María Vaccarezza

Long-term follow-up of the ketogenic diet for refractory epilepsy: multicenter Argentinean experience in 216 pediatric patients.

PURPOSE In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes. MATERIALS AND METHODS we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010. RESULTS One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75-99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox-Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures. CONCLUSION The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.

Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype–Phenotype Correlations

Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype–phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of phosphorylated ChAT of seven CHAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys, and p.Ser694Cys, in HEK‐293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal stability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp, and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active‐site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met, which is located far from both active and substrate‐binding sites, produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes.

Dietary therapy is not the best option for refractory nonsurgical epilepsy

The ketogenic diet (KD) is currently a well‐established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow‐up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new‐generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself.

Epilepsia partialis continua associated with levamisole.

Epilepsia partialis continua is defined as a spontaneous regular or irregular clonic muscular twitching affecting a limited part of the body, occurring for a minimum of 1 hour and recurring at intervals of less than 10 seconds. Levamisole is used as an immunomodulating medication in patients with recurrent aphthous ulcers. Evidence suggests that it can induce multifocal inflammatory leukoencephalopathy. We describe the clinical neuroimaging and ictal electroencephalographic findings in an adolescent with epilepsia partialis continua caused by the administration of levamisole with cortical and subcortical lesions. To our knowledge, this is the first report that describes the association of epilepsia partialis continua cortical lesions detected by magnetic resonance imaging and levamisole that were not previously described.

Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group

Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre‐KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow‐up, side events, and KDT discontinuation. It has been helpful in outlining a state‐of‐the‐art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institutions practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.