Joseph M. Dooley

LAMOTRIGINE-ASSOCIATED RASH: RISK/BENEFIT CONSIDERATIONS IN ADULTS AND CHILDREN

Summary: Purpose: Lamotrigine (LTG) is an antiepileptic drug (AED) recently released in several countries. It is effective for a variety of seizure types in adults and children both as an add‐on agent and in monotherapy, and is generally well tolerated. This report reviews the apparent risk factors for rash associated with LTG to determine whether and how the risk of serious rash can be minimized in practice.

Incidence of Epilepsy in Childhood and Adolescence: A Population-Based Study in Nova Scotia from 1977 to 1985

Summary: Data from a regional EEG laboratory allowed us to identify almost all children in Nova Scotia (population 850,000) with one or more unprovoked, afebrile seizures from 1977 through 1985. We then reviewed hospital and pediatric neurology physician charts to limit cases to those with two or more definite afebrile seizures between the ages of 1 month and 16 years. In all, 693 children developed epilepsy: typical childhood absence seizures (AS) (97), either generalized tonic‐clonic (GTCs) or partial seizures either secondarily generalized or not (511), and other generalized seizure types, including infantile spasms (IS) as well as myoclonic, akinetic, tonic, and atypical AS (85). The incidence of epilepsy was 118 in 100,000 for children aged < 1 year, 48 in 100,000 for those aged 1–5 years, 43 in 100,000 for those aged 6–10 years, and 21 in 100,000 for those aged 11–15 years. The incidence for each year of age between 1 and 10 years was remarkably constant (mean 46 in 100,000 ± 7 SD). Comparison of the incidence rates showed significant differences for those aged <1 year as compared with all others, and for those aged >10 years as compared with those aged 1–10 years. We conclude that the incidence of epilepsy is highest in the first year of life, plateaus in early childhood, and decreases markedly after age 10 years. The overall incidence of epilepsy in childhood is lower than that reported in previous studies.

WHAT TYPES OF EPILEPSY ARE PRECEDED BY FEBRILE SEIZURES? A POPILATION‐BASED STUDY OF CHILDREN

In a population of 850,000, the authors studied afebrile seizures that follow febrile seizures. Review of all paediatric EEGs identified 504 children with epilepsy beginning between 1977 and 1985. Follow‐up averaged 85 months. 14‐9 per cent had preceding febrile seizures: 13 per cent complex partial, 13 per cent partial/secondary generalized and 22 per cent generalized tonicclonic. The rate of preceding febrile seizures did not vary with the cause of epilepsy. Prolonged febrile seizures were not associated with any particular afebrile seizure type. Of 17 with preceding prolonged febrile seizures, seven developed intractable epilepsy: 17‐9 per cent of the total intractable cases. Only two developed idiopathic intractable complex partial seizures after prolonged febrile seizures. The authors conclude that febrile seizures most often precede generalized tonic‐clonic afebrile seizures. Prolonged febrile seizures rarely precede idiopathic intractable complex partial seizures. The febrile seizure tendency may be a fundamental marker of an individuals seizure threshold.

If a first antiepileptic drug fails to control a child's epilepsy, what are the chances of success with the next drug ?

OBJECTIVE This study was carried out to determine how often a childs epilepsy is controlled and remits if a first antiepileptic drug (AED) fails to control seizures. STUDY DESIGN We used the Nova Scotia population-based epilepsy study, which identified children between 1977 and 1985 who had two or more unprovoked seizures without progressive cause and followed them up for at least 4 years. Seizure types were partial, primary, and secondarily generalized (excluding absence seizures). The study documented success or failure of the initial AED in the first year of treatment, as well as long-term seizure control and remission. RESULTS The number of eligible children was 417, with an average follow-up period of 8 years. The initial prescribed AEDs were phenobarbital (48%), carbamazepine (38%), and phenytoin (11%). Overall, 345 (83%) children received only one AED in the first year of treatment; 61% became free of seizures and no longer required AED treatment at the end of follow-up (remission). Only 4% of those treated with a single AED during the first year later experienced intractable epilepsy. In contrast, 72 of 417 (17%) had inadequate seizure control with their first AED and received a second AED, with only 42% having complete remission of their epilepsy. The 72 children in whom seizures were not controlled with the first AED were more likely to have neurologic deficits (p = 0.01) and complex partial seizures (p = 0.01), and 29% had intractable epilepsy (p < 0.0001). CONCLUSIONS If the first AED is not efficacious, the outcome is less favorable, although many children will have remission of their epilepsy. Invasive or complex treatments for epilepsy with partial and generalized tonic-clonic seizures should not be used until at least two AEDs have failed to control seizures.

