A. G. Christina Bergqvist

Fasting versus Gradual Initiation of the Ketogenic Diet: A Prospective, Randomized Clinical Trial of Efficacy

Summary:  Purpose: The ketogenic diet (KD) is a 90% fat diet that is an effective treatment for intractable epilepsy. Rapid initiation of the KD requires hospital admission because of the complexity of the protocol and frequent mild and moderate adverse events. The purpose of the study was to compare the efficacy of a gradual KD initiation with the standard KD initiation preceded by a 24‐ to 48‐h fast.

Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet.

BACKGROUND The ketogenic diet (KD) is a high-fat, low-carbohydrate, and protein diet that effectively treats intractable epilepsy (IE). OBJECTIVE The purpose of this study was to measure the change in bone mineral content (BMC) in children with IE treated with the KD for 15 mo. DESIGN Prepubertal children >or=5 y of age with IE were eligible. A 4:1 ketogenic diet was maintained for 15 mo, and whole-body and spine BMCs were measured with dual-energy X-ray absorptiometry. Z scores were generated by comparing the children with IE with a cohort of 847 healthy children. Other measurements included demographics, anthropometry, serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, electrolytes, and dietary intake. All measurements were performed at baseline and at 3, 6, 12, and 15 mo. Longitudinal mixed effects models were used to analyze change in BMC over time. RESULTS Twenty-five children (9 girls, 16 boys) with IE [age (x +/- SD): 7.3 +/- 1.9 y] participated. Growth and bone health status were suboptimal as were serum 25-OHD concentrations and dietary intake of calcium and vitamin D. Whole-body and spine BMC-for-age both declined by 0.6 z score/y and whole-body and spine BMC-for-height declined 0.7 z score/y and 0.4 z score/y, respectively. Height declined 0.5 z score/y. Body mass index (BMI; in kg/m(2)) z score, age, and ambulation were positive predictors of BMC, which declined sharply over 15 mo of KD treatment. CONCLUSION Bone health in children with IE was poor, particularly for younger nonambulatory children with low BMI status. The KD resulted in progressive loss of BMC. The mechanism is unclear. Further studies are needed.

Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia.

Summary:  Purpose: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET.

Selenium Deficiency Associated with Cardiomyopathy : A Complication of the Ketogenic Diet

Summary:  Purpose: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy.

Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet.

Summary:  Purpose: The aim of this study was to describe vitamin D status in children with intractable epilepsy prescribed newer antiepileptic drugs (AEDs) before initiation of and during 15‐month treatment with the ketogenic diet (KD).

The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus

Prolonged status epilepticus (SE) can be refractory to conventional interventions, with high rates of subsequent morbidity and mortality. A high fat, low protein, low carbohydrate ketogenic diet (KD) has been used successfully to treat intractable epilepsy. However, its possible role in prolonged SE has not been well described. We report successful use of the KD in two adult patients with prolonged nonconvulsive SE (NCSE) refractory to multiple other interventions. Our observations suggest induction of ketosis may be a novel strategy to safely and effectively treat status in adults even after weeks to months of refractory seizures. Although there are few data regarding the use of the ketogenic diet in the treatment of adult epilepsy syndromes, it may be an option for the treatment of adults with refractory, prolonged SE.

TREATMENT OF ACQUIRED EPILEPTIC APHASIA WITH THE KETOGENIC DIET

Acquired epileptic aphasia remains a poorly understood entity, which is frequently difficult to treat. Previously described treatment modalities have included antiepileptic drugs, corticosteroids, intravenous immunoglobulin, and multiple subpial transections. We describe three patients with acquired epileptic aphasia refractory to traditional treatments who were successfully treated with the ketogenic diet. All three patients had lasting improvement of their language, behavior, and seizures for 26, 24, and 12 months, respectively. This is the first reported series of patients with acquired epileptic aphasia successfully treated with the ketogenic diet, and suggests a new therapeutic alternative for patients with this often difficult-to-treat disorder. (J Child Neurol 1999;14:696-701).

Combined ketogenic diet and vagus nerve stimulation : Rational polytherapy?

Summary:  Objective: The concept of “rational polypharmacy” has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies.

Severe combined immunodeficiency resulting from mutations in MTHFD1.

Folate and vitamin B12 metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.

Early EEG improvement after ketogenic diet initiation

PURPOSE This study examines electroencephalographic (EEG) changes in children with medication resistant epilepsy treated with the ketogenic diet (KD). METHODS Routine EEGs were obtained prior to KD initiation, then one month and three months later. Changes in EEG background slowing and frequency of interictal epileptiform discharges (IEDs) were evaluated using power spectrum analysis and manual determination of spike index. KD responders were compared to non-responders to determine if baseline or early EEG characteristics predicted treatment response (>50% seizure reduction) at three months. RESULTS Thirty-seven patients were evaluated. No differences in baseline EEG features were found between responder groups. Frequency of IEDs declined in 65% of patients as early as one month, by a median of 13.6% (IQR 2-33). Those with a ten percent or greater improvement in IED frequency at one month were greater than six times more likely to be KD responders (OR 6.5 95% CI 0.85-75 p=0.03). Qualitative and quantitative measures of EEG background slowing improved in the whole cohort, but did not predict responder status. CONCLUSION Baseline predictors of KD response remain elusive. Most patients experienced a reduction in IEDs and improvement in EEG background slowing after KD initiation. Reduction of IEDs at one month strongly predicted KD responder status at three months.