Sara E. Hocker

Predictors of Outcome in Refractory Status Epilepticus

OBJECTIVE To further characterize the demographics, outcomes, and prognostic factors for refractory status epilepticus (RSE). DESIGN Retrospective analysis of all the episodes of RSE treated between January 1, 1999, and August 30, 2011. SETTING Neurointensive care unit within a tertiary referral center, Mayo Clinic, Rochester, Minnesota. PATIENTS Refractory status epilepticus was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial first- and second-line therapies. Exclusion criteria were aged younger than 18 years, anoxic/myoclonic SE, psychogenic SE, simple partial SE, and absence SE. MAIN OUTCOME MEASURES Functional outcome was defined by modified Rankin scale (mRS) dichotomized into good (mRS, 0-3) and poor (mRS, 4-6). Functional decline was defined as a change in mRS greater than 1 from hospital admission to discharge. RESULTS We identified 63 consecutive episodes of non-anoxic RSE in 54 patients. Anesthetic agents were used in 55 episodes (87.30%), and duration of drug-induced coma was (mean [SD]) 11.0 (17.9) days. In-hospital mortality was 31.75% (20 of 63 episodes). Poor functional outcome at discharge occurred in 48 of 63 episodes (76.19%). Hospital length of stay was (mean [SD]) 27.7 (37.3) days. Duration of drug-induced coma (P=.03), arrhythmias requiring intervention (P=.01), and pneumonia (P=.01) were associated with poor functional outcome. Prolonged mechanical ventilation was associated with mortality (P=.04). Seizure control without suppression-burst or isoelectric electroencephalogram predicted good functional recovery (P=.01). Age, history of epilepsy, previous SE, type of SE, and anesthetic drug used were not associated with functional outcome. CONCLUSIONS Three-quarters of patients with RSE have a poor outcome. Achieving control of the SE without requiring prolonged drug-induced coma or severe electroencephalographic suppression portends better prognosis.

Ketogenic diet for adults in super-refractory status epilepticus

Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy

IntroductionCefepime, a broad spectrum antibiotic, is commonly prescribed in intensive care units (ICU) and may be an overlooked cause of neurologic symptoms such as encephalopathy, myoclonus, seizures, and coma. We aimed to characterize cefepime neurotoxicity in the ICU.MethodsWe performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1, 2009 and December 31, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method.ResultsThis study included 100 patients. The mean age was 65.8 years (± 12.7 years). The median daily average dose of cefepime was 2.5 (IQR 2.0 to 3.5) grams. The median treatment duration was 6 (IQR 4 to 10) days. Renal failure in any form was present in 84 patients. Chronic kidney disease affected 40 patients, and 77 had acute kidney injury. Cefepime neurotoxicity occurred in 15 patients. Of these, seven were considered definite cases, three probable, and five possible. Neurotoxic symptoms included impaired consciousness (n = 13), myoclonus (n = 11), disorientation (n = 6), and nonconvulsive status epilepticus (n = 1). The dose of cefepime was appropriately adjusted for renal clearance in 64 patients (75.3%) without cefepime neurotoxicity and four patients (28.6%) with neurotoxicity (P = 0.001). Chronic kidney disease was present in 30 patients (35.3%) without neurotoxicity and in 10 (66.7%) of those with neurotoxicity (P = 0.04).ConclusionsCritically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Myoclonus and impaired consciousness are the predominant clinical manifestations. Neurotoxic symptoms occur more often when the cefepime dose is not adjusted for renal function, but can still occur despite those modifications.

Indicators of Central Fever in the Neurologic Intensive Care Unit

IMPORTANCE Fever is common in critically ill neurologic patients. Knowledge of the indicators of central fever may allow greater antibiotic stewardship in this era of rapidly developing super-resistant microorganisms. OBJECTIVE To develop a model to differentiate central from infectious fever in critically ill neurologic patients with fever of an undetermined cause. DESIGN, SETTING, AND PARTICIPANTS Retrospective data collection from January 1, 2006, through December 31, 2010, at a 20-bed neurologic intensive care unit of a large teaching hospital. Consecutive patients 18 years and older admitted for 48 hours or longer with a core body temperature higher than 38.3 °C on at least 1 measurement for 2 consecutive days. Patients with alternative identified causes of noninfectious fever were excluded. In total, 526 patients were included in the final analysis. MAIN OUTCOMES AND MEASURES Percentage incidence and odds ratios of variables associated with central fever. Fever was classified as infectious if there was culture growth of a pathogenic species or documented clinical diagnosis of infection treated with antibiotics. Remaining patients were considered to have central fever. Continuous fever lasting longer than 6 hours for 2 or more consecutive days was considered persistent. RESULTS Fever was central in 246 patients (46.8%). Patients with infectious fever were older (mean, 57.4 vs 53.5 years; P = .01) and had a longer length of stay in the neurologic intensive care unit (mean, 12.1 vs 8.8 days; P < .001). Central fever was more likely to occur within 72 hours of admission to the neurologic intensive care unit (76.4% vs 60.7%; P < .001) and tended to be persistent (26.4% vs 18.6%; P = .04). Blood transfusion (odds ratio [OR], 3.06; 95% CI, 1.63-5.76); absence of infiltrate on chest x-ray (3.02; 1.81-5.05); diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor (6.33; 3.72-10.77); and onset of fever within 72 hours of hospital admission (2.20; 1.23-3.94) were independent predictors of central fever on multivariable analysis. The combination of negative cultures; absence of infiltrate on chest radiographs; diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor; and onset of fever within 72 hours of admission predicted central fever with a probability of .90. CONCLUSIONS AND RELEVANCE We provide a reliable model to differentiate central fever from infectious fever in critically ill neurologic patients, allowing clinicians to select patients in whom antibiotics may be safely discontinued despite ongoing fever.

