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.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy. METHODS: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood- and brain-derived DNA samples were sequenced using high-coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect-2 and confirmed using high-coverage Amplicon-EZ sequencing. RESULTS: Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. SIGNIFICANCE: This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.

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.

Neurosurgery for intractable epilepsy in pregnancy: A case report.

We describe the management of a 39-year-old woman with intractable focal epilepsy whose condition deteriorated during pregnancy and who required emergency neurosurgery. A literature search did not identify any previous reports of epilepsy surgery in pregnancy. To our knowledge, this is the first time surgery was planned and executed in rapid order with a successful outcome, without obstetrical or surgical complications and seizure freedom achieved. The value of rapid communication between established women's health advanced nurse practitioner clinics, the multidisciplinary Epilepsy Surgery Group and specialist Obstetrical Epilepsy service is highlighted. A care cycle for pregnant women with refractory epilepsy is proposed.

A retrospective study of the correlation between duration of monitoring in the epilepsy monitoring unit and diagnostic yield.

OBJECTIVE: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield. METHOD: A retrospective review of patients admitted into the epilepsy monitoring unit (EMU) for the diagnostic evaluation of paroxysmal events was performed. Patients' demographic, clinical characteristics, and vEEG data were analyzed. In the cohort of patients with DOM > 7 days, the reasons for prolonged DOM were identified and the differences in clinical characteristics and vEEG data between conclusive and inconclusive studies were analyzed. RESULT: A total of 501 patients were included. Four hundred and thirty-six (87 %) patients had conclusive studies. Of these patients, 67.9 % patients with conclusive studies received diagnosis within the first 7 days of monitoring with the highest on day 7. The likelihood of conclusive studies decreased beyond 7 days. A total of 175 had DOM > 7 days, of which 140 (80 %) had conclusive studies. In the cohort with DOM > 7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, first event recorded before day 5 of admission and ≥1 events recorded during vEEG monitoring were more likely to have conclusive studies. The most common reason for prolonging DOM beyond 7 days was to adequately record multiple semiologically distinctive events (76 %). CONCLUSION: Our study supports that longer DOM is associated with an increase in diagnostic yield. More than one-third of our cohort were monitored beyond 7 days with majority (80 %) being conclusive. Our findings may guide clinicians in planning the DOM and predicting the likelihood of conclusive vEEG studies in patients with prolonged DOM based on the clinical characteristics and vEEG data.

Exoscope aided trans-sulcal minimally invasive parafascicular resection of a paediatric brainstem pilocytic astrocytoma using a tubular retractor system.

The surgical management of brainstem glioma is challenging and has significant morbidity. Advances in surgical armamentarium has presented the opportunity to tackle these lesions. We present the case of a paediatric patient with a 2.3cm midbrain pilocytic astrocytoma. With the aid of tractography, neuro-navigation, 3-dimensional exoscope and a tubular retractor, near total resection of the tumour was achieved through a trans-sulcal para-fascicular approach without permanent injury to the corticospinal tract. To our knowledge this is the first report of a brainstem tumour resected using this approach and demonstrates what can be achieved with synergistic utility of evolving technologies in neurosurgery.

How I do it: parietal trans-sulcal para-fascicular approach to lateral thalamic/internal capsule cavernous malformation.

BACKGROUND: The surgical management of deep brain lesions is challenging, with significant morbidity. Advances in surgical technology have presented the opportunity to tackle these lesions. METHODS: We performed a complete resection of a thalamic/internal capsule CM using a tubular retractor system via a parietal trans-sulcal para-fascicular (PTPF) approach without collateral injury to the nearby white matter tracts. CONCLUSION: PTPF approach to lateral thalamic/internal capsule lesions can be safely performed without injury to eloquent white matter fibres. The paucity of major vessels along this trajectory and the preservation of lateral ventricle integrity make this approach a feasible alternative to traditional approaches.

Ictal asystole during long-term video-EEG; semiology, localization, and intervention.

Ictal arrhythmias are disturbances of cardiac conduction that occur during clinical or electrographic seizures. Ictal asystole (IA) is rare, and its incidence can range from 0.3-0.4% in patients with epilepsy who were monitored by video-EEG (van der Lende et al., 2015). We report on ten patients (six males and four females) with an age ranging from 31 to 70 years old) who were monitored in our video-EEG (VEEG) unit over the last eight years. These patients were selected based on the history of documented ictal asystole during inpatient VEEG monitoring). In our series the mean latency from the seizure onset to the onset of ictal asystole was 22 seconds and the mean duration of the IA was 15.8 seconds. During the asystolic phase the seizures may clinically continue or syncopal signs may supervene. In our case series all the patients had either left or right temporal lobe epilepsy, six of which were lesional. We found two patterns of ictal semiology in our series. The first group of patients included five patients who experienced a rapid onset of IA in their seizure and the second group where the latency of ictal asystole was relatively late. All our cohort had a permanent pacemaker following the diagnosis, six of these patients have been event free since placement.

Jaw Clonus: A Rhythmic Oscillatory Movement, but Not Tremor.

