Sudden And Unexpected Death In Epilepsy Research Articles

Assessment of an under-mattress sensor as a seizure detection tool in an adult epilepsy monitoring unit

ObjectiveBecause of SUDEP (Sudden and unexpected death in epilepsy) and other direct consequences of generalized tonic-clonic seizures, the use of efficient seizure detection tool may be helpful for patients, relatives and caregivers. We aimed to evaluate an under-mattress detection tool (EMFIT®) in real-life hospital conditions, in particular its sensitivity and false alarm rate (FAR), as well as its impact on patient care. MethodsWe carried out a retrospective study on a cohort of patients with epilepsy admitted between September 2017 and June 2021 to Amiens University Hospital for a video-EEG of at least 24 h, during which at least one epileptic seizure was recorded. All video-EEGs records were analyzed visually in order to assess the sensitivity of the under-mattress tool (triggering of the alarm) and to classify the seizure type (convulsive/non convulsive). We also considered whether nurses intervened during the seizure, and the time of their intervention if applicable. An additional prospective survey was conducted over 272 days to analyze the FAR of the tool. ResultsA total of 220 seizures were included in the study, from 55 patients, including 23 convulsive seizures from 15 patients and 197 non-convulsive seizures. Sensitivity for convulsive seizure detection was 69.6%. As expected, none of the non-convulsive seizures was detected. The false alarm rate was 0.007/day. Median trigger time was 74 s, decreasing to 5 s for generalized tonic-clonic seizure. The frequency of nurses’ intervention during convulsive seizures was significantly greater in case of the alarm triggering (100% vs 57%, p<0.02). SignificanceThese results suggest that EMFIT® sensor is able to detect convulsive seizures with good sensitivity and low FAR, and allows caregivers to intervene more often in the event of a nocturnal seizure. This would be an interesting complementary tool to better secure the patients with epilepsy during hospitalization or at home.

Review: Neuropathology findings in autonomic brain regions in SUDEP and future research directions.

Autonomic dysfunction is implicated from clinical, neuroimaging and experimental studies in sudden and unexpected death in epilepsy (SUDEP). Neuropathological analysis in SUDEP series enable exploration of acquired, seizure-related cellular adaptations in autonomic and brainstem autonomic centres of relevance to dysfunction in the peri-ictal period. Alterations in SUDEP compared to control groups have been identified in the ventrolateral medulla, amygdala, hippocampus and central autonomic regions. These involve neuropeptidergic, serotonergic and adenosine systems, as well as specific regional astroglial and microglial populations, as potential neuronal modulators, orchestrating autonomic dysfunction. Future research studies need to extend to clinically and genetically characterized epilepsies, to explore if common or distinct pathways of autonomic dysfunction mediate SUDEP. The ultimate objective of SUDEP research is the identification of disease biomarkers for at risk patients, to improve post-mortem recognition and disease categorisation, but ultimately, for exposing potential treatment targets of pharmacologically modifiable and reversible cellular alterations.

Ictal and Interictal Cardiac Manifestations in Epilepsy. A Review of Their Relation With an Altered Central Control of Autonomic Functions and With the Risk of SUDEP.

There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.

Seizure-related death in children with epilepsy

Children with epilepsy have a significantly higher rate of death than the general population. The cause of premature death among epileptics is contributed by the underlying cause, coexisting neurologic compromise and the epilepsy itself. Mortality directly related to seizures in paediatric epilepsy is the subject of this review. Seizure-related deaths in epileptics arise from status epilepticus, aspiration pneumonia, as well as sudden and unexpected death in epilepsy (SUDEP). Epilepsy per se enhances the risks of accidents and suicide. Children with epilepsy who are otherwise neurologically intact and with normal neuroimaging findings have an exceedingly low risk of seizure-related death. Poor compliance to antiepileptic drugs (AED) , poor ly co nt rol led (intractable and refractory) seizures, impaired cognition, structural/ metabolic aetiology and antiepileptic drug polypharmacy tend to carry poor prognosis. Therefore, parents need to be appropriately advised about the risk of seizurerelated premature death. Early identification, compliance with AED prescription, and treatment of comorbid conditions can reduce mortality risk and improve health outcomes in children with epilepsy. Children with intractable types of epilepsy may benefit from medical marijuana and neurosurgery.Keywords: Childhood epilepsy, seizure-related death, prevention

The autopsy in sudden unexpected adult death: Epilepsy

Summary There are up to 500 epilepsy-related deaths annually in the UK, many of which are unwitnessed. Likely mechanisms for sudden and unexpected death in epilepsy (SUDEP) are cerebrogenic cardiac arrhythmias, or central respiratory depression occurring during the peri-ictal period. Pathologists should be informed of the circumstances of the death, severity of seizures, seizure control and the certainty of the clinical diagnosis of epilepsy; this allows accurate clinicopathological correlation. SUDEP autopsies include neuropathological assessment, histological examination of other organs and toxicology, and require the elimination of other causes of sudden death. Macroscopic (non-fatal) abnormalities described in SUDEP include evidence of previous cerebral injury, hippocampal sclerosis and cerebellar atrophy. Histological examination may reveal neuronal loss and gliosis consistent with seizure-related brain injury. Hippocampal sclerosis shows subfield-specific patterns of neuronal loss, granule cell dispersion and mossy fibre sprouting. Rarely, acute neuronal injury is seen as evidence of a more recent cerebral event. This article discusses the pathological findings and possible mechanisms in SUDEP, and future directions for pathology-based research.

