Current state of the epilepsy drug and device pipeline.

The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well-tolerated treatments, but also precision treatments for rare epilepsies and seizure-monitoring devices. We summarize major recent and ongoing innovations in diagnostic and therapeutic products presented at the seventeenth Epilepsy Therapies & Diagnostics Development (ETDD) conference, which occurred May 31 to June 2, 2023, in Aventura, Florida. Therapeutics under development are targeting genetics, ion channels and other neurotransmitters, and many other potentially first-in-class interventions such as stem cells, glycogen metabolism, cholesterol, the gut microbiome, and novel modalities for delivering electrical neuromodulation.

Challenges and directions in epilepsy diagnostics and therapeutics: Proceedings of the 17th Epilepsy Therapies and Diagnostics Development conference.

Substantial efforts are underway toward optimizing the diagnosis, monitoring, and treatment of seizures and epilepsy. We describe preclinical programs in place for screening investigational therapeutic candidates in animal models, with particular attention to identifying and eliminating drugs that might paradoxically aggravate seizure burden. After preclinical development, we discuss challenges and solutions in the design and regulatory logistics of clinical trial execution, and efforts to develop disease biomarkers and interventions that may be not only seizure-suppressing, but also disease-modifying. As disease-modifying treatments are designed, there is clear recognition that, although seizures represent one critical therapeutic target, targeting nonseizure outcomes like cognitive development or functional outcomes requires changes to traditional designs. This reflects our increasing understanding that epilepsy is a disease with profound impact on quality of life for the patient and caregivers due to both seizures themselves and other nonseizure factors. This review examines selected key challenges and future directions in epilepsy diagnostics and therapeutics, from drug discovery to translational application.

Rare Spontaneous Attenuation of Childhood Inflammatory Cerebral Adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a neurodegenerative peroxisomal disorder with variable clinical phenotypes. Childhood cerebral ALD (CCALD) is at the most severe end of the disease spectrum. In CCALD, the clinical manifestations include increasing deficits in behavior, vision, hearing, coordination, and motor function, as well as seizures. Without treatment, CCALD often results in apparent vegetative state within 1 to 2 years of appearance of initial signs and symptoms. We present the case of a boy with classic inflammatory CCALD who exhibited spontaneous attenuation in disease progression. While extremely rare, spontaneous arrest of disease progression may occur in boys with inflammatory CCALD.

Natural history of conduction abnormalities in a patient with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is a rare mitochondrial disorder characterized by large-scale deletion or rearrangement of mitochondrial DNA, which is usually not inherited but occur spontaneously probably at the germ cell level or very early in embryonic development by Mehndiratta et al. (Neurol India 50:162-167, 2002). Neuromuscular and cardiac conduction abnormalities are most commonly involved in these patients, which may have subtle presenting signs.

Fasciculations in Children.

Fasciculations are the most common form of spontaneous muscle contraction. They frequently occur in healthy individuals. However, there are a minority of situations that fasciculations are observed in association with specific neurologic disorders. Publications concerning the evaluation of pediatric patients experiencing fasciculations are limited. These children may undergo invasive or expensive diagnostic investigations that are unnecessary. Moreover, without careful consideration of differential diagnoses, rare neuromuscular disorders that present with fasciculations in the pediatric age group can be under-recognized by pediatric neurologists. This review examines the most important pediatric disorders presenting with fasciculations and other spontaneous muscle contractions to guide pediatric neurologists in evaluating these children.

Hereditary Neuropathy with Liability to Pressure Palsies.

Investigators from 4 pediatric hospitals in Canada analyzed the clinical presentation and electrophysiological data of 12 children with hereditary neuropathy with liability to pressure palsies (HNPP), caused by PMP22 gene deletion.