Ronan Kilbride

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.

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.

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.

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.

Clinical examination for outcome prediction in nontraumatic coma.

Objectives:Determine the utility of the neurologic examination in comatose patients from nontraumatic causes in the modern era. Design:Prospective observational study. Setting:Single academic medical center. Patients:Data from 500 patients in nontraumatic coma collected sequentially from 2000 to 2007 in the emergency department and neuroscience, medical, and cardiac intensive care units. Interventions:None. Measurements and Main Results:Clinical data were collected on days 0, 1, 3, and 7. Outcome was assessed at 6 months; good outcome was determined at two levels by modified Rankin Scale, ⩽3 as independence and ⩽4 as moderate but not severe disability. A classification and regression tree analysis was performed to determine prognostic variables, creating predictive algorithms of good vs. poor outcome for each day. Patients with coma attributable to subarachnoid hemorrhage (4/80; 5%) or global hypoxic-ischemic injury (20/202, 10%) were more likely to achieve good outcomes. The pupillary reflex was an important determinant, regardless of day or modified Rankin Scale cut point (mean odds ratio 12.51, range [6.01, 22.56] for modified Rankin Scale ⩽3; mean odds ratio 19.26, range [5.38, 42.26] for modified Rankin Scale ⩽4). A less robust effect was seen for oculocephalic reflexes (mean odds ratio 62.61, range [2.24, 177] for modified Rankin Scale ⩽3; mean odds ratio 34.13, range [4.95, 89.93] for modified Rankin Scale ⩽4). The motor response was selected as a predictor of outcome only on day 0 (odds ratio 2.35, 95% confidence interval 0.64-5.74 for modified Rankin Scale ⩽3; odds ratio 2.1, 95% confidence interval 0.81–4.24 for modified Rankin Scale score ⩽4). Age was not associated with outcome. Conclusions:The clinical neurologic examination remains central to determining prognosis in nontraumatic coma. Additional clinical and diagnostic variables may also aid in outcome prediction for specific disease states. (Crit Care Med 2012; 40:–1156)

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.

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.

Revising the “Rule of Three” for inferring seizure freedom

Purpose:  How long after starting a new medication must a patient go without seizures before they can be regarded as seizure‐free? A recent International League Against Epilepsy (ILAE) task force proposed using a “Rule of Three” as an operational definition of seizure freedom, according to which a patient should be considered seizure‐free following an intervention after a period without seizures has elapsed equal to three times the longest preintervention interseizure interval over the previous year. This rule was motivated in large part by statistical considerations advanced in a classic 1983 paper by Hanley and Lippman‐Hand. However, strict adherence to the statistical logic of this rule generally requires waiting much longer than recommended by the ILAE task force. Therefore, we set out to determine whether an alternative approach to the Rule of Three might be possible, and under what conditions the rule may be expected to hold or would need to be extended.

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.

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.