Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger.

Dichloroacetate (DCA) is a naturally occurring xenobiotic that has been used as an investigational drug for over 50 years. Originally found to lower blood glucose levels and alter fat metabolism in diabetic rats, this small molecule was found to serve primarily as a pyruvate dehydrogenase kinase inhibitor. Pyruvate dehydrogenase kinase inhibits pyruvate dehydrogenase complex, the catalyst for oxidative decarboxylation of pyruvate to produce acetyl coenzyme A.

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus.

Using approximations based on presumed U.S. time zones, we characterized day and nighttime seizure patterns in a patient-reported database, Seizure Tracker.

New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and Outcomes.

Background: Many pediatric patients presenting with status epilepticus have no history of seizures.

Methods: We retrospectively analyzed the clinical characteristics of patients aged one month to 21 years who presented during six consecutive years with convulsive status epilepticus and without a history of seizures. New-onset refractory status epilepticus was defined as status epilepticus refractory to two lines of treatment, without an identified cause in the first 48 hours.

Phenotype of GABA-transaminase deficiency.

Objective: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype.

Methods: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil.

Results: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth.

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency.

The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity.

A pediatric epilepsy diagnostic tool for use in resource-limited settings: A pilot study.

Objective: It is estimated that nearly 80% of the 50 million people affected with epilepsy globally live in regions where specialist care and diagnostic tests are scarce and care is often delivered through a primary health provider with limited training. To improve diagnostic accuracy of the history and physical examination, we developed and piloted a questionnaire to discriminate between focal versus generalized epilepsy, with the future goal to guide medication choices.

Methods: Through literature review and retrospective chart review of 75 children with epilepsy at Boston Children's Hospital, a 15-item questionnaire was developed.

Effectiveness of once-daily high-dose ACTH for infantile spasms.

There is insufficient evidence to recommend a specific protocol for treatment of infantile spasms (IS) and a lack of standardization among, and even within, institutions. Twice-daily dosing (for the first two weeks) of high-dose natural ACTH for IS is used by many centers and recommended by the National Infantile Spasms Consortium (NISC). Conversely, it is our practice to use once-daily dosing of high-dose natural ACTH for IS.

Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

Background: Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access.

Methods: Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed.

Addressing the growing cancer burden in the wake of the AIDS epidemic in Botswana: The BOTSOGO collaborative partnership.

Botswana has experienced a dramatic increase in HIV-related malignancies over the past decade. The BOTSOGO collaboration sought to establish a sustainable partnership with the Botswana oncology community to improve cancer care. This collaboration is anchored by regular tumor boards and on-site visits that have resulted in the introduction of new approaches to treatment and perceived improvements in care, providing a model for partnership between academic oncology centers and high-burden countries with limited resources.

Assessment of techniques used to evaluate the effect of posture and cardiac output on cerebral autoregulation.

In this study, the role of cardiac output in Cerebral Autoregulation was assessed. Mean arterial pressure, cerebral blood flow velocity (middle and anterior cerebral artery), stroke volume, cardiac output, total peripheral resistance and cerebral autoregulatory index were assessed in 3 healthy young males and 4 healthy young females during seated and upright thigh cuff testing. Two different methods (long axis left ventricular echocardiography and Modelflow) of evaluating stroke volume and cardiac output were compared.