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.

Triggered: Discovery of Neurocysticercosis Following Self-Administered Albendazole.

A 25-year-old man with no medical history presented with a seizure one month after taking a self-administered dose of albendazole. Magnetic resonance imaging (MRI) of the brain revealed multiple ring-enhancing lesions, and the workup confirmed neurocysticercosis (NCC). Treatment with antiparasitics was delayed due to concern for worsening symptoms from the presence of cysts in the midbrain and hippocampus. The balance between treating NCC and limiting cerebral inflammation is delicate and relies on judgment from a multispecialty clinical team. In this case, corticosteroids and antiepileptics alone prevented additional seizures but failed to reduce the overall inflammation of cysts and the progression of the disease. Evidence of new cysts on MRI at week 13 from the onset of symptoms was evidence of an acute, evolving infectious process. Treatment with albendazole and praziquantel was initiated at 13 weeks from the onset of symptoms, and by 31 weeks, nearly all cysts had resolved with minimal residual inflammation.

Combined Responsive Neurostimulation and Focal Resection for Super Refractory Status Epilepticus: A Systematic Review and Illustrative Case Report.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a neurologic emergency with high mortality and morbidity. Although medical algorithms typically are effective, when they do fail, options may be limited, and neurosurgical intervention should be considered. METHODS: We report a case of SRSE treated acutely with responsive neurostimulation (RNS) and focal surgical resection after intracranial monitoring. We also conducted a systematic review of the literature for neurosurgical treatment of SRSE (e.g., neurostimulation). Only published manuscripts were considered. RESULTS: Our patient's seizure semiology consisted of left facial twitching with frequent evolution to bilateral tonic-clonic convulsions. Stereoelectroencephalography and grid monitoring identified multiple seizure foci. The patient underwent right RNS placement with cortical strip leads over the lateral primary motor and premotor cortex as well as simultaneous right superior temporal and frontopolar resection. Status epilepticus resolved 21 days after surgical resection and placement of the RNS. The systematic review revealed 15 case reports describing 17 patients with SRSE who underwent acute neurosurgical intervention. There were 3 patients with SRSE with RNS placement as a single modality, all of whom experienced cessation of SE. Four patients with SRSE received vagus nerve stimulation (3 as a single modality and 1 with combined corpus callosotomy), of whom 1 had SE recurrence at 2weeks. Two patients with SRSE received deep brain stimulation, and the remaining 8 underwent surgical resection; none had recurrence of SE. CONCLUSIONS: RNS System placement with or without resection can be a viable treatment option for select patients with SRSE. Early neurosurgical intervention may improve seizure outcomes and reduce complications.

Isolated Agenesis of Septum Pellucidum and Adult-Onset Seizure Tendency With Eye Closure Sensitivity.

Septum pellucidum is a thin midline membrane that separates the anterior horns of the lateral ventricle. Agenesis of septum pellucidum (ASP) is considered a continuum of forebrain maldevelopment. Isolated ASP is a rare radiographic finding of unclear significance. We report a case of a 42-year-old male with ASP who presented with a new-onset seizure and eye closure sensitivity seen in the electroencephalogram. Magnetic resonance imaging of the brain confirmed the ASP. In the absence of data about the association between seizure and ASP, further studies are needed to determine its significance.

New-Onset Seizure With Possible Limbic Encephalitis in a Patient With COVID-19 Infection: A Case Report and Review.

With the outbreak of COVID-19 (coronavirus disease 2019) as a global pandemic, various of its neurological manifestations have been reported. We report a case of a 54-year-old male with new-onset seizure who tested positive for severe acute respiratory syndrome coronavirus 2 from a nasopharyngeal swab sample. Investigative findings, which included contrast-enhancing right posterior temporal lobe T2-hyperintensity on brain magnetic resonance imaging, right-sided lateralized periodic discharges on the electroencephalogram, and elevated protein level on cerebrospinal fluid analysis, supported the diagnosis of possible encephalitis from COVID-19 infection. The findings in this case are placed in the context of the existing literature.

Latency to First Event is Shorter in Psychogenic Non-epileptic Seizures than in Epileptic Seizures in an Epilepsy Monitoring Unit.

