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European Heart Journal. Case Reports May 2024Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent...
BACKGROUND
Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent pacing should be avoided whenever possible. Cardioneuroablation may obviate the need for a pacemaker in well-selected patients.
CASE SUMMARY
A previously healthy 24-year-old woman was referred to the emergency department after recurrent episodes of transient loss of consciousness (TLOC). The electrocardiogram (ECG) and the echocardiogram were normal. An electroencephalogram (EEG) showed intermittent, generalized pathological activity. During EEG under photostimulation, the patient developed a short-term TLOC followed by brachial myocloni, while the concurrent ECG registered a progressive bradycardia, which turned into a complete atrioventricular block and sinus arrest with asystole for 14 s. Immediately after, the patient regained consciousness without sequelae. The episode was interpreted as cardioinhibitory convulsive syncope. However, due to the pathological EEG findings, an underlying epilepsy with ictal asystole could not be fully excluded. Therefore, an antiseizure therapy was also started. After discussing the consequences of pacemaker implantation, the patient agreed to undergo a cardioneuroablation and after 72 h without complications, she was discharged home. At 10 months, the patient autonomously discontinued the antiepileptics. The follow-up EEG displayed unspecific activities without clinical correlations. An implantable loop recorder didn't show any relevant bradyarrhythmia. At 1-year follow-up, the patient remained asymptomatic and without syncopal episodes.
DISCUSSION
Reflex syncope must be considered in the differential diagnosis of seizures. The cardioneuroablation obviated the need for a pacemaker and allowed for the withdrawal of anticonvulsants, originally started on the premise of seizure.
PubMed: 38807945
DOI: 10.1093/ehjcr/ytae256 -
Biomedicines May 2024Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug indicated as monotherapy for adults with newly diagnosed epilepsy and as adjunctive therapy for...
Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug indicated as monotherapy for adults with newly diagnosed epilepsy and as adjunctive therapy for the treatment of partial seizures. Our aim was to assess the effectiveness and safety of both acute and repeated ESL administration against reflex audiogenic seizures, as shown by the Genetic Audiogenic Seizures Hamster from Salamanca (GASH/Sal). Animals were subject to the intraperitoneal administration of ESL, applying doses of 100, 150 and 200 mg/kg for the acute study, whereas a daily dose of 100 mg/kg was selected for the subchronic study, which lasted 14 days. In both studies, the anticonvulsant effect of the therapy was evaluated using neuroethological methods. To assess the safety of the treatment, behavioral tests were performed, hematological and biochemical liver profiles were obtained, and body weight was monitored. In addition, the ESL levels in blood were measured after the acute administration of a 200 mg/kg dose. Treatment with ESL caused a reduction in seizure severity. No statistically significant differences were detected between the selected doses or between the acute or repeated administration of the drug. To summarize, the intraperitoneal administration of ESL is safe and shows an anticonvulsant effect in the GASH/Sal.
PubMed: 38791083
DOI: 10.3390/biomedicines12051121 -
Cureus Mar 2024We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted...
We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted family history of tremulous movements. Yet the characteristics of his finger movements were irregular and not typical of essential tremor (ET). Electrophysiological examinations, including video EEG, showed no epileptic discharges, and brain MRI results were normal. However, somatosensory evoked potentials (SEP) revealed the presence of giant SEP, and a positive cortical (C)-reflex was observed, leading to a clinical diagnosis of benign adult familial myoclonus epilepsy (BAFME). Management with valproic acid and perampanel resulted in a significant reduction of symptoms. This case highlights the necessity of considering BAFME in the differential diagnosis for atypical tremorous finger movements, especially with a relevant family history, and the critical role of electrophysiological findings indicative of cortical hyperexcitability.
PubMed: 38629017
DOI: 10.7759/cureus.56303 -
Frontiers in Neurology 2024The gene encodes synapsin I, variants within the gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies...
