The Optimal pressure reactivity index range is disease-specific: A comparison between aneurysmal subarachnoid hemorrhage and traumatic brain injury.

PURPOSE: Impaired cerebral pressure autoregulation is common and detrimental after acute brain injuries. Based on the prevalence of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH) patients compared to traumatic brain injury (TBI), we hypothesized that the type of autoregulatory disturbance and the optimal PRx range may differ between these two conditions. The aim of this study was to determine the optimal PRx ranges in relation to functional outcome following aSAH and TBI, respectively. METHODS: In this observational study, 487 aSAH patients and 413 TBI patients, treated in the neurointensive care, Uppsala, Sweden, between 2008 and 2018, were included. The percentage of good monitoring time (%GMT) of PRx was calculated within 8 intervals covering the range from -1.0 to + 1.0, and analyzed in relation to favorable outcome (GOS-E 5 to 8). RESULTS: In multiple logistic regressions, a higher %GMTs of PRx in the intervals -1.0 to -0.5 and + 0.75 to + 1.0 were independently associated with a lower rate of favorable outcome in the aSAH cohort. In a similar analysis in the TBI cohort, only positive PRx in the interval + 0.75 to + 1.0 was independently associated with a lower rate of favorable outcome. CONCLUSION: Extreme PRx values in both directions were unfavorable in aSAH, possibly as high PRx could indicate proximal vasospasm with exhausted distal vasodilatory reserve, while very negative PRx could reflect myogenic hyperreactivity with suppressed cerebral blood flow. Only elevated PRx was unfavorable in TBI, possibly as pressure passive vessels may be a more predominant pathomechanism in this disease.

Individualized Autoregulation-Derived Cerebral Perfusion Targets in Aneurysmal Subarachnoid Hemorrhage: A New Therapeutic Avenue?

Background: Cerebral perfusion pressure (CPP) is an important target in aneurysmal subarachnoid hemorrhage (aSAH), but it does not take into account autoregulatory disturbances. The pressure reactivity index (PRx) and the CPP with the optimal PRx (CPPopt) are new variables that may capture these pathomechanisms. In this study, we investigated the effect on the outcome of certain combinations of CPP or ΔCPPopt (actual CPP-CPPopt) with the concurrent autoregulatory status (PRx) after aSAH. Methods: This observational study included 432 aSAH patients, treated in the neurointensive care unit, at Uppsala University Hospital, Sweden. Functional outcome (GOS-E) was assessed 1-year postictus. Heatmaps of the percentage of good monitoring time (%GMT) of PRx/CPP and PRx/ΔCPPopt combinations in relation to GOS-E were created to visualize the association between these variables and outcome. Results: In the heatmap of the %GMT of PRx/CPP, the combination of lower CPP with higher PRx values was more strongly associated with lower GOS-E. The tolerance for lower CPP values increased with lower PRx values until a threshold of -0.50. However, for decreasing PRx below -0.50, there was a gradual reduction in the tolerance for lower CPP. In the heatmap of the %GMT of PRx/ΔCPPopt, the combination of negative ΔCPPopt with higher PRx values was strongly associated with lower GOS-E. In particular, negative ΔCPPopt together with PRx above +0.50 correlated with worse outcomes. In addition, there was a transition toward an unfavorable outcome when PRx went below -0.50, particularly if ΔCPPopt was negative. Conclusions: The PRx levels influenced the association between CPP/ΔCPPopt and outcome. Thus, this variable could be used to individualize a safe CPP-/ΔCPPopt-range.

The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt). METHODS: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio. RESULTS: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10. CONCLUSIONS: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.

A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease.

BACKGROUND: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. METHODS: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. RESULTS: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. CONCLUSIONS: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.

Trends in incidence and treatments of spontaneous subarachnoid hemorrhage- a 10 year hospital based study.

BACKGROUND: Improved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment. METHODS: The study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases. RESULTS: Endovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5-8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data. CONCLUSIONS: The incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.

Should Patients with Traumatic Brain Injury with Significant Contusions be Treated with Different Neurointensive Care Targets?

BACKGROUND: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions. METHODS: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60-70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than - 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months. RESULTS: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome. CONCLUSIONS: In patients with TBI with significant contusions, CPP within 60-70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice.

Cerebrovascular reactivity (PRx) and optimal cerebral perfusion pressure in elderly with traumatic brain injury.