Objective: The objective was to study latency to first event among patients with psychogenic nonepileptic seizures compared (PNES) to epileptic seizures (ES) in an epilepsy monitoring unit (EMU). Introduction: PNES are common imitators of ES. This study investigates latency to first event in patients with PNES compared to patients with ES. Methods: We performed a retrospective chart review of patients admitted to our EMU from March 2016 to October 2017. We identified patients with PNES and ES. Patients with other nonepileptic events and mixed PNES (epilepsy plus PNES) were excluded. Patient demographics, baseline seizure frequency, length of EMU stay and time from admission to first event were recorded. Results: In total, 111 patients with PNES and 121 patients with ES were included. The mean age (in years) was 42 and 38, respectively. The average baseline seizure frequency was four times higher in the PNES group than the ES group. Greater than half (52%) of the patients with PNES and about one third (38%) of the patients with ES had an event within the first 24 hours. The average time to first event was 20.88 hours for the PNES group and 30.99 hours for the ES group (p<0.01). The median latency to first event was 14 hours for the PNES group and 23 hours for the ES group. The average length of EMU stay was significantly longer in the ES group (70.82 hours) than the PNES group (53.95 hours). Conclusion: The average time to first event is shorter for PNES than in ES. In patients with high pre-EMU clinical suspicion for PNES, relatively shorter EMU monitoring (24 to 48 hours) can confirm diagnosis. This phenomenon might improve cost-effectiveness of EMU monitoring in patients with PNES.

Generalized paroxysmal fast activity in EEG: An unrecognized finding in genetic generalized epilepsy.

OBJECTIVE: To study generalized paroxysmal fast activity (GPFA) in patients with genetic generalized epilepsy (GGE). INTRODUCTION: GPFA is an electroencephalographic (EEG) finding in patients with symptomatic generalized epilepsy consisting of 15-25Hz bifrontally predominant generalized fast activity seen predominantly in sleep. Historically GPFA is linked to epileptic encephalopathy with drug resistant epilepsy and intellectual disability. However, GPFA has been rarely described as an atypical finding in patients with GGE without negative prognostic implication. We report cognitive profile and seizure characteristics in seven patients with GGE and GPFA. METHODS: The Vanderbilt EMU and EEG reports were searched for the keywords "idiopathic generalized epilepsy", "GPFA"and "generalized spike and wave discharges (GSWD)". We reviewed the EEG tracings and the electronic medical records of patients thus identified. The seizure type, frequency, neurological work-up, clinical profile and imaging data were recorded. RESULTS: Awake and sleep states were captured on EEGs of all patients. On EEG tracing review six patients were confirmed to have GSWD and GPFA; one patient had GPFA but no GSWD. All patients had normal cognitive function. Four had a normal brain MRI and one a normal head CT (two were never imaged). None of the patients had tonic seizures. The main seizure type was generalized tonic-clonic seizures (GTCS) in five patients, absence in two. Age at onset of epilepsy ranged from 4 to 24years. The mean GTC seizure frequency at the time of EEG was 3; two patients were seizure free on two antiepileptic drugs (AEDs). CONCLUSIONS: GPFA can be an unrecognized electrographic finding in patients with genetic generalized epilepsy. While GPFA remains an important diagnostic EEG feature for epileptic encephalopathy (Lennox-Gastaut syndrome) it is not specific for this diagnosis. Thus, GPFA may have a spectrum of variable phenotypic expression. The finding of GPFA is not necessarily indicative of unfavorable outcome.

Relationship between high-frequency oscillations and spikes in a case of temporal lobe epilepsy.

OBJECTIVE: The aim of this case report was to study the relationship between high-frequency oscillations (HFOs), spikes, and seizures in a patient with temporal lobe epilepsy. INTRODUCTION: During intracranial electroencephalography (EEG), HFOs are thought to be a marker for the seizure onset zone (SOZ). High-frequency oscillations are classified into ripples with frequencies of 70-200 Hz and fast ripples with frequencies of 200-500 Hz. Although HFOs are thought to be a marker for the SOZ, their relationship to spikes has not been studied in detail, especially within the SOZ. METHODS: We studied the time course of ripples and spikes in a patient undergoing intracranial EEG. Medications were discontinued on day one. She suffered three seizures on day three. Her SOZ was in the left hippocampus, which displayed abundant ripples and spikes. Ripples, spikes with simultaneous ripples, and spikes without ripples were counted for this study. RESULTS: We found that ripples and spikes in the SOZ had a marked diurnal variation. Ripples, spikes with ripples, and spikes without ripples increased and decreased in concert until just before seizure onset, when ripples and spikes with ripples increased markedly. Spikes without ripples did not increase. CONCLUSIONS: These results support ripples as a marker for SOZ and show that they co-occur with spikes. Seizure onset was heralded by an increase in ripples and spikes with ripples, without an increase in spikes without ripples. We hypothesize that spikes associated with ripples may have a somewhat different pathophysiological mechanism than spikes not associated with ripples, differences that may be relevant for the timing of seizure onset.

Medical Marijuana for Epilepsy?

Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring.