A 38-Year-Old Woman With REM Predominant Central Sleep Apnea After Bulbar Infarction.

CASE PRESENTATION: A 38-year-old previously healthy woman was referred to our sleep center for recurrent witnessed breathing arrest during sleep. She had been brought to the ED 3 months earlier because of sudden onset of dizziness with nausea and vomiting, numbness and weakness of the left limb, less clear speech, double vision, dysphagia, and choking cough while drinking water. Brain MRI showed an acute cerebral infarction in the left medulla oblongata (Fig 1). High-resolution MRI showed vertebral artery dissection (Fig 2). Antiplatelet aggregation, lipid reduction, plaque stabilization, and trophic nerve treatments were administered, and the left limb strength, speech, and swallowing function improved. She complained of poor sleep and difficulties with memory.

Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

Metabolic Imaging of Acute Ischemic Stroke (PET, 1Hydrogen Spectroscopy, 17Oxygen Imaging, 23Sodium MRI, pH Imaging).

Acute stroke imaging plays a vital and time-sensitive role in therapeutic decision-making. Current clinical workflows widely use computed tomography (CT) and magnetic resonance (MR) techniques including CT and MR perfusion to estimate the volume of ischemic penumbra at risk for infarction without acute intervention. The use of imaging techniques aimed toward evaluating the metabolic derangements underlying a developing infarct may provide additional information for differentiating the penumbra from benign oligemia and infarct core. The authors review several modalities of metabolic imaging including PET, hydrogen and oxygen spectroscopy, sodium MRI, and pH-weighted MRI.

Glycated serum protein is independently associated with progressive infarction in patients with acute ischemic stroke.

OBJECTIVE: This study investigated the relationship between glycated serum protein (GSP) and progressive infarction (PI). METHODS: From April 2017 to December 2020, we recruited 477 patients within 48 hours after the onset of acute ischemic stroke into this case-control study. Demographic characteristics, clinical information, and laboratory and neuroimaging data were recorded after admission. RESULTS: PI occurred in 144 (30.8%) patients. Patients with PI had higher initial National Institute of Health Stroke Scale (NIHSS) scores, higher discharge NIHSS scores, higher modified Rankin scale scores at 3 months after onset, higher GSP levels, lower prothrombin times, and lower creatinine levels than patients without PI. The likelihood of PI increased with increases in the GSP quartile. Multiple regression analysis revealed that high GSP levels (>2.14 mmol/L) were independently associated with PI. Subgroup analyses identified high GSP levels as an independent predictor of PI in patients with large artery atherosclerosis (third quartile: odds ratio [OR] = 3.793; 95% confidence interval [CI] = 1.555-9.250; fourth quartile: OR = 2.675; 95% CI = 1.056-6.776) and anterior circulation small vessel occlusion (fourth quartile: OR = 13.859; 95% CI = 2.024-94.885). CONCLUSIONS: GSP might be an independent predictor for PI in certain patients with acute ischemic stroke.

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging.

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Estimation of prognosis in patients after decompressive craniectomy after malignant hemispheric infarction: multifactorial scoring scale.

BACKGROUND: Patient's age is considered to be one of the most relevant factors in selecting surgical candidates for decompressive hemicraniectomy after malignant hemispheric infarction. However, questions about surgical indication in older patients, patients with consciousness disorder or patients with large infarctions remain unanswered. OBJECTIVE: Our aim was to design a multifactorial scoring scale based on a combination of patient-specific factors in order to optimize the assessment of prognosis in patients after hemicraniectomy malignant strokes. METHODS: In this prospective observational study with a one-year follow-up, we assessed clinical and imaging data of patients who underwent decompressive hemicraniectomy due to malignant brain infarction. Barthel index was used as a single outcome measure to distinguish favorable vs. unfavorable outcomes. Associations between multiple variables and clinical outcome were assessed. Subsequently, a design of a predictive scoring system was proposed. RESULTS: Age of the patient, preoperative level of consciousness, midline shift, and volume of infarction showed a significant association with postoperative Barthel index. According to the identified factors, a multifactorial prognostic scoring system was introduced, aimed to distinguish between favorable and unfavorable outcomes. Using ROC analysis, it has achieved an AUC of 0.74 (95%CI 0.58‒0.89, p=0.01)CONCLUSIONS: Prediction of postoperative outcome should be based on multiple variables. Our scale, based on the clinical and imaging data, can be used during decision-making to estimate potential benefit of decompressive craniectomy in patients after malignant brain infarction (Tab. 5, Fig. 1, Ref. 32). Text in PDF www.elis.sk Keywords: decompressive hemicraniectomy, malignant hemispheric infarction, indication, outcome, prediction.

