High posterior cerebral artery flow predicts ischemia recurrence in patients with internal carotid artery occlusion

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p = <0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia

Screening tools for early neuropsychological impairment after aneurysmal subarachnoid hemorrhage

Background Although most aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from neuropsychological disabilities, outcome estimation is commonly based only on functional disability scales such as the modified Rankin Scale (mRS). Moreover, early neuropsychological screening tools are not used routinely. Objective To study whether two simple neuropsychological screening tools identify neuropsychological deficits (NPDs), among aSAH patients categorized with favorable outcome (mRS 0-2) at discharge. Methods We reviewed 170 consecutive aSAH patients that were registered in a prospective institutional database. We included all patients graded by the mRS at discharge, and who had additionally been evaluated by a neuropsychologist and/or occupational therapist using the Montreal Cognitive Assessment (MoCA) and/or Rapid Evaluation of Cognitive Function (ERFC). The proportion of patients with scores indicative of NPDs in each test were reported, and spearman correlation tests calculated the coefficients between the both neuropsychological test results and the mRS. Results Of the 42 patients (24.7%) that were evaluated by at least one neuropsychological test, 34 (81.0%) were rated mRS 0-2 at discharge. Among these 34 patients, NPDs were identified in 14 (53.9%) according to the MoCA and 8 (66.7%) according to the ERFC. The mRS score was not correlated with the performance in the MoCA or ERFC. Conclusion The two screening tools implemented here frequently identified NPDs among aSAH patients that were categorized with favorable outcome according to the mRS. Our results suggest that MoCA or ERFC could be used to screen early NPDs in favorable outcome patients, who in turn might benefit from early neuropsychological rehabilitation.Peer reviewe

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system

High posterior cerebral artery flow predicts ischemia recurrence in patients with internal carotid artery occlusion

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p = &lt;0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia

The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity

Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects' individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects' individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33-0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation

Neurosurgery outcomes and complications in a monocentric 7-year patient registry

Introduction Capturing adverse events reliably is paramount for clinical practice and research alike. In the era of “big data”, prospective registries form the basis of clinical research and quality improvement. Research question To present results of long-term implementation of a prospective patient registry, and evaluate the validity of the Clavien-Dindo grade (CDG) to classify complications in neurosurgery. Materials and methods A prospective registry for cranial and spinal neurosurgical procedures was implemented in 2013. The CDG – a complication grading focused on need for unplanned therapeutic intervention – was used to grade complications. We assess construct validity of the CDG. Results Data acquisition integrated into our hospital workflow permitted to include all eligible patients into the registry. We have registered 8226 patients that were treated in 11994 surgeries and 32494 consultations up until December 2020. Similarly, we have captured 1245 complications on 6308 patient discharge forms (20%) since full operational status of the registry. The majority of complications (819/6308 ​= ​13%) were treated without invasive treatment (CDG 1 or CDG 2). At discharge, there was a clear correlation of CDG and the Karnofsky Performance Status (KPS, rho ​= ​-0.29, slope -7 KPS percentage points per increment of CDG) and the length of stay (rho ​= ​0.43, slope 3.2 days per increment of CDG)

BOLD Cerebrovascular Reactivity as a Novel Marker for Hemodynamic Impairment in Symptomatic Cerebrovascular Steno-Occlusive Disease

Blood oxygenation-level dependent measure of cerebrovascular reactivity (BOLD-CVR) is a novel imaging approach to identify patients with symptomatic cerebrovascular steno-occlusive disease (SOD) exhibiting hemodynamic impairment, and therefore are at high risk for recurrent ischemic stroke. The BOLD-CVR technique is based on a BOLD signal response to hypercapnia (i.e., a carbon dioxide – CO$_2$ – stimulus) to gauge cerebrovascular reserve capacity. By using the percent BOLD signal change per mmHg CO2, cerebrovascular reactivity (CVR) can be determined quantitatively on a voxel-by-voxel basis. BOLD-CVR, the indicator of how much cerebrovascular reserve capacity remains, can therefore be used as a surrogate for hemodynamic impairment, and thereby potentially inform about the risk for recurrent ischemic stroke. In this thesis, I have investigated the ability of BOLD-CVR to identify and quantitatively map cerebral hemodynamic impairment in symptomatic patients with cerebrovascular steno-occlusive disease. In Chapter 3, the ability of BOLD-CVR mapping to identify hemodynamically relevant symptomatic unilateral internal carotid artery (ICA) occlusion and high-grade ICA stenosis was demonstrated. In patients with symptomatic unilateral ICA occlusion the role of primary and secondary collateral activation in the presence of impaired CVR was further elucidated. Ipsilateral leptomeningeal collateral activation (measured with transcranial Doppler (TCD) ultrasound and defined as flow increase of > 30 % in the ipsilateral second (P2) segment of the posterior cerebral artery (PCA-P2) compared with the contralateral P2 segment) was identified as the sole collateral pathway to be associated with impaired BOLD-CVR. In the following project we have shown increased PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. Moreover, BOLD-CVR impairment was observed with cut-off value of 85 cm/s indicating hemodynamic failure stage 2. These novel hemodynamic imaging parameters have merit for both, the acute and chronic stage of ischemic stroke (Chapter 4). In Chapter 5, our effort was set to introduce specific BOLD-CVR cut-off points to classify vascular territories of the anterior circulation into different hemodynamic failure stages. BOLD-CVR showed an accuracy of >0.7 for all vascular territories for both the hemodynamic failure stage 1 and hemodynamic failure stage 2 cut-off points indicating that standardized BOLD-CVR harbors a strong diagnostic capability to provide specific BOLD-CVR cut-off points for hemodynamic failure staging. Finally, in Chapter 6, further evidence of hemodynamic component for crossed cerebellar diaschisis (CCD) phenomenon in symptomatic patients with cerebrovascular SOD was demonstrated. In summary, the results of my thesis show that the novel BOLD-CVR technique harbors important capacity to identify and quantitatively map hemodynamic impairment in symptomatic patients with cerebrovascular SOD. Furthermore, the technique has a strong potential to improve clinical decisions for a wide stroke population especially if an association to increased stroke risk will be shown in the future investigations

Molecular signature of brain arteriovenous malformation hemorrhage: a systematic review

BACKGROUND The mechanisms of brain arteriovenous malformation (bAVM) development, formation and progress are still poorly understood. By gaining more knowledge about the molecular signature of bAVM in relation to hemorrhage, we might be able to find biomarkers associated with this serious complication, which can function as a goal for further research and can be a potential target for gene therapy. AIMS To provide a comprehensive overview of the molecular signature of bAVM-related hemorrhage We conducted a systematic review, following PRISMA guidelines, of articles published in Embase, Medline, Cochrane central, Scopus, and Chinese databases (CNKI, Wanfang). SUMMARYOF REVIEW Our search identified 3,944 articles, of which 3,108 remained after removal of duplicates. After title, abstract and full text screening 31 articles were included for analysis. The results show an overview of molecular characteristics. Several genetic polymorphisms are identified which increase the risk of bAVM rupture by increasing the expression of certain inflammatory cytokines (IL-6, IL-17A, IL-1β and TNF-α), NOTCH pathways, MMP-9 and VEGFA. CONCLUSIONS Several molecular factors are associated with the risk of bAVM-related hemorrhage These factors are associated with increased inflammation on the cellular level and changes in the endothelium leading to instability of the vessel wall. Further investigation of these biomarkers regarding hemorrhage rates, together with their relationship with noninvasive diagnostic methods, should be a goal of future studies to improve the patient specific risk estimation and future treatment options

Outcome comparison between surgically treated brain arteriovenous malformation hemorrhage and spontaneous intracerebral hemorrhage

BACKGROUND Case fatality and poor outcome rates are different between brain arteriovenous malformation associated intracerebral hemorrhage (bAVM-ICH) and spontaneous intracerebral hemorrhage (SICH). These outcome rates, however, have never been compared in patients who need neurosurgical evacuation of the intracerebral hemorrhage (ICH). OBJECTIVE To compare the short- and long-term functional outcome between surgically treated patients with bAVM-ICH and SICH. METHODS We collected data from surgically treated ICH patients at the department of neurosurgery, University hospital Zurich, from January 2015 to July 2018. We performed logistic regression analysis to compare the functional outcome between groups, adjusting for demographics, admission characteristics and stroke risk factors. RESULTS A total of 26 bAVM-ICH and 115 SICH patients were included in the final analysis. Patients with bAVM-ICH were younger and less likely to have hypertension without significant differences in ICH volume, hematoma location, intraventricular hemorrhage and other stroke risk factors. A significantly better functional outcome rate was seen in bAVM-ICH patients at short- and long-term follow-up. These differences remained significant after adjusting for confounders. CONCLUSIONS Patients with a bAVM who need surgical evacuation of an ICH have a more favorable outcome than surgically treated patients with spontaneous ICH, even after correction for confounding factors, such as younger age and less premorbid hypertension