Hsin-Hsi Tsai

Background: The simplified Edinburgh criteria enable diagnosis of cerebral amyloid angiopathy–associated lobar intracerebral hemorrhage when magnetic resonance imaging is unavailable. However, their applicability to Asian populations, which have higher frequencies of deep perforator arteriopathy, remains uncertain. Methods: We retrospectively analyzed 2 cohorts of patients with spontaneous lobar intracerebral hemorrhage at National Taiwan University Hospital. Patients in the magnetic resonance imaging cohort (2015–2022) who underwent acute computed tomography (CT) and magnetic resonance imaging were classified using the modified Boston criteria. CT imaging predictors were selected by elastic net penalized logistic regression following prespecified clinical exclusions, and a logistic regression model with risk stratification was developed. Bootstrap optimism correction with uniform shrinkage was applied for internal validation. Histopathologic validation was performed in an independent cohort from 2016 to 2023. Results: Eighty‐seven patients were analyzed. The Edinburgh criteria yielded a suboptimal area under the receiver operating characteristic curve of 0.654 (95% CI, 0.547–0.761). The Asian CT criteria (absence of old lacune, cortical involvement, and presence of cortical atrophy) achieved an apparent area under the receiver operating characteristic curve of 0.843 (optimism‐corrected 0.834; DeLong P =0.002 versus Edinburgh). The rule‐in specificity for the high‐risk group was 85.1% (95% CI, 72.3%–92.6%), and the rule‐out sensitivity for the low‐risk group was 85.0% (95% CI, 70.9%–92.9%). Histopathologic validation confirmed a rule‐out sensitivity of 83.3% and a rule‐in specificity of 92.9%. Decision curve analysis demonstrated superior net benefit across threshold probabilities from 2% to 79%. Conclusions: The simplified Edinburgh criteria may have limited applicability for Asian populations. The proposed Asian CT criteria offer improved discrimination and may facilitate CT‐based cerebral amyloid angiopathy diagnosis in Asian patients with lobar intracerebral hemorrhage.

BACKGROUND: The meningeal lymphatic system contributes to hematoma resolution and neurological recovery after intracerebral hemorrhage (ICH). We previously demonstrated that intraperitoneal cilostazol administration promotes dural lymphatic growth and enhances clearance of intracerebrally injected red blood cells; however, the antiplatelet effects of cilostazol raise safety concerns in ICH, potentially limiting clinical translation. Here, we evaluated whether oral cilostazol at clinical-equivalent doses in mice enhances dural lymphatic function and improves outcomes after ICH. METHODS: ICH was induced by collagenase injection to model microvascular rupture. Cilostazol was orally administered to ICH mice at clinically equivalent doses, given at different time points and for varying durations. Prolymphangiogenic effects of cilostazol were examined in healthy in vivo and ex vivo meninges. Flow cytometry and immunofluorescence were performed to assess lymphatic endothelial cell proliferation and dural lymphatic remodeling. Lymphatic function was evaluated by in vivo live imaging and histological analysis of fluorescent tracer drainage. Short- and long-term histopathologic and behavioral outcomes were also evaluated. RESULTS: Oral cilostazol treatment initiated either 3 hours or 3 days after ICH enhanced dural lymphatic coverage and function, accompanied by reduced hematoma volume, neuronal injury, synapse loss, and long-term neurological deficits. Cilostazol increased CD31 ⁺ PDPN ⁺ lymphatic endothelial cells in ex vivo meninges, induced dural lymphatic hyperplasia, and enhanced lymphatic drainage in healthy mice. Both pretreatment and delayed treatment of cilostazol did not increase hematoma volume but rather improved ICH outcomes. CONCLUSIONS: By promoting dural lymphatic remodeling and drainage, cilostazol facilitates hematoma resolution and neurological recovery after ICH. Cilostazol treatment does not exacerbate initial bleeding or provoke hematoma expansion in the experimental ICH. These findings support clinical translation and provide mechanistic and dosing rationale for an ongoing phase II randomized trial (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06504576).

Background: Early etiological diagnosis of cognitive impairment is challenging. Amyloid PET improves diagnostic accuracy but is costly and limited in availability. Plasma phosphorylated tau-217 (p-tau217) has emerged as a scalable, minimally invasive biomarker. Objective: This study aimed to evaluate the diagnostic and prognostic utility of amyloid PET and plasma p-tau217 in older adults with early cognitive impairment. Methods: We prospectively enrolled 100 adults aged ≥ 65 years with mild cognitive impairment or mild dementia. Participants underwent comprehensive clinical evaluation, brain MRI, ¹⁸ F-florbetaben amyloid PET, and plasma p-tau217 analysis. Longitudinal cognitive decline was assessed over a median follow-up of 1.3 years. Results: Amyloid PET was positive in 45% and resulted in diagnostic revision in 39%. Plasma p-tau217 levels were significantly higher in amyloid-positive individuals (1.178 ± 0.652 versus 0.642 ± 0.940 pg/mL, p < 0.001) and accurately identified amyloid positivity (AUC = 0.855). Both amyloid PET positivity (HR = 6.61, 95% CI 2.36–18.50; p < 0.001) and elevated p-tau217 (HR = 4.43, 95% CI 1.83–10.68; p = 0.001) independently predicted faster cognitive decline. Combined biomarker analysis revealed a stepwise risk stratification, with dual-positive individuals showing the most rapid deterioration (global p < 0.001). Among amyloid-positive patients, elevated p-tau217 further distinguished those with faster progression (p = 0.035). Conclusions: Amyloid PET and plasma p-tau217 provide complementary diagnostic and prognostic value. While PET refines etiological diagnosis, p-tau217 serves as a robust predictor of amyloid status and cognitive trajectory. Integrating these biomarkers improves risk stratification and may facilitate patient selection for disease-modifying therapies.

