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Background: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. Methods: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. Results: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776–6.818, p < 0.001; OR 3.415, 95% CI: 1.863–6.258, p < 0.001). Conclusions: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.

Advanced glycation end products (AGEs) are suggested to play a potential role in the progression of Parkinson's disease (PD). The association between urinary levels of pentosidine, one of the best-characterized AGEs, and clinical conditions such as motor severity and cognition were investigated in patients with PD. Data on the clinical characteristics and urinary levels of pentosidine for 44 drug-naïve patients aged 60 years or older with PD were collected. The association between urinary pentosidine levels and severity of motor symptoms and cognition was analyzed using the Montreal Cognitive Assessment Scale (MoCA). Urinary pentosidine values increased with age (R

A 73-year-old man developed delayed-onset multiple cranial neuropathies of cranial nerves V, VII and VIII, and segmental paresis in the ipsilateral upper extremity related to the C4 to Th1 segment, after all skin lesions with varicella zoster (VZV) on the left neck of the C3-4 dermatome had dried and crusted over. On admission, cerebrospinal fluid (CSF) revealed pleocytosis (all mononuclear cells, 12/μl). Treatment was started with intravenous acyclovir (10 mg/kg, every 8 h for 14 days) and methylprednisolone (1,000 mg/day for 3 days). Four days after starting treatment, left segmental paresis was improved, but the multiple cranial neuropathies persisted. Oral prednisolone (0.5 mg/kg/day) was administered for 5 days, then tapered off. All neurological symptoms had disappeared by hospital day 23. Of particular interest was the discrepancy between skin regions affected by VZV (C3-4) and the regions of cranial neuropathy (cranial nerves V, VII, and VIII) and muscle weakness innervated by C4-Th1. Although CSF was negative for VZV DNA according to PCR testing, the antibody index for VZV was elevated. This suggests intrathecal synthesis of VZV antibodies and supports the diagnosis of VZV meningitis. Also, all cranial nerves involved in this case were reported to have the cranial nerve ganglia where VZV could have established latency and been reactivated. This suggests concurrent reactivation on each cranial nerve ganglia without cutaneous lesions, as zoster sine herpete. In addition, anastomoses among the upper cervical nerves, which are found in some patients, may have contributed to this condition. These mechanisms underlie various neurological symptoms associated with VZV infection.

Background: Liver fibrosis (LF) is reported to affect the development of cerebral small vessel disease (SVDs) including cerebral microbleeds (CMBs). The Fibrosis-4 (Fib4) index is a simple and non-invasive scoring method for detecting LF. Herein, we investigated the association between the severity of LF and the presence or distribution of CMBs. Methods: From October 2012 to May 2022, patients with acute ischemic stroke within 24 hours from onset were retrospectively enrolled. Exclusion criteria were those associated with malignancy or missing clinical data including MRI findings before treatment started, or functional outcome at 3 months after discharge. The distribution of CMBs were classified on MRI as strictly lobar, or not (deep/ infratentorial or mixed area). FIB-4 index is calculated as follows: FIB-4 = [age (years)*aspartate aminotransferase (U/L)] / [platelet count (10 9 /L) *√alanine aminotransferase (U/L)]. We analyzed the association between the severity of LF, according to the tertile of Fib4 index; mild-LF (Fib4 index < 1.30), moderate-LF (1.30 ≤ Fib4 index < 2.67), severe-LF (2.67 ≤ Fib4 index), and the presence and distribution of CMBs. Results: 614 subjects (median age 69 years, 435 men) were retrospectively enrolled. Fib4 index were higher in order of only lobar, deep/ infratentorial or mixed area, and none CMBs ( p < 0.001). Also, severe LF group showed the highest number of CMBs (p < 0.001). Age on admission (OR 1.040, 95% CI 1.020-1.050, p < 0.001), hypertension (OR 1.840, 95%CI 1.260-2.690, p = 0.002), and anti-thrombotic drugs using (OR 1.500, 95% CI 1.020-2.190, p = 0.038) were independently associated with the presence of CMBs. In anatomical distribution of CMBs, Fib4 index (OR 0.701, 95%CI 0.505-0.974, p = 0.034) were only independent predictive factor of the CMBs on D/I or mixed area. Conclusion: The novel association between silent LF and the distribution of CMBs as located in only lobar were established.