The gene encodes synapsin I, variants within the gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with variants and explores the genotype-phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties. His elder brother exhibited a distinct clinical phenotype, experiencing sudden seizures during sleep at the age of 16, accompanied by hippocampal sclerosis. Whole exome sequencing (WES) confirmed a pathogenic variant, c.1647_1650dup (p. Ser551Argfs*134), inherited in an X-linked manner from their mother. Notably, this variant displayed diverse clinical phenotypes in the two brothers and one previously reported case in the literature. Retrospective examination of variants revealed an association between truncating variants and the pathogenicity of REs, and non-truncating variants are more related to developmental delay/intellectual disability (DD/ID). In summary, this study contributes to understanding complex neurodevelopmental disorders associated with , highlighting the clinical heterogeneity of gene variants and emphasizing the necessity for comprehensive genetic analysis in elucidating the pathogenic mechanisms of such diseases.
PubMed: 38576531
DOI: 10.3389/fneur.2024.1359287 -
Frontiers in Pain Research (Lausanne,... 2024Cluster headache (CH) is one of the worst primary headaches that remain underdiagnosed and inappropriately treated. There are recent advances in the understanding of... (Review)
Review
Cluster headache (CH) is one of the worst primary headaches that remain underdiagnosed and inappropriately treated. There are recent advances in the understanding of this disease and available treatments. This paper aims to review CH's recent clinical and pathophysiological findings, diagnosis, and treatment. We performed a narrative literature review on the socio-demographics, clinical presentations, pathophysiological findings, and diagnosis and treatment of CH. CH affects 0.1% of the population with an incidence of 2.07-9.8/100,00 person-years-habitants, a mean prevalence of 53/100,000 inhabitants (3-150/100,000 inhabitants). The male-to-female ratio remains inconclusive, as the ratio of 4.3:1 has recently been modified to 1.3-2.6, possibly due to previous misdiagnosis in women. Episodic presentation is the most frequent (80%). It is a polygenetic and multifactorial entity that involves dysfunction of the trigeminovascular system, the trigeminal autonomic reflex, and the hypothalamic networks. An MRI of the brain is mandatory to exclude secondary etiologies. There are effective and safe pharmacological treatments oxygen, sphenopalatine, and great occipital nerve block, with the heterogeneity of clinical trial designs for patients with CH divided into acute, transitional, or bridge treatment (prednisone) and preventive interventions. In conclusion, CH remains underdiagnosed, mainly due to a lack of awareness within the medical community, frequently causing a long delay in reaching a final diagnosis. Recent advances in understanding the principal risk factors and underlying pathophysiology exist. There are new therapeutic possibilities that are effective for CH. Indeed, a better understanding of this challenging pathology will continue to be a subject of research, study, and discoveries in its diagnostic and therapeutic approach.
PubMed: 38524268
DOI: 10.3389/fpain.2024.1373528 -
International Journal of Molecular... Feb 2024The aim of this study was to investigate the comparative antiseizure activity of the -enantiomers of ,-fenfluramine and ,-norfenfluramine and to evaluate the...
The aim of this study was to investigate the comparative antiseizure activity of the -enantiomers of ,-fenfluramine and ,-norfenfluramine and to evaluate the relationship between their concentration in plasma and brain and anticonvulsant activity. ,-Fenfluramine, ,-norfenfluramine and their individual enantiomers were evaluated in the mouse maximal electroshock seizure (MES) test. ,-Fenfluramine, ,-norfenfluramine and their individual -enantiomers were also assessed in the DBA/2 mouse audiogenic seizure model. All compounds were administered intraperitoneally. Brain and plasma concentrations of the test compounds in DBA/2 mice were quantified and correlated with anticonvulsant activity. In the MES test, fenfluramine, norfenfluramine and their enantiomers showed comparable anticonvulsant activity, with ED values between 5.1 and 14.8 mg/kg. In the audiogenic seizure model, -norfenfluramine was 9 times more potent than ,-fenfluramine and 15 times more potent than -fenfluramine based on ED (1.2 vs. 10.2 and 17.7 mg/kg, respectively). Brain concentrations of all compounds were about 20-fold higher than in plasma. Based on brain EC values, -norfenfluramine was 7 times more potent than ,-fenfluramine and 13 times more potent than -fenfluramine (1940 vs. 13,200 and 25,400 ng/g, respectively). EC values for metabolically formed ,-norfenfluramine and -norfenfluramine were similar to brain EC values of the same compounds administered as such, suggesting that, in the audiogenic seizure model, the metabolites were responsible for the antiseizure activity of the parent compounds. Because of the evidence linking -norfenfluramine to ,-fenfluramine to cardiovascular and metabolic adverse effects, their -enantiomers could potentially be safer follow-up compounds to ,-fenfluramine. We found that, in the models tested, the activity of -fenfluramine and -norfenfluramine was comparable to that of the corresponding racemates. Based on the results in DBA/2 mice and other considerations, -norfenfluramine appears to be a particularly attractive candidate for further evaluation as a novel, enantiomerically pure antiseizure medication.
