Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Epstein-Barr virus-positive monoclonal lymphoplasmacytic proliferation associated with neurosyphilis in an immunocompetent patient: A case report.

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.

Correlation between pretreatment and follow-up infarct volume using CT perfusion imaging: the Bayesian versus singular value decomposition method.

PURPOSE: Pretreatment ischemic core volume is conceptually equal to follow-up infarct volume (FIV) in patients with successful recanalization. However, there is sometimes an absolute volume difference (AD) between pretreatment core volume and FIV. The aim was to compare the AD values between the Bayesian and the singular value decomposition (SVD) methods with time from onset-to-imaging in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy. METHODS: Consecutive AIS patients were included if they had the following: (1) anterior large vessel occlusion (internal carotid or middle cerebral artery); (2) within 24 h of onset; (3) pretreatment CT perfusion (CTP); (4) successful recanalization (mTICI ≥ 2b); and (5) 24-h diffusion-weighted imaging (DWI). FIV was measured on 24-h DWI. The AD value between FIV and the pretreatment core volume was calculated for Bayesian and SVD methods. Spearman's rank correlation coefficient (rho) was calculated as appropriate. RESULTS: In the 47 patients enrolled (25 men; median age 78 years; median baseline National Institutes of Health Stroke Scale, 22), the median time from onset-to-imaging and onset-to-recanalization was 136 and 220 min, respectively. Shorter onset-to-imaging time was correlated with a larger AD value, and more trend was seen in the SVD method (rho = - 0.28, p = 0.05) compared with the Bayesian method (rho = - 0.08). A larger pretreatment core volume was correlated with a larger AD value, and this tendency was slightly stronger for the SVD (rho = 0.63, p < 0.01) than for the Bayesian (rho = 0.32, p = 0.03) method. CONCLUSIONS: The Bayesian method might be more correlated with FIV than the SVD method in patients with a large ischemic lesion immediately after stroke onset, but not perfect.

Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma.

The current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less invasive, non-surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell-free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method.

Visualisation of the non-linear correlation between age and poor outcome in patients with aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To visualise the non-linear correlation between age and poor outcome at discharge in patients with aneurysmal subarachnoid haemorrhage (SAH) while adjusting for covariates, and to address the heterogeneity of this correlation depending on disease severity by a registry-based design. METHODS: We extracted data from the Japanese Stroke Databank registry for patients with SAH treated via surgical clipping or endovascular coiling within 3 days of SAH onset between 2000 and 2017. Poor outcome was defined as a modified Rankin Scale Score ≥3 at discharge. Variable importance was calculated using machine learning (random forest) model. Correlations between age and poor outcome while adjusting for covariates were determined using generalised additive models in which spline-transformed age was fit to each neurological grade of World Federation of Neurological Societies (WFNS) and treatment. RESULTS: In total, 4149 patients were included in the analysis. WFNS grade and age had the largest and second largest variable importance in predicting the outcome. The non-linear correlation between age and poor outcome was visualised after adjusting for other covariates. For grades I-III, the risk slope for unit age was relatively smaller at younger ages and larger at older ages; for grade IV, the slope was steep even in younger ages; while for grade V, it was relatively smooth, but with high risk even at younger ages. CONCLUSIONS: The clear visualisation of the non-linear correlation between age and poor outcome in this study can aid clinical decision making and help inform patients with aneurysmal SAH and their families better.

Measuring Quality of Care for Ischemic Stroke Treated With Acute Reperfusion Therapy in Japan　- The Close The Gap-Stroke.

BACKGROUND: In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min). CONCLUSIONS: Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.

Survival in patients with glioblastoma at a first progression does not correlate with isocitrate dehydrogenase (IDH)1 gene mutation status.

BACKGROUNDS: Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting. METHODS: A total of 171 patients with newly diagnosed glioblastoma, either 'primary' glioblastoma or 'secondary' glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122). RESULTS: IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with 'primary' glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When 'primary' glioblastoma and 'secondary' glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035). CONCLUSIONS: These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with 'primary' glioblastoma and pretreated 'secondary' glioblastoma, and further warrant investigation in prospective studies.

Is using intracerebral hemorrhage scoring systems valid for mortality prediction in surgically treated patients?

