Oligoepilepsy and lifelong seizure susceptibility in epilepsy with generalized tonic-clonic seizures alone: Experience at an adult tertiary center.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is the least studied syndrome within the idiopathic generalized epilepsy (IGE) spectrum. We characterize a large cohort of adult patients with GTCA to understand natural history and drug responsiveness. METHODS: In this retrospective single-center study using our epilepsy electronic record, we evaluated clinical characteristics, seizure outcomes, anti-seizure medication (ASM) response including seizure recurrence after ASM withdrawal, and sex differences in a cohort of GTCA patients aged ≥17 years. RESULTS: Within a cohort of 434 IGE patients, 87 patients (20 %) with GTCA were included. The mean age was 34.9 years (range 17-73 years). Forty-six patients (52.8 %) were females. Seventy-two patients (82.8 %) were seizure-free and 15 (17.2 %) had active epilepsy over the previous 12 months. Thirty-four patients (39.1 %) had ≤5 lifetime seizures, aligning with a prior definition of 'oligoepilepsy'. Sixty-five patients (74.7 %) were treated with monotherapy, 19 (21.8 %) were treated with polytherapy, and three were not taking any ASM. Levetiracetam (37.9 %) was the most commonly prescribed ASM, followed by lamotrigine (32.1 %) and valproate (31 %). Seventeen patients (19.5 %) attempted to withdraw their ASM. The rate of seizure recurrence after ASM withdrawal was 88.2 % (15/17), including two patients who relapsed more than 20 years after ASM discontinuation. Females had more seizures in their lifetime and had trialed more ASM compared to males. SIGNIFICANCE: GTCA has a relatively good prognosis, with most patients becoming seizure-free on monotherapy. The high rate of seizure recurrence after ASM withdrawal supports lifetime seizure susceptibility. We found potential sex differences in seizure outcomes and ASM response, although further research is needed to validate this finding.

Vagus nerve stimulation in refractory idiopathic generalised epilepsy: An Irish retrospective observational study.

OBJECTIVE: Refractory idiopathic generalised epilepsy (IGE; also known as genetic generalised epilepsy) is a clinical challenge due to limited available therapeutic options. While vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant focal epilepsy, there is limited evidence supporting its efficacy for refractory IGE. METHODS: We conducted a single-centre retrospective analysis of adult IGE patients treated with VNS between January 2003 and January 2022. We analysed the efficacy, safety, tolerability, stimulation parameters and potential clinical features of VNS response in this IGE cohort. RESULTS: Twenty-three IGE patients were implanted with VNS between January 2003 and January 2022. Twenty-two patients (95.65%) were female. The median baseline seizure frequency was 30 per month (interquartile range [IQR]= 140), including generalised tonic-clonic seizures (GTCS), absences, myoclonus, and eyelid myoclonia with/without absences. The median number of baseline anti-seizure medications (ASM) was three (IQR= 2). Patients had previously failed a median of six ASM (IQR= 5). At the end of the study period, VNS therapy remained active in 17 patients (73.9%). amongst patients who continued VNS, thirteen (56.5% of the overall cohort) were considered responders (≥50% seizure frequency reduction). Amongst the clinical variables analysed, only psychiatric comorbidity correlated with poorer seizure outcomes, but was non-significant after applying the Bonferroni correction. Although 16 patients reported side-effects, none resulted in the discontinuation of VNS therapy. SIGNIFICANCE: Over half of the patients with refractory IGE experienced a positive response to VNS therapy. VNS represents a viable treatment option for patients with refractory IGE, particularly for females, when other therapeutic options have been exhausted.

Cryptogenic New Onset Refractory Status Epilepticus (NORSE) in adults-Infectious or not?

INTRODUCTION: In the majority of cases of New Onset Refractory Status Epilepticus (NORSE) in adults, a cause is discovered. However, some cases of NORSE remain undiagnosed, i.e. cryptogenic. They are usually presumed to be due to infectious encephalitis and typically have devastating consequences. We describe our experience with six adults who presented with NORSE and raise the possibility of non-infectious causes. METHODS: Retrospective case series from an epilepsy service in a tertiary care urban hospital. We compare the clinical features of these cases with patients who develop NORSE in the setting of clinically-defined encephalitis from the California Encephalitis Project (most of whom are etiologically cryptogenic) as well as with patients who develop NORSE in the setting of proven infectious encephalitis. RESULTS: We describe 6 previously-normal adults with NORSE where a cause was not established despite an exhaustive search. With an average duration of 36 days (range 6-68), the in-hospital and long-term morbidities were high; one patient died of the propofol infusion syndrome. In contradistinction to NORSE in the setting of etiologically-proven infectious encephalitis, these patients were afebrile and the abnormalities evident during their evaluation could be attributed to the ictal activity itself. Neuropathological examination revealed non-specific findings in 4 patients. CONCLUSIONS: Though an underlying etiology remains unproven in these patients, we contend that NORSE is etiologically heterogeneous, with a proportion of cases due to non-infectious causes. Further study of this poorly understood form of status epilepticus is needed.

