Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness.

BACKGROUND: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations. METHODS: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome. RESULTS: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19]). CONCLUSIONS: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

Vertebro-Vertebral Fistula Occlusion Using a Woven EndoBridgeTM-Device.

Vertebro-vertebral fistulas (VVFs) are vascular lesions that may develop after trauma or spontaneously in association with connective tissue disorders. We present a rare case of a post-traumatic VVF in a young patient presenting with a painless swelling and a bruit in her left upper neck. Digital subtraction angiography showed an arteriovenous fistula between the left vertebral artery (VA) and the vertebral venous plexus with significant steal phenomenon. Endovascular therapy was performed using a Woven EndoBridgeTM (WEB)-device combined with coils that allowed preservation of the VA. The patient fully recovered from her symptoms and follow-up imaging showed stable occlusion. In conclusion, VVFs can be effectively treated using intrasaccular flow diverters such as the WEB-device, allowing for complete and stable occlusion while preserving the parent artery.

Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study.

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study 'Consciousness in neurocritical care cohort study using EEG and fMRI' (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77-0.80) and 0.71 (95% CI 0.77-0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71-0.86) and 0.83 (95% CI 0.75-0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.

Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes.

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref <1.09 nmol/L) and a tumor biopsy confirmed the diagnosis of a paraganglioma. Phenoxybenzamine and Labetalol were used in high doses ((Dibenyline®, 90 mg x 3 daily) and labetalol (Trandate®, 200 + 300 + 300 mg daily) to stabilize blood pressure. The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.

Temperature change in children undergoing magnetic resonance imaging-An observational cohort study.

AIM: An increasing number of children undergo magnetic resonance imaging requiring anesthesia or sedation to ensure their immobility; however, magnetic resonance imaging may increase body temperature whereas sedation or anesthesia may decrease it. We investigated changes in body temperature in children who underwent sedation or anesthesia for magnetic resonance imaging. METHODS: Children aged 12 weeks-12 years undergoing anesthesia and magnetic resonance imaging were included in this prospective observational study. Tympanic body temperature was measured before and after magnetic resonance imaging, and the difference between measurements was calculated. Associations between the temperature difference and patient- or procedure-related factors were evaluated with linear and logistic regression analysis. RESULTS: A total of 74 children were included, of whom 5 (7%) had a temperature increase ≥0.5°C. Mean temperature difference was -0.24°C (SD 0.48) for the entire group and -0.28°C for the youngest children (0-2 years). The temperature difference correlated positively with the duration of imaging (unadjusted coefficient 0.26, 95% confidence interval (CI), (0.01; 0.52)). CONCLUSION: In this study of sedated or anesthetized children undergoing magnetic resonance imaging, clinically relevant increases in body temperature above 0.5°C were only found in a few patients. However, longer imaging duration tended to be associated with increased body temperature.

Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men.

The Scandinavian winter-swimming culture combines brief dips in cold water with hot sauna sessions, with conceivable effects on body temperature. We study thermogenic brown adipose tissue (BAT) in experienced winter-swimming men performing this activity 2-3 times per week. Our data suggest a lower thermal comfort state in the winter swimmers compared with controls, with a lower core temperature and absence of BAT activity. In response to cold, we observe greater increases in cold-induced thermogenesis and supraclavicular skin temperature in the winter swimmers, whereas BAT glucose uptake and muscle activity increase similarly to those of the controls. All subjects demonstrate nocturnal reduction in supraclavicular skin temperature, whereas a distinct peak occurs at 4:30-5:30 a.m. in the winter swimmers. Our data leverage understanding of BAT in adult human thermoregulation, suggest both heat and cold acclimation in winter swimmers, and propose winter swimming as a potential strategy for increasing energy expenditure.

Assessing response to stroke thrombolysis: validation of 24-hour multimodal magnetic resonance imaging.

