Duration of postictal impaired awareness after bilateral tonic-clonic seizures: EEG and patient characteristics.

OBJECTIVE: Ictal and postictal phenomena that may impact the duration of postictal impaired awareness have not been well studied. Postictal unresponsiveness invariably occurs following bilateral tonic-clonic seizures (BTCS). Bilateral tonic-clonic seizures are a major risk factor for sudden unexpected death in epilepsy (SUDEP). We quantify the effects of seizure characteristics on postictal recovery of awareness following BTCS. Factors include: the total seizure duration, the duration of the tonic phase of a BTCS, presence of postictal generalized EEG suppression (PGES), duration of postictal tonic electromyographic discharge, peri-ictal respiratory dysfunction, patient age, duration of epilepsy, and gender. METHODS: Fifty-eight patients admitted to the epilepsy monitoring unit with BTCS were studied. Forty-one had unilateral onset temporal seizures. The remainder had bitemporal onsets, extratemporal onsets, undetermined onsets, or were generalized at onset. Following the first BTCS, time to initial recovery of awareness and its possible association with patient and seizure characteristics as well as peri-ictal respiratory dysfunction were evaluated. The presence or absence of postictal agitation was noted. RESULTS: The severity of respiratory dysfunction and seizure characteristics were not associated with time to initial recovery of awareness. A shorter time to recovery of awareness was significantly associated with a younger age (p = 0.007). Postictal agitation was more common in males (p = 0.023). SIGNIFICANCE: Focal seizures may impair awareness by active inhibition of subcortical arousal mechanisms. Focal seizures progressing to bilateral tonic-clonic seizures (BTCS) result in further widespread cerebral dysfunction impacting postictal awareness. MRI studies show accelerated brain aging in patients with temporal lobe epilepsy. Our findings suggest that patient age, as a surrogate marker for the lifetime burden of seizures, results in a progressive worsening in time to recovery after BTCS by an increasing negative impact on networks involved in arousal.

Seizure-related apneas have an inconsistent linkage to amygdala seizure spread.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a frequent cause of death in epilepsy. Respiratory dysfunction is implicated as a critical factor in SUDEP pathophysiology. Human studies have shown that electrical stimulation of the amygdala resulted in apnea, indicating that the amygdala has a role in respiration control. Unilateral amygdala stimulation resulted in immediate onset of respiratory dysfunction occurring only during nose breathing. In small numbers of patients, some but not all spontaneous seizures resulted in apnea occurring shortly after seizure spread to the amygdala. With this study we aimed to determine whether seizure onset or spread to the amygdala was necessary and sufficient to cause apnea. METHODS: We investigated the temporal relationship between apnea/hypopnea (AH) onset and initial seizure involvement within the amygdala in patients with implanted depth electrodes. RESULTS: Data from 17 patients (11 female) with 47 seizures were analyzed. With seven seizures (three patients), AH preceded amygdala seizure involvement by 2 to 55 seconds. There was no AH with four seizures (three patients) that involved the amygdala. With eight seizures (four patients) AH occurred within 2 seconds following amygdala seizure onset. With 28 seizures, AH started >2 seconds after amygdala seizure onset (range 3-158 seconds). Following seizure onset, there was a significant difference between AH onset time and amygdala seizure onset (P < .001). The mean ± standard deviation (SD) AH onset was 27.8 ± 41.06 seconds, and the mean time to amygdala involvement was 8.83 ± 20.19 seconds. SIGNIFICANCE: There is a wide range of AH onset times relative to amygdala seizure involvement. With some seizures, amygdala seizure involvement occurs without AH. With other seizures, AH precedes amygdala seizures, suggesting that, with spontaneous seizures, involvement of the amygdala may not be crucial to induction of AH with all seizures. Other pathophysiology impacting brainstem respiratory networks may be of greater relevance to seizure-triggered apneas.

Superior accuracy and precision of SEEG electrode insertion with frame-based vs. frameless stereotaxy methods.

