Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

Drug-resistant temporal lobe epilepsy with temporal encephaloceles: How far to resect.

PURPOSE: This study sought to evaluate the impact of surgical extent on seizure outcome in drug-resistant temporal lobe epilepsy (DR-TLE) with temporal encephaloceles (TE). METHODS: This was a single-institution retrospective study of patients who underwent surgery for DR-TLE with TE between January 2008 and December 2020. The impact of surgical extent on seizure outcome was evaluated. In a subset with dominant DR-TLE, the impact of surgical extent on neuropsychometric outcome was evaluated. RESULTS: Thirty-four patients were identified (female, 56%; median age at surgery, 43 years). TE were frequently overlooked on initial magnetic resonance imaging (MRI), with encephaloceles only detected after repeat or expert re-review of MRI, additional multi-modal imaging, or intra-operatively in 31 (91%). Sixteen (47%) underwent limited resections, including encephalocele resection only (n = 5) and encephalocele resection with more extensive temporal corticectomy sparing the amygdala and hippocampus (n = 11). The remainder (n = 18, 53%) underwent standard anterior temporal lobectomy and amygdalohippocampectomy (ATLAH). Limited resection was performed more frequently on the left (12/17 vs. 4/17, p = 0.015). Twenty-seven patients (79%) had a favourable outcome (Engel I/II), and 17 (50%) were seizure-free at the last follow-up (median seizure-free survival of 27.3 months). There was no statistically significant difference in seizure-free outcomes between limited resection and ATLAH. In dominant DR-TLE, verbal memory decline was more likely after ATLAH than limited resection (3/4 vs. 0/9, p = 0.014). CONCLUSION: Expert re-review of imaging and multi-modal advanced imaging improved TE identification. There was no statistical difference in seizure-free outcomes based on surgical extent. Preservation of verbal memory supports limited resection in dominant temporal cases.

EEG Source Localization in Temporal Encephaloceles: Concordance With Surgical Resection and Clinical Outcomes.

PURPOSE: Temporal encephaloceles are a cause of drug-resistant temporal lobe epilepsy; however, their relationship with epileptogenesis is unclear, and optimal surgical resection is uncertain. EEG source localization (ESL) may guide surgical decision-making. METHODS: We reviewed patients at Mayo Clinic Rochester with drug-resistant temporal lobe epilepsy and temporal encephaloceles, who underwent limited resection and had 1-year outcomes. EEG source localization was performed using standard density scalp EEG of ictal and interictal activity. Distance from dipole and standardized low-resolution brain electromagnetic tomography (sLORETA) solutions to the encephalocele were measured. Concordance of ESL with encephalocele and surgical resection was compared with 1-year surgical outcomes. RESULTS: Seventeen patients met criteria. The mean distances from ESL results to encephalocele center for dipole and sLORETA analyses were 23 mm (SD 9) and 22 mm (SD 11), respectively. Ten patients (55.6%) had Engel I outcomes at 1 year. Dipole-encephalocele distance and sLORETA-encephalocele distance were significantly longer in patients with Engel I outcome and patients whose encephalocele was contained by sLORETA had worse outcome as well; however, multiple logistic regression analysis found that only containment of encephalocele by the sLORETA current density was significant (P < 0.05), odds ratio 0.12 (95% confidence interval [0.021, 0.71]). CONCLUSIONS: EEG source localization of scalp EEG localizes near encephaloceles, however, typically not in the encephalocele itself; this may be due to scalp EEG sampling propagated activity or alternatively that the seizure onset zone extends beyond the herniated cortex. Surprisingly, we observed increased ESL to encephalocele distances in patients with excellent surgical outcomes. Larger cohort studies including intracranial EEG data are needed to further explore this finding.

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.

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.