Leptomeningeal metastasis of breast cancer during neo-adjuvant chemotherapy in a 38-year-old woman: a case report.

Background: Breast cancer accounts for 5% of the population who develop central nervous system metastasis, which is only second to the lung cancer. Breast cancer metastasis to the brain including parenchymal brain metastasis (BM) and leptomeningeal metastasis (LM). Compared with BM, LM is a more rare but aggressive metastatic diagnosis with poor outcome. Case Description: We reported a 38-year-old woman presented to the neurology department due to progressive headache for 1 month, accompanied with dizziness, nausea, vomiting and neck pain. During hospitalization, she experienced paroxysmal loss of consciousness twice. Five months prior to this visit, her first visit was diagnosed with breast cancer on the right side which was of triple-negative subtype and with homolateral axillary lymph node involvement by biopsy. After the clinician assessment she had received six cycles of TCb (docetaxel/carboplatin) neo-adjuvant chemotherapy. During the period of neo-adjuvant chemotherapy, she did not report the presence of severe neurological symptoms. Twenty days ago, she underwent right breast-conserving surgery and the postoperative evaluation was ypT1N3M0 stage and Miller-Payne grade 2. Head computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI) didn't find typical brain imaging changes. No other signs of metastasis were seen in the CT examinations of the patient's chest and abdomen. Finally, lumbar puncture with cerebrospinal fluid (CSF) analysis showed the presence of malignant cells. Given the patient's clinical history and new neurologic symptoms, the diagnosis was LM from breast cancer. Various treatment modalities including intrathecal thiotepa, oral temozolomide (TMZ) and whole-brain radiation therapy (WBRT) had been used, but none of them showed significant benefit for survival. Conclusions: Breast cancer metastasis to the brain, especially LM, should be given sufficient vigilance and attention at the beginning of the diagnosis and treatment, particularly in triple-negative breast cancer patients who are at high risk. Symptoms of LM may be masked by the chemotherapy adverse effects. The results of MRI and CT may show negative results, thus lumbar puncture with CSF should be done promptly if LM is highly suspected in clinical practice. Early prevention, early detection and timely treatment are crucial according to the poor prognosis.

Effect of bleeding risk prediction on decision making of intravenous thrombolysis before thrombectomy: a subgroup analysis of DIRECT-MT.

BACKGROUND: The major concern for bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the potentially increased risk of symptomatic intracerebral hemorrhage (sICH). Thus we conducted this study to clarify whether evaluation of individual bleeding risk could assist in the decision to perform IVT before EVT. METHODS: The study was a subgroup analysis of a randomized trial evaluating the safety and efficacy of IVT before EVT. The SEDAN (blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign, Age, and National Institutes of Health Stroke Score) score, GRASPS (Glucose, Race, Age, Sex, systolic blood Pressure, and Severity of stroke) score, and SITS-SICH (Safe Implementation of Thrombolysis in Stroke-Symptomatic Intracerebral Hemorrhage) score were used to evaluate individual bleeding risk. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Binary logistic regression with an interaction term was used to estimate treatment effect modification to clarify whether direct EVT was more beneficial in patients with a higher sICH risk, while adjunctive IVT before EVT was more beneficial in patients with a lower sICH risk. RESULTS: Among 658 randomized patients, 639 (361 men, 56.5%; median age 69 (IQR 61-76) years) were included in the study. With the SITS-SICH score as an example, adjusted OR for functional independence with EVT alone was 1.12 (95% CI 0.68 to 1.82) in patients with a lower sICH risk (SITS-SICH score 0-4) and 0.92 (0.53 to 1.60) in those with a higher sICH risk (SITS-SICH score 5-15). There were no treatment-by-bleeding-risk interactions for all dichotomized mRS outcomes based on the three scores (all p>0.05). CONCLUSIONS: We found no evidence that clinicians can decide whether to omit IVT before EVT based on an individualized assessment of bleeding risk.

Prediction of Acute Myocardial Infarction in Asian Patients With Acute Ischemic Stroke: The CTRAN Score.

