Emergency Free-Hand Bedside Catheter Evacuation of Large Intracerebral Hematomas Following Thrombolysis for Ischemic Stroke: A Case Series.

INTRODUCTION: Symptomatic intracerebral hemorrhage (sICH) following systemic thrombolysis for ischemic stroke is often devastating, and open surgical evacuation is considered dangerous due to the increased risk of perioperative bleeding, and stereotactic placement of a catheter is too time-consuming. We therefore evaluated the feasibility of a free-hand bedside catheter technique for emergency hematoma evacuation. METHODS: Patients who had a supratentorial sICH after thrombolysis, a hematoma volume > 30 ml, and an ensuing reduction in vigilance were consecutively treated with acute minimally invasive catheter hematoma evacuation. Catheter insertion and trajectory were planned via 3D-reconstructed computed tomography (CT) scan, and free-hand insertion of an external ventricular catheter into the core of the hematoma was performed bedside, followed by careful blood aspiration. Cranial CT was used to verify catheter position and residual hematoma volume. In cases, where the residual volume exceeded 15 ml, urokinase (5000 IE) was administered into the clot every 6 h until the volume decreased to < 15 ml. RESULTS: In all six patients, catheter aspiration immediately reduced hematoma volume by 77%, from 73 ± 20 ml to 17 ± 16 ml (p = 0.028). In four patients, the hematoma was almost completely removed (< 10 ml) by singular aspiration. In the remaining two patients with a residual hematoma size > 15 ml, consecutive urokinase application resulted in a further reduction to 1 ml and 15 ml, respectively, after 30 h. The median National Institues of Health Stroke Scale/Score after sICH was 19.5 points, rapidly decreasing to 11 after catheter aspiration (p = 0.027), and further improving to 4 at discharge. No procedure-related complications were observed. CONCLUSIONS: Emergency free-hand bedside catheter aspiration is a reasonable option for hematoma evacuation in large thrombolysis-associated sICH when performed by experienced neurosurgeons. Larger studies would help in determining the generalizability of our findings to other centers and assessing their impact on functional outcome.

Large Vessel Occlusion in Acute Stroke.

Background and Purpose- To date, no clinical score has become widely accepted as an eligible prehospital marker for large vessel occlusion (LVO) and the need of mechanical thrombectomy (MT) in ischemic stroke. On the basis of pathophysiological considerations, we propose that cortical symptoms such as aphasia and neglect are more sensitive indicators for LVO and MT than motor deficits. Methods- We, thus, retrospectively evaluated a consecutive cohort of 543 acute stroke patients including patients with ischemia in the posterior circulation, hemorrhagic stroke, transient ischemic attack, and stroke mimics to best represent the prehospital setting. Results- Cortical symptoms alone showed to be a reliable indicator for LVO (sensitivity: 0.91; specificity: 0.70) and MT (sensitivity: 0.90; specificity: 0.60) in acute stroke patients, whereas motor deficits showed a sensitivity of 0.85 for LVO (specificity: 0.53) and 0.87 for MT (specificity: 0.48). Conclusions- We propose that in the prehospital setting, the presence of cortical symptoms is a reliable indicator for LVO and its presence justifies transportation to an MT-capable center.

