Prolactin levels in sudden unexpected death in epilepsy

PURPOSE: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure. METHODS: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy. RESULTS: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects. CONCLUSIONS: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure.     

Elevated CK-MB mass and plasma brain-type natriuretic peptide concentrations following convulsive seizures in children and adolescents: Possible evidence of subtle cardiac dysfunction

Purpose:   To evaluate the presence of myocardial injury during convulsive seizures in children and adolescents by determining serum concentrations of cardiac troponin I (cTnI), creatine kinase-MB mass (CK-MB mass), and plasma brain-type natriuretic peptide (BNP).
Methods:   Thirty-one children (20 boys; mean age, 6.6 ± 5.34 years) with convulsive seizures and 50 healthy children were enrolled. Serum cTnI, CK-MB mass, and plasma BNP concentrations were analyzed 12 h after the seizure and repeated 7 days thereafter in the patient group and obtained one time in the control group.
Results:   The difference between serum concentrations of cTnI obtained 12 h and 7 days after the seizure was not statistically significant. cTnI levels 12 h postictal and those in control subjects also were not significantly different. CK-MB mass and BNP at the 12th h were higher than those obtained on the 7th day (p  <  0 . 05 and p  <  0 . 001, respectively). Children with seizures had increased levels of CK-MB mass and BNP 12 h after seizure than control subjects (p  <  0 . 05 and p  <  0 . 001, respectively). The results of electrocardiography (ECG) recordings, which were obtained up to 30 min after seizure activity, were completely normal in patients with seizure.
Conclusion:   Normal cTnI levels are not indicative of overt myocardial necrosis in patients with seizures. However, markedly elevated BNP concentrations together with elevated CK-MB mass levels do suggest subtle cardiac dysfunction in patients with seizure, and further large-scale studies are warranted.     

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.     

Comparison of Mesial Versus Neocortical Onset Temporal Lobe Seizures: Neurodiagnostic Findings and Surgical Outcome

Summary: We compared historical features, surface EEG findings, results of intracarotid sodium amobarbital memory testing (IAT), and outcome after anterotemporal lobectomy (ATL) in patients with mesiotemporal lobe seizure onset with those with more diffuse temporal lobe seizure onset (intracranial EEG). Forty-eight patients evaluated consecutively between July 1985 and October 1991 with both scalp/sphenoidal and intracranial EEG were shown to have seizures originating in one temporal lobe. No patients had temporal lobe tumor or vascular malformation. Thirty-seven of the 48 patients had seizure onset in the amygdale/hippocampus (amyg/hipp). Eleven of the 48 had either temporal neocortical onset or simultaneous amydhipp and neocortical onset. Patients with mesial onset seizures were more likely to have lateralized memory impairment on I AT (p = 0.05). We noted a trend toward a difference in age of first risk for epilepsy between the two groups (p = 0.09) but not for a difference in any specific risk factor. There were no significant differences in surface EEG interictal findings. Unlike in previous studies, comparison of outcome between the two groups showed no difference in seizure-free outcome. Sudden unexpected death (SUD) was more frequent in neocortical seizure patients who were not seizure-free (p < 0.05).     

Seizure-related cardiac repolarization abnormalities are associated with ictal hypoxemia

