Prospective Evaluation of a Modified Apnea Test in Brain Death Candidates that Does Not Require Disconnection from the Ventilator.

BACKGROUND: The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO2) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative. METHODS: The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO2 increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented. RESULTS: The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO2) was lower than the pre-mAT PaO2, whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO2. In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg. CONCLUSIONS: The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803.

[Prospective investigation of extracranial duplex sonography for the detection of cerebral circulatory arrest in patients with irreversible loss of brain function]. / Prospektive Untersuchung der extrakraniellen Duplexsonographie zum Nachweis des zerebralen Perfusionsstillstands bei Patienten mit irreversiblem Hirnfunktionsausfall.

BACKGROUND: A broader distribution of bedside color-coded duplex sonography (CCD) for detection of cerebral circulatory arrest (CCA) would be important to improve its use in the diagnosis of irreversible loss of brain function (ILBF-Dx). QUESTION: Is extracranial compared to the commonly applied transcranial CCD of the brain-supplying vessels (ECCD vs. TCCD) equivalent for the detection of CCA in ILBF-Dx regarding specificity and sensitivity? MATERIAL AND METHODS: Study period January 2019-June 2022, screening of 136 and inclusion of 114 patients with severe brain lesions > 24 h after onset of fixed and dilated pupils, apnea and completed ILBF-Dx. Exclusion of patients without brainstem areflexia and guideline-conform applicability of CCD. Complementary ECCD (and TCCD, if other method used for irreversibility detection). RESULTS: Detection of ILBF (ILBF+) in 86.8% (99/114), no ILBF (ILBF-) in 13.2% (15/114). ECCD was fully feasible in all patients; findings matching CCA were found in 94/99 ILBF+ cases (ECCD+) and not in 5 patients (ECCD-). All 15 patients with ILBF- showed ECCD- findings. Thus, the specificity of ECCD was 1.0, and the sensitivity was 0.949. TCCD showed CCA in 56 patients (TCCD+), and ECCD+ was also found in all of them. An inconclusive result of TCCD in ILBF+ was found in 38 cases, with parallel ECCD+ in all of these patients. In 20 cases, TCCD did not show CCA (TCCD-), these also showed ECCD-. Of these patients 15 were ILBF- and 5 were ILBF+. DISCUSSION: TCCD was not completely feasible or inconclusive in one third of the cases, whereas ECCD was always feasible. ECCD showed high validity with respect to the detection of CCA. Therefore, the possibility of using ECCD alone to detect CCA in ILBF-Dx should be discussed.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Impact of Stereotactic Ventriculocisternostomy on Delayed Cerebral Infarction and Outcome After Subarachnoid Hemorrhage.

Background and Purpose- Delayed cerebral infarction (DCI) is an important cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage is a new method for DCI prevention. Here, we assess the effects of implementing STX-VCS in an unselected aSAH patient population of a tertiary referral center. Methods- Retrospective cohort study of all consecutive aSAH patients admitted to a neurosurgical referral center during a 7-year period (April 2012 to April 2019). Midterm STX-VCS was introduced and offered to patients at high risk for DCI. We compared the incidence and burden of DCI, neurological outcome, and the use of induced hypertension and endovascular rescue therapy in this consecutive aSAH population 3.5 years before versus 3.5 years after STX-VCS became available. Results- Four hundred thirty-six consecutive patients were included: 222 BEFORE and 214 AFTER. Fifty-seven of 214 (27%) patients received STX-VCS. Stereotactic procedures resulted in one (2%) subdural hematoma. Favorable neurological outcome at 6 months occurred in 118 (53%) patients BEFORE and 139 (65%) patients AFTER (relative risk, 0.79 [95% CI, 0.66-0.95]). DCI occurred in 40 (18.0%) patients BEFORE and 17 (7.9%) patients AFTER (relative risk, 0.68 [95% CI, 0.57-0.86]), and total DCI volumes were 8933 (100%) and 3329 mL (36%), respectively. Induced hypertension was used in 97 (44%) and 30 (15%) patients, respectively (relative risk, 0.55 [95% CI, 0.46-0.65]). Thirty (13.5%) patients BEFORE versus 5 (2.3%) patients AFTER underwent endovascular rescue therapies (relative risk, 0.17 [95% CI, 0.07-0.42]). Conclusions- Selecting high-risk patients for STX-VCS reduced the DCI incidence, burden, and related mortality in a consecutive aSAH patient population. This was associated with an improved neurological outcome.