Background: Patients with acute ischemic stroke (AIS) are susceptible to acute myocardial infarction (AMI), which would lead to a dramatic increase of in-hospital mortality. Objectives: The authors established and validated an easy-used model to stratify the risk of in-hospital AMI among patients with AIS. Methods: We consecutively included patients with AIS who were admitted within 7 days from symptom onset in our prospectively maintained database (NCT04487340) from January 2016 to December 2020. In the derivation cohort from 70 centers, we developed a score to predict in-hospital AMI by integrating the bedside-accessible predictors identified via multivariable logistic regression. Then in the validation cohort from 22 centers, we externally evaluated the performance of this score. Results: Overall, 96,367 patients were included. In-hospital AMI occurred in 392 (0.41%) patients. The final model, named CTRAN, incorporated 5 predictors including the history of coronary heart disease, malignant tumor, renal insufficiency, age, and baseline National Institutes of Health Stroke Scale score. The CTRAN score was confirmed in the validation cohort using receiver operating characteristic curve, which yielded an area under the curve of 0.758 (95% CI: 0.718-0.798). Conclusions: The CTRAN score could be a good tool for clinicians to identify patients with AIS at high in-hospital AMI risk.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

Brain Iron Deposits in Thalamus Is an Independent Factor for Depressive Symptoms Based on Quantitative Susceptibility Mapping in an Older Adults Community Population.

Objectives: With the trend of an aging population, an increasing prevalence of late-life depression has been identified. Several studies demonstrated that iron deposition was significantly related to the severity of symptoms in patients with depression. However, whether brain iron deposits influence depressive symptoms is so far unclear in the community of older adults. We measured iron deposition in deep intracranial nucleus by quantitative susceptibility mapping (QSM) and aimed to explore the relationship between iron deposition and depressive symptoms. Methods: We reviewed the data of a community population from CIRCLE study, which is a single-center prospective observational study that enrolled individuals above 40 years old with cerebral small vessel disease (SVD), while free of known dementia or stroke. We evaluated regional iron deposits on QSM, measured the volume of white matter hyperintensities (WMHs) on T2 fluid-attenuated inversion recovery, and assessed depressive symptoms by Hamilton depression scale (HDRS). We defined depressive symptom as HDRS > 7. Results: A total of 185 participants were enrolled. Participants in depressive symptom group had higher QSM value in thalamus than control group (18.79 ± 14.94 vs 13.29 ± 7.64, p = 0.003). The QSM value in the thalamus was an independent factor for the presence of depressive symptoms (OR = 1.055; 95% CI: 1.011-1.100; p = 0.013). The regional QSM values in other areas were not associated with HDRS score (all p > 0.05). No significant correlations were observed between WMHs volume and HDRS score (p > 0.05), or regional QSM values and WMHs volume (all p > 0.05). Conclusions: Our study demonstrated that iron deposits in the thalamus were related to the depressive symptoms in older adults.

Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy.

AIMS: We sought to investigate the risk factors of blood-brain barrier (BBB) disruption, and its potential impact on 90-day clinical outcome in acute ischemic stroke (AIS) patients after reperfusion therapy. METHODS: Consecutive acute anterior circulation AIS patients imaged with computed tomographic perfusion (CTP) before reperfusion therapy were included. Tmax >6 s was used for the volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was calculated as the average relative permeability-surface area product (rPS) within the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo-c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained at 90-day post-stroke. RESULTS: A total of 187 patients were included, among whom the median age was 73 (61-80) years and 76 (40.6%) were women. Median baseline NIHSS score was 12 (7- 16). Ninety-eight (52.4%) patients had mRS score >2. Increased rPShypo-i and rPShypo-c were both independently associated with males and large infarct volume. The increased rPShypo-i was also independently associated with a history of atrial fibrillation and high NIHSS score. Multivariable analysis showed higher rPShypo-c was independently associated with higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018). CONCLUSION: BBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Different risk factors for poor outcome between patients with positive and negative susceptibility vessel sign.

PURPOSE: The absence of the susceptibility vessel sign (negative SVS) on gradient-recalled echo or susceptibility-weighted imaging (SWI) in thrombolytic therapy has not been well studied. Since positive and negative SVS may have different components, we aimed to investigate the difference in risk factors for clinical outcome between patients with positive and negative SVS. METHODS: We retrospectively examined clinical and imaging data from 85 consecutive patients with acute ischemic stroke with middle cerebral artery occlusion who underwent SWI before intravenous thrombolysis (IVT). We then examined the predictors of negative SVS and the risk factors for a poor outcome (defined as modified Rankin Scale score ≥3) 3 months after IVT in subgroup analysis. RESULTS: Multivariate regression analysis indicated that previous antiplatelet use (OR 0.076; 95% CI 0.007 to 0.847; p=0.036) and shorter time from onset to treatment (OR 1.051; 95% CI 1.003 to 1.102; p=0.037) were inversely associated with poor outcome in patients with negative SVS, while higher baseline National Institutes of Health Stroke Scale (NIHSS) score was associated with poor outcome in patients with positive SVS (OR 1.222; 95% CI 1.084 to 1.377; p=0.001). CONCLUSIONS: The risk factors for clinical outcome after IVT in patients with negative SVS may differ from those with positive SVS.

