scholarly journals Postictal brainstem hypoperfusion and risk factors for sudden unexpected death in epilepsy

Neurology ◽  
2020 ◽  
Vol 95 (12) ◽  
pp. e1694-e1705
Author(s):  
Jonathan Liu ◽  
Joseph S. Peedicail ◽  
Ismael Gaxiola-Valdez ◽  
Emmy Li ◽  
Victoria Mosher ◽  
...  

ObjectiveSince the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequent bilateral tonic-clonic seizures (BTCS), our aim was to determine whether postictal hypoperfusion in brainstem respiratory centers (BRCs) is more common following tonic-clonic seizures.MethodsWe studied 21 patients with focal epilepsies who underwent perfusion imaging with arterial spin labeling MRI. Subtraction maps of cerebral blood flow were obtained from the postictal and baseline scans. We identified 6 regions of interest in the brainstem that contain key BRCs. Patients were considered to have postictal BRC hypoperfusion if any of the 6 regions of interest were significantly hypoperfused.ResultsAll 6 patients who experienced BTCS during the study had significant clusters of postictal hypoperfusion in BRCs compared to 7 who had focal impaired awareness seizures (7/15). The association between seizure type studied and the presence of BRC hypoperfusion was significant. Duration of epilepsy and frequency of BTCS were not associated with postictal brainstem hypoperfusion despite also being associated with risk for SUDEP.ConclusionPostictal hypoperfusion in brainstem respiratory centers occurs more often following BTCS than other seizure types, providing a possible explanation for the increased risk of SUDEP in patients who regularly experience BTCS.

2010 ◽  
Vol 70 (3) ◽  
pp. 665-670 ◽  
Author(s):  
FA. Scorza ◽  
RM. Cysneiros ◽  
RM. Arida ◽  
VC. Terra ◽  
HR. Machado ◽  
...  

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.


2019 ◽  
Vol 121 (1) ◽  
pp. 177-187 ◽  
Author(s):  
Isabel D. Derera ◽  
Katalin Cs. Smith ◽  
Bret N. Smith

Sudden unexpected death in epilepsy (SUDEP) is among the leading causes of death in people with epilepsy. Individuals with temporal lobe epilepsy (TLE) have a high risk for SUDEP because the seizures are often medically intractable. Neurons in the nucleus tractus solitarii (NTS) have been implicated in mouse models of SUDEP and play a critical role in modulating cardiorespiratory and autonomic output. Increased neuronal excitability of inhibitory, GABAergic neurons in the NTS develops during epileptogenesis, and NTS dysfunction has been implicated in mouse models of SUDEP. In this study we used the pilocarpine-induced status epilepticus model of TLE (i.e., pilo-SE mice) to investigate the A-type voltage-gated K+ channel as a potential contributor to increased excitability in GABAergic NTS neurons during epileptogenesis. Compared with age-matched control mice, pilo-SE mice displayed an increase in spontaneous action potential frequency and half-width 9–12 wk after treatment. Activity of GABAergic NTS neurons from pilo-SE mice showed less sensitivity to 4-aminopyridine. Correspondingly, reduced A-type K+ current amplitude was detected in these neurons, with no change in activation or inactivation kinetics. No changes were observed in Kv4.1, Kv4.2, Kv4.3, KChIP1, KChIP3, or KChIP4 mRNA expression. These changes contribute to the increased excitability in GABAergic NTS neurons that develops in TLE and may provide insight into potential mechanisms contributing to the increased risk for cardiorespiratory collapse and SUDEP in this model. NEW & NOTEWORTHY Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in epilepsy, and dysfunction in central autonomic neurons may play a role. In a mouse model of acquired epilepsy, GABAergic neurons in the nucleus tractus solitarii developed a reduced amplitude of the A-type current, which contributes to the increased excitability seen in these neurons during epileptogenesis. Neuronal excitability changes in inhibitory central vagal circuitry may increase the risk for cardiorespiratory collapse and SUDEP.


