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Prominent juxtacortical white matter lesion hallmarks NOTCH3-related intracerebral haemorrhage

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Stroke & Vascular Neurology 2022年第1期7卷 38-46页

作者： Chih-Hao Chen Hao-Chia Hsu Yu-Wen Cheng Ya-Fang Chen Sung-Chun Tang Jiann-Shing Jeng Neurology National Taiwan University HospitalTaipeiTaiwan Department of Neurology National Taiwan University HospitalTaipeiTaiwan Department of Neurology National Taiwan University Hospital Hsinchu BranchHsinchuTaiwan Medical Imaging National Taiwan University HospitalTaipeiTaiwan

Background and purpose NOTCH3 p.R544C mutation accounts for 5%of spontaneous intracerebral haemorrhage(ICH)in East Asian patients.We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation.The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation,including burden of white matter lesion(WML),degree of brain atrophy,number of lacunes,prominent juxtacortical WML and prominent lobar lacunes,were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH(mean age,61 years;male,68%;ICH volumes,14.1±17.8 mL),13 patients(4.3%)carried NOTCH3 p.R544C mutation.The clinical features,haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers.The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML(69.2%vs 17.8%,p<0.001),and the effects were not driven by ageing as seen in patients without mutation.Prominent juxtacortical WML(area under receiver operating characteristic curve=0.76)outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model(OR,20.9;95%CI 4.94 to 88.6).Conclusion In patients with spontaneous ICH,the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.

关键词： NOTCH3 intracerebral white

Pertussis toxin–induced inflammatory response exacerbates intracerebral haemorrhage and ischaemic stroke in mice

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Stroke & Vascular Neurology 2022年第1期7卷 29-37页

作者： Ming Zou Yan Feng Yuwhen Xiu Yan Li Ying Zhang Junwan Fan Haowen Li Jingli Cao Wenyan He Wei-Na Jin Tianjin Neurological Institute Tianjin Medical University General HospitalTianjinChina China National Clinical Research Center for Neurological Diseases/Advanced Innovation Center for Human Brain Protection Beijing Tiantan HospitalBeijingChina

Background Stroke is a devastating disease,including intracerebral haemorrhage(ICH)and ischaemic stroke.Emerging evidences indicate that systemic inflammatory cascades after stroke contribute to brain damage.However,the direct effects and features of systemic inflammation on brain injury,especially comparing between ischaemic and haemorrhagic stroke,are still obscure.Methods Pertussis toxin(PT)was used to build a pro-inflammatory milieu after ICH and ischaemic stroke in mouse model.The neurodeficits,stroke lesion,immune response and blood–brain barrier(BBB)destruction were assessed.Results In ICH mouse model,PT-induced systemic inflammation exacerbated neurological deficits,and enlarged haemorrhage lesion and perihaematomal oedema.We also found promoted leucocyte infiltration and inflammatory cytokine release into the brain after PT treatment.Moreover,the integrity of the BBB was further disrupted after receiving PT.Furthermore,we demonstrated that PT enhanced brain inflammation and aggravated stroke severity in middle cerebral artery occlusion mouse model.Conclusions Our results suggest that PT increases inflammatory response that exacerbates brain injury after ICH or ischaemic stroke in mouse model.

关键词： inflammatory inflammation intracerebral

Impact and risk factors of sepsis on long-term outcomes after spontaneous intracerebral hemorrhage

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Chinese Medical Journal 2022年第8期135卷 1006-1008页

作者： Jie Lin Minglian He Binbin Tan Xue Yang Yuhong Li Jishu Xian Hua Feng Yujie Chen Department of Neurosurgery and State Key Laboratory of Trauma Burn and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Clinical Research Center for Neurosurgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China.

To the Editor:Spontaneous intracerebral hemorrhage(sICH)has a high incidence of acute cerebrovascular illness in elderly people in China,with high mortality and long-term functional impairment among survivors.However,there is still controversy over whether secondary infection during the course of hospitalization after ICH has a negative impact on long-term function.

关键词： hemorrhage mortality intracerebral

Magnesium:pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage

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Neural Regeneration Research 2019年第7期14卷 1116-1121页

作者： Jason J.Chang Rocco Armonda Nitin Goyal Adam S.Arthur Department of Critical Care Medicine MedStar Washington Hospital Center Department of Neurology Georgetown University School of Medicine Department of Neurosurgery Georgetown University School of Medicine Department of Neurology University of Tennessee Health Science Center Semmes Murphey Clinic Department of Neurosurgery University of Tennessee Health Science Center

intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.

