Evaluation of FRESH scores in predicting outcome and quality of life after aneurysmal subarachnoid haemorrhage in a European patient cohort.

BACKGROUND: Despite aneurysmal subarachnoid haemorrhage (aSAH) patients often experiencing physical and mental disabilities impacting their quality of life (QoL), routine assessment of long-term QoL data and predictive tools are limited. This study evaluates the newly developed "functional recovery expected after subarachnoid haemorrhage" (FRESH) scores with long-term outcomes and QoL in European aSAH patients. METHODS: FRESH, FRESH-cog, and FRESH-quol scores were retrospectively obtained from aSAH patients. Patients were contacted, and the modified Rankin Scale (mRS), extended short form-36 (SF-36), and telephone interview for cognitive status (TICS) were collected and performed. The prognostic and empirical outcomes were compared. RESULTS: Out of 374 patients, 171 patients (54.1%) completed the SF-36, and 154 patients completed the TICS. The SF-36 analysis showed that 32.7% had below-average physical component summary (PCS) scores, and 39.8% had below-average mental component summary (MCS) scores. There was no significant correlation between the FRESH score and PCS (p = 0.09736), MCS (p = 0.1796), TICS (p = 0.7484), or mRS 10-82 months (average 46 months) post bleeding (p = 0.024), respectively. There was also no significant correlation found for "FRESH-cog vs. TICS" (p = 0.0311), "FRESH-quol vs. PCS" (p = 0.0204), "FRESH-quol vs. MCS" (p = 0.1361) and "FRESH-quol vs. TICS" (p = 0.1608). CONCLUSIONS: This study found no correlation between FRESH scores and validated QoL tools in a European population of aSAH patients. The study highlights the complexity of reliable long-term QoL prognostication in aSAH patients and emphasises the need for further prospective research to also focus on QoL as an important outcome parameter.

Clinical Outcome Prediction of Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage: the SHELTER-Score.

BACKGROUND: Despite intensive research on preventing and treating vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH), mortality and morbidity rates remain high. Early brain injury (EBI) has emerged as possibly the major significant factor in aSAH pathophysiology, emphasizing the need to investigate EBI-associated clinical events for improved patient management and decision-making. This study aimed to identify early clinical and radiological events within 72 h after aSAH to develop a conclusive predictive EBI score for clinical practice. METHODS: This retrospective analysis included 561 consecutive patients with aSAH admitted to our neurovascular center between 01/2014 and 09/2022. Fourteen potential predictors occurring within the initial 72 h after hemorrhage were analyzed. The modified Rankin Scale (mRS) score at 6 months, discretized to three levels (0-2, favorable; 3-5, poor; 6, dead), was used as the outcome variable. Univariate ordinal regression ranked predictors by significance, and forward selection with McFadden's pseudo-R2 determined the optimal set of predictors for multivariate proportional odds logistic regression. Collinear parameters were excluded, and fivefold cross-validation was used to avoid overfitting. RESULTS: The analysis resulted in the Subarachnoid Hemorrhage Associated Early Brain Injury Outcome Prediction score (SHELTER-score), comprising seven clinical and radiological events: age (0-4 points), World Federation of Neurosurgical Societies (0-2.5 points), cardiopulmonary resuscitation (CPR) (2 points), mydriasis (1-2 points), midline shift (0.5-1 points), early deterioration (1 point), and early ischemic lesion (2 points). McFadden's pseudo-R2 = 0.339, area under the curve for death or disability 0.899 and 0.877 for death. A SHELTER-score below 5 indicated a favorable outcome (mRS 0-2), 5-6.5 predicted a poor outcome (mRS 3-5), and ≥ 7 correlated with death (mRS 6) at 6 months. CONCLUSIONS: The novel SHELTER-score, incorporating seven clinical and radiological features of EBI, demonstrated strong predictive performance in determining clinical outcomes. This scoring system serves as a valuable tool for neurointensivists to identify patients with poor outcomes and guide treatment decisions, reflecting the great impact of EBI on the overall outcome of patients with aSAH.

Blood Pressure Affects the Early CT Perfusion Imaging in Patients with aSAH Reflecting Early Disturbed Autoregulation.