Unfavorable neurological outcome in diabetic patients with acute ischemic stroke is associated with incomplete recanalization after intravenous thrombolysis.

OBJECTIVE: To assess the impact of diabetes on neurological outcome and recanalization in acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: Clinical data of 419 consecutive patients with AIS who received IVT between June 2009 and April 2014. Based on the medical history and new diagnosis, the patients were divided into groups with and without diabetes. Neurological outcomes at 24 h, 7 days and 3 months after IVT were evaluated. Favorable outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score decrease ≥4 points from baseline or 0 at 24 h, NIHSS decrease ≥8 points or 0 at day 7, or modified Rankin scale ≤1 at 3 months after IVT. Recanalization on non-invasive imaging was evaluated in patients with large vessel occlusion (LVO) according to thrombolysis in myocardial infarction grades. RESULTS: Among 419 patients, 98 (23.4%) had diabetes. Multivariable analyses showed that comorbidity of diabetes was an independent predictor of unfavorable outcome at 24 h (OR=0.534, 95% CI 0.316 to 0.903, p=0.019), at day 7 (OR=0.382, 95% CI 0.220 to 0.665, p=0.001), and at 3 months (OR=0.464, 95% CI 0.266 to 0.808, p=0.007). In patients with LVO, diabetes was an independent predictor of incomplete recanalization 24 h after IVT (OR=0.268, 95% CI 0.075 to 0.955, p=0.042). CONCLUSIONS: Diabetic patients with AIS had unfavorable neurological outcome, potentially linked to incomplete recanalization after IVT.

Brain iron deposition in white matter hyperintensities: a 3-T MRI study.

Iron accumulation has been implicated in the pathogenesis of demyelinating diseases. Therefore, we hypothesized that abnormal high cerebral iron deposition may be involved in the development of white matter hyperintensities (WMHs). We used R2* relaxometry to assess whether iron levels in different brain regions correlate with the severity of WMHs. This technique has been recently validated in a postmortem study to demonstrate in vivo brain iron accumulation in a quantitative manner. Fifty-two consecutive WMH patients and 30 healthy controls with 3-T magnetic resonance imaging (MRI) were reviewed in this study. We measured WMH volume (as a marker of the severity of WMHs) on MRI, and the transverse relaxation rate R2*, as an estimate of iron content in seven brain regions. We found that R2* in globus pallidus was associated with WMH volume after adjusting for sociodemographic variables (partial correlation coefficient = 0.521, P < 0.001) and in a multivariate analysis adjusted for common vascular risk factors (partial correlation coefficient = 0.572, P = 0.033). Regional R2* in globus pallidus was also significantly higher in WMHs than in controls (P = 0.042). Iron content in globus pallidus, as assessed by R2* relaxometry, is independently linked to the severity of WMHs in our cohort of patients, suggesting that iron deposition in the brain may play a role in the pathogenesis of WMHs. This may provide prognostic information on patients with WMHs and may have implications for therapeutic interventions in WMHs.

Evaluation of brain iron content based on magnetic resonance imaging (MRI): comparison among phase value, R2* and magnitude signal intensity.

BACKGROUND AND PURPOSE: Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn't commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. METHODS: We measured both phase values and R2* in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2* and brain iron. RESULTS: We found phase value correlated with R2* in substantia nigra (r = -0.723, p<0.001) and putamen (r = -0.514, p = 0.010), while no correlations in red nucleus (r = -0.236, p = 0.268) and globus pallidus (r = -0.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = -0.593, p = 0.002), substantia nigra (r = -0.521, p = 0.009), globus pallidus (r = -0.750, p<0.001) and putamen (r = -0.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = -0.982, P<0.001). CONCLUSIONS: Our study indicates that phase value may not be used for assessing the iron content in some brain regions especially globus pallidus. The new magnitude method is highly consistent with R2* especially in globus pallidus, and we assume that this approach may be acceptable as an index of iron content in iron-rich brain regions.