Purpose: Cardiac arrhythmias and respiratory disturbances have been proposed as likely causes for sudden unexpected death in epilepsy. Oxygen desaturation occurs in one‐third of patients with localization‐related epilepsy (LRE) undergoing inpatient video–electroencephalography (EEG) telemetry (VET) as part of their presurgical workup. Ictal‐related oxygen desaturation is accompanied by hypercapnia. Both abnormal lengthening and shortening of the corrected QT interval (QTc) on electrocardiography (ECG) have been reported with seizures. QTc abnormalities are associated with increased risk of sudden cardiac death. We hypothesized that there may be an association between ictal hypoxemia and cardiac repolarization abnormalities. Methods: VET data from patients with refractory LRE were analyzed. Consecutive patients having at least one seizure with accompanying oxygen desaturation below 90% and artifact‐free ECG data were selected. ECG during the 1 min prior to seizure onset (PRE) and during the ictal/postictal period with accompanying oxygen desaturation below 90% (DESAT) was analyzed. Consecutive QT and RR intervals were measured. In the same patients, DESAT seizures were compared with seizures without accompanying oxygen desaturation below 90% (NODESAT). For NODESAT seizures, QT and RR intervals for 2 min after seizure onset were measured. Key Findings: Thirty‐seven DESAT seizures were analyzed in 17 patients with localization‐related epilepsy. A total of 2,448 QT and RR intervals were analyzed during PRE. During DESAT, 1,554 QT and RR intervals were analyzed. Twelve of the 17 patients had at least one NODESAT seizure. A total of 19 NODESAT seizures were analyzed, including 1,558 QT and RR intervals during PRE and 3,408 QT and RR intervals during NODESAT. The odds ratio for an abnormally prolonged (>457 ms) QTcH (Hodges correction method) during DESAT relative to PRE was 10.64 (p < 0.0001). The odds ratio for an abnormally shortened (<372 ms) QTcH during DESAT relative to PRE was 1.65 (p < 0.0001). Seizure‐related shortening and prolongation of QTc during DESAT were also observed when Fridericia correction of the QT was applied. During DESAT seizures, the mean range of QT values (QTr) (61.14 ms) was significantly different from that during PRE (44.43 ms) (p = 0.01). There was a significant association between DESAT QTr and oxygen saturation nadir (p = 0.025) and between DESAT QTr and duration of oxygen desaturation (p < 0.0001). Both QTcH prolongation and shortening also occurred with NODESAT seizures. A seizure‐associated prolonged QTcH was more likely during DESAT than NODESAT, with an odds ratio of 4.30 (p < 0.0001). A seizure‐associated shortened QTcH was more likely during DESAT than NODESAT with an odds ratio of 2.13 (p < 0.0001). Significance: We have shown that the likelihood of abnormal QTcH prolongation is increased 4.3‐fold with seizures that are associated with oxygen desaturation when compared with seizures that are not accompanied with oxygen desaturation. The likelihood of abnormally shortened QTcH increases with seizures that are accompanied by oxygen desaturation with an odds ratio of 2.13 compared with that in seizures without desaturations. There is a significant association between the depth and duration of oxygen desaturation and QTr increase. These findings may be related to the pathophysiology of SUDEP.     

Ictal tachycardia: its discriminating potential between temporal and extratemporal seizure foci.

A wide variety of CNS lesions have been associated with changes in heart rate (HR). However, in epileptic patients their value to lateralize seizure onset remains controversial. This study aims to assess if HR changes associated with partial onset seizures could be useful in lateralizing seizure onset. We analysed HR changes on 100 seizures from 38 consecutive patients (mean age: 27.5 years) admitted for video-EEG telemetry monitoring. We evaluated the R-R interval 30 seconds before the seizure onset and 10, 20 and 120 seconds after the onset. We assessed whether there was a correlation between HR changes and seizure type, left/right differences and different semiological components for each seizure. We recorded 100 seizures. Three non-lateralized seizures were excluded from the analysis; 63/97 (65%) had left hemisphere onset, mainly from the temporal lobe (57.7%). The mean baseline HR was 77 beats per minute Ictal tachycardia (HR: > or = 107.06 beats per minute) was detected in 32 seizures, with ictal onset from the mesial temporal lobe structures in 23/32; 16/32 occurred during the first 10 seconds and 16/32 during the next 20 seconds from the seizure onset independently of the site of origin. Among the different semiological components for each seizure, only dystonic posturing and automatism correlated with HR increments. We did not find bradycardia in our series. Ictal tachycardia occurs most frequently with seizures arising from the mesial temporal lobe and it may not reliably predict the lateralization of seizure onset.     

The prevalence of prolonged cerebral seizures at the first treatment in a course of electroconvulsive therapy

BACKGROUND: It has been suggested that prolonged cerebral seizures are more prevalent in contemporary practice than realized partly because they may go undetected in the absence of monitoring by electroencephalogram (EEG). The previous report on this topic from Scotland concerned only patients taking part in research and may not be generalizable to routine clinical practice; moreover, the EEG monitoring was not all carried out at a standardized point in the course of treatment. OBJECTIVE: We sought to establish the prevalence of prolonged cerebral seizures in a representative sample from routine clinical practice in Edinburgh and do so at the first treatment, when the risk is greatest. METHOD: Two-channel EEG monitoring was conducted at the first treatment in a new course given to 100 individual consecutive patients. RESULTS: The titration had to be curtailed for anesthetic reasons in 2 patients, and no cerebral seizure was induced. Electroencephalogram measurement of seizure duration was practicable in only 95 of the remaining patients. Two cerebral seizures longer than 120 seconds were detected. One seizure ended spontaneously after 158 seconds and was associated with a generalized convulsion lasting 77 seconds. One was medically terminated after 180 seconds and was associated with a generalized convulsion lasting 122 seconds; this patient had an encephalopathy during the index illness. CONCLUSIONS: The prevalence of prolonged seizures in our routine clinical practice was 1% to 2%, depending on the definition of prolonged cerebral seizure activity.     