BACKGROUND: Early computed tomography perfusion (CTP) is frequently used to predict delayed cerebral ischemia following aneurysmatic subarachnoid hemorrhage (aSAH). However, the influence of blood pressure on CTP is currently controversial (HIMALAIA trial), which differs from our clinical observations. Therefore, we aimed to investigate the influence of blood pressure on early CTP imaging in patients with aSAH. METHODS: We retrospectively analyzed the mean transit time (MTT) of early CTP imaging within 24 h after bleeding prior to aneurysm occlusion with respect to blood pressure shortly before or after the examination in 134 patients. We correlated the cerebral blood flow with the cerebral perfusion pressure in the case of patients with intracranial pressure measurement. We performed a subgroup analysis of good-grade (World Federation of Neurosurgical Societies [WFNS] I-III), poor-grade (WFNS IV-V), and solely WFNS grade V aSAH patients. RESULTS: Mean arterial pressure (MAP) significantly correlated inversely with the mean MTT in early CTP imaging (R = - 0.18, 95% confidence interval [CI] - 0.34 to - 0.01, p = 0.042). Lower mean blood pressure was significantly associated with a higher mean MTT. Subgroup analysis revealed an increasing inverse correlation when comparing WFNS I-III (R = - 0.08, 95% CI - 0.31 to 0.16, p = 0.53) patients with WFNS IV-V (R = - 0.2, 95% CI - 0.42 to 0.05, p = 0.12) patients, without reaching statistical significance. However, if only patients with WFNS V are considered, a significant and even stronger correlation between MAP and MTT (R = - 0.4, 95% CI - 0.65 to 0.07, p = 0.02) is observed. In patients with intracranial pressure monitoring, a stronger dependency of cerebral blood flow on cerebral perfusion pressure is observed for poor-grade patients compared with good-grade patients. CONCLUSIONS: The inverse correlation between MAP and MTT in early CTP imaging, increasing with the severity of aSAH, suggests an increasing disturbance of cerebral autoregulation with the severity of early brain injury. Our results emphasize the importance of maintaining physiological blood pressure values in the early phase of aSAH and preventing hypotension, especially in patients with poor-grade aSAH.

Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) is often caused by irruption of intracerebral hemorrhage (ICH) of basal ganglia or thalamus into the ventricular system. Instillation of recombinant tissue plasminogen activator (rtPA) via an external ventricular drainage (EVD) has been shown to effectively decrease IVH volumes while the impact of rtPA instillation on ICH volumes remains unclear. In this series, we analyzed volumetric changes of ICH in patients with and without intrathecal lysis therapy. METHODS: Between 01/2013 and 01/2019, 36 patients with IVH caused by hemorrhage of basal ganglia, thalamus or brain stem were treated with rtPA via an EVD (Group A). Initial volumes were determined in the first available computed tomography (CT) scan, final volumes in the last CT scan before discharge. During the same period, 41 patients with ICH without relevant IVH were treated without intrathecal lysis therapy at our neurocritical care unit (Group B). Serial CT scans were evaluated separately for changes in ICH volumes for both cohorts using OsiriX DICOM viewer. The Wilcoxon signed-rank test was performed for statistical analysis in not normally distributed variables. RESULTS: Median initial volume of ICH for treatment Group A was 6.5 ml and was reduced to 5.0 ml after first instillation of rtPA (p < 0.01). Twenty-six patients received a second treatment with rtPA (ICH volume reduction 4.5 to 3.3 ml, p < 0.01) and of this cohort further 16 patients underwent a third treatment (ICH volume reduction 3.0 ml to 1.5 ml, p < 0.01). Comparison of first and last CT scan in Group A confirmed an overall median percentage reduction of 91.7% (n = 36, p < 0.01) of ICH volumes and hematoma resolution in Group A was significantly more effective compared to non-rtPA group, Group B (percentage reduction = 68%) independent of initial hematoma volume in the regression analysis (p = 0.07, mean 11.1, 95%CI 7.7-14.5). There were no adverse events in Group A related to rtPA instillation. CONCLUSION: Intrathecal lysis therapy leads to a significant reduction in the intraparenchymal hematoma volume with faster clot resolution compared to the spontaneous hematoma resorption. Furthermore, intrathecal rtPA application had no adverse effect on ICH volume.