Natural course of perihemorrhagic edema after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is only limited knowledge on the time course of perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH). We aimed to investigate the chronological PHE course and its relation to in-hospital mortality in a large retrospective ICH cohort. METHODS: Patients with supratentorial ICH treated at our institution between 2006 and 2009, who had received at least 3 CT scans in the course of conservative treatment, were included in the present analysis. PHE at Days 1, 2, 3, 4 to 6, 7 to 11, 12 to 16, 17 to 21, and >22 was assessed using a threshold based semiautomatic volumetric algorithm. A chart review was performed to achieve data on duration of stay, ventilation, treatment with external ventricular drains, and in-hospital mortality. RESULTS: Two hundred nineteen patients aged 69.9±10.5 years with deep (n=103) or lobar (n=116) ICH were included in the study. Mean ICH volume was 35.7±31.5 mL. Mean absolute PHE volume significantly increased from initially 32.6±29.9 mL to 63.7±46.7 mL at Days 7 to 11. No significant changes were observed at later time points. ICH volume was strongly correlated with absolute PHE volume (ρ=0.8, P<0.001) and inversely correlated with relative PHE (ρ=-0.4 to -0.5, P<0.001). Increase in absolute PHE between Days 1 and 3 was significantly predictive for in-hospital mortality (P=0.014, ExpB=1.04). CONCLUSIONS: PHE develops early after ICH and doubles within the first 7 to 11 days after the initial bleeding event. This additional mass effect may contribute to secondary clinical deterioration and mortality, especially in larger ICH. Because of its inverse correlation with ICH volume, relative PHE may not be suitable for analyses considering the clinical impact of PHE.

Dose effect of intraventricular fibrinolysis in ventricular hemorrhage.

BACKGROUND AND PURPOSE: The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH). METHODS: Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7 ± 1 and 10 ± 1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months. RESULTS: The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3, P=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4 ± 4.2 mL versus 8.8 ± 8.1 mL; P=0.01) and 10 (1.4 ± 2.8 mL versus 4.9 ± 65.8 mL; P=0.005). Total clot half-life was 78 ± 43 hours in the low-dose and 56 ± 25 hours in the high-dose group (P=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months. CONCLUSIONS: Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).

Early continuous hypertonic saline infusion in patients with severe cerebrovascular disease.

OBJECTIVE: To study the safety and the effects of early continuous hypertonic saline infusion in patients with cerebral edema and underlying cerebrovascular disease. DESIGN: Retrospective analysis. SETTING: University medical center. PATIENTS: Neurologic intensive care unit population with mixed cerebrovascular diseases. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 2008 and December 2009, 100 patients with severe intracerebral hemorrhage, cerebral ischemia, or aneurysmal subarachnoid hemorrhage and signs of intracranial hypertension received within ≤72 hrs after symptom onset a continuous infusion of hypertonic saline (3%, target sodium 145-155 mmol/L, target osmolality 310-320 mOsm/kg) over 13 (4-23) days. We analyzed the frequency of episodes with elevated intracranial pressure (new anisocoria or intracranial pressure >20 mm Hg for ≥20 mins), inhospital mortality, and the occurrence of adverse effects theoretically associated with hypertonic saline. The findings were compared with those of a historical control group (n = 115, 2007-2008) with equal underlying disease. In the treatment group, fewer episodes of critically elevated intracranial pressure (92 vs. 167, p = .027) in fewer patients (50 of 100 = 50.0% vs. 69 of 115 = 60.0% patients, p = .091) were observed, and inhospital mortality was significantly decreased (17.0% vs. 29.6%, p = .037). Adverse events, including cardiac arrhythmia, heart, liver or renal dysfunction, or pulmonary edema, occurred in both groups to a similar extent. CONCLUSIONS: Early and continuous infusion of hypertonic saline in patients with severe cerebrovascular disease and impending intracranial hypertension is safe and might reduce the frequency of intracranial pressure crises and mortality rate. A randomized controlled trial is warranted to confirm our findings and to evaluate the effects of hypertonic saline on functional outcomes.

Prognostic significance of third ventricle blood volume in intracerebral haemorrhage with severe ventricular involvement.

