Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Iatrogenic cerebral amyloid angiopathy in older adults.

BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.

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.

Harboring Cnm-expressing Streptococcus mutans in the oral cavity relates to both deep and lobar cerebral microbleeds.

BACKGROUND: Cerebral microbleeds (CMBs) influence long-term prognoses of stroke patients. Streptococcus mutans expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm-positive S. mutans with CMBs. METHODS: Acute stroke patients were selected from a single-center registry database. Oral carriage of Cnm-positive or Cnm-negative S. mutans was determined using polymerase chain reaction assays. The associations of Cnm-positive S. mutans with CMB number and specifically the presence of >10 CMBs were examined using quasi-Poisson and logistic regression models, respectively. RESULTS: This study included 3154 stroke patients, of which 428 patients (median [interquartile range] age, 73.0 [63.0-81.0] years; 269 men [62.9%]) underwent oral bacterial examinations. In total, 326 patients harbored S. mutans. After excluding four patients without imaging data, we compared patients with Cnm-positive (n = 72) and Cnm-negative (n = 250) S. mutans. Harboring Cnm-positive S. mutans was independently associated with the presence of >10 CMBs (adjusted odds ratio 2.20 [1.18-4.10]) and higher numbers of deep and lobar CMBs (adjusted risk ratio 1.61 [1.14-2.27] for deep; 5.14 [2.78-9.51] for lobar), but not infratentorial CMBs, after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy. CONCLUSIONS: Harboring Cnm-positive S. mutans was independently associated with a higher number of CMBs in deep and lobar locations. Reducing Cnm-positive S. mutans in the oral cavity may serve as a novel therapeutic approach for stroke.

An autopsy case report of neuronal intermediate filament inclusion disease presenting with predominantly upper motor neuron features.

We describe an autopsy case of neuronal intermediate filament inclusion disease (NIFID), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused-in-sarcoma (FUS) inclusions (FTLD-FUS). A 57-year-old man developed dysarthria and dysphagia. One year and five months later, he was admitted to a hospital, and pseudobulbar palsy and right upper motor neuron signs were observed on examination. Needle electromyography revealed no active or chronic denervation. His neurological symptoms gradually deteriorated, and behavioral alterations occurred. He died of hemoperitoneum secondary to rupture of a ureteric tumor. The total duration of the disease was six years and 10 months. Neuropathologically, the frontal cortex, including the motor cortex, and the pyramidal tract were severely affected, whereas the lower motor neurons in the spinal cord and brainstem were mildly damaged. The striatum and substantia nigra were also severely damaged. Hyaline conglomerate inclusions, neuronal cytoplasmic inclusions with a distinct eosinophilic core (so-called cherry spot), Pick body-like inclusions, and eosinophilic round inclusions were observed in the remaining neurons. Immunohistochemical examination revealed that these inclusions were immunoreactive for FUS. HC inclusions were also immunoreactive for α-internexin and phosphorylated neurofilament protein. FUS-immunoreactive NCIs were abundant in the basal ganglia but not in the hippocampus, in contrast to previously reported NIFID cases. Furthermore, Bunina bodies identified by immunohistochemistry for cystatin C were also observed in the lower motor neurons. Bunina bodies may be present in NIFID. This case confirms the pathological heterogeneity of NIFID and supports the notion of the difference between amyotrophic lateral sclerosis and NIFID.

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.

Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-ß Protein Precursor Transgenic Mice.

A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-ß (Aß) protein in Aß Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aß. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aß deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of Aß-positive vessels × severity of amyloid burden of Aß-positive vessels) were evaluated in the brain of mice aged 15 and 21-23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21-23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann-Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice.

Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study.

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (ß = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (ß = -0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.

Dural arteriovenous fistula manifesting as pontine hemorrhage at the craniocervical junction.

Craniocervical junction (CCJ) dural arteriovenous fistula (DAVF) manifesting as intracerebral hemorrhage is extremely rare. We report the first case of CCJ-DAVF manifesting as pontine hemorrhage. A 69-year-old male presented with a pontine hemorrhage manifesting as a sudden onset of right hemiparesis and dysarthria. Digital subtraction angiography revealed a CCJ-DAVF fed by the meningeal branches of the right vertebral artery. The patient underwent surgical ligation of the cerebral draining veins to prevent re-bleeding. The postoperative course was uneventful. The patient had no neurological deficit after 1 month rehabilitation.