关键词： intracerebral hemorrhage stroke,magnesium vasodilation hemostasis blood-brain barrier perihematomal edema

sTWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage

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Stroke & Vascular Neurology 2021年第4期6卷 528-535,I0011,I0012页

作者： Andrés da Silva-Candal Iria López-Dequidt Manuel Rodriguez-Yañez PauloÁvila-Gómez JoséManuel Pumar JoséCastillo Tomás Sobrino Francisco Campos Ramón Iglesias-Rey Pablo Hervella Clinical Neurosciences Research Laboratory(LINC) Health Research Institute of Santiago de Compostela(IDIS)Santiago de CompostelaSpain Department of Neurology Hospital Clínico UniversitarioSantiago de CompostelaSpain Department of Neuroradiology Hospital Clínico UniversitarioSantiago de CompostelaSpain

Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic ICH.Clinical and biochemical parameters were analysed.sTWEAK levels were measured by ELISA.LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury.The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage.Poor functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary endpoint.Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.Results We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 months.Conclusion sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.

关键词： TWEAK intracerebral specificity

Microwave based detector for continuous assessment of intracerebral hemorrhage

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Science China(Technological Sciences) 2019年第3期62卷 365-372页

作者： JIANG Yu Hao ZHAO MinJi WANG Lu YANG Li JU Yang Medical Electronics and Information Technology Engineering Research Center Chongqing University of Posts and Communications Department of Mechanical Science and Engineering Graduate School of Engineering Nagoya University Bioengineering College Chongqing University

Continuous detecting of the rate and size of hematoma expansion is crucial for intracerebral hemorrhage management and treatment. To continuously assess intracerebral hemorrhage in human head, a novel nondestructive microwave head detecting system is presented in this study. An open-ended cylindrical waveguide is employed as sensing antenna, which is operated associated with a coaxial cable for signal transmission and data acquisition. Measurement of amplitude data over the frequency range of 100–400 MHz is processed to evaluate the changes in intracerebral hemorrhage, based on the system's operating principle that the sensor functions as a resonant cavity. Furthermore, 3D printed anatomically and dielectrically realistic human head phantoms with different lesions are fabricated to verify the efficacy of this proposed hemorrhagic stroke assessment system.It is worth noting that the quantitative results show that the system operating in TE_(111) mode is able to detect intracerebral hemorrhage size change as small as 1 cm^3, demonstrating the possibility of this proposed head evaluating system in future preclinical trials.

关键词： microwave evaluation intracerebral hemorrhage

Myocardial ischemic changes of electrocardiogram in intracerebral hemorrhage: A case report and review of literature

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World Journal of Clinical Cases 2019年第21期7卷 3603-3614页

作者： Xue-Qi Lin Liang-Rong Zheng Department of Cardiovascular The First Affiliated Hospital of Zhejiang University

BACKGROUND Cardiac injury may occur after acute pathology of central nervous system(CNS)without any evidence of primary cardiac diseases.The resulting structural and/or functional changes are called cerebrocardiac syndrome(CCS).The great majority of studies have been performed in patients with subarachnoid hemorrhage(SAH),while CCS data after intracerebral hemorrhage(ICH)are rare.It may cause diagnostic and therapeutic pitfalls for the clinician due to a lack of specific clinical manifestations and diagnostic methods.Understanding the underlying pathophysiological and molecular mechanism(s)following cerebrovascular incidents will help to implement prevention and treatment strategies to improve the prognosis.CASE SUMMARY A 37-year-old man with a history of hypertension presented to our department on an emergency basis because of a sudden dizziness and left limb weakness.Cerebral computed tomography(CT)suggested ICH in the occipital and parietal lobes,and the chosen emergency treatment was hematoma evacuation.Left ventricular(LV)dysfunction occurred after the next 48 h and the electrocardiogram(ECG)showed non-ST elevation myocardial infarction.CCS was suspected first in the context of ICH due to the negative result of the coronary CT angiogram.CONCLUSION Misinterpretation of ischemic-like ECGs may lead to unnecessary or hazardous interventions and cause undue delay of rehabilitation after stroke.Our objective is to highlight the clinical implications of CCS and we hope the differential diagnoses will be considered in patients with acute CNS diseases.