Efficacy and safety of combined intraventricular fibrinolysis with lumbar drainage for prevention of permanent shunt dependency after intracerebral hemorrhage with severe ventricular involvement: A randomized trial and individual patient data meta-analysis.

OBJECTIVE: Intraventricular hemorrhage (IVH) is a negative prognostic factor in intracerebral hemorrhage (ICH) and is associated with permanent shunt dependency in a substantial proportion of patients post-ICH. IVH treatment by intraventricular fibrinolysis (IVF) was recently linked to reduced mortality rates in the CLEAR III study and IVF represents a safe and effective strategy to hasten clot resolution that may reduce shunt rates. Additionally, promising results from observational studies reported reductions in shunt dependency for a combined treatment approach of IVF plus lumbar drains (LDs). The present randomized, controlled trial investigated efficacy and safety of a combined strategy-IVF plus LD versus IVF alone-on shunt dependency in patients with ICH and severe IVH. METHODS: This randomized, open-label, parallel-group study included patients aged 18 to 85 years, prehospital modified Rankin Scale ≤3, ICH volume < 60ml, Glasgow Coma Scale of <9, and severe IVH with tamponade of the third and fourth ventricles requiring placement of external ventricular drainage (EVD). Over a 3-year recruitment period, patients were allocated to either standard treatment (control group receiving IVF consisting of 1mg of recombinant human tissue plasminogen activator every 8 hours until clot clearance of third and fourth ventricles) or a combined treatment approach of IVF and-upon clot clearance of third and fourth ventricles-subsequent placement of an LD for drainage of cerebrospinal fluid (CSF; intervention group). The primary endpoint consisted of permanent shunt placement indicated after a total of three unsuccessful EVD clamping attempts or need for CSF drainage longer than 14 days in both groups. Secondary endpoints included IVF- and LD-related safety, such as bleeding or infections, and functional outcome at 90 and 180 days. Conducted endpoint analyses used individual patient data meta-analyses. The study was registered at clinicaltrials.gov (NCT01041950). RESULTS: The trial was stopped upon predefined interim analysis after 30 patients because of significant efficacy of tested intervention. The primary endpoint was analyzed without dropouts and was reached in 43% (7 of 16) of the control group versus 0% (0 of 14) of the intervention group (p = 0.007). Meta-analyses were based on overall 97 patients, 45 patients receiving IVF plus LD versus 42 with IVF only. Meta-analyses on shunt dependency showed an absolute risk reduction of 24% for the intervention (LD, 2.2% [1 of 45] vs no-LD, 26.2% [11 of 42]; odds ratio [OR] = 0.062; confidence interval [CI], 0.011-0.361; p = 0.002). Secondary endpoints did not show significant differences for CSF infections (OR = 0.869;CI, 0.445-1.695; p = 0.680) and functional outcome at 90 days (OR = 0.478; CI, 0.190-1.201; p = 0.116), yet bleeding complications were significantly reduced in favor of the intervention (OR = 0.401; CI, 0.302-0.532; p < 0.001). INTERPRETATION: The present trial and individual patient data meta-analyses provide evidence that, in patients with severe IVH, as compared to IVF alone, a combined approach of IVF plus LD treatment is feasible and safe and significantly reduces rates of permanent shunt dependency for aresorptive hydrocephalus post-ICH. ANN NEUROL 2017;81:93-103.

COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke (COTTIS): a pilot study.

BACKGROUND: To evaluate the feasibility and safety of a fast initiation of cooling to a target temperature of 35°C by means of transnasal cooling in patients with anterior circulation large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT). METHODS: Patients with an LVO onset of <24 hour who had an indication for EVT were included in the study. Transnasal cooling (RhinoChill) was initiated immediately after the patient was intubated for EVT and continued until an oesophageal target temperature of 35°C was reached. Hypothermia was maintained with surface cooling for 6-hour postrecanalisation, followed by active rewarming (+0.2°C/hour). The primary outcome was defined as the time required to reach 35°C, while secondary outcomes comprised clinical, radiological and safety parameters. RESULTS: Twenty-two patients (median age, 77 years) were included in the study (14 received additional thrombolysis, 4 additional stenting of the proximal internal carotid artery). The median time intervals were 309 min for last-seen-normal-to-groin, 58 min for door-to-cooling-initiation, 65 min for door-to-groin and 123 min for door-to-recanalisation. The target temperature of 35°C was reached within 30 min (range 13-78 min), corresponding to a cooling rate of 2.6 °C/hour. On recanalisation, 86% of the patients had a body temperature of ≤35°C. The median National Institutes of Health Stroke Scale at admission was 15 and improved to 2 by day 7, and 68% of patients had a good outcome (modified Rankin Scale 0-2) at 3 months. Postprocedure complications included asymptomatic bradycardia (32%), pneumonia (18%) and asymptomatic haemorrhagic transformation (18%). CONCLUSION: The combined application of hypothermia and thrombectomy was found to be feasible in sedated and ventilated patents. Adverse events were comparable to those previously described for EVT in the absence of hypothermia. The effect of this procedure will next be evaluated in the randomised COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke-2 trial.

Minimally-invasive bedside catheter haematoma aspiration followed by local thrombolysis in spontaneous supratentorial intracerebral haemorrhage: a retrospective single-center study.

Background and purpose: The role of surgery in the treatment of intracerebral haemorrhage (ICH) remains controversial. Whereas open surgery has failed to show any clinical benefit, recent studies have suggested that minimal invasive procedures can indeed be beneficial, especially when they are applied at an early time point. This retrospective study therefore evaluated the feasibility of a free-hand bedside catheter technique with subsequent local lysis for early haematoma evacuation in patients with spontaneous supratentorial ICH. Methods: Patients with spontaneous supratentorial haemorrhage of a volume of >30 mL who were treated with bedside catheter haematoma evacuation were identified from our institutional database. The entry point and evacuation trajectory of the catheter were based on a 3D-reconstructed CT scan. The catheter was inserted bedside into the core of the haematoma, and urokinase (5,000 IE) was administered every 6 h for a maximum of 4 days. Evolution of haematoma volume, perihaemorrhagic edema, midline-shift, adverse events and functional outcome were analyzed. Results: A total of 110 patients with a median initial haematoma volume of 60.6 mL were analyzed. Haematoma volume decreased to 46.1 mL immediately after catheter placement and initial aspiration (with a median time to treatment of 9 h after ictus), and to 21.0 mL at the end of urokinase treatment. Perihaemorrhagic edema decreased significantly from 45.0 mL to 38.9 mL and midline-shift from 6.0 mm to 2.0 mm. The median NIHSS score improved from 18 on admission to 10 at discharge, and the median mRS at discharge was 4; the latter was even lower in patients who reached a target volume ≤ 15 mL at the end of local lysis. The in-hospital mortality rate was 8.2%, and catheter/local lysis-associated complications occurred in 5.5% of patients. Conclusion: Bedside catheter aspiration with subsequent urokinase irrigation is a safe and feasible procedure for treating spontaneous supratentorial ICH, and can immediately reduce the mass effects of haemorrhage. Additional controlled studies that assess the long-term outcome and generalizability of our findings are therefore warranted. Clinical trial registration: [www.drks.de], identifier [DRKS00007908].

