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Article ; Online: Reactive oxygen species in status epilepticus.

Walker, Matthew C

Epilepsia open

2023 Volume 8 Suppl 1, Page(s) S66–S72

Abstract: It has long been recognized that status epilepticus can cause considerable neuronal damage, and this has become one of its defining features. The mechanisms underlying this damage are less clear. Excessive activation of NMDA receptors results in large ... ...

Abstract	It has long been recognized that status epilepticus can cause considerable neuronal damage, and this has become one of its defining features. The mechanisms underlying this damage are less clear. Excessive activation of NMDA receptors results in large rises in internal calcium, which eventually lead to neuronal death. Between NMDA receptor activation and neuronal death are a number of intermediary steps, key among which is the generation of free radicals and reactive oxygen and nitrogen species. Although it has long been thought that mitochondria are the primary source for reactive oxygen species, more recent evidence has pointed to a prominent role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme localized in cell membranes. There is burgeoning in vivo and in vitro evidence that therapies that target the production or removal of reactive oxygen species are not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. Moreover, combining therapies targeted at inhibiting NADPH oxidase and at increasing endogenous antioxidants seems to offer the greatest benefits.
MeSH term(s)	Humans ; Reactive Oxygen Species/metabolism ; Status Epilepticus/drug therapy ; Antioxidants/metabolism ; Antioxidants/pharmacology ; NADPH Oxidases/metabolism ; Mitochondria/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism
Chemical Substances	Reactive Oxygen Species ; Antioxidants ; NADPH Oxidases (EC 1.6.3.-) ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2023-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9239
ISSN (online)	2470-9239
DOI	10.1002/epi4.12691
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Clinical advances in the understanding, diagnosis, and treatment of epilepsy.

Walker, Matthew C

Current opinion in neurology

2020 Volume 33, Issue 2, Page(s) 161–162

Language	English
Publishing date	2020-02-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000000804
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Zs.A 2524: Show issues

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Article ; Online: Status epilepticus: what's new for the intensivist.

Benghanem, Sarah / Robieux, Estelle Pruvost / Neligan, Aidan / Walker, Matthew C

Current opinion in critical care

2024 Volume 30, Issue 2, Page(s) 131–141

Abstract: Purpose of review: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, ... ...

Abstract	Purpose of review: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. Recent findings: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. Summary: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.
MeSH term(s)	Humans ; Status Epilepticus/diagnosis ; Status Epilepticus/drug therapy ; Seizures/drug therapy ; Valproic Acid/therapeutic use ; Levetiracetam/therapeutic use ; Benzodiazepines/therapeutic use ; Encephalitis ; Anticonvulsants/therapeutic use
Chemical Substances	Valproic Acid (614OI1Z5WI) ; Levetiracetam (44YRR34555) ; Benzodiazepines (12794-10-4) ; Anticonvulsants
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1235629-3
ISSN	1531-7072 ; 1070-5295
ISSN (online)	1531-7072
ISSN	1070-5295
DOI	10.1097/MCC.0000000000001137
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Article ; Online: How accurately do adult patients report their absence seizures?

Pizarro, Joao / O'Sullivan, Suzanne / Walker, Matthew C

Epilepsia open

2023 Volume 8, Issue 2, Page(s) 641–644

Abstract: We depend upon self-reporting to determine seizure frequency for epilepsy management decisions, but people often misreport their seizures. Here, we determined misreporting rates in adults with absence seizures, undergoing inpatient video-EEG telemetry ( ... ...

Abstract	We depend upon self-reporting to determine seizure frequency for epilepsy management decisions, but people often misreport their seizures. Here, we determined misreporting rates in adults with absence seizures, undergoing inpatient video-EEG telemetry (VET) or outpatient ambulatory electroencephalography (aEEG). Under-reporting rates were based on VET data, where behavior could be assessed, whilst over-reporting was assessed using both VET and aEEG. Forty-two patients (31 female and 11 males, median age 28.5 years) and 759 reported absence seizures were included in this study. Overall, only 24% of the 759 reported seizures had an associated EEG correlate, indicating a high over-reporting rate, which occurred in 57% of patients. Age, sex, time of epilepsy, VET versus aEEG, epilepsy syndrome, or medication were not significant predictors of over-reporting. In the VET group in which we could assess both over- and under-reporting (22 patients), only 2 patients correctly reported their seizures, and patients were predominantly over-reporters or under-reporters, not both. Only 26% of 423 absence seizures were reported. Use of zonisamide or valproate was associated with under-reporting, possibly through an impact on attention. These findings indicate that self-reported absence seizures are a poor measure to use for treatment decisions due to both over- and under-reporting.
MeSH term(s)	Male ; Humans ; Adult ; Female ; Seizures/diagnosis ; Seizures/drug therapy ; Epilepsy, Absence/diagnosis ; Epilepsy, Absence/drug therapy ; Zonisamide ; Valproic Acid/therapeutic use ; Inpatients
Chemical Substances	Zonisamide (459384H98V) ; Valproic Acid (614OI1Z5WI)
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9239
ISSN (online)	2470-9239
DOI	10.1002/epi4.12689
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Article ; Online: The role of trained and untrained dogs in the detection and warning of seizures.

