The impact of transcranial direct current stimulation on cerebral vasospasm in a rat model of subarachnoid hemorrhage.

Transcranial direct current stimulation (tDCS) has been shown to induce changes in cortical excitability and perfusion in a rat ischemic stroke model. Since perfusion disturbances are a common phenomenon, not only in ischemic but also in hemorrhagic stroke, tDCS might have a possible beneficial effect on cerebral perfusion in hemorrhagic stroke as well. We applied tDCS in a rat model of subarachnoid hemorrhage (SAH) and evaluated its impact on vasospasm. SAH was induced using the double-hemorrhage rat model. TDCS was applied on day 3 and 4. For vasospasm assessment magnetic resonance angiography was performed on day 1, day 2 and day 5. A total of 147 rats were operated, whereat 72 rats died before day 5 and 75 rats survived the whole experiment and could be analyzed. The cathodal group consisted of 26 rats, the anodal group included 24 rats. Thirteen rats served as controls without tDCS, and twelve rats underwent a sham operation. The cathodal group revealed the lowest incidence of new vasospasm on day 5 (p = 0.01), and the lowest mean number of vasospastic vessels per rat (p = 0.02). TDCS influences the vasospasm incidence in an SAH-model in rats, where cathodal-tDCS was associated with a lower vasospasm incidence and severity.

Intrahematomal catheter placement with connection to the ventricular system allows more effective thrombolysis of combined intracerebral and intraventricular hematomas.

Intracerebral hematomas (ICH) with intraventricular hemorrhage (IVH) are associated with high morbidity. Catheter-based thrombolysis with recombinant tissue plasminogen activator (rtPA) allows a faster hematoma resolution compared to conservative treatment. However, simultaneous thrombolysis of ICH and IVH is not achievable because the ependyma hinders ICH-lysis if rtPA is given into the ventricles and inversely. We evaluated if the thrombolysis efficacy is enhanced by placing an intrahematomal catheter reaching the ventricle. Patients with ICH plus IVH treated with catheter-based thrombolysis were retrospectively analyzed. Group 1 included patients with an intrahematomal catheter reaching the ventricles and group 2 patients with a catheter placed exclusively in the ICH. The relative hematoma volume reduction (RVR) of ICH and IVH within 3 days was calculated. Furthermore, the patients' outcome, the hydrocephalus incidence, and the infection rate were evaluated. A total of 74 patients were analyzed, of whom 49% had a catheter reaching the ventricle. The mean ICH-RVR (68% vs. 58%, p = 0.0001) and IVH-RVR were significantly higher in group 1 compared to group 2. In group 1, infections occurred more often compared to group 2 (31% vs. 6%, p = 0.005). There was no difference in outcome and in hydrocephalus incidence between both groups. The catheter reaching the ventricles allows simultaneous and more effective thrombolysis of ICH and IVH. We assume that the fibrinolytic property of cerebrospinal fluid itself and a washout effect contribute to these findings. In patients with ICH plus IVH, catheter positioning through the hematoma into the ventricle, and subsequent fibrinolytic therapy should be considered.

Intracerebral Hemorrhage-Score Allows a Reliable Prediction of Mortality in Patients with Spontaneous Intracerebral Hemorrhage Managed by Fibrinolytic Therapy.

OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Prognosis estimation would be helpful for the treatment decision making in ICH patients. The ICH-score was published in 2001 to estimate the 30-day mortality in conservatively treated patients with ICH. We evaluated the reproducibility of the ICH-score in ICH patients undergoing fibrinolytic therapy. METHODS: We performed a retrospective analysis of patients with supratentorial ICH managed by fibrinolytic therapy and evaluated the 30-day mortality. The ICH-score was then applied to match the mortality in our patients with the mortality predicted by the ICH-score. The ICH-score is based on parameters available at admission: age, hematoma volume, intraventricular expansion, and clinical status according to the Glasgow Coma Scale. RESULTS: A total of 233 patients were analyzed. The 30-day mortality rate was 30% (70/233). An age of ≥80 years was associated with a significantly higher mortality rate (OR 2.26, chi-square test p = 0.01). A hematoma volume of ≥30 mL led significantly more often to 30-day mortality (OR 3.72, chi-square test p = 0.01). The mortality was significantly higher in the patients with intraventricular hemorrhage (2.97, chi-square test p = 0.003). The ICH-score showed a significant correlation with mortality (chi-square test, p < 0.0001). The following mortality rates were estimated using the ICH-score in our cohort: 1 = 0% (0/13), 2 = 0% (0/51), 3 = 1.3% (1/82), 4 = 43% (13/31), 5 = 100% (56/56). CONCLUSION: The ICH-score not only allows a reliable estimation of the 30-day mortality in patients with ICH treated conservatively but also treated by clot lysis. Compared to conservative treatment, the fibrinolytic therapy reduced the 30-day mortality in the patients with ICH-scores 1-4. Patients with ICH-score 5 do not have a benefit of fibrinolytic therapy and should no longer be considered to be candidates for fibrinolytic therapy.