Background and ObjectivesIntracerebral hemorrhage (ICH) is a deadly form of stroke with no established medical treatment to promote hematoma resorption. Cilostazol accelerates hematoma clearance in...

Background: Intracerebral hemorrhage (ICH) survivors are at increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared with population controls; however, little is known about the annual rates and risk factors for MACE. Methods: We searched Medline, Embase, and trial registries systematically in April 2024 for studies of adults with ICH, reporting either a MACE composite outcome or both ischemic and hemorrhagic outcomes, with at least one year of follow-up. We excluded studies limited to secondary ICH or isolated non-ICH intracranial hemorrhages. We used the QUIPS tool to assess studies’ risk of bias. The primary outcome was the rate of MACE. We used a random-effects meta-analysis to estimate the annual event rate (per 100 person-years, expressed as %) for each outcome. We conducted subgroup analyses and meta-regression to explore heterogeneity. Results: We included 26 studies, involving 198,289 ICH survivors. Individual studies’ reported annual rate of MACE ranged 4.2–14.6%. The pooled annual rate of recurrent ICH was 2.1% (95% confidence interval (CI) = 1.7–2.6; 26 studies; I ² = 94%) and of ischemic stroke was 2.0% (95% CI = 1.5–2.7; 24 studies; I ² = 95%). Meta-regression analyses identified one statistically significant association between a higher prevalence of atrial fibrillation and an increased risk of ischemic stroke. Discussion: The rates of recurrent ICH and ischemic stroke were comparable among ICH survivors, but evidence about other MACE outcomes remains limited. An individual participant data meta-analysis is needed to investigate the predictors of MACE outcomes, which may help inform risk stratification and prognosis among ICH survivors.

Background: Spontaneous intracerebral hemorrhage (ICH) is strongly associated with the development of long‐term cognitive impairment and neuropsychiatric symptoms (NPS), particularly affective disturbances including depression and anxiety. Although small vessel disease (SVD) underlies most cases of ICH, the contribution of SVD to persistent affective symptoms and the effects of cognitive dysfunction on NPS remain unclear. Methods: We prospectively recruited 95 survivors of spontaneous ICH (median, 5.7 years post‐ICH) between 2021 and 2025 from stroke clinics using standardized clinical protocols. NPS were assessed using the Neuropsychiatric Inventory Questionnaire. Cognitive status was evaluated; brain magnetic resonance imaging was performed to quantify SVD markers. Logistic regression and mediation analyses were used to examine the associations between SVD burden, affective symptoms, and cognition. Results: Affective symptoms were the most prevalent NPS subsyndrome (37.9%), followed by apathy/vegetative symptoms (32.6%). Patients with affective symptoms showed greater cognitive impairment and higher hypertensive SVD burden, including higher numbers of deep cerebral microbleeds (4.0±5.9 versus 1.2±1.9, P =0.010) and lacunes (47.2% versus 23.7%, P =0.024) than those without affective symptoms. In the multivariable model, deep cerebral microbleeds (adjusted odds ratio, 1.215 [95% CI , 1.03–1.43], P =0.021), but not lacunes, were independently associated with affective symptoms. Mediation analysis revealed that cognitive impairment partially mediated this relationship (indirect effect P =0.012; 35.9% of total effect). Conclusions: Affective symptoms are common long‐term outcomes after ICH; deep perforator arteriopathy, especially with the form of deep cerebral microbleeds, contribute to these symptoms; cognitive dysfunction only partly mediates this association. There is a need to screen NPS and evaluate microvascular pathology to assess emotional health post ICH.

Background: Intracerebral hemorrhage (ICH) is a manifestations of sporadic cerebral small vessel disease, and the survivors are predisposed to higher long-term risks of vascular events. Intracranial carotid artery calcification (ICAC), a potential marker for arteriosclerosis, is a risk factor for stroke but their roles in ICH is unknown. We aimed to investigate the prevalence and morphological subtypes of ICAC and their associations with long-term vascular events in ICH survivors. Materials and methods: Survivors of spontaneous ICH treated at a single center in Taiwan were included. ICAC was assessed by non-contrast CT; morphology was evaluated and categorized as intimal, internal elastic lamina (IEL), or mixed subtype. Patients were followed up for two years. Associations between calcification subtypes and follow-up events (stroke, cardiovascular event, death) were explored using multivariable Cox regression models. Results: Overall, 462 (80.1%) survivors of ICH had ICAC—223 (38.6%) were categorized as IEL calcification, 216 (37.4%) as intimal calcification, and 23 (4.0%) as mixed type calcification—and 115 patients (19.9%) had no calcification. Patients with IEL calcification were older than patients with intimal or no calcification (p < 0.001). Age (p < 0.001), diabetes (p = 0.010), and reduced renal function (p = 0.001) were independently associated with IEL calcification. During 2-years of follow-up, IEL calcification was not associated with a significant difference in the risk of recurrent ICH (HR=2.8 [0.8‒9.7]), but was associated with higher risks of incident ischemic stroke (HR = 9.0 [1.0‒77.4]), vascular mortality (HR = 13.6 [1.7‒1772.4], and all-cause mortality (HR = 13.9 [1.8‒105.8]). Conclusions: ICAC is common among ICH survivors and the subtype of IEL calcification may potentially have prognostic value for long-term vascular events.