Topics: Mice; Animals; Fenfluramine; Norfenfluramine; Anticonvulsants; Follow-Up Studies; Mice, Inbred DBA; Epilepsy, Reflex; Seizures
PubMed: 38473769
DOI: 10.3390/ijms25052522 -
International Journal of Molecular... Jan 2024To explore the processes of epileptogenesis/ictogenesis, this study determined the age-dependent development of the functional abnormalities in astroglial transmission...
To explore the processes of epileptogenesis/ictogenesis, this study determined the age-dependent development of the functional abnormalities in astroglial transmission associated with pannexin1-hemichannel using a genetic rat model of autosomal dominant sleep-related hypermotor epilepsy (ADSHE) named 'S286L-TG'. Pannexin1 expression in the plasma membrane of primary cultured cortical astrocytes and the orbitofrontal cortex (OFC), which is an ADSHE focus region, were determined using capillary immunoblotting. Astroglial D-serine releases induced by artificial high-frequency oscillation (HFO)-evoked stimulation, the removal of extracellular Ca, and the P2X7 receptor agonist (BzATP) were determined using ultra-high performance liquid chromatography (UHPLC). The expressions of pannexin1 in the plasma membrane fraction of the OFC in S286L-TG at four weeks old were almost equivalent when compared to the wild type. The pannexin1 expression in the OFC of the wild type non-statistically decreased age-dependently, whereas that in S286L-TG significantly increased age-dependently, resulting in relatively increasing pannexin1 expression from the 7- (at the onset of interictal discharge) and 10-week-old (after the ADSHE seizure onset) S286L-TG compared to the wild type. However, no functional abnormalities of astroglial pannexin1 expression or D-serine release through the pannexin1-hemichannels from the cultured astrocytes of S286L-TG could be detected. Acutely HFO-evoked stimulation, such as physiological ripple burst (200 Hz) and epileptogenic fast ripple burst (500 Hz), frequency-dependently increased both pannexin1 expression in the astroglial plasma membrane and astroglial D-serine release. Neither the selective inhibitors of pannexin1-hemichannel (10PANX) nor connexin43-hemichannel (Gap19) affected astroglial D-serine release during the resting stage, whereas HFO-evoked D-serine release was suppressed by both inhibitors. The inhibitory effect of 10PANX on the ripple burst-evoked D-serine release was more predominant than that of Gap19, whereas fast ripple burst-evoked D-serine release was predominantly suppressed by Gap19 rather than 10PANX. Astroglial D-serine release induced by acute exposure to BzATP was suppressed by 10PANX but not by Gap19. These results suggest that physiological ripple burst during the sleep spindle plays important roles in the organization of some components of cognition in healthy individuals, but conversely, it contributes to the initial development of epileptogenesis/ictogenesis in individuals who have ADSHE vulnerability via activation of the astroglial excitatory transmission associated with pannexin1-hemichannels.
Topics: Animals; Rats; Astrocytes; Connexin 43; Epilepsy, Reflex; Prefrontal Cortex; Serine; Sleep; Connexins
PubMed: 38338895
DOI: 10.3390/ijms25031619 -
International Journal of Molecular... Jan 2024Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are...
Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are resistant to PB. Previous animal studies have shown that in postnatal day P7 mice pups with ischemic stroke induced by unilateral carotid ligation, the tyrosine receptor kinase B (TrkB) antagonist ANA12 (N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide, 5 mg/kg) improved the efficacy of PB in reducing seizure occurrence. To meet optimal standards of effectiveness, a wider range of ANA12 doses must be tested. Here, using the unilateral carotid ligation model, we tested the effectiveness of higher doses of ANA12 (10 and 20 mg/kg) on the ability of PB to reduce seizure burden, ameliorate cell death (assessed by Fluoro-Jade staining), and affect neurodevelopment (righting reflex, negative geotaxis test, open field test). We found that a single dose of ANA12 (10 or 20 mg/kg) given 1 h after unilateral carotid ligation in P7 pups reduced seizure burden and neocortical and striatal neuron death without impairing developmental reflexes. In conclusion, ANA12 at a range of doses (10-20 mg/kg) enhanced PB effectiveness for the treatment of perinatal ischemia-related seizures, suggesting that this agent might be a clinically safe and effective adjunctive agent for the treatment of pharmacoresistant neonatal seizures.
Topics: Animals; Mice; Anticonvulsants; Animals, Newborn; Disease Models, Animal; Seizures; Phenobarbital; Epilepsy; Ischemia; Hypoxia-Ischemia, Brain
PubMed: 38338726
DOI: 10.3390/ijms25031447 -
Clinical Neurophysiology : Official... Mar 2024Investigate sleep and temporal lobe epilepsy (TLE) effects on brain networks derived from electroencephalography (EEG).
OBJECTIVE
Investigate sleep and temporal lobe epilepsy (TLE) effects on brain networks derived from electroencephalography (EEG).
METHODS
High-density EEG was recorded during non-rapid eye movement (NREM) sleep stage 2 (N2) and wakefulness in 23 patients and healthy controls (HC). Epochs without epileptic discharges were source-reconstructed in 72 brain regions and connectivity was estimated. We calculated network integration and segregation at global (global efficiency, GE; average clustering coefficient, avgCC) and hemispheric level. These were compared between groups across frequency bands and correlated with the individual proportion of wakefulness- or sleep-related seizures.
RESULTS
At the global level, patients had higher delta GE, delta avgCC and theta avgCC than controls, irrespective of the vigilance state. During wakefulness, theta GE of patients was higher than controls and, for patients, theta GE during wakefulness was higher than during N2. Wake-to-sleep differences in TLE were notable only in the ipsilateral hemisphere. Only measures from wakefulness recordings correlated with the proportion of wakefulness- or sleep-related seizures.
CONCLUSIONS
TLE network alterations are more prominent during wakefulness and at lower frequencies. Increased integration and segregation suggest a pathological 'small world' configuration with a possible inhibitory role.
SIGNIFICANCE
Network alterations in TLE occur and are easier to detect during wakefulness.
Topics: Humans; Epilepsy, Temporal Lobe; Eye Movements; Wakefulness; Epilepsy, Reflex; Sleep; Seizures
PubMed: 38335766
DOI: 10.1016/j.clinph.2024.01.003 -
Neurologia Apr 2024Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a...
INTRODUCTION
Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship.
OBJECTIVE
Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy.
METHODS
We conducted a cross-sectional study of patients under 18 years of age with epilepsy, assessing sleep disorders using the Spanish-language version of the Sleep Disturbance Scale for Children (SDSC), and sleep habits using an original questionnaire.
RESULTS
The sample included 153 patients. Eighty-four percent of our sample presented some type of sleep alteration. The most frequent alterations were sleep-wake transition disorders (53%), sleep initiation and maintenance disorders (47.7%), and daytime sleepiness (44.4%). In 70% of cases, the patients' parents reported that their child "slept well," although sleep disorders were detected in up to 75.7% of these patients. Many patients had poor sleep habits, such as using electronic devices in bed (16.3%), requiring the presence of a family member to fall asleep (39%), or co-sleeping or sharing a room (23.5% and 30.5%, respectively). Those with generalised epilepsy, refractory epilepsy, nocturnal seizures, and intellectual disability were more likely to present sleep disorders. In contrast, poor sleep habits were frequent regardless of seizure characteristics.
CONCLUSIONS
Sleep disorders and poor sleep habits are common in children with epilepsy. Their treatment can lead to an improvement in the quality of life of the patient and his/her family, as well as an improvement in the prognosis of epilepsy.
Topics: Humans; Child; Male; Female; Adolescent; Cross-Sectional Studies; Quality of Life; Sleep; Sleep Wake Disorders; Epilepsy, Reflex
PubMed: 38307413
DOI: 10.1016/j.nrleng.2024.01.011