Magnetic Resonance Imaging Patterns Revealing Muscle Pathology and Clinical Features in Idiopathic Inflammatory Myopathies.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes, and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features. METHODS: New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics. RESULTS: Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb, and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, p= 0.005), perimysium (OR 6.0, p= 0.014), and fascia (OR 16.9, p< 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, p< 0.001) and Gottron sign (OR 8.05, p= 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, p= 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, p= 0.006) and malignancy (OR 8.49, p= 0.002). CONCLUSION: Muscle MRI holds promise in predicting muscle pathology, disease subtypes, and clinical manifestations of IIMs.

Clinical characteristics, brain magnetic resonance imaging findings and diagnostic approach of the primary central nervous system vasculitis according to angiographic classification.

OBJECTIVES: To determine the diagnostic accuracy for high-resolution vessel wall image (HR-VWI) and brain biopsy according to angiographical classification in patients with primary central nervous system vasculitis (PCNSV). METHODS: We extracted the patients with PCNSV who underwent the complete brain MRI protocol and cerebral vascular image from Cleveland Clinic prospective CNS vasculopathy Bioregistry. The large-medium vessel variant (LMVV) was defined as patients with cerebral vasculature indicating vasculitis in proximal or middle arterial segments, whereas vessel involvements in smaller distal branches or normal angiography were considered as the small vessel variant (SVV). We compared clinical demographics, magnetic resonance imaging (MRI) findings, and diagnostic approaches between two variants. RESULTS: In this case-control study that included 34 PCNSV patients, the LMVV group comprised a total of 11 patients (32.4%), and 23 patients (67.6%) were classified as the SVV group. The LMVV had more strong/concentric vessel wall enhancement on HR-VWI (LMVV: 90% (9/10) vs. SVV: 7.1% (1/14), p<0.001). By contrast, meningeal/parenchymal contrast enhancement lesion was more frequently observed in the SVV group (p=0.006). The majority of SVV was diagnosed by brain biopsy (SVV: 78.3% vs. LMVV: 30.8%, p=0.022). The diagnostic accuracy of the brain biopsy was 100% (18/18) in SVV and 57.1% (4/7) in LMVV, respectively (p=0.015). CONCLUSIONS: Diagnostic approach for PCNSV differs concerning the affected vessel size. HR-VWI is a useful imaging modality for the diagnosis of LMVV. Brain biopsy remains the gold standard for proving PCNSV with SVV but is still positive in almost one-third of LMVV.

Serial vessel wall enhancement pattern on high-resolution vessel wall magnetic resonance imaging and clinical implications in patients with central nervous system vasculitis.

OBJECTIVES: High-resolution vessel wall imaging (HR-VWI) often demonstrates strong and concentric vessel wall enhancement (VWE) in patients with central nervous system vasculitis (CNS-V). However, little is known about follow-up VWE characteristics and monitoring the response to treatments. The aim of this study was to investigate serial VWE patterns and its clinical practice through the management of CNS-V. METHODS: We extracted 9 patients with diagnosed of CNS-V who underwent serial HR-VWI (baseline, 1st follow-up, and 2nd follow-up) from Cleveland Clinic CNS vasculopathy registry. VWE were analysed in 17 intracranial artery segments. VWE was graded on a 3-point scale (0; none, 1; mild/eccentric, and 2; strong/concentric). VWE grade for each arterial segment was summed to create a total VWE score. We investigated the relationship between serial VWE patterns and clinical course. RESULTS: In unique 153 intracranial arterial segments, 39 arteries (25.5%) had strong/concentric VWE on baseline HR-VWI. The positive rates of concentric VWE have decreased to 12.4% (19/153) at 1st follow-up and (10/153) 6.5% at 2nd follow-up, respectively (p<0.001). Mean total VWE scores have significantly decreased over time courses (p=0.034). Two patients had relapse at 1st follow-up image. In relapse cases, mean total VWE scores have worsened at 1st follow-up (baseline:2.0 to 1st follow-up: 6.0). After intensive immunosuppressive treatment, mean VWE scores have improved at 2nd follow-up (1st follow-up: 6.0 to 2nd follow-up: 2.0). CONCLUSIONS: Decreasing contrast VWE at follow-up images may indicate good response to treatment in CNS-V. By contrast, relapse patients might have temporal VWE worsening during the clinical course.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Associated With a Novel In-Frame Mutation in the NOTCH3 Gene in a Japanese Patient.