The Sudden Unexplained Death Syndrome in Epilepsy: Demographic, Clinical, and Postmortem Features

Sudden unexplained death syndrome (SUDS) accounts for about 10% of deaths in patients with epilepsy. It is associated with subtherapeutic postmortem serum antiepileptic drug (AED) levels but no anatomic cause of death on autopsy. The mechanisms of death are not known. We investigated 44 cases of SUDS for details of seizure history, treatment, medical and psychological history, events at the time of death, and postmortem findings. Cases of status epilepticus, drowning or other identifiable causes of death were excluded. Two groups emerged: five children with uncontrolled seizures receiving multiple AEDs and good compliance with medications, and 39 adults with less frequent seizures, often receiving monotherapy, but noncompliant with medications. Four children (80%) but only one adult (3%) had fully therapeutic postmortem AED levels. Sixty-three percent of adults recently had experienced an unusually stressful life event. Investigation of the circumstances at the time of death suggested two possible modes of death: (a) a seizure with an immediately fatal arrhythmia, or, (b) a seizure, recovery, then delayed secondary respiratory arrest or arrhythmia. Even though the mechanisms of death are unknown, the risk of SUDS may be reduced by encouraging patients to be compliant with medications, especially in times of unusual life stress.     

Periictal cerebral tissue hypoxemia: A potential marker of SUDEP risk

Cerebral oximetry has not been explored in patients experiencing seizures in the epilepsy monitoring unit (EMU). The purpose of our study was to evaluate the feasibility of periictal measurement of cerebral oxygenation using noninvasive cerebral tissue oximetry and to determine whether there was evidence of cerebral hypoxemia during generalized seizures. Cerebral oxygen saturation findings were subsequently correlated with sudden unexpected death in epilepsy (SUDEP) risk factors. We prospectively evaluated six patients admitted to our EMU with histories of generalized tonic–clonic seizures (GTCS) with prolonged scalp electroencephalography (EEG) and two regional cerebral oxygen saturation (rSO₂) sensors. Minimum rSO₂ values were recorded in the 5 min preceding seizure onset, during the seizure, and in the 5 min following seizure offset. SUDEP risk was assessed using the SUDEP‐7 Inventory. Cerebral oximetry was well tolerated, with a mean duration of rSO₂ monitoring of 81.1 h. Cerebral oxygen saturation data were available from at least one sensor in 9 (90%) of 10 seizures; only 6 (60%) of 10 seizures had useable periictal digital pulse oximetry data. GTCS were associated with significantly lower minimum ictal (p = 0.003) and postictal (p = 0.004) %rSO₂ values than the minimum preictal value. Patients with at least one seizure with a %rSO₂ decrease of ≥20% tended to have higher SUDEP‐7 Inventory scores (mean SUDEP‐7 Inventory score 7 ± 2.8) versus patients without recorded desaturations (4.3 ± 0.5, p = 0.08). Larger studies are needed to determine the value of cerebral oximetry in the identification of patients at risk of SUDEP.     

Postictal language assessment and lateralization of complex partial seizures

We performed a prospective study of ictal and postictal language function after 105 temporal lobe complex partial seizures in 26 patients. Seizure localization was verified by a greater than 90% reduction in seizure frequency after temporal lobectomy. At the time of the seizure, the patient was asked to read a test phrase aloud until it was read correctly and clearly. In all 62 seizures originating from the left temporal lobe, the patient took more than 68 seconds to read the test phrase correctly (mean, 321.9 seconds); in 42 of 43 seizures from the right temporal lobe, the patient read the test phrase in less than 54 seconds (mean, 19.7 seconds). Postictal paraphasias occurred in 46 of 62 seizures from the left temporal lobe (11 of 14 patients). In this study, quantifying the time delay in reading a test phrase lateralized seizure onset in all 26 patients tested, proving significantly more accurate than any other single noninvasive presurgical test.     