Background and Purpose: Delayed leukoencephalopathy (DL) following ischemic stroke with large vessel occlusion (LVO) is rarely reported and the pathophysiology is unclear. We aimed to investigate the incidence, clinical characteristics of DL following acute ischemic stroke. Methods: Consecutive ischemic stroke patients were screened. Inclusion criteria were: 1) onset to door time within 7 days; and 2) availability of initial and a second or more MRI after 14 days from onset with DWI, FLAIR, and MRA. We defined DL as newly detected diffuse hyperintensities restricted to the white matter on FLAIR mostly accompanied with partial DWI hyperintensities after 14 days from onset. First, we estimated the incidence of DL and whether a LVO would be a factor associated with DL following all the acute ischemic stroke. Second, limiting the patients with LVO, we evaluated the incidence and the factors associated with DL. Results: We screened 1,857 consecutive ischemic stroke patients. Of all, 792 with all the acute ischemic stroke (573 (72%) male, median age 67 years), and 183 with LVO (128 (70%) male, median age 67 years) were included in each analysis. DL were detected in 18 patients in all the acute ischemic stroke (2%), and 17 in patients with LVO (9%) (Figure). First, LVO was strongly associated with DL following all the acute ischemic stroke (OR 62.3, 95% CI 8.23 to 471, p p = 0.019), NIHSS score at admission (OR 1.06, 95% CI 1.01 to 1.11, p = 0.014), complete recanalization (OR unable to calculate due to 100% prevalence in DL group, p p Conclusions: DL is not an uncommon phenomenon especially after LVO. Age, neurological severity, mechanical thrombectomy, and complete recanalization might be related to DL.

Background and Purpose: To compare clinical features including carotid ultrasound findings, especially carotid plaque features, between patients with and without aortic complicated lesion (ACL) in embolic stroke of undetermined source (ESUS). Methods: Patients were selected from a comprehensive stroke center between April 2013 and April 2022. Inclusion criteria were: 1) consecutive ischemic stroke patients 2) who fulfilled ESUS criteria based on NAVIGATE-ESUS trial, and 3) who underwent transesophageal echocardiogram (TEE), and 4) admitted 7 days from onset. We compared clinical features, including carotid ultrasound findings in common carotid artery and internal carotid artery such as carotid plaque thickness on the each side, maximum carotid plaque thickness and carotid plaque laterality ratio defined as maximum left carotid plaque thickness divided by maximum right carotid plaque thickness, between ESUS patients with ACL (ACL-ESUS) and without ACL (non ACL-ESUS). Results: We screened 2,066 consecutive ischemic stroke patients, including 177 ESUS patients (136 [77%] male, median age 64 years old). Of all, 35 patients had ACL (30 [86%] male, median age 71 years old, Figure A). ACL-ESUS showed older age (ACL-ESUS vs. non ACL-ESUS; 71 vs. 64 years old, p = 0.004), higher frequency of having carotid plaque more than 1.6mm ipsilateral to the infarct (82% vs. 53%, p = 0.013), higher frequency of having cortical lesion (46% vs. 26%, p = 0.023), and higher carotid plaque laterality ratio (1.18 vs. 1.00, p = 0.042). In multivariable analysis, demonstrating cortical lesion (OR 2.86, 95%CI 1.03-7.92, p = 0.043), carotid plaque laterality ratio (OR 2.75, 95%CI 1.03-7.32, p =0.043) were independently associated with ACL (Figure B). Conclusions: In ESUS patients, higher carotid plaque laterality ratio was associated with ACL, suggesting TEE should be conducted to reveal ACL in ESUS patients with left-dominant carotid plaque.

Background and Purpose: Blood viscosity (BV) is associated with blood stagnation leading to thrombosis. Some polyunsaturated fatty acids (PUFAs) are said to have an antithrombotic effect. First, we aimed to determine the association between BV and the presence of the susceptivity vessel sign (SVS) in patients with cardioembolism (CE) due to atrial fibrillation (AF). Second, we aimed to reveal the association between BV and PUFAs levels. Methods: Consecutive patients with ischemic stroke who met the following inclusion criteria were included: 1) patients with CE, defined by TOAST classification, secondary to AF; 2) onset to door time within 24 h; 3) availability of MRI, including susceptibility-weighted images, obtained at our hospital before IV rt-PA and/or MT; and 4) availability of PUFAs measurements on the day of or the day after the hospital visit. Hematocrit-derived BV at high shear rate (300 sec -1 ) was calculated using the following formula: BV = 1.4175+ 5.878*Ht - 12.98*Ht 2 + 31.964*Ht 3 (Ht = Hematocrit/100). First, we assessed whether BV could be associated with the presence of SVS. Second, we evaluated whether some PUFAs (dihomo-γ-linolenic acid [DGLA], arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid) levels could be the factors associated with BV. Results: We screened 1,720 consecutive ischemic stroke patients and included 137 patients (95 [69%] male, median age 73 years). Of 137, SVS was observed in 83 (61%) patients. In multivariable logistic regression analysis, BV was independently associated with the presence of SVS (odds ratio [OR] 0.391, 95% confidence interval [CI] 0.18-0.86, p = 0.02, Figure). Multiple linear regression analysis revealed a significant positive association between DGLA levels and BV (unstandardized coefficient 0.01, 95% confidence interval 0.01 to 0.02, p < 0.01). Conclusions: Lower BV might be related to the presence of SVS with CE due to AF and DGLA level might be positively associated with BV.

Background and Purpose: Ischemic stroke developed while bathing (ISB) occasionally causes fatal accident. Factors associated with ISB remain unclear. We aimed to estimate the clinical characteristics of ISB, especially the subtype of stroke and the association between cerebral small vessel disease (CSVD) markers. Methods: Consecutive patients with ischemic stroke ≤48 h from onset who underwent MRI during the hospitalization were included. We divided patients into ISB and non-ISB group to analyze differences in clinical characteristics, especially the stroke subtype based on TOAST classification and the association between CSVD markers. The CSVD markers were evaluated by MRI and defined as old lacunes, white matter hyperintensities scale (separately scored by periventricular hyperintensity [PVH] and deep and subcortical white matter hyperintensity), the number of cerebral microbleeds (CMBs) categorized as lobar, deep, and infratentorial lesions, and the scale of enlarged perivascular space in the basal ganglia and centrum semiovale. Results: We screened 2,112 consecutive patients with ischemic stroke including 1,517 patients (1,070 [71%] male, median age 69 years). Of these patients, 52 (3%) were included in ISB group. In univariable analysis, ISB group showed higher frequency of large-artery atherosclerosis ( p = 0.004), lower frequency of cardioembolism ( p = 0.008), smaller number of cerebral microbleeds in deep lesions ( p = 0.025) and lower grade of PVH ( p = 0.023). ISB group showed a lower NIHSS score on admission ( p = 0.002). However, there was no difference in mRS score at 3 months from the onset. In the multivariable analysis (Figure), large-artery atherosclerosis (OR 2.46, 95% CI 1.21-5.01, p = 0.013) and CMBs in deep lesions (OR 0.75, 95% CI 0.58-0.98, p = 0.038) showed independently associated with ISB. Conclusions: ISB showed higher frequency of large-artery atherosclerosis, however, had a less association with the presence of CMBs in deep lesions.

We report a case of anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis following nivolumab treatment. The patient was successfully treated with pulse steroid therapy and high-dose intravenous immunoglobulin, followed by oral glucocorticoid treatment. Immune checkpoint inhibitors, such as nivolumab, may induce not only myositis as an immune-related adverse event but also dermatomyositides as a paraneoplastic syndrome by distracting immune tolerance. Differentiating between pathologies is warranted if patients develop myositis after immune checkpoint inhibitor administration.

Background and Purpose The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Methods Using male Sprague-Dawley rats (n = 14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. Results The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3–8 min). Median infarct volume was 386 mm3 (IQR, 354–420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P

Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity.To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function.Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1 mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19 weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis.In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group.Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

Some patients with Parkinson’s disease (PD) present with pareidolia, an illusion of a meaningless stimulus as a familiar object known to the observer. Since the striatum is associated with processing of visual information, we investigated correlations of pareidolia with motor symptoms and striatal dopaminergic function. A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naive PD patients. A number of images in which a participant noticed an illusory face (number of illusory responses) were compared with motor assessment scores and uptake of 123I-ioflupane in the striatum. Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p

Background and objectives Communication-type medical smartphone applications enable text, neuroimaging, photos, and videos to be shared securely among the stroke team. Our aim was to investigate whether use of a smartphone application would shorten the duration from admission to reperfusion therapy in patients with hyper-acute ischemic stroke. Methods Enrolled were acute ischemic stroke patients who underwent reperfusion therapy (intravenous tissue plasminogen activator (IV t-PA) and mechanical thrombectomy (MT)) at our hospital between October 2012 and September 2018. We divided the patients into two groups based on the date of availability on smartphones of communication-type medical application: (1) Control group, conventional communication prior to September 2015, and (2) App group, communication via the smartphone app from October 2015 onwards. We compared door-to-image time (DIT), image-to-needle time (INT), door-to-needle time (DNT) for thrombolysis, and DIT, image-to-puncture time (IPT), and door-to-puncture time (DTP) for thrombectomy between the groups. Results We retrospectively enrolled 139 patients (68% male; median age, 69 years; median NIHSS score, 7) who were assigned into the App group (n = 86) and Control group (n = 53). Of the overall patients, 109 underwent IV t-PA (IV t-PA alone, 79 patients), and 63 underwent MT (MT alone, 30 patients), and 33 patients underwent combined IV t-PA and MT. There was no significant difference in DIT between the App and Control groups (23 min vs. 22 min, p = 0.493). DNT, DPT, INT, and IPT were significantly shorter in the App group than in the Control group (DNT, 62 min for the App group vs. 72 min for Control group, p = 0.038; INT, 42 vs. 48 min, p = 0.009; DPT, 106 vs. 129 min, p = 0.046; IPT, 89 vs. 117 min, p = 0.004). Conclusion The present findings indicate that communication-type medical smartphone apps have potential for shortening the time elapsed between admission and reperfusion therapy, especially INT and IPT. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05132-2.

Since smartphone applications are revolutionizing telemedicine, a new application specifically for stroke care (JOIN) was designed. Addition of the JOIN smartphone application to the stroke treatment workflow in our hospital was assessed. JOIN has key functions that may improve the care of stroke patients, including the ability to (1) exchange information such as patient data and medical images in real-time throughout the entire process of patient management; (2) track each step of the protocol from door to discharge; and (3) facilitate real-time interaction of all team members via text, audio, and a video chat system. Two periods, 2.7 years before the implementation of JOIN (Pre-JOIN) with 37 patients and 2.2 years after (Post-JOIN) with 54 patients, were compared, and the workflow for all 91 patients who had a cerebral infarction and were treated with tissue plasminogen activator (tPA) and/or thrombectomy between October 2012 and July 2017 was reviewed. There were noticeable reductions in overall patient management time, including times for door-to-imaging, starting tPA treatment, and endovascular intervention with JOIN. Staff members were unanimously satisfied with JOIN, due to the increased efficiency of information exchange and the ability for real-time discussions with different professionals when needed. No significant changes in patient outcomes (as assessed by modified Rankin Scale [mRS] scores) at 3 months and in the total cost for the treatment were observed. A smartphone-based application with the capability of sharing information instantaneously among healthcare professionals facilitated time-sensitive, acute care of ischemic stroke patients.

Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in chronic intracerebral hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate the effects and safety of rTMS in acute spontaneous ICH.We prospectively performed HF-rTMS on consecutive patients with ICH within 24 h from onset between April 2019 and August 2021. The inclusion criterion was (1) persistent paralysis, with an NIHSS scale of 1 or higher for at least 3 days after onset. The exclusion criteria were (1) cortical, subcortical, and cerebellar ICH, (2) disturbance of consciousness, and (3) over 80 years of age. For the purpose of comparison, we used a conventional rehabilitation group whose patients met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. We also compared the two groups regarding clinical background and outcome.Enrolled in the study were a total of 44 patients. Of the patients, 22 (50%) were in the rTMS group. The median (IQR) time from onset to the start of rTMS was 9 (6-12) days. There were no cases of epilepsy or exacerbation of NIHSS after the start of rTMS. Favorable outcome (modified Rankin Scale score of between 0 and 2) at 3 months was frequently observed in the rTMS group (73% vs 27%, p = 0.006). HF-rTMS was independently associated with favorable outcome at 3 months (OR = 11.5, 95% CI = 2.194-60.447, p = 0.004).HF-rTMS may be safe and effective in acute ICH patients.

Aim This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708). Methods A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. Results The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). Conclusions In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P

Objective The presence of deep venous thrombosis (DVT) in a cryptogenic stroke (CS) patient with a right-to-left shunt (RLS) may lead to the development of paradoxical embolism. The aim of the present was to investigate the prevalence of DVT and pulmonary embolism (PE) in CS patients and the clinical features of CS in relation to DVT location and the presence of PE. Methods The medical records of 903 patients with cerebral infarction were retrospectively reviewed. For patients with a diagnosis of CS, contrast saline transcranial color-coded sonography was performed to identify an RLS. DVT and PE were assessed by duplex ultrasonography and/or contrast-enhanced computed tomography. Proximal DVT (P-DVT) was defined as DVT in the popliteal, femoral, or iliac veins, and distal DVT (D-DVT) was defined as DVT at other locations. The patients were divided into three groups: CS with P-DVT and/or PE (P-DVT/PE) group; CS with D-DVT (D-DVT) group; and CS without DVT (no DVT) group. Results Seventy-two (37%) of 194 patients with CS had an RLS. The median time to first DVT examination from stroke onset was three days. Twenty-nine percent of CS patients with an RLS had DVT. The P-DVT/PE group comprised 8.3% of the CS patients with an RLS and included a larger number of patients with multi-territory infarction than the D-DVT group. The D-DVT and P-DVT/PE groups tended to be female and older, while the P-DVT/PE group tended to have pre-stroke disability. Conclusion CS patients, especially those with multi-territory lesions, should be immediately examined for DVT and PE.

Introduction and Objectives: The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. Methods: Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, p = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, p = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0–1 at 3 months from onset). Conclusions: Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.

Background: Lacunar infarct (LI) is a heterogeneous disorder of cerebral small vessel. Hierarchical clustering (HC) is useful for exploring potential underlying clinical phenotype in heterogeneous disease. Our aim is to identify the predictive factors of poor functional outcome in LI to classify the subjects into distinct subgroups using HC and compare the clinical variables including clinical outcome among groups. Methods: From October 2012 to April 2020, LI patients within 24 hours from the onset were enrolled. We used a HC k-means clustering algorithm on patients’ baseline data. We also compared clinical outcome among each cluster groups. Results: Among 187 patients (144 male, median age 66 years old, median NIHSS score2), three clusters were identified. Cluster1(58%), mostly comprised of younger patients (p 2-6 was 4% of cluster1, 100% of cluster 2 and 12% of cluster 3 (p=0.001). In multivariate logistic regression analysis, the phenotype of cluster was the strongest predictor of poor functional outcome (OR 16.1, 95% CI 6.04-42.9, p Conclusion: Three clusters with different clinical outcome were identified. The phenotype of cluster was the strongest predictive factor of poor functional outcome. Further study to identify whether management of these components provide different clinical outcome was warranted.

Background and Purpose: Repetitive transcranial magnetic stimulation (rTMS) in chronic intracranial hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate safety and effects of rTMS in acute ICH. Methods: We prospectively performed high-frequency rTMS to consecutive patients with acute ICH within 24 hours from onset between April 2019 and March 2021. Exclusion criteria were: 1) subcortical ICH; 2) ventricular perforation; 3) history of symptomatic stroke; 4) surgical management for ICH; 5) disturbance of consciousness; 6) over 80 years old at admission; and 7) convulsion after onset. Inclusion criterion was 1) persistent paralysis with a NIHSS scale 1 of higher for at least 3 days after onset. The comparison was made with historical control group; patients who met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of NIHSS score in rTMS group. We also compared clinical background and outcome among groups. Results: A total of 40 patients (29 male, median age 56 years, median NIHSS score on admission 13) were enrolled. Of them, 18 patients (45%) were rTMS group. The median (IQR) time from onset to the start of rTMS is 9 (6-12) days. There were no case of epilepsy or exacerbation of NIHSS after the start of rTMS. There were no significant differences in median age (54 years vs 57 years, p=0.70), median hemorrhage volume at admission (9.3 ml vs 11.3 ml, p=0.43) or median NIHSS score on admission (13 vs 12, p=0.99) among groups. Favorable 90 days outcome (modified Rankin Scale score of 0-2) was frequently observed in rTMS group (67% vs 27%, p = 0.02). Conclusion: High-frequency rTMS may be safe and effective in acute intracranial hemorrhage patients.

Background and Purpose: Recent several studies demonstrated that percutaneous patent foramen ovale (PFO) closure reduced the risk of stroke recurrence for patients with cryptogenic stroke and PFO. Our aim of this retrospective study is to evaluate the usefulness of transcranial color flow imaging (TC-CFI) in the diagnosis of anatomically high risk PFO, in which percutaneous PFO closure is expected to be more effective in preventing embolism. Methods: Subjects were ischemic stroke patients who were investigated the presence of right-to-left shunt (RLS) using TC-CFI and transesophageal echocardiography (TEE). Anatomically high risk PFO evaluated by TEE were defined as satisfying one or more of the following findings: 1) large shunt (more than 20 microbubbles (MB) identified in the left ventricular system), 2) atrial septal aneurism, and 3) the presence of shunt without Valsalva maneuver (VM). TC-CFI was performed in the middle cerebral artery and/or intracranial vertebral artery once without VM and three times with VM, respectively. The number of microembolic signals from MB was determined using international Consensus Criteria (ICC). The accuracy of TC-CFI for high risk PFO diagnosed by TEE was calculated, and then the positive rate of TC-CFI in detecting high risk PFO was also analyzed by TC-CFI’s findings (A: ICC grade II or higher, B: positive without VM, and C: positive on multiple times or in multiple vessels). Results: We analyzed 176 patients (41 females, mean age 64 years) admitted to our facility from July 2019 to July 2021. Of them, 44 patients (25%) had PFO, and 29 patients (16%) were high risk. The diagnostic power of TC-CFI was sufficient, with sensitivity of 93%, specificity of 80%, and accuracy of 89%. The positive rate of each finding was significantly higher in C than in A and B (A: 23%, B: 39%, and C: 55%. P=0.04). Conclusions: To perform the TC-CFI procedure frequently in multiple vessels is useful for screening of high risk PFO.

