Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

Modifiable Cardiovascular Risk Factors in Patients With Sporadic Cerebral Cavernous Malformations: Obesity Matters.

BACKGROUND AND PURPOSE: This study aims to assess the influence of modifiable cardiovascular risk factors on hemorrhage risk of sporadic cerebral cavernous malformations (CCMs). METHODS: From 1219 consecutive CCM patients (2003-2018), adult subjects with sporadic CCM and complete magnetic resonance imaging were included. We evaluated presence of intracerebral hemorrhage (ICH) as mode of presentation, occurrence of ICH during follow-up and risk factors arterial hypertension, diabetes, hyperlipidemia, nicotine abuse, and obesity (body mass index >30 kg/m2). Impact of risk factors on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. We performed Kaplan-Meier and Cox regression to analyze cumulative 5-year risk for (re)bleeding. RESULTS: We included 682 patients with CCM. The univariate logistic regression showed a significant relationship (odds ratio=1.938 [95% CI, 1.120-3.353], P=0.018) between obesity and ICH as mode of presentation. Multivariate adjusted logistic regression confirmed significant correlation with odds ratio=1.902 (95% CI, 1.024-3.532, P=0.042). Cox regression did not identify predictors for occurrence of (re)hemorrhage (P>0.05; hazard ratios: arterial hypertension 1.112 [95% CI, 0.622-1.990], diabetes 0.850 [95% CI, 0.208-3.482], hyperlipidemia 0.719 [95% CI, 0.261-1.981], nicotine abuse 1.123 [95% CI, 0.591-2.134], and obesity 0.928 [95% CI, 0.416-2.070]). CONCLUSIONS: This study provides evidence that obesity may be a risk factor for CCM hemorrhage. It was significantly associated with ICH as mode of presentation. Other risk factors (arterial hypertension, diabetes, hyperlipidemia, and current nicotine abuse) showed no such effect. None of the factors showed to be independent predictors for cumulative 5-year risk of (re)bleeding.

Brain Tissue Oxygen Response as Indicator for Cerebral Lactate Levels in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Early detection of cerebral ischemia and metabolic crisis is crucial in critically ill subarachnoid hemorrhage (SAH) patients. Variable increases in brain tissue oxygen tension (PbtO2) are observed when the fraction of inspired oxygen (FiO2) is increased to 1.0. The aim of this prospective study was to evaluate whether a 3-minute hyperoxic challenge can identify patients at risk for cerebral ischemia detected by cerebral microdialysis. METHODS: Twenty consecutive severe SAH patients undergoing continuous cerebral PbtO2 and microdialysis monitoring were included. FiO2 was increased to 1.0 for 3 minutes (the FiO2 challenge) twice a day and PbtO2 responses during the FiO2 challenges were related to cerebral microdialysis-measures, ie, lactate, the lactate-pyruvate ratio, and glycerol. Multivariable linear and logistic regression models were created for each outcome parameter. RESULTS: After predefined exclusions, 274 of 400 FiO2 challenges were included in the analysis. Lower absolute increases in PbtO2 (∆PbtO2) during FiO2 challenges were significantly associated with higher cerebral lactate concentration (P<0.001), and patients were at higher risk for ischemic lactate levels >4 mmol/L (odds ratio 0.947; P=0.04). Median (interquartile range) ∆PbtO2 was 7.1 (4.6 to 12.17) mm Hg when cerebral lactate was >4 mmol/L and 10.2 (15.76 to 14.24) mm Hg at normal lactate values (≤4 mmol/L). Median ∆PbtO2 was significantly lower during hypoxic than during hyperglycolytic lactate elevations (4.6 vs. 10.6 mm Hg, respectively; P<0.001). Lactate-pyruvate ratio and glycerol levels were mainly determined by baseline characteristics. CONCLUSIONS: A 3-minute FiO2 challenge is an easy to perform and feasible bedside diagnostic tool in SAH patients. The absolute increase in PbtO2 during the FiO2 challenge might be a useful surrogate marker to estimate cerebral lactate concentrations and might be used to identify patients at risk for impending ischemia.

Role of brain natriuretic peptide in the prediction of long-term surgical outcome of chronic subdural hematoma.

OBJECTIVE: To investigate the role of brain natriuretic peptide (BNP) in predicting long-term functional outcome and develop a new predictive score of poor functional outcome after surgery for chronic subdural hematoma (cSDH). METHODS: Patients with cSDH that were surgically treated in our department between November 2016 and December 2019 were included in the study. Pre- and postoperative plasma BNP and clinical condition were prospectively recorded. At follow-up (5-6 months), a simplified modified Rankin Scale (mRS) questionnaire was conducted through a standardized telephone interview. A poor outcome was defined by a mRS > 3. Based on predictors of the long-term functional outcome, a score was calculated. Its accuracy was tested using the area under the curve (AUC) of the receiver operating characteristic analysis. RESULTS: In total, 119 patients were analyzed (median age: 76 years, range: 44-94 years). Preoperative plasma BNP (BNP-1) was elevated in 77 patients (64.7%). For the follow-up phone interview, 101 patients (84.8%) were available. In the multivariate analysis, poor outcome at follow-up could be predicted using BNP-1 (p = 0.034), age (p = 0.036), motor deficit (p = 0.013) and Glasgow coma scale score on admission (p = 0.008). The "Functional Long-term Outcome Predictive score" (FLOP-score) was therefore computed, and revealed an excellent discriminative capacity compared to other scores, with an AUC of 0.86 (0.77-0.95). CONCLUSIONS: Preoperative plasma BNP is an independent predictor of functional outcome at follow-up. Using the FLOP-score, the risk of experiencing a poor outcome could accurately be predicted.

Detrimental effects of intrahospital transport on cerebral metabolism in patients suffering severe aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Intrahospital transport for CT scans is routinely performed for neurosurgical patients. Particularly in the sedated and mechanically ventilated patient, intracranial hypertension and blood pressure fluctuations that might impair cerebral perfusion are frequently observed during these interventions. This study quantifies the impact of intrahospital patient transport on multimodality monitoring measurements, with a particular focus on cerebral metabolism. METHODS: Forty intrahospital transports in 20 consecutive patients suffering severe aneurysmal subarachnoid hemorrhage (SAH) under continuous intracranial pressure (ICP), brain tissue oxygen tension (pbtO2), and cerebral microdialysis monitoring were prospectively included. Changes in multimodality neuromonitoring data during intrahospital transport to the CT scanner and the subsequent 10 hours were evaluated using linear mixed models. Furthermore, the impact of risk factors at transportation, such as cerebral vasospasm, cerebral hypoxia (pbtO2 < 15 mm Hg), metabolic crisis (lactate-pyruvate ratio [LPR] > 40), and transport duration on cerebral metabolism, was analyzed. RESULTS: During the transport, the mean ICP significantly increased from 7.1 ± 3.9 mm Hg to 13.5 ± 6.0 mm Hg (p < 0.001). The ICP exceeded 20 mm Hg in 92.5% of patients; pbtO2 showed a parallel rise from 23.1 ± 13.3 mm Hg to 28.5 ± 23.6 mm Hg (p = 0.02) due to an increase in the fraction of inspired oxygen during the transport. Both ICP and pbtO2 returned to baseline values thereafter. Cerebral glycerol significantly increased from 71.0 ± 54.9 µmol/L to 75.3 ± 56.0 µmol/L during the transport (p = 0.01) and remained elevated for the following 9 hours. In contrast, cerebral pyruvate and lactate levels were stable during the transport but showed a significant secondary increase 1-8 hours and 2-9 hours, respectively, thereafter (p < 0.05). However, the LPR remained stable over the entire observation period. Patients with extended transport duration (more than 25 minutes) were found to have significantly higher levels of cerebral pyruvate and lactate as well as lower glutamate concentrations in the posttransport period. CONCLUSIONS: Intrahospital transport and horizontal positioning during CT scans induce immediate intracranial hypertension and an increase in cerebral glycerol, suggesting neuronal injury. Afterward, sustained impairment of neuronal metabolism for several hours could be observed, which might increase the risk of secondary ischemic events. Therefore, intrahospital transport for neuroradiological imaging should be strongly reconsidered and only indicated if the expected benefit of imaging results outweighs the risks of transportation.

Hemorrhage from cerebral cavernous malformations: The role of associated developmental venous anomalies.

OBJECTIVE: To determine the role of associated developmental venous anomalies (DVAs) in intracranial hemorrhage (ICH) caused by cerebral cavernous malformations (CCMs). METHODS: We analyzed patient registry data of 1,219 patients with cavernous malformations treated in our institution between 2003 and 2018. Patients with spinal and familial CCM and patients without complete MRI data were excluded. The impact of various variables on ICH as a mode of presentation was assessed with multivariate binary logistic regression analysis. Kaplan Meier/Cox regression analysis was performed to analyze cumulative 5-year-risk for (re)hemorrhage and to identify baseline predictors of this outcome. RESULTS: Seven hundred thirty-one patients with CCM were included. Multivariate logistic regression confirmed a statistically significant negative correlation with DVA (odds ratio [OR] 0.635 [95% confidence interval (CI) 0.459-0.878]) and positive correlation with brainstem localization (OR 6.277 [95% CI 4.287-9.191]) with ICH as the mode of presentation. Among 731 patients, 76 experienced (re)hemorrhage during 2,338 person-years of follow-up. Overall cumulative 5-year risk was 24.1% (95% CI 21.1%-27.5%). Cox regression analysis revealed initial presentation with ICH (hazard ratio [HR] 8.0 [95% CI 3.549-18.122]) and brainstem localization (HR 2.9 [95% CI 1.756-4.765]) as independent baseline predictors of (re)hemorrhage. Presence of DVA added no independent prognostic information (HR 1.1 [95% CI 0.717-1.885]). CONCLUSION: Patients with CCM with associated DVA are at lower risk to present with ICH. During untreated 5-year follow-up, they showed equal (re)hemorrhage risk compared to patients with CCM without DVA.

Intra-Arterial Papaverine-Hydrochloride and Transluminal Balloon Angioplasty for Neurointerventional Management of Delayed-Onset Post-Aneurysmal Subarachnoid Hemorrhage Vasospasm.

OBJECTIVE: After subarachnoid hemorrhage, delayed onset vasospasm can result in devastating ischemic stroke. The phenomenon of delayed cerebral ischemia (DCI) is not yet fully understood, and the correlation of angiographic vasospasm and cerebral infarction is still unclear. Therefore, we investigated the effect of endovascular treatment on the angiographic response and occurrence of DCI. METHODS: Eighty patients with subarachnoid hemorrhage and serious cerebral vasospasm underwent endovascular treatment using intra-arterial papaverine-hydrochloride (IAP) or transluminal balloon angioplasty (TBA). The angiographic response and infarction rate were classified using the pre- and postinterventional angiographic images and computed tomography scans. RESULTS: In 90% of patients, vasospasm could be improved. In most cases (78.8%), IAP was used. Retreatment after IAP was necessary in 32.9% of patients but never after TBA. A total of 233 vascular territories were treated in 128 procedures. Angiographic improvement was observed in 66.5% of territories, which was significantly associated with early intervention (P = 0.02), the use of TBA (P = 0.01), and the dose of papaverine-hydrochloride (P = 0.01). DCI occurred in 47.5% of the patients. Territorial infarction was associated with a poor Hunt and Hess grade (P = 0.03), day of aneurysm treatment (P = 0.01), severe vasospasm before (P = 0.02) and after (P = 0.03) treatment, and number of interventions (P = 0.01). However, the infarction rate was independent of the angiographic response. CONCLUSION: The discrepancy of excellent angiographic results and the high incidence of DCI might stem from an inaccurate or a delayed diagnosis of impending ischemia. In view of the limited time window, optimized peri-interventional management and continuous cerebral multimodality neuromonitoring might be crucial for the ideal timing of endovascular procedures to prevent cerebral infarctions.