Novel partial deletions, frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy.

BACKGROUND AND PURPOSE: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features. METHODS: Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study. RESULTS: CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features. CONCLUSIONS: Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.

Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy.

BACKGROUND AND AIM: Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear. METHODS: A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes. RESULTS: At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P < .001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P < .001). CONCLUSIONS: Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy.

Spontaneous Dissection of Both Vertebral Arteries Diagnosed with Three-Dimensional T1-Weighted Image.

A 48-year-old woman spontaneously developed occipital pain, without any other neurological deficit. A brain magnetic resonance angiography showed narrowing, irregular dilatation, and aneurysmal formation in both the vertebral arteries (VA). According to these findings and the clinical course, we diagnosed the patient with spontaneous VA dissection. There was no finding suggesting cerebral infarction or subarachnoid hemorrhage. Three-dimensional T1-weighted magnetic resonance imaging performed 27 days after first onset of headache revealed a crescent-shaped high-intensity lesion in both the VA walls. These findings indicated that the lesions in both VAs were equally in the subacute phase. Follow-up three-dimensional T1-weighted imaging indicated that the high-intensity signals in both VAs disappeared at almost the same time. This case report presents imaging evidence showing that spontaneous dissection occurred simultaneously in both the VAs.

Association Between Absolute Eosinophil Count and Complex Aortic Arch Plaque in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Eosinophil counts are thought to be associated with atherosclerosis and aortic arch plaques. However, whether these associations exist among patients with acute ischemic stroke remains unclear. We aimed to evaluate the association between absolute eosinophil count (AEC) and aortic arch plaques among these patients. METHODS: Consecutive acute ischemic stroke patients undergoing transesophageal echocardiography were retrospectively analyzed. Complex aortic arch plaques (CAPs) were defined as plaques ≥4 mm in thickness, with ulcer, or with mobile component. RESULTS: A total of 430 patients (289 male, mean age 69.8±11.4 years) were enrolled. Patients with CAPs (n=169) showed higher mean AEC than those without (167±174/µL versus 127±127/µL; P=0.007). Multivariate analysis showed that increased AEC was independently associated with the presence of CAPs (odds ratio, 2.09; 95% confidence interval, 1.21-3.65). CONCLUSIONS: Among patients with acute ischemic stroke, increased AEC was independently associated with the presence of CAPs. Our results suggest that AEC may be a useful predictor for the presence of CAPs in these patients.

A Case of Hypertensive Encephalopathy with Enlarged Optic Nerve Sheath Measured by Transorbital Sonography.

This case report describes our experience in using transorbital sonography to evaluate pathological changes in the central nervous system in hypertensive encephalopathy. A 49-year-old man with nausea, headache, and mild confusion was diagnosed with hypertensive encephalopathy by brain magnetic resonance imaging (MRI), which revealed vasogenic edema in the bilateral thalamus and the brain stem. Lumbar puncture showed no severe intracranial hypertension. Transorbital sonography showed an increase in the optic nerve sheath diameter (ONSD). Repeated examination revealed a return of the ONSD to an almost normal range after a reduction in blood pressure and a resolution of symptoms. An improvement in cerebral vasogenic edema was confirmed by brain MRI. ONSD might be related to the severity of cerebral vasogenic edema. Repeated measurement of ONSD by transorbital sonography may be useful to assess the pathological course and the effect of treatment in hypertensive encephalopathy.

Multiple Infarcts Are Associated With Long-Term Stroke Recurrence and All-Cause Mortality in Cryptogenic Stroke Patients.