Background and Purpose: The difference among anterior and posterior circulation stroke regarding vascular risk factors is commonly known. Our aim is to verify the difference of clinical backgrounds between anterior and posterior circulation in hyperacute stroke with large vessel occlusion (LVO) caused by atherosclerotic occlusion (AO). Methods: This multicenter, retrospective study included LVO patients who were performed revascularization therapy (thrombectomy, intravenous thrombolysis, or both) between October 2017 and May 2021. The definition of AO was the fixed residual stenosis/occlusion at the initially occluded lesion confirmed in the second angiographic imaging performed 7 days later from symptom onset. The patients were dichotomized by LVO location, anterior or posterior. Traditional risk factors and laboratory data were compared. Results: Among the 1770 consecutive stroke patients admitted during the study period, 162 patients (104 men, median age 76 years old) were enrolled in our study. AO was diagnosed in 41 patients (25%; 27% of anterior circulation vs. 17% of posterior, P=0.291). In total cohort, patients with anterior circulation showed higher frequency of atrial fibrillation, lower glycosylated hemoglobin level, higher D dimer level, and higher brain natriuretic peptide level (Figure 1 black bar). The cohort of AO patients had a similar tendency (Figure 1 blue bar). Conclusion: One fourth of patients with LVO are AO. In anterior circulation stroke with AO, attention should be paid to stroke recurrence due to not only atherosclerosis but embolism.

Background and Purpose: Our aim is to investigate the factors of outcome in ESUS with possible embolic source (PES) caused by non-high risk cardiac sources, malignancy, and mild atherosclerosis. Methods: Patients were selected from a comprehensive stroke center between April 2013 and April 2021. Inclusion criteria were: 1) consecutive ischemic stroke patients who fulfilled ESUS criteria based on NAVIGATE-ESUS trial, 2) who underwent TEE 3) who admitted our hospital within 7 days from stroke onset 4) pre stroke modified Rankin scale (mRS) score below 1 and 5) available mRS score at 3 months from stroke onset. PES included atrial cardiopathy (large left atrium diameter, slow out flow in left atrium appendage, and frequent premature atrium contraction), left ventricular dysfunction (history of heart failure, abnormal ventricular wall motion, and reduced ejection fraction), cardiac valve disease, right-to-left shunt, malignancy, and atherosclerosis (ipsilateral carotid plaque and aortic complicated lesion). We compared PES, between mRS score 0-1 (favorable outcome group) and mRS score 2-6 (unfavorable outcome group). Results: We screened 1,824 consecutive ischemic stroke patients, including 191 in ESUS patients. 159 (83%) patients were ESUS with PES. Of all, 33 patients had unfavorable outcomes (25 [76%] male, median age 64 years old, Figure A). Higher National Institute of Health Stroke Scale score on admission (OR 4.50, 95%CI 1.96-10.30, p p =0.028) were independently associated with unfavorable outcome (Figure B). Conclusions: Atherothrombotic emboli may contribute to outcome of ESUS with PES.

