Seizures and premature death in mice with targeted Kv1.1 deficiency in corticolimbic circuits DOI Creative Commons
Kelsey Paulhus, Edward Glasscock

Brain Communications, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 24, 2024

Abstract Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death, likely stemming from seizure activity disrupting vital brain centres controlling heart and breathing function. However, understanding SUDEP's anatomical basis mechanisms remains limited, hampering risk evaluation prevention strategies. Prior studies using a neuron-specific Kcna1 conditional knockout mouse model SUDEP identified primary importance brain-driven contributing to sudden cardiorespiratory dysregulation; yet, underlying neurocircuits have not been identified. Using Emx1-Cre driver, we generated new lacking excitatory neurons cortex, hippocampus, amygdala select vagal afferents. To test whether absence Kv1.1 forebrain corticolimbic circuits sufficient induce spontaneous seizures, premature mortality dysfunction, performed survival EEG, ECG, plethysmography (EEG-ECG-Pleth) recordings. We demonstrate mice. During monitoring, fortuitously captured one event, which showed generalized tonic-clonic that initiated respiratory dysfunction culminating failure. In addition, observed abnormalities are common during non-fatal seizures mice, but mostly absent interictal periods, implying ictal, interictal, impairment as more reliable indicator risk. These results point critical neural substrates affirm seizure-related cardiac failure death.

Язык: Английский

Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception DOI Open Access
Ayse S. Dereli,

Auriane Apaire,

Riëm El Tahry

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1598 - 1598

Опубликована: Фев. 13, 2025

Sudden unexpected death in epilepsy (SUDEP) is a critical concern for individuals suffering from epilepsy, with respiratory dysfunction playing significant role its pathology. Fatal seizures are often characterized by central apnea and hypercapnia (elevated CO2 levels), indicating failure ventilatory control. Research has shown that both human patients animal models exhibit reduced hypercapnic response the interictal (non-seizure) period, suggesting an impaired ability to regulate breathing high levels. This review examines of chemoreceptors-specifically retrotrapezoid nucleus, raphe nuclei, nucleus tractus solitarius, locus coeruleus, hypothalamus this These structures sensing maintaining homeostasis. Emerging evidence also implicates neuropeptidergic pathways within these chemoreceptive regions SUDEP. Neuropeptides like galanin, pituitary adenylate cyclase-activating peptide (PACAP), orexin, somatostatin, bombesin-like peptides may modulate chemosensitivity function, potentially exacerbating during seizures. Understanding mechanisms linking chemoreception, control, signaling essential developing targeted interventions reduce risk SUDEP patients.

Язык: Английский

Процитировано

1

Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation DOI Open Access
Arsen Hunanyan,

Amitesh Verma,

Minu‐Tshyeto Bidzimou

и другие.

Epilepsia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 11, 2025

Abstract Objective This study was undertaken to test the following hypotheses in Atp1a3 Mashl/+ mouse (which carries most common human ATP1A3 (the major subunit of neuronal Na + /K –adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death epilepsy (SUDEP) occurs during seizures and is due terminal apneas some lethal cardiac arrhythmias others; mice have central cardiorespiratory dysregulation abnormal respiratory drive. Methods Comparison made littermate wild‐type groups using (1) simultaneous vivo video‐telemetry recordings electroencephalogram, electrocardiogram, breathing; (2) whole‐body plethysmography; (3) hypoglossal nerve recordings. Results In mice, SUDEP consistently occurred that were more severe than preterminal seizures; seizure clustering periods preceding SUDEP; slowing breathing rate (BR) heart observed preictally before (4) sequence as follows: bradypnea with bradycardia/cardiac arrhythmias, then apnea, followed by arrhythmias. Compared wild‐type, mutants showed resting BR variability but no difference PR, QRS, QTc, or RR intervals; firing response hypoxia; plethysmography, consisting baseline predisposition apnea responses challenge. Significance , an alternating hemiplegia childhood (AHC) model, also a revealing model ‐ATPase mutation resulting drive progressive concurrent worsening epilepsy. results from seizure‐triggered bradypnea/bradycardia Because many epilepsy/SUDEP models other etiologies manifest secondary ATPase deficiency, future studies those may benefit considering possible contributions dysfunction too.

Язык: Английский

Процитировано

0

Pathophysiology of SUDEP: How far are we from understanding? DOI Creative Commons

E Boglietti,

Diane N. Haddad, Laurent Bezin

и другие.

Revue Neurologique, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Sudden and unexpected death in epilepsy patients (SUDEP) is the leading cause of suffering from drug-resistant epilepsy. A significant number studies have been conducted both animal models to examine initial cascade events that directly as well factors contribute long-term risk SUDEP. This review aims discuss main pathophysiological hypotheses are currently considered clinical pre-clinical Studies highlighted SUDEP typically triggered by a seizure, with central fatal apnea primary death. Findings also suggest chronic impairments respiratory regulation may risk, serotonin dysfunction playing key role associated abnormalities. These insights on pathophysiology better assessment, though gaps remain understanding precise mechanisms linking transient peri-ictal dysfunction.