Arterial spin-labeling MR imaging of cerebral hemorrhages.

INTRODUCTION: The purpose of this study is to identify the characteristics of brain perfusion measured by arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cerebral hemorrhages. METHODS: Brain blood flow values (CBF-ASL values) for cerebral and cerebellar hemispheres and segmented cerebral regions were measured by ASL-MRI in 19 putaminal hemorrhage patients and 20 thalamic hemorrhage patients in acute or subacute stages. We assessed the lateralities of CBF-ASL values and the relationships between CBF-ASL values and other imaging findings and clinical manifestations. RESULTS: Both the 19 putaminal hemorrhage patients and the 20 thalamic hemorrhage patients had significantly low CBF-ASL values of the contralateral cerebellum in subacute stage, suggesting that ASL-MRI might delineate crossed cerebellar diaschisis (CCD). Ipsilateral low CBF-ASL values were observed in frontal lobes and thalami with a putaminal hemorrhage and lentiform nuclei, temporal lobes, and parietal lobes with a thalamic hemorrhage, suggesting that ASL-MRI showed the ipsilateral cerebral diaschisis (ICD). In the putaminal hemorrhage patients, the hematoma volume negatively affected both the bilateral cerebellar and cerebral hemispheric CBF-ASL values. In the thalamic hemorrhage patients, a concomitant intraventricular hemorrhage caused low cerebral hemispheric CBF-ASL values. CONCLUSION: The use of ASL-MRI is sensitive to the perfusion abnormalities and could thus be helpful to estimate functional abnormalities in cerebral hemorrhage patients.

Basal ganglia cerebral microbleeds and global cognitive function: the Kashima Scan Study.

BACKGROUND: We previously showed that global cognitive function was associated with deep or infratentorial (D/I) cerebral microbleeds (CMBs) in a Japanese healthy cohort. We continually recruited participates and performed further investigation to focus on the impact of different distributions of D/I CMBs on gradient-echo magnetic resonance imaging on global cognitive function. METHODS: A total of 1392 subjects including subjects without CMBs (n = 1335), with D/I CMBs limited to the basal ganglia (BG; BG group, n = 33), thalamus (thalamus group, n = 14), and infratentorial area (infratentorial group, n = 10) were included in analyses. Subjects with strictly lobar CMBs (n = 43) were excluded, but subjects in the BG, thalamus, and infratentorial groups could also have lobar CMBs. The mini-mental state examination (MMSE) was administered to determine global cognitive function; scores less than 27 or more than 1.5 standard deviations (SDs) below the age-education-related mean were regarded as impaired. RESULTS: In the multivariable logistic regression analyses, hypertension and severe white matter hyperintensities were associated with the BG group and the thalamus group. In multivariable logistic regression analysis of the association between D/I CMBs classification and impaired MMSE score, only the BG group consistently displayed associations with both MMSE score less than 27 (odds ratio [OR], 5.96; 95% confidence interval [CI], 2.08-17.09) and MMSE score more than 1.5 SDs below the age-education-related mean (OR, 3.34; 95% CI, 1.24-8.99). In the BG group, adjusted mean scores of total MMSE and "attention and calculation" were lower compared with subjects without CMBs. CONCLUSIONS: In our study of D/I CMBs, only BG CMBs have strong association with global cognitive function. This association was independent of CMBs in other location.

Associations for progression of cerebral small vessel disease burden in healthy adults: the Kashima scan study.

To investigate the association between vascular risk factors and progression of cerebral small vessel disease (SVD), we conducted a longitudinal study with neurologically healthy cohort composed mostly of middle-aged adults (n = 665, mean age, 57.7 years). Subjects, who had both baseline data of brain health examinations including MRI and follow-up MRI at least 1 year after the baseline MRI, were included this study. The presence of features of SVD, including lacunes, cerebral microbleeds, white matter hyperintensity, and basal ganglia perivascular spaces were summed to obtain "total SVD score" (range, 0-4). Progression of SVD was evaluated among subjects with a total SVD score of ≤ 3 and was defined as a ≥ 1 point increase in that score at follow-up relative to baseline. As the primary analysis, multivariate logistic regression analyses were performed to determine the associations of progression of SVD at baseline. The median follow-up period was 7.3 years and progression of SVD was observed in 154 subjects (23.2%). Even after adjustment with confounders multivariate logistic regression analyses showed that progression of SVD was associated with age (per 10-year increase, odds ratio [OR]: 2.08, 95% confidence interval [CI] 1.62-2.67), hypertension (OR 1.55, 95%CI 1.05-2.29), systolic blood pressure (BP) (per standard deviation [SD] increase, OR 1.27, 95%CI 1.04-1.54), diastolic BP (per SD increase, OR 1.23, 95%CI 1.01-1.50), and mean arterial pressure (per SD increase, OR 1.27, 95%CI 1.04-1.55). Age and high blood pressure appear to play key roles in the progression of cerebral small vessel burden after mid-life.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Stroke scale items associated with neurologic deterioration within 24 hours after recombinant tissue plasminogen activator therapy.

It is unclear when and which neurologic deficits should be examined within 24 hours after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke. Relationships between serial changes in National Institutes of Health Stroke Scale (NIHSS) subscores and neurologic deterioration (ND) within the first 24 hours after therapy were investigated in 43 consecutive patients. The NIHSS score was measured by neurologists 28 times within 24 hours after therapy. Assessments of subscores associated with ND, defined as the first change 4 or more points from baseline, were performed at 15 minutes (most frequent time of the first ND), 120 minutes (median time of the first ND), and 24 hours after therapy. Seventeen of 43 patients (age range, 55-94 years) showed ND. Of the NIHSS subscores, increases in scores for loss of consciousness (15 minutes, P = .001; 120 minutes, P = .026; 24 hours, P = .018) and motor limbs total (15 minutes, P = .014; 120 minutes, P = .031) were related to deterioration. Items such as questions, gaze, visual fields, ataxia, language, dysarthria, and extinction/inattention were not related to deterioration at any time. In conclusion, ND of ischemic stroke patients treated with intravenous rt-PA therapy was frequently seen within 120 minutes after therapy. Items such as loss of consciousness and motor limbs total may be considered indices for monitoring neurologic deficits after therapy.

[A case of atezolizumab- and bevacizumab-induced myositis showing high intensity in the pterygoid muscles, soft palate, and tongue on STIR-MRI].

A 61-year-old woman was treated with atezolizumab plus bevacizumab for hepatocellular carcinoma with peritoneal dissemination. Blood tests revealed elevated creatine kinase (CK) that peaked at 2,657 U/l. After two cycles of atezolizumab plus bevacizumab combination therapy, she complained of progressive dysarthria and dysphagia. Needle electromyography showed myopathic changes. Initial MRI showed high signal intensity in the orbicularis oris muscle, soft palate, tongue, pterygoid muscles, and paravertebral muscles on STIR images. Myositis-specific autoantibodies were not detected. Based on these findings, the patient was diagnosed with immune checkpoint inhibitor-associated myositis. The clinical symptoms improved after administration of oral prednisone, and follow-up MRI showed reduced extent of areas of high signal intensity and almost complete resolution of signal abnormality in the paravertebral muscles. The CK level normalized after 1 months of oral steroid administration. MRI of the head and neck, including the tongue and soft palate, may be useful in diagnosis and for evaluating therapeutic efficiency in cases of bulbar symptoms that occur following the introduction of immune checkpoint inhibitors.

Visualization of axonal and volume currents in median nerve compound action potential using magnetoneurography.

OBJECTIVE: Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials. METHODS: The median nerves of both upper arms of five healthy individuals were investigated. The propagating magnetic field of the action potential was recorded using magnetoneurography, reconstructed into a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes. RESULTS: Reconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conductor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approximately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones. CONCLUSIONS: Magnetoneurography allows the visualization and quantitative evaluation of action currents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings. SIGNIFICANCE: Magnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.

Intravenous Alteplase at 0.6 mg/kg for Unknown Onset Stroke with Prior Antithrombotic Medication: THAWS Randomized Clinical Trial.

AIM: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. METHODS: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication. RESULTS: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication. CONCLUSION: Alteplase appears more beneficial in patients with prior antithrombotic medication.