Multiscale X-ray phase-contrast CT unveils the evolution of bile infarct in obstructive biliary disease.

Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.

Transverse spinal cord infarction following immunoglobulin treatment in a patient with exfoliative dermatitis: A case report.

RATIONALE: Transverse spinal cord infarction (SCI) is rare but highly disabling. Aortic thrombosis was described as one of the most common etiologies. Thromboembolic complications associated with intravenous immunoglobulin (IVIG) have been reported. PATIENT CONCERNS: A previously well, 64-year-old man who was given the treatment of IVIG (0.4 g/kg/d for 5 days) for exfoliative dermatitis 2 weeks before, progressively developed flaccid paraplegia of lower extremities, loss of all sensations below T3 level and urinary incontinence within 50 minutes. DIAGNOSES: A diagnosis of SCI and pulmonary embolism was made. IVIG was considered the possible cause. INTERVENTIONS: Anticoagulation treatment and continuous rehabilitation were administered. OUTCOMES: The neurologic deficiency of the patient was partially improved at the 3-year follow-up. LESSONS: The rapid development of severe deficits within 4 hours mostly contributes to the diagnosis of SCI. Heightened awareness of possible thrombotic events is encouraged for a month-long period following IVIG therapy.

Brain frailty associated with stroke events in anterior circulation large artery occlusion.

OBJECTIVE: To investigate the factors associated with brain frailty and the effect of brain frailty in patients with anterior circulation large artery occlusion (AC-LAO). METHODS: 1100 patients with AC-LVO consecutively admitted to the Second Hospital of Hebei Medical University, North China between June 2016 and April 2018 were retrospectively analyzed. The variables associated with brain frailty and stroke outcome were analyzed by ANOVA analysis, the Mann-Whitney U test and multiple linear regression. Based on previous research. Brain frailty score comprises 1 point each for white matter hyperintensity (WMH), old infarction lesions, and cerebral atrophy among 983 participants with baseline brain magnetic resonance imaging or computed tomography. RESULTS: Among AC-LAO participants, baseline brain frailty score ≥ 1 was common (750/983, 76.3%). Duration of hypertension > 5 years (mean difference [MD] 0.236, 95% CI 0.077, 0.395, p = 0.004), multiple vessel occlusion (MD 0.339, 95% CI 0.068, 0.611, p = 0.014) and basal ganglia infarction (MD -0.308, 95% CI -0.456, -0.160, p < 0.001) were independently associated with brain frailty score. Brain frailty score was independently associated with stroke events, and higher brain frailty scores were associated with higher rates of stroke events (p < 0.001). However, brain frailty has no independent effect on short-term outcome of ACI in AC-LAO patients. CONCLUSIONS: In AC-LAO patients, older age, duration of hypertension > 5 years, and multiple vessel occlusion influenced the brain frailty score. Brain frailty score was independently associated with the occurrence of stroke events in AC-LAO patients.

[Colchicine alleviates myocardial ischemia-reperfusion injury in mice by activating AMPK].