SUDEP in the Netherlands: A retrospective study in a tertiary referral center

To evaluate risk factors for sudden and unexpected death in epilepsy (SUDEP) in a high-risk population, i.e. patients treated in a Dutch tertiary referral center for epilepsy. All patients who died between January 1999 and April 2004 while under treatment of the epilepsy center were identified. Based on clinical data, deaths were classified as definite, probable, possible or non-SUDEP. Potential risk factors were compared in SUDEP cases and non-SUDEP cases. SUDEP incidence was 1.24 per 1000 patient years. SUDEP patients died at a younger age than patients from the control group of non-SUDEP deaths with epilepsy and had an earlier onset of epilepsy. However, the frequently mentioned factors in previous studies, i.e. male sex, generalized tonic-clonic seizures, high seizure frequency, specific AEDs, polytherapy with several AEDs, mental retardation, psychiatric illness and psychotropic comedication, were not found to be correlated with SUDEP. Even in this high-risk population of patients with refractory epilepsy, treated in a tertiary referral center, SUDEP is not a frequently occurring phenomenon. Specific risk factors could not be identified within an already high-risk population.

Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP-70 and c-Jun immunohistochemistry.

Post-mortem and neuropathological examination in sudden and unexpected death in epilepsy (SUDEP) shows no specific lesions and the exact cause and mechanism of death in these cases remains undetermined. There is clinical evidence to support the fact that SUDEP is a seizure-mediated event, and patients with poorly controlled seizures are at higher risk. We aimed to identify any evidence of acute neuronal injury in SUDEP cases at post-mortem to support that a recent seizure had occurred. We analysed the distribution and frequency of heat shock protein (HSP)-70 and c-Jun immunopositive neurones in the hippocampus in 18 SUDEP cases and 22 control cases, both markers being nonspecific but early and reliable indicators of acute neuronal injury. Post-mortem control groups included patients with epilepsy with cause of death other than SUDEP (including status epilepticus and accidental death), and patients with sudden cardiac death without an epilepsy history. An additional surgical control group included patients with refractory epilepsy and hippocampal sclerosis who had undergone temporal lobectomy. Semiquantitative analysis of the distribution of HSP-70 staining showed significantly more SUDEP cases with positively labelled neurones in hippocampal subfields compared to epilepsy and cardiac post-mortem controls (P < 0.001) but not compared to the epilepsy surgical controls (P = 0.4). No significant difference in immunostaining patterns between groups was seen in the parahippocampal gyrus with HSP-70 or with c-Jun in either the hippocampus or parahippocampal gyrus regions. The detection of HSP-70 positive neurones in the hippocampus in SUDEP is supportive of ante-mortem neuronal injury including a recent seizure prior to death.

Cardiac Dysrhythmia Associated with the Immediate Postictal State after Maximal Electroshock in Freely Moving Rat

Cardiac autonomic changes accompany complex partial seizures and generalized tonic-clonic seizures, and participate, at least partially, in the sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate variability (HRV) is one of the simplest ways of providing insight into autonomic functions. The entropy quantifies the repetition of complex patterns in a signal and refers to systems randomness, regularity, and predictability. Clinical investigations have reported that entropy decreases in patients with a high risk of sudden cardiac death. The goal of this study was to evaluate the effects of the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate postictal stage in the model of the freely moving rat. Entropy changes were correlated with the high and low frequencies of spectral analysis, which reflect the participation of the sympathetic and parasympathetic activities. MES-induced arrhythmia is characterized by an HRV increase, an imbalance in favor of the parasympathetic activity, and a decrease in the entropy. Entropy decrease was restricted to the duration of the arrhythmia, suggesting that the postictal arrhythmia may be associated with a higher risk of lethal cardiac complications. Nevertheless, entropy changes did not correlate with spectral changes. The results suggest that the imbalance demonstrated in the spectral domain explains only partially the contribution of each autonomic system in the complexity of the heart rate during the postictal state.

Pathological Findings in Sudden and Unexpected Death in Epilepsy (SUDEP)

Pathological Findings in Sudden and Unexpected Death in Epilepsy (SUDEP)

Amygdala sclerosis in sudden and unexpected death in epilepsy

Sclerosis of the amygdala is a not uncommon finding in patients with chronic epilepsy. The amygdala has efferent connections, via the central nuclei, to cardioregulatory centres in the medulla. Experimental studies have suggested that damage to the central nucleus may be of functional significance in patients with sudden and unexpected death in epilepsy (SUDEP) in particular with regard to their susceptibility to cardiac arrhythmias. We investigated this possibility by carrying out a quantitative immunohistochemical analysis of the patterns of neuronal loss and gliosis in three amygdala subnuclei (central, basal and lateral) in post mortem material from 15 SUDEP cases and seven normal controls. We identified significant neuronal loss in the medial division of the lateral amygdaloid nucleus in SUDEP cases but not in central or basal nuclei. These patterns of cell loss in the amygdala do not differ from previous studies in both humans and animal models of chronic epilepsy suggesting that there is not a specific pattern of amygdaloid sclerosis in SUDEP patients which could implicate a functional role for this nucleus in the mechanism of the sudden death.