Stephan Rüegg

Anesthetic drugs in status epilepticus: Risk or rescue? A 6-year cohort study

Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs.

Thrombolysis in Stroke Mimics: Frequency, Clinical Characteristics, and Outcome

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is usually based on clinical assessment, blood test results, and CT findings. Intravenous thrombolysis of stroke mimics may occur but has not been studied in detail. Methods— We determined frequency, clinical characteristics, and outcome of mimic patients versus patients with stroke treated with intravenous thrombolysis using data of a prospective, single-center thrombolysis data bank. Results— Among 250 patients, 243 (97.2%) had strokes and 7 (2.8%) were mimics. Seizure was the most frequent diagnosis among mimics. There was a trend toward lower National Institutes of Health Stroke Scale scores in mimics (9.9±4.2) compared with strokes (13.7±5.4; P=0.06). Global aphasia without hemiparesis was the presenting symptom in 3 (42.9%) mimics versus 8 (3.3%) strokes (P=0.002). Orolingual angioedema, symptomatic intracranial hemorrhage, and asymptomatic intracranial hemorrhage occurred in 3 (1.2%), 13 (5.3%), and 30 (12.3%) patients with stroke, but were absent in mimics. After 3 months, 6 (85.7%) mimics and 86 (35.4%) strokes had a modified Rankin Scale score of 0 to 1 (P=0.01). Conclusions— Only few patients receiving intravenous thrombolysis did eventually have a final diagnosis other than stroke, ie, mostly seizures. Their outcome was favorable. Although clinical features differed between the stroke and the mimic groups, the differences were not distinctive enough to allow assigning individual patients to either of the groups. Multimodal neuroimaging or electroencephalographic recordings may be helpful for this assignment. However, their potential benefit has to be weighed against the potential harm of delayed thrombolysis.

Cerebral perfusion in sepsis-associated delirium.

IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100β (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

Intravenous levetiracetam: Treatment experience with the first 50 critically ill patients

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with no known interactions and a favorable profile of adverse events. These properties make it a good candidate for use in critically ill patients. An intravenous formulation of LEV was recently approved. The present study retrospectively assesses the safety and efficacy of LEV in the first 50 critically ill patients treated with intravenous LEV. Indications for use were seizure prophylaxis, acute symptomatic seizures, and all forms of status epilepticus. There were no major adverse effects, although less prominent changes may have been masked by the already severely compromised condition of these patients. Two patients (4%) had transiently lowered platelet counts (55,000 and 82,000, respectively). Efficacy, defined as cessation of seizure activity or prevention of its recurrence, was observed in 41 of 50 patients (82%). Antiepileptic treatment of critically ill patients with LEV seems to be effective and safe according to the data for this small cohort, but this observation warrants further prospective investigation in a larger number of patients.

Rituximab stabilizes multifocal motor neuropathy increasingly less responsive to IVIg

The authors report a patient with anti-GM1 antibody-negative multifocal motor neuropathy (MMN) who was increasingly less responsive to IV immunoglobulins (IVIgs). Five yearly courses of the monoclonal anti-CD20 antibody rituximab were well tolerated and extended the interval of IVIg administration from 7 to 12 days (corresponding to 42% reduction of IVIg) during this period. Rituximab may be a benefit for patients with MMN.

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study

IntroductionThe Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff.MethodsIn this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care.ResultsIn a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%).ConclusionsThe FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care.

Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU

Purpose:  Status epilepticus (SE) is an important neurologic emergency requiring treatment on an intensive care unit (ICU). Although convulsive SE is self‐evident, the diagnosis of nonconvulsive SE (NCSE) depends on electroencephalography (EEG) confirmation. Previous work showed that 82% of patients with SE had NCSE in our ICU. We hypothesize that continuous video‐EEG monitoring (CVEM) may increase the diagnostic yield in patients with SE, especially NCSE, and leave fewer patients undiagnosed.