The susceptibility vessel sign (SVS) on susceptibility-weighted image, a magnetic resonance imaging technique, reveals thrombi as hypointense signals. We aimed to examine the association between polyunsaturated fatty acid (PUFA) levels and the presence of the SVS and its length in cardioembolism due to atrial fibrillation (AF).Consecutive ischemic stroke patients who met the following inclusion criteria were screened: 1) patients with cardioembolism, defined by Trial of ORG 10172 in Acute Stroke Treatment, secondary to AF; 2) onset to door time within 24 h; 3) availability of magnetic resonance images, including susceptibility-weighted images, obtained at our hospital before performing recanalizing therapy; and 4) availability of PUFA measurements on the day of or the day after the hospital visit. We evaluated whether PUFA levels might be associated with the presence of the SVS and its length.We retrospectively screened 1720 consecutive ischemic stroke patients, and included 137 patients (95 (69%) male, median age 73 years) who met the inclusion criteria in the analyses. In binomial logistic regression analysis, lower dihomo-γ-linolenic acid (DGLA) level was associated with the presence of SVS (odds ratio 0.545, 95% confidence interval 0.374 to 0.794, p = 0.002). Multiple linear regression analysis revealed a significant negative association between DGLA levels and SVS length (unstandardized coefficient -7.430, 95% confidence interval -13.256 to -1.603, p = 0.013).Low DGLA level is associated with the presence of SVS and its length in patients with cardioembolism secondary to AF.

Eculizumab, a humanized monoclonal antibody, is a complement inhibitor indicated for refractory generalized myasthenia gravis (MG). However, there are limited data on the safety of eculizumab for MG during coronavirus disease 2019 (COVID-19) infection. We report a case in which eculizumab was continued for MG after contracting COVID-19, followed by a favorable outcome.

To determine the impact of old lacunes and their sites on the prognosis of one-sided supratentorial intracerebral hemorrhage (ICH) by classifying lacunes sites in relation to anatomical structures using MRI.Consecutive patients with one-sided supratentorial ICH ≤72 h from onset to door who underwent MRI were retrospectively included. The sites of old lacunes were categorized as follows: deep subcortical white matter, caudate head, lentiform, posterior limb and genu of the internal capsule, thalamus, and brainstem. We also evaluated all other cerebral small vessel disease markers. An unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 months after onset. We investigated whether old lacunes in particular locations were related to unfavorable outcomes.We included 186 patients with one-sided supratentorial ICH (126 [68%] males, median age 62 years). Of 186 patients, 65 (35%) patients had unfavorable outcomes. Factors associated with unfavorable outcomes were age (OR 2.261, 95% CI 1.332-3.839, p = 0.003), National Institutes of Health Stroke Scale [NIHSS] score at admission (OR 1.175, 95% CI 1.090-1.267, p 0.001), and old thalamic lacunes contralateral to the hematoma (OR 3.805, 95% CI 1.009-14.340, p = 0.048). Patients with old thalamic lacunes contralateral to the hematoma tended to have arm (p = 0.006) and leg (p = 0.011) motor impairment on the paralyzed side at discharge as estimated by the NIHSS score.Old thalamic lacunes contralateral to the hematoma may be related to unfavorable outcomes in ICH.

Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) has been reported as useful to diagnose tuberculous meningitis and hypertrophic pachymeningitis (HP). The case of a 59-year-old woman with impaired vision and an auditory disturbance due to massive intracranial HP is presented. Although acid-fast bacillus cultures and polymerase chain reaction tests for Mycobacterium tuberculosis in the CSF were negative, tuberculous HP was diagnosed clinically because of the high ADA in CSF, and anti-tuberculosis drugs were administered with prednisolone because idiopathic HP (IHP) could not be ruled out. Since the impaired vision worsened with prednisolone reduction despite the continuation of anti-tuberculosis drugs, a dural biopsy was performed, and the patient was diagnosed with IHP. ADA is associated with lymphocyte proliferation and differentiation and increased by activation of cell-mediated immunity. Elevated CSF-ADA might be caused by lymphocyte infiltration in the thickened dura mater.

To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions.Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated.We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI.High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.

The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Using male Sprague Dawley rats (n = 10), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using an X-ray fluoroscopy to establish local occlusion. All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Eight (80%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (20%). The median operating time was 8 min. All rats of occlusion MCA revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 (median 1, interquartile range 1–3) at 24 h after the induction of ischemia. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range 267–333) 24 h after the left MCA bifurcation occlusion. We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable which is well confined within the territory supplied by the MCA, and reproducibility of this model is 80%. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.