BACKGROUND: Imaging is used as a surrogate for clinical outcome in early-phase stroke trials. Assessment of infarct growth earlier than the standard 90 days used for clinical end points may be equally accurate and more practical. OBJECTIVE: To compare assessment of the effect of reperfusion therapies using 24-hour vs day 90 magnetic resonance imaging. DESIGN: Infarct volume was assessed on diffusion-weighted imaging (DWI) at baseline and 24 hours after stroke onset and on fluid-attenuated inversion recovery images at day 90. The DWI and fluid-attenuated inversion recovery lesions were manually outlined by 2 independent raters, and the volumes were averaged. Interrater consistency was assessed using the median difference in lesion volume between raters. SETTING: Referral center. Patients  Imaging data were available for 83 patients; 77 of these patients received thrombolysis. MAIN OUTCOME MEASURES: Infarct volume at 24 hours and 90 days. RESULTS: The 24-hour DWI infarct volume had a strong linear correlation with day 90 fluid-attenuated inversion recovery infarct volume (r = 0.98, 95% confidence interval, 0.97-0.99). Recanalization had a significant effect on infarct evolution between baseline and 24 hours but not between 24 hours and day 90. Infarct growth from baseline was significantly reduced by recanalization, whether assessed at 24 hours or day 90. Infarct volume at either time point predicted functional outcome independent of age and baseline stroke severity. Interrater agreement was better for DWI than fluid-attenuated inversion recovery (1.4 mL [8%] vs 1.8 mL [17%]; P = .002). CONCLUSIONS: Assessment of final infarct volume using DWI at 24 hours captures the effect of reperfusion therapies on infarct growth and predicts functional outcome similarly to imaging at day 90. This has the potential to reduce loss to follow-up in trials and may add early prognostic information in clinical practice.

Safety and efficacy of MRI-based selection for recombinant tissue plasminogen activator treatment: responder analysis of outcome in the 3-hour time window.

INTRODUCTION: The use of MRI may alter the target population for intravenous recombinant tissue plasminogen activator (rtPA) treatment relative to conventional CT. If selection changes, it remains crucial to demonstrate safety and efficacy of rtPA for the overall population, as well as in subpopulations hypothesized to benefit from MRI. MATERIALS AND METHODS: Clinical outcome and incidence of symptomatic intracerebral hemorrhage (ICH) was recorded in 112 consecutive patients treated with intravenous rtPA (0-3 h) with MRI as first-choice imaging modality. According to the responder analysis, favorable outcome was separately defined for mild (NIHSS <8; n = 51), moderate (NIHSS 8-14; n = 30) and severe (NIHSS >14; n = 31) stroke. RESULTS: Eighty-three patients were treated with rtPA after MRI, and 29 after CT. Adjusted for baseline severity, 42% of all patients had a favorable outcome, compared to 37% in NINDS. Among patients with severe stroke, MR-selected patients showed a good outcome in 52% of patients compared to 29% in NINDS (p < 0.05). Symptomatic ICH occurred in 2 patients (1.9 %), and 7 patients died during hospitalization (6.3%). CONCLUSION: MRI-based rtPA is safe and time-efficient. Outcome data compares well with NINDS data. Diagnostic information obtained from multimodal MRI may affect the target group. Our data support the hypothesized benefit of MRI in patients with severe stroke.

Upgraded acute stroke care including thrombolysis is associated with reduced length of hospital stay among non-stroke patients.

BACKGROUND: Implementing thrombolytic therapy in a stroke unit (SU) profoundly affects the resources available to all patients admitted for suspected acute stroke. We examined the benefits of an acute stroke service to non-stroke patients in terms of length of hospitalization, and estimated the economic impact in terms of derived costs. METHODS: We performed a historical follow-up study of 792 non-stroke patients admitted to our SU for suspected stroke before, during and after implementing thrombolysis as part of our service. Data on demographic and clinical characteristics, including imaging data and final diagnoses, and length of stay (LOS) were collected prospectively. Multivariate logistic regression analysis was performed to identify variables associated with LOS. RESULTS: Median LOS for non-stroke patients in the SU decreased from 43.8 h (interquartile range, 19-96) to 23.5 h (16-44) after implementing thrombolytic therapy. Total hospital LOS for non-stroke patients decreased from 52.7 (22-147) to 28.7 (21-124) h during the same period. Initial magnetic resonance imaging was associated with shorter LOS in the SU. The derived cost reductions from shorter LOS reduced the costs of implementing recombinant tissue plasminogen activator treatment. CONCLUSIONS: Stroke care reorganization following the introduction of thrombolytic treatment was associated with a 50% reduction in LOS for non-stroke patients admitted to the SU. Reduced LOS in the SU for non-stroke patients could further add to the cost-effectiveness of thrombolytic treatment.