BACKGROUND AND PURPOSE: Brain infarct patterns that are observed via diffusion-weighted imaging are useful for classifying stroke subtypes. However, it is unclear whether infarct patterns can predict long-term outcomes in cryptogenic stroke patients. Herein, we investigated the association between acute brain infarct patterns and long-term stroke outcomes in cryptogenic stroke patients. METHODS: Acute cryptogenic stroke patients were consecutively enrolled between April 2008 and March 2012. Diffusion-weighted imaging ischemic lesion patterns were classified as single lesions, scattered lesions in one vascular territory, or multiple lesions in multiple vascular territories. Survivors (at discharge) were followed up for 3 years after stroke onset. RESULTS: A total of 272 cryptogenic stroke patients (132 women; aged 72±13 years) were enrolled. Among these patients, 169 (62.1%) had a single lesion, 38 (14.0%) had scattered lesions, and 65 (23.9%) had multiple lesions. Next, 261 patients (96.0%) were evaluated to assess right-to-left shunting, and 61 patients (23.4%) exhibited right-to-left shunting. On patient admission, right-to-left shunting and increased D-dimer levels were independently associated with multiple lesions but not single or scattered lesions. During the follow-up period (median, 1093 days), 30 patients (11.0%) developed recurrent stroke and 35 patients (12.9%) died. Multivariate Cox proportional hazard analyses showed that multiple infarcts were independently associated with recurrent stroke and all-cause mortality (hazard ratio, 3.79; 95% confidence interval, 2.24-6.37; P<0.001). CONCLUSIONS: Multiple brain infarcts on diffusion-weighted imaging were independently associated with long-term stroke outcomes in cryptogenic stroke patients.

Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19.

The coronavirus disease 2019 (COVID-19) remains an epidemic worldwide. Most patients suffer residual symptoms, the so-called "Long COVID," which includes respiratory and neuropsychiatric symptoms. Brain Fog, one of the symptoms of Long COVID, is a major public health issue because it can impair patients' quality of life even after recovery from the disease. However, neither the pathogenesis nor the treatment of this condition remains unknown. We focused on serum ferritin levels in this study and collected information on the onset of Brain Fog through questionnaires and found that high ferritin levels during hospitalization were associated with the occurrence of Brain Fog. In addition, we excluded confounders as far as possible using propensity score analyses and found that ferritin was independently associated with Brain Fog in most of the models. We conducted phase analysis and evaluated the interaction of each phase with ferritin levels and Brain Fog. We found a positive correlation between serum ferritin levels during hospitalization and Brain Fog after COVID-19. High ferritin levels in patients with Brain Fog may reflect the contribution of chronic inflammation in the development of Brain Fog. This study provides a novel insight into the pathogenic mechanism of Brain Fog after COVID-19.

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study.

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

Quantitative behavioral evaluation of a non-human primate stroke model using a new monitoring system.

Background: Recently, the common marmoset (Callithrix jacchus) has attracted significant interest as a non-human primate stroke model. Functional impairment in non-human primate stroke models should be evaluated quantitatively and successively after stroke, but conventional observational assessments of behavior cannot fully fit this purpose. In this paper, we report a behavioral analysis using MarmoDetector, a three-dimensional motion analysis, in an ischemic stroke model using photosensitive dye, along with an observational behavioral assessment and imaging examination. Methods: Ischemic stroke was induced in the left hemisphere of three marmosets. Cerebral infarction was induced by intravenous injection of rose bengal and irradiation with green light. The following day, the success of the procedure was confirmed by magnetic resonance imaging (MRI). The distance traveled, speed, activity time, and jumps/climbs were observed for 28 days after stroke using MarmoDetector. We also assessed the marmosets' specific movements and postural abnormalities using conventional neurological scores. Results: Magnetic resonance imaging diffusion-weighted and T2-weighted images showed hyperintense signals, indicating cerebral infarction in all three marmosets. MarmoDetector data showed that the both indices immediately after stroke onset and gradually improved over weeks. Neurological scores were the worst immediately after stroke and did not recover to pre-infarction levels during the observation period (28 days). A significant correlation was observed between MarmoDetector data and conventional neurological scores. Conclusion: In this study, we showed that MarmoDetector can quantitatively evaluate behavioral changes in the acute to subacute phases stroke models. This technique can be practical for research on the pathophysiology of ischemic stroke and for the development of new therapeutic methods.

Heterogeneity of Stroke in Patients with Systemic Lupus Erythematosus.

