Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets.

Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies.

A pharmacogenetic study of perampanel: association between rare variants of glutamate receptor genes and outcomes.

The selection of antiseizure medication usually requires a trial-and-error process. Our goal is to investigate whether genetic markers can predict the outcome of perampanel (PER) use in patients with epilepsy. The studied participants were selected from our previous epilepsy genetics studies where whole exome sequencing was available.

Validating Prediction Tools for Autoimmune Encephalitis in Adult Taiwanese Patients: A Retrospective Study.

Autoimmune encephalitis (AE) is a neurological emergency. We aimed to analyze the application and effectiveness of the currently available prediction tools for AE patients in Taiwan. We retrospectively collected 27 AE patients between January 2008 and December 2019.

The Genetics of Primary Familial Brain Calcification: A Literature Review.

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances.

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control.

Introduction: Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and/or synaptic antigens. We previously demonstrated that S100A6 was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood-brain barrier (BBB). In this study, we focused on the epigenetic regulation of S100A6, the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies.

ADCY5-related dyskinesia: a case report.

Adenylyl cyclase 5 (ADCY5) related dyskinesia is a rare disorder characterized by early-onset paroxysmal choreoathetosis, dystonia, myoclonus, or a combination of the above, which primarily involved the limbs, face, and neck. Other common clinical features are axial hypotonia and episodic exacerbation of dyskinesia. Both sporadic and inherited cases have been reported and the predomiant mode of inheritance is autosomal dominant.

Evaluation of Cardiovascular Concerns of Intravenous Lacosamide Therapy in Epilepsy Patients.

Objective: Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability and epilepsies. In addition to the brain, VGSCs are also abundant enriched in cardiac tissues and are responsible for normal cardiac rhythm. Theoretically, sodium channel blocking antiseizure medications (SCB-ASMs) may have unwanted cardiac side effects.

The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia.

Background: Periventricular nodular heterotopia (PVNH) is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. PVNH often cause epilepsy, psychomotor development or cognition problem. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology.

Response to Sodium Channel blocking Antiseizure medications and coding polymorphisms of Sodium Channel genes in Taiwanese epilepsy patients.

Background: Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs due to altering the effect of ASMs on blocking sodium channels.

Methods: We conducted a retrospective study of epilepsy patients followed up at the Neurological Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan between January 2010 and December 2018.

Hippocampal Malrotation: A Genetic Developmental Anomaly Related to Epilepsy?

Hippocampal malrotation (HIMAL) is an increasingly recognized neuroimaging feature but the clinical correlation and significance in epilepsies remain under debate. It is characterized by rounded hippocampal shape, deep collateral, or occipitotemporal sulcus, and medial localization of the hippocampus. In this review, we describe the embryonic development of the hippocampus and HIMAL, the qualitative and quantitative diagnosis issues, and the pathological findings of HIMAL.

Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study.

Concerns of drug-drug interactions (DDIs) between anti-seizure medications (ASMs) and non-vitamin K oral anticoagulants (NOACs) have emerged in recent case reports and guidelines. Theoretically, the induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme and permeability glycoprotein (P-GP) efflux transporter protein systems may reduce the effect of NOACs. We aimed to investigate whether such DDIs are clinically relevant in a real-world situation.

S100A6 Promotes B Lymphocyte Penetration Through the Blood-Brain Barrier in Autoimmune Encephalitis.

Autoimmune encephalitis (AE) is a severe neurological disease. The brain of the AE patient is attacked by a dysregulated immune system, which is caused by the excessive production of autoantibodies against neuronal receptors and synaptic proteins. AE is also characterized by the uncontrolled B lymphocyte infiltration through the blood-brain barrier (BBB) layer, and the investigation of the underlying mechanism involved in this infiltration may facilitate the discovery of novel therapies for AE.

Predicting the Functional Outcome of Adult Patients with Status Epilepticus.

Patients that survive status epilepticus (SE) may suffer from neurological and cognitive deficits that cause severe disabilities. An effective scoring system for functional outcome prediction may help the clinician in making treatment decisions for SE patients. Three scoring systems, namely the Status Epilepticus Severity Score (STESS), the Epidemiology-Based Mortality Score in Status Epilepticus (EMSE), and the Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), have been developed in the past decade to predict the outcomes of patients with SE.

Perampanel Treatment for Refractory Status Epilepticus in a Neurological Intensive Care Unit.

Background/objective: Perampanel is a novel anti-epileptic drug (AED) which acts as a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist to reduce glutamate-mediated postsynaptic excitation. Previous animal studies and a few case reports/series have suggested that it may be effective to treat refractory status epilepticus (RSE).

Methods: We retrospectively reviewed 67 consecutive patients with RSE, of whom 22 received perampanel.

The Different Clinical Features Between Autoimmune and Infectious Status Epilepticus.

The prognosis of status epilepticus (SE) is highly related to the underlying etiology. Inflammation of the central nervous system (CNS), including infection and autoimmune encephalitis, is one of the treatable conditions causing SE. The initial presentation of infectious and autoimmune CNS disorders can be quite similar, which may be difficult to differentiate at the beginning.

Risk factors for seizures after cranioplasty.

Purpose: Cranioplasty can improve a patient's psychosocial and cognitive functions after decompressive craniectomy, however seizures are a common complication after cranioplasty. The risk factors for early and late seizures after cranioplasty are unclear. This study is to evaluate the risk factors for early and late seizure after cranioplasty.

A Fluorescent Glucose Transport Assay for Screening SGLT2 Inhibitors in Endogenous SGLT2-Expressing HK-2 Cells.

The sodium-dependent glucose transporters 2 (SGLT2) plays important role in renal reabsorption of urinal glucose back to plasma for maintaining glucose homeostasis. The approval of SGLT2 inhibitors for treatment of type 2 diabetes highlights the SGLT2 as a feasible and promising drug target in recent years. Current methods for screening SGLT2 inhibitors are complex, expensive and labor intensive.

Effects of antiepileptic drugs on thyroid hormone function in epilepsy patients.

Purpose: Patients with epilepsy are frequently required to take antiepileptic drugs (AEDs) for a long period of time. Many studies have shown that AEDs have a negative influence on endocrine function including the thyroid gland, however the risk factors for the development of low thyroid function in these patients are unclear. This study aimed to determine the potential risk factors of low thyroid function in patients with epilepsy.

Drug interaction between valproic acid and carbapenems in patients with epileptic seizures.

Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA.

Interictal serum brain-derived neurotrophic factor level reflects white matter integrity, epilepsy severity, and cognitive dysfunction in chronic temporal lobe epilepsy.

Objective: Most patients with temporal lobe epilepsy (TLE) have epileptic foci originating from the medial temporal lobe, particularly the hippocampus. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor mainly expressed in the hippocampus, though it is not known whether the circulating level of BDNF reflects cognitive performance or white matter structural changes in chronic TLE.

Methods: Thirty-four patients with TLE and 22 healthy controls were enrolled for standardized cognitive tests, diffusion tensor imaging, and serum BDNF measurement.

Insula Volume and Salience Network Are Associated with Memory Decline in Parkinson Disease: Complementary Analyses of Voxel-Based Morphometry versus Volume of Interest.

Objective. We investigated structural brain change in subjects with a clinical diagnosis of Parkinson disease with mild cognitive impairment (PD-MCI) and examined its relationship with memory impairment. Methods.

Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled.

Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups.

Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values.