While intracerebral hemorrhage (ICH) scoring systems provide mortality and morbidity prediction, the actual mortality rates seem to be lower than those predicted by scoring systems in our clinical impression. To assess the validity of the ICH score and the Surgical Swedish ICH (SwICH) score, we retrospectively reviewed surgically treated ICH patients between 2012 and 2019. Uni- and multivariate analyses were performed to identify variables in predicting 30-day mortality. We identified 203 patients (mean ICH score 2.7; mean SwICH score 2.0). The actual 30-day mortality was 7%, which was significantly lower than those predicted by the ICH and the SwICH scores (55% and 16%, respectively; p < 0.001). Both scores were strongly correlated with the modified Rankin scale (mRS) at discharge (correlation coefficient 0.97 and 0.98; critical value 0.81). The only significant prognostic factors for the 30-day mortality by multivariate analysis were anisocoria (p = 0.03) and preoperative Glasgow Coma Scale (p = 0.03). These two factors also predicted mRS at discharge (p < 0.001). After discharge, 15% of patients improved regarding mRS and 29% of wheelchair-bound patients gained the ability to ambulate. No significant relationship existed between the degree of recovery after discharge and preoperative ICH score (p = 0.25). The ICH and SwICH scores were more valid in predicting morbidity, rather than mortality after surgical intervention for ICH. Anisocoria and Glasgow Coma Scale < 7 were the only two factors that predicted 30-day mortality and morbidity at discharge.

Negative impact of Interhospital Transfer on Clinical Outcomes of Mechanical Thrombectomy for Fast Progressive Stroke.

OBJECTIVES: The time-dependence of the clinical outcome of mechanical thrombectomy is higher in the "fast progressor" in whom cerebral ischemia progresses rapidly. The impact of time-consuming interhospital transfer (IT) on the clinical outcome of such patients is unknown. The effect on clinical outcomes of IT of fast progressors was investigated. METHODS: Among the patients enrolled in the Tokyo/Tama REgistry of Acute endovascular Thrombectomy, fast progressor cerebral ischemia cases were retrospectively investigated. In this study, a fast progressor was defined as a case with an Alberta Stroke Program Early CT Score less than 6 and last known well (LKW) to arterial puncture within 6 h. Patients' background characteristics, treatment progress, and the modified Rankin Scale (mRS) score at 3 months were examined. RESULTS: Of a total of 1182 patients, 92 (7.8%) were included, with 76 patients in the direct transfer (DT) group, and 16 patients in the IT group. Median LKW to reperfusion was 190 min and 272 min, respectively (P<.001). The number of patients with mRS scores 0-2 at three months was 22 (28.9%) in the DT group and 1 (6.2%) in the IT group. Interhospital transfer was an independent factor associated with worse outcomes (odds ratio 0.08, 95% confidence interval 0.01-0.87, P=.038). CONCLUSION: This study showed that, among fast progressor patients, the IT group had a worse prognosis than the DT group. To provide good clinical outcomes for fast progressor patients, those who are likely to undergo mechanical thrombectomy should be sent directly to a thrombectomy-capable center.

PKD1-Associated Arachnoid Cysts in Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVES: the prevalence of intracranial aneurysms and arachnoid cysts is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. A genotype correlation was reported for intracranial aneurysms, but it is unclear for arachnoid cysts. Therefore, the genotype correlation with intracranial aneurysms and arachnoid cysts was investigated in ADPKD. MATERIALS AND METHODS: intracranial aneurysms and arachnoid cysts were screened by magnetic resonance imaging (MRI), and PKD genotypes were examined using next-generation sequencing for 169 patients with ADPKD. RESULTS: PKD1-, PKD2- and no-mutation were identified in 137, 24 and 8 patients, respectively. Intracranial aneurysms and arachnoid cysts were found in 34 and 25 patients, respectively, with no significant difference in frequency. Genotype, sex, estimated glomerular filtration rate and age at ADPKD diagnosis significantly affected the age at brain MRI. The proportional hazard risk analyzed using the age at brain MRI adjusted by these four variables was 5.0-times higher in the PKD1 group than in the PKD2 group for arachnoid cysts (P = 0.0357), but it was not different for intracranial aneurysms (P = 0.1605). Arachnoid cysts were diagnosed earlier in the PKD1 group than in the PKD2 group (54.8 vs 67.7 years, P = 0.0231), but no difference was found for intracranial aneurysms (P = 0.4738) by Kaplan-Meier analysis. CONCLUSIONS: this study demonstrated the correlation between arachnoid cysts and PKD1 mutation. The reported association of arachnoid cysts with advanced renal disease may be due to the common correlation of these factors with PKD1 mutation.