BACKGROUND: Stereotactic electroencephalography (SEEG) has largely become the preferred method for intracranial seizure localization in epileptic patients due to its low morbidity and minimally invasive approach. While robotic placement is gaining popularity, many centers continue to use manual frame-based and frameless methods for electrode insertion. However, it is unclear how these methods compare in regard to accuracy, precision, and safety. Here, we aim to compare frame-based insertion using a CRW frame (Integra®) and frameless insertion using the StealthStation™ S7 (Medtronic®) navigation system for common temporal SEEG targets. METHODS: We retrospectively examined electrode targets in SEEG patients that were implanted with either frame-based or frameless methods at a level 4 epilepsy center. We focused on two commonly used targets: amygdala and hippocampal head. Stealth station software was used to merge pre-operative MR with post-operative CT images for each patient, and coordinates for each electrode tip were calculated in relation to the midcommissural point. These were compared to predetermined ideal coordinates in regard to error and directional bias. RESULTS: A total of 81 SEEG electrodes were identified in 23 patients (40 amygdala and 41 hippocampal head). Eight of 45 electrodes (18%) placed with the frameless technique and 0 of 36 electrodes (0%) placed with the frame-based technique missed their target and were not clinically useful. The average Euclidean distance comparing actual to ideal electrode tip coordinates for frameless vs. frame-based techniques was 11.0 mm vs. 7.1 mm (p < 0.001) for the amygdala and 12.4 mm vs. 8.5 mm (p < 0.001) for the hippocampal head, respectively. There were no hemorrhages or clinical complications in either group. CONCLUSIONS: Based on this series, frame-based SEEG insertion is significantly more accurate and precise and results in more clinically useful electrode contacts, compared to frameless insertion using a navigation guidance system. This has important implications for centers not currently using robotic insertion.

Tonic electromyographic activity following bilateral tonic-clonic seizures is associated with periictal respiratory dysfunction and postictal generalized EEG suppression.

OBJECTIVE: No biomarkers reliably predict risk for sudden unexpected death in epilepsy (SUDEP). Postictal generalized electroencephalography (EEG) suppression (PGES) is a possible biomarker for SUDEP risk. However, its utility in predicting SUDEP remains uncertain. We had observed that postictal tonic electromyography (PTEMG) activity follows some generalized convulsive seizures (GCS). PTEMG activity and PGES may have a common pathophysiologic basis. PGES is associated with periictal respiratory distress. There is evidence that tonic EMG occurs with brain hypoxia. Thus PTEMG activity may be related to seizure-associated hypoxemia. Pronounced variation occurs among expert clinicians in identifying PGES, thereby limiting its utility as a biomarker. Characteristics of PTEMG activity and its relationship to preceding GCS have not been explored. We studied PTEMG activity characteristics, its relationship to the preceding seizure and associated respiratory dysfunction. METHODS: We reviewed 145 GCS in 66 patients undergoing video-EEG telemetry (VET). The presence of PTEMG activity was defined when tonic EMG occurred for at least 3 seconds following seizure termination and was identified with filter settings at 5-200 Hz. Duration of PTEMG activity, the seizure, PGES, seizure-associated peripheral capillary oxygen saturation (SpO2 ) change, and end-tidal CO2 were analyzed. We compared data from GCS with and without PTEMG activity. RESULTS: Ninety of 145 seizures with GCS had PTEMG activity. The remainder had postictal slowing without PTEMG activity, and cessation of activity was followed by EEG slowing. Duration of the initial PTEMG discharge was 39.1 (mean) ± (standard deviation) 17.9 seconds. SpO2 nadir was lower (P = 0.005) in seizures with PTEMG activity than in those without (72% vs 77%). End-tidal CO2 was higher (P = 0.05) in seizures with PTEMG activity than in those without (63  vs 56 mm Hg). PGES duration was 35.6 ± 22.2 seconds and associated with duration of PTEMG activity (P < 0.001). SIGNIFICANCE: The novel finding is that PTEMG activity occurs following 62% of GCS and that seizures with PTEMG activity have greater severity of respiratory dysfunction than seizures without. PTEMG activity is readily discerned by visual analysis of VET at appropriate filter settings and has the potential of being a complementary or surrogate biomarker of PGES for assessing SUDEP risk.

Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic-clonic seizures in sleep and wakefulness.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic-clonic seizures (GTCS) in sleep. Postictal generalized electroencephalography (EEG) suppression (PGES), postictal immobility, and periictal respiratory dysfunction are potential risk factors for SUDEP. We sought to determine whether there was a difference in respiratory dysfunction, PGES, and postictal immobility for GTCS occurring during wakefulness or sleep. METHODS: We retrospectively analyzed video-EEG telemetry data in the epilepsy-monitoring unit. Patients' state at seizure onset and seizure characteristics were identified. Respiratory parameters and heart rate were recorded. Presence and duration of PGES and time to first postictal nonrespiratory movement were recorded. RESULTS: There were 165 seizures in 67 patients. There was no significant difference in the duration of postictal immobility in GTCS occurring out of wakefulness or sleep (p = 0.280). Oxygen desaturation nadir (p = 0.572) and duration of oxygen desaturation were not significantly different for GTCS starting during sleep or wakefulness (p = 0.992). PGES occurred more frequently when seizure onset was in sleep than in wakefulness (p = 0.004; odds ratio [OR] 2.760). There was no difference in the duration of PGES between the two groups. SIGNIFICANCE: PGES occurs more commonly after GTCS in sleep than in wakefulness but, in the epilepsy-monitoring unit (EMU), a patient's state at seizure onset does not affect the degree of respiratory dysfunction or duration of postictal immobility. In sleep, outside the hospital setting, GTCS are likely to go unnoticed. Postictal immobility in prone patients prevents head repositioning and unimpeded air exchange. A positive feedback cycle ensues with increasing respiratory distress, potentiating postictal immobility and PGES and eventually leading to asystole. Our findings suggest that the high incidence of nocturnal SUDEP may be related to the unsupervised environment during sleep rather than the severity of sleep-related respiratory dysfunction or PGES duration in the immediate postictal period.

Potentially high-risk cardiac arrhythmias with focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures are associated with the duration of periictal hypoxemia.

OBJECTIVE: To investigate potentially high-risk cardiac arrhythmias (PHAs) following focal to bilateral tonic-clonic seizures (FBTCSs) and generalized tonic-clonic seizures (GTCSs) and to study the association of PHAs with seizure characteristics and the severity of associated ictal respiratory dysfunction. METHODS: Electrocardiographic (EKG) and pulse oximetry (SpO2 ) data were recorded concurrently with video-electroencephalographic telemetry in the epilepsy monitoring unit (EMU). One minute of preictal EKG, the ictal EKG, and 2 min of ictal/postictal data were reviewed for each seizure. Nonsustained ventricular tachycardia, bradyarrhythmia, and/or sinus pauses were considered as PHAs. FBTCSs/GTCSs with PHAs were compared to those that had only ictal sinus tachycardia. RESULTS: Data from 69 patients with 182 FBTCSs/GTCSs with usable SpO2 and EKG recordings were available. There were 10 FBTCSs/GTCSs in 10 patients with a PHA. The presence of PHAs was not associated with seizure duration or SpO2 nadir. FBTCSs/GTCSs with a PHA were significantly associated with the duration of oxygen desaturation < 90% when compared with FBTCSs/GTCSs with only sinus tachycardia (Mann-Whitney, p = 0.042). Desaturation duration of <100 s was not significantly associated with occurrence of PHAs (p = 0.110) when compared with seizures that had only sinus tachycardia. The odds ratio for occurrence of PHA was 7.86 for desaturation durations ≥ 125 s versus desaturations < 125 s (p = 0.005). The odds ratio increased to 13.09 for desaturation durations ≥ 150 s (p < 0.001). Preictal and ictal/postictal arrhythmias occurred with focal seizures that did not progress to FBTCSs. Four patients with focal seizures had ictal/postictal PHAs without preictal PHAs. Two of these patients had evidence for prior cardiac disturbance. SIGNIFICANCE: PHAs following a single FBTCS/GTCS in the EMU are significantly associated with the duration of ictal/postictal hypoxemia. It is possible that FBTCS/GTCS-associated hypoxemia may trigger fatal cardiac arrhythmias in a subset of susceptible patients dying of sudden unexpected death in epilepsy.

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction.