Язык: Английский

Процитировано

0

SUDEP Case-Control Study Nested in a Prospective Cohort of Drug-Resistant Focal Epilepsy DOI
Philippe Ryvlin,

Margaux Huot,

Luc Valton

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Lethal Interactions of neuronal networks in epilepsy mediated by both synaptic and volume transmission indicate approaches to prevention DOI
Carl L. Faingold

Progress in Neurobiology, Год журнала: 2025, Номер 249, С. 102770 - 102770

Опубликована: Апрель 19, 2025

Язык: Английский

Процитировано

0

Epilepsy Research Institute UK Sudden Unexpected Death in Epilepsy (SUDEP) workshop: Identifying the pre-clinical and clinical priorities for SUDEP research DOI Creative Commons
Hannah Pickard, Samantha Ashby,

David Sibree

и другие.

Epilepsy & Behavior, Год журнала: 2025, Номер 171, С. 110473 - 110473

Опубликована: Май 22, 2025

The Epilepsy Research Institute's Mortality, Morbidity and Risk Theme workshop on Sudden Unexpected Death in (SUDEP) brought together a diverse group of stakeholders, including basic science researchers, clinicians clinical charity partners, bereaved individuals people with epilepsy to identify important gaps pre-clinical SUDEP research. Collectively, the highlighted recommendations for future research address several identified need develop infrastructures that utilise data-driven approaches reduce risk. National global cross-institution collaborations will be fundamental driving these efforts forward.

Язык: Английский

Процитировано

0

Seizure‐related death exhibits a circadian rhythm independent of seizure timing or sleep in a mouse model of Dravet syndrome DOI Creative Commons
Benjamin L. Kreitlow,

Ana T. Novella‐Maciel,

Ariana M. Hernández Vázquez

и другие.

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Abstract Sudden unexpected death in epilepsy (SUDEP) is the most extreme consequence of epilepsy. SUDEP typically occurs at night. Because humans sleep night, these nighttime deaths are often attributed to seizures arising from sleep. Nocturnal mice also experience more seizure‐associated during nighttime. This could represent timing that under circadian control. To examine this, male and female Scn1a R1407X/+ mice, a model epileptic encephalopathy Dravet syndrome, which patients spontaneous result death, were housed constant darkness seizure associated was assessed. We found sudden following persists peaks subjective rhythm independent potentially fatal frequently occurred while awake. Potentially resulted prolonged unconsciousness, exhibited peaking These findings provide support for regulation, sleep, risk death. Nighttime may increase via multiple mechanisms, as evident by peak profoundly impaired consciousness image Key points epilepsy, or SUDEP, devastating outcome intractable Converging lines evidence indicate there time‐of‐day preference with occurring Several animal models syndrome (DS), including one employed our study, recapitulate key features DS patients, high rate seizure‐related Here, we removed light/dark photocycles, housing animals darkness, identify preponderance suggesting this regulation. further carefully characterize vs . non‐fatal prove be useful biomarkers predict become fatal.

Язык: Английский

Процитировано

0

Sudden unexpected death in epilepsy: respiratory vs. cardiac contributions DOI
Susan Lin, Theodore H. Schwartz, Geoffrey S. Pitt

и другие.

Cardiovascular Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 7, 2024

Abstract Sudden unexpected death in epilepsy (SUDEP) poses a significant risk to life expectancy for individuals with epilepsy. Mechanistic insight, while incomplete, has advanced through clinical observational studies and animal models. Yet we lack preventative therapies, which will depend on understanding SUDEP mechanisms. Recurrent convulsive seizures are the major factor. Cardiorespiratory dysfunction precedes SUDEP, but whether cardiac arrhythmias proximate culprits remains be determined. Here, highlight recent data from mouse models that provide increasing support respiratory depression decreasing evidence tachyarrhythmia-induced SUDEP. Further, review genetic chemoconvulsant have enabled deeper how initiated central nervous system propagate autonomic drive seizure-induced subsequent rather than supporting arrhythmia cause. Ongoing research continue identify predictive biomarkers, improve models, translate basic into precision medicine approaches. Identifying brainstem circuits vulnerable apnoea enable therapeutic interventions enhance quality of

Язык: Английский

Процитировано

1

Seizures and premature death in mice with targeted Kv1.1 deficiency in corticolimbic circuits DOI Creative Commons
Kelsey Paulhus, Edward Glasscock

Brain Communications, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 24, 2024

Abstract Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death, likely stemming from seizure activity disrupting vital brain centres controlling heart and breathing function. However, understanding SUDEP's anatomical basis mechanisms remains limited, hampering risk evaluation prevention strategies. Prior studies using a neuron-specific Kcna1 conditional knockout mouse model SUDEP identified primary importance brain-driven contributing to sudden cardiorespiratory dysregulation; yet, underlying neurocircuits have not been identified. Using Emx1-Cre driver, we generated new lacking excitatory neurons cortex, hippocampus, amygdala select vagal afferents. To test whether absence Kv1.1 forebrain corticolimbic circuits sufficient induce spontaneous seizures, premature mortality dysfunction, performed survival EEG, ECG, plethysmography (EEG-ECG-Pleth) recordings. We demonstrate mice. During monitoring, fortuitously captured one event, which showed generalized tonic-clonic that initiated respiratory dysfunction culminating failure. In addition, observed abnormalities are common during non-fatal seizures mice, but mostly absent interictal periods, implying ictal, interictal, impairment as more reliable indicator risk. These results point critical neural substrates affirm seizure-related cardiac failure death.

Язык: Английский

Процитировано

0