Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Childhood migraine.

Migraines are a common and often undiagnosed and undertreated problem in children of all ages. Migraine symptoms can vary dramatically in terms of character and severity, from brief self-limited headaches to prolonged events with complex neurologic and systemic symptoms. Identification of migraines requires an index of suspicion in any child with acute recurrent headaches or neurologic symptoms. Diagnosis remains predominately based on the patient's history of symptoms and supported by a positive family history. Neurodiagnostic tests are often unnecessary and of value predominately to exclude nonmigraine disorders that may present with similar symptoms. A number of recent advances in our understanding of the pathophysiology and genetics of migraines have occurred, and continued progress in these exciting areas of investigation is anticipated. Identification of genetic markers in individuals with FHM is potentially the first step in discovery of genetic markers that may be useful in other migraine syndromes and may lead to the development of new therapeutic interventions. The movement from a vascular to integrated neurovascular pathogenesis for migraine headaches is already being translated into the study of new pharmacologic treatments, such as nitric oxide inhibitors and continued development of 5-HT1 agonist (triptans) medications. Although not currently approved for use in children, triptans are being widely evaluated in clinical trials. As additional triptans and new dosage formulations are developed and approved, it is anticipated that the treatment of migraine headaches in children may change significantly in the next several years.

The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study.

PURPOSE: To assess neurocognitive and behavioral performance in children with idiopathic epilepsy (CWE, n = 74), their siblings without epilepsy (control, n = 23), and children with migraine (CWM, n = 13), and to identify medical factors related to learning or behavioral problems in CWE. METHODS: Subjects, ages 8-13 years with IQs of >/=80, completed a neurocognitive test battery annually for

Increased muscular beta-hydroxyacyl CoA dehydrogenase with McArdle's disease.

Enzymes of energy production were measured in muscle homogenates and in individual muscle fibers from 5 patients with McArdle's disease. Individual fibers were investigated to determine whether fibers of all types were completely devoid of glycogen phosphorylase activity and whether the involved fibers might be biochemically altered in a fiber type dependent manner to enhance the energy-generating capabilities of the cells through other metabolic pathways. Using highly sensitive biochemical assays, a complete absence of glycogen phosphorylase, a and b, activity was found in fibers of all types in the McArdle's patients. Levels of enzymes representing glycolysis, the Krebs cycle, and high energy phosphate metabolism were essentially normal in each fiber type, indicating an apparent lack in metabolic adaptation of these energy pathways to the absence of glycogen utilization. However, a key enzyme in the beta-oxidation of fatty acids (beta-hydroxyacyl CoA dehydrogenase, beta OAC) was elevated in all patients, and substantially in 4 of the 5. This suggested that lipid substrates can provide support for oxidative endurance capacity in some patients. Individual fiber analyses indicated that the compensation involved fibers of all types.

Auditory processing deficit in a patient with Rett syndrome.

Because of the consistent and prominent language failure in Rett syndrome, a patient with the characteristic phenotype was tested for subtle auditory processing deficits by visual reinforcement audiometry. In spite of excellent detection threshold and frequency discrimination, frequency sweep discrimination was at a chance level. This discrimination is normally performed by 5-8 month old infants. This observation suggests a defect in the specialized units of the inferior colliculus or higher auditory centers which subserve frequency sweep discrimination.

A method for branched-chain amino acid aminotransferase activity in microgram and nanogram tissue samples.

A method for branched-chain amino acid aminotransferase is described which is based on running the reaction in the reverse of the usual direction with glutamate and alpha-ketoisocaproate as substrates. The alpha-ketoglutarate generated is reduced with glutamate dehydrogenase and NADH. For sensitivity in the nanomole range, the NAD+ generated is measured directly by converting to the highly fluorescent strong alkali product. For smaller samples, down to the 0.2- to 2-pmol range, the NAD+ is amplified by enzymatic cycling.

Biochemistry of rat single muscle fibres in newly assembled motor units following nerve crush.

A partial crush was applied surgically to the common peroneal nerves of rats, producing motor deficits lasting 4 weeks; the tibialis anterior muscles supplied by the crushed nerves were removed 5 weeks after recovery along with the contralateral control muscles. Myosin ATPase staining following pre-incubation at pH 4.5 was used to determine fibre types and to demonstrate areas of fibre-type grouping in the reinnervated areas of the muscles. Enzyme activities of lactate dehydrogenase (LDH), adenylokinase (AK) and malate dehydrogenase (MDH) were measured using micro-analytical techniques on the individual fibres within the histochemically identical groups and on fibres of the same types selected from areas of the test muscle or the contralateral control which appeared normal. The results show that the degree of enzymatic variation among single fibres reinnervated by a common axon is very small when compared to the general fibre population and, moreover, to fibres of the same histochemical type. Enzyme variability within the newly formed motor units was only slightly greater than the variability reported for normal motor units (Nemeth, Pette & Vrbová, 1981). The results indicate that skeletal muscle fibres originally having great differences in levels of enzyme activity, as demonstrated in the general fibre population, acquire considerable enzymatic similarity following reinnervation by a common motor neurone.