Clinical significance of intracranial hemorrhage after thrombectomy detected solely by magnetic resonance imaging and not by computed tomography.

BACKGROUND AND OBJECTIVE: Whether intracranial hemorrhage (ICH) detected using magnetic resonance imaging (MRI) affects the clinical outcomes of patients with large-vessel occlusion (LVO) treated with mechanical thrombectomy (MT) remains unclear. This study investigated the clinical features of ICH after MT detected solely by MRI. METHODS: This was a retrospective analysis of patients with acute ischemic stroke and occlusion of the internal carotid artery or middle cerebral artery treated with MT between April 2011 and March 2021. Among 632 patients, patients diagnosed with no ICH using CT, with a pre-morbid modified Rankin Scale (mRS) score ≤ 2, and those who underwent MRI including T2* and computed tomography (CT) within 72 h from MT were enrolled. The main outcomes were the association between ICH detected solely by MRI and clinical outcomes at 90 days. Poor clinical outcomes were defined as mRS score > 2 at 90 days after onset. RESULTS: Of the 246 patients, 29 (12%) had ICH on MRI (MRI-ICH(+)), and 217 (88%) were MRI-ICH(-). There was no significant difference between number of patients with MRI-ICH(+) experiencing poor (10 [12%]) and favorable (19 [12%]) outcomes. The mRS score at 90 days between patients with MRI-ICH (+) and MRI-ICH(-) was not significantly different (2 [1-4] vs. 2 [1-4], respectively). Higher age and lower ASPECTS were independent risk factors for poor outcomes, as shown by multivariate regression analysis. MRI-ICH(+) status was not associated with poor outcomes. CONCLUSIONS: ICH detected by MRI alone did not influence clinical outcomes in patients with LVO treated with MT.

The effect of asymptomatic intracranial hemorrhage after mechanical thrombectomy on clinical outcome.

BACKGROUND AND OBJECTIVE: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty. METHODS: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset. RESULTS: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH. CONCLUSIONS: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset.

Hyperglycemia and Outcomes in Patients with Successful Reperfusion by Mechanical Thrombectomy.

Background This study examined whether or not hyperglycemia on admission is associated with poor outcomes in patients with successful reperfusion by mechanical thrombectomy (MT). Methods Consecutive patients with acute anterior circulation stroke and large-vessel occlusion treated with MT were evaluated. Hyperglycemia was defined as a blood glucose level of >140 mg/dL on admission. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction of grade 2b or 3. A poor clinical outcome 90 days after the onset was defined as a modified Rankin Scale score of 4-6. We compared characteristics, including outcomes, between the normoglycemic (≤140 mg/dL) and hyperglycemic groups. In addition, the association between hyperglycemia and outcomes was evaluated in patients with successful reperfusion using MT. Results The participants comprised 407 patients (median age, 76.5 years old; 58.0% men; median NIHSS (National Institutes of Health Stroke Scale) score, 17). The site of occlusion was the ICA (Internal Carotid Artery) in 119 patients (29.2%) and the M1 in 178 patients (43.7%). Normoglycemia, hyperglycemia, successful reperfusion, and poor outcomes were found in 138 (33.9%), 269 (66.1%), 320 (78.6%), and 141 (34.4%) patients, respectively. Poor outcomes were more frequent in hyperglycemic patients (61.6%) than in normoglycemic patients (43.9%, P=0.001). Among patients with successful reperfusion, poor outcomes were more frequent in hyperglycemic patients (57.8%) than in normoglycemic patients (37.9%; P<0.001). In patients with successful reperfusion, a multivariate regression analysis identified hyperglycemia as a factor associated with poor outcomes (odds ratio, 2.151; confidence interval, 1.166-3.970; P=0.014). Conclusions Among all patients, hyperglycemia on admission was associated with a poor outcome in those treated with MT. Regarding the presence of successful reperfusion by MT, patients with successful reperfusion had such effects.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP.

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

A differential detailed diffusion-weighted imaging-ASPECTS for cerebral infarct volume measurement and outcome prediction.

BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

Mechanical Thrombectomy Treatment More than 16 h after Last Known Well for Patients with Large Vessel Occlusion.