Effects of seizure repetition on postictal and interictal neurocardiac regulation in the rat

PURPOSE: Human epilepsy is associated with abnormalities in cardiac regulation, as measured by reductions of heart rate variability (HRV) and approximate entropy (ApEn), but it is not known how these abnormalities are related to seizure experience. METHODS: Baseline electrocardiogram (ECG) was recorded from seizure-naive rats. They were subjected daily to maximal electroshock (MES), which induced tonic seizures with hindlimb extension, for a total of 10 days. ECG was obtained for 30 min before and after the first and last seizure. R-R variability, spectral variability, and ApEn were calculated to determine changes in pre- and postictal cardiac regulation. Before the last seizure, interictal parameters were compared with baseline values to determine changes in interictal HRV as a consequence of seizure repetition. Postictal values obtained after the last seizure were compared with the initial postictal data to look for changes in postictal cardiac regulation. RESULTS: During the postictal state, a mild, but significant, loss of ApEn was present after either the first or last seizure. Seizure repetition induced loss of R-R variability and high-frequency spectral band, which was present both interictally and postictally. CONCLUSIONS: The results suggest that convulsive seizures are associated with an immediate reduction of the complexity of cardiac rhythm regulation, as reflected by reductions of ApEn. Seizure repetition may induce long-term neural abnormalities in neurocardiac regulatory systems, especially parasympathetic, which limit appropriate autonomic responses. These acquired abnormalities may, in turn, predispose individuals to cardiac arrhythmia and sudden unexpected death in epilepsy.     

Can patients perform volitional motor acts at the start of a seizure?

A seizure warning device might allow some individuals with partial seizures to protect themselves against consequences of seizures, but a prerequisite is the ability to take volitional action in response to a warning. The authors reviewed consecutive seizures in their epilepsy monitoring unit to determine whether patients could squeeze an event bulb, as instructed, at the start of their seizure. Only complex partial seizures with EEG changes and with the patient on camera were analyzed. Data were obtained from 77 patients, 42 with scalp monitoring and 35 with depth electrodes. Forty-seven percent had a left-hemisphere focus, 42% a right-hemisphere focus, and 11% multifocal seizures. The seizure focus was temporal in 68%. A magnetic resonance imaging consistent with mesial temporal sclerosis was seen in 29% of patients. Overall, 44% of the patients made at least one attempt to reach for the event bulb at the start of their seizures. Among the 72% of patients who gave a history of auras, 53% were able to press the event bulb compared to 20% with no history of auras (P = 0.016). EEG changes occurred a mean of 2.9+/-30.5 seconds after reaching for the bulb for scalp-recorded seizures (n = 20), and 16.2+/-13.7 seconds before behavior for depth-recorded seizures (n = 14, difference significant at P = 0.02). Neither seizure focus nor seizure laterality influenced the ability to press the event bulb. The authors conclude that nearly half of individuals with complex partial seizures can take volitional motor action at the start of their seizure. A method to enhance the intensity and timeliness of a seizure warning would not be wasted.     

Repeated amygdala-kindled seizures induce ictal rebound tachycardia in rats

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. In the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly.     

Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk

Purpose: Most people with epilepsy who die suddenly and whose death is attributed to sudden unexpected death in epilepsy (SUDEP) are found in or by the bed for unknown reasons. We assessed whether those with sleep‐related SUDEP were more likely to have nocturnal seizures, and whether seizure patterns (diurnal vs. nocturnal) differed from people dying suddenly and living controls with epilepsy. Methods: Seizure patterns in a cohort of 154 people with epilepsy who died suddenly and after autopsy conformed to the definition of SUDEP and 616 controls living with epilepsy were classified as having “exclusively diurnal” or “nocturnal seizures.” Comparisons were made between the groups. SUDEP was classified as sleep‐related or non–sleep‐related based on eyewitness accounts and the circumstances surrounding death. Key Findings: SUDEP was primarily a sleep‐related (58%) and unwitnessed (86%) event. If sleep‐related, SUDEP was more likely to be unwitnessed [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6–12]. Those with sleep‐related SUDEP were more likely to have a history of nocturnal seizures than those who had non–sleep‐related SUDEP (OR 3.6, 95% CI 1.4–9.4). Those who died were more likely to have a history of nocturnal seizures than living controls (OR 3.9, 95% CI 2.5–6.0). After correction for previously established SUDEP risk factors ( Langan et al., 2005 ), the presence of nocturnal seizures remained significant (OR 2.6, 95% CI 1.3–5.0). Significance: Nocturnal seizures seem to be an independent risk factor for SUDEP. These findings underscore the importance of preventive measures, which may include night supervision.     

Anoxia–ischemia: A mechanism of seizure termination in ictal asystole

Cerebral anoxia–ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self-termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia–ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously.     