2021 ◽  
Vol 8 ◽  
Author(s):  
Enrice Huenerfauth ◽  
Jasmin Nessler ◽  
Johannes Erath ◽  
Andrea Tipold

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.


Neurology ◽  
2020 ◽  
Vol 95 (18) ◽  
pp. e2509-e2518 ◽  
Author(s):  
Olafur Sveinsson ◽  
Tomas Andersson ◽  
Peter Mattsson ◽  
Sofia Carlsson ◽  
Torbjörn Tomson

ObjectiveWe conducted a nationwide case–control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs) mono- or polytherapy, adherence, antidepressants, neuroleptics, β-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk.MethodsIncluded were 255 SUDEP cases and 1,148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for potential risk factors including type of epilepsy, living conditions, comorbidity, and frequency of generalized tonic-clonic seizures (GTCS).ResultsPolytherapy, especially taking 3 or more AEDs, was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI 0.14–0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31–0.97), valproic acid (OR 0.53, 95% CI 0.29–0.98), and levetiracetam (OR 0.49, 95% CI 0.27–0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although numbers were limited, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI 0.02–0.61). Having nonadherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58–4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI 0.11–0.99) but selective serotonin reuptake inhibitor use was not.ConclusionThese results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the effort to reduce SUDEP risk and suggest that comedication with statins may reduce risk.


Neurology ◽  
2020 ◽  
Vol 95 (14) ◽  
pp. e2009-e2015
Author(s):  
Sándor Beniczky ◽  
Guido Rubboli ◽  
Athanasios Covanis ◽  
Michael R. Sperling

ObjectiveTo test the hypothesis that absence seizures can evolve to generalized tonic-clonic seizures, we documented electroclinical features of this novel seizure type.MethodsIn 4 large video-EEG databases, we identified recordings of seizures starting with impaired awareness that, without returning to baseline interictal state, evolved to generalized tonic-clonic seizures. We extracted the detailed semiologic and electrographic characteristics of these seizures, and we documented the clinical background, diagnoses, and therapeutic responses in these patients.ResultsWe identified 12 seizures from 12 patients. All seizures started with a period of impaired awareness and bursts of generalized spike or polyspike and slow-wave discharges, the hallmark of absence seizures. Without returning to baseline, the nonmotor (absence) phase was followed by tonic-clonic convulsions. We called this novel generalized seizure type absence-to-bilateral-tonic-clonic seizure. Most patients had idiopathic generalized epilepsies, although with a high incidence of unusual features and poor therapeutic response.ConclusionsAbsence-to-bilateral-tonic-clonic seizures are a novel generalized seizure type. Clinicians should be aware of this seizure for correctly diagnosing patients. This novel seizure type may further elucidate generalized ictogenesis.


Neurology ◽  
2017 ◽  
Vol 88 (17) ◽  
pp. 1674-1680 ◽  
Author(s):  
Cynthia Harden ◽  
Torbjörn Tomson ◽  
David Gloss ◽  
Jeffrey Buchhalter ◽  
J. Helen Cross ◽  
...  

Objective:To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified.Methods:Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus.Results:Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0–17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16–0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64–2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence).Recommendations:Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.


2018 ◽  
Vol 10 (3) ◽  
pp. 63-70
Author(s):  
E. D. Belousova ◽  
M. A. Shkolnikova

It is well known that sudden unexpected death in epilepsy (SUDEP) is one of the most significant factors of mortality in epileptic patients. There is an increased risk of SUDEP in genetic epileptic encephalopathies (EE), partly because those syndromes are associated with mutations in the “neurocardiac” genes, which have been implicated in both epilepsy and cardiac arrhythmias. In these clinical conditions, functions of ion selective channels (sodium, potassium and etc.) are affected; for example, in children with Dravet syndrome, the risk of SUDEP is 40 times higher than that in children with common epilepsy syndromes. In a murine model of SCN1A epilepsy, a prolongation of QT interval coincided with a seizure; in addition, an excessive excitability of cultured cardiomyocytes was demonstrated. A high risk of SUDEP is characteristic for EE caused by mutation in the SCN8A gene. Other prognostic biomarkers of SUDEP may include mutations in sodium channel genes, such as SCN4A, SCN10A, and SCN11A. Our knowledge about SUDEP associated with potassium channel dysfunctions is still very limited. There are likely some mutations in other genes, that can modify (increase or decrease) the risk of SUDEP in EE. If patients with genetic EE are indeed at a high risk for SUDEP, they must be followed up by cardiologists alongside with neurologists. Provided this hypothesis is proved, any newly diagnosed arrhythmia should be carefully monitored and treated (with medications and/or interventions), in order to improve the survival rate in genetic EE.