BACKGROUND AND PURPOSE: Intraventricular haemorrhage (IVH) is an independent predictor of poor outcome in spontaneous intracerebral haemorrhage (ICH). Larger IVH volume and increasing number of affected ventricles have been associated with worse prognosis, however, little is known about the prognostic value of blood volume in the different parts of the ventricular system. Therefore, the correlation of IVH volume in the third, fourth and lateral ventricles with outcome in patients with ICH and severe IVH, treated with intraventricular fibrinolysis (IVF), was investigated. METHODS: Patients with ICH <40 ml, severe IVH and acute hydrocephalus were treated with IVF. The course of IVH volume for each ventricle was measured by CT based volumetry. Outcome at 90 days was assessed by a telephone follow-up survey and correlated with initial IVH volume. RESULTS: 50 patients aged 62.5±10.3 years with spontaneous ICH (12.5±10.8 ml) and severe IVH (33.5±25 ml) were included. Clearance of the third and fourth ventricle from blood occurred after 3±1.9 days. Initial IVH volume in the third ventricle (3.8±3.3 ml) was predictive for poor outcome (OR 2.6 per ml, p=0.02). Correlation between larger IVH volume in the fourth ventricle and poor outcome showed a trend towards significance (p=0.07). Total IVH volume and lateral ventricle IVH volume were not correlated with outcome. CONCLUSION: Despite rapid clot removal, initial IVH volume in the third ventricle was a strong and independent negative predictor. This is possibly explained by irreversible damage of brainstem structures by the initial mass effect of IVH.

Intraventricular fibrinolysis for intracerebral hemorrhage with severe ventricular involvement.

Intraventricular hemorrhage (IVH) has been associated with poor prognosis in patients with spontaneous intracerebral hemorrhage. Several factors contribute to the deleterious effects of IVH, including direct mass effects of the ventricular blood clot on ependymal and subependymal brain structures, mechanical and inflammatory impairment of the Pacchioni granulations by blood and its breakdown products, and disturbance of physiological cerebrospinal fluid (CSF) circulation. Acute obstructive hydrocephalus represents a major life-threatening complication of IVH and is usually treated with an external ventricular drainage (EVD). However, treatment with EVD alone is frequently not sufficiently effective due to obstruction of the catheter by blood. In the past two decades, intraventricular fibrinolysis (IVF) has been increasingly used for maintenance of EVD functionality and acceleration of ventricular clot resolution in such patients. Unfortunately, there is no prospective, randomized controlled trial addressing the effect of IVF on clinical outcome. The available data on IVF consist of small retrospective case series, case reports, and a few prospective case-control studies, which are the subject of the present review article. All these studies, when considered in their entirety, suggest that IVF has a positive impact on mortality and functional outcome, and could be considered as a treatment option for selected patients.

Lumbar catheter for monitoring of intracranial pressure in patients with post-hemorrhagic communicating hydrocephalus.

BACKGROUND: We investigated the feasibility and accuracy of intracranial pressure (ICP)-measurement by lumbar drainage (LD) catheter in patients with post-hemorrhagic communicating hydrocephalus (PHCH). METHODS: Patients with subarachnoid hemorrhage (SAH, n = 21) or spontaneous ganglionic hemorrhage (ICH, n = 22) with ventricular involvement and the need for external ventricular drainage (EVD) due to acute hydrocephalus were included. When EVD weaning was not feasible due to persistent hydrocephalus, an additional LD was placed, after which EVD was clamped off. During this overlap period, patients underwent simultaneous pressure recording via EVD ("EVD-ICP") and LD ("LD-ICP"). Testing included manual compression of the jugular veins and body-posture changes from supine to 30° position. After EVD removal, we evaluated sensitivity and specificity of ICP-rise >20 mmHg during continuous monitoring via LD for the detection of persistent PHCH using additional evaluation with computed tomography (CT). RESULTS: A total of 1,806 measurements were performed in 43 patients. "LD-ICP" was strongly correlated to "EVD-ICP", with determination coefficients R(2) for the baseline measurements and each of the maneuvers ranging from 0.95-0.99, and slopes ranging 0.96-1.01. Sensitivity of "LD-ICP" >20 mmHg for detection of persistent PHCH as compared to CT was 81% and specificity was 100%. Two patients with severe SAH developed reversible signs of herniation after gradually increasing differences between "LD-ICP" and "EVD-ICP" indicated a cranio-spinal pressure gradient, likely due to cerebrospinal fluid overdrainage via LD. CONCLUSION: ICP measured via LD highly and reliably correlated to ICP measured via EVD in patients with PHCH.