Objective The underlying pathophysiology varies according to stroke subtype. However, stroke heterogeneity among patients with systemic lupus erythematosus (SLE) remains unstudied. We hypothesized that the contribution of SLE to stroke might vary according to its subtype and investigated the associations of SLE and various stroke subtypes. Methods Diagnostic codes and electronic medical records were used to identify 70 patients with SLE who developed acute cerebral infarction or intracerebral hemorrhaging at four tertiary referral hospitals between 2008 and 2018. Intracerebral hemorrhaging was classified as lobar or deep, while cerebral infarction was classified according to the SSS-TOAST criteria. Physician notes were used to identify SLE activity, and their prevalences were compared among stroke subtypes. Outcomes were collected from the patients' medical records. Results The most common stroke subtype in patients with SLE was that of undetermined causes (31%), followed by small artery occlusion (16%), cardioaortic embolism (13%), other causes (11%), lobar hemorrhaging (10%), deep hemorrhaging (10%), and large artery atherosclerosis (9%). Stroke onset occurred during a period of high SLE activity in 21 patients (30%). The proportion of patients with high SLE activity varied according to stroke subtype (p=0.039) and was highest for cerebral infarction with undetermined causes. Stroke recurrence or death was observed in 40% of patients within 5 years after the initial stroke onset. Conclusion The contributions of SLE to stroke varied significantly according to the stroke subtype. Given the unfavorable prognosis, close stroke subtype-specific observation by rheumatologists and stroke specialists is recommended after stroke events.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Predicting hemorrhagic transformation after large vessel occlusion stroke in the era of mechanical thrombectomy.

Serum biomarkers are associated with hemorrhagic transformation and brain edema after cerebral infarction. However, whether serum biomarkers predict hemorrhagic transformation in large vessel occlusion stroke even after mechanical thrombectomy, which has become widely used, remains uncertain. In this prospective study, we enrolled patients with large vessel occlusion stroke in the anterior circulation. We analyzed 91 patients with serum samples obtained on admission. The levels of matrix metalloproteinase-9 (MMP-9), amyloid precursor protein (APP) 770, endothelin-1, S100B, and claudin-5 were measured. We examined the association between serum biomarkers and hemorrhagic transformation within one week. Fifty-four patients underwent mechanical thrombectomy, and 17 patients developed relevant hemorrhagic transformation (rHT, defined as hemorrhagic changes ≥ hemorrhagic infarction type 2). Neither MMP-9 (no rHT: 46 ± 48 vs. rHT: 15 ± 4 ng/mL, P = 0.30), APP770 (80 ± 31 vs. 85 ± 8 ng/mL, P = 0.53), endothelin-1 (7.0 ± 25.7 vs. 2.0 ± 2.1 pg/mL, P = 0.42), S100B (13 ± 42 vs. 12 ± 15 pg/mL, P = 0.97), nor claudin-5 (1.7 ± 2.3 vs. 1.9 ± 1.5 ng/mL, P = 0.68) levels on admission were associated with subsequent rHT. When limited to patients who underwent mechanical thrombectomy, the level of claudin-5 was higher in patients with rHT than in those without (1.2 ± 1.0 vs. 2.1 ± 1.7 ng/mL, P = 0.0181). APP770 levels were marginally higher in patients with a midline shift ≥ 5 mm than in those without (79 ± 29 vs. 97 ± 41 ng/mL, P = 0.084). The predictive role of serum biomarkers has to be reexamined in the mechanical thrombectomy era because some previously reported serum biomarkers may not predict hemorrhagic transformation, whereas the level of APP770 may be useful for predicting brain edema.

Stroke Severity and Outcomes in Patients With Newly Diagnosed Atrial Fibrillation.