Endovascular aneurysm closure during out of office hours is not related to complications or outcome.

PURPOSE: A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. METHODS: We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. RESULTS: Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53-1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68-1.97 and 1.16 95% CI 0.56-2.29, respectively) compared to patients treated during office hours. CONCLUSION: In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

Meteorological factors for subarachnoid hemorrhage in the greater Düsseldorf area revisited: a machine learning approach to predict the probability of admission of patients with subarachnoid hemorrhage.

BACKGROUND: Reported data regarding the relation between the incidence of spontaneous subarachnoid hemorrhage (SAH) and weather conditions are conflicting and do so far not allow prognostic models. METHODS: Admissions for spontaneous SAH (ICD I60.*) 2009-2018 were retrieved form our hospital data base. Historical meteorological data for the nearest meteorological station, Düsseldorf Airport, was retrieved from the archive of the Deutsche Wetterdienst (DWD). Airport is in the center of our catchment area with a diameter of approximately 100 km. Pearson correlation matrix between mean daily meteorological variables and the daily admissions of one or more patients with subarachnoid hemorrhage was calculated and further analysis was done using deep learning algorithms. RESULTS: For the 10-year period from January 1, 2009 until December 31, 2018, a total of 1569 patients with SAH were admitted. No SAH was admitted on 2400 days (65.7%), 1 SAH on 979 days (26.7%), 2 cases on 233 days (6.4%), 3 SAH on 37 days (1.0%), 4 in 2 days (0.05%), and 5 cases on 1 day (0.03%). Pearson correlation matrix suggested a weak positive correlation of admissions for SAH with precipitation on the previous day and weak inverse relations with the actual mean daily temperature and the temperature change from the previous days, and weak inverse correlations with barometric pressure on the index day and the day before. Clustering with admission of multiple SAH on a given day followed a Poisson distribution and was therefore coincidental. The deep learning algorithms achieved an area under curve (AUC) score of approximately 52%. The small difference from 50% appears to reflect the size of the meteorological impact. CONCLUSION: Although in our data set a weak correlation of the probability to admit one or more cases of SAH with meteorological conditions was present during the analyzed time period, no helpful prognostic model could be deduced with current state machine learning methods. The meteorological influence on the admission of SAH appeared to be in the range of only a few percent compared with random or unknown factors.

Correction to: Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage.

The author name Kerim Beseoglu has been corrected and the details given in this correction are correct.

Barrel Stave Osteotomy Decompression for Acute Brain Injury in Infants: Technical Note.

Decompressive craniectomy (DC) is rarely required in infants, but when performed several aspects should be considered: These youngest patients are vulnerable to blood loss and cranial reconstruction can be challenging due to skull growth and bone flap resorption. On the other hand, infants have thin and flexible bone and osteogenic potential. The authors propose a technique which makes use of these unique aspects by achieving decompression with the craniofacial method of barrel stave osteotomy, aiming to achieve adequate DC, limit perioperative risks and facilitate subsequent cranial reconstruction.

Decompressive craniectomy for acute ischemic stroke.

Malignant stroke occurs in a subgroup of patients suffering from ischemic cerebral infarction and is characterized by neurological deterioration due to progressive edema, raised intracranial pressure, and cerebral herniation. Decompressive craniectomy (DC) is a surgical technique aiming to open the "closed box" represented by the non-expandable skull in cases of refractory intracranial hypertension. It is a valuable modality in the armamentarium to treat patients with malignant stroke: the life-saving effect has been proven for both supratentorial and infratentorial DC in virtually all age groups. This leaves physicians with the difficult task to decide who will require early or preemptive surgery and who might benefit from postponing surgery until clear evidence of deterioration evolves. Together with the patient's relatives, physicians also have to ascertain whether the patient will have acceptable disability and quality of life in his or her presumed perception, based on preoperative predictions. This complex decision-making process can only be managed with interdisciplinary efforts and should be supported by continued research in the age of personalized medicine.

From decompressive craniectomy to cranioplasty and beyond-a pediatric neurosurgery perspective.

PURPOSE: Decompressive craniectomy (DC) is an established neurosurgical emergency technique. Patient selection, optimal timing, and technical aspects related to DC and subsequent cranioplasty remain subjects of debate. For children, the overall degree of evidence is low, compared with randomized controlled trials (RCTs) in adults. METHODS: Here, we present a detailed retrospective analysis of pediatric DC, covering the primary procedure and cranioplasty. Results are analyzed and discussed in the light of modern scientific evidence, and conclusions are drawn to stimulate future research. RESULTS: The main indication for DC in children is traumatic brain injury (TBI). Primary and secondary DC is performed with similar frequency. Outcome appears to be better than that in adults, although long-term complications (especially bone flap resorption after autologous cranioplasty) are more common in children. Overt clinical signs of cerebral herniation prior to DC are predictors of poor outcome. CONCLUSIONS: We conclude that DC is an important option in the armamentarium to treat life-threatening intracranial hypertension, but further research is warranted, preferentially in a multicenter prospective registry.

Prediction of outcome after aneurysmal subarachnoid haemorrhage using data from patient admission.

OBJECTIVES: The pathogenesis leading to poor functional outcome after aneurysmal subarachnoid haemorrhage (aSAH) is multifactorial and not fully understood. We evaluated a machine learning approach based on easily determinable clinical and CT perfusion (CTP) features in the course of patient admission to predict the functional outcome 6 months after ictus. METHODS: Out of 630 consecutive subarachnoid haemorrhage patients (2008-2015), 147 (mean age 54.3, 66.7% women) were retrospectively included (Inclusion: aSAH, admission within 24 h of ictus, CTP within 24 h of admission, documented modified Rankin scale (mRS) grades after 6 months. Exclusion: occlusive therapy before first CTP, previous aSAH, CTP not evaluable). A random forests model with conditional inference trees was optimised and trained on sex, age, World Federation of Neurosurgical Societies (WFNS) and modified Fisher grades, aneurysm in anterior vs. posterior circulation, early external ventricular drainage (EVD), as well as MTT and Tmax maximum, mean, standard deviation (SD), range, 75th quartile and interquartile range to predict dichotomised mRS (≤ 2; > 2). Performance was assessed using the balanced accuracy over the training and validation folds using 20 repeats of 10-fold cross-validation. RESULTS: In the final model, using 200 trees and the synthetic minority oversampling technique, median balanced accuracy was 84.4% (SD 0.7) over the training folds and 70.9% (SD 1.2) over the validation folds. The five most important features were the modified Fisher grade, age, MTT range, WFNS and early EVD. CONCLUSIONS: A random forests model trained on easily determinable features in the course of patient admission can predict the functional outcome 6 months after aSAH with considerable accuracy. KEY POINTS: • Features determinable in the course of admission of a patient with aneurysmal subarachnoid haemorrhage (aSAH) can predict the functional outcome 6 months after the occurrence of aSAH. • The top five predictive features were the modified Fisher grade, age, the mean transit time (MTT) range from computed tomography perfusion (CTP), the WFNS grade and the early necessity for an external ventricular drainage (EVD). • The range between the minimum and the maximum MTT may prove to be a valuable biomarker for detrimental functional outcome.

Decompressive hemicraniectomy for malignant middle cerebral artery infarction including patients with additional involvement of the anterior and/or posterior cerebral artery territory-outcome analysis and definition of prognostic factors.

BACKGROUND: According to current evidence, adding decompressive craniectomy (DC) to best medical therapy reduces case fatality rate of malignant middle cerebral artery infarction by 50-75%. There is currently little information available regarding the outcome of subgroups, in particular of patients with extensive infarctions exceeding the territory of the middle cerebral artery. METHODS: The records of 101 patients with large hemispheric infarctions undergoing DC were retrospectively reviewed. Twenty-seven patients had additional ACA and/or PCA infarcts. Sequential CTs were used for postoperative follow-up. Intracranial pressure (ICP) was monitored via a ventricular catheter in comatose patients. The main aim of treatment was to keep midline shift below 10 mm and ICP below 20 mmHg. If midline shift increased despite preceding DC, repeat surgery with removal of clearly necrotic tissue was considered. For the current analysis, Glasgow Coma Scale (GCS) at 14 days and modified Rankin Scale (mRS) at 3 months were used as outcome parameters. mRS 2 and 3 were defined as "moderate disability", mRS 4 as "severe disability", and mRS 5 and 6 as "poor outcome". These outcome parameters were correlated to age, gender, side, vascular territory, and time delay after stroke, GCS at the time of decompression, maximum ICP, maximum midline shift, and delay of maximum shift. RESULTS: The median age of the 39 female and 62 male patients was 56 years (range, 5-79 years). Overall, 12 patients died in the acute stage (11.9%). Twenty-three (22.8%) patients recovered to moderate disability at 3 months (mRS ≤ 3), 45 (44.6%) to severe disability and 33 (32.6%) suffered a poor outcome (mRS 5 or 6). Twenty patients (19.8%) required additional necrosectomy due to secondary increasing midline shift and/or intracranial hypertension. Patients recovering to moderate disability at 3 months were in the median 10 years younger than patients with less favorable outcome (P < 0.001) and had a higher GCS prior to surgery (P < 0.001). Eleven of the 27 patients with infarctions exceeding the MCA territory needed secondary surgery, indicating a higher necrosectomy rate as for isolated MCA infarction. At 3 months, the distribution of the outcomes in terms of mRS was comparable between the patients suffering from extended infarctions and patients having isolated MCA stroke. Infarctions exceeding the territory of the middle cerebral artery were seen in 30% of the group recovering to moderate disability and thus as frequent as in the groups suffering a less favorable outcome. CONCLUSIONS: Intensified postoperative management including possible secondary decompression with necrosectomy may further reduce case fatality rate of patients with large hemispheric infarction. Age above 60 years and severely reduced level of consciousness are the most significant factors heralding unfavorable recovery. Patients suffering infarctions exceeding the MCA territory have a comparable chance of favorable recovery as patients with isolated MCA infarction.

Impact of spinal cord compression from intradural and epidural spinal tumors on perioperative symptoms-implications for surgical decision making.

Spinal cord or cauda equina compression (SCC) is an increasing challenge in clinical oncology due to a higher prevalence of long-term cancer survivors. Our aim was to determine the clinical relevance of SCC regarding patient outcome depending on different tumor entities and their anatomical localization (extradural/intradural/intramedullary). We retrospectively analyzed 230 patients surgically treated for SCC. Preoperative status for pain and neurological impairment were correlated to the degree of compression, tumor location, and early as well as short-term follow-up outcome parameters. Interestingly, we did not observe any differences between intradural-extramedullary compared to extradural tumors. Unilaterally localized tumors were likely to present with pain (72.9 %, p < 0.01), whereas concentric growth was associated with motor deficits (41.0 %, p < 0.01, as primary symptom, 49.3 % on admission, p < 0.05). In concentric tumors, the pain pattern was diffuse (40.5 % vs. 17.5 in unilateral disease, p < 0.01), whereas unilateral tumors resulted in localized pain (61.4 % local axial or radicular, p < 0.01). Diffuse pain, patients without a sensory or motor deficit, progressive disease, cervical localization, and a higher degree of stenosis were identified as beneficial for an early improvement in pain (p < 0.05). Notably, 29 % of patients with unchanged pain and 30.8 % with unchanged neurologic function at day 7 postoperative improved during follow-up (p < 0.001). Our data demonstrate that the preoperative tumor anatomy in patients with SCC was closely related to their presenting symptoms and early clinical outcome. The detailed analysis elucidates the biology of SCC and might thereby aid in determining which patients will benefit from surgery.