Isolated Cervical Myelitis in Lyme Disease: A Rare Manifestation of Acute Neuroborreliosis.

Neuroborreliosis is the neurological manifestation of Lyme disease, a tick-borne infectious multi-system disease caused by Borrelia burgdorferi sensu lato. It appears in 3 to 15% of all cases of acute Lyme disease, and includes meningitis, cranial neuritis, and painful radiculoneuritis as the most common manifestations. We report a case of acute neuroborreliosis that manifested as extended isolated cervical myelitis. Not only the manifestation as isolated myelitis in the early stages of borreliosis represents a rarity, but also the strong contrast between mild clinical symptoms and pronounced imaging findings in this case is remarkable.

Long-term outcome changes after mechanical thrombectomy for anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) improves early clinical outcome in patients with acute ischemic stroke but insights on determinants of long-term outcome after MT treatment are scarce. METHODS: Data from stroke patients with anterior circulation large vessel occlusion of a prospective MT registry (01/2014-06/2017) of a large comprehensive stroke center were analyzed regarding clinical outcome between short- (3 months) and long-term (12 months) assessment reflected by a change of modified Rankin scores (∆mRS). Secondary endpoints included favorable long-term outcome (mRS 0-2). Multi-variable regression analysis was performed to identify determinants of outcome changes and favorable outcome at long term. RESULTS: Of 264 patients included, 42.0% showed a favorable long-term outcome. Longitudinal analysis found that some individuals still improved, but no overall mRS difference between short and long-term follow-up was detected [∆mRS - 0.004 (95% CI - 0.020; 0.013); p = 0.672]. Right hemispheric stroke [∆mRS 0.286 (0.011; 0.561); p = 0.043] and high NIHSS at discharge [∆mRS, 0.039 (0.004; 0.074); p = 0.029] were associated with a longitudinal mRS decline. Favorable long-term outcome was associated with successful recanalization (p < 0.0001). CONCLUSIONS: A significant number of patients with MT experience a favorable long-term outcome. Outcomes remained stable between short- and long-term follow-up, but some individuals may still show improvement beyond short-term rehabilitation. Right hemispheric stroke and clinical stroke severity at hospital discharge may be frail predictors for delayed decline of functional status, whereas successful recanalization remains a positive outcome predictor. Death rarely occurs beyond 3 months after MT treatment.

Intraventricular fibrinolysis and lumbar drainage for ventricular hemorrhage.

BACKGROUND AND PURPOSE: Both intraventricular fibrinolysis (IVF) and lumbar drainage (LD) may reduce the need for exchange of external ventricular drainage (EVD) and shunt surgery in patients with intracerebral hemorrhage and severe intraventricular hemorrhage. We investigated the feasibility and safety of IVF followed by early LD for the treatment of posthemorrhagic hydrocephalus. METHODS: This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (n=32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if "LD weaning" was unsuccessful for >10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale. RESULTS: IVF resulted in fast clearance of the third and fourth ventricles (73+/-50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105+/-59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding. CONCLUSIONS: In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.

Immediate Reversal of Dabigatran by Idarucizumab Prior to Laboratory and Imaging Results in Acute Stroke.

We report a case of intravenous thrombolysis in acute ischemic stroke of anterior choroidal artery following the antagonization of dabigatran with idarucizumab. No secondary complication, like hemorrhagic or thrombotic/thrombembolic event, of neither idarucizumab nor subsequent intravenous thrombolysis emerged. The recent approval of idarucizumab enables intravenous thrombolysis despite preexisiting oral anticoagulation with dabigatran, but raises the question of the optimal management and work flow of patients under medication with dabigatran and with acute neurological deficit, highly suspicious for an acute cerebrovascular event. In contrast to hitherto case reports and series, here, we explicitly refrained from awaiting the results of the thrombin time, as a marker for present anticoagulation by dabigatran, as well as the results of cerebral imaging before administration of idarucizumab. Based on the presented case we propose this approach to minimize door-to-needle time of intravenous thrombolysis in acute ischemic stroke and thus to enhance the chance for a good outcome.