Here, we report a case involving a 67-year-old Japanese woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel in-frame complex rearrangement in the NOTCH3 gene. The patient had gradually developed cognitive impairment since the occurrence of an ischemic stroke at the age of 53 years. Her mother had a history of stroke and dementia. Fluid-attenuated inversion recovery magnetic resonance imaging of the brain showed hyperintense lesions in the bilateral temporal poles, external capsules, and periventricular white matter accompanied by multiple cerebral microbleeds on T2*-weighted gradient-echo imaging. A novel in-frame mutation (c.598_610delinsAGAACCC) resulting in the loss of Cys201 in the fifth epidermal growth factor-like repeat of NOTCH3 was identified; this led to a diagnosis of CADASIL. In summary, we report a novel pathogenic mutation (NOTCH3 c.598_610delinsAGAACCC; p.Pro200_Ser204delinsArgThrPro) associated with CADASIL. Further investigations should elucidate the genotype-phenotype correlations in patients with this in-frame complex rearrangement.

Safety of Anticoagulant Therapy Including Direct Oral Anticoagulants in Patients With Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (<7 days from onset), spontaneous ICH were retrospectively enrolled from a prospective registry. Whether to start anticoagulation was at the attending physicians' discretion, and thromboembolic or hemorrhagic events during hospitalization were analyzed. A total of 236 patients (80 women [34%]; median age 69 [interquartile range 61-79] years; National Institutes of Health stroke scale score 7 [3-16]) were enrolled. Of them, 47 patients (20%) had an indication for anticoagulant therapy (33 had atrial fibrillation, 14 developed deep vein thrombosis), and 41 of 47 patients (87%) were actually treated with anticoagulant therapy (DOACs were used in 34 patients) after a median of 7 days from ICH onset. There was neither hematoma expansion nor excessive hemorrhagic complications during hospitalization after starting anticoagulant therapy. CONCLUSIONS: Anticoagulant therapy was conducted for approximately 90% of anticoagulation-indicated patients after a median of 7 days from ICH onset. The predominant anticoagulant medications were DOACs. Anticoagulant therapy started from the acute phase of ICH should be safe.

Characteristics of Acute Spontaneous Intracerebral Hemorrhage in Patients Receiving Oral Anticoagulants.

OBJECTIVE: We investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. METHODS: Patients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. RESULTS: Of the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). CONCLUSIONS: DOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

Anticoagulants, Reperfusion Therapy, and Outcomes in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation　- A Single-Center, 6-Year Experience of 546 Consecutive Patients.

BACKGROUND: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period. Methods and Results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively). CONCLUSIONS: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

Insufficient Warfarin Therapy Is Associated With Higher Severity of Stroke Than No Anticoagulation in Patients With Atrial Fibrillation and Acute Anterior-Circulation Stroke.

BACKGROUND: Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF.Methods and Results:From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women; median age, 79 years; IQR, 71-86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients <70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10; OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91; P=0.039) compared with no anticoagulant therapy. CONCLUSIONS: Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

Low Free Triiodothyronine at Admission Predicts Poststroke Infection.

BACKGROUND: Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. METHODS: We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men; age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. RESULTS: We diagnosed 107 patients (20.6%; pneumonia, 65; urinary tract infection, 19; others, 23) with PSIs. While age (P <.001), body mass index (P = .0012), preadmission modified Rankin scale score (P = .0001), National Institutes of Health Stroke Scale score on admission (P <.001), admission FT3 level (P <.001), atrial fibrillation (P <.001), and ischemic heart disease (P = .0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL; P = .0251), Q3 (2.56-2.89 pg/mL; P = .0007), or Q4 (≥2.90 pg/mL; P = .0010) quartiles of FT3 levels. Moreover, low FT3 levels (<2.29 pg/mL) were independently associated with PSI occurrence (P = .0013). CONCLUSIONS: Low FT3 levels at admission are independently associated with PSI occurrence.

Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke.

BACKGROUND AND PURPOSE: The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS: We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS: Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS: Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke.

The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke.

BACKGROUND: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. METHODS: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. RESULTS: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). CONCLUSION: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.

Post Stroke Dysglycemia and Acute Infarct Volume Growth: A Study Using Continuous Glucose Monitoring.

BACKGROUND: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. METHODS: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. RESULTS: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC >140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). CONCLUSION: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke.

Clinical characteristics associated with abnormal diffusion-weighted images in patients with transient cerebral ischemic attack.