Epilepsy‐related mortality is low in children: A 30‐year population‐based study in Olmsted County,MN

Purpose: Epilepsy is a common childhood neurologic disorder, affecting 0.5–1% of children. Increased mortality occurs due to progression of underlying disease, seizure‐related accidents, suicide, status epilepticus, aspiration during seizures, and sudden unexplained death in epilepsy (SUDEP). Previous studies show mortality rates of 2.7–6.9 per 1,000 person‐years. Potential risk factors include poor seizure control, intractable epilepsy, status epilepticus, tonic–clonic seizures, mental retardation, and remote symptomatic cause of epilepsy. Few population‐based studies of mortality and SUDEP in childhood‐onset epilepsy have been published. The purpose of this study is to report mortality and SUDEP from a 30‐year population‐based cohort of children with epilepsy. Methods: The Medical Diagnostic Index of the Rochester Epidemiology Project was searched for all codes related to seizure and convulsion in children living in Olmsted County, Minnesota and of ages birth through 17 years from 1980 through 2009. The medical records of these children were reviewed to identify all those with new‐onset epilepsy, and to abstract other baseline and follow‐up information. Potential risk factors including seizure type, epilepsy syndrome, history of status epilepticus, the presence and severity of neurologic impairment, and epilepsy outcome was reviewed. Epilepsy outcome was characterized by seizure frequency, number of antiseizure medications (antiepileptic drugs, AEDs) used, and number of AEDs failed due to lack of efficacy, and epilepsy intractability at 1 year and 2, 3, 5, 10, 15, and 20 years after epilepsy onset. We followed all children through their most recent visit to determine vital status, cause of death, and whether autopsy was performed. Key Findings: From 1980 to 2009, there were 467 children age birth through 17 years diagnosed with epilepsy while residents of Olmsted County, Minnesota, and who had follow‐up beyond the time of epilepsy diagnosis. Children were followed for a median of 7.87 years after the time of diagnosis (range 0.04–29.49 years) for a total of 4558.5 person‐years. Sixteen (3.4%) of the children died, or 3.51 deaths per 1,000 person‐years. Two deaths were epilepsy related (12.5%) for a rate of 0.44 per 1,000 person‐years. One of these children died of probable SUDEP and one died of aspiration during a seizure. The remaining 14 deaths (87.5%) were caused by other complications of underlying disease. Several risk factors for mortality were found, including abnormal cognition, abnormal neurologic examination, structural/metabolic etiology for epilepsy, and poorly controlled epilepsy. Significance: Although mortality in children with epilepsy was higher than what would be expected in the general pediatric population, death occurred significantly more in children with neurologic impairment and poorly controlled epilepsy. Epilepsy‐related death, including SUDEP, was rare and mortality due to epilepsy alone was similar to the expected mortality in the general population (observed deaths = 2, expected deaths = 1.77; standardized mortality ratio 1.13, 95% confidence interval 0.19–3.73, p = 0.86). By contrast, most children died of complications of the underlying neurologic disease or unrelated disease rather than the epilepsy.     

Seizure worsening and its predictors after epilepsy surgery

Purpose: This study aims to investigate seizure worsening and its predictors after epilepsy surgery. Methods: A retrospective chart review of patients who underwent unilobar epilepsy surgery between 1990 and 2007 and had recurrence of at least one seizure was performed. Seizure worsening was defined as an increase in total average monthly seizure frequency, average monthly generalized tonic–clonic seizures (GTCS), new‐onset GTCS, or new‐onset status epilepticus. The occurrence of sudden unexpected death in epilepsy (SUDEP) was captured. Multivariate logistic regression analysis was used to identify predictors of worsening. Key Findings: A total of 276 patients with postoperative seizure recurrence were identified. Monthly average seizure frequency worsening occurred in 9.8%, GTC worsening in 8.0%, new‐onset GTCs in 1.4%, new‐onset status epilepticus in 2.2%, and death from SUDEP in 1.4%. A higher risk of worsening was seen with extratemporal resections as compared to temporal lobe surgeries (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.21–7.95; p = 0.018), and in patients with low preoperative seizure frequency <30 seizures/month (OR 14.82, 95% CI 2.81–275.41; p = 0.0003). Predictors of increased GTCs included an incomplete resection (OR 3.98, 95% CI 1.39–12.59; p = 0.010) and multiple recorded ictal patterns (OR 5.91, 95% CI 1.20–26.96; p = 0.030). Multiple seizure semiologies correlated with worsening after temporal lobe resections. Significance: The most vulnerable patients for seizure worsening following epilepsy surgery include those with extratemporal resections, incomplete resections, and multiple recorded ictal patterns.     

Postictal generalized EEG suppression is linked to seizure-associated respiratory dysfunction but not postictal apnea

Purpose: The relationship of postictal generalized electroencephalography (EEG) suppression (PGES) with sudden unexpected death in epilepsy (SUDEP) is controversial. It has been suggested that PGES is associated with respiratory inhibition leading to SUDEP, but the relationship between PGES and respiratory depression is unknown. Respiratory rate and amplitude of airflow increase following seizures but there is persistent hypercapnia and hypoxemia. To determine whether seizures with PGES result in respiratory dysfunction, we analyzed respiratory parameters recorded during video‐EEG telemetry in patients with localization‐related epilepsy. Methods: Secondarily generalized convulsive seizures (GC) with PGES on scalp EEG or bilateral postictal attenuation (BA) on intracranial recordings were compared to GC without PGES/BA. Oxygen desaturation nadir and duration, end‐tidal CO₂ (ETCO₂), apnea duration, and duration of the seizure and of the convulsive component were compared in GC with or without PGES/BA. Key Findings: There was no significant difference between GC with (n = 30) or without PGES/BA (n = 72) for total seizure duration or duration of the convulsion. GC with PGES/BA had a mean oxygen desaturation nadir of 68.8 ± 11.8% (71.5, 43–88) (mean ± standard deviation [median, range]) that was lower (p = 0.002) than seizures without PGES/BA (76.31 ± 10.17% [79, 42–93]). The duration of desaturation was significantly longer and peak ETCO₂ higher in GC with PGES/BA. There was no difference in apnea duration. Apnea did not start during PGES/BA and did not typically extend into the postictal period in GC with or without PGES/BA. Significance: PGES is not associated with postictal central apnea but is more likely related to the severity of seizure‐associated intrinsic pulmonary dysfunction.     

Heart rate variability analysis indicates preictal parasympathetic overdrive preceding seizure‐induced cardiac dysrhythmias leading to sudden unexpected death in a patient with epilepsy

Evidence for seizure‐induced cardiac dysrhythmia leading to sudden unexpected death in epilepsy (SUDEP) has been elusive. We present a patient with focal cortical dysplasia who has had epilepsy for 19 years and was undergoing presurgical evaluation. The patient did not have any cardiologic antecedents. During long‐term video–electroencephalography (EEG) monitoring, following a cluster of secondarily generalized tonic–clonic seizures (GTCS), the patient had prolonged postictal generalized EEG suppression, asystole, followed by arrhythmia, and the patient died despite cardiopulmonary resuscitation. Analysis of heart rate variability showed a marked increase in the parasympathetic activity during the period preceding the fatal seizures, compared with values measured 1 day and 7 months before, and also higher than the preictal values in a group of 10 patients with GTCS without SUDEP. The duration of the QTc interval was short (335–358 msec). This unfortunate case documented during video‐EEG monitoring indicates that autonomic imbalance and seizure‐induced cardiac dysrhythmias contribute to the pathomechanisms leading to SUDEP in patients at risk (short QT interval). A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Clinical and electroencephalographic features of simple partial seizures

The clinical and electroencephalographic features of 87 simple partial seizures in 14 patients were studied with video-EEG telemetry. The patients were able to respond to verbal stimuli during all seizures and, later, could clearly recall ictal events. To determine whether the EEG changes in simple partial seizures could be reliably observed, a reader blindly reviewed four EEGs of equal duration for each seizure. These EEGs consisted of one ictal and three nonictal recordings obtained at predetermined times before the seizure. There were 27 motor seizures (mean duration, 86 seconds; range, 2 to 250 seconds), all involving clonic movements of the head and/or upper extremities; 8 (30%) of these had a sensory component (pain in 6, paresthesia in 2). An EEG change, usually localized spikes or sharp waves over the contralateral or both rolandic regions, was identifiable in nine (33%) of the motor seizures. The 60 nonmotor seizures (mean duration, 63 seconds; range, 8 to 375 seconds) involved a variety of symptoms, including somatosensory/special sensory (3 seizures), autonomic (26 seizures), cognitive (1 seizure), affective (14 seizures), and mixed, or more than one category of nonmotor symptoms (16 seizures). In only nine (15%) of the nonmotor seizures was there an ictal EEG change, usually localized spikes or paroxysmal theta activity over the temporal region. Overall, among the 87 simple partial seizures, only 18 (21%) revealed ictal EEG changes. Thus, a normal EEG is common during simple partial seizures and does not exclude the diagnosis.