Cardiac injury in refractory status epilepticus

Purpose:  We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE).

Long‐term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome

Seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), which is reported in up to 70% of cases, and antiepileptic drugs (AEDs) are commonly prescribed. There is a paucity of data regarding the risk of subsequent seizures following resolution of PRES, and therefore the optimal duration of treatment with AEDs is currently unknown. The objective of this study was to identify the frequency of recurrent seizures and epilepsy following recovery from PRES.

Sensitivity of quantitative EEG for seizure identification in the intensive care unit

Objective: To evaluate the sensitivity of quantitative EEG (QEEG) for electrographic seizure identification in the intensive care unit (ICU). Methods: Six-hour EEG epochs chosen from 15 patients underwent transformation into QEEG displays. Each epoch was reviewed in 3 formats: raw EEG, QEEG + raw, and QEEG-only. Epochs were also analyzed by a proprietary seizure detection algorithm. Nine neurophysiologists reviewed raw EEGs to identify seizures to serve as the gold standard. Nine other neurophysiologists with experience in QEEG evaluated the epochs in QEEG formats, with and without concomitant raw EEG. Sensitivity and false-positive rates (FPRs) for seizure identification were calculated and median review time assessed. Results: Mean sensitivity for seizure identification ranged from 51% to 67% for QEEG-only and 63%–68% for QEEG + raw. FPRs averaged 1/h for QEEG-only and 0.5/h for QEEG + raw. Mean sensitivity of seizure probability software was 26.2%–26.7%, with FPR of 0.07/h. Epochs with the highest sensitivities contained frequent, intermittent seizures. Lower sensitivities were seen with slow-frequency, low-amplitude seizures and epochs with rhythmic or periodic patterns. Median review times were shorter for QEEG (6 minutes) and QEEG + raw analysis (14.5 minutes) vs raw EEG (19 minutes; p = 0.00003). Conclusions: A panel of QEEG trends can be used by experts to shorten EEG review time for seizure identification with reasonable sensitivity and low FPRs. The prevalence of false detections confirms that raw EEG review must be used in conjunction with QEEG. Studies are needed to identify optimal QEEG trend configurations and the utility of QEEG as a screening tool for non-EEG personnel. Classification of evidence review: This study provides Class II evidence that QEEG + raw interpreted by experts identifies seizures in patients in the ICU with a sensitivity of 63%–68% and FPR of 0.5 seizures per hour.

Detection of Spreading Depolarization with Intraparenchymal Electrodes in the Injured Human Brain

BackgroundSpreading depolarization events following ischemic and traumatic brain injury are associated with poor patient outcome. Currently, monitoring these events is limited to patients in whom subdural electrodes can be placed at open craniotomy. This study examined whether these events can be detected using intra-cortical electrodes, opening the way for electrode insertion via burr hole.MethodsAnimal work was carried out on adult Sprague–Dawley rats in a laboratory setting to investigate the feasibility of recording depolarization events. Subsequently, 8 human patients requiring craniotomy for traumatic brain injury or aneurysmal subarachnoid hemorrhage were monitored for depolarization events in an intensive care setting with concurrent strip (subdural) and depth (intra-parenchymal) electrode recordings.Results(1) Depolarization events can be reliably detected from intra-cortically placed electrodes. (2) A reproducible slow potential change (SPC) waveform morphology was identified from intra-cortical electrodes on the depth array. (3) The depression of cortical activity known to follow depolarization events was identified consistently from both intra-cortical and sub-cortical electrodes on the depth array.ConclusionsIntra-parenchymally sited electrodes can be used to consistently identify depolarization events in humans. This technique greatly extends the capability of monitoring for spreading depolarization events in injured patients, as electrodes can be sited without the need for craniotomy. The method provides a new investigative tool for the evaluation of the contribution of these events to secondary brain injury in human patients.

Successful Delayed Thrombolysis for Cerebral Venous and Dural Sinus Thrombosis: A Case Report and Review of the Literature

Cerebral venous and dural sinus thrombosis (CVDST) is a rare but not uncommon life-threatening disease accounting for less than 1% of stroke, affecting people of any age group, predominantly the extremes of age. CVDST carries a variable prognosis: although the majority of cases are associated with complete recovery, outcome may be fatal in less than 10% of patients. Thrombolysis has been widely used in CVDST in patients with rapidly deteriorating symptoms who fail to improve despite adequate anticoagulation, but the exact therapeutic time window remains unclear. We report a case of CVDST with rapid clinical deterioration despite therapeutic anticoagulation treated with direct endovascular thrombolysis with intravenous recombinant tissue plasminogen activator 1 week after presentation with complete recovery, and we present a review of the literature on the efficacy and safety of thrombolysis in CVDST.

Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus

Objective: To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults. Methods: We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes. Results: Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died. Conclusions: KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials. Classification of evidence: This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis.