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Objective: Prolonged postictal generalized electroencephalographic suppression (PGES) is a potential biomarker for sudden unexpected death in epilepsy (SUDEP), which may be associated with dysfunctional autonomic responses and serotonin signaling. To better understand molecular mechanisms, PGES duration was correlated to 5HT1A and 5HT2A receptor protein expression and RNAseq from resected hippocampus and temporal cortex of temporal lobe epilepsy patients with seizures recorded in preoperative evaluation., Methods: Analyses included 36 cases (age = 14-64 years, age at epilepsy onset = 0-51 years, epilepsy duration = 2-53 years, PGES duration = 0-93 s), with 13 cases in all hippocampal analyses. 5HT1A and 5HT2A protein was evaluated by Western blot and histologically in hippocampus (n = 16) and temporal cortex (n = 9). We correlated PGES duration to our previous RNAseq dataset for serotonin receptor expression and signaling pathways, as well as weighted gene correlation network analysis (WGCNA) to identify correlated gene clusters., Results: In hippocampus, 5HT2A protein by Western blot positively correlated with PGES duration (p = .0024, R 2  = .52), but 5HT1A did not (p = .87, R 2  = .0020). In temporal cortex, 5HT1A and 5HT2A had lower expression and did not correlate with PGES duration. Histologically, PGES duration did not correlate with 5HT1A or 5HT2A expression in hippocampal CA4, dentate gyrus, or temporal cortex. RNAseq identified two serotonin receptors with expression that correlated with PGES duration in an exploratory analysis: HTR3B negatively correlated (p = .043, R 2  = .26) and HTR4 positively correlated (p = .049, R 2  = .25). WGCNA identified four modules correlated with PGES duration, including positive correlation with synaptic transcripts (p = .040, Pearson correlation r = .52), particularly potassium channels (KCNA4, KCNC4, KCNH1, KCNIP4, KCNJ3, KCNJ6, KCNK1). No modules were associated with serotonin receptor signaling., Significance: Higher hippocampal 5HT2A receptor protein and potassium channel transcripts may reflect underlying mechanisms contributing to or resulting from prolonged PGES. Future studies with larger cohorts should assess functional analyses and additional brain regions to elucidate mechanisms underlying PGES and SUDEP risk., (© 2022 International League Against Epilepsy.)

Sudden unexpected death in epilepsy (SUDEP) is a tragic and unexpected cause of death in patients with a known diagnosis of epilepsy. It occurs in up to 6.3 to 9.3/1,000 patients with drug-resistant epilepsy. The main three risk factors associated with SUDEP are the presence of generalized tonic-clonic seizures, the presence of a seizure in the past year, and an intellectual disability. There are several mechanisms that can result in SUDEP. The most likely sequence of events appears to be a convulsive seizure, overactivation of the autonomic nervous system, cardiorespiratory dysfunction, and death. While the risk of SUDEP is relatively high in patients with drug-resistant epilepsy, studies indicate that more than 50% of patients and caregivers are unaware of the diagnosis. Counseling about the diagnosis and preventative measures at the time of diagnosis is important. There are numerous interventions that may reduce the risk of SUDEP, including conservative measures such as nocturnal surveillance with a bed partner (where applicable) and automated devices. Optimizing seizure control with antiseizure medications and surgical interventions can result in a reduced risk of SUDEP., Competing Interests: None declared., (Thieme. All rights reserved.)

