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Cerebral microbleeds (MBs) have been found in patients with cognitive decline. We aimed to examine whether MBs are associated with motor or cognitive decline in patients with Parkinson’s disease (PD). We enrolled 135 PD patients and 34 healthy controls. All participants underwent brain MRI and plasma biomarker assays, including tau, Aβ42, Aβ40, and α-synuclein. PD with dementia (PDD) was operationally defined as Mini-Mental State Examination (MMSE) score < 26 and advanced motor stage was defined as Hoehn-Yahr stage ≥ 3 during “on” status. The association between MBs and disease severity was examined using multivariate logistic regression models. More lobar MBs were observed in PD patients than controls (20.7% vs. 3.3%, p  = 0.031). PDD patients had more lobar MBs (33.3% vs. 15.6%, p  = 0.034), more white matter hyperintensity ( p  = 0.021) and reduced hippocampal volume ( p  = 0.001) than PD with normal cognition. The presence of lobar MB (odds ratio = 2.83 [95% confidence interval 1.04–7.70], p  = 0.042) and severe white matter hyperintensity (3.29 [1.21–8.96], p  = 0.020) was independently associated with PDD after adjusting for vascular risk factors and other confounders. Furthermore, plasma Aβ40 levels were associated the MMSE score ( p  = 0.004) after adjusting for age and sex. Our findings demonstrated that lobar MBs, reduced hippocampal volume, and elevated plasma Aβ40 levels are associated with PDD.

Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days 5 and 7 post SAH. Furthermore, treatment of cultured rat fetal NSCs with the CSF collected from rats on days 5 and 7 post SAH enhanced their proliferation, differentiation, and migration. Enzyme-linked immunosorbent assay (ELISA) of the CSF detected a marked increase in the concentration of brain-derived neurotrophic factor (BDNF). Treating the cultured NSCs with recombinant BDNF (at the same concentration as that in the CSF) or with CSF from SAH rats, directly, stimulated proliferation, differentiation, and migration to a similar extent. BDNF expression was upregulated in the SVZ of rats on days 5 and 7 post SAH, and BDNF release occurred from NSCs, astrocytes, and microglia in the SVZ. These results indicate that SAH triggers the expression of BDNF, which promotes the proliferation, differentiation, and migration of NSCs in the SVZ after SAH.

In-hospital stroke (IHS) is an uncommon but serious medical emergency. Early recanalization through endovascular thrombectomy (EVT) may offer a vital therapeutic choice. This study compared the clinical features and outcomes between IHS and community-onset stroke (COS). From a single-center registry of 2813 patients with ischemic stroke, those who had received EVT for acute ischemic stroke were included and classified into the IHS and COS groups based on their stroke onset scenario. We compared the outcomes including successful recanalization, symptomatic intracranial hemorrhage, functional independence (modified Rankin Scale score, 0-2) at 90 days, and mortality between the two groups. A total of 24 patients with IHS (mean age, 70 years; 54% men) and 105 patients with COS (mean age, 73 years; 47% men) were included. The most frequently reported reasons for admission in patients with IHS were cardiovascular and oncological diseases. The initial National Institutes of Health Stroke Scale (NIHSS) scores and main occluded vessels were similar between the two groups. Patients with IHS received a higher number of active malignancy diagnoses, were more likely to withhold antithrombotic agents, and exhibited higher prestroke functional dependency. The median onset-to-puncture time was 192 min in IHS and 217 min in COS (P = 0.15). The percentages of successful recanalization (79% vs 71%), symptomatic hemorrhage (0% vs 9%), functional independence (42% vs 40%), and mortality (17% vs 12%) were comparable between the two groups. After adjustment for covariates, initial NIHSS scores and successful recanalization were the most important predictors for functional independence at 90 days. Despite having disadvantages at baseline, patients with IHS could still benefit from timely EVT to achieve favorable outcomes. A well-designed acute stroke protocol tailored for IHS should be developed.