Assessment of tissue permeability by early CT perfusion as a surrogate parameter for early brain injury after subarachnoid hemorrhage.

OBJECTIVE: The severity of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) correlates with delayed cerebral ischemia (DCI) and outcome. A disruption of the blood-brain barrier is part of EBI pathophysiology. The aim of this study was to assess tissue permeability (PMB) by CT perfusion (CTP) in the acute phase after aSAH and its impact on DCI and outcome. METHODS: CTP was performed on day 3 after aSAH. Qualitative and quantitative analyses of all CTP parameters, including PMB, were performed. The areas with increased PMB were documented. The value of an early PMB increase as a predictor of DCI and outcome according to the modified Rankin Scale (mRS) grade 3 to 24 months after aSAH was assessed. Possible associations of increased PMB with the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) and with early perfusion deficits, as radiographic EBI markers, were evaluated. RESULTS: A total of 69 patients were enrolled in the study. An increased PMB on early CTP was detected in 10.1% (7/69) of all patients. A favorable outcome (mRS grade ≤ 2) occurred in 40.6% (28/69) of all patients. DCI was detected in 25% (17/69) of all patients. An increased PMB was a predictor of DCI (logistic regression, p = 0.03) but not of outcome (logistic regression, p = 0.40). The detection of increased PMB predicted DCI with a sensitivity of 25%, a specificity of 94%, a positive predictive value of 57%, and a negative predictive value of 79% (chi-square test p = 0.03). Early perfusion deficits were seen in 68.1% (47/69) of the patients, a finding that correlated with DCI (p = 0.005) but not with the outcome. No correlation was found between the SEBES and increased PMB. CONCLUSIONS: Changes in PMB can be detected by early CTP after aSAH, which correlates with DCI. Future studies are needed to evaluate the time course of PMB changes and their interaction with therapeutic measures.

MR-angiography allows defining severity grades of cerebral vasospasm in an experimental double blood injection subarachnoid hemorrhage model in rats.

OBJECTIVE: Magnetic resonance (MR) imaging has been used for the detection of cerebral vasospasm (VSP) related infarction in experimental subarachnoid hemorrhage (eSAH) in rats. Conventional angiography is generally used to visualize VSP, which is an invasive technique with a possible increase in morbidity and mortality. In this study we evaluated the validity of MR-angiography (MRA) in detecting VSP and its feasibility to define VSP severity grades after eSAH in rats. METHODS: SAH was induced using the double-hemorrhage model in 12 rats. In two rats, saline solution was injected instead of blood (sham group). MR was performed on day 1, 2 and on day 5. T1-, T2-, T2*-weighted and time-of-flight MR sequences were applied, which were analyzed by two blinded neuroradiologists. Vessel narrowing of 25-50% was defined as mild, 50-75% as moderate and >75% as severe VSP. RESULTS: We performed a total of 34 MRAs in 14 rats. In 14 rats, MRA was performed on day 2 and day 5. In six rats MRA was additionally performed on day1 before the blood injection. A good visualization of cerebral vessels was possible in all cases. No VSP was seen in the sham group neither on day 2 nor on day 5. We found vasospasm on day 2 in 7 of the 14 rats (50%) whereas all 7 rats had mild and one rat had additionally moderate and severe vasospasm in one vessel, respectively. On day 5 we found vasospasm in 8 of the 14 rats (60%) whereas 4 rats had severe vasospasm, 1 rat had moderate vasospasm and 3 rats demonstrated mild vasospasm. In 4 of the 14 rats (30%) an ischemic lesion was detected on day 5. Three of these rats had severe vasospasm and one rat had mild vasospasm. Severe vasospasm on day 5 was statistically significant correlated with the occurrence of ischemic lesions (Fisher's Exact test, OR 19.5, p = 0.03). CONCLUSIONS: MRA is a noninvasive diagnostic tool, which allows a good visualization of the cerebral vasculature and provides reproducible results concerning the detection of VSP and the differentiation into three severity grades in rats. Future studies are needed to directly compare MRA with conventional angiography.