Botulinum toxin A as a treatment for excessive drooling in children

Drooling is problematic for some neurologically impaired children. Botulinum toxin A injection to salivary glands has effectively reduced drooling in adults but has only recently been used to treat children. This was a preliminary study to determine the efficacy and safety of botulinum toxin in children. Children identified as having severe daily drooling were enrolled. The preinjection assessment included measurement of the amount and frequency of drool. Each parotid gland was injected with 5 U of botulinum toxin A. Follow-up was for a minimum of 16 weeks. Nine children were enrolled, 4-17 years of age. All children had moderate or severe mental retardation. At week 4, all patients had a reduced drooling frequency and eight of nine patients had a reduction in the weight of saliva. Overall, five of nine parents (55%) deemed the treatment successful. This preliminary study demonstrates that botulinum toxin A is a relatively effective treatment for some children with significant drooling without serious side effects.

Does the number of seizures before treatment influence ease of control or remission of childhood epilepsy? Not if the number is 10 or less

Article abstract-Using a population-based regional cohort of 479 children with epilepsy, we studied the effect of the number of pretreatment afebrile seizures on seizure control and remission. The number of pretreatment seizures varied from 1 to 20. For the first 10 pretreatment seizures, there was no significant difference or trend in (1) the proportion of children who were seizure free long enough to attempt stopping medication (mean, 70%), (2) the number of breakthrough seizures before control was achieved, or (3) the proportion of children who were seizure free after stopping medication for the first time (mean, 70%). More patients with more than 10 pretreatment seizures had complex partial seizures (59%) than those with 10 or fewer seizures (16%) (p < 0.00001). We conclude that there does not appear to be any penalty for seizure control or early remission of epilepsy if medication is delayed for up to 10 pretreatment seizures. NEUROLOGY 1996;46: 41-44

Benign Rolandic Epilepsy: Atypical Features Are Very Common:

The objective of this study was to determine the frequency of atypical clinical and electrographic features in children with benign rolandic epilepsy. A retrospective case series design was employed in the setting of a tertiary care pediatric hospital. Forty-two children with benign rolandic epilepsy were seen through our neurology department between January 1, 1991, and December 31, 1993. Their charts were reviewed for atypical clinical features, imaging studies and results, total number of seizures at initial presentation and last follow-up, and use of anticonvulsants. Atypical clinical features included status epilepticus, developmental delay, daytime-only seizures, screaming as a seizure component, and postictal Todds paresis. All children had at least one electroencephalogram, and these records were reviewed for atypical electrographic features such as unusual location, atypical spike morphology, and abnormal background. Atypical clinical features were seen in 50% of patients and atypical electrographic features in 31%. Computed tomographic scans were performed in 15 patients and were consistently normal. Treatment with anticonvulsant medication was initiated in 40%. Although patients with atypical features did not have an increased seizure frequency, they were more likely to undergo imaging studies (P < .01) and to be commenced on anticonvulsant medication (P < .02). Our experience suggests that atypical clinical and electrographic features are the rule rather than the exception in benign rolandic epilepsy. Further work must be done to develop a reliable definition of this common entity. (J Child Neurol 1995;10:455-458).

Relation of Pregnancy and Neonatal Factors to Subsequent Development of Childhood Epilepsy: A Population-Based Cohort Study

OBJECTIVE. We examined the effect of pregnancy and neonatal factors on the subsequent development of childhood epilepsy in a population-based cohort study. PATIENTS AND METHODS. Children born between January 1986 and December 2000 in Nova Scotia, Canada were followed up to December 2001. Data on pregnancy and neonatal events and on diagnoses of childhood epilepsy were obtained through record linkage of 2 population-based databases: the Nova Scotia Atlee Perinatal Database and the Canadian Epilepsy Database and Registry. Factors analyzed included events during the prenatal, labor and delivery, and neonatal time periods. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals. RESULTS. There were 648 new cases of epilepsy diagnosed among 124207 live births, for an overall rate of 63 per 100000 person-years. Incidence rates were highest among children <1 year of age. In adjusted analyses, factors significantly associated with an increased risk of epilepsy included eclampsia, neonatal seizures, central nervous system (CNS) anomalies, placental abruption, major non-CNS anomalies, neonatal metabolic disorders, neonatal CNS diseases, previous low birth weight infant, infection in pregnancy, small for gestational age, unmarried, and not breastfeeding infant at the time of discharge from hospital. CONCLUSIONS. Our study supports the concept that prenatal factors contribute to the occurrence of subsequent childhood epilepsy.

The prognosis and treatment of headaches in children: a ten year follow-up

The prognosis and methods of treating headaches were studied in a group of children, 10 years after their initial diagnosis in 1983. Follow-up was achieved for 77 patients (81%). Headaches persisted in 72.7% but were much improved in 81.3%. Medication use was uncommon, with non-prescription medications used by 30.3% and prescription medications by only two. These data suggest that although childhood onset headaches are likely to persist, children who receive early education regarding the use of non-pharmaceutical methods of headache control appear to rely on these methods even after an interval of 10 years.

Self‐Reported Headache Frequency and Features Associated With Frequent Headaches in Canadian Young Adolescents

Objective.—To explore the associated factors for frequent headache among young adolescent Canadians.