BACKGROUND: Precise associations between clinical characteristics of transient ischemic attack (TIA) patients and diffusion-weighted imaging (DWI) positivity are still controversial. Thus, the purposes of this were to investigate the clinical characteristics associated with DWI positivity in patients with TIA and to develop a risk score for the prediction of DWI positivity in TIA. METHODS: Between April 2008 and June 2011, we retrospectively enrolled consecutive patients, who were admitted to our hospital with TIA and underwent DWI within 24 hours of admission. Patients were divided into a DWI-positive or DWI-negative group. The clinical characteristics of the 2 groups were compared, and a DWI positivity score was determined for each patient. We calculated the DWI positivity score by assigning a point value of 1 to the following factors: blood urea nitrogen to serum creatinine (BUN/Cr) ratio greater than 17.5, glucose greater than 161 mg/dL, and brain natriuretic peptide (BNP) greater than 55.4 pg/dL. Values below these cutoffs were given a value of 0, and the 3 point values were summed to obtain the final DWI positivity score (from 0 to 3). RESULTS: A total of 41 patients (median age = 62 years; 8 women) were enrolled in this study. There were 14 (35%) patients with DWI positivity. The median of the BUN/Cr ratio, blood glucose, and BNP were significantly higher in the DWI-positive than that in the DWI-negative group. As the DWI positivity score increased, there was an increased rate of DWI positivity. CONCLUSIONS: Our data indicate that seminal scores that included BUN/Cr ratio, glucose, and BNP contributed to DWI positivity in TIA patients.

Maintenance hemodialysis independently increases the risk of early death after acute intracerebral hemorrhage.

BACKGROUND: It is unknown whether the clinical features and outcomes of intracerebral hemorrhage (ICH) patients who undergo maintenance hemodialysis (HD) at the time of ICH are similar to those of general ICH patients. METHODS: We retrospectively examined the medical records of ICH patients admitted to the Stroke Center of Kawasaki Medical School Hospital within 7 days of ICH onset between April 2004 and June 2011. Patients were classed as HD or non-HD, and clinical characteristics were compared between the two groups. ICH volume was measured on admission CT and follow-up CT scan (< 24 h after admission). Hematoma enlargement was defined as a hematoma that increased by more than 33% of its initial volume. Early death was defined as all-cause death within 14 days of ICH onset. The factors associated with early death were determined using multivariate logistic regression analysis. RESULTS: Five hundred and seven patients (320 males; 69.0 years old, interquartile range 59.0-79.0) were enrolled in the study. Thirty-six (7.2%) were receiving maintenance HD at the time of ICH and formed the HD group, and the remaining 471 patients formed the non-HD group. Use of antithrombotic agents prior to ICH was more common in the HD group than in the non-HD group (41.7 vs. 21.9%; p = 0.012). Brainstem (30.6 vs. 11.3%; p = 0.003) and lobar (19.4 vs. 6.6%; p = 0.013) hematoma locations were more common in the HD group than in the non-HD group. Enlargement of ICH volume was more common in the HD group than in the non-HD group (25.8 vs. 10.2%; p = 0.015). Early death was more common in the HD group than in the non-HD group (33.3 vs. 9.3%; p < 0.001). On the multivariate logistic regression analysis adjusted for age, sex and renal dysfunction, National Institutes of Health Stroke Scale score > 20 [odds ratio (OR) 27.40, 95% confidence interval (CI) 9.69-77.44; p < 0.001], ICH volume > 30 ml (OR 9.53, 95% CI 3.82-23.77; p < 0.001), HD (OR 6.42, 95% CI 1.39-29.76; p = 0.017), the use of antithrombotic agents (OR 3.04, 95% CI 1.22-7.56; p = 0.017) and glucose > 150 mg/dl (OR 2.51, 95% CI 1.01-6.26; p = 0.047) were independent factors associated with early death. CONCLUSION: Maintenance HD is independently associated with early death in ICH patients.

Quantitative CTA vascular calcification, atherosclerosis burden, and stroke mechanism in patients with ischemic stroke.

BACKGROUND: Vascular calcification is recognized as the advanced stage of atherosclerosis burden. We hypothesized that vascular calcium quantification in CT angiography (CTA) would be helpful to differentiate large artery atherosclerosis (LAA) from other stroke etiology in patients with ischemic stroke. METHODS: We studied 375 acute ischemic stroke patients (200 males, mean age 69.9 years) who underwent complete CTA images of the aortic arch, neck, and head. The automatic artery and calcification segmentation method measured calcification volumes in the intracranial internal carotid artery (ICA), cervical carotid artery, and aortic arch using deep-learning U-net model and region-grow algorithms. We investigated the correlations and patterns of vascular calcification in the different vessel beds among stroke etiology by age category (young: <65 years, intermediate: 65-74 years, older ≥75 years). RESULTS: Ninety-five (25.3%) were diagnosed with LAA according to TOAST criteria. Median calcification volumes were higher by increasing the age category in each vessel bed. One-way ANOVA with Bonferroni correction showed calcification volumes in all vessel beds were significantly higher in LAA compared with other stroke subtypes in the younger subgroup. Calcification volumes were independently associated with LAA in intracranial ICA (OR; 2.89, 95% CI 1.56-5.34, P = .001), cervical carotid artery (OR; 3.40, 95% CI 1.94-5.94, P < .001) and aorta (OR; 1.69, 95%CI 1.01-2.80, P = .044) in younger subsets. By contrast, the intermediate and older subsets did not show a significant relationship between calcification volumes and stroke subtypes. CONCLUSION: Atherosclerosis calcium volumes in major vessels were significantly higher in LAA compared to non-LAA stroke in younger age.