Identifying large vessel occlusion at first glance in telemedicine.

BACKGROUND: Telemedicine has rapidly emerged as an important tool in emergency neurology. In particular, reliable biomarkers of large vessel occlusions (LVOs) are critically necessary in order to identify the need for in-hospital mechanical thrombectomy (MT). Based on pathophysiological factors, we propose that the presence of head and/or gaze deviation alone signifies cortical hypoperfusion and is therefore a highly sensitive marker for the presence of LVO. METHODS: We retrospectively analyzed a cohort of 160 patients, examined via telemedicine and suspected to have had an acute stroke; this included patients with ischemic or hemorrhagic stroke, transient ischemic attack, and stroke mimics. An assessment of head and gaze deviation and NIHSS score evaluation was performed. In a second analysis, patients who only had ischemia in the anterior circulation (n = 110) were evaluated. RESULTS: Head and/or gaze deviation alone was found to be a reliable marker of LVO (sensitivity: 0.66/specificity: 0.92), as well as a sound indicator for MT (0.82/0.91), in patients with suspected ischemic stroke. The performance of this indicator further improved when patients with ischemia in the anterior circulation only were assessed (LVO: 0.70/0.93; MT: 0.86/0.90). In both analyses, head and/or gaze deviation served as a better indicator for LVO or MT compared to the prevalence of motor deficits or aphasia. Of note, in patients who had ischemia in the anterior circulation, head and/or gaze deviation performed better than the NIHSS score as an indicator for MT. CONCLUSION: These findings confirm that the presence of head and/or gaze deviation serves as a reliable biomarker in stroke-based telemedicine for the diagnosis of LVO, as well as a strong indicator for MT. Furthermore, this marker is just as reliable as the NIHSS score but easier to assess. We therefore suggest that any stroke patient who displays head and/or gaze deviation should immediately be scheduled for vessel imaging and subsequently transported to a MT-competent center.

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. Objective: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. Design, Setting, and Participants: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. Intervention: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Main Outcomes and Measures: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Results: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). Conclusion and Relevance: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT01258257.

Antibody-mediated status epilepticus: a retrospective multicenter survey.

BACKGROUND: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. OBJECTIVES: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. METHODS: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. RESULTS: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17-69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55-69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. CONCLUSION: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.

Exclusive color-coded duplex sonography of extracranial vessels reliably confirms brain death: A prospective study.

Background: Transcranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability. Methods: A total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from 01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for >30 min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result. Results: All patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG (n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%). Conclusions: The use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. This makes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted. Trial registration: https://www.drks.de, DRKS00017803.

Basic Surveillance Parameters Improve the Prediction of Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Background: To establish a practical risk chart for prediction of delayed cerebral infarction (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) by using information that is available until day 5 after ictus. Methods: We assessed all consecutive patients with aSAH admitted to our service between September 2008 and September 2015 (n = 417). The data set was randomly split into thirds. Two-thirds were used for model development and one-third was used for validation. Characteristics that were present between the bleeding event and day 5 (i.e., prior to >95% of DCI diagnoses) were assessed to predict DCI by using logistic regression models. A simple risk chart was established and validated. Results: The amount of cisternal and ventricular blood on admission CT (Hijdra sum score), early sonographic vasospasm (i.e., mean flow velocity of either intracranial artery >160 cm/s until day 5), and a simplified binary level of consciousness score until day 5 were the strongest predictors of DCI. A model combining these predictors delivered a high predictive accuracy [the area under the receiver operating characteristic (AUC) curve of 0.82, Nagelkerke's R 2 0.34 in the development cohort]. Validation of the model demonstrated a high discriminative capacity with the AUC of 0.82, Nagelkerke's R 2 0.30 in the validation cohort. Conclusion: Adding level of consciousness and sonographic vasospasm between admission and postbleed day 5 to the initial blood amount allows for simple and precise prediction of DCI. The suggested risk chart may prove useful for selection of appropriate candidates for interventions to prevent DCI.

Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution.

BACKGROUND AND PURPOSE: Mass effect of hematoma and the associated perihematomal edema are commonly responsible for neurological deterioration after intracerebral hemorrhage. Efficacy of surgical and medical therapy is limited. We studied the effect of early continuous hypertonic saline infusion on development of perihematomal edema after severe spontaneous supratentorial hemorrhage. METHODS: Patients with spontaneous lobar and basal ganglia/thalamic bleeding >30 mL (n=26) were treated with early (<72 hours) continuous hypertonic saline infusion (3%) to achieve sodium of 145 to 155 mmol/L and osmolality of 310 to 320 mOsmol/kg. Evolution of absolute edema volume and relative edema volume (ratio absolute edema volume/initial hematoma volume) was assessed on repeated cranial CT and compared to historical patients (n=64) identified on database with hematoma >30 mL. RESULTS: In the treatment group, absolute edema volume was significant smaller between day 8 and day 14 (P(absolute edema volume)= 0.04) and relative edema volume was significant smaller between day 2 and day 14 (P(relative edema volume)=0.02). Intracranial pressure crisis (>20 mm Hg for >20 minutes or new anisocoria) occurred less frequently in the treatment group (12 versus 56; P=0.048). In-hospital mortality was 3 (11.5%) in the hypertonic saline group and 16 (25%) in the control group (P=0.078). Side effects theoretically associated with hypertonic saline including cardiac arrhythmia and acute heart and renal failure occurred in both groups to a similar extent. CONCLUSIONS: Early and continuous infusion of hypertonic saline in patients with severe spontaneous intracerebral hemorrhage was feasible and safe. The beneficial effect of this treatment regimen on edema evolution and outcome has to be demonstrated in a controlled trial.

Lethal varicella-zoster virus reactivation without skin lesions following renal transplantation.

Patients after solid organ transplantation are at increased risk of developing herpes zoster and are more likely to develop major complications such as cutaneous dissemination, post-herpetic neuralgia and visceral organ involvement. We report on a 68-year-old woman being varicella-zoster virus (VZV)-seropositive prior to transplantation, who developed fatal VZV meningoencephalitis after renal transplantation presenting with non-specific neurologic symptoms. The case illustrates that VZV reactivation may occur in renal transplant recipients in the absence of skin lesions. Approaches towards risk assessment pre-transplantation and prophylactic regimens for the prevention of VZV recurrence are needed.

Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) shows perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH) with high contrast, but the procedure is often difficult or not available for clinical use. The aim of the present study was to establish and validate an observer independent method for quantification of PHE on computed tomography (CT) by comparing with simultaneously performed MRI. METHODS: Patients with spontaneous supratentorial ICH were included. Twenty-two patients received coregistered MRI and CT on day 1, and 27 patients on day 5 after admission. Volumes for PHE and ICH were measured (i) manually on CT, (ii) manually on MRI (fluid-attenuated inversion recovery sequence), and (iii) threshold based on CT. To identify optimal threshold values (Hounsfield units) for best correlation of CT with MRI, upper and lower thresholds were adjusted gradually until the PHE volume on CT best fitted the PHE volume on MRI. The established threshold range was prospectively validated in another 15 patients. RESULTS: A threshold range 5-33 Hounsfield units (HU) resulted in best correlation both on days 1 and 5. Using these thresholds in the validation group, PHE volumes on CT and MRI were highly comparable (31 ± 26 ml vs. 30 ± 27 ml) with good correlation (R(2) = 0.96, P < 0.01) and high inter- (0.96) and intraobserver (0.96) reliability. Manually traced PHE on CT was significantly larger (37.3 ± 37 ml vs. 30 ± 27 ml, P < 0.01) with worse inter- (0.89) and intraobserver (0.90) reliability. CONCLUSIONS: Threshold-based CT volumetry of PHE with a threshold range 5-33 HU is a reliable and observer independent method for quantification of PHE after spontaneous ICH.

