Anup D. Patel

Quality improvement in neurology: Epilepsy Update Quality Measurement Set.

Epilepsy is a common, debilitating, and costly disease. It is estimated that 2.2 million people in the United States are diagnosed with epilepsy, and 150,000 new cases of epilepsy are diagnosed in the United States annually.1 However, epilepsy prevalence might be underestimated due to numerous social issues that accompany a diagnosis of epilepsy.2 People with epilepsy have poorer overall health status, impaired intellectual and physical functioning, and a greater risk for accidents and injuries.1–3 It is estimated that the annual direct medical cost of epilepsy in the United States is

Pharmacological Treatment of Neonatal Seizures: A Systematic Review

9.6 billion, and this estimate does not include indirect costs from losses in quality of life or productivity.1

GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects

Pharmacologic treatment options for neonatal seizures have expanded over the past 2 decades, and there is no consensus on optimal treatment strategy. We systematically reviewed the published literature to determine which medication(s) are most effective for treating neonatal seizures, by retrieving trials and observational investigations via PubMed (through August 2011) that focused on pharmacological seizure treatment of neonates (≤ 28 days old) and utilized continuous or amplitude-integrated EEG to confirm seizure diagnosis and cessation. Our search identified 557 initial articles and 14 additional studies after reference reviews, with 16 meeting inclusion criteria. Of these, 2 were randomized trials and only 3 additional investigations included comparison groups. We found limited evidence regarding the best pharmacologic treatment for neonatal seizures, but were able to devise a treatment algorithm from available data. These findings have the potential to serve as a clinical reference and to inform the design of comparative effectiveness investigations for neonatal antiepileptics.

Two patients with a GRIN2A mutation and childhood-onset epilepsy.

Background We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Results Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. Conclusions In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies.

Complex Febrile Seizures: A Practical Guide to Evaluation and Treatment

BACKGROUND N-methyl-D-aspartate is a key neurotransmitter within the central nervous system and its dysfunction can play an important role in epilepsy. Mutations of genes involving the N-methyl-D-aspartate receptor have been implicated in a wide variety of neuropsychiatric disorders including epilepsy, specifically, within the glutamate receptor ionotropic N-methyl-D-aspartate 2A (GRIN2A). PATIENTS We report two patients with a glutamate receptor ionotropic N-methyl-D-aspartate 2A mutation who presented with epilepsy. CONCLUSIONS Individuals with a glutamate receptor ionotropic N-methyl-D-aspartate 2A mutation exhibit a broad clinical spectrum.

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome

Febrile seizures are the most common type of childhood seizures, affecting 2% to 5% of children. A complex febrile seizure is one with focal onset, one that occurs more than once during a febrile illness, or one that lasts more than 10 to 15 minutes. Confusion still exists on the proper evaluation of a child presenting with a complex febrile seizure. There are ongoing research attempts to determine the link between complex febrile seizures and epilepsy. Further clarification and understanding of this disorder would be of great benefit to primary care providers and child neurologists.

A Case Series Using a Care Management Checklist to Decrease Emergency Department Visits and Hospitalizations in Children With Epilepsy

Objective To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. Methods Patients aged 4–10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N-desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol). Safety assessments were clinical laboratory tests, physical examinations, vital signs, ECGs, adverse events (AEs), seizure frequency, and suicidality. Results Thirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC0–t). CBD did not affect concomitant AED levels, apart from an increase in N-CLB (except in patients taking stiripentol). The most common AEs on CBD were pyrexia, somnolence, decreased appetite, sedation, vomiting, ataxia, and abnormal behavior. Six patients taking CBD and valproate developed elevated transaminases; none met criteria for drug-induced liver injury and all recovered. No other clinically relevant safety signals were observed. Conclusions Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated. Classification of evidence This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.

Obtaining genetic testing in pediatric epilepsy

Each year, 1 million people are seen in an emergency department for seizures or epilepsy. We implemented a care management checklist for patients with frequent visits. A database was searched for patients with the highest number of emergency department visits and/or unplanned hospitalizations in 2011. Four patients were selected. A care management checklist was implemented in 2012. Compliance with the office visits, number of emergency department visits and/or hospitalizations, and the associated costs were tracked following implementation of the checklist for 2011 and 2012. These 4 epilepsy patients accounted for 46 visits in the year 2011 with associated health care costs of

Variables associated with emergency department and/or unplanned hospital utilization for children with epilepsy

380,209. Following a year using a care management checklist, the same patients accounted for 11 visits with a cost reduction of

Neurological Manifestations of Medical Child Abuse.

188,130. Using a care management checklist was useful in these 4 epilepsy patients to decrease emergency department visits and/or unplanned hospitalizations. A limitation of this study is its small numbers.