MRI detection of early blood-brain barrier disruption: parenchymal enhancement predicts focal hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: Blood-brain barrier disruption may be a predictor of hemorrhagic transformation (HT) in ischemic stroke. We hypothesize that parenchymal enhancement (PE) on postcontrast T1-weighted MRI predicts and localizes subsequent HT. METHODS: In a prospective study, 33 tPA-treated stroke patients were imaged by perfusion-weighted imaging, T1 and FLAIR before thrombolytic therapy and after 2 and 24 hours. RESULTS: Postcontrast T1 PE was found in 5 of 32 patients (16%) 2 hours post-thrombolysis. All 5 patients subsequently showed HT compared to 11 of 26 patients without PE (P=0.043, specificity 100%, sensitivity 31%), with exact anatomic colocation of PE and HT. Enhancement of cerebrospinal fluid on FLAIR was found in 4 other patients, 1 of which developed HT. Local reperfusion was found in 4 of 5 patients with PE, whereas reperfusion was found in all cases of cerebrospinal fluid hyperintensity. CONCLUSIONS: PE detected 2 hours after thrombolytic therapy predicts HT with high specificity. Contrast-enhanced MRI may provide a tool for studying HT and targeting future therapies to reduce risk of hemorrhagic complications.

[Imaging of the pathophysiology in acute stroke]. / Billeddiagnostik af patofysiologien ved akut apopleksi.

Recent developments in neuroimaging have changed the diagnostic aspect of acute stroke and improved our understanding of stroke pathophysiology. Both diffusion weighted MR imaging and CT are capable of detecting the infarcted volume damaged by cytotoxic edema. However, within six hours of stroke onset, DWI has both higher sensitivity and specificity than CT. Perfusion weighted MR imaging and perfusion CT can identify the tissue at risk surrounding the core of the infarct. CT and MR-angiography contribute important information concerning the intra and extracerebral arteries.

[Thrombolysis of apoplexy patients. A year's experience and results in Aarhus Hospital]. / Trombolyse af apopleksipatienter. Første års erfaringer og resultater på Arhus Sygehus.

INTRODUCTION: Treatment of acute stroke with thrombolysis within three hours is a challenging aspect of the organization of state-of-the-art stroke care. Indication for thrombolysis is based on studies where CT was used as a diagnostic tool. MR-based techniques are in some aspects superior to CT, though the scan times are longer. In this study, the feasibility and effectiveness of MR-based thrombolysis was examined. MATERIALS AND METHODS: Prospective registration of patient time delays, demographics, initial NIHSS (National Institute of Health Stroke Scale) and MR data for all patients referred to Aarhus Hospital with symptoms of acute stroke was done over a one-year period. For patients receiving thrombolysis, additional MR data, complications, NIHSS at follow-up (2 hours, 24 hours, 7 days and 3 months) and modified Rankin score at 3 months were recorded. Results were compared to the data in the international thrombolysis database (SITS-MOST). RESULTS: During the period, 112 patients were referred and 86 were scanned using MR techniques. 22 patients received thrombolysis (17/5 after MR/CT). 54% of patients had a good outcome at 3 months (mRS = 0-1) compared to 34% in SITS-MOST (n.s). No symptomatic haemorrhages were recorded; mortality was 9% (13% in SITS-MOST). Treatment was not delayed compared to SITS-MOST despite the longer MR scan time. CONCLUSION: Effective organization of treatment with thrombolysis using MR imaging is feasible. The MR techniques were beneficial in decision making and did not cause delay of treatment. Thrombolysis in this setup was as efficient with respect to outcome and complications as was that recorded in the SITS-MOST register.

Ischemic injury detected by diffusion imaging 11 minutes after stroke.

A 78-year-old woman suffered a stroke inside a magnetic resonance scanner while being imaged because of a brief transient ischemic attack 2 hours earlier. Diffusion-weighted images obtained 11 minutes after stroke showed tissue injury not found on initial images. The data show early, abrupt diffusion changes in hypoperfused tissue, adding to our understanding of the progression of microstructural abnormalities in the hyperacute phase of stroke.