INTRODUCTION: Mechanical thrombectomy (MT) has been reported to be effective within 24 h after last known well (LKW) by the DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) trial and within 16 h after LKW by the DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. However, there have been few reports of MT more than 16 h after LKW, and the efficacy and safety of MT more than 24 h after LKW have not yet been demonstrated. We evaluated the efficacy and safety of MT more than 16 h after LKW. METHODS: Using data from the Nippon Medical School Hospital MT registry from April 2011 to August 2022, consecutive patients with anterior circulation large vessel occlusion (LVO) and prehospital modified Rankin scale (mRS) scores of 0-3 were enrolled. Patients were classified into the following three groups: early group (LKW <6 h), middle group (LKW 6-16 h), and late group (LKW >16 h). The clinical characteristics and outcomes were compared among these three groups. RESULTS: Among 778 patients in the MT registry, 624 were enrolled. The early group included 432 patients, the middle group included 123 patients, and the late group included 69 patients. The patients had a median age of 77 years (interquartile range, 68-83), and 359 were male (57.5%). The median prehospital mRS score was 1 (interquartile range, 1-1), median National Institutes of Health Stroke Scale score on admission was 17 (interquartile range, 10-23), and median Alberta Stroke Program Early CT Score was 10 (interquartile range, 8-10). Regarding safety and efficacy, the proportions of cases with successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b-3; 85.4% vs. 92.7% vs. 88.7%; p = 0.47), symptomatic intracranial haemorrhage (6.4% vs. 5.7% vs. 7.2%; p = 0.99), mRS score ≤3 at 90 days (52.0% vs. 60.2% vs. 44.9%; p = 0.11), and mRS score of 6 at 90 days (11.3% vs. 10.6 vs. 8.7%; p = 0.37) were not significantly different between the three groups. CONCLUSION: Patients who received MT more than 16 h after LKW experienced the same safety and efficacy as those who received MT at 0-16 h after LKW. MT more than 16 h after LKW may be safe and effective for stroke patients with LVO.

The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. METHODS: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. RESULTS: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59-79] years; National Institutes of Health Stroke Scale score 9 [17][3-17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19-1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19-2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44-0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01-1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55-0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73-1.14, p = 0.395). CONCLUSION: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

Stenting for Common Carotid Artery Stenosis Using the Sheath Pull-Through Technique.

Objective: We report the "sheath pull-through technique" for stenting of common carotid artery stenosis (CCAS). Case Presentations: In this technique, an 8-10 Fr super-long sheath (SLS) 55-65 cm is inserted into the femoral artery and the brachiofemoral pull-through technique is subsequently used, improving the support of the sheath itself. We pulled both ends of a pull-through wire to further improve the support of SLS, stabilizing guiding catheter (GC) during the procedure in two cases. Conclusion: This technique stabilizes GC during CCAS stenting.

Impact of onset-to-groin puncture time within three hours on functional outcomes in mechanical thrombectomy for acute large-vessel occlusion.

Introduction Endovascular treatment for acute ischemic stroke with acute large-vessel occlusion (ALVO) has established benefits, and rapid treatment is vital for mechanical thrombectomy in ALVO. Time from onset of stroke to groin puncture (OTP) is a practical and useful clinical marker, and OTP should be shortened to obtain the maximum benefit of thrombectomy. Objective The aim of the present study was to assess the impact of early treatment of anterior circulation stroke within three hours after symptom onset and to evaluate the role of OTP in determining outcomes after endovascular therapy. Methods Consecutive patients with acute stroke due to major artery (internal carotid or middle cerebral arteries) occlusion who underwent endovascular recanalization between March 2014 and January 2017 were retrospectively evaluated. Patients were stratified by OTP into three categories: 0-≤3 h, >3-≤6 h, and >6 h. The primary outcome measure was a 90-day modified Rankin scale score of 0-2 (good outcome). Results Data were analyzed from 100 patients (mean age, 76.6 years; mean National Institutes of Health Stroke Scale score, 17). Groin puncture occurred within 0-≤3 h in 51 patients, >3-≤6 h in 28, and >6 h in 21. Median OTP in each group was 126 min (range, 57-168 min), 238 min (range, 186-360 min) and 728 min (range, 365-1492 min), respectively. On multivariable logistic regression analysis, category of OTP represented an independent predictor of patient outcome (adjusted odds ratio, 0.48; 95% confidence interval, 0.25-0.93; p = 0.029). Conclusions OTP is a prehospital and in-hospital workflow-based indicator. In this single-center study, OTP was found to independently affect functional outcomes after endovascular stroke treatment.

Effect of repeated allogeneic bone marrow mononuclear cell transplantation on brain injury following transient focal cerebral ischemia in rats.