Convulsive seizures are the most consistently reported risk factor for SUDEP. However, the precise mechanisms by which convulsive seizures trigger fatal cardiopulmonary changes are still unclear. Additionally, it is not clear why some seizures cause death when most do not. This article reviews the physiologic changes that occur during and after convulsive seizures and how these may contribute to SUDEP. Seizures activate specific cortical and subcortical regions that can cause potentially lethal cardiorespiratory changes. Clinical factors, including sleep state, medication treatment and withdrawal, positioning and posturing during seizures, and underlying structural or genetic conditions may also affect specific aspects of seizures that may contribute to SUDEP. While seizure control, either through medication or surgical treatment, is the primary intervention that reduces SUDEP risk, unfortunately, seizures cannot be fully controlled despite maximal treatment in a significant proportion of people with epilepsy. Thus specific interventions to prevent adverse seizure-related cardiopulmonary consequences are needed. The potential roles of repositioning/stimulation after seizures, oxygen supplementation, cardiopulmonary resuscitation and clinical treatment options in reducing SUDEP risk are explored. Ultimately, understanding of these factors may lead to interventions that could reduce or prevent SUDEP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the appropriate clinical setting, the presence of interictal epileptiform abnormalities (IEAs) on EEG supports the diagnosis of epilepsy. However, the absence of epileptiform abnormalities on EEG cannot exclude a diagnosis of epilepsy. The goal of our study is to determine the prevalence of IEAs in patients with confirmed epilepsy, determined by having at least one epileptic seizure recorded during video-EEG monitoring. In addition, we aimed to analyze the time to recording IEAs and seizures in correlation with patient age, duration of epilepsy, and seizure focus localization. We retrospectively evaluate EEG data for all patients admitted to the epilepsy monitoring unit over a 2-year period. Of the 151 patients included, 129 (86%) patients had IEAs and 22 (14%) patients had no IEAs. Age and duration of epilepsy were not independent predictors of whether IEAs were present on EEG. The duration of EEG monitoring and time to first seizure did not influence IEA detection. In patients with IEAs, the mean time to the first IEA was 1.57 days. By day 5, IEAs were observed in 95% of the patients who had IEAs present on EEG (82% of total patients). The majority (75%) of patients also had their first seizure by day 5. We concluded that five days of EEG recording is optimal to detect IEAs and seizures, and that more prolonged recording has a low yield. Failure to detect IEAs should be interpreted with caution, and is not useful for diagnostic purposes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures., Methods: We prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO 2 ), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27)., Results: Postictal serum 5-HT levels were increased over interictal levels for seizures without ICA ( p = 0.01), compared to seizures with ICA ( p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels ( p < 0.001), but not in patients with seizures with PCCA ( p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA ( p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA ( p = 0.03) compared to those with PCCA ( p = 0.42)., Conclusions: The data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study., (© 2019 American Academy of Neurology.)

Objective: Ictal (ICA) and postconvulsive central apnea (PCCA) have been implicated in sudden unexpected death in epilepsy (SUDEP) pathomechanisms. Previous studies suggest that serotonin reuptake inhibitors (SRIs) and benzodiazepines (BZDs) may influence breathing. The aim of this study was to investigate if chronic use of these drugs alters central apnea occurrence in patients with epilepsy., Methods: Patients with epilepsy admitted to epilepsy monitoring units (EMUs) in nine centers participating in a SUDEP study were consented. Polygraphic physiological parameters were analyzed, including video-electroencephalography (VEEG), thoracoabdominal excursions, and pulse oximetry. Outpatient medication details were collected. Patients and seizures were divided into SRI, BZD, and control (no SRI or BZD) groups. Ictal central apnea and PCCA, hypoxemia, and electroclinical features were assessed for each group., Results: Four hundred and seventy-six seizures were analyzed (204 patients). The relative risk (RR) for ICA in the SRI group was half that of the control group (p = 0.02). In the BZD group, ICA duration was significantly shorter than in the control group (p = 0.02), as was postictal generalized EEG suppression (PGES) duration (p = 0.021). Both SRI and BZD groups were associated with smaller seizure-associated oxygen desaturation (p = 0.009; p ≪ 0.001). Neither presence nor duration of PCCA was significantly associated with SRI or BZD (p ≫ 0.05)., Conclusions: Seizures in patients taking SRIs have lower occurrence of ICA, and patients on chronic treatment with BZDs have shorter ICA and PGES durations. Preventing or shortening ICA duration by using SRIs and/or BZD in patients with epilepsy may play a possible role in SUDEP risk reduction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a major cause of epilepsy-related mortality. SUDEP is highly linked to seizures, with most deaths occurring after convulsive seizures in sleep. In most cases of SUDEP, convulsive seizures appear to directly trigger catastrophic cardiorespiratory dysfunction leading to death. In the last few decades, many pathophysiological mechanisms have been proposed to explain the sequence of events leading to death. Patients with epilepsy often have underlying autonomic dysfunction, as measured by heart rate variability and other testing modalities. Additionally, seizures often trigger acute cardiac and respiratory dysfunction. While sinus tachycardia is the most common cardiac finding during seizures, asystole and malignant tachyarrhythmias may also occur. Seizures can also lead to respiratory dysfunction, including central ictal and obstructive apnea related to laryngospasm. Available data suggest that there could be underlying autonomic dysfunction, potentially related to genetic, medication, and other factors that might predispose individuals to sudden catastrophic cardio-respiratory dysfunction in the setting of a seizure, resulting in SUDEP. Further exploration of this possible link is needed. Patients with medically refractory epilepsy are at the highest risk, and adequate management via medical therapy to control convulsive seizures, or surgical intervention may decrease the SUDEP risk. Recently, many automated seizure detection systems have been developed to detect convulsive seizures, which may enable caregivers to more closely monitor individuals with epilepsy. Improved identification of seizures may be important for patients with refractory epilepsy as close supervision and timely intervention after a seizure could potentially reduce the risk of SUDEP.

