Anna Belmonte

Lamotrigine and seizure aggravation in severe myoclonic epilepsy

Summary: Purpose: In severe myoclonic epilepsy of infancy (SME), multiple drug‐resistant focal and generalized seizure types occur. Lamotrigine (LTG), found effective in many generalized and partial seizures, has been little used in severe childhood epilepsy syndromes with multiple seizure types. We studied the effects of LTG in SME.

Antiepileptic Drug-Induced Worsening of Seizures in Children

Summary: Antiepileptic drugs (AEDs) may aggravate preexisting seizures and trigger new seizure types. However, the extent and mechanisms of this problem are unclear, for several reasons. AED trials are not designed to detect worsening of seizures, severe childhood epilepsies may fluctuate in severity, and worsening of seizures may be over‐hastily ascribed to the introduction of a new AED. Moreover, the seizure and the epilepsy type may have been incorrectly diagnosed. The problem is identification of true aggravation of epilepsy in the absence of overdosage or toxicity. This is a common and clinically important problem that concerns both established and newer AEDs, but the biologic mechanisms involved are unknown. An increase in seizure frequency due to overdosage has been reported with phenytoin but is rare with other AEDs. Paradoxical reaction has been reported with carbamazepine (CBZ), benzodiazepines, and vigabatrin (VGB). Exacerbation of seizures may also occur during AED‐induced encephalopathy or hepatopathy. An inappropriate choice of the AED (i.e., a purely pharmacodynamic mechanism) can induce worsening when CBZ or VGB is used in absence and myoclonic seizures. Further research should determine whether seizure exacerbation is associated with the type of epilepsy or with the type of EEG abnormality. Recent evidence indicates that lamotrigine is inappropriate in severe myoclonic epilepsy. Some childhood epileptic encephalopathies have been affected by certain seizure‐worsening mechanisms. Whether this is due to a predisposition in specific syndromes or to an increased risk for adverse effects in patients undergoing multiple AED manipulations is unclear. Furthermore, some syndromes are not the sum of accompanying seizure types but have unique neurobiology.

Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment

Summary: Purpose: To describe an 11‐year‐old girl with symptomatic localization‐related epilepsy and normal intelligence who developed reversible mental deterioration and pseudoatrophic brain changes while receiving valproate (VPA).

Myoclonic status epilepticus following high-dosage lamotrigine therapy

An 8-year-old girl with Lennox-Gastaut syndrome showed a partial reduction in seizure frequency when lamotrigine (LTG), 15 mg/kg per day, was added to clobazam (CLB) and vigabatrin (VGB). An increase in LTG dosage to 20 mg/kg per day produced no further improvement and was followed by myoclonic status epilepticus. The condition developed insidiously and ultimately became stable. Video-EEG polygraphy and jerk-locked back-averaged EEG demonstrated continuous myoclonus of cortical origin. Discontinuation of LTG resulted in rapid disappearance of clinical and electrophysiological manifestations of myoclonic status epilepticus. No episodes of myoclonus occurred in the subsequent 2 years, during which CLB and VGB were kept unchanged. The striking response to drug discontinuation suggests that LTG may have played a role in the precipitation of status, possibly within the context of paradoxical intoxication.

Adolescent Onset of Idiopathic Photosensitive Occipital Epilepsy After Remission of Benign Rolandic Epilepsy

Summary: Purpose: We describe 2 girls, aged 19 years, who experienced a rolandic seizure at ages 4 and 5, respectively, together with the interictal EEG features of benign rolandic epilepsy (BRE). In adolescence both patients developed photosensitive occipital seizures accompanied by spontaneous and photic‐induced occipital EEG paroxysms.

Delayed appearance of interictal EEG abnormalities in early onset childhood epilepsy with occipital paroxysms.

Childhood epilepsy with occipital paroxysms is an age-related idiopathic focal epilepsy. Occipital EEG paroxysms are considered necessary for diagnosis. We carried out a close clinical and EEG follow-up (range, 2-12 years; mean, 6 years 7 months; median, 7 years) in 24 patients (age range, 4-19 years; mean, 11 years 8 months; median, 11 years). In five children with early seizure onset and particularly benign prognosis without any treatment, EEG abnormalities appeared 3-10 months after the first seizure. Four of them exhibited the ictal pattern of versive seizures with vomiting. Our findings confirm that in the early idiopathic focal seizure disorders, interictal EEG abnormalities may be lacking at the beginning of the disorder.

Paroxysmal tonic upgaze of childhood with ataxia: a benign transient dystonia with autosomal dominant inheritance

Paroxysmal tonic upgaze of childhood with ataxia is a rare form of age related dystonia. Out of 12 previously reported cases, three had a clinical history of similar symptoms occurring in at least one first degree relative belonging to the same or two consecutive generations. Autosomal dominant inheritance was therefore hypothesized. We report on a family in which the disorder appeared in three consecutive generations between ages 6 and 11 months, disappearing gradually and spontaneously between ages 18 to 24 months. All affected individuals had normal neurologic development. The pedigree analysis of previously reported cases and of the family reported herein provides strong evidence that the disorder may be inherited as an autosomal dominant trait and represents a form of transient paroxysmal dystonia with benign long-term prognosis.

Prospective study of first-line vigabatrin monotherapy in childhood partial epilepsies

This was a prospective open comparative pilot study to assess the efficacy and tolerability of first-line vigabatrin monotherapy in childhood partial epilepsies. Two groups of patients were recruited over the same period. The vigabatrin monotherapy group comprised 40 patients (18 male, 22 female; mean age at last visit 7.5 years); the comparative carbamazepine monotherapy group comprised 40 consecutive clinic patients (22 male, 18 female; mean age at last visit 7.8 years). Seizures disappeared in 82% of vigabatrin patients and in all carbamazepine patients with idiopathic partial epilepsy, and in 50% of vigabatrin patients and 55% of carbamazepine patients with symptomatic partial epilepsy. Interictal EEG abnormalities decreased in vigabatrin patients more than in carbamazepine patients (P < 0.05). Tolerability was good in vigabatrin patients, but four out of 37 showed mild irritability by the end of the trial. Persistent sedation was observed in eight of the 40 patients receiving carbamazepine. No patient had drug therapy discontinued because of side-effects. During vigabatrin long-term monotherapy, efficacy and good clinical tolerability were maintained. These results suggest that vigabatrin may be an alternative first-line treatment for childhood partial epilepsies. Further blinded comparative randomized trials are needed.

Add-On Lamotrigine Treatment in Children and Young Adults With Severe Partial Epilepsy: An Open, Prospective, Long-Term Study

We evaluated the efficacy and safety of lamotrigine in 41 children and young adults (age range, 3-25 years; mean, 12 years) with drug-resistant, partial epilepsies, based on a prospective, add-on study Patients had severe symptomatic/cryptogenic partial epilepsies (mean seizure frequency = 3.6/day), resistant to one to four major antiepileptic drugs. Mean seizure frequency significantly decreased (P < .001) throughout the period of treatment. A good response (>50% seizure reduction) was observed in 15 patients of whom 6 were seizure-free (follow-up: 12-48 months). Higher responder rate was found among cryptogenic epilepsies and epilepsies symptomatic of cerebral malformation, whereas patients with posthypoxicischemic perinatal damage were poor responders. Lamotrigine discontinuation was mainly due to lack of efficacy (46% of patients), whereas only 2 patients developed a transient skin rash and did not drop out. Lamotrigine represents a valuable treatment for severe partial epilepsies of childhood that have proved resistant to previous antiepileptic drugs. (J Child Neurol 2000;15:671-674).