OBJECTIVE: To investigate the protective effect of colchicine against myocardial ischemia-reperfusion injury (I/R) and explore the underlying mechanism. METHODS: H9C2 cells exposed to hypoxia/reoxygenation (H/R) were treated with 3 nmol/L colchicine, after which the changes in cell viability were assessed using MTT assay, and AMPK phosphorylation, the expressions of NOX4, NRF2, SOD2, BAX, Bcl-2, and cleaved caspase-3 were detected with Western blotting. Male C57BL/6 mice were randomized into sham operation, I/R, I/R+colchicine, and I/R+colchicine+dorsomorphin (DSMP) groups. After the treatments, myocardial expressions of p-AMPK/AMPK, 8-OHdG, cleaved caspase-3, mitochondrial BAX (Mito-BAX), and cytoplasmic cytochrome C (Cyt-Cyto C) were examined and cardiac functions, infarct area, ATP content, and serum levels of lactic dehydrogenase (LDH) and cardiac troponin T (cTnT) levels were assessed. RESULTS: In H9C2 cells, H/R exposure significantly reduced AMPK phosphorylation and expressions of NRF2, SOD2, and Bcl-2, lowered cell viability, and up-regulated the expressions of NOX4, BAX, and cleaved caspase-3 (P < 0.05), and these changes were obviously alleviated by colchicine treatment (P < 0.05). In the mouse models, myocardial I/R injury significantly reduced myocardial AMPK phosphorylation level, ATP content, and expressions of NRF2, SOD2 and Bcl-2, caused cardiac function impairment, enhanced NOX4, Mito-BAX, Cyt-Cyto C, BAX, 8-OHdG, and cleaved caspase-3 expressions, and increased infarct area and serum LDH and cTnT levels (P < 0.05). Colchicine treatment significantly reversed the damaging effects of I/R (P < 0.05), but its protective effects was obviously antagonized by DSMP (P < 0.05). CONCLUSION: Colchicine alleviates myocardial I/R injury and protects cardiac function in mice by reducing myocardial oxidative stress and apoptosis via activating AMPK.

What Is a Meaningful Difference When Using Infarct Volume as the Primary Outcome?: Results From the HERMES Database.

BACKGROUND: Ischemic stroke lesion volume at follow-up is an important surrogate outcome for acute stroke trials. We aimed to assess which differences in 48-hour lesion volume translate into meaningful clinical differences. METHODS: We used pooled data from 7 trials investigating the efficacy of endovascular treatment for anterior circulation large vessel occlusion in acute ischemic stroke. We assessed 48-hour lesion volume follow-up computed tomography or magnetic resonance imaging. The primary outcome was a good functional outcome, defined as modified Rankin Scale (mRS) scores of 0 to 2. We performed multivariable logistic regression to predict the probability of achieving mRS scores of 0 to 2 and determined the differences in 48-hour lesion volume that correspond to a change of 1%, 5%, and 10% in the adjusted probability of achieving mRS scores of 0 to 2. RESULTS: In total, 1665/1766 (94.2%) patients (median age, 68 [interquartile range, 57-76] years, 781 [46.9%] female) had information on follow-up ischemic lesion volume. Computed tomography was used for follow-up imaging in 83% of patients. The median 48-hour lesion volume was 41 (interquartile range, 14-120) mL. We observed a linear relationship between 48-hour lesion volume and mRS scores of 0 to 2 for adjusted probabilities between 65% and 20%/volumes <80 mL, although the curve sloped off for lower mRS scores of 0-2 probabilities/higher volumes. The median differences in 48-hour lesion volume associated with a 1%, 5%, and 10% increase in the probability of mRS scores of 0 to 2 for volumes <80 mL were 2 (interquartile range, 2-3), 10 (9-11), and 20 (18-23) mL, respectively. We found comparable associations when assessing computed tomography and magnetic resonance imaging separately. CONCLUSIONS: A difference of 2, 10, and 20 mL in 48-hour lesion volume, respectively, is associated with a 1%, 5%, and 10% absolute increase in the probability of achieving good functional outcome. These results can inform the design of future stroke trials that use 48-hour lesion volume as the primary outcome.

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

BACKGROUND: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. METHODS: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC. RESULTS: Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). CONCLUSIONS: FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.

High-density cortical µECoG arrays concurrently track spreading depolarizations and long-term evolution of stroke in awake rats.