PURPOSE: Cerebral perfusion pressure (CPP) guidance by cerebral pressure autoregulation (CPA) status according to PRx (correlation mean arterial blood pressure (MAP) and intracranial pressure (ICP)) and optimal CPP (CPPopt = CPP with lowest PRx) is promising but little is known regarding this approach in elderly. The aim was to analyze PRx and CPPopt in elderly TBI patients. METHODS: A total of 129 old (≥ 65 years) and 342 young (16-64 years) patients were studied using monitoring data for MAP and ICP. CPP, PRx, CPPopt, and ΔCPPopt (difference between actual CPP and CPPopt) were calculated. Logistic regression analyses with PRx and ΔCPPopt as explanatory variables for outcome. The combined effects of PRx/CPP and PRx/ΔCPPopt on outcome were visualized as heatmaps. RESULTS: The elderly had higher PRx (worse CPA), higher CPPopt, and different temporal patterns. High PRx influenced outcome negatively in the elderly but less so than in younger patients. CPP close to CPPopt correlated to favorable outcome in younger, in contrast to elderly patients. Heatmap interaction analysis of PRx/ΔCPPopt in the elderly showed that the region for favorable outcome was centered around PRx 0 and ranging between both functioning and impaired CPA (PRx range - 0.5-0.5), and the center of ΔCPPopt was - 10 (range - 20-0), while in younger the center of PRx was around - 0.5 and ΔCPPopt closer to zero. CONCLUSIONS: The elderly exhibit higher PRx and CPPopt. High PRx influences outcome negatively in the elderly but less than in younger patients. The elderly do not show better outcome when CPP is close to CPPopt in contrast to younger patients.

Absolute Contusion Expansion Is Superior to Relative Expansion in Predicting Traumatic Brain Injury Outcomes: A Multi-Center Observational Cohort Study.

Contusion expansion (CE) is a potentially treatable outcome predictor in traumatic brain injury (TBI), and a suitable end-point for hemostatic therapy trials. However, there is no consensus on the definition of clinically relevant CE, both in terms of measurement criteria (absolute vs. relative volume increase) and cutoff values. In light of this, the aim of this study was to assess the predictive abilities of different CE definitions on outcome. We performed a multi-center observational cohort study of adults with moderate-to-severe TBI treated in an intensive care unit. The exposure of interest was CE, defined as the absolute and relative volume change between the first and second computed tomography scan. The primary outcome was the Glasgow Outcome Scale (GOS) at 6-12 months post-injury, dichotomized into unfavorable (GOS ≤3) or favorable (GOS ≥4). The secondary outcome was all-cause mortality. In total, 798 patients were included, with a median duration of 7.0 h between the first and second CT scan. The median absolute and relative CE was 1.5 mL (interquartile range [IQR] 0.1-8.3 mL) and 100% (IQR 10-530%), respectively. Both CE forms were independently associated with unfavorable GOS. Absolute CE outperformed relative CE in predicting both unfavorable GOS (area under the curve [AUC]: 0.65 vs. 0.60, p = 0.002) and all-cause mortality (AUC: 0.66 vs. 0.60, p = 0.003). For dichotomized CE, absolute cutoffs of 1-10 mL yielded the best results. We conclude that absolute CE demonstrates stronger outcome correlation than relative CE. In studies focusing on lesion progression in TBI, it may be advantageous to use absolute CE as the primary outcome metric. For dichotomized outcomes, cutoffs between 1 and 10 mL are suggested, depending on the desired sensitivity-specificity balance.

Thiopental and decompressive craniectomy as last-tier ICP-treatments in aneurysmal subarachnoid hemorrhage: is functional recovery within reach?

The study aimed to investigate the indication and functional outcome after barbiturates and decompressive craniectomy (DC) as last-tier treatments for elevated intracranial pressure (ICP) in aneurysmal subarachnoid hemorrhage (aSAH). This observational study included 891 aSAH patients treated at a single center between 2008 and 2018. Data on demography, admission status, radiology, ICP, clinical course, and outcome 1-year post-ictus were collected. Patients treated with thiopental (barbiturate) and DC were the main target group.Thirty-nine patients (4%) were treated with thiopental alone and 52 (6%) with DC. These patients were younger and had a worse neurological status than those who did not require these treatments. Before thiopental, the median midline shift was 0 mm, whereas basal cisterns were compressed/obliterated in 66%. The median percentage of monitoring time with ICP > 20 mmHg immediately before treatment was 38%, which did not improve after 6 h of infusion. Before DC, the median midline shift was 10 mm, and the median percentage of monitoring time with ICP > 20 mmHg before DC was 56%, which both significantly improved postoperatively. At follow-up, 52% of the patients not given thiopental or operated with DC reached favorable outcome, whereas this occurred in 10% of the thiopental and DC patients.In summary, 10% of the aSAH cohort required thiopental, DC, or both. Thiopental and DC are important integrated last-tier treatment options, but careful patient selection is needed due to the risk of saving many patients into a state of suffering.

Cerebrovascular reserve in moyamoya disease: relation to cerebral blood flow, capillary dysfunction, oxygenation, and energy metabolism.

Background: Cerebral hemodynamics in moyamoya disease (MMD) is complex and needs further elucidation. The primary aim of the study was to determine the association of the cerebrovascular reserve (CVR) with cerebral blood flow (CBF) disturbances, oxygen extraction fraction (OEFmax), and energy metabolism (CMRO2max) in MMD, using arterial spin label magnetic resonance imaging (ASL-MRI) before and after acetazolamide administration. Methods: Thirty-nine ASL-MRI scans with a concurrent acetazolamide challenge from 16 MMD patients at the Uppsala University Hospital, Sweden, 2016-2021, were retrospectively analyzed. CBF was assessed before and 5, 15, and 25 min after acetazolamide administration, and the maximal response CVRmax was used for further analyses. Dynamic susceptibility contrast (DSC) MRI was performed 30 min after acetazolamide injection, and the data were analyzed using the Cercare Medical Neurosuite to assess capillary transit time heterogeneity (CTTH; indicating microvascular function), OEFmax, and CMRO2max. Results: In the ACA territory, a lower CVRmax was associated with lower baseline CBF, higher CTTH, and higher OEFmax but not with CMRO2max in generalized estimating equation models. In the MCA territory, lower CVRmax was associated with lower baseline CBF and higher CMRO2max but not with CTTH and OEFmax.. Conclusion: Altogether, a compromised CVR in MMD patients reflected disturbances in macro-/microvascular blood flow, oxygenation, and CMRO2. ASL-MRI with acetazolamide challenge is a feasible and radiation-free alternative to positron emission tomography (PET) imaging in MMD.

Intracranial lesion features in moderate-to-severe traumatic brain injury: relation to neurointensive care variables and clinical outcome.

BACKGROUND: The primary aim was to determine the association of intracranial hemorrhage lesion type, size, mass effect, and evolution with the clinical course during neurointensive care and long-term outcome after traumatic brain injury (TBI). METHODS: In this observational, retrospective study, 385 TBI patients treated at the neurointensive care unit at Uppsala University Hospital, Sweden, were included. The lesion type, size, mass effect, and evolution (progression on the follow-up CT) were assessed and analyzed in relation to the percentage of secondary insults with intracranial pressure > 20 mmHg, cerebral perfusion pressure < 60 mmHg, and cerebral pressure autoregulatory status (PRx) and in relation to Glasgow Outcome Scale-Extended. RESULTS: A larger epidural hematoma (p < 0.05) and acute subdural hematoma (p < 0.001) volume, greater midline shift (p < 0.001), and compressed basal cisterns (p < 0.001) correlated with craniotomy surgery. In multiple regressions, presence of traumatic subarachnoid hemorrhage (p < 0.001) and intracranial hemorrhage progression on the follow-up CT (p < 0.01) were associated with more intracranial pressure-insults above 20 mmHg. In similar regressions, obliterated basal cisterns (p < 0.001) were independently associated with higher PRx. In a multiple regression, greater acute subdural hematoma (p < 0.05) and contusion (p < 0.05) volume, presence of traumatic subarachnoid hemorrhage (p < 0.01), and obliterated basal cisterns (p < 0.01) were independently associated with a lower rate of favorable outcome. CONCLUSIONS: The intracranial lesion type, size, mass effect, and evolution were associated with the clinical course, cerebral pathophysiology, and outcome following TBI. Future efforts should integrate such granular data into more sophisticated machine learning models to aid the clinician to better anticipate emerging secondary insults and to predict clinical outcome.

ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury: the combined effect of insult intensity and duration on outcome.

PURPOSE: The aim was to investigate the combined effect of insult intensity and duration, regarding intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal CPP (CPPopt), on clinical outcome in pediatric traumatic brain injury (TBI). METHOD: This observational study included 61 pediatric patients with severe TBI, treated at the Uppsala University Hospital, between 2007 and 2018, with at least 12 h of ICP data the first 10 days post-injury. ICP, PRx, CPP, and ∆CPPopt (actual CPP-CPPopt) insults were visualized as 2-dimensional plots to illustrate the combined effect of insult intensity and duration on neurological recovery. RESULTS: This cohort was mostly adolescent pediatric TBI patients with a median age at 15 (interquartile range 12-16) years. For ICP, brief episodes (minutes) above 25 mmHg and slightly longer episodes (20 min) of ICP 20-25 mmHg correlated with unfavorable outcome. For PRx, brief episodes above 0.25 as well as slightly lower values (around 0) for longer periods of time (30 min) were associated with unfavorable outcome. For CPP, there was a transition from favorable to unfavorable outcome for CPP below 50 mmHg. There was no association between high CPP and outcome. For ∆CPPopt, there was a transition from favorable to unfavorable outcome when ∆CPPopt went below -10 mmHg. No association was found for positive ∆CPPopt values and outcome. CONCLUSIONS: This visualization method illustrated the combined effect of insult intensity and duration in relation to outcome in severe pediatric TBI, supporting previous notions to avoid high ICP and low CPP for longer episodes of time. In addition, higher PRx for longer episodes of time and CPP below CPPopt more than -10 mmHg were associated with worse outcome, indicating a potential role for autoregulatory-oriented management in pediatric TBI.

ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease.

PURPOSE: Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients. METHODS: Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery. RESULTS: Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events. CONCLUSION: Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.

Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.

Introduction: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD. Methods: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography. Results: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol. Conclusion: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

Lumbar puncture-verified subarachnoid hemorrhage: bleeding sources, need of radiological examination, and functional recovery.

BACKGROUND: The primary aim was to determine the diagnostic yield of vascular work-up, the clinical course during neurointensive care (NIC), and rate of functional recovery for patients with computed tomography (CT)-negative, lumbar puncture (LP)-verified SAH. METHODS: In this retrospective study, 1280 patients with spontaneous SAH, treated at our NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiological examinations (CT angiography (CTA) and digital subtraction angiography (DSA)), treatments, and functional outcome (GOS-E) at 12 months were evaluated. RESULTS: Eighty (6%) out of 1280 SAH patients were computed tomography (CT)-negative, LP-verified cases. Time between ictus and diagnosis was longer for the LP-verified SAH cohort in comparison to the CT-positive patients (median 3 vs 0 days, p < 0.001). One fifth of the LP-verified SAH patients exhibited an underlying vascular pathology (aneurysm/AVM), which was significantly less common than for the CT-verified SAH cohort (19% vs. 76%, p < 0.001). The CTA- and DSA-findings were consistent in all of the LP-verified cases. The LP-verified SAH patients exhibited a lower rate of delayed ischemic neurological deficits, but no difference in rebleeding rate, compared to the CT-verified cohort. At 1-year post-ictus, 89% of the LP-verified SAH patients had recovered favorably, but 45% of the cases did not reach good recovery. Having an underlying vascular pathology and an external ventricular drainage were associated with worse functional recovery (p = 0.02) in this cohort. CONCLUSIONS: LP-verified SAH constituted a small proportion of the entire SAH population. Having an underlying vascular pathology was less frequent in this cohort, but still occurred in one out of five patients. Despite the small initial bleeding in the LP-verified cohort, many of these patients did not reach good recovery at 1 year, this calls for more attentive follow-up and rehabilitation in this cohort.

Autoregulatory Management in Traumatic Brain Injury: The Role of Absolute Pressure Reactivity Index Values and Optimal Cerebral Perfusion Pressure Curve Shape.

The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. To determine the association between CPP and the relatively best PRx (CPPopt), the percentage of monitoring time of ΔCPPopt (actual CPP-CPPopt) ±5 mm Hg was analyzed in relation to GOS-E. To determine the association between CPP and the relatively best PRx within a certain absolute PRx range (curve shape), both the percentage of ΔCPPopt within the absolute limits of reactivity (PRx <0.00, < 0.15, etc.) and within certain confidence intervals of PRx-deterioration (+0.025, +0.05 etc.) from CPPopt were analyzed in relation to GOS-E. The heatmap of PRx and absolute CPP versus outcome indicated that the CPP range (55-75 mm Hg) associated with favorable outcome was wider when PRx was below 0, whereas the upper CPP-threshold decreased as PRx increased. CPPopt could be calculated during 53% of the monitoring time. Higher percentage of monitoring time with ΔCPPopt ±5 mm Hg, ΔCPPopt within the reactivity-thresholds (PRx <0.30), and ΔCPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.

Autoregulatory Cerebral Perfusion Pressure Insults in Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: The Role of Insult Intensity and Duration on Clinical Outcome.

BACKGROUND: This single-center, retrospective study investigated the outcome effect of the combined intensity and duration of differences between actual cerebral perfusion pressure (CPP) and optimal cerebral perfusion pressure (CPPopt), and also for absolute CPP, in patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 378 TBI and 432 aSAH patients treated in a neurointensive care unit between 2008 and 2018 with at least 24 hours of CPPopt data during the first 10 days following injury, and with 6-month (TBI) or 12-month (aSAH) extended Glasgow Outcome Scale (GOS-E) scores, were included in the study. ∆CPPopt-insults (∆CPPopt=actual CPP-CPPopt) and CPP-insults were visualized as 2-dimensional plots to highlight the combined effect of insult intensity (mm Hg) and duration (min) on patient outcome. RESULTS: In TBI patients, a zone of ∆CPPopt ± 10 mm Hg was associated with more favorable outcome, with transitions towards unfavorable outcome above and below this zone. CPP in the range of 60 to 80 mm Hg was associated with higher GOS-E, whereas CPP outside this range was associated with lower GOS-E. In aSAH patients, there was no clear transition from higher to lower GOS-E for ∆CPPopt-insults; however, there was a transition from favorable to unfavorable outcome when CPP was <80 mm Hg. CONCLUSIONS: TBI patients with CPP close to CPPopt exhibited better clinical outcomes, and absolute CPP within the 60 to 80 mm Hg range was also associated with favorable outcome. In aSAH patients, there was no clear transition for ∆CPPopt-insults in relation to outcome, whereas generally high absolute CPP values were associated overall with favorable recovery.

Intracranial Pressure Variability: A New Potential Metric of Cerebral Ischemia and Energy Metabolic Dysfunction in Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: It was recently reported that lower intracranial pressure variability (ICPV) is associated with delayed ischemic neurological deficits and unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to determine whether lower ICPV also correlated with worse cerebral energy metabolism after aSAH. METHODS: A total of 75 aSAH patients treated in the neurointensive care unit at Uppsala University Hospital, Sweden between 2008 and 2018 and with both intracranial pressure and cerebral microdialysis (MD) monitoring during the first 10 days after ictus were included in this retrospective study. ICPV was calculated with a bandpass filter limited to intracranial pressure slow waves with a wavelength of 55 to 15 seconds. Cerebral energy metabolites were measured hourly with MD. The monitoring period was divided into 3 phases; early (days 1 to 3), early vasospasm (days 4 to 6.5), and late vasospasm (days 6.5 to 10). RESULTS: Lower ICPV was associated with lower MD-glucose in the late vasospasm phase, lower MD-pyruvate in the early vasospasm phases, and higher MD-lactate-pyruvate ratio (LPR) in the early and late vasospasm phases. Lower ICPV was associated with poor cerebral substrate supply (LPR >25 and pyruvate <120 µM) rather than mitochondrial failure (LPR >25 and pyruvate >120 µM). There was no association between ICPV and delayed ischemic neurological deficit, but lower ICPV in both vasospasm phases correlated with unfavorable outcomes. CONCLUSION: Lower ICPV was associated with an increased risk for disturbed cerebral energy metabolism and worse clinical outcomes in aSAH patients, possibly explained by a vasospasm-related decrease in cerebral blood volume dynamics and cerebral ischemia.

Temperature Changes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Relation to Injury Pattern, Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome.

BACKGROUND: The aim was to study the course of body temperature in the acute phase of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in relation to the primary brain injury, cerebral physiology, and clinical outcome. METHODS: In this observational study, 166 patients with aSAH treated at the neurosurgery department at Uppsala University Hospital in Sweden between 2008 and2018 with temperature, intracranial pressure (ICP), and microdialysis (MD) monitoring were included. The first 10 days were divided into the early phase (days 1-3) and the vasospasm phase (days 4-10). RESULTS: Normothermia (temperature = 36-38 °C) was most prevalent in the early phase. A lower mean temperature at this stage was univariately associated with a worse primary brain injury, with higher Fisher grade and higher MD glycerol concentration, as well as a worse neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the early phase. There was a transition toward an increased burden of hyperthermia (temperature > 38 °C) in the vasospasm phase. This was associated with concurrent infections but not with neurological or radiological injury severity at admission. Elevated temperature was associated with higher MD pyruvate concentration, lower rate of an MD pattern indicative of ischemia, and higher rate of poor neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the vasospasm phase. The associations between temperature and clinical outcome did not hold true in multiple logistic regression analyses. CONCLUSIONS: Spontaneously low temperature in the early phase reflected a worse primary brain injury and indicated a worse outcome prognosis. Hyperthermia was common in the vasospasm phase and was more related to infections than primary injury severity but also with a more favorable energy metabolic pattern with better substrate supply, possibly related to hyperemia.