Background and Purpose: Once a stroke occurs in a patient with atrial fibrillation (AF), it is likely to be severe. Patients with newly diagnosed AF after stroke and those with known AF before stroke have different background characteristics, yet the difference in stroke severity has not been sufficiently evaluated. In the current study, we compared the stroke severity and in-hospital outcomes between these patient groups. Methods: We retrospectively analyzed a database of 196 patients with acute ischemic stroke and AF between January 2010 and October 2019. We divided the patients into two groups: patients with "newly diagnosed AF" and those with "known AF." We assessed the stroke severity using the National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital outcomes using the modified Rankin Scale (mRS) score at discharge. Results: The proportion of newly diagnosed AF was 33% (64/196). There were no differences in age, hypertension, diabetes mellitus, and past history of heart failure between patients with newly diagnosed AF and those with known AF. Patients with newly diagnosed AF were associated with a lower proportion of male sex (male; 50 vs. 67%, p < 0.05), a lower proportion of past history of stroke (12 vs. 35%, p < 0.01), a lower CHA2DS2-VASc score (median [interquartile range]; 3 [2-4] vs. 3.5 [3-5], p < 0.01), and a lower proportion of pre-stroke oral anticoagulation (5 vs. 59%, p < 0.01). There were no differences in the NIHSS score on admission (12 [4-19] vs. 9 [3-19]) or the mRS score at discharge (3 [1-5] vs. 3 [1-5]). After adjustment for relevant covariates, newly diagnosed AF was not associated with the NIHSS score on admission [adjusted common odds ratio (OR), 0.85; 95% confidence interval (CI), 0.45-1.60] or the mRS score at discharge (adjusted common OR, 1.67; 95% CI, 0.88-3.18). After propensity score matching, newly diagnosed AF was not associated with the NIHSS score on admission (adjusted common OR, 0.91; 95% CI, 0.48-1.73) and the mRS score at discharge (adjusted common OR, 1.77; 95% CI, 0.92-3.43). Conclusion: Stroke severity and in-hospital outcomes in patients with newly diagnosed AF did not differ from those in patients with known AF after adjustment for clinically relevant factors. The importance of detection of latent AF and subsequent anticoagulation in preventing severe stroke should be further emphasized.

High neutrophil/lymphocyte ratio at cancer diagnosis predicts incidence of stroke in cancer patients.

Although cancer increases the incidence and severity of ischaemic stroke, there is no reliable method for predicting ischaemic stroke in cancer patients. To evaluate the prognostic capacity of the neutrophil-to-lymphocyte ratio at cancer diagnosis for predicting the incidence of ischaemic stroke, we used a hospital-based cancer registry that contained clinical data from all patients treated for cancer at Osaka University Hospital between 2007 and 2015. The neutrophil-to-lymphocyte ratio was calculated after dividing absolute neutrophil counts by absolute lymphocyte counts. These counts were obtained within 1 month after cancer diagnosis. The primary endpoint was new-onset ischaemic stroke within 2 years after cancer diagnosis. Of the 18 217 included cancer patients (median age: 65.2 years), 69 (0.38%) had ischaemic stroke. Unadjusted Cox regression analysis stratified by cancer site demonstrated that each 1-unit increase in the neutrophil-to-lymphocyte ratio was associated with a significant 7.2% increase in the risk of an ischaemic stroke event (95% confidence interval 1.041-1.103, P < 0.001). Survival tree analysis and the Kaplan-Meier method suggested that patients with and without atrial fibrillation who had increased neutrophil-to-lymphocyte ratios had a higher risk of ischaemic stroke. Multivariate Cox proportional hazard models, adjusted for cancer site and stage, revealed that patients with high neutrophil-to-lymphocyte ratios (>15) had higher ischaemic stroke risk than patients with low neutrophil-to-lymphocyte ratios (<5). This was true among cancer patients both with (hazard ratio 11.598; 95% confidence interval 0.953-141.181) and without (hazard ratio 7.877; 95% confidence interval 2.351-26.389) atrial fibrillation. The neutrophil-to-lymphocyte ratio at cancer diagnosis is associated with the incidence of ischaemic stroke among cancer patients and might thus be useful for identifying patients at high risk of ischaemic stroke, allowing us to guide future preventive interventions.

Time-outcome relationship in acute large-vessel occlusion exists across all ages: subanalysis of RESCUE-Japan Registry 2.

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time-outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (< 70, 70 to < 80, and ≥ 80 years), the mRS scores at 90 days were analyzed according to 4 categories of onset-to-reperfusion time (< 180, 180 to < 240, 240 to < 300, and ≥ 300 min). In each age subgroup, the distributions of mRS scores were better with shorter onset-to-reperfusion times. The adjusted common odds ratios for better outcomes per 1-category delay in onset-to-reperfusion time were 0.66 (95% CI 0.55-0.80) in ages < 70 years, 0.66 (95% CI 0.56-0.79) in ages 70 to < 80 years, and 0.83 (95% CI 0.70-0.98) in ages ≥ 80 years. Early reperfusion was associated with better outcomes across all age subgroups. Achieving early successful reperfusion is important even in elderly patients.