OBJECTIVE: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit. METHOD: We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. RESULTS: Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. SIGNIFICANCE: The duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) risk reduction remains a critical aim in epilepsy care. To date, only aggressive medical and surgical efforts to control seizures have been demonstrated to be of benefit. Incomplete understanding of SUDEP mechanisms limits the development of more specific interventions. Periictal cardiorespiratory dysfunction is implicated in SUDEP; postictal electroencephalography (EEG) suppression, coma, and immobility may also play a role. Nocturnal supervision is protective against SUDEP, presumably by permitting intervention in the case of a life-threatening event. Resuscitative efforts were implemented promptly in near-SUDEP cases but delayed in SUDEP deaths in the Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) study. Nursing interventions--including repositioning, oral suctioning, and oxygen administration--reduce seizure duration, respiratory dysfunction, and EEG suppression in the epilepsy monitoring unit (EMU), but have not been studied in outpatients. Cardiac pacemakers or cardioverter-defibrillator devices may be of benefit in a few select individuals. A role for implantable neurostimulators has not yet been established. Seizure detection devices, including those that monitor generalized tonic-clonic seizure-associated movements or cardiorespiratory parameters, may provide a means to permit timely periictal intervention. However, these and other devices, such as antisuffocation pillows, have not been adequately investigated with respect to SUDEP prevention.

Impact of periictal interventions on respiratory dysfunction, postictal EEG suppression, and postictal immobility.

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Seizure-related respiratory dysfunction (RD), the duration of postictal generalized electroencephalography (EEG) suppression (PGES), and duration of postictal immobility (PI) may be important in the pathophysiology of SUDEP. Periictal interventions may reduce the risk of SUDEP. METHODS: We assessed the impact of periictal nursing interventions on RD, PGES, and PI duration in patients with localization-related epilepsy and secondarily generalized convulsions (GCs) recorded during video-EEG telemetry in the epilepsy monitoring unit. Video-EEG data were retrospectively reviewed. Interventions including administration of supplemental oxygen, oropharyngeal suction, and patient repositioning were evaluated. Interventions were performed based on nursing clinical judgment at the bedside and were not randomized. The two-sided Wilcoxon rank-sum test was used to compare GCs with and those without intervention. Robust simple linear regression was used to assess the association between timing of intervention and duration of hypoxemia (SaO(2) < 90%), PGES, and PI using data from only the first GC for each patient. KEY FINDINGS: Data from 39 patients with 105 GCs were analyzed. PGES >2 s occurred following 31 GCs in 16 patients. There were 21 GCs with no intervention (NOINT) and 84 GC with interventions (INT). In the INT group, the duration of hypoxemia was shorter (p = 0.0014) when intervention occurred before hypoxemia onset (mean duration 53.1 s) than when intervention was delayed (mean duration 132.42 s). Linear regression indicated that in GCs with nursing interventions, earlier intervention was associated with shorter duration of hypoxemia (p < 0.0001) and shorter duration of PGES (p = 0.0012). Seizure duration (p < 0.0001) and convulsion duration (p = 0.0457) were shorter with earlier intervention. PI duration was longer for GCs with PGES than GCs without PGES (p < 0.0001). The mean delay to first active nonrespiratory movement following GCs with PGES was 251.96 s and for GC without PGES was 66.06 s. The duration of PI was positively associated with lower SaO(2) nadir (p = 0.003) and longer duration of oxygen desaturation (p = 0.0026). There was no association between PI duration and seizure duration (p = 0.773), between PI duration and PGES duration (p = 0.758), or between PI duration and the timing of first intervention relative to seizure onset (p = 0.823). PGES did not occur in the NOINT group. The mean duration of desaturation was longer (110.9 vs. 49.9 s) (p < 0.0001), mean SaO(2) nadir was lower (72.8% vs. 79.7%) (p = 0.0086), and mean end-tidal CO(2) was higher (58.6 vs. 50.3 mmHg) (p = 0.0359) in the INT group compared with the NOINT group. The duration of the seizure or of the convulsive component was not significantly different between the INT and NOINT groups. SIGNIFICANCE: Early periictal nursing intervention was associated with reduced duration of RD and reduced duration of PGES. These findings suggest the possibility that such interventions may be effective in reducing the risk of SUDEP in the outpatient setting. Validation of these preliminary data with a prospective study is needed before definitive conclusions can be reached regarding the efficacy of periictal interventions in reducing the risk of SUDEP.

Reading Epilepsy and Language Processing: A Proposed Role for Semantic Salience.