Spreading depolarizations (SDs) are widely recognized as a major contributor to the progression of tissue damage from ischemic stroke even if blood flow can be restored. They are characterized by negative intracortical waveforms of up to -20 mV, propagation velocities of 3 - 6 mm/min, and massive disturbance of membrane ion homeostasis. High-density, micro-electrocorticographic (µECoG) epidural electrodes and custom, DC-coupled, multiplexed amplifiers, were used to continuously characterize and monitor SD and µECoG cortical signal evolution in awake, moving rats over days. This highly innovative approach can define these events over a large brain surface area (~ 3.4 × 3.4 mm), extending across the boundaries of the stroke, and offers sufficient electrode density (60 contacts total per array for a density of 5.7 electrodes / mm2) to measure and determine the origin of SDs in relation to the infarct boundaries. In addition, spontaneous ECoG activity can simultaneously be detected to further define cortical infarct regions. This technology allows us to understand dynamic stroke evolution and provides immediate cortical functional activity over days. Further translational development of this approach may facilitate improved treatment options for acute stroke patients.

Hypointense signal lesion on susceptibility-weighted imaging as a potential indicator of vertebral artery dissection in medullary infarction.

Vertebral artery dissection (VAD) is often associated with medullary infarction; however, an underlying cause may be underestimated. This study aimed to assess the diagnostic potential of hypointense signal lesions along the arterial pathways using susceptibility-weighted imaging (SWI) as a feasible indicator of VAD in medullary infarction. A retrospective analysis was conducted using clinical data, brain magnetic resonance imaging, and angiography records of 79 patients diagnosed with medullary infarction between January 2014 and December 2021. Patients were categorized into an angiography-confirmed dissection group and a non-dissection group based on imaging findings. A new possible dissection group was identified using SWI, including cases with hypointense signals along the arteries without calcification or cardioembolism. We compared the clinical characteristics of the two groups before and after the addition of the hypointense signal as a marker of VAD. The angiography-confirmed dissection group included 12 patients (15%). Among patients lacking angiographic VAD evidence, 14 subjects displayed hypointense signals on SWI: nine patients along the vertebral artery and five subjects at the posterior inferior cerebellar artery without calcification or cardioembolism. The newly classified dissection group was younger, had a lower prevalence of diabetes mellitus and stroke history, and revealed increased headaches compared to the non-dissection group. Hypointense signal detection on SWI in medullary infarctions shows promise as a diagnostic indicator for VAD. Suspicion of VAD is needed when the hypointense signal on SWI is noted, and considering different treatment strategies with angiographic follow-up will be helpful.

Thrombolysis increases the risk of persistent headache attributed to ischemic stroke: A prospective observational study.

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.

Deviation From Personalized Blood Pressure Targets Correlates With Worse Outcome After Successful Recanalization.

BACKGROUND: Personalized blood pressure (BP) management for patients with acute ischemic stroke after successful endovascular thrombectomy lacks evidence. We aimed to investigate whether the deviation of BP from cerebral autoregulation limits is associated with worse outcomes. METHODS AND RESULTS: We determined autoregulation by measuring mean velocity index and calculated the percentage of time and the burden (defined as the time-BP area) with BP outside the autoregulatory limits of each subject within 48 hours after endovascular thrombectomy. In total, 91 patients with large vessel occlusion stroke who had achieved successful recanalization were prospectively enrolled between May 2020 and February 2022. The burden with BP outside the autoregulatory limits was associated with poor outcome (modified Rankin Scale score 3-6) at 90 days (adjusted odds ratio, 1.28 [95% CI, 1.03-1.59]). The percentage of time with BP out of the autoregulatory limits was correlated with early neurological deterioration (National Institute of Health Stroke Scale scores increased ≥2 at 7 days) (adjusted odds ratio, 1.38 [95% CI, 1.04-1.83]). The burden of BP that decreased below the autoregulatory lower limit was associated with significant infarct growth (volume of infarct growth >11.6 mL) at 7 days (adjusted odds ratio, 1.21 [95% CI, 1.01-1.44]). The percentage of time that BP exceeded the autoregulatory upper limit was associated with symptomatic intracranial hemorrhage within 48 hours (adjusted odds ratio, 1.55 [95% CI, 1.02-2.34]). CONCLUSIONS: Both the percentage of time and the burden of BP that deviates from the autoregulation-preserved range are associated with unfavorable clinical outcomes. This study highlights the potential benefits of autoregulation-guided BP management strategy after successful recanalization.