Impact of Coronavirus Disease 2019 on Time Delay and Functional Outcome of Mechanical Thrombectomy in Tokyo, Japan.

OBJECTIVES: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan. MATERIALS AND METHODS: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020). RESULTS: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days. CONCLUSIONS: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic.

Improving Acute In-Hospital Stroke Care by Reorganization of an In-Hospital Stroke Code Protocol.

BACKGROUND AND PURPOSE: Delays in recognition and assessment of in-hospital strokes (IHS) can lead to poor outcomes. The aim was to examine whether reorganized IHS code protocol can reduce treatment time. METHODS: IHS code protocol was developed, educational workshops were held for medical personnel. In the protocol, any medical personnel should directly consult a stroke neurologist before any diagnostic studies. Time intervals were compared between the pre- and post-implementation periods and between direct consultation with a stroke neurologist (DC group) and non-DC group in the post-implementation period. RESULTS: A total of 145 patients were included (pre, 42; post, 103). Time from recognition to stroke neurologist assessment (91 vs. 35 min, p = 0.002) and time from recognition to neuroimaging (123 vs. 74, p = 0.013) were significantly lower in the post-implementation period. Time from stroke neurologist assessment to groin puncture was significantly lower (135 vs. 81, p = 0.037). In the post-implementation period, DC group showed significant time savings from last known well (LKW) to recognition (93 vs. 260, p = 0.001), LKW to stroke neurologist assessment (145 vs. 378, p = 0.001), and recognition to stroke neurologist assessment (16 vs. 76, p < 0.001) compared with non-DC group. CONCLUSIONS: Reorganization of IHS code protocol reduced time from stroke recognition to assessment and treatment time. Reorganized IHS code and direct consultation with a stroke neurologist improved the initial response time.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. RESULTS: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00). CONCLUSION: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy.

OBJECTIVE: The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. METHODS: Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. RESULTS: Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. CONCLUSIONS: Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.

Tokyo Metropolitan Stroke Emergency Medical Services for Interventional Stroke Treatment: The Tama-REgistry of Acute Thrombectomy (TREAT) Study.

OBJECTIVE: It is not clear how patients with large vessel occlusion (LVO) who have undergone mechanical thrombectomy (MT) were transported to hospitals by emergency medical services. Here, we describe the current status of the stroke delivery system in a large city. METHODS: We investigated data from 328 patients (male, n = 199; average age, 74.8 ± 12.9 years) who underwent MT at 12 facilities in the Tama area of Tokyo, between January 2015 and December 2017. The patients were classified according to the destination institution as Stroke A eligible (group A, n = 266 [8.2%]), Tertiary critical care center (group T; n = 35 [10.7%]), and other destinations such as emergency rooms (group O; n = 27 [8.2%]), and then reasons for using Emergency Medical Service (EMS) services and outcomes were compared among the groups. RESULTS: Rates of milder stroke, and middle cerebral artery occlusion were significantly higher in group A than T, whereas that of vertebral-basilar artery occlusion was significantly lower in group A than in groups T and O. The amount of elapsed time from door to picture (DTP) was significantly lower in group A. The time from onset to recanalization, as well as rates of successful recanalization and favorable outcomes (90-day modified Rankin scale 0-2) did not significantly differ regardless of destination. CONCLUSIONS: Most patients with LVO in the Tama area were categorized into group A. DTP was significantly lower in group A.

Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Widening Time Disparities between Two Paradigms: Tama-REgistry of Acute Endovascular Thrombectomy.