Luff, Grace C / Belluomo, Ilaria / Lugarà, Eleonora / Walker, Matthew C

Epilepsy & behavior : E&B

2023 Volume 150, Page(s) 109563

Abstract: Seizure unpredictability plays a major role in disability and decreased quality of life in people with epilepsy. Dogs have been used to assist people with disabilities and have shown promise in detecting seizures. There have been reports of trained ... ...

Abstract	Seizure unpredictability plays a major role in disability and decreased quality of life in people with epilepsy. Dogs have been used to assist people with disabilities and have shown promise in detecting seizures. There have been reports of trained seizure-alerting dogs (SADs) successfully detecting when a seizure is occurring or indicating imminent seizures, allowing patients to take preventative measures. Untrained pet dogs have also shown the ability to detect seizures and provide comfort and protection during and after seizures. Dogs' exceptional olfactory abilities and sensitivity to human cues could contribute to their seizure-detection capabilities. This has been supported by studies in which dogs have distinguished between epileptic seizure and non-seizure sweat samples, probably though the detection of volatile organic compounds (VOCs). However, the existing literature has limitations, with a lack of well-controlled, prospective studies and inconsistencies in reported timings of alerting behaviours. More research is needed to standardize reporting and validate the results. Advances in VOC profiling could aid in distinguishing seizure types and developing rapid and unbiased seizure detection methods. In conclusion, using dogs in epilepsy management shows considerable promise, but further research is needed to fully validate their effectiveness and potential as valuable companions for people with epilepsy.
MeSH term(s)	Animals ; Humans ; Dogs ; Prospective Studies ; Quality of Life ; Seizures/diagnosis ; Epilepsy/diagnosis ; Smell
Language	English
Publishing date	2023-12-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2023.109563
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Article ; Online: Editorial.

Walker, Matthew C

Current opinion in neurology

2017 Volume 30, Issue 2, Page(s) 165–166

MeSH term(s)	Anticonvulsants/therapeutic use ; Electroencephalography ; Epilepsy/classification ; Epilepsy/diagnosis ; Epilepsy/drug therapy ; Humans ; Seizures/physiopathology
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2017-02-15
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000000421
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Article ; Online: The role of aberrant neural oscillations in the hippocampal-medial prefrontal cortex circuit in neurodevelopmental and neurological disorders.

Shing, Nathanael / Walker, Matthew C / Chang, Pishan

Neurobiology of learning and memory

2022 Volume 195, Page(s) 107683

Abstract: The hippocampus (HPC) and medial prefrontal cortex (mPFC) have well-established roles in cognition, emotion, and sensory processing. In recent years, interests have shifted towards developing a deeper understanding of the mechanisms underlying ... ...

Abstract	The hippocampus (HPC) and medial prefrontal cortex (mPFC) have well-established roles in cognition, emotion, and sensory processing. In recent years, interests have shifted towards developing a deeper understanding of the mechanisms underlying interactions between the HPC and mPFC in achieving these functions. Considerable research supports the idea that synchronized activity between the HPC and the mPFC is a general mechanism by which brain functions are regulated. In this review, we summarize current knowledge on the hippocampal-medial prefrontal cortex (HPC-mPFC) circuit in normal brain function with a focus on oscillations and highlight several neurodevelopmental and neurological disorders associated with aberrant HPC-mPFC circuitry. We further discuss oscillatory dynamics across the HPC-mPFC circuit as potentially useful biomarkers to assess interventions for neurodevelopmental and neurological disorders. Finally, advancements in brain stimulation, gene therapy and pharmacotherapy are explored as promising therapies for disorders with aberrant HPC-mPFC circuit dynamics.
MeSH term(s)	Humans ; Prefrontal Cortex/physiology ; Hippocampus/physiology ; Cognition ; Nervous System Diseases ; Neural Pathways/physiology
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223366-3
ISSN	1095-9564 ; 1074-7427
ISSN (online)	1095-9564
ISSN	1074-7427
DOI	10.1016/j.nlm.2022.107683
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Article ; Online: Pathophysiology of status epilepticus.