Objective: To characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy., Methods: This 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., Results: We 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)., Conclusions: PCCA 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., (© 2018 American Academy of Neurology.)

Observations in witnessed Sudden Unexpected Death in Epilepsy (SUDEP) suggest that a fatal breakdown of the central autonomic control could play a major role in SUDEP. A previous MR study found volume losses in the mesencephalon in focal epilepsy that were more severe and extended into the lower brainstem in two patients who later died of SUDEP. The aims of this study were to demonstrate an association (1) between brainstem volume loss and impaired autonomic control (reduced heart rate variability [HRV]); (2) between brainstem damage and time to SUDEP in patients who later died of SUDEP. Two populations were studied: (1) Autonomic system function population (ASF, 18 patients with focal epilepsy, 11 controls) with HRV measurements and standardized 3 T MR exams. (2) SUDEP population (26 SUDEP epilepsy patients) with clinical MRI 1-10 years before SUDEP. Deformation-based morphometry of the brainstem was used to generate profile similarity maps from the resulting Jacobian determinant maps that were further characterized by graph analysis to identify regions with excessive expansion indicating significant volume loss or atrophy. The total number of regions with excessive expansion in ASF was negatively correlated with HRV (r = -.37, p = .03), excessive volume loss in periaqueductal gray/medulla oblongata autonomic nuclei explained most of the HRV associated variation (r/r 2  = -.82/.67, p < .001). The total number of regions with excessive expansion in SUDEP was negatively correlated with time to SUDEP (r = -.39, p = .03), excessive volume loss in the raphe/medulla oblongata at the obex level explained most of the variation of the time between MRI to SUDEP (r/r 2  = -.60/.35,p = .001). Epilepsy is associated with brainstem atrophy that impairs autonomic control and can increase the risk for SUDEP if it expands into the mesencephalon., (© 2018 Wiley Periodicals, Inc.)

Although there is no strict consensus, some studies have reported that Postictal generalized EEG suppression (PGES) is a potential electroencephalographic (EEG) biomarker for risk of sudden unexpected death in epilepsy (SUDEP). PGES is an epoch of EEG inactivity after a seizure, and the detection of PGES in clinical data is extremely difficult due to artifacts from breathing, movement and muscle activity that can adversely affect the quality of the recorded EEG data. Even clinical experts visually interpreting the EEG will have diverse opinions on the start and end of PGES for a given patient. The development of an automated EEG suppression detection tool can assist clinical personnel in the review and annotation of seizure files, and can also provide a standard for quantifying PGES in large patient cohorts, possibly leading to further clarification of the role of PGES as a biomarker of SUDEP risk. In this paper, we develop an automated system that can detect the start and end of PGES using frequency domain features in combination with boosting classification algorithms. The average power for different frequency ranges of EEG signals are extracted from the prefiltered recorded signal using the fast fourier transform and are used as the feature set for the classification algorithm. The underlying classifiers for the boosting algorithm are linear classifiers using a logistic regression model. The tool is developed using 12 seizures annotated by an expert then tested and evaluated on another 20 seizures that were annotated by 11 experts.