SUMMARY: Reading epilepsy is a relatively rare reflex epilepsy syndrome that typically presents as orofacial reflex myoclonus triggered by reading. Seizures are thought to be because of activation of hyperexcitable language-related pathways in the dominant hemisphere that subsequently spreads to adjacent motor cortices. More difficult reading tasks are thought to be more provocative of seizures regardless of semantic understanding of the text. The authors sought to better characterize the role of text difficulty and comprehension in triggering seizures in a 27-year-old patient with reading epilepsy. As a part of his epilepsy monitoring unit admission, the patient underwent a series of reading trials with increasing semantic salience and/or difficulty, including pseudo-reading of colors and foreign-language texts, which demonstrated a positive correlation between spike count and clinical events and increasing semantic salience. This suggests that our novel reading task may be able to differentiate between different processes in the reading pathway and that increased semantic relevance of the text, rather than increased difficulty per se, can be associated with increased seizures in reading epilepsy. The authors theorize that this may be associated with his atypical (nondominant) right hemispheric seizure focus and propose that further study of patients with reading epilepsy syndrome may help elucidate the neurobiological networks involved in reading and language processing.

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 CO(2) (ETCO(2) ), 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 ETCO(2) 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.

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.

The impact of sub specialization within functional neurosurgery on patient outcomes in a comprehensive epilepsy center.

BACKGROUND: One in three patients with epilepsy are medication-refractory and may benefit from investigations and operative treatment at a comprehensive epilepsy center. However, while these centers have capabilities for advanced seizure monitoring and surgical intervention, they are not required to have a functional neurosurgeon who is primarily focused in epilepsy surgery. Therefore, the objective of this study is to determine the impact of having a sub-specialized, epilepsy-focused functional neurosurgeon on patient outcomes. METHODS: We conducted a retrospective chart review for all patients who underwent surgical intervention for medically refractory epilepsy at a Level 4 comprehensive Epilepsy Center from 2008 through 2019. Data was divided into two groups: group 1 comprised patients who had surgery before the hiring of a dedicated epilepsy-focused functional neurosurgeon in 2016, and group 2 was afterwards. We compared surgical procedures, significant complications, and seizure outcomes. RESULTS: A total of 101 patients underwent 105 operations (52 in group 1 and 53 in group 2), not including intracranial EEG insertion. Compared to group 1, group 2 had more surgeries performed per year (15.1 vs. 6.5), and a significantly lower Engel score at last follow-up (1.78 vs. 2.57; p < 0.001). There was no difference in percentage of cases undergoing iEEG, and no difference in complication rates. CONCLUSIONS: In this series, the hiring of a sub-specialized functional neurosurgeon dedicated to epilepsy surgery in a comprehensive epilepsy center was associated with an increase in surgical volume and improved seizure outcomes.

Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two deaths in video-EEG-monitored patients.

Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in patients with epilepsy, with cardiorespiratory dysfunction and a primary cessation of cerebral function proposed as causes. We report two cases of SUDEP in patients with intractable temporal lobe epilepsy undergoing video-EEG (electroencephalography) telemetry at two centers. Both had secondarily generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes in these two patients are reported herein. Ictal/postictal hypoventilation may contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure of recovery of cortical function and eventual cardiac failure.

Serotonin reuptake inhibitors are associated with reduced severity of ictal hypoxemia in medically refractory partial epilepsy.

Ictal respiratory dysfunction occurs in patients with epilepsy and may contribute to sudden unexplained death in epilepsy (SUDEP). Fluoxetine reverses respiratory arrest in a mouse model of epilepsy, suggesting that selective serotonin reuptake inhibitors (SSRIs) may reduce ictal respiratory dysfunction. Video­electroencephalography (EEG) and pulse oximetry data from 496 seizures in 73 consecutive patients with partial epilepsy was reviewed, including 87 seizures in 16 patients taking SSRIs (SSRI+) and 409 seizures in 57 patients not taking SSRIs (SSRI)). The proportion of ictal-related oxygen desaturation <85% with partial seizures without secondary convulsions in SSRI+ patients was reduced relative to SSRI) patients (p = 0.011). There was no statistically significant difference in ictal oxygen desaturation for secondarily generalized convulsions. SSRIs are associated with reduced likelihood of ictal oxygen desaturation in patients with partial seizures.

Respiratory changes with seizures in localization-related epilepsy: analysis of periictal hypercapnia and airflow patterns.