BACKGROUND: The Tama-REgistry of Acute endovascular Thrombectomy (TREAT) is a multicenter registry of endovascular thrombectomy in the Tama area of Tokyo. The objective of this study was to confirm the real-world status of 2 paradigms of transportation. METHODS: This was a retrospective analysis of data from TREAT. Patients were divided into 2 groups and 2 periods: directly admitted to an endovascular thrombectomy-capable center (ECC; group D)/secondary transfer from a non-ECC (group S), and the first period/the second period. Transfer distance, workflow metrics, and clinical outcomes were analyzed. RESULTS: A total of 326 patients, including 264 in group D and 62 in group S, were analyzed. The median distance from the onset-to-ECC was 3.62km for group D and 7.87km for group S (P < .001). The median onset-to-needle (OTN) time was longer for group S (168 minutes) than group D (138 minutes; P = .006). The median onset-to-reperfusion (OTR) time was significantly shorter for group D (247 minutes) than for group S (304 minutes; P = .029). With respect to the 2 periods, there was no significant difference in onset-to-puncture time between the 2 groups in the first period (207 minutes versus 243.5 minutes, respectively, P = .50), while there was one in the second period (164 minutes versus 246.5 minutes, respectively, P = .02). CONCLUSIONS: This region-wide registry study showed longer OTN and OTR times, with no improvement of the time course over time in patients transported via non-ECCs. These results should be used to create a regional medical policy for the management of acute ischemic stroke.

Subcutaneous Heparin Therapy for Patients with Cancer-Associated Stroke.

BACKGROUND: Anticoagulation therapy, particularly subcutaneous heparin therapy, is recommended for cancer-associated thrombosis. However, not starting or discontinuing anticoagulation was not rare. The aim of the present study was to examine the practical issues related to anticoagulation therapy and effects of subcutaneous heparin therapy for cancer-associated stroke. METHODS: Patients with cancer-associated stroke in our stroke center between October 2014 and August 2017 who were diagnosed as having acute ischemic stroke based on diffusion-weighted imaging were retrospectively enrolled. Baseline clinical characteristics, heparin injection, reasons for no subcutaneous heparin therapy, and clinical outcomes were collected. RESULTS: A total of 59 patients with cancer-associated stroke (75 ± 10 years old, male 42%) were enrolled. Lung cancer was the most frequently observed cancer (n = 17, 29%), followed by gastric cancer (n = 8, 14%) and pancreatic cancer (n = 8, 14%). Of the 19 patients (32%) who underwent subcutaneous heparin therapy, it was discontinued in 9 (47%), mainly because of patients' medical conditions (deterioration of cancer or hemorrhagic complication). Ten patients with long-term subcutaneous heparin therapy did not have stroke recurrence. In contrast, among nine patients who discontinued subcutaneous heparin therapy, three (33%) had recurrence of ischemic stroke. Of the 40 patients without subcutaneous heparin therapy, the main reasons for no subcutaneous heparin therapy were the patients' medical conditions (n = 22, 55%). CONCLUSIONS: Although subcutaneous heparin therapy was given to only one third of cancer-associated stroke patients, long-term subcutaneous heparin therapy might prevent recurrence of cancer-associated stroke.

Thrombectomy for Stroke at 6-24 hours without Perfusion CT Software for Patient Selection.

BACKGROUND: Although, thrombectomy for stroke more than 6 hours after onset supported by automated perfusion computed tomography (CT) software (RAPID, iSchemaView) is effective, this software is not available in Japan. This study aimed to elucidate the efficacy of thrombectomy 6-24 hours after onset in our patient cohort using conventional imaging mismatch. METHODS: Of 586 ischemic stroke patients who underwent thrombectomy registered from January 2015 to December 2017, patients with occlusion of the intracranial internal carotid artery or middle cerebral artery, who had last been known to be well 6-24 hours earlier and who had a prestroke modified Rankin scale (mRS) score 0 or 1 were enrolled. Clinical outcomes were the scores of the utility-weighted (UW) mRS, which ranges from 0 (death) to 10 (no symptom or disability), and the rate of functional independence (mRS score of 0-2) at 90 days. RESULTS: This study sample included 31 patients. The median baseline National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 13-20), and the median Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score was 7 (IQR, 5-8). The median interval between the time that the patient was last known well and revascularization was 741 (IQR, 641-818) minutes. The mean UW mRS score at 90 days was 5.3, the rate of functional independence was 32%, and the 90-day mortality rate was 13%. CONCLUSIONS: Thrombectomy 6-24 hours after onset which can be performed with conventional imaging mismatch might be secured for improving functional independence in stroke patients.