ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ1-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6-oxo-pipecolic acid (6-oxo-PIP) also accumulates in the urine, CSF and plasma of ALDH7A1-deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6-oxo-PIP in urine from a cohort of 30 patients where α-AASA was elevated and showed that it was above the normal range in all those above 6 months of age. However, 6-oxo-PIP levels were within the normal range in 33% of the patients below 6 months of age. Levels increased with age and correlated with a decrease in α-AASA levels. Longitudinal analysis of urine samples from ALDH7A1-deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6-oxo-PIP remained elevated whilst α-AASA decreased. Similar to α-AASA, we found that elevated urinary excretion of 6-oxo-PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6-oxo-PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long-term side effects.
- MeSH
- aldehyddehydrogenasa nedostatek genetika MeSH
- biologické markery * moč MeSH
- dítě MeSH
- epilepsie moč MeSH
- kojenec MeSH
- kyselina 2-aminoadipová moč analogy a deriváty MeSH
- kyseliny pipekolové * moč MeSH
- lidé MeSH
- lysin nedostatek moč MeSH
- mitochondriální aldehyddehydrogenasa nedostatek genetika MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- pyridoxin nedostatek moč terapeutické užití MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.
- MeSH
- dítě MeSH
- DNA MeSH
- epilepsie * komplikace MeSH
- fokální kortikální dysplazie * MeSH
- komplex proteinů jaderného póru * MeSH
- lidé MeSH
- midazolam MeSH
- molekulární chaperony * MeSH
- nemoci mozku * MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- refrakterní epilepsie * genetika chirurgie MeSH
- status epilepticus * genetika chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Klíčová slova
- cenobamát,
- MeSH
- antikonvulziva * aplikace a dávkování MeSH
- dospělí MeSH
- epilepsie * chirurgie farmakoterapie MeSH
- klinické rozhodování MeSH
- kvalita života MeSH
- léková rezistence MeSH
- lidé MeSH
- statistika jako téma MeSH
- záchvaty chirurgie farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- cenobamát,
- MeSH
- antikonvulziva * škodlivé účinky terapeutické užití MeSH
- epilepsie farmakoterapie MeSH
- klinická studie jako téma MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
Hypertenze, tedy zvýšení krevního tlaku nad 140/90 mm Hg, je spojena s poškozením řady orgánů. Mezi cílové orgány hypertenze patří i mozek. Klinické projevy zahrnují hypertenzní encefalopatii, syndrom reverzibilní encefalopatie v zadním povodí a cévní mozkové příhody. Chronická hypertenze se podílí na strukturálních a funkční změnách mozkové tkáně, které mohou vyústit v klinicky manifestní postižení kognitivních funkcí a rozvoj demence. Patofyziologický podklad hypertenzí navozeného postižení mozku je komplexní. Časný záchyt hypertenze a její adekvátní léčba jsou klíčové pro snižování rizika vzniku neurologických komplikací.
Hypertension, defined as an increase in blood pressure above 140/90 mmHg, is associated with damage to a number of organs, including the brain. Clinical manifestations include hypertensive encephalopathy, posterior reversible encephalopathy syndrome, and cerebrovascular accidents. Chronic hypertension contributes to structural and functional changes in brain tissue, which can lead to clinically manifest impairment of cognitive functions and the development of dementia. The pathophysiological basis of brain damage induced by hypertension is complex. Early detection of hypertension and its adequate treatment are crucial for reducing the risk of neurological complications.
- MeSH
- antihypertenziva farmakologie terapeutické užití MeSH
- cévní mozková příhoda etiologie farmakoterapie prevence a kontrola MeSH
- eklampsie MeSH
- epilepsie etiologie MeSH
- homeostáza fyziologie MeSH
- hypertenze * komplikace patofyziologie MeSH
- hypertenzní encefalopatie etiologie MeSH
- kognitivní poruchy etiologie MeSH
- lidé MeSH
- nemoci mozku * etiologie MeSH
- syndrom zadní leukoencefalopatie etiologie MeSH
- Check Tag
- lidé MeSH
Syndrom Dravetové je závažnou vývojovou a epileptickou encefalopatií se začátkem v kojeneckém věku, která se projevuje farmakorezistentní epilepsií a četnými komorbiditami. Typická je provokace záchvatů zvýšenou teplotou. Léčba onemocnění je obtížná. V chronické medikaci by měl být první volbou valproát, dalšími přidanými léky klobazam, stiripentol, fenfluramin, kanabidiol, topiramát. Pacienti musí být vybaveni SOS medikací pro zvládnutí záchvatů v domácím prostředí. V léčbě je nutné se vyhnout blokátorům sodíkových kanálů, aplikace fenytoinu v epileptickém statu je však přípustná. Kromě protizáchvatové léčby je nutné věnovat pozornost i nefarmakologické léčbě komorbidit.