PURPOSE: The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient-years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one-third of seizures in localization-related epilepsy. We now report on respiratory changes in the ictal/postictal period including changes in end-tidal CO2 (ETCO2) that correlate directly with alveolar CO(2) , allowing a precise evaluation of seizure-related respiratory disturbances. METHODS: One hundred eighty-seven seizures were recorded in 33 patients with localization-related epilepsy, with or without secondarily generalized convulsions, undergoing video-electroencephalography (EEG) telemetry with recording of respiratory data. RESULTS: The ictal/postictal ETCO2 increase from baseline was 14 ± 11 mm Hg (11, -1 to 50) [mean ± standard deviation (SD) (median, range)]. ETCO2 peak was at or above 50 mm Hg with 35 of 94 seizures, 60 mm Hg with 15, and 70 mm Hg with five seizures. Eleven of the 33 patients had seizures with ETCO2 elevation above 50 mm Hg. The duration of ictal/postictal ETCO(2) increase above baseline was 424 ± 807 s (154, 4 to 6225). The duration of ictal apnea was 49 ± 46 s (31, 6-222); most ictal apneic events were central. Oxygen desaturation to 60% or less occurred with 10 seizures, including five that did not progress to generalized convulsions. Respiratory rate and amplitude increased postictally. The peak ictal ETCO2 change and duration of change were not associated with apnea duration or seizure duration. Peak ETCO2 change was significantly associated with contralateral seizure spread. CONCLUSIONS: Severe and prolonged increases in ETCO2 occur with seizures. Postictally, respiratory effort is not impaired. Ictally triggered ventilation-perfusion inequality from pulmonary shunting or transient neurogenic pulmonary edema may account for these findings.

Depression in epilepsy is associated with lack of seizure control.

Depression is common in patients with epilepsy and the strongest predictor of poor quality of life. Few studies have assessed the association of uncontrolled seizures with depression. We used the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), a validated six-item self-report questionnaire, to assess the relationship between depression, seizure control, and antiepileptic drug (AED) and antidepressant drug usage. Two hundred ninety-eight patients were studied. Twenty percent of patients with any epileptic seizures over a 6-month period had NDDI-E scores >15, consistent with major depression. Higher NDDI-E scores were associated with higher seizure frequency (P<0.0002). The prevalence ratio of NDDI-E scores >15 in patients with no seizures versus any seizure in the past 6 months was 0.48 (95% CI = 0.26-0.88). Higher NDDI-E scores were associated with the number of AEDs taken (P = 0.0023). Major depression is associated with uncontrolled seizures, with a prevalence double that of patients whose seizures are controlled.

Severity of Peri-ictal Respiratory Dysfunction With Epilepsy Duration and Patient Age at Epilepsy Onset.

Respiratory dysfunction preceding death is fundamental in sudden unexpected death in epilepsy (SUDEP) pathophysiology. Hypoxia occurs with one-third of seizures. In temporal lobe epilepsy, there is volume loss in brainstem regions involved in autonomic control and increasing neuropathological changes with duration of epilepsy suggesting increasingly impaired regulation of ventilation. In animal models, recurrent hypoxic episodes induce long-term facilitation (LTF) of ventilatory function, however, LTF is less robust in older animals. LTF of ventilation may, to some degree, ameliorate the deleterious effects of progressive brainstem atrophy. We investigated the possibility that the duration of epilepsy, or age at epilepsy onset, may impact the severity of seizure-associated respiratory dysfunction. Patients with focal epilepsy undergoing video-EEG telemetry in the epilepsy monitoring unit (EMU) were studied. We found a significant relationship between age at epilepsy onset and duration of peri-ictal oxygen desaturation for focal seizures not progressing to bilateral tonic-clonic seizures, with longer duration of peri-ictal oxygen desaturation in patients with epilepsy onset at an older age but no significant relationships between duration of epilepsy or age at EMU admission and ventilatory dysfunction. Our findings suggest an intriguing possibility that LTF of ventilation may be protective when epilepsy starts at a younger age.

Ictal apnea linked to contralateral spread of temporal lobe seizures: Intracranial EEG recordings in refractory temporal lobe epilepsy.