Drip-and-Ship for Thrombectomy Treatment in Patients With Acute Ischemic Stroke Leads to Inferior Clinical Outcomes in a Stroke Network Covering Vast Rural Areas Compared to Direct Admission to a Comprehensive Stroke Center.

Introduction: Organizing regional stroke care considering thrombolysis as well as mechanical thrombectomy (MTE) remains challenging in light of a wide range of regional population distribution. To compare outcomes of patients in a stroke network covering vast rural areas in southwestern Germany who underwent MTE via direct admission to a single comprehensive stroke center [CSC; mothership (MS)] with those of patients transferred from primary stroke centers [PSCs; drip-and-ship (DS)], we undertook this analysis of consecutive stroke patients with MTE. Materials and Methods: Patients who underwent MTE at the CSC between January 2013 and December 2016 were included in the analysis. The primary outcome measure was 90-day functional independence [modified Rankin score (mRS) 0-2]. Secondary outcome measures included time from stroke onset to recanalization/end of MTE, angiographic outcomes, and mortality rates. Results: Three hundred and thirty-two consecutive patients were included (MS 222 and DS 110). Median age was 74 in both arms of the study, and there was no significant difference in baseline National Institutes of Health Stroke Scale scores (median MS 15 vs. 16 DS). Intravenous (IV) thrombolysis (IVT) rates differed significantly (55% MS vs. 70% DS, p = 0.008). Time from stroke onset to recanalization/end of MTE was 112 min shorter in the MS group (median 230 vs. 342 min, p < 0.001). Successful recanalization [thrombolysis in cerebral infarction (TICI) 2b-3] was achieved in 72% of patients in the MS group and 73% in the DS group. There was a significant difference in 90-day functional independence (37% MS vs. 24% DS, p = 0.017), whereas no significant differences were observed for mortality rates at 90 days (MS 22% vs. DS 17%, p = 0.306). Discussion: Our data suggest that patients who had an acute ischemic stroke admitted directly to a CSC may have better 90-day outcomes than those transferred secondarily for thrombectomy from a PSC.

Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The prognosis of spontaneous intracerebral hemorrhage (sICH) is poor because of the mass effect arising from the hematoma and the associated peri-hemorrhagic edema, leading to increased intracranial pressure. Because the efficacy of surgical and anti-edematous treatment strategies is limited, we investigated the effects of mild induced hypothermia in patients with large sICH. METHODS: Twelve patients with supratentorial sICH >25 mL were treated by hypothermia of 35 degrees C for 10 days. Evolution of hematoma volume and perifocal edema was measured by cranial CT. Functional outcome was assessed after 90 days. These patients were compared to patients (n=25; inclusion criteria: sICH volume >25 mL, no acute restriction of medical therapy on admission) from the local hemorrhage data bank (n=312). Side effects of hypothermia were analyzed. RESULTS: All patients from both groups needed mechanical ventilation and were treated in a neurocritical care unit. All hypothermic patients (mean age, 60+/-10 years) survived until day 90, whereas 7 patients died in the control group (mean age, 67+/-7 years). Absolute hematoma size on admission was 58+/-29 mL (hypothermia) compared to 57+/-31 mL (control). In the hypothermia group, edema volume remained stable during 14 days (day 1, 53+/-43 mL; day 14, 57+/-45 mL), whereas edema significantly increased in the control group from 40+/-28 mL (day 1) to 88+/-47 mL (day 14). ICH continuously dissolved in both groups. Pneumonia rate was 100% in the hypothermia group and 76% in controls (P=0.08). No significant side effects of hypothermia were observed. CONCLUSIONS: Hypothermia prevented the increase of peri-hemorrhagic edema in patients with large sICH.