关键词： Stroke intracerebral hemorrhage Cerebrocardiac syndrome Cardiac insufficiency Non-ST elevation myocardial infraction Case report Neurogenic stunned myocardium

Effects of recombinant adenovirus-mediated hypoxia-inducible factorlalpha gene on proliferation and differentiation of endogenous neural stem cells in rats following intracerebral hemorrhage

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 762-767页

作者： Zhen Yu Li-Fen Chen Ling Tang Chang-Lin Hu Department of Neurology Second Affiliated Hospital of Chongqing Medical University Department of Neurology University-Town Hospital of Chongqing Medical University

Objective:To investigate the effects of adenovirus(Ad)-mediated hypoxia-inducible factor-1alpha(HIF-1α)gene on proliferation and differentiation of endogenous neural stem cells(NSCs)in rats following intracerebral hemorrhage(ICH)and the underlying mechanisms.Methods:A total of 120 specific pathogen-free,adult,male Sprague-Dawley rats were included in this study.After establishment of ICH models in rats,PBS,Ad,or Ad-HIF-1αwas administered via the ischemic ventricle.On the 1st,7th,14th,21st and 28th d after ICH,rat neurological deficits were scored,doublecortin(DCX)expression in the subventricular zone cells was detected by immunohistochemical staining,and 5-bromo-2'-deoxyuridine(Brdtl)-,BrdU/DCX-,and BrdU/glial fibrillary acidic prolein-posilive cells in the subventricular zone were counted using immumofluorescence method among PBS,Ad,and Ad-HIF-1αgroups.Results:On the 7th,14th,21st and 28th d after ICH,neurological deficit scores in the Ad-HIF-1αgroup were significantly lower than in the PBS and Ad groups(P<0.05).In the Ad-HIF-lαgroup,DCX expression was significantly increased on the 7th d,peaked on the 14th d,and then gradually decreased.In the Ad-HIF-1αgroup,BrdU-positive cells were significantly increased over time course,and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point(P<0.01 or 0.05).On the 7th,14th,21st and 28th d after ICH,the number of DCX-,BrdU-,BrdU/DCX-,and BrdU/DCX-positive cells in the Ad-HIF-1αgroup was significantly greater than in the PBS and Ad groups(P<0.05).Conclusions:HIF-1αgene can promote the proliferation,migration and differentiation of endogenous neural stem cells after ICH,thereby contributing to neurofunctional recovery after ICH.

关键词： Hypoxia-inducible factor-lalpha Endogenous neural stem cells Adenovirus intracerebral hemorrhage

Prognostic value of intracranial pressure monitoring for the management of hypertensive intracerebral hemorrhage following minimally invasive surgery

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World Journal of Emergency Medicine 2020年第3期11卷 169-173页

作者： Xiao-ru Che Yong-jie Wang Hai-yan Zheng Department of Cardiology Zhejiang Province People’s HospitalHangzhouChina Department of Cardiology People’s Hospital of Hangzhou Medical CollegeHangzhouChina Department of Neurosurgery the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Neurosurgery the Fouth Affi liated Hospital of Zhejiang University School of MedicineYiwuChina

BACKGROUND:The incidence of hypertensive intracerebral hemorrhage(HICH)has been increasing during the recent years in low-and middle-income countries.With high mortality and morbidity rates,it brings huge burden to the families.It lacks evidence regarding the application of intracranial pressure(ICP)monitoring in HICH.In the current study,the authors aimed to evaluate whether ICP monitoring could make any difference on the prognosis of HICH patients after minimally invasive surgery.METHODS:A retrospective review of 116 HICH patients admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine,between 2014 and 2016,was performed.The effects of ICP monitoring on 6-month mortality and favorable outcomes were evaluated by univariate and logistic regression analysis.RESULTS:ICP monitors were inserted into 50 patients.Patients with ICP monitoring had a significantly better outcome(P<0.05).The average in-hospital duration in patients with ICP monitoring was shorter than that in the patients without ICP monitoring(16.68 days vs.20.47 days,P<0.05).Mortality rates between ICP monitoring and no ICP monitoring did not differ significantly(16.0%vs.15.1%,P=0.901).On univariate analysis,age,Glasgow Coma Scale(GCS)on admission and presence of ICP monitor were independent predictors of 6-month favorable outcomes.CONCLUSION:ICP monitoring is associated with a better 6-month functional outcome compared with no ICP monitoring.Future study is still needed to confirm our results and elucidate which subgroup of HICH patients will benefit most from the minimally invasive surgical intervention and ICP monitoring.

关键词： Hypertensive intracerebral hemorrhage Intracranial pressure Minimally invasive surgery