PURPOSE: Respiratory mechanisms are implicated in sudden unexpected death in epilepsy (SUDEP). We previously demonstrated a high incidence of ictal hypoxemia in temporal lobe seizures. We now report on the temporal relationship between ictal apnea and seizure onset and spread in patients undergoing video-EEG (electroencephalography) telemetry (VET) with intracranial electrodes. METHODS: Ten patients with medically refractory temporal lobe epilepsy (TLE) undergoing VET were studied. Data from synchronously recorded digital pulse oximetry (SaO(2)), end-tidal CO(2) (ETCO(2)), nasal airflow, abdominal excursions, and electrocardiography were obtained. RESULTS: Sixty-one seizures were captured. SaO(2) in the ictal/postictal period was available for 52 seizures, apnea onset times for 27 seizures, and ETCO(2) for 16 seizures. Apneas occurred only when seizures spread to the contralateral temporal lobe. The mean delay to apnea onset was significantly shorter after contralateral seizure spread (2.87 s) than after seizure onset (58.4 s); p < 0.001. The mean SaO(2) nadir with partial seizures or partial seizures prior to secondary generalization was 89.4 +/- 8.6% (91.5, 69-100). Following generalized convulsions the mean oxygen saturation nadir was 75.8 +/- 10.6% (78.5, 58-90). ETCO(2) elevations occurred with each ictal desaturation below 85%. CONCLUSIONS: There is a close temporal relationship between spread of seizures to the contralateral hemisphere and the onset of seizure-associated apnea. Apnea onsets are more tightly linked to time of contralateral spread than to time of seizure onset. Patients with TLE in whom there is evidence of contralateral seizure spread may be at higher risk for ictal-related respiratory dysfunction than those in whom seizures remain unilateral.

Ictal hypoxemia in localization-related epilepsy: analysis of incidence, severity and risk factors.

Ictal hypoxemia has been reported in small series of cases and may contribute to sudden unexpected death in epilepsy (SUDEP). We sought to determine the incidence and severity of ictal hypoxemia in patients with localization-related epilepsy undergoing in-patient video-EEG telemetry. We examined whether seizure-associated oxygen desaturation was a consequence of hypoventilation and whether factors such as seizure localization and lateralization, seizure duration, contralateral spread of seizures, patient position at seizure onset and body mass index influenced ictal-related hypoxemia. A total of 304 seizures with accompanying oxygen saturation data were recorded in 56 consecutive patients with intractable localization-related epilepsy; 51 of 304 seizures progressed to generalized convulsions. Pulse oximetry showed oxygen desaturations below 90% in 101 (33.2%) of all seizures with or without secondary generalization, with 31 (10.2%) seizures accompanied by desaturations below 80% and 11 (3.6%) seizures below 70%. The mean duration of desaturation below 90% was 69.2 +/- 65.2 s (47; 6-327). The mean oxygen saturation nadir following secondary generalization was 75.4% +/- 11.4% (77%; 42-100%). Desaturations below 90% were significantly correlated with seizure localization [P = 0.005; odds ratio (OR) of temporal versus extratemporal = 5.202; 95% CI = (1.665, 16.257)], seizure lateralization [P = 0.001; OR of right versus left = 2.098; 95% CI = (1.078, 4.085)], contralateral spread of seizures [P = 0.028; OR of contralateral spread versus no spread = 2.591; 95% CI = (1.112, 6.039)] and gender [P = 0.048; OR of female versus male = 0.422; 95% CI = (0.179, 0.994)]. In the subset of 253 partial seizures without secondary generalized convulsions, 34.8% of seizures had desaturations below 90%, 31.8% had desaturations below 80% and 12.5% had desaturations below 70%. The degree of desaturation was significantly correlated with seizure duration (P = 0.001) and with electrographic evidence of seizure spread to the contralateral hemisphere (P = 0.003). Central apnoeas or hypopnoeas occurred with 50% of 100 seizures. Mixed or obstructive apnoeas occurred with 9% of these seizures. End-tidal carbon dioxide (ETCO2) was recorded in seven patients (19 seizures). The mean increase in ETCO2 from preictal baseline was 18.6 +/- 17.7 mm Hg (13.2; 2.8-77.8). In these 19 seizures, all oxygen desaturations below 85% were accompanied by an increase in ETCO2. Ictal hypoxemia occurs often in patients with localization-related epilepsy and may be pronounced and prolonged; even with seizures that do not progress to generalized convulsions. Oxygen desaturations are accompanied by increases in ETCO2, supporting the assumption that ictal oxygen desaturation is a consequence of hypoventilation. Ictal hypoxemia and hypercapnia may contribute to SUDEP.