Relationship of the vascular territory affected by delayed cerebral ischemia and the location of the ruptured aneurysm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the area most at risk of delayed cerebral ischemia (DCI) in relation to the location of the ruptured aneurysm in patients with aneurysmal subarachnoid hemorrhage (aSAH) and, therefore, help to choose the site for focal multimodal neuromonitoring. METHODS: We retrospectively analyzed angiographic findings, CCT scans, and patient charts of patients who were admitted with aSAH to our neurosurgical intensive care unit between 2009 and 2017. DCI was defined as infarction on CCT 2-6 weeks after aSAH. RESULTS: DCI occurred in 17.9% out of 357 included patients. A DCI occurring in the vascular territory of the artery carrying the ruptured aneurysm was found in 81.0% of patients with anterior circulation aneurysms but only in 16.7% with posterior circulation aneurysms (Fisher's exact, p=0.003). The vascular territory most frequently showing a DCI was the ipsilateral MCA territory (86.7%) in ICA aneurysms, the contra- (71.4%) and the ipsilateral (64.3%) ACA territory in ACA aneurysms, the right (93.8%) and the left (81.3%) ACA territory in AcomA aneurysms, and the ipsilateral MCA territory in MCA aneurysms (69.2%) as well as in VA/PICA/SCA aneurysms (100.0%). DCI after the rupture of a BA aneurysm occurred with 33.3% in 6 out of 8 vascular territories, respectively. DCI of multiple vascular territories occurred in 100.0% of BA aneurysms, 87.5% of AcomA aneurysms, 71.4% of ACA aneurysms, 40.0% of ICA aneurysms, 38.5% of MCA aneurysms, and 33.3% of VA/PICA/SCA aneurysms. DISCUSSION: Few studies exist that could determine the area most at risk of a DCI after an aSAH. Our data could identify the territory most at risk for DCI with a probability of > 60% except for BA aneurysms, which showed DCI in various areas and patients suffering from multiple DCIs. Either the ipsilateral ACA or MCA were affected by the DCI in about 80% of ACA and more than 90% of AcomA, ICA, MCA, and VA/PICA/SCA aneurysms. Therefore, local intraparenchymal neuromonitoring in the ACA/MCA watershed area might detect the vast majority of DCIs for all aneurysm locations, except for BA aneurysms. In ACA and AcomA aneurysms, bilateral DCI of the ACA territory was common, and bilateral probe positioning might be considered for monitoring high-risk patients. Non-focal monitoring methods might be preferably used after BA aneurysm rupture.

Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage - Serum D-dimer and C-reactive Protein as Early Markers.

BACKGROUND: Identifying patients at risk for delayed cerebral ischemia after an aneurysmal subarachnoid hemorrhage remains challenging and both delayed treatment and over-treatment are reasonable concerns. OBJECTIVE: To evaluate the role of the serum markers C-reactive protein, white blood count, and d-dimer as prognostic factors for the occurrence of delayed cerebral ischemia. METHODS: All patients admitted within 24 hours after an aneurysmal subarachnoid hemorrhage were included over a 6-year period. The World Federation of Neurosurgery and Fisher grading scales as well as the extended Glasgow Outcome Scale were documented at discharge and after a 3-to-6-month follow-up period. C-reactive protein, d-dimer, white blood count, and procalcitonin were assessed on admission, day 1, day 4, day 9, day 14, and at discharge. Radiologically confirmed delayed cerebral ischemia before discharge was the primary endpoint. Severe angiographic vasospasm and outcome were used as secondary endpoints. RESULTS: Delayed cerebral ischemia occurred in 19.6% of the 138 patients included. Delayed cerebral ischemia correlated with severe vasospasm and with a worse outcome. Serum C-reactive protein levels were higher in patients with severe vasospasm during the period of vasospasm. D-dimer levels on admission correlated with Fisher grades. Delayed cerebral ischemia occurred more frequently in patients with Fisher grade IV hemorrhage, if d-dimer levels were higher on admission. The cut-off was .445 µg/ml. CONCLUSION: Our observations support a multifactorial genesis for delayed cerebral ischemia, including vasospasm and microthrombotic and inflammatory processes. Serum d-dimer levels greater than .445 µg/ml might be a predictor for the occurrence of delayed cerebral ischemia in patients with a Fisher grade IV aneurysmal subarachnoid hemorrhage.

Effect of Intra-Arterial and Intravenous Nimodipine Therapy of Cerebral Vasospasm After Subarachnoid Hemorrhage on Cerebrovascular Reactivity and Oxygenation.

BACKGROUND: For the treatment and prevention of delayed cerebral ischemia after subarachnoid hemorrhage, the vasodilating agent nimodipine (NDP) is widely employed. This study investigates the effect of NDP on cerebrovascular autoregulation, assessed by pressure reactivity index (PRx), and brain tissue oxygenation (pbrO2) when given continuously intravenously as an intra-arterial bolus or during continuous intra-arterial therapy. METHODS: Computerized continuous neuromonitoring data (intracranial pressure, mean arterial pressure, cerebral perfusion pressure [CPP], pbrO2, PRx) of 105 patients with aneurysmal SAH were retrospectively evaluated. The effect of NDP on all parameters was compared when applied intra-arterially for the treatment of severe macrovasospasm leading to perfusion deficits as either bolus treatment (n = 111 in 37 patients) or continuous infusion (n = 20 patients) to patients without or with only mild macrovasospasm who received either intravenous NDP or no NDP at all. RESULTS: Compared with patients without treatment, the intravenous application of NDP was associated with a significantly higher PRx. Autoregulation was strongly and long lastingly affected (high PRx) in continuous intra-arterial NDP infusion, accompanied by a sustained improvement of pbrO2. Intra-arterial bolus NDP application resulted as well in a significant increase of pbrO2 and PRx; the induced effect, however, was transient and subsided within 6 hours. Intracranial pressure, mean arterial pressure, and CPP were not affected during the monitoring period. CONCLUSION: The pharmacologically induced alteration of the cerebrovascular autoregulation by NDP correlates with changes of pbrO2 and indicates a beneficial effect on cerebral blood flow if CPP is maintained. This effect is limited to a few hours after bolus treatment and milder for intravenous compared with intra-arterial application.

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. METHODS: Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n = 4) or with primary severe vasospasm (n = 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. RESULTS: The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n = 5) or disappeared (n = 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. CONCLUSIONS: In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.