AIMS: Transplantation of bone marrow mononuclear cells (BMMCs) exerts neuroprotection against cerebral ischemia. We examined the therapeutic timepoint of allogeneic BMMC transplantation in a rat model of focal cerebral ischemia, and determined the effects of repeated transplantation outside the therapeutic window. MAIN METHODS: Male Sprague-Dawley rats were subjected to 90 minute focal cerebral ischemia, followed by intravenous administration of 1 × 10(7) allogeneic BMMCs or vehicle at 0, 3 or 6 h after reperfusion or 2 × 10(7) BMMCs 6 h after reperfusion. Other rats administered 1 × 10(7) BMMCs at 6 h after reperfusion received additional BMMC transplantation or vehicle 9 h after reperfusion. Infarct volumes, neurological deficit scores and immunohistochemistry were evaluated 24 or 72 h after reperfusion. KEY FINDINGS: Infarct volumes at 24 h were significantly decreased in transplantation rats at 0 and 3 h, but not at 6 h, after reperfusion, compared to vehicle-treatment. Even high dose BMMC transplantation at 6h after reperfusion was ineffective. Repeated BMMC transplantation at 6 and 9h after reperfusion reduced infarct volumes and significantly improved neurological deficit scores at 24 and 72 h. Immunohistochemistry showed repeated BMMC transplantation reduced ionized calcium-binding adapter molecule 1, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine expression at 24 and 72 h after reperfusion. SIGNIFICANCE: Intravenous allogeneic BMMCs were neuroprotective following transient focal cerebral ischemia, and the therapeutic time window of BMMC transplantation was >3 h and <6 h after reperfusion in this model. Repeated transplantation at 6 and 9 h after reperfusion suppressed inflammation and oxidative stress in ischemic brains, resulting in improved neuroprotection.

Continuous oral administration of atorvastatin ameliorates brain damage after transient focal ischemia in rats.

AIMS: Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats. MAIN METHODS: Male Sprague-Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24h and 7 days after reperfusion. KEY FINDINGS: Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion. SIGNIFICANCE: These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses.

Histopathological evaluation of left atrial appendage thrombogenesis removed during surgery for atrial fibrillation.

BACKGROUND: In this study, we histopathologically assessed left atrial appendages (LAAs) resected during surgical treatment for atrial fibrillation (AF) to elucidate the mechanism of intra-LAA thrombus formation in valvular AF. METHODS: The clinicopathological study of resected LAA was made on 56 valvular AF cases: 28 with mitral regurgitation (MR), 3 with mitral stenosis, and 25 with mitral stenosis and MR. Pathological findings of thrombi in LAA were compared with clinical features, including history of valvular diseases and embolism, and findings of echocardiography. Results were analyzed using chi2 test, Fisher exact method, or Welch t test. RESULTS: Two types of mural thrombi were found in LAA: membranous (M)-thrombi and polypoid-shape (P)-thrombi. M-thrombi were found on LAA endocardium in 48 (86%) patients. All of the P-thrombi were observed on preexisting M-thrombi. More patients showed thrombi in the LAA orifice than in the tip (P < .001), especially in cases of MR (21 patients; P < .01). By echocardiography, MR flow was classified into 3 directions: toward the roof, anteroseptal, or posterolateral wall of the left atrium. Patients with MR jet flow against the posterolateral wall near the LAA entrance had a higher risk of LAA thrombi (P = .007). CONCLUSIONS: Instability of M-thrombi, including surface rupture before complete organization, relates to P-thrombi formation that results in high incidence of embolism in AF patients.

Histopathological features of the resected left atrial appendage as predictors of recurrence after surgery for atrial fibrillation in valvular heart disease.

BACKGROUND: A histopathological assessment of left atrial appendages (LAA) resected during surgical treatment for atrial fibrillation (AF) was made, with the aim of improving the prediction of postoperative AF recurrence. METHODS AND RESULTS: This clinicopathological study involved 57 surgical cases of valvular AF and 34 age- and sex-matched control autopsy cases with a history of sinus rhythm. LAA from the cases with valvular AF showed greater hypertrophy of cardiomyocytes (p<0.0001), greater nuclear enlargement (p<0.0001), more bizarre nuclei (BN; p<0.0001), and more intercellular fibrosis (ICF; p<0.001). Partial disarray of cardiomyocytes and fatty infiltration were recognized in both the AF and control groups. Thirty-seven cases had maintained sinus rhythm after surgery from 7 months to 10 years. AF recurred within a month of surgery in 17 and after a month in 3; there was no significant difference in histopathological features between them. These 20 cases had more cellular hypertrophy (p<0.025), nuclear enlargement (p<0.025), BN (p<0.01), and ICF (p<0.025) than those who maintained sinus rhythm after surgery. CONCLUSIONS: The histopathological findings for LAA reflected the underlying valvular diseases; however, the most reliable predictors of postoperative AF recurrence were hypertrophy of cardiomyocytes, bizarre shaped nuclei, and extensive ICF.