Walker, Matthew C

Neuroscience letters

2016 Volume 667, Page(s) 84–91

Abstract: Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures. Both human and animal data indicate that the longer a seizure lasts, the less likely it ...

Abstract	Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures. Both human and animal data indicate that the longer a seizure lasts, the less likely it is to stop. Recent evidence suggests that there is a critical transition from an ictal to a post-ictal state, associated with a transition from a spatio-temporally desynchronized state to a highly synchronized state, respectively. As SE continues, it becomes progressively resistant to drugs, in particular benzodiazepines due partly to NMDA receptor-dependent internalization of GABA(A) receptors. Moreover, excessive calcium entry into neurons through excessive NMDA receptor activation results in activation of nitric oxide synthase, calpains, and NADPH oxidase. The latter enzyme plays a critical part in the generation of seizure-dependent reactive oxygen species. Calcium also accumulates in mitochondria resulting in mitochondrial failure (decreased ATP production), and opening of the mitochondrial permeability transition pore. Together these changes result in status epilepticus-dependent neuronal death via several pathways. Multiple downstream mechanisms including inflammation, break down of the blood-brain barrier, and changes in gene expression can contribute to later pathological processes including chronic epilepsy and cognitive decline.
MeSH term(s)	Animals ; Hippocampus/metabolism ; Hippocampus/physiopathology ; Humans ; Mitochondria/metabolism ; Neurons/metabolism ; Reactive Oxygen Species/metabolism ; Seizures/metabolism ; Seizures/physiopathology ; Status Epilepticus/metabolism ; Status Epilepticus/physiopathology
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2016-12-20
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2016.12.044
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Article ; Online: Advances in the management of generalized convulsive status epilepticus: what have we learned?

Neligan, Aidan / Rajakulendran, Sanjeev / Walker, Matthew C

Brain : a journal of neurology

2021 Volume 144, Issue 5, Page(s) 1336–1341

Abstract: Convulsive status epilepticus is the most serious manifestation of an epileptic diathesis. In the early stages (5-30 min), there exists class A evidence to support the efficacy of benzodiazepines as first-line treatment. As status epilepticus progresses ... ...

Abstract	Convulsive status epilepticus is the most serious manifestation of an epileptic diathesis. In the early stages (5-30 min), there exists class A evidence to support the efficacy of benzodiazepines as first-line treatment. As status epilepticus progresses into the later stages, the evidence for treatment becomes less robust until we are depending upon short case series and case reports for the treatment of refractory status epilepticus. However, the past year saw the publication of three randomized controlled trials in the setting of benzodiazepine-resistant established convulsive status epilepticus: the EcLiPSE and ConSEPT studies, compared levetiracetam to phenytoin in children; and the ESETT study compared fosphenytoin, levetiracetam and sodium valproate in adults and children. In addition, the emergence of data from the SENSE study, a multicentre multinational prospective cohort study and the publication of a systematic review and meta-analysis of the mortality of status epilepticus over the past 30 years, has brought the treatment of status epilepticus into sharp focus. In this update we provide a detailed analysis of these studies and their impact on clinical practice. We review contentious areas of management in status epilepticus where a consensus is lacking and advance the case for more research on existing and alternative treatment strategies.
MeSH term(s)	Anticonvulsants/therapeutic use ; Humans ; Status Epilepticus/drug therapy
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2021-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awab049
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Article ; Online: Response: Drug resistance in epilepsy: A reappraisal of the definition is needed.

Galanopoulou, Aristea S / Auvin, Stéphane / Moshé, Solomon L / Potschka, Heidrun / Rocha, Luisa / Walker, Matthew C

Epilepsia

2023 Volume 65, Issue 1, Page(s) 240–241

MeSH term(s)	Humans ; Epilepsy/diagnosis ; Epilepsy/drug therapy ; Drug Resistance
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Letter
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17818
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