A precision approach to therapeutic drug monitoring of valproate to evaluate markers of toxicity

Abstract

Objective

Treatment with valproic acid (VPA) is associated with risk of liver toxicity. The aim of this study was to use a precision approach to investigate pharmacokinetic variability of both total and unbound serum concentrations of VPA and perform complementary biochemical analyses to evaluate possible markers of toxicity in a clinical setting.

Methods

Therapeutic drug monitoring (TDM) data (2018–2022) including total and free unbound serum concentrations of VPA, measurements of concomitantly used antiseizure medications, and biochemical analyses of ammonia and liver enzymes were ...

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Striatal interdependencies in focal seizures: Insights from stereoelectroencephalographic functional connectivity analysis

Abstract

Objective

We investigated the interdependency between striatal activity and the electrophysiological dynamics of the cortical epileptogenic zone using intracerebral stereoelectroencephalographic recordings in patients with drug-resistant epilepsy. We performed both qualitative and quantitative analyses of ictal striatal activity and its synchronization with the cerebral cortex to gain deeper insight into the striatal contribution to seizure regulation.

Methods

Thirty-one patients were retrospectively included. The Epileptogenicity Index (EI) was computed, high EI values corresponded to structures in the epileptogenic zone (EZ), and brain regions with sustained ...

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Comparative effectiveness of second‐line treatments for epileptic spasms

Abstract

Objective

This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS).

Methods

Infants aged 2–24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high-dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis. Treatment ...

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Neuropsychological and neurobehavioral outcomes of responsive neurostimulation in epilepsy: A systematic review and meta‐analysis

Abstract

Objective

The Responsive Neurostimulation System (RNS) is a US Food and Drug Administration-approved closed-loop brain neurostimulation device for patients with drug-resistant epilepsy. Given the cognitive/neurobehavioral impact of epilepsy and the putative neuroplasticity with neuromodulation, we aimed to understand the effect of RNS on cognition.

Methods

We systematically searched four databases, PubMed/Medline, EMBASE, Web of Science, and Cochrane, from inception until April 2025. Primary outcomes were neuropsychological tests in global intellectual functioning and across five cognitive domains: language, memory, executive functioning, visuospatial functioning, and ...

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GABRA2‐related encephalopathy: Identification of two phenotypes with distinctive electroclinical features

Abstract

Pathogenic variants in γ-aminobutyric acid type A (GABAA) receptor subunit genes are increasingly associated with epilepsy and neurodevelopmental disorders. Pathogenic variants in GABRA2, encoding the α-2 subunit of GABAA receptors, have been recently reported. This study aims to better delineate the phenotypic spectrum of GABRA2 pathogenic variants. We conducted a retrospective multicenter study, analyzing six new patients with GABRA2 pathogenic variants identified through a French national collaboration. Clinical, electroencephalographic (EEG), and genetic data were reviewed alongside a literature analysis of ...

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Dysmorphic neurons with ultralow intrinsic excitability are paradoxically hyperexcitable in neural network in a mouse model of focal cortical dysplasia type II

Abstract

Objective

Focal cortical dysplasia type II (FCDII) is one of the most common causes of refractory epilepsy. Hyperactivated mechanistic target of rapamycin (mTOR) pathway resulting from genetic mutations underlies FCDII, but it remains controversial and poorly understood whether the dysmorphic neurons play a role in cortical hyperexcitability.

Methods

Here, we performed whole-cell recordings from dysmorphic neurons and nearby normal-appearing neurons in an FCDII mouse model with a PIK3CA mutation to examine intrinsic excitability and excitatory/inhibitory (E/I) synaptic inputs. To decipher the net effects ...

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Malformations of cortical development: Embryology and epilepsy

Abstract

One in seven patients with focal epilepsy has a malformation of cortical development (MCD) as underlying cause. Understanding normal cortical development combined with knowledge of where, when, and what goes wrong in different types of MCD provides insight into the mechanisms of epileptogenesis. Three different steps can be distinguished in the development of the neocortex: proliferation, migration, and organization. These three steps occur at different locations, partly overlapping in time. In this review, we illustrate and correlate normal embryology to ...

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Association of maternal epilepsy with perinatal outcomes, and an exploration of prenatal antiseizure medication: A population‐based retrospective cohort study

Abstract

Objective(s)

Pregnancy in women with epilepsy is associated with adverse perinatal outcomes, but debate remains as to role of epilepsy or of prenatal antiseizure medication (ASM), or both. We aimed to investigate the association between maternal epilepsy and perinatal outcomes, and to explore the role of prenatal ASM exposure.

Methods

Retrospective population-based cohort study using linked routinely-collected health data (Scotland, 2009–2021). We included women with at least one singleton pregnancy. Our exposures included (1) maternal epilepsy, identified using International Classification of Diseases, Tenth ...

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Development of a qualitative data analysis codebook for peri‐ictal behavior in suspected functional seizures

Abstract

Objective

Factors that can precipitate and/or prolong functional seizure events are often challenging to identify. We aimed to develop a methodology to investigate peri-ictal behaviors in subjects experiencing functional seizures and those around them in their home environment.

Methods

We conducted an iterative, four-phase process to develop a codebook for operationalizing peri-functional seizure behavior that involved observation of 37 functional seizures across 14 participants in the pre-ictal, ictal, and post-ictal phases. First, researchers reviewed and discussed the literature to devise a conceptual framework. ...

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A multihospital, single health system validation of International Classification of Diseases, 10th Revision, Clinical Modification coding for status epilepticus in the United States

Abstract

Status epilepticus (SE) is a common, life-threatening neurologic emergency. Understanding population-level outcomes after SE requires a validated case definition, yet International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes of SE have not been well-validated in US populations since adoption in 2015. We aimed to determine whether the ICD-10-CM code-based definitions accurately identify SE in the in-hospital setting. The population included all ages (excluding neonates) admitted to a Mount Sinai Health System (MSHS) intensive care unit (ICU) in 2019. ...

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