Efficacy of the ketogenic diet: which epilepsies respond?

We report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty-four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty-nine (48%) of 61 patients were responders at 3 months. Two children became seizure-free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic-atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet.

Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity.

PURPOSES: To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied. METHODS: Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria. RESULTS: Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively.

Hypothalamic-pituitary dysfunction in survivors of childhood brain tumors in Prasat Neurological Institute.

OBJECTIVE: To assess hypothalamic-pituitary dysfunction in childhood brain tumor survivors in Prasat Neurological Institute. MATERIAL AND METHOD: Between October 2007 and September 2008, 19 brain tumor survivor children in Prasat Neurological Institute without recurrence at least 2 years after complete treatment were included in the present study. The patients were categorized according to brain tumor location into directly (DHPA) (9 cases) and indirectly (IDHPA) (10 cases) involving hypothalamic-pituitary axis. All patients were treated by surgery. Furthermore, six cases were combined with radiation and chemotherapy and 10 cases were combined with radiation therapy only. Growth Hormone (GH) stimulation test by clonidine and/or L-Dopa, ACTH stimulation test and thyroid function test (TFT) were done. RESULTS: The mean age at diagnosis was 9.9 +/- 4.6 years old and the interval from diagnosis to study was 5.8 +/- 2.2 years. Seven DHPA (77%) and seven IDHPA patients (70%) had low peak GH with significant lower level in the former group (p < 0.05). Six of seven DHPA (85%) and one IDHPA patients (10%) had low response to ACTH stimulation test. All DHPA (100%) and 10% IDHPA patients had central hypothyroidism. By ACTH stimulation test in DHPA patients, hypocortisolism was detected in five and excluded in one who later stopped prednisolone after prolonged continuation. The central hypothyroidism was newly detected in two DHPA patients and replacement therapy was initiated GH deficiency (GHD) was detected by GH stimulation test in 73% of overall brain tumors. Growth hormone therapy would be considered in the appropriate GHD patients. CONCLUSION: With effective therapy and improving survival rates of brain tumor children, hypothalamic-pituitary dysfunction in either DHPA or IDHPA group should be regularly monitored to prevent further morbidity and improve quality of life.