Nils Hecht

Delayed Cerebral Ischemia and Spreading Depolarization in Absence of Angiographic Vasospasm after Subarachnoid Hemorrhage

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

Propagation of cortical spreading depolarization in the human cortex after malignant stroke

Objective: To investigate hemodynamic response pattern and spatiotemporal propagation of cortical spreading depolarization in the peri-infarct region of malignant hemispheric stroke. Methods: In this prospective observational case study we used intraoperative laser speckle technology to measure cerebral blood flow in patients with malignant hemispheric stroke. Additionally, postoperative occurrence of cortical spreading depolarization was monitored using a subdural recording strip for electrocorticography and infarct progression was assessed by serial MRI. Results: In 7 of 20 patients, 19 blood flow changes typical of cortical spreading depolarizations occurred during a 20-minute period. Thirteen events were characterized by increase, 2 by biphasic response, and 4 by decrease of blood flow. Propagation velocity ranged from 1.7 to 9.2 mm/min and propagation area from 0.1 to 4.8 cm2. Intrinsic optical signal alterations preceded and low-frequency vascular fluctuations were suppressed during the hemodynamic responses. A mean number of 56 ± 82 cortical spreading depolarizations per patient was recorded and a mean infarct progression of 30 ± 13 cm3 was detected in 5 of 7 patients. Conclusions: We visualize the spatiotemporal propagation of spreading depolarizations in the human cerebral cortex intraoperatively. In patients with focal ischemia, multiple cortical spreading depolarizations with either hyperemic or hypoemic flow responses occurred. Our data suggest that, in patients with focal ischemia, cortical spreading depolarizations are associated with both unfavorable and protective hemodynamic responses.

Intraoperative monitoring of cerebral blood flow by laser speckle contrast analysis

OBJECT Currently, reliable low-cost and noninvasive techniques to assess cerebral perfusion in the operating room are not available. The authors report on their first clinical experience with laser speckle contrast analysis (LASCA) as a complementary imaging tool for the noninvasive and dynamic assessment of cerebral blood flow (CBF) during neurovascular surgery. The purpose of this preliminary study was to address the general feasibility of LASCA in terms of handling and image quality and to provide an example of its clinical implications. METHODS Laser speckle contrast analysis was performed in patients undergoing cerebral revascularization procedures for the treatment of hemodynamic compromise and complex aneurysms. The portable LASCA device was centered over the surgical field, and continuous 5-minute recordings of relative CBF were obtained. In the case of flow augmentation for hemodynamic compromise, CBF monitoring was performed before and after completion of the anastomosis. In the case of flow replacement for parent artery sacrifice, CBF monitoring was performed during consecutive 30-second test occlusions of the radial artery graft after proximal internal carotid artery sacrifice and the subsequent initiation of blood flow through the bypass. RESULTS In all cases, the authors achieved good visualization of relative CBF in addition to flow imaging in both the bypass graft and the cortical vasculature. During a sudden CBF decrease after test occlusion of the radial artery graft and subsequent flow initiation through the bypass, LASCA allowed immediate visualization and measurement of relative CBF in excellent spatiotemporal resolution. CONCLUSIONS In this study LASCA offered noninvasive and rapid intraoperative assessment of relative CBF, which can be used for optimizing neurovascular procedures.

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Cerebral Hemodynamic Reserve and Vascular Remodeling in C57/BL6 Mice Are Influenced by Age

Background and Purpose— Age is the most important risk factor for ischemic stroke. Recent experiments evidenced an age-associated rarefaction of the native collateral vasculature. The purpose of this study was to assess in what way age and arteriogenesis influence cortical perfusion and recovery of hemodynamic impairment in aged and young C57/BL6 mice. Methods— After model establishment of chronic cerebral hypoperfusion in the C57/BL6 strain, sustained hemodynamic impairment was induced by permanent unilateral internal carotid artery occlusion in animals aged 4 to 6 weeks, 12 weeks, and 18 months. Functional and morphological outcome was assessed by laser speckle imaging before and during acetazolamide challenge on Days 0, 3, 7, and 14 and latex/carbon black angiography and immunohistochemistry on Day 21. Results— Although internal carotid artery occlusion did not result in a reduction of baseline perfusion, it led to significant hemodynamic impairment in all age groups. Furthermore, baseline perfusion in sham and cerebrovascular reactivity after internal carotid artery occlusion were significantly lower in animals aged 18 months (468±57 Flux; 20.8%±17%) compared with mice aged 4 to 6 weeks (568±120 Flux; 30.3%±17%) and 12 weeks (591±72 Flux; 34.2%±12%) from the beginning until Day 7 of the monitoring period. Functional outcome was in line with a 27% reduction of native leptomeningeal anastomoses in aged mice and only limited collateral outgrowth compared with young animals. Strikingly, all age groups reached spontaneous functional compensation by Day 14. Conclusions— Next to limited collateral remodeling, our results suggest that a hampered cerebrovascular response with age could intensify the risk for hemodynamic stroke in the elderly.

Laser speckle imaging allows real-time intraoperative blood flow assessment during neurosurgical procedures.

Currently, there is no adequate technique for intraoperative monitoring of cerebral blood flow (CBF). To evaluate laser speckle imaging (LSI) for assessment of relative CBF, LSI was performed in 30 patients who underwent direct surgical revascularization for treatment of arteriosclerotic cerebrovascular disease (ACVD), Moyamoya disease (MMD), or giant aneurysms, and in 8 control patients who underwent intracranial surgery for reasons other than hemodynamic compromise. The applicability and sensitivity of LSI was investigated through baseline perfusion and CO2 reactivity testing. The dynamics of LSI were assessed during bypass test occlusion and flow initiation procedures. Laser speckle imaging permitted robust (pseudo-) quantitative assessment of relative microcirculatory flow and standard bypass grafting resulted in significantly higher postoperative baseline perfusion values in ACVD and MMD. The applicability and sensitivity of LSI was shown by a significantly reduced CO2 reactivity in ACVD (9.6 ± 9%) and MMD (8.5 ± 8%) compared with control (31.2 ± 5%; P < 0.0001). In high- and intermediate-flow bypass patients, LSI was characterized by a dynamic real-time response to acute perfusion changes and ultimately confirmed a sufficient flow substitution through the bypass graft. Thus, LSI can be used for sensitive and continuous, non-invasive real-time visualization and measurement of relative cortical CBF in excellent spatial-temporal resolution.

Oxygen availability and spreading depolarizations provide complementary prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage patients

Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.

Routine intensive care unit-level care after elective craniotomy: time to rethink.

t is reasonable to question the assumptions upon which clinical decisions are made. Neurosurgeons, for example, I fear not being able to recognize a postoperative complication that could require immediate surgical and/or medical attention, such as a postoperative hematoma, hydrocephalus, or seizure. Consequently, patients undergoing elective craniotomy have traditionally been monitored in an intensive care unit (ICU) setting overnight, which was thought to reduce the incidence and potential seriousness of early postoperative complications. Although the gut instinct of an experienced surgeon should never be underestimated, it should also not present the sole indicator for clinical decision making. The benefit of routine ICU admission after elective craniotomies in particular remains unproven, and evidence reaching as far back as 30 years already suggested that specific ICU interventions after elective craniotomies are not required in the majority of patients before discharge to the regular ward (5, 7).

Endothelial progenitor cells augment collateralization and hemodynamic rescue in a model of chronic cerebral ischemia.

Surgical flow augmentation for treatment of cerebral hemodynamic impairment remains controversial. Here, we investigated the benefit of endothelial progenitor cell (EPC) treatment in a rat model of chronic cerebral hypoperfusion. At repeated time points after 3-vessel occlusion (3-VO), animals were treated with 1 × 10 6 Dil-labeled (a) ex vivo-expanded embryonic-EPC (e-EPC), (b) cyclic AMP-differentiated embryonic-endothelial progenitor-derived cells (e-EPDC as biologic control) or, (c) saline. The cerebrovascular reserve capacity (CVRC) was assessed immediately before and on days 7 and 21 after 3-VO. Structural effects were assessed by latex perfusion, immunohistochemistry, and intravital fluorescence video microscopy on day 21. Three-vessel occlusion resulted in a significant impairment of the CVRC with better functional recovery after treatment with e-EPC (16.4 ± 8%) compared with e-EPDC (3.7 ± 8%) or saline (6.4 ± 9%) by day 21 (P<0.05), which was paralleled by a significant increase in the vessel diameters of the anterior Circle of Willis, a significantly higher number of leptomeningeal anastomoses and higher parenchymal capillary density in e-EPC-treated animals. Interestingly, despite in vivo interaction of e-EPC with the cerebral endothelium, e-EPC incorporation into the cerebral vasculature was not observed. Our results suggest that EPC may serve as a novel therapeutic agent in clinical trials for nonsurgical treatment of chronic cerebral hemodynamic impairment.

Excitotoxicity and Metabolic Changes in Association With Infarct Progression

Background and Purpose— We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression. Methods— In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period. Results— Initial stroke volume ranged from 122 to 479 cm3 with a median of 295 cm3. Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm3; range, 19–93 cm3). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate–pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12–36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups. Conclusions— Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.