The Effect of Chemotherapy on Stroke Risk in Cancer Patients.

BACKGROUND: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We investigated how chemotherapy affects stroke risk in cancer patients. METHODS: Of 27,932 patients in a hospital-based cancer registry (which contains clinical data on all patients treated for cancer at Osaka University Hospital) screened between 2007 and 2015, medical records of 19,006 patients with complete data were investigated. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. RESULTS: Of 19,006 patients, 5,887 (31%) were in the chemotherapy group. Stroke occurred in 44 (0.75%) and 51 (0.39%) patients in the chemotherapy and nonchemotherapy group, respectively. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than those in the nonchemotherapy group (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.75). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). CONCLUSION: In our study, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

Futile complete recanalization: patients characteristics and its time course.

As the goal of mechanical thrombectomy is shifting toward mTICI-3 rather than mTICI-2b, we sought to clarify the limitation of the effect of mTICI-3. A post-hoc analysis of a registry of large-vessel occlusion stroke from 46 centers was conducted. Among 2,420 registered patients, 725 patients with anterior circulation occlusion who achieved successful reperfusion were analyzed. We compared outcomes between patients with mTICI-3 and mTICI-2b, and investigated how the effect of mTICI-3 changed according to baseline characteristics and time course. The proportion of patients with favorable outcomes (mRS 0-2 at day 90) was higher among patients with mTICI-3 compared to those with mTICI-2b (adjusted OR, 2.10; 95% CI, 1.49-2.97). There was no heterogeneity in the effect of mTICI-3 with respect to age, neurological deficit, alteplase use, occluded vessels, or infarct size. mTICI-3 was associated with favorable outcomes when the puncture-to-reperfusion time was <80 minutes (adjusted OR, 2.28; 95% CI, 1.52-3.41), but not when the puncture-to-reperfusion time was ≥80 minutes. A significant heterogeneity was found in the effect of mTICI-3 reperfusion across the puncture-to-reperfusion time subgroups (P for interaction = 0.025). Until when operators should continue the procedure after mTICI-2b has been achieved, needs to be studied.

Mechanical thrombectomy in acute ischemic stroke patients with left ventricular assist device.

OBJECTIVES: As the number of patients with left ventricular assist device (LVAD) implantation has been increasing, treatment of LVAD-related ischemic stroke is becoming a critical issue. We sought to clarify the features of mechanical thrombectomy in LVAD-related stroke with large vessel occlusion. METHODS: In a multi-center, retrospective case-control study, we compared 20 LVAD-related strokes with 33 non-LVAD strokes, all of which had large vessel occlusion in the anterior circulation treated with mechanical thrombectomy. A comparative histopathological examination of the retrieved thrombi was also performed. RESULTS: Successful reperfusion was achieved in 75% of the LVAD-related strokes. The time from onset to reperfusion was similar to that of non-LVAD strokes, but the total number of device passes required for reperfusion (median, 2.5 versus 1, P = 0.01) and the incidences of post-procedural parenchymal and subarachnoid hemorrhage (25% versus 3%, P = 0.02 and 55% versus 15%, P = 0.01, respectively) were higher in LVAD-related strokes. Symptomatic intracranial hemorrhage occurred in 4 patients (20%) with LVAD-related strokes. The histopathological analysis revealed that the ratio of erythrocyte components was significantly lower in thrombi retrieved from patients with LVAD-related stroke than in those with non-LVAD stroke (19 ± 6% versus 41 ± 17%, P = 0.01). CONCLUSIONS: Mechanical thrombectomy is feasible in patients with LVAD-related stroke. However, repetitive device passes are needed to achieve successful reperfusion mainly because of the structurally organized thrombi, and the higher risk of hemorrhagic complications should be considered, while offering this therapeutic alternative.