Correct Outcome Prognostication via Sonographic Volumetry in Supratentorial Intracerebral Hemorrhage.

Introduction: The intracerebral hemorrhage (ICH)-score is used for estimation of patients' prognosis. The hemorrhage volume calculated from computed tomography (CT) contributes as one main factor. Several studies have proven that dimensions of an ICH may be displayed sufficiently by transcranial sonography (TCS). Yet, the adequacy of ICH-volumetry via TCS in calculating the ICH-score and its use as prognostic tool has not been studied. Methods: Forty consecutive patients with supratentorial ICH diagnosed via CT were included in this prospective observational pilot study. 45 examination-series via CT and TCS were done in order to perform an ICH-volumetry and calculate the ICH-score. Volume was calculated using the ABC/2 estimation. Results of both imaging techniques were compared regarding quantification of ICH- volume and correct prognostication. A modified Rankin Scale (mRS)-score of 0-3 points was valued as good outcome. Results: The imaging techniques did not show a difference in volumetry (p = 0.794) and TCS derived hemorrhage volume correlated significantly with ICH-volume measured on CT-scans. Calculated ICH-scores also did not differ (p = 0.323). Patients with an ICH-score larger than 2 points were predicted to experience a poor outcome at discharge with mRS 4-6 points, and the prognostication of the outcome was correct. Patients with a good outcome showed a smaller ICH-volume (11.2 ± 9.1ml) than patients with a poor outcome (38.2 ± 41.2 ml; p = 0.002). Conclusion: Volumetry in supratentorial ICH via TCS is feasible and the prognostication with the ICH-score based on its results is comparable to CT-imaging and sufficient.

Antiedema therapy in ischemic stroke.

Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive.

Characterizing tissue fate after transient cerebral ischemia of varying duration using quantitative diffusion and perfusion imaging.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient-cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28). METHODS: Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical 60-minute transient ischemia and permanent ischemia group. RESULTS: ADC-derived lesions markedly decreased on reperfusion at 35 minutes to an average of 15+/-5% of prereperfusion lesion size (P<0.00001). At 24 hours, lesion volume as determined by T2 imaging increased again to 51+/-10% of prereperfusion lesion size. In the 95-minute group, ADC lesions only briefly decreased on reperfusion and then secondarily enlarged at 180 minutes, almost reaching prereperfusion lesion volume. Pixel-based analysis demonstrated that >85% of mismatch pixels were salvaged by reperfusion independent of ischemia duration. Recanalization at 35, 60, and 95 minutes resulted in recovery of 46%, 28%, and 9% of core pixels, respectively. Core and mismatch pixels that were ultimately salvaged had persistently higher (P<0.001) CBF values during ischemia in all reperfusion groups, associated with higher (P<0.05) ADC values. CONCLUSIONS: This study demonstrated substantial salvage of mismatch tissue after reperfusion independent of ischemia duration and substantial permanent recovery of initial core pixels with early reperfusion. Severity of CBF reduction during ischemia seems to be the main factor determining tissue fate.

Safe Intravenous Thrombolysis after Traumatic Cardiopulmonary Resuscitation with Rib Fractures: A Case Report.

We report a case of successful intravenous thrombolysis for a distal middle cerebral artery occlusion shortly after traumatic cardiopulmonary resuscitation due to an episode of ventricular tachycardia. A high prevalence of fatal cardiac arrhythmias in acute stroke patients raises the question of safety when administrating thrombolytic therapy after traumatic cardiopulmonary resuscitation; guidelines do not provide a satisfactory statement about this. Our case suggests that intravenous tissue-type plasminogen activator for acute ischemic stroke can be administered after a thorough risk-to-benefit evaluation without major adverse effects in patients after traumatic cardiopulmonary resuscitation, as bleeding complications seem rare and can be monitored and treated.

Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging.

BACKGROUND AND PURPOSE: Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging. METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO. RESULTS: While the ADC-derived lesion volume increased rapidly during the first 120 min after MCAO and essentially stopped growing after 3 hours in SD rats, ADC lesion in WK rats increased progressively during the entire 210-min period and was significantly smaller at all time points (P<0.05). The abnormal perfusion volume correlated highly with the TTC-defined infarct size in both groups. In WK rats, the abnormal perfusion volume was significantly larger than the abnormal diffusion volume up to 90 min after MCAO (P<0.001), whereas the diffusion/perfusion mismatch was significant (P<0.001) only at 45 min in SD rats. ADC-CBF scatterplots analysis revealed a slower and less robust ADC decline over time in WK rats in pixels with severe (<20% of normal) and moderate (21 to 40% of normal) CBF reduction. CONCLUSIONS: This study demonstrated substantial differences in acute ischemic lesion evolution between SD and WK rats. These interstrain variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.

Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model.

Dimethyl sulfoxide (DMSO) has a variety of biological actions that suggest efficacy as a neuroprotectant. We (1) tested the neuroprotective potential of DMSO at different time windows on infarct size using 2,3,5-triphenyltetrazolium staining and (2) investigated the effects of DMSO on ischemia evolution using quantitative diffusion and perfusion imaging in a permanent middle cerebral artery occlusion (MCAO) model in rats. In experiment 1, DMSO treatment (1.5 g/kg intravenously over 3 h) reduced infarct volume 24 h after MCAO by 65% (P<0.00001) when initiated 20 h before MCAO, by 44% (P=0.0006) when initiated 1 h after MCAO, and by 17% (P=0.11) when started 2 h after MCAO. Significant infarct reduction was also observed after a 3-day survival in animals treated 1 h after MCAO (P=0.005). In experiment 2, treatment was initiated 1 h after MCAO and maps for cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were acquired before treatment and then every 30 mins up to 4 h. Cerebral blood flow characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the ADC-derived lesion volume essentially stopped progressing during DMSO treatment, resulting in a persistent diffusion/perfusion mismatch. This effect was mainly observed in the cortex. Our data suggest that DMSO represents an interesting candidate for acute stroke treatment.

Perfusion and diffusion imaging in acute focal cerebral ischemia: temporal vs. spatial resolution.

High-resolution diffusion- (DWI) and perfusion-weighted (PWI) imaging may provide substantial benefits in accurate delineation of normal, ischemic, and at-risk tissue. We compared the capability of low (400 x 400 microm(2)) and high (200 x 200 microm(2)) spatial resolution imaging in characterizing the spatiotemporal evolution of the ischemic lesion in a permanent middle artery occlusion (MCAO) model in rats. Serial measurements of cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed. Lesion volumes were calculated by using viability thresholds or by visual inspection, and correlated with infarct volume defined by TTC staining at 24 h after MCAO. At the very early phase of ischemia, high-resolution resulted in a significantly larger ADC-derived lesion volume and a smaller PWI/DWI mismatch. At 3 h after MCAO, ADC and CBF lesions showed similar robust correlations with TTC-defined infarct volumes for both groups using previously established thresholds. When lesions were determined visually, low-resolution resulted in a substantial overestimation of TTC-defined infarct volume and a lower inter-observer reliability (r = 0.75), whereas high-resolution produced an excellent correlation with TTC-defined infarct volume and inter-observer reliability (r = 0.96). In conclusion, high-resolution MRI resulted in substantial temporal averaging of the ischemic lesion during the early phase, but was clearly superior in visual determination of final infarct size. Low-resolution reasonably evaluated the temporal and spatial evolution of ischemia when thresholds were used.