2009 ◽  
Vol 67 (2a) ◽  
pp. 209-213 ◽  
Author(s):  
Rui A. Gomes ◽  
Silvana Kesrouani ◽  
Jenner Cruz ◽  
Alexandre L. Silva ◽  
Tânia M.G. Henriques ◽  
...  

Of the many risk factors suggested for sudden unexpected death in epilepsy (SUDEP), higher frequency of seizures is a very consistent issue. Following this reasoning, it has been established that hemodialysis-associated seizure is a complication of dialysis procedure. Based on these facts, this study investigated a possible association between cardiovascular abnormalities and SUDEP among patients with chronic renal insufficiency in regular hemodialysis program. For that, a retrospective medical history of 209 patients was reviewed to investigate the occurrence of convulsive seizures and EKG abnormalities during dialytic program. Three patients presented generalized tonic-clonic seizures, one had partial seizure with secondary generalization, and one presented unclassified seizure. Any EKG abnormalities and SUDEP event were found in all patients evaluated. In conclusion, the present findings demonstrated uncommon the occurrence of seizures and also SUDEP. Probably, the main justification to not allow us to demonstrated a direct relation between SUDEP and cardiovascular diseases in hemodialysis are the reduced number of cases examined.


2022 ◽  
Vol 9 ◽  
Author(s):  
Catherine Ellis ◽  
Anna Pease ◽  
Joanna Garstang ◽  
Debbie Watson ◽  
Peter S. Blair ◽  
...  

Background: Advice to families to follow infant care practices known to reduce the risks of Sudden Unexpected Death in Infancy (SUDI) has led to a reduction in deaths across the world. This reduction has slowed in the last decade with most deaths now occurring in families experiencing social and economic deprivation. A systematic review of the literature was commissioned by the National Child Safeguarding Practice Review Panel in England. The review covered three areas: interventions to improve engagement with support services, parental decision-making for the infant sleep environment, and interventions to improve safer sleep practices in families with infants considered to be at risk of SUDI.Aim: To describe the safer sleep interventions tested with families with infants at risk of SUDI and investigate what this literature can tell us about what works to reduce risk and embed safer sleep practices in this group.Methods: Eight online databases were systematically searched in December 2019. Intervention studies that targeted families with infants (0–1 year) at increased risk of SUDI were included. Studies were limited to those from Western Europe, North America or Australasia, published in the last 15 years. The Quality Assessment Tool for Studies with Diverse Designs was applied to assess quality. Data from included studies were extracted for narrative synthesis, including mode of delivery using Michie et al.'s Mode of Delivery Taxonomy.Results: The wider review returned 3,367 papers, with 23 intervention papers. Five types of intervention were identified: (1) infant sleep space and safer sleep education programs, (2) intensive or targeted home visiting services, (3) peer educators/ambassadors, (4) health education/raising awareness interventions, (5) targeted health education messages using digital media.Conclusion: Influencing behavior in families with infants at risk of SUDI has traditionally focused on “getting messages across,” with interventions predominantly using education and awareness raising mechanisms. This review found evidence of interventions moving from “information giving” to “information exchange” models using personalized, longer term relationship-building models. This shift may represent an improvement in how safer sleep advice is implemented in families with infants at risk, but more robust evidence of effectiveness is required.Systematic Review Registration:https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/901091/DfE_Death_in_infancy_review.pdf, identifier: CRD42020165302.


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