To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH). Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models. PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR] = 15.7 [3.0-80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR = 6.2 [1.9-20.0], p = .002). In the non-CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6-95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6-20.3], p = .008) after adjusting for confounders. Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH.

Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with \"Stroke Code\" (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. The study period was divided into the \"pre-SC era\" (January 2006 to July 2010) and \"SC era\" (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.

In Pompe disease, deficient lysosomal acid α-glucosidase (GAA) activity causes glycogen accumulation in the muscles, which leads to weakness, cardiomyopathy, and respiratory failure. Although glycogen accumulation also occurs in the nervous system, the burden of neurological deficits in Pompe disease remains obscure. In this study, a neuron-specific gene therapy was administered to Pompe mice through intracerebroventricular injection of a viral vector carrying a neuron-specific promoter. The results revealed that gene therapy increased GAA activity and decreased glycogen content in the brain and spinal cord but not in the muscles of Pompe mice. Gene therapy only slightly increased the muscle strength of Pompe mice but substantially improved their performance on the rotarod, a test measuring motor coordination. Gene therapy also decreased astrogliosis and increased myelination in the brain and spinal cord of Pompe mice. Therefore, a neuron-specific treatment improved the motor coordination of Pompe mice by lowering glycogen accumulation, decreasing astrogliosis, and increasing myelination. These findings indicate that neurological deficits are responsible for a significant burden in Pompe disease.

BackgroundTau pathology is observed in cerebral amyloid angiopathy (CAA) and is related to cognitive impairment and neurodegeneration. However, the relationship between tau pathology and amyloid accumulation in the vasculature is unknown. We aimed to assess if regional associations exist between vascular amyloid and tau protein in sporadic CAA.MethodWe assessed cerebral amyloid and hyperphosphorylated tau in patients with probable CAA or Alzheimer’s disease (AD) using 11C-Pittsburgh compound B (PiB) and 18F-T807 positron emission tomography (PET). PET data for each region of interest were extracted using an automated anatomical labelling atlas. We generated correlation matrices to investigate the regional correlations between PiB and T807 uptake, which were further adjusted for multiple comparisons. We evaluated if the severity of regional cortical superficial siderosis (cSS) mediates these associations.Results67 patients with CAA (38 with intracerebral haemorrhage and 29 with cognitive impairment) and 21 patients with AD were included. Significant correlations between amyloid and tau PET uptake were observed in regions of interest for the temporal, parietal and occipital lobes in CAA (adjusted p<0.05); these correlations were not observed in AD. In CAA, the severity of regional cSS correlated positively with T807 uptake in the temporal (β=0.108, 95% CI 0.030 to 0.186, p=0.007) and occipital lobes (β=0.088, 95% CI 0.008 to 0.168, p=0.032). Regional cSS showed no mediating effect on the association between PiB and T807 in the occipital and temporal lobes.ConclusionsIn CAA, tau pathology exhibits significant regional in situ correlations with amyloid deposition in the posterior brain, which suggests a distinct pathophysiology to AD.

Objective F‐18‐fluorothymidine (FLT) is a positron emission tomography (PET) tracer for imaging cell proliferation in vivo. We aimed to assess FLT uptake as a marker for cerebral cell proliferation in a rat model of ischemic stroke and patients with cerebral infarct, correlating with disease severity and outcomes. Methods Cerebral FLT PET was performed in rats subjected to transient middle cerebral artery occlusion (MCAO) and patients with cerebral infarct. PET data were analyzed and expressed as average standardized uptake value ratios (SUVRs) using cerebellar cortex as reference. Infarct volume was analyzed by 2,3,5‐triphenyltetrazolium chloride staining in rats and by magnetic resonance imaging in patients. Neurological function was assessed using modified Neurological Severity Score (mNSS) for rats and National Institutes of Health Stroke Scale (NIHSS) for patients. Results Seven days post‐MCAO, rats' FLT PET displayed higher SUVRs in the infarcted brain, declining gradually until Day 28. FLT‐binding ratio (SUVR in the infarcted brain divided by that in contralateral side) correlated positively with stroke severity (p < 0.001), and to early mNSS decline in rats with mild to moderate stroke severity (p = 0.031). In 13 patients with cerebral infarct, FLT PET showed high SUVR in the infarcted regions. FLT‐binding ratio correlated positively with infarct volume (p = 0.006). Age‐adjusted initial NIHSS (p = 0.035) and early NIHSS decline (p = 0.076) showed significance or a trend toward positive correlation with the FLT‐binding ratio. Interpretation In vivo FLT PET detects poststroke cerebral cell proliferation, which is associated with stroke severity and/or outcomes in MCAO rats and patients with cerebral infarct.