Dravet syndrome is a developmental and epileptic encephalopathy starting in infancy and its main features are drug -resistant epilepsy and several co-morbidities. Seizures are typically provoked by increased temperature. The treatment of Dravet syndrome is challenging. The first antiseizure drug should be valproic acid, while clobazam, stiripentol, fenfluramine, canabidiol or topiramate are usually added later. All the patients must have rescue medication for home management of seizures. Sodium channel blockers should not be used for chronic treatment, but phenytoin can be administered to stop status epilepticus. Non-pharmacological treatment of co-morbidities should be addressed as well.
- Klíčová slova
- stiripentol, fenfluramin,
- MeSH
- dioxolany aplikace a dávkování farmakologie terapeutické užití MeSH
- epilepsie myoklonické * farmakoterapie patologie MeSH
- kanabidiol aplikace a dávkování farmakologie terapeutické užití MeSH
- klobazam aplikace a dávkování farmakologie terapeutické užití MeSH
- komorbidita MeSH
- kyselina valproová aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- selektivní inhibitory zpětného vychytávání serotoninu aplikace a dávkování farmakologie terapeutické užití MeSH
- topiramat aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: Precise localization of the epileptogenic zone is critical for successful epilepsy surgery. However, imbalanced datasets in terms of epileptic vs. normal electrode contacts and a lack of standardized evaluation guidelines hinder the consistent evaluation of automatic machine learning localization models. METHODS: This study addresses these challenges by analyzing class imbalance in clinical datasets and evaluating common assessment metrics. Data from 139 drug-resistant epilepsy patients across two Institutions were analyzed. Metric behaviors were examined using clinical and simulated data. RESULTS: Complementary use of Area Under the Receiver Operating Characteristic (AUROC) and Area Under the Precision-Recall Curve (AUPRC) provides an optimal evaluation approach. This must be paired with an analysis of class imbalance and its impact due to significant variations found in clinical datasets. CONCLUSIONS: The proposed framework offers a comprehensive and reliable method for evaluating machine learning models in epileptogenic zone localization, improving their precision and clinical relevance. SIGNIFICANCE: Adopting this framework will improve the comparability and multicenter testing of machine learning models in epileptogenic zone localization, enhancing their reliability and ultimately leading to better surgical outcomes for epilepsy patients.
- MeSH
- dospělí MeSH
- elektrokortikografie metody normy MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- refrakterní epilepsie * chirurgie patofyziologie MeSH
- strojové učení * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hyponatremia is a typical side effect of antiseizure drugs from the dibenzazepine family. The study investigated the prevalence of hyponatremia in patients with epilepsy who were treated with eslicarbazepine. We aimed to determine the prevalence of hyponatremia, reveal the factors leading to the discontinuation of treatment, and identify possible risk factors for the development of hyponatremia including the dose dependency. The medical records of 164 patients with epilepsy taking eslicarbazepine in our center were analyzed. The overall prevalence of hyponatremia was 30.5%. The prevalence of mild hyponatremia, seen in 14%-20% of patients, was not dose dependent. The prevalence of moderate and severe hyponatremia was significantly dose dependent. The severity of hyponatremia was significantly dose dependent. Severe hyponatremia was found in 6.1% of patients. Hyponatremia was asymptomatic in the majority of cases, and in 48% did not require any management. Hyponatremia was the reason for discontinuation in 6.2% of patients. The major risk factor for developing hyponatremia was older age. The study shows that eslicarbazepine-induced hyponatremia is usually mild and asymptomatic. It usually does not require any management and seldom leads to treatment discontinuation. Hyponatremia is dose dependent. Another major risk for developing hyponatremia (besides dose) is older age.