Life-threatening posterior reversible encephalopathy syndrome in the cerebellum treated by posterior fossa decompression.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome associated with various clinical conditions, such as headache, encephalopathy, and seizures. It is reversible if a prompt diagnosis is made and treatment undertaken. We report a 52-year-old male with hypertensive crisis. Progressing somnolence and an unresponsive left pupil occurred. MRI revealed an intra-axial hyperintensity of the cerebellum and brainstem and occlusive hydrocephalus suggestive of encephalitis or a tumor. Because of the life-threatening clinical picture, posterior fossa decompression was performed. Histopathology failed to identify any pathology. After decompression, the edema improved immediately. Under life-threatening conditions, a decompressive craniectomy in PRES seems to achieve the same results as supportive treatment.

Extracorporeal decarboxylation in patients with severe traumatic brain injury and ARDS enables effective control of intracranial pressure.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) with concomitant impairment of oxygenation and decarboxylation represents a complex problem in patients with increased intracranial pressure (ICP). Permissive hypercapnia is not an option to obtain and maintain lung-protective ventilation in the presence of elevated ICP. Pumpless extracorporeal lung assist (pECLA) devices (iLA Membrane Ventilator; Novalung, Heilbronn, Germany) can improve decarboxylation without aggravation associated with invasive ventilation. In this pilot series, we analyzed the safety and efficacy of pECLA in patients with ARDS and elevated ICP after severe traumatic brain injury (TBI). METHODS: The medical records of ten patients (eight male, two female) with severe ARDS and severe TBI concurrently managed with external ventricular drainage in the neurointensive care unit (NICU) were retrospectively analyzed. The effect of pECLA on enabling lung-protective ventilation was evaluated using the difference between plateau pressure and positive end-expiratory pressure, defined as driving pressure (ΔP), during the 3 days preceding the implant of pECLA devices until 3 days afterward. The ICP threshold was set at 20 mmHg. To evaluate effects on ICP, the volume of daily cerebrospinal fluid (CSF) drainage needed to maintain the set ICP threshold was compared pre- and postimplant. RESULTS: The ΔP values after pECLA implantation decreased from a mean 17.1 ± 0.7 cm/H2O to 11.9±0.5 cm/H2O (p = 0.011). In spite of this improved lung-protective ventilation, carbon dioxide pressure decreased from 46.6 ± 3.9 mmHg to 39.7 ± 3.5 mmHg (p = 0.005). The volume of daily CSF drainage needed to maintain ICP at 20 mmHg decreased significantly from 141.5 ± 103.5 ml to 62.2 ± 68.1 ml (p = 0.037). CONCLUSIONS: For selected patients with concomitant severe TBI and ARDS, the application of pECLA is safe and effective. pECLA devices improve decarboxylation, thus enabling lung-protective ventilation. At the same time, potentially detrimental hypercapnia that may increase ICP is avoided. Larger prospective trials are warranted to further elucidate application of pECLA devices in NICU patients.

The value of perfusion computed tomography (PCT) imaging after aneurysmal subarachnoid hemorrhage: a review of the current data.

BACKGROUND AND PURPOSE: The estimation of the extent of early brain injury (EBI) and sensitive detection of delayed cerebral ischemia (DCI) remains a major challenge in the context of aneurysmal subarachnoid hemorrhage (aSAH). Cerebral perfusion computed tomography (PCT) imaging is increasingly used as an additional diagnostic tool to monitor early brain injury as well as delayed cerebral ischemia after aSAH. Here, we review the current literature as well as the resulting implications and illustrate our institutional experience with PCT imaging in this context. METHODS: The current literature on PCT imaging for SAH was identified based on a search of the PubMed database. Patient cohorts were dichotomized according to the time of PCT after ictus into early PCT (<72 h after ictus) and subsequent PCT (>72 h after ictus). The specific aspects and findings of PCT at different times are compared and discussed. RESULTS: Sixteen relevant publications were identified, nine of which focused on early PCT and seven on subsequent PCT diagnostics after aSAH. Early PCT provided relevant details on the extent of EBI and identified patients at risk for developing DCI, whereas subsequent PCT imaging facilitated the monitoring and detection of DCI. CONCLUSIONS: The present review demonstrates that PCT imaging is able to detect EBI as well as DCI in patients experiencing aSAH. As a consequence, this technique should be routinely implemented in monitoring strategies for this patient population.

Perioperative measures to improve outcome after subarachnoid hemorrhage-revisiting the concept of secondary brain injury.

Progress in the management of aneurysmal subarachnoid hemorrhage (SAH) is reflected most clearly in a continuously decreasing case fatality rate over the last decades. The purpose of the present review is to identify the relevant factors responsible for this progress and to outline future possibilities of improvement. Although data on intracerebral hemorrhage and ischemic stroke are less homogeneous, the respective data suggest that reduction of case fatalities could also be achieved with these types of stroke. Therefore, advances of general neurocritical care may be the common denominator responsible for the decreasing case fatality rates. Additionally, a change in practice with regard to treatment of elderly patients that is more active may also be a factor. Regarding SAH, the majority of unfavorable outcomes is still related to early or delayed cerebral injury. Therefore, efforts to pharmacologically prevent secondary neuronal damage are likely to play a certain role in achieving improvement in overall outcome. However, the data from previous randomized clinical trials conducted during the last three decades does not strongly support this. A clear benefit has only been proven for oral nimodipine, whereas other calcium antagonists and the rho-kinase inhibitors were not conclusively shown to have a significant effect on functional outcome, and all other tested substances disappointed in clinical trials. Regarding ischemic stroke and traumatic brain injury, intensive clinical research has also been conducted during the last 30 years to improve outcome and to minimize secondary neuronal injury. For ischemic stroke, treatment focusing on reversal of the primary pathomechanism, such as thrombolysis, proved effective, but none of the pharmacological neuroprotective concepts resulted in any benefit. To date, decompressive hemicraniectomy has been the only effective effort focused at reducing secondary damage that resulted in a clear reduction of mortality. In the case of traumatic brain injury, none of the pharmacological or other efforts to limit secondary damage met our hopes. In summary, although limited, pharmacotherapy to limit delayed neuronal injury is more effective for SAH than for ischemic stroke and traumatic brain injury. The disappointing results of most trials addressing secondary damage force one to question the general concept of mechanisms of secondary damage that do not also have a positive side in the natural course of the disease. For example, in the case of SAH, the data from the Cooperative Study from the 1960s showed that vasospasm to some degree protects against rerupture of unsecured aneurysms. Thus, one could argue from an evolutionary standpoint that the purpose of vasospasm was not exclusively a detrimental or suicide pathomechanism, but an attempt to protect against life-threating aneurysm rerupture. Because of the above-discussed arguments, SAH may indeed differ from ischemic stroke and traumatic brain injury with regard to the usefulness of blocking secondary mechanisms pharmacologically. Further efforts to limit vasospasm should therefore be made, and the most promising drugs, calcium antagonists, deserve further development. Because, with various drugs, systemic side effects counteracted the local beneficial effect, future efforts should focus on topical administration of drugs instead of systemic administration. Furthermore, efforts for a better understanding of the variations of the calcium channels and the interplay between the different types of calcium channels should be made.

Age of collagen in intracranial saccular aneurysms.

BACKGROUND AND PURPOSE: The chronological development and natural history of cerebral aneurysms (CAs) remain incompletely understood. We used (14)C birth dating of a main constituent of CAs, that is, collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to investigate this further. METHODS: Forty-six ruptured and unruptured CA samples from 43 patients and 10 cadaveric human cerebral arteries were obtained. The age of collagen, extracted and purified from excised CAs, was estimated using (14)C birth dating and correlated with CA and patient characteristics, including the history of risk factors associated with atherosclerosis and potentially aneurysm growth and rupture. RESULTS: Nearly all CA samples contained collagen type I, which was <5 years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, CAs from patients with a history of risk factors (smoking or hypertension) contained significantly younger collagen than CAs from patients with no risk factors (mean, 1.6±1.2 versus 3.9±3.3 years, respectively; P=0.012). CAs and cerebral arteries did not share a dominant structural protein, such as collagen type I, which would allow comparison of their collagen turnover. CONCLUSIONS: The abundant amount of relatively young collagen type I in CAs suggests that there is an ongoing collagen remodeling in aneurysms, which is significantly more rapid in patients with risk factors. These findings challenge the concept that CAs are present for decades and that they undergo only sporadic episodes of structural change.