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. OBJECTIVE: In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. METHODS: This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. RESULTS: Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. CONCLUSIONS: The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39307.

Clinical characteristics and management of headache in patients with myeloproliferative neoplasms.

Background: Headache is frequently reported as a neurological manifestation of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythaemia. This study sought to clarify the clinical characteristics and response to treatment of headaches in patients with MPNs. Methods: We prospectively studied 137 patients with MPNs. The following information was gathered to assess the features of headache at baseline and at follow-up (>6 months): (1) average duration of headache attacks, (2) number of headache days per month, (3) numerical rating scale (NRS), (4) Headache Impact Test-6 (HIT-6), and (5) Migraine Disability Assessment (MIDAS). We compared those parameters for headaches between the baseline and follow-up interviews according to the management. Results: Thirty-seven (27.0%) patients had headache. The prevalence of headaches gradually decreased with increasing age (Age ≤ 49 years: 61.0%, 50-59 years: 38.5%, 60-69 years: 17.2%, 70-79 years: 5.1%, and ≥80 years: 0.0%, P < 0.001). Multiple logistic regression analysis showed that younger age, but not platelet counts or the JAK2 V617F mutation, was independently associated with headaches (Odds Ratios 2.004, 95% confidence intervals 1.293-3.108, P = 0.002). Scintillating scotomas were present in 22 (59.5%) of 37 patients with headaches, while four patients developed sudden headaches that lasted for only 0-10 min. Follow-up interviews were available for 31 (83.8%) of 37 patients with headaches. Twenty-one (67.7%) patients were treated with low-dose aspirin (100 mg once daily) [low-dose aspirin alone: n = 9; combined cytoreductive therapy: n = 12] for headache management. All parameters for headache [average duration of headache attacks, number of headache days per month, NRS score, HIT-6 score, and MIDAS score (all P < 0.001)] were significantly improved at follow-up in patients taking low-dose aspirin. However, there were no significant differences in these parameters of headaches in patients who did not receive low-dose aspirin. Conclusion: Headaches is common in patients with MPNs, particularly in younger patients. MPN-related headaches may be managed by using low-dose aspirin and controlling MPNs.

[Beneficial effects of rituximab in a case of anti-myelin antibody-associated neuropathy].

We report here in a 61-year-old woman in whom sensory disturbance predominantly affecting the distal portion of the limbs progressed over the course of 1 year. Blood tests showed IgM monoclonal gammopathy as well as the presence of anti-myelin-associated glycoprotein (MAG) antibody. Nerve conduction studies revealed significant prolongation of distal latency, and sural nerve biopsy showed IgM deposition on the myelin sheath. She was diagnosed as suffering anti-MAG neuropathy. High-dose intravenous immunoglobulin therapy proved to be ineffective and her symptoms progressed. Therefore, rituximab was administered and the sensory disturbance improved. Although no detailed studies on rituximab therapy for anti-MAG neuropathy have been reported in Japan, the present findings suggest that rituximab may be more effective than immunoglobulin therapy and other conventional therapies that have been used for autoimmune neuropathies.

Neuromyelitis optica spectrum disorder with deafness and an extensive brainstem lesion.

A 49-year-old woman developed vomiting, hiccups, double vision, and bilateral ptosis, after which tinnitus and deafness appeared. Head magnetic resonance imaging (MRI) showed a brainstem lesion focused on the midbrain and pons. Anti-aquaporin 4 (AQP4) antibody was positive, and there was no evidence of optic neuritis or myelitis, leading to the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The auditory brainstem response (ABR) showed no derivation of wave V on left stimulation and extended latency between waves III and V on right stimulation, so impairment between the midbrain and pons was suspected. It was useful to evaluate head MRI and the ABR for identification of the location of auditory pathway dysfunction.