Predictors for good functional outcome after neurocritical care.

INTRODUCTION: There are only limited data on the long-term outcome of patients receiving specialized neurocritical care. In this study we analyzed survival, long-term mortality and functional outcome after neurocritical care and determined predictors for good functional outcome. METHODS: We retrospectively investigated 796 consecutive patients admitted to a non-surgical neurologic intensive care unit over a period of two years (2006 and 2007). Demographic and clinical parameters were analyzed. Depending on the diagnosis, we grouped patients according to their diseases (cerebral ischemia, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), meningitis/encephalitis, epilepsy, Guillain-Barré syndrome (GBS) and myasthenia gravis (MG), neurodegenerative diseases and encephalopathy, cerebral neoplasm and intoxication). Clinical parameters, mortality and functional outcome of all treated patients were analyzed. Functional outcome (using the modified Rankin Scale, mRS) one year after discharge was assessed by a mailed questionnaire or telephone interview. Outcome was dichotomized into good (mRS ≤ 2) and poor (mRS ≥ 3). Logistic regression analyses were calculated to determine independent predictors for good functional outcome. RESULTS: Overall in-hospital mortality amounted to 22.5% of all patients, and a good long-term functional outcome was achieved in 28.4%. The parameters age, length of ventilation (LOV), admission diagnosis of ICH, GBS/MG, and inoperable cerebral neoplasm as well as Therapeutic Intervention Scoring System (TISS)-28 on Day 1 were independently associated with functional outcome after one year. CONCLUSIONS: This investigation revealed that age, LOV and TISS-28 on Day 1 were strongly predictive for the outcome. The diagnoses of hemorrhagic stroke and cerebral neoplasm leading to neurocritical care predispose for functional dependence or death, whereas patients with GBS and MG are more likely to recover after neurocritical care.

Sympathetic cardiovascular hyperactivity precedes brain death.

OBJECTIVE: The time preceding brain death is associated with complex dysregulation including autonomic dysfunction that may compromise organ perfusion, thus inducing final organ failure. In this study, we assessed autonomic function in patients prior to brain death. METHODS: In 5 patients (2 women, median 60 years, age range 52-75 years) with fatal cerebral hemorrhage or stroke and negative prognosis, we monitored RR-intervals (RRI), systolic and diastolic blood pressure (BP), and oxygen saturation. Adjustment of mechanical ventilation remained constant. We assessed autonomic function from spectral powers of RRI and BP in the mainly sympathetic low- (LF, 0.04-0.15 Hz) and parasympathetic high-frequencies (HF, 0.15-0.5 Hz), and calculated the RRI-LF/HF-ratio as index of sympathovagal balance. Three patients required norepinephrine (0.5-1.6 mg/h) for up to 72 h to maintain organ perfusion. Norepinephrine was reduced to 0.2-0.5 mg/h within 2 h before brain death was diagnosed according to the criteria of the German Medical Association. Wilcoxon test compared average values of ten 2-min epochs determined 2-3 h (measurement 1) and 1 h (measurement 2) before brain death. RESULTS: We found higher systolic (127.3 ± 15.9 vs. 159.4 ± 44.8 mmHg) and diastolic BP (60.1 ± 15.6 vs. 74.0 ± 15.2 mmHg), RRI-LF/HF-ratio (1.2 ± 1.6 vs. 3.9 ± 4.0), and BP-LF-powers (2.7 ± 4.8 vs. 23.1 ± 28.3 mmHg²) during measurement 2 than during measurement 1 (p < 0.05). CONCLUSIONS: The increase in BPs, in sympathetically mediated BP-LF-powers, and in the RRI-LF/HF-ratio suggests prominent sympathetic activity shortly before brain death. Prefinal sympathetic hyperactivity might cause final organ failure with catecholamine-induced tissue damage which impedes post-mortem organ transplantation.