The current review updates our knowledge regarding sudden unexpected death in epilepsy patient (SUDEP) risks, risk factors, and investigations of putative biomarkers based on suspected mechanisms of ...SUDEP.
The overall incidence of SUDEP in adults with epilepsy is 1.2/1000 patient-years, with surprisingly comparable figures in children in recently published population-based studies. This risk was found to decrease over time in several cohorts at a rate of -7% per year, for unknown reasons. Well established risk factors include frequency of generalized tonic-clonic seizures, while adding antiepileptic treatment, nocturnal supervision and use of nocturnal listening device appear to be protective. In contrast, recent data failed to demonstrate the predictive value of heart rate variability, periictal cardiorespiratory dysfunction, and postictal generalized electroencephalography suppression. Preliminary findings suggest that brainstem and thalamic atrophy may be associated with a higher risk of SUDEP. Novel experimental and human data support the primary role of generalized tonic-clonic seizure-triggered respiratory dysfunction and the likely contribution of altered brainstem serotoninergic neurotransmission, in SUDEP pathophysiology.
Although significant progress has been made during the past year in the understanding of SUDEP mechanisms and investigation of numerous potential biomarkers, we are still missing reliable predictors of SUDEP beyond the well established clinical risk factors.
OBJECTIVE:To identify limbic sites of respiratory control in the human brain, and by extension, the symptomatogenic zone for central apnea.
METHODS:We used direct stimulation of anatomically, ...precisely placed stereotactic EEG electrodes to analyze breathing responses. We prospectively studied 3 patients who were explored with stereotactically implanted depth electrodes. The amygdala and hippocampus, as well as extralimbic sites (orbitofrontal, temporal tip, and temporal neocortex), were investigated.
RESULTS:Individual stimulation of the amygdala and hippocampal head consistently elicited central apnea in the expiratory phase, as did exquisitely focal hippocampal seizures.
CONCLUSIONS:These findings confirm that hippocampus and amygdala are limbic breathing control sites in humans, as well as the symptomatogenic zone for central apneic seizures.
Thalamic neuromodulation can be an effective therapeutic option for select patients with medically refractory epilepsy. However, successful outcome depends on several factors, beginning with ...appropriate patient and thalamic target selection. Among thalamic targets, the anterior (ANT) and centromedian (CeM) nuclei have the greatest clinical evidence for efficacy. However, the place of thalamic neuromodulation in the treatment armamentarium for intractable seizures is at the tail end of a long list of options. It's relative efficacy, if any, in relation to other treatment modalities however, can be inferred. As we will discuss, considerable work remains to be done in optimal targeting of thalamic nuclei, appropriate to the epilepsy syndrome and seizure type of the individual patient, which may change our current understanding of the place of thalamic neuromodulation on a range of treatment modality efficacies. Currently, it appears that ANT DBS is most efficacious for limbic epilepsies whereas CM, for generalized, multifocal (especially frontotemporal) epilepsies. Based on controlled studies, the efficacy of ANT and CeM DBS is roughly in line with other neuromodulatory therapies (i.e. RNS, VNS) when assessed within the cohort of patients for which the therapy is indicated. Much improvement is needed to render thalamic DBS more efficacious, and use of optimal targeting strategies, especially direct targeting, can positively affect outcomes. Thalamic neuromodulation is still in its infancy; however, clinical advances in this therapy are being realized.
•Thalamic DBS is an effective therapy for select patients with refractory epilepsy.•Thalamic DBS efficacy is roughly in line with other neuromodulatory therapies.•The ANT and CeM subnuclei have greatest clinical evidence for efficacy.•Additional research is needed to elucidate indications for thalamic DBS.•Accurate targeting appears critical to optimal outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective:
Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 1 in 5 deaths in patients with epilepsy, but its cause remains unexplained. A recorded seizure resulting in death in ...our center appeared to suggest that postictal generalized electroencephalographic (EEG) suppression (PGES) and apnea are implicated in SUDEP. Our objective was to determine the association between PGES, as a possible identifiable EEG marker of profound postictal cerebral dysfunction, and SUDEP.
Methods:
We studied 10 adult patients from our video‐telemetry database who had 30 documented epileptic seizures during video‐EEG recording and who later died of SUDEP. They were compared with 30 matching live controls with 92 epileptic seizures taken from the same database. Clinical and EEG findings were analyzed.
Results:
PGES was seen in 15/30 (50%) case and 35/92 (38%) control seizures. A Mann‐Whitney U test showed that PGES was significantly longer in the generalized motor seizures of the SUDEP group (p < 0.001). After adjustment for variables, odds ratio analysis of all seizures indicated significantly elevated odds of SUDEP with PGES durations of >50 seconds (p < 0.05). Beyond 80 seconds, the odds were quadrupled (p < 0.005). After adjustment for variables, for each 1‐second increase in duration of PGES, the odds of SUDEP increased by a factor of 1.7%(p < 0.005).
Interpretation:
Prolonged PGES (>50 seconds) appears to identify refractory epilepsy patients who are at risk of SUDEP. Risk of SUDEP may be increased in direct proportion to duration of PGES. Profound postictal cerebral dysfunction, possibly leading to central apnea, may be a pathogenetic mechanism for SUDEP. ANN NEUROL 2010
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
OBJECTIVETo characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy.
METHODSThis was a prospective, multicenter epilepsy monitoring study ...of autonomic and breathing biomarkers of sudden unexpected death in epilepsy (SUDEP) in patients ≥18 years old with intractable epilepsy and monitored GCS. Video-EEG, thoracoabdominal excursions, nasal airflow, capillary oxygen saturation, and ECG were analyzed.
RESULTSWe studied 148 GCS in 87 patients. Nineteen patients had generalized epilepsy; 65 had focal epilepsy; 1 had both; and the epileptogenic zone was unknown in 2. Ictal central apnea (ICA) preceded GCS in 49 of 121 (40.4%) seizures in 23 patients, all with focal epilepsy. Postconvulsive central apnea (PCCA) occurred in 31 of 140 (22.1%) seizures in 22 patients, with generalized, focal, or unknown epileptogenic zones. In 2 patients, PCCA occurred concurrently with asystole (near-SUDEP), with an incidence rate of 10.2 per 1,000 patient-years. One patient with PCCA died of probable SUDEP during follow-up, suggesting a SUDEP incidence rate 5.1 per 1,000 patient-years. No cases of laryngospasm were detected. Rhythmic muscle artifact synchronous with breathing was present in 75 of 147 seizures and related to stertorous breathing (odds ratio 3.856, 95% confidence interval 1.395–10.663, p = 0.009).
CONCLUSIONSPCCA occurred in both focal and generalized epilepsies, suggesting a different pathophysiology from ICA, which occurred only in focal epilepsy. PCCA was seen in 2 near-SUDEP cases and 1 probable SUDEP case, suggesting that this phenomenon may serve as a clinical biomarker of SUDEP. Larger studies are needed to validate this observation. Rhythmic postictal muscle artifact is suggestive of post-GCS breathing effort rather than a specific biomarker of laryngospasm.
The electrical potential produced by the cardiac activity sometimes contaminates electroencephalogram (EEG) recordings, resulting in spiky activities that are referred to as electrocardiographic ...(EKG) artifact. For a variety of reasons it is often desirable to automatically detect and remove these artifacts. Especially, for accurate source localization of epileptic spikes in an EEG recording from a patient with epilepsy, it is of great importance to remove any concurrent artifact. Due to similarities in morphology between the EKG artifacts and epileptic spikes, any automated artifact removal algorithm must have an extremely low false-positive rate in addition to a high detection rate. In this paper, an automated algorithm for removal of EKG artifact is proposed that satisfies such criteria. The proposed method, which uses combines independent component analysis and continuous wavelet transformation, uses both temporal and spatial characteristics of EKG related potentials to identify and remove the artifacts. The method outperforms algorithms that use general statistical features such as entropy and kurtosis for artifact rejection.
Summary
Objective
To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it.
Methods
...We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death.
Results
Three patients (two definite and one probable) had SUDEP. They had a typical high SUDEP risk profile with longstanding intractable epilepsy and frequent generalized tonic–clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound electroencephalography (EEG) suppression. In two patients, patterns of cardiorespiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS).
Significance
SUDEP almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near‐SUDEP cases without a seizure have not yet been reported in literature. When nonmonitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of nonseizure SUDEP; such deaths may not be prevented by seizure detection–based devices. SUDEP risk in patients with epilepsy may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one episode of seizure ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent ...changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p<0.01). Decreased entropy, indicative of increased tissue homogeneity, appeared in major autonomic (ventromedial prefrontal cortex, hippocampus, dorsal and ventral medulla, deep cerebellar nuclei), motor (sensory and motor cortex), or both motor and autonomic regulatory sites (basal-ganglia, ventral-basal cerebellum), and external surfaces of the pons. The anterior and posterior thalamus and midbrain also showed entropy declines. Only a few isolated regions showed increased entropy. Among the spared autonomic regions was the anterior cingulate and anterior insula; the posterior insula and cingulate were, however, affected. The entropy alterations overlapped areas of tissue changes found earlier with volumetric measures, but were more extensive, and indicate widespread injury to tissue within critical autonomic and breathing regulatory areas, as well as prominent damage to more-rostral sites that exert influences on both breathing and cardiovascular regulation. The entropy measures provide easily-collected supplementary information using only T1-weighted images, showing aspects of tissue integrity other than volume change that are important for assessing function.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose of Review
The unpredictability and apparent randomness of epileptic seizures is one of the most vexing aspects of epilepsy. Methods or devices capable of detecting seizures may help prevent ...injury or even death and significantly improve quality of life. Here, we summarize and evaluate currently available, unimodal, or polymodal detection systems for epileptic seizures, mainly in the ambulatory setting.
Recent Findings
There are two broad categories of detection devices: EEG-based and non-EEG-based systems. Wireless wearable EEG devices are now available both in research and commercial arenas. Neuro-stimulation devices are currently evolving and initial experiences of these show potential promise. As for non-EEG devices, different detecting systems show different sensitivity according to the different patient and seizure types. Regardless, when used in combination, these modalities may complement each other to increase positive predictive value.
Summary
Although some devices with high sensitivity are promising, practical widespread use of such detection systems is still some way away. More research and experience are needed to evaluate the most efficient and integrated systems, to allow for better approaches to detection and prediction of seizures. The concept of closed-loop systems and prompt intervention may substantially improve quality of life for patients and carers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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