Outcome predictors for status epilepticus—what really counts

In adult patients with status epilepticus (SE)—a life-threatening state of ongoing or repetitive seizures—the current evidence regarding outcome prediction is based on clinical, biochemical and EEG determinants. These predictors of outcome involve clinical features such as age, history of prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at SE onset. The clinical risk–benefit calculation between the danger of undertreated persistent seizure activity and, conversely, the potential damage from unwarranted aggressive treatments remains a constant challenge. Improved knowledge of outcome determinants, as well as increased availability of reliable outcome prediction models early in the course of SE, is paramount for optimization of treatment of patients who develop this disorder. In this Review, we discuss the major prognostic determinants of outcome in SE. Through consideration of studies that provide measures of association between predictors of SE outcome and death, we propose a detailed—but as yet unvalidated—paradigm for assessment of these predictors during the course of SE. Such an algorithm could guide the organization of results from existing trials and provide direction with regard to the parameters that should be monitored in future studies of SE.

Bilateral vertebral artery occlusion resulting from giant cell arteritis: report of 3 cases and review of the literature.

Giant cell arteritis (GCA) is known to affect the extracranial part of the vertebral arteries. Bilateral vertebral artery occlusion (BVAO) is a rare but serious neurologic condition. We report 3 patients with autopsy-proven (2 patients) or clinically diagnosed (1 patient) GCA causing BVAO. A review of the literature concerning BVAO revealed 5 other cases of BVAO resulting from GCA and 110 cases with underlying arteriosclerotic disease.Our 3 patients (mean age, 66 yr; range, 60–78 yr) with BVAO resulting from GCA all had initial severe headache followed by the onset of stepwise progressive, partly side-alternating neurologic deficits due to bilateral infarctions in the vertebrobasilar circulation territory. This course, more accelerated in BVAO due to GCA than in BVAO of arteriosclerotic origin, seems to be a typical, if not particular, clinical syndrome. BVAO was the first clinical manifestation of GCA in 1 of our patients and in 1 published case. From a clinical view, BVAO resulting from GCA differs from BVAO of arteriosclerotic origin by the much higher mortality rate (75% versus 19%, respectively), the presence of headache (100% versus 22%), fever (50% versus 0%), and elevated erythrocyte sedimentation rate (ESR in all GCA cases >45 mm/h; no data in the arteriosclerotic patient group), but not by the neurologic signs themselves.Therapy of BVAO resulting from GCA is purely empiric. In view of the serious prognosis, we propose treatment with intravenous high-dose glucocorticoids and additional immunosuppression with cyclophosphamide; the use of anticoagulation depends on the individual patient’s estimated risk-benefit profile.Although BVAO due to GCA is rare, physicians and especially rheumatologists or neurologists should be aware of this entity because of its high mortality in patients without immediate introduction of a high-dose immunosuppressive therapy. Suspicion of GCA should arise in a patient aged over 50 years with no other vascular risk factors suffering from bilateral symptoms of ischemia in the vertebrobasilar territory, with a quickly progressing stepwise course and with headache, fever, or history of myalgia. ESR and temporal artery biopsy should be performed without delay. Early diagnosis of GCA is necessary for immediate initiation of intensive antiinflammatory and immunosuppressive treatment, without which progressive deterioration and systemic involvement are likely to be fatal.

Independent external validation of the status epilepticus severity score

Objectives:A clinical scoring system for patients with status epilepticus was developed for predicting outcome, planning the level of monitoring needed, and guiding treatment. The aim was to confirm the external validity and transportability of the Status Epilepticus Severity Score prediction functions for outcome in adult patients with status epilepticus. Design:Observational cohort study. Setting:Tertiary academic medical care center. Patients:Consecutive adult ICU patients with status epilepticus. Interventions:None. Measurements and Main Results:History of seizures, age, seizure type, and level of consciousness were determined at status epilepticus onset, in order to calculate the Status Epilepticus Severity Score. The main outcome measure was the ability to accurately predict the outcome of status epilepticus by measures of discrimination and calibration. Among 171 status epilepticus patients with a mean age of 64.1 years (± 16.3), mortality was 18%. The receiver operating characteristic curve for prediction of death by the Status Epilepticus Severity Score had an area under the curve of 0.744 with an optimal cutoff point greater than or equal to 4. Hosmer-Lemeshow statistics revealed good calibration of the Status Epilepticus Severity Score (chi-square goodness-of-fit test = 1.39; p = 0.845). Conclusions:This study is the first independent external validation of the predictive accuracy of the Status Epilepticus Severity Score and its transportability to ICU patients with status epilepticus. Measures of discrimination and calibration indicated that Status Epilepticus Severity Score performed reasonably well on our cohort of ICU patients with status epilepticus. However, the specific optimal cutoff point for survival versus death in our cohort was different than proposed.