Background: Jaw clonus is rhythmic, oscillatory contraction of jaw muscles induced by stretch and is caused by lesions of the descending motor neurons in the corticopontine tracts. Phenomenology shown: We illustrate jaw clonus elicited with jaw activation and upon testing of the jaw jerk in a patient with amyotrophic lateral sclerosis. Educational value: This video clearly demonstrates the uncommon sign of jaw clonus, a finding which needs to be distinguished from tremor and should direct the examiner to consider lesions of the corticopontine fibres, including amyotrophic lateral sclerosis.

Recurrent catamenial status epilepticus: Is it rare or an under recognized phenomenon in women with epilepsy?

•Recurrent catamenial status epilepticus may occur in generalized and focal epilepsy.•Documenting the menstrual cycles and perimenstrual video-EEG help the diagnosis.•Hormonal treatment including menstrual suppressive therapies may be used.

Simultaneous occurrence of nonepileptic and epileptic seizures during a single period of in-patient video-electroencephalographic monitoring.

Epilepsy and psychogenic nonepileptic seizures (PNES) can coexist and may present in two forms: sequential and simultaneous. In sequential presentations, epileptic seizures (ES) are treated and PNES emerge later. Simultaneous recording of ES and PNES by video-electroencephalogram (vEEG) is less well described. We retrospectively reviewed all patients diagnosed with PNES by vEEG following standard seizure induction practices over a 21-month period. Within this cohort, we established the prevalence of coexisting epilepsy using clinical and electrographic data acquired from our epilepsy-specific patient record. We identified patients with simultaneous PNES and ES recorded during a single vEEG admission, establishing the frequency and emergent timing of each type. Of our 262 monitored patients, 59 were diagnosed with PNES. Nineteen of the patients with PNES had coexisting epilepsy (prevalence rate of 7.3% or 32% of those with PNES). Sixteen patients had PNES and ES recorded during the same admission, and the remaining three patients had sequential PNES following successful treatment of ES. PNES occurred earlier (mean, within 1.21 days), with ES occurring later (mean, within 4.86 days). The simultaneous occurrence of PNES and ES recorded during a single admission is more common than previously reported. Identifying this group of patients may require a significantly longer period of vEEG monitoring and a detailed analysis of each individual's historical seizure events.

Hippocampography Guides Consistent Mesial Resections in Neocortical Temporal Lobe Epilepsy.

Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is unknown. Hippocampal electrocorticography maximizes seizure freedom by identifying normal-appearing epileptogenic tissue for resection and minimizes neuropsychological deficit by limiting resection to demonstrably epileptogenic tissue. We examined whether standardized hippocampal electrocorticography (hippocampography) guides resection for more consistent hippocampectomy than unguided resection in conventional electrocorticography focused on the lesion. Methods. Retrospective chart reviews any kind of electrocorticography (including hippocampography) as part of combined lesionectomy, anterolateral temporal lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen underwent hippocampography-guided mesial temporal resection. Hippocampography was associated with 2.6 times more consistent resection. The range of hippocampal resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p = 0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably epileptogenic tissue, hippocampography significantly reduces resection variability for more consistent hippocampectomy than unguided resection in conventional electrocorticography. More consistent hippocampal resection may avoid overresection, which poses greater neuropsychological risk, and underresection, which jeopardizes postoperative seizure freedom.

The human burst suppression electroencephalogram of deep hypothermia.

OBJECTIVE: Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. METHODS: We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. RESULTS: Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. CONCLUSIONS: These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. SIGNIFICANCE: These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression.

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.

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.

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.

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.

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.

Pathology of bilateral pulvinar degeneration following long duration status epilepticus.

PURPOSE: To define the neuropathological findings of pulvinar degeneration seen in long duration status epilepticus. METHODS: We review the clinical, radiologic, neurophysiologic, investigational and neuropathological findings on a 27 year old woman who died after 162 days of prolonged refractory status epilepticus. RESULTS: Continuous EEG monitoring confirmed recurrent uncontrolled seizure activity bilaterally and independently, most frequent in the right fronto-temporal region. Initial MRI of the brain was normal. Repeat study until on day 127 of admission showed advanced changes, with bilateral pulvinar T2/FLAIR hyperintensities. The autopsy revealed sharply defined, grey, soft, granular nodules in each medial pulvinar nucleus. Microscopically these consisted of sharply defined paucicellular areas with loss of neurons and myelin and with numerous macrophages in their centers, surrounded by reactive astrocytes with relatively spared of axons. The spinal cord at cervical and thoracic levels showed symmetric spongy vacuolation in the central part of the dorsal columns and lateral corticospinal tracts, with mild myelin loss, relatively preserved axons. The pathological lesions found in this case in thepulvinar are somewhat similar to the pathologic lesions described in Wernicke's encephalopathy. Those found in the spinal cord of our patient resemble characteristic features of B12 related subacute combined degeneration. CONCLUSION: Characteristic pulvinar degeneration may be found as an acquired phenomenon in prolonged refractory status epilepticus. We hypothesize that the neuropathological findings result from an excessive focal metabolic demand, secondary to neuronal network over activation in the setting of prolonged, frequent bi-temporal seizures.

Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study.

PURPOSE: To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). METHODS: Multicenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. KEY FINDINGS: Permanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control ("possible" or "likely" responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9 mg/kg/h, when ketamine was introduced at least 8 days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24 h of ketamine initiation (16% vs. 56%, p = 0.0047). SIGNIFICANCE: Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.