Early-onset childhood absence epilepsy: is it a distinct entity?

Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early-onset CAE is not a homogeneous condition. The debate as to whether early-onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early-onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.

MRI findings in pediatric ophthalmoplegic migraine: a case report and literature review.

Ophthalmoplegic migraine (also recognized as a cranial neuralgia) is a form of migraine characterized by recurrent episodes of headache with ophthalmoplegia related to paresis of cranial nerves III, IV, or VI, with onset typically in childhood. These symptomatic episodes may persist for several hours or for several weeks, months, or permanently. To date, the exact etiology of ophthalmoplegic migraine remains unknown. In previous case reports, ophthalmoplegic migraine may or may not be associated with changes seen on magnetic resonance imaging. Contrast-enhanced magnetic resonance imaging performed during symptomatic and postsymptomatic periods in patients with ophthalmoplegic migraine may hold great value in identifying the pathophysiologic features of oculomotor nerve palsies. Of cases demonstrating abnormal magnetic resonance imaging, a majority show improved but persistent changes on repeat imaging. The present report describes a case of recurrent ophthalmoplegic migraine in a 16-year-old girl. Although the patient presented with ophthalmoplegic migraine during this episode in the same manner as her prior episodes, enhancement of the cranial nerve III on magnetic resonance imaging was evident during the eighth episode whereas previous imaging had been normal. Complete resolution of enhancement of the oculomotor nerve on repeat imaging adds to the few cases that have shown such findings in patients with recurrent ophthalmoplegic migraine. A review of previous reported cases of ophthalmoplegic migraine is offered.

Epileptic seizures in the pediatric intensive care unit setting.

PURPOSE: The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting are not well characterized. Adult ICU studies reveal an incidence of seizures ranging from 0.8% to 3.3%, with vascular, metabolic abnormalities, and drug withdrawal being the most common etiologies. The objective of this study is to investigate the clinical characteristics of seizures in children admitted to the PICU at our institution. METHODS: We performed a retrospective review of all patients with diagnoses of seizures or epilepsy, admitted to our PICU from 2002 to 2004. Of 6,820 admissions, 32 patients, aged one month to 19 years had seizures in the PICU. RESULTS: The incidence of seizures was 0.5%. Developmental delay or mental retardation was present in 37% of patients. Seizures were generalized in 26 (81%), and focal in 6 (19%); 34% had status epilepticus. The etiology of seizures was epilepsy in 11 (34%). Seizures that do not meet the diagnosis of epilepsy were diagnosed in 21 (66%) including post-craniotomy in five (23%), febrile seizures in three (14%), encephalitis in three (14%), and hydrocephalus in three (14%). Thirty-one patients (97%) were initially treated with either lorazepam or fosphenytoin. CONCLUSIONS: Seizures in PICU have different clinical characteristics from those in adults. Recognizing the common seizure etiologies in PICU is likely to lead to a more prompt and effective treatment. Antiepileptic drug prophylaxis may be useful in post-craniotomy patients. A neurological consultation and EEG evaluation are of the utmost importance to help rule in or out epileptic disorders in the PICU.

Efficacy and tolerability of topiramate in children younger than 2 years old.

To evaluate the efficacy and tolerability of topiramate in children with epilepsy younger than 2 years of age, we retrospectively reviewed the records of patients treated at our institution between 2001 and 2003. Thirteen children ages 5 to 23 months, five boys and eight girls, were identified. Seizure types were partial (five), generalized tonic-clonic (three), myoclonic (one), and infantile spasms (four). The mean age at seizure onset was 9.7 months. Topiramate was started at a mean age of 11.4 months (4-23 months). The number of antiepileptic drugs prior to topiramate therapy ranged from zero to four. One patient had been on the ketogenic diet. Topiramate was used as monotherapy in seven children and as polytherapy in six children. Mean follow-up was 14 months. The mean dose of topiramate was 8.8 mg/kg/day (2.5-18 mg/kg/day). The degree of seizure reduction was as follows: > 75% in five (38.5%) children, 50% to 75% in three (23%) children, and 0 to 25% in five (38.5%) children. Three of four (75%) patients with infantile spasms had a > 75% reduction in seizures. Adverse effects occurred in two children, including lethargy, hyperthermia, and anorexia. In children younger than 2 years of age, for whom the antiepileptic drug armamentarium is limited, topiramate appears to be an efficacious and safe therapeutic alternative for a variety of seizure types.

Efficacy of lacosamide as adjunctive therapy in children with refractory epilepsy.

Lacosamide is a US Food and Drug Administration (FDA)-approved antiepileptic drug for patients 17 years or older with partial epilepsy. There are sparse data on children. The objective of our study was to evaluate its efficacy/safety in children with refractory epilepsy. Forty children (mean age 14.3 years) were treated with lacosamide at our institution (adjunctive therapy in 36, monotherapy in 4). Fifteen patients had symptomatic focal epilepsy, 2 had cryptogenic focal epilepsy, 20 had symptomatic generalized epilepsy, and 3 had cryptogenic generalized epilepsy. Two had juvenile myoclonic epilepsy and 5 had Lennox-Gastaut syndrome. Forty-two percent had at least >50% reduction in seizure frequency, and 6 became seizure free. Average dose was 7 mg/kg/d and average follow-up was 9.2 months. Responders had a 76.5% mean decrease in seizures. Fifteen children experienced an adverse reaction and 7 discontinued lacosamide (4: Ineffective, I: insurance denial, 1: tremor, 1: behavior). Lacosamide is effective and well-tolerated in children with refractory epilepsy.

Mitochondrial dysfunction in migraine.

Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the most characteristic ones being direct observation in muscle biopsy of ragged red and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and demonstration of giant mt with paracrystalline inclusions. (3) Genetic evidence: Recent studies have identified specific mutations responsible for migraine susceptibility. However, the investigation of the mtDNA mutations found in classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and Leber hereditary optic neuropathy) has not demonstrated any association. Recently, 2 common mtDNA polymorphisms (16519C→T and 3010G→A) have been associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause disease through impaired replication of mtDNA, including migraine. Further studies to investigate the relationship between mtDNA and migraine will require very large sample sizes to obtain statistically significant results. (4) Therapeutic evidence: Several agents that have a positive effect on mt metabolism have shown to be effective in the treatment of migraines. The agents include riboflavin (B2), coenzyme Q10, magnesium, niacin, carnitine, topiramate, and lipoic acid. Further study is warranted to learn how mt interact with other factors to cause migraines. This will facilitate the development of new and more specific treatments that will reduce the frequency or severity or both of this disease.

Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis.

OBJECTIVES: To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the relationship between clinical course and MRI findings and (2) the response to plasmapheresis in a subgroup of patients. METHODS: A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998-2003. RESULTS: Diagnosis was established by clinical signs and symptoms, cerebrospinal fluid changes and multifocal involvement of deep gray and white matter based on MRI. Initial therapy was high-dose methylprednisolone and intravenous immunoglobulin in 12 patients. One child improved spontaneously. Six of 12 children did not improve with corticosteroid treatment. All 6 had an acute progressive course neurologically, and 5 of them also showed a delay in the onset of neuroimaging changes, eventually developing lesions in the deep gray matter and brainstem. This latter group received 5 sessions of plasmapheresis and recovered over the course of several months with varying degrees of residual neurologic deficits. CONCLUSIONS: Presentation of ADEM with delayed development of MRI lesions in deep gray matter and brainstem may herald a prolonged clinical course and lack of response to glucocorticoid therapy. Plasmapheresis might be an effective therapeutic intervention in these patients. The role of plasmapheresis versus corticosteroids and intravenous immunoglobulin as a primary treatment of ADEM needs to be investigated further.