Intra-stimulation discharges: an overlooked cortical electrographic entity triggered by direct electrical stimulation.

OBJECTIVE: Intra-stimulation discharges (IDs) can occur during language mapping, are largely unrecognized, and may precede the occurrence of after-discharges (ADs) and seizures. This study aimed to identify predictors of ID occurrence and determine whether IDs increase the probability of triggered ADs. METHODS: A total of 332 stimulation events performed during language mapping were analyzed in 3 patients who underwent intracranial EEG recordings during evaluations for epilepsy surgery. IDs were identified in 76 stimulation events. The relationships between IDs and the stimulus current intensity, stimulation duration, and proximity to regions of abnormal cortical excitability [characterized by the presence of baseline epileptiform discharges (BEDs)] were determined using regression analysis. RESULTS: The presence of BEDs in close proximity to stimulation, an increase in stimulus intensity by 1 mA, and an increase in stimulation duration by 1s independently increased the odds of triggering IDs by 7.40, 1.37, and 1.39 times, respectively. All IDs were triggered during stimulations in the temporal lobe. The occurrence of IDs increased the odds of triggering ADs 5-fold. CONCLUSIONS: Longer stimulations, higher currents, and the presence of BEDs at the stimulation site increase the probability of ID occurrence, which in turn increases the probability of triggering ADs. SIGNIFICANCE: Attention to IDs may improve the safety and precision of neurophysiologic mapping.

The probability of seizures during EEG monitoring in critically ill adults.

OBJECTIVE: To characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG). METHODS: Retrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far. RESULTS: Seizures occurred in 27% (168/625). The first seizure occurred early (<30min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities. CONCLUSIONS: Seizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities. SIGNIFICANCE: These findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients.

Dorsal column mapping via phase reversal method: the refined technique and clinical applications.

BACKGROUND: Safe resection of intramedullary spinal cord tumors can be challenging, because they often alter the cord anatomy. Identification of neurophysiologically viable dorsal columns (DCs) and of neurophysiologically inert tissue, eg, median raphe (MR), as a safe incision site is crucial for avoiding postoperative neurological deficits. We present our experience with and improvements made to our previously described technique of DC mapping, successfully applied in a series of 12 cases. OBJECTIVE: To describe a new, safe, and reliable technique for intraoperative DC mapping. METHODS: The right and left DCs were stimulated by using a bipolar electric stimulator and the triggered somatosensory evoked potentials recorded from the scalp. Phase reversal and amplitude changes of somatosensory evoked potentials were used to neurophysiologically identify the laterality of DCs, the inert MR, as well as other safe incision sites. RESULTS: The MR location was neurophysiologically confirmed in all patients in whom this structure was first visually identified as well as in those in whom it was not, with 1 exception. DCs were identified in all patients, regardless of whether they could be visually identified. In 3 cases, negative mapping with the use of this method enabled the surgeon to reliably identify additional inert tissue for incision. None of the patients had postoperative worsening of the DC function. CONCLUSION: Our revised technique is safe and reliable, and it can be easily incorporated into routine intramedullary spinal cord tumor resection. It provides crucial information to the neurosurgeon to prevent postoperative neurological deficits.

Phase reversal technique decreases cortical stimulation time during motor mapping.

Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in supratentorial surgery. Electrical cortical stimulation is guided by anatomic landmarks towards the precentral gyrus, with recording of the triggered primary motor responses (TPMR) in the contralateral hemibody. Thus, factors such as distortion of the pericentral anatomy, small surgical fields, brain shifts and miscalibrated neuronavigational systems may lengthen the process and result in unnecessary stimulations, increasing the probability of triggering seizures. We hypothesized that central sulcus localization via the median somatosensory evoked potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon, resulting in prompt identification of the PMC with minimal electrical stimulation. Multivariate Cox regression was used to study the impact of MSSEP PRT on time spent performing electrical cortical stimulation to TPMR. The analysis was adjusted for presence of increased cortical excitability, high motor thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized motor mapping procedures for brain tumor resection and epilepsy surgery. Phase reversal and change morphology of the recorded somatosensory evoked potentials quadrupled (hazard ratio [HR] 4.13, p<0.0001) and doubled (HR 2.14, p=0.02) the rate of obtaining TPMR, respectively. A 1mA increase in motor threshold decreased the rate by 9% (HR 0.91, p=0.0002). Afterdischarges triggered before TPMR and lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23, p<0.0001) and 48% (HR 0.52, p=0.04), respectively. Informative PRT decreases stimulation time. Afterdischarges triggered before TPMR, high motor thresholds and lesions close to the PMC increase it.

Intraoperative functional cortical mapping of language.

Intraoperative neurophysiologic monitoring endeavors to preserve the integrity of the nervous system at a time of potential risk. The examination of language function in the operative setting is a unique task that requires a detailed and systematic approach to be carried out efficiently and reliably in this dynamic environment. In this review, we detail the technique used to identify eloquent language cortex during awake craniotomy. This technique requires a coordinated effort to testing, which is reliant on preoperative assessment and structured approach to functional cortical mapping by the surgical, anesthetic, and neurophysiology teams. Despite the intricate nature of this modality of testing, the accurate identification of language areas facilitates neurosurgeries for tumor and focal epilepsy syndromes in the dominant cerebral hemisphere, which depend on maximal margins of resection for best outcomes.

Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG.

OBJECTIVE: To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients. METHODS: We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG. RESULTS: Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p < 0.001). In the 3 patients without epileptiform abnormalities on initial EEG but with subsequent seizures, the first epileptiform discharge or electrographic seizure occurred within the first 4 hours of recording. CONCLUSIONS: In patients without epileptiform abnormalities during the first 4 hours of recording, no seizures were subsequently detected. Therefore, EEG features early in the recording may indicate a low risk for seizures, and help determine whether extended monitoring is necessary.

Predictors of clamp-induced electroencephalographic changes during carotid endarterectomies.

OBJECTIVE: Electroencephalograms (EEGs) detect clamp-induced cerebral ischemia during carotid endarterectomy (CEA) and thus impact management and minimize the risk of perioperative stroke. We hypothesized that age, preoperative neurologic symptoms, ≥70% contralateral carotid and bilateral vertebral stenosis increase the probability of clamp-induced EEG changes, whereas ≥70% unilateral carotid stenosis does not. METHODS: This is an observational cohort study of 299 patients who underwent CEA with EEG monitoring at a single large urban academic medical center in 2009. Univariate and multivariate logistic regression were used. RESULTS: Seventy percent or greater ipsilateral carotid stenosis decreases the odds of clamp-induced neurophysiologic dysfunction (odds ratio [OR] = 0.43, 95% confidence interval [CI] [0.18, 0.99], P = 0.04) after adjustment for symptomatic status, degree contralateral carotid or vertebral stenosis, and age. Preoperative neurologic symptoms, ≥70% contralateral carotid stenosis, and bilateral extracranial vertebral stenosis independently increase these odds (OR 2.62, 95% CI [1.32, 5.18], P = 0.005; OR 2.84, 95% CI [1.27, 6.34], P = 0.01; and OR 3.58, 95% CI [1.02, 12.53], P = 0.04, respectively), after adjustment for the other factors. Age ≥70 years has no significant impact. CONCLUSIONS: Preoperative neurologic symptoms, ≥70% contralateral carotid, and bilateral vertebral stenosis increase the probability of clamp-induced ischemia as detected by intraoperative EEG, while ≥70% ipsilateral carotid stenosis decreases it.

How seizure detection by continuous electroencephalographic monitoring affects the prescribing of antiepileptic medications.

OBJECTIVES: To assess the effect of continuous electroencephalographic monitoring on the decision to treat seizures in the inpatient setting, particularly in the intensive care unit. DESIGN: Retrospective cohort study. SETTING: Medical and neuroscience intensive care units and neurological wards. PATIENTS: Three hundred consecutive nonelective continuous electroencephalographic monitoring studies, performed on 287 individual inpatients over a 27-month period. MAIN OUTCOME MEASURES: Epileptiform electroencephalographic abnormalities and changes in antiepileptic drug (AED) therapy based on the electroencephalographic findings. RESULTS: The findings from the continuous electroencephalographic monitoring led to a change in AED prescribing in 52% of all studies with initiation of an AED therapy in 14%, modification of AED therapy in 33%, and discontinuation of AED therapy in 5% of all studies. Specifically, the detection of electrographic seizures led to a change in AED therapy in 28% of all studies. CONCLUSIONS: The findings of continuous electroencephalographic monitoring resulted in a change in AED prescribing during or after half of the studies performed. Most AED changes were made as a result of the detection of electrographic seizures.