Purpose: To describe a series of patients with ictal coughing to estimate its occurrence and characterize the clinical features and differential diagnoses., Methods: We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 7-year period (2010-2016) for the occurrence of the term "cough" in the text body. All the extracted reports were reviewed and patients with at least one documented ictal coughing at the epilepsy monitoring unit (EMU) were included in the study., Results: During the study period, 2487 patients were investigated at our EMU. Seven patients (0.28%) had at least one documented seizure accompanied by coughing. Four patients (0.16%) had epilepsy and three patients (0.12%) had psychogenic nonepileptic seizures (PNES). All patients with epilepsy had focal onset epilepsy; ictal coughing was not associated with any particular localization or lateralization., Conclusion: We add to the literature on ictal coughing by providing additional information on its differential diagnosis and clinical features. Ictal coughing is a rare finding among patients evaluated at the EMUs. The differential diagnoses for ictal coughing include epilepsy and PNES. Epileptic ictal coughing is a rare semiological finding in patients with epilepsy and when present, it is invariably associated with focal epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Our objective was to determine the significance of PGES as a possible EEG marker of increased risk for SUDEP and explore factors that influence PGES., Methods: We identified 17 patients who died due to definite or probable SUDEP and 52 living control patients with drug resistant focal epilepsy who underwent EEG monitoring and least one seizure recorded on EEG. We reviewed 305 seizures on EEG and when available, on video, for presence or absence of PGES, the duration of PGES immediately after seizure end, seizure type, state seizure occurred (sleep vs. wake), tonic duration and time from seizure onset to initial nursing intervention. We noted that majority (93% in SUDEP group and 83% living controls) with PGES had additional brief bursts of suppression. We measured the time from the end of seizure to end of last brief suppression to determine the time to final PGES., Results: SUDEP patients had statistically significant shorter PGES duration compared to living controls (unadjusted: -32.8s, 95%CI[-54.5, -11.2], adjusted: -39.5s, 95% CI[-59.4, -19.6]). SUDEP status was associated with longer time to final PGES compare to living controls, but this was not statistically significant. Earlier nursing intervention was associated with shorter seizure duration. PGES occurred only after GCS. Time to nursing intervention, tonic duration or state did not have a statistically significant effect on PGES., Conclusions: PGES is an equivocal marker of increased SUDEP risk. Earlier nursing intervention is associated with shorter seizure duration and may play a role in reducing risk of SUDEP., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Epilepsy is associated with interictal and ictal autonomic dysfunction. Seizures can immediately cause increases in blood pressure (BP) and heart rate (HR). However, it is unknown whether uncontrolled seizures, particularly when frequent, might chronically elevate the BP or HR. Additionally, it is unknown whether the interictal BP and HR is altered in individuals who are at risk for SUDEP, compared with other individuals with epilepsy. SUDEP often occurs in patients with highly refractory epilepsy. Such individuals might be at risk for a state of chronically heightened sympathetic tone, which might affect the HR and BP interictally. This study compared the resting awake interictal HR and BP in individuals who subsequently died due to SUDEP and compared these to HR and BP in two control epilepsy groups (refractory and controlled). While the overall HR and BP are similar between groups, there is a trend toward a higher diastolic BP and more stable HR in individuals who subsequently died due to SUDEP, compared with epilepsy controls. These data suggest that there may be specific types of interictal autonomic dysfunction in individuals at risk for SUDEP. Such abnormalities might serve as markers for those at elevated risk for SUDEP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: To determine the frequency, nature, and risk factors associated with physical injuries in patients with epilepsy., Methods: In this retrospective cohort study, patients 18years of age and older with active epilepsy for at least 1year were included. A questionnaire (including age, gender, education, type of epilepsy, seizure frequency, having aura, drug compliance, polypharmacy, comorbidity, type and place of injury) was completed from patients and healthy individuals. Statistical analyses were performed using multiple logistic regression and Chi-square tests., Results: 264 patients with epilepsy and 289 healthy participants were studied. Among patients, 8.7% reported severe injuries and 44.3% had mild injuries. Most patients reported soft tissue injuries, followed by dental injury, burn, and head injury. Severe injuries were 2.9 times more frequent among patients having generalized tonic-clonic seizures (GTCS) compared to healthy control; this was not statistically significant (P=0.07). No patient reported having severe injuries due to SPS, myoclonic or absence seizures. Mild injuries were 10.3 times more frequent among those with GTCS compared to healthy control (P=0.001). The relative risk for having injury in patients compared to control group was 3.42 (95% confidence interval: 2.50-4.69). Injury was significantly related to having GTCSs, illiteracy, having fall with seizures, comorbidity and having uncontrolled seizures., Conclusion: Physical injuries are common in patients with epilepsy; however most of these injuries are mild. Severe injuries rarely occur in patients with seizures other than GTCS., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

We describe a case of a patient with Lennox-Gastaut syndrome who had asystole and sinus bradycardia during interictal epileptiform abnormalities on EEG. Video-EEG/EKG monitoring prior to corpus callosotomy recorded consistent prolongation of the R-R interval on the EKG during bursts of epileptiform abnormalities (generalized paroxysmal fast activity), which became transiently more pronounced after surgery. These findings reveal that interictal epileptiform abnormalities may cause significant cardiac arrhythmias in some individuals., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a significant cause of death for people with epilepsy. Recent research suggests that multiple factors may contribute and that both cardiac and respiratory mechanisms are involved. Both human and animal data suggest that specific genetic factors might play a role in some cases. Recent animal data suggest that serotonin might affect respiratory mechanisms and may be involved. Both cardiac and respiratory abnormalities are more likely with generalized tonic-clonic seizures. Uncontrolled epilepsy, particularly with generalized tonic-clonic seizures, appears to be the most highly associated modifiable risk factor for SUDEP.

Purpose: To evaluate whether the postoperative, antiepileptic drug (AED) regimen influences seizure recurrence after anterior temporal lobectomy when considering the putative mechanism of action and possible neuroprotective effects., Methods: This was a retrospective study. Patients who had an anterior temporal lobectomy for refractory epilepsy, whose preoperative MRI indicated mesial temporal sclerosis, were included. Postoperative AED regimens were compared with regard to seizure-outcome, considering the putative mechanism of action (sodium channel blockers, non-sodium channel blockers, and mixed mechanisms) or possible neuroprotective effect (levetiracetam, topiramate, tiagabine and zonisamide versus others). Time-to-event (first seizure after surgery) analysis was used to produce a Kaplan-Meier estimate of seizure recurrence, and groups were compared using Cox proportional hazard analysis., Results: 226 patients (103 males and 123 females; mean age 42 +/- 11 years) were studied. The rates of postoperative seizure recurrence were not significantly different between the three groups regardless of the use of AEDs with different mechanisms of action (p = 0.23). Fifty patients were receiving possibly neuroprotective AEDs and 176 patients were not. Rates of seizure recurrence were not significantly different between these two groups either (p = 0.11). The differences between one-year seizure-free rates were not significant when we compared levetiracetam versus phenytoin or carbamazepine., Discussion: There appeared to be no advantage or disadvantage to either prescribing drugs with different mechanisms of action or using drugs with possible neuroprotective effect after temporal lobectomy. Prospective studies with larger sample sizes may be of benefit to further explore this issue.

Corpus callosotomy is a palliative surgical procedure that is suitable for some patients with intractable seizures who are not candidates for focal resective surgery. The rationale for this procedure is based on the hypothesis that the corpus callosum is a critical pathway for interhemispheric spread of epileptic activity. Efficacy and relatively low permanent morbidity in corpus callosotomy for medically intractable epilepsy have been demonstrated by more than six decades of experience. Callosotomy best ameliorates drop attacks (tonic and atonic seizures), though tonic-clonic, absence, and frontal lobe complex partial seizures often respond as well. In addition to seizure reduction, behavior and quality of life may improve. Hence, callosotomy is justified as a therapy for appropriate patients with intractable epilepsy.

Objectives: To assess prognosis after late relapse in patients who are seizure free for the first 5 years after epilepsy surgery., Methods: Patients who were seizure free for the first 5 years after resective epilepsy surgery were included. Date of first seizure recurrence, current seizure status, medication, age, and type of surgery were prospectively registered. Non-parametric statistics were used., Results: One hundred and fifty-nine patients were studied. Thirty-two had at least one recurrent seizure. Time to event analysis showed an annual relapse rate of 4% between years 5 and 10 after surgery. At study termination, 143 of 159 patients (89.9%) were in terminal remission. For 30 patients with late relapse and at least 1-year follow-up thereafter, 53% were in terminal remission and 30% had experienced only rare or nocturnal seizures. Medication use was not associated either with likelihood of relapse or entering remission after relapse., Conclusions: Patients who are seizure free for the first 5 years after epilepsy surgery remain at risk for seizure recurrence. These relapses are often isolated events, and the long-term prognosis after relapse is often good. Relapse rates were similar in patients on and off AEDs, but the relation between AED taper and relapse is uncertain since patient groups may not be similar.

Epilepsy is associated with significantly increased morbidity and mortality from a variety of causes. Patients with epilepsy have approximately two to three times the risk of death from any cause compared with persons without epilepsy. Seizures may cause significant trauma, drowning, and accidental injury. Many of the deaths in persons with epilepsy are directly related to seizures, accidents and injuries arising from seizures, and the underlying condition resulting in seizures. This review focuses on recent data regarding seizure-related injury and mortality.

A 40-year-old man with a left frontotemporal grade II oligodendroglioma developed seizures that were refractory to 14 antiepileptic medications, the ketogenic diet, and epilepsy surgery. With temozolomide therapy, his seizure frequency gradually changed from 30 partial seizures per day to a single simple partial seizure in 6 months. No additional therapeutic measures were introduced during this time. This reduction in seizure frequency appears attributable solely to temozolomide therapy.

Mortality rates are higher in people with refractory epilepsy than in the general population. We assessed mortality rates in a prospectively followed cohort who had epilepsy surgery, to examine the factors related to mortality and to assess the relationship between seizure control and mortality. Five hundred eighty-three patients were evaluated. Mortality was strongly related to seizure control (p = 0.001), with 18 deaths observed in patients with recurrent seizures (mortality rate = 11.4 per 1,000 person-years) and 1 death in patients with no recurrent seizures (mortality rate = 0.85 deaths per 1,000 person-years). Patients with generalized epilepsy who had corpus callosotomy had a higher mortality rate than patients who had resective or transective surgery. The side of surgery and gender did not influence mortality rates. The standardized mortality ratio was 5.75 for patients with recurrent seizures and was significantly higher for females than males. These data show that the excess mortality associated with refractory epilepsy is eliminated after epilepsy surgery when seizures are abolished and suggest that epilepsy surgery reduces the risk of epilepsy-associated death.

Purpose: Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality for patients with epilepsy. Cardiac factors may be involved and were evaluated in this study., Methods: EEG and ECG data for 21 patients with definite (n = 6) or probable (n = 15) SUDEP were compared with data from a group of 43 patients with refractory partial epilepsy. ECG abnormalities and heart rate (HR) changes were correlated with clinical data., Results: Fourteen patients died in their sleep; two were awake. Ictal maximal HR (90 seizures from 16 of 21 patients) was significantly higher in SUDEP (mean, 149 beats/min, BPM) than in comparison patients (mean, 126 BPM; p < 0.001). Greater increases in HR were associated with seizures arising from sleep (78 BPM increase) than from wakefulness (47 BPM; p < 0.001) in SUDEP, as compared with the non-SUDEP group (52 BPM in sleep, 43 BPM in wakefulness; p = 0.27). Ictal cardiac repolarization and rhythm abnormalities occurred in 56% of SUDEP (including two atrial fibrillation, two ventricular premature depolarizations, two marked sinus arrhythmia, two atrial premature depolarizations, one junctional escape, one ST-segment elevation), and 39% of comparison patients (p = 0.39). No specific seizure onset (laterality or lobe) was associated with SUDEP., Conclusions: This study reveals, for the first time, evidence of increased autonomic stimulation (as measured by HR) associated with seizures, particularly in sleep, in patients with SUDEP, as compared with a clinically similar group of patients with refractory epilepsy.

Vagal nerve stimulation is an approved adjunctive treatment for medically intractable epilepsy. Although it is generally well tolerated, some patients experience pain, coughing, or hoarseness during stimulation. Lowering the pulse width in these patients alleviates pain and reduces voice alteration without loss of efficacy. This allows more optimal programming of stimulation intensities.

Objectives We investigated the seasonal pattern in births of patients with temporal lobe epilepsy and mesial temporal sclerosis. We hypothesized that the seasonal pattern in births of these patients is different from that in the general population. Materials and methods In this retrospective study, all patients who were evaluated for epilepsy surgery at Jefferson Comprehensive Epilepsy Center, Thomas Jefferson, Philadelphia, USA, between 1986 and 2014 and had a diagnosis of mesial temporal sclerosis (made by definite imaging findings of atrophy and/or sclerosis) were included. The seasonality in births of patients was compared with the seasonal pattern in the live births of the general population from Pennsylvania State. Results Two hundred and eighty-two patients (146 females and 136 males) were studied. The seasonality pattern in birth of patients was not statistically different from that in the general population. Conclusions The observed contradictory findings among various studies indicate the need for further studies to elucidate whether season of birth brings the possibility of acquiring various epilepsy syndromes in the future. To investigate any possible association between season of birth and epilepsy, we suggest avoid pooling all patients with epilepsy together. [ABSTRACT FROM AUTHOR]