Objective Despite celecoxib, a cyclooxygenase‐2 inhibitor, promoting functional recovery from intracerebral hemorrhage (ICH) by reducing inflammation‐mediated perihematomal edema in rat models, the evidence of its effects on patient outcomes remains limited. As nonsteroidal anti‐inflammatory drugs (NSAIDs) alleviate inflammation by inhibiting cyclooxygenase‐2, this study aimed to assess the impact of non‐aspirin NSAIDs on ICH outcomes. Methods Patients with acute ICH admitted to our hospital between January 2015 and December 2020 were prospectively enrolled and retrospectively categorized based on pre‐ or post‐ICH use of non‐aspirin NSAIDs. Outcomes were assessed using the modified Rankin Scale (mRS) score at 3 months, survival at 1 year, and mortality at long‐term follow‐up. Results Among 976 patients with acute ICH, 2.0% and 15.0% were non‐aspirin NSAID users before and after ICH, respectively. Post‐ICH non‐aspirin NSAID use was associated with a reduced 1‐year mortality risk (adjusted odds ratio [aOR] 0.30, p = 0.001) and long‐term mortality risk (adjusted hazard ratio 0.56, p = 0.043), but not good functional outcomes (mRS 0–2) (aOR 0.98, p = 0.940). In the subgroup analyses, post‐ICH use might be linked to good functional outcomes in patients with lobar hemorrhage or in those without surgical intervention. Pre‐ICH non‐aspirin NSAID use was not associated with these outcomes in the overall population, but it might be linked to increased mortality in subgroups with lobar hemorrhage, cerebral amyloid angiopathy, hyperlipidemia, or without intraventricular hemorrhage. Interpretation The post‐ICH use of non‐aspirin NSAIDs reduced mortality. Future studies are warranted to identify specific non‐aspirin NSAID regimens that can significantly improve the outcomes of patients with ICH.

The cerebral hypoperfusion caused by chronic progressive stenosis or occlusion of intracranial arteries in moyamoya disease can be treated by direct bypass or indirect revascularization procedures. The extent of collaterals from the external carotid artery (ECA) after indirect revascularization surgery is the key point of angiographic follow-up, and the invasiveness of angiography impelled us to investigate the role of ultrasonography in the evaluation of collaterals. We hypothesized that the collaterals shown on angiography might produce corresponding hemodynamic changes in color Doppler ultrasonography. We prospectively recruited moyamoya patients who underwent indirect revascularization surgery and received both preoperative and postoperative angiography and color Doppler ultrasound studies. The collaterals on angiography were graded according to Matsushima method. A total of 21 patients (age, 17 ± 10.2 years) with 24 operated hemispheres were enrolled. Patients who showed better collateral establishment by angiography had higher end-diastolic velocity (EDV), lower resistance index (RI), and larger flow volume in the superficial temporal artery (STA) and ECA (all p < 0.05). In STA, increase of EDV greater than 13.5 cm/sec or reduction of RI greater than 0.19 after operation corresponded to 94% of Matsushima grade A+B. In ECA, post-operative EDV greater than 22 cm/sec or increase of EDV greater than 6.4 cm/sec also corresponded to 94% of Matsushima grade A+B. Our findings revealed potential roles of color Doppler ultrasonography in identifying patients with poor collaterals after indirect revascularization procedures.