Fibrinogen deposition promotes neuroinflammation and fibrin-derived γ377-395 peptide ameliorates neurological deficits after ischemic stroke.

BACKGROUND: Fibrin(ogen) deposition in the central nervous system (CNS) contributes to neuropathological injury; however, its role in ischemic stroke is unknown. In this study, we identified fibrinogen as a novel proinflammatory regulator of post-stroke neuroinflammation and revealed the neuro-protection effect of fibrin-derived γ377-395peptide in stroke. METHODS: Fibrinogen depletion and fibrinogen-derived γ377-395peptide treatment were performed 2 h after establishing a permanent middle cerebral artery occlusion (pMCAO) model. The infarction volume, neurological score, fibrin(ogen) deposition, and inflammatory response were evaluated 24 h after occlusion. Both in vivo and in vitro studies were conducted to assess the therapeutic potential of the γ377-395peptide in blocking the interactions between fibrin(ogen) and neutrophils. RESULTS: Fibrin(ogen) deposited in the infarct core promoted post-stroke inflammation and exacerbated neurological deficits in the acute phase after stroke onset. Reducing fibrinogen deposition resulted in a decrease in infarction volume, improved neurological scores, and reduced inflammation in the brain. Additionally, the presence of neutrophil accumulation near fibrin(ogen) deposits was observed in ischemic lesions, and the engagement of fibrin(ogen) by integrin receptor αMß2 promoted neutrophil activation and post-stroke inflammation. Finally, inhibiting fibrin(ogen)-mediated neutrophil activation using a fibrinogen-derived γ377-395peptide significantly attenuated neurological deficits. CONCLUSIONS: Fibrin(ogen) is a crucial regulator of post-stroke inflammation and contributes to secondary brain injury. The inflammation induced by fibrin(ogen) is primarily driven by neutrophils during acute ischemic stroke and can be ameliorated using the fibrin-derived γ377-395peptide. Targeting the fibrin(ogen)-mediated neuropathological process represents a promising approach for neuroprotective therapy after stroke while preserving its beneficial coagulation function.

Increased Intracranial Arterial Pulsatility and Microvascular Brain Damage in Pseudoxanthoma Elasticum.

BACKGROUND AND PURPOSE: Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. MATERIALS AND METHODS: Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. RESULTS: Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (ß = 0.10; 95% CI, 0.01-0.18). CONCLUSIONS: Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.

Superficial small cerebellar infarcts in cerebral amyloid angiopathy on 3 T MRI: A preliminary study.

BACKGROUND: Strictly superficial cerebellar microbleeds and cerebellar superficial siderosis have been considered markers of advanced cerebral amyloid angiopathy (CAA), but there are few studies on cerebellar ischemic lesions in CAA. We investigated the presence of superficial small cerebellar infarct (SCI) ≤15 mm and its relation to magnetic resonance imaging (MRI) markers in patients with probable CAA. METHODS: Eighty patients with probable CAA were retrospectively evaluated. The presence of superficial SCIs was examined, along with cerebellar microbleeds and cerebellar superficial siderosis, using 3-T MRI. Lobar cerebral microbleeds, cortical superficial siderosis (cSS), enlargement of the perivascular space in the centrum semiovale, and white matter hyperintensity were assessed and the total CAA-small vessel disease (SVD) score was calculated. RESULTS: Nine of the 80 patients (11.3%) had a total of 16 superficial SCIs. By tentatively defining SCI <4 mm as cerebellar microinfarcts, 8 out of 16 (50%) superficial SCIs corresponded to cerebellar microinfarcts. The total CAA-SVD score was significantly higher in patients with superficial SCIs (p = 0.01). The prevalence of cSS (p = 0.018), cortical cerebral microinfarct (p = 0.034), and superficial cerebellar microbleeds (p = 0.006) was significantly higher in patients with superficial SCIs. The number of superficial cerebellar microbleeds was also significantly higher in patients with superficial SCIs (p = 0.001). CONCLUSIONS: Our results suggest that in patients with CAA, superficial SCIs (including microinfarcts) on MRI may indicate more severe, advanced-stage CAA. These preliminary findings should be verified by larger prospective studies in the future.