSI and were interviewed by professionals with respect to adequacy of adjustment in eight psychosocial areas. At least one parent or guardian was also interviewed. Inter‐ rater reliability of professional ratings in each area was established. Using an item‐by‐item, empirically based technique, eight psychosocial scales were developed as well as thrée validity scales. Reliability of the scales was established by both internal consistency and test‐rétést procedures. Results for each adolescent are presented in profile form. These results give a visual display of the types and extent of problems that likely would be identified in a detailed professional assessment. It is anticipated that the APSI will be of value in a variety of treatment and research contexts.

Second primaries in children with central nervous system tumors

Among 670 children diagnosed with central nervous system tumors before age 20 and recorded in the Connecticut Tumor Registry, nine had a second neoplasm as well. From known age-specific and year-specific cancer incidence figures for Connecticut, the expected number of second neoplasms for the series of 670 is 0.99; therefore the relative risk is 9.1 (95% confidence limits: 4.0, 17.3). Three patients developed two central nervous system tumors, while 0.16 were expected, giving a relative risk of 19 (95% confidence limits: 3.8, 55). Six patients developed two neoplasms in childhood, versus 0.66 expected; the relative risk of this event is 9.1 (95% confidence limits: 3.3, 20). In four cases of lapse in time between the diagnosis of the first and second tumor, the first tumor had been treated with radiation. Five cancers occurred in parents or siblings of these nine patients, versus 0.91 expected; the relative risk is 5.5 (95% confidence limits: 1.2, 10.0). Three of these relatives had leukemia, while only 0.04 cases were expected (relative risk = 75). We conclude that not only is a child with CNS cancer at increased risk for other cancers, but such a child with two cancers is often part of a familial cluster with increased risk of cancer.

First Febrile Seizures Characteristics of the Child, the Seizure, and the Illness

Through interviews with parents, data were gathered about 910 first febrile seizures in children aged 8 to 34 months. A male preponderance of 57% was found (P <.001). In 29% of cases, there was a family history of febrile seizures. Eighteen percent of seizures were focal, and 7% lasted 15 minutes or more. Focal seizures were much more likely to be of long duration (P <.001). Otitis media was diagnosed in 32% of cases, and tonsillitis or upper respiratory infection in 12%. When compared to febrile seizures after the first birthday, febrile seizures in children aged 8 to 11 months were more than twice as likely to be longer than 15 minutes (P= .015). They were also much more likely to be followed by further seizures in the same illness (P <.001). Thus, febrile seizures in children younger than 1 year are more likely to have the characteristics known to increase the risk of later nonfebrile seizures.

Adrenocorticotropic Hormone Controls Infantile Spasms Independently of Cortisol Stimulation

Summary: Infantile spasms constitute a severe seizure disorder unresponsive to standard anticonvulsants. Both prednisone and adrenocorticotropic hormone (ACTH) have produced remission of seizures in some patients. The mechanisms of action of these hormones are not known. Eight infants with infantile spasms were treated with prednisone for 2 weeks. This controlled the seizures in two patients. In the remaining six patients, prednisone was continued and ACTH was added. This treatment produced cessation of spasms in four patients. Serum prednisone and cortisol were measured at a number of points during treatment. In infants receiving prednisone and then prednisone plus ACTH, serum cortisol was suppressed to about one‐quarter of baseline levels with the initiation of prednisone, and remained suppressed during ACTH administration. We conclude that ACTH can exert its effect on infantile spasms in the setting of adrenal suppression, and can act without stimulating endogenous cortisol production. A CNS site of action is suggested and should be sought.

Epilepsy in Schizencephaly: Abnormal Cortical Organization Studied by Somatosensory Evoked Potentials

Summary: Median nerve short‐latency somatosensory evoked potentials (MN‐SSEP) are recorded from the scalp to assess parietal lobe function and from the cortex to identify primary sensory and motor areas before epilepsy surgery. Nevertheless, the origins of many of the MN‐SSEP waveforms and the reliability of this technique for localizing the central sulcus are not definitively known. We studied a child with a unilateral, closed, right parietal schizencephalic cleft and frequent simple partial seizures before the child underwent cortical resection. The sensory examination, neuroimaging, and electrical brain stimulation findings indicated a normal thalamus and an abnormal parietal lobe. Scalp‐recorded MN‐SSEPs showed intact widespread N18 potentials bilaterally, but absent right, although normal left parietal N20 and P27 waveforms. Cortically recorded MN‐SSEPs could not localize the central sulcus owing to an absence of the expected negative potential over the right postcentral gyrus and the presence of waves with abnormal latencies over the precentral cortex. These findings suggest that: (a) the N18 potential probably originates at or below the level of the thalamus, (b) the N20 and P27 peaks are most likely generated by parietal cortex or white matter, and (c) cortically recorded MN‐SSEPs can fail to localize the central sulcus before epilepsy surgery when congenital anomalies exist in the parietal lobe.