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Epilepsia Jun 2024A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape...
OBJECTIVES
A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts.
METHODS
In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results.
RESULTS
These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed.
SIGNIFICANCE
An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical "treatment gap."
PubMed: 38943543
DOI: 10.1111/epi.18030 -
Epileptic Disorders : International... Jun 2024
PubMed: 38943531
DOI: 10.1002/epd2.20257 -
Epileptic Disorders : International... Jun 2024Pupillary changes can be an important semiologic feature in focal epilepsy. Though the subcortical networks involving pupillomotor function have been described, cortical...
Pupillary changes can be an important semiologic feature in focal epilepsy. Though the subcortical networks involving pupillomotor function have been described, cortical generators of pupillary dilation and constriction in humans are not well known. In this report, we describe a case of pupillary constriction occurring during seizures in a patient with drug resistant focal epilepsy. On stereoelectroencephalography, onset was noted within the posterior segment of the right intraparietal sulcus and direct cortical electrical stimulation of these electrode contacts reproduced pupillary constriction associated with habitual seizures. This is the first case report to describe ictal pupillary constriction during SEEG with confirmation of the cortical localization by direct cortical electrical stimulation. The posterior segment of the right intraparietal sulcus localization of pupillary constriction may aid in surgical evaluation patients with drug resistant focal epilepsy.
PubMed: 38943530
DOI: 10.1002/epd2.20252 -
Epilepsia Jun 2024To investigate the repercussions of the war in Ukraine on people with epilepsy (PWE), focusing on access to health care, seizure control, quality of life (QoL),...
OBJECTIVE
To investigate the repercussions of the war in Ukraine on people with epilepsy (PWE), focusing on access to health care, seizure control, quality of life (QoL), psychological distress, anxiety, and depression; and to identify the key factors influencing these measures.
METHODS
Consecutive PWE, ≥18 years of age, presenting to one of seven health centers across Ukraine were invited to complete a self-administered survey in 2023. The survey gathered information on clinical and demographic aspects, geographic displacement, and access to care and medications. It also contained five valid questionnaires exploring psychological distress (Kessler-10), QoL with the EuroQOL-5D-5L (EQ-5D-5L), depression with the Neurological Disorders in Epilepsy scale (NDDIE), anxiety with the Hospital Anxiety and Depression Scalae-Anxiety (HADS-A), and epilepsy severity with the Global Assessment of the Severity of Epilepsy scale (GASE). Multivariate linear regression models assessed the relationship between measures of mental health and QoL and their potential predictors. Ethical approval was obtained from the Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, Ukraine.
RESULTS
Among 305 participants (mean age 38 years), 40% were female and 44% had to change residence because of the war. Seizures worsened during the war in 52% of those with active epilepsy and 42% of those with well-controlled epilepsy. Difficulties accessing health care and anti-seizure medications occurred in 25% and 34% of PWE, respectively, and was worse among those who were displaced. According to the mental health instruments, 46% suffered psychological distress, 62% experienced anxiety, 50% were depressed, and 59% rated their epilepsy as somewhat severe or worse. Statistically significant predictors of psychological distress, anxiety, and depression included female gender, more severe epilepsy, increased seizures during the war, and requiring mental health support.
SIGNIFICANCE
The war significantly disrupted access to health care and availability of medication in PWE, who suffer from significant anxiety, depression, and psychological distress. We identify high-risk factors that can guide resource allocation for prevention and treatment.
PubMed: 38943522
DOI: 10.1111/epi.18052 -
Epileptic Disorders : International... Jun 2024
PubMed: 38943519
DOI: 10.1002/epd2.20260 -
Epileptic Disorders : International... Jun 2024
PubMed: 38943518
DOI: 10.1002/epd2.20258 -
Epilepsia Jun 2024This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure-free for at least...
OBJECTIVE
This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure-free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post-ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures.
METHODS
We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure-free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures.
RESULTS
Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure-free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post-ischemic stroke epilepsy (odds ratio [OR] = .267, 95% confidence interval [CI] = .075-.946), genetic generalized epilepsy (OR = .559; 95% CI = .319-.978), intellectual disability (OR = 2.768, 95% CI = 1.271-6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056-1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12-month seizure freedom at the last visit.
SIGNIFICANCE
This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure-free patients on their further seizure prognosis.
PubMed: 38943516
DOI: 10.1111/epi.18048 -
Archiv Der Pharmazie Jun 2024Anticonvulsant drug discovery has achieved significant progress; however, pharmacotherapy of epilepsy continues to be a challenge for modern medicine and pharmacy. To...
Anticonvulsant drug discovery has achieved significant progress; however, pharmacotherapy of epilepsy continues to be a challenge for modern medicine and pharmacy. To expand the chemical space of heterocycles as potential antiepileptic agents, herein we report on the synthesis and evaluation of anticonvulsant properties of a series of thiopyrano[2,3-d]thiazoles. The studied heterocycles are characterized by satisfactory drug-likeness and pharmacokinetics properties, calculated in silico using SwissADME. The anticonvulsant activity of thiopyrano[2,3-d]thiazole derivatives was evaluated in vivo using the subcutaneous pentylenetetrazole test. Three hits, that is, compounds 12, 14, and 16, that caused a pronounced anticonvulsant effect were identified. Derivatives 12, 14, and 16 positively affected the latent period of onset of clonic seizures, number of seizures, mortality rate, and duration of the seizure period of animals under experimental conditions. The anticonvulsant properties of compound 14 were equivalent to the effect of the reference drug, sodium valproate. All hit compounds are characterized by satisfying toxicity properties in the human lymphocytes and HEK293 cell line. The most active hit 14 possesses a potential affinity with the GABA receptor in the molecular docking study and forms a stable complex in the molecular dynamics experiments equal to diazepam. Preliminary SAR results were obtained and discussed based on screening data.
PubMed: 38943436
DOI: 10.1002/ardp.202400357 -
Tropical Medicine & International... Jun 2024
PubMed: 38943256
DOI: 10.1111/tmi.14027 -
Biochemical Pharmacology Jun 2024GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily... (Review)
Review
GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore, in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases.
PubMed: 38942087
DOI: 10.1016/j.bcp.2024.116395