Elizabeth A. Garofalo

Generalized spike-waves, multiple loci, and clinical course in children with EEG features of benign epilepsy of childhood with centrotemporal spikes.

Summary: In 41 patients with EEG features of benign epilepsy of childhood with centrotemporal spikes (BECCT), we noted associated generalized spike‐wave discharges (GSWD) in 14.6% and multiple independent sharp wave foci in 9.8%. The presence or absence of these EEG features was not predictive of the clinical course. The high incidence of GSWD in children with BECCT suggests a possible relation in the expression of these two EEG traits.

Spinal cord schistosomiasis: A pediatric case mimicking intrinsic cord neoplasm

We present the clinical, myelographic, MRI, and histologic data on a 7‐year‐old girl with confirmed Schistosoma mansoni infection of the spinal cord. MRI of the granulomatous spinal lesion revealed extensive enlargement of the cord in the T11‐12 area, with some intramedullary swelling extending to T‐5 through T‐7. The clinical manifestations of spinal schistosomiasis can be diverse, and there should be a high index of suspicion for all patients from endemic areas. NEUROLOGY 1991;41:755‐757

Valproic acid and thrombocytopenia in children: A case-controlled retrospective study

Thrombocytopenia in association with valproic acid (VPA) therapy has been reported in patients of various ages with incidences ranging from 1 to 32%. To evaluate this association in a pediatric population, we retrospectively studied 167 children treated with VPA at our institution between 1989 and 1993. Ninety-one patients on VPA monotherapy and 76 on VPA polytherapy (VPA plus 1 to 3 other antiepileptic drugs) were compared with 92 age- and sex-matched control patients treated with antiepileptic drugs other than VPA. Study variables included patient age, most recent platelet count, VPA dose, dose/kg, and serum VPA level. Thrombocytopenia, defined as a platelet count < 200 x 10(3)/mm3, was present in 21.6% of the children treated with VPA (26.4% in those on VPA monotherapy and 15.8% in those on VPA polytherapy) but in only 5.4% of controls untreated with VPA. Serum VPA level was the highest risk factor for the development of thrombocytopenia in these patients (P = .0001) and greater age also independently predicted thrombocytopenia. The dose of VPA or dose/kg were not independent predictors of thrombocytopenia (P = .0025). The degree of thrombocytopenia was mild among these patients, reflected in the absence of significant difference in mean platelet count between the three groups and the absence of any bleeding complication or excessive bruising. We conclude from these findings that the risk for children developing severe thrombocytopenia with bleeding complications while taking VPA is low and that mild thrombocytopenia does not necessarily mandate discontinuing the drug. Because higher serum VPA levels do predict thrombocytopenia, platelet counts should be closely monitored after dose escalation in such patients.

Asymmetric hypsarrhythmia : clinical electroencephalographic and radiological findings

Summary: Twenty‐six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4‐year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptic form activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxic‐ischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically.

EEG abnormalities aid diagnosis of Rett syndrome

Nine girls with Rett syndrome had 22 electroencephalographic studies performed over 5 years. Nineteen walking tracings demonstrated moderate background slowing. Focal epileptiform activity was observed in 13 studies, 10 of which had bilateral independent foci. Spikes were invariably maximal in central regions, diphasic or triphasic, and of very short duration. In 3 patients, epileptiform activity preceded clinical seizures by up to 2 years. Two children had spontaneous hyperpnea preceding apnea during wakefulness with further background slowing. Video monitoring of 2 children revealed that episodic behavioral changes were not seizures. Ten of 12 sleep recordings had abnormal background activity with absent or rudimentary spindles. Normal activity occurred only in girls younger than 2 1/2 years of age. Epileptiform activity was markedly increased during sleep in 8 tracings in which both wakefulness and sleep were obtained. It was characterized by bilaterally independent and bisynchronous spike-and-wave activity, maximal in parasagittal areas. One patient had bursts of high-voltage slow-wave activity followed by attenuation. No apneic episodes were recorded during sleep. In Rett syndrome, electroencephalographic abnormalities include background slowing, centrally located short-duration spikes, and increased epileptiform activity during sleep. This activity commonly preceded clinical seizures in patients studied at initial presentation.

Carbamazepine‐Induced Tics

A variety of movement disorders are known to occur in association with carbamazepine (CBZ) therapy in adults and children, but development of tics has been described infrequently and only in patients with underlying Tourettes syndrome or other movement disorders. We report 3 children with epilepsy who developed facial motor tics after initiation of CBZ for complex partial seizures. All 3 had documented CBZ blood levels in the therapeutic range at the time, and none had other symptoms or signs of clinical intoxication. Neurologic examinations were normal in 2 and showed developmental de lay of expressive language in the third. Brain imaging was normal in all. After development of the tics in 2, CBZ was continued at the same or higher dose, and the tics abated and then ceased spontaneously ≤6 months. In the third child, the tics ceased after CBZ discontinuation. These cases demonstrate that CBZ can induce simple motor tics in children. These idiosyncratic reactions may be transient and do not always necessitate drug discontinuation.

Epileptiform abnormalities during sleep in Rett syndrome

We recorded all-night electroencephalograms (EEGs)/polysomnograms on 2 consecutive nights from 4 children (ages 4-11 years) with Rett syndrome. The first 10 sec of each 60 sec epoch were analyzed with counts of left and right hemisphere spikes and correlated with sleep stage. Spike counts were lowest during wakefulness. Spikes were most frequent over parasagittal regions during all sleep stages and varied from 0.28 +/- 0.03 to 40.4 +/- 0.7 (mean +/- S.E.M.) spikes/hemisphere/min. Spike counts were 51-109% higher during NREM sleep than during REM sleep. In 3 of 4 subjects, spikes were most frequent during light NREM sleep. Spikes increased in frequency during the second half of the night. We conclude that in Rett syndrome, epileptiform activity is maximally expressed in stage 1-2 NREM sleep and during the early morning hours. Sleep EEG features may be useful in the diagnosis of Rett syndrome.

Clinical Development of Antiepileptic Drugs for Children

SummaryA clinical development plan specific to children is a necessary component of every development plan for a new antiepileptic drug (AED). In the last decade, considerable discussion has occurred in the medical and regulatory communities, resulting in specific pediatric drug development legislation. Ethical issues are a foremost consideration in the design and conduct of studies. The timing of clinical studies differs between adults and children. In general, studies in children will not be performed until efficacy and safety has been demonstrated in adults. Exceptions include development of AEDs for seizure types seen only in children. Formulation preparation and dosing selection are often more challenging in children. Clinical trials including pharmacokinetic studies will be conducted in patients. A relatively small number of children, given subdivision into age groups and seizure types, are available for study. Clinical trials must be designed with children in mind, adjusting the length of the trials and the choice of controls. Efficacy extrapolation from adults may be considered for partial seizures in children, but not in infants. Seizure counts remain an appropriate efficacy endpoint; however, ascertainment in infants and younger children may require EEG monitoring. Safety specific to growing and developing children must be evaluated and long-term effects monitored.