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  • 1
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    Abstract WP280: Caveolin-1, Ring Finger Protein 213, and Endothelial Function in Moyamoya Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. suppl_1 ( 2016-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Background: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 (RNF213) was identified as a susceptibility gene for MMD in East Asian. However, the pathogenesis of MMD is still unclear. Methods: We prospectively analyzed clinical data for 139 patients with MMD (108 definite MMD, 31 probable MMD) and 61 patients with intracranial atherosclerotic stroke (ICAS), and 68 healthy subjects. We compared the genetic (RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor [VEGF] and receptor [VEGFR2] , and antagonizing cytokine [endostatin]) and endothelial dysfunction (asymmetric dimethylarginine [ADMA] , nitric oxide and its metabolites [nitrite and nitrate]), between patients with MMD and ICAS. We then performed the path analysis to evaluate whether a certain protein biomarker mediates the association the genetic and MMD. Results: Caveolin-1 level was decreased in patients with MMD and this level was markedly decreased in RNF213 variant carriers. Circulating factor such as VEGF and receptor were not different among the groups. Markers for endothelial dysfunction were significantly higher in patients with ICAS, but normal in MMD. The path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 level that led to MMD. The level of combined marker of MMD (caveolin-1) and ICAS (ADMA, marker for endothelial dysfunction) predicted MMD with a good sensitivity and specificity. Conclusions: Our results indicate that MMD is primarily caveolae disorder, dysregulation of endothelial vesicular trafficking and signal transduction, but not related to endothelial dysfunction or dysregulation of circulating cytokines.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.47.suppl_1.wp280
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 2
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    No Association of RNF213 Polymorphism with Reversible Cerebral Vasoconstriction Syndrome
    XMLink ; 2020
    In:  Journal of Clinical Neurology Vol. 16, No. 2 ( 2020), p. 330-
    Details
    In: Journal of Clinical Neurology, XMLink, Vol. 16, No. 2 ( 2020), p. 330-
    Type of Medium: Online Resource
    ISSN: 1738-6586 , 2005-5013
    URL: Article
    DOI: 10.3988/jcn.2020.16.2.330
    Language: English
    Publisher: XMLink
    Publication Date: 2020
    detail.hit.zdb_id: 2500489-X
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  • 3
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    Caveolin-1, Ring finger protein 213 , and endothelial function in Moyamoya disease
    SAGE Publications ; 2016
    In:  International Journal of Stroke Vol. 11, No. 9 ( 2016-12), p. 999-1008
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 11, No. 9 ( 2016-12), p. 999-1008
    Abstract: Moyamoya disease is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 ( RNF213) was identified as a susceptibility gene for Moyamoya disease in East Asian countries. However, the pathogenesis of Moyamoya disease remains unclear. Methods We prospectively analyzed clinical data for 139 patients with Moyamoya disease (108 bilateral Moyamoya disease, 31 unilateral Moyamoya disease), 61 patients with intracranial atherosclerotic stroke, and 68 healthy subjects. We compared the genetic ( RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor (VEGF) and receptor (VEGFR2), and antagonizing cytokine (endostatin)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA), and nitric oxide and its metabolites (nitrite and nitrate)) between patients with Moyamoya disease and intracranial atherosclerotic stroke. We then performed path analysis to evaluate whether a certain protein biomarker mediates the association between genes and Moyamoya disease. Results Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Circulating factors such as VEGF and VEGFR2 did not differ among the groups. Markers for endothelial dysfunction were significantly higher in patients with intracranial atherosclerotic stroke but normal in those with Moyamoya disease. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. The level of combined marker of Moyamoya disease (caveolin-1) and intracranial atherosclerotic stroke (ADMA, an endothelial dysfunction marker) predicted Moyamoya disease with good sensitivity and specificity. Conclusion Our results suggest that Moyamoya disease is a caveolae disorder but is not related to endothelial dysfunction or dysregulation of circulating cytokines.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/1747493016662039
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2211666-7
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  • 4
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    Distinct Roles of Endothelial Dysfunction and Inflammation in Intracranial Atherosclerotic Stroke
    S. Karger AG ; 2017
    In:  European Neurology Vol. 77, No. 3-4 ( 2017), p. 211-219
    Details
    In: European Neurology, S. Karger AG, Vol. 77, No. 3-4 ( 2017), p. 211-219
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 The aim of the study was to evaluate the differential roles of endothelial dysfunction and inflammation in intracranial atherosclerotic stroke (ICAS). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We prospectively recruited 262 patients with acute cerebral infarcts caused by ICAS and 75 individuals with no history of stroke as controls. Markers of endothelial dysfunction (asymmetric dimethylarginine, ADMA) and inflammation (lipoprotein-associated phospholipase A2, Lp-PLA 〈 sub 〉 2 〈 /sub 〉 ) were measured. Acute ischemic lesions were measured in terms of their size, composition, and patterns. Subclinical microangiopathy (degree of leukoaraiosis) and macroangiopathy (presence/number of asymptomatic stenoses) were graded in each patient. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Compared to normal controls, serum levels of ADMA (0.69 ± 0.14 vs. 0.47 ± 0.10, 〈 i 〉 p 〈 /i 〉 〈 0.001) and Lp-PLA 〈 sub 〉 2 〈 /sub 〉 (138.1 ± 116.8 vs. 19.0 ± 58.0, 〈 i 〉 p 〈 /i 〉 〈 0.001) were elevated in patients with ICAS. A high ADMA serum level was associated with greater prevalence of preclinical microangiopathy and macroangiopathy. Contrastingly, an elevated serum Lp-PLA 〈 sub 〉 2 〈 /sub 〉 level was associated with larger ischemic lesions, a greater number of lesions, and a larger cortical pattern. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Endothelial dysfunction and inflammation have distinct effects in ICAS patents; endothelial dysfunction is associated with the underlying micro- and macro-atherosclerotic burden, whereas inflammation is associated with acute infarct volume and pattern.
    Type of Medium: Online Resource
    ISSN: 0014-3022 , 1421-9913
    URL: Article
    DOI: 10.1159/000460816
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1482237-4
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  • 5
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    Abstract TP123: RNF213 Polymorphisms as a Susceptible Gene for Intracranial Atherosclerosis: A High-Resolution MRI and Conventional Angiography Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. suppl_1 ( 2016-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Background: Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that Ring Finger 213 (RNF213 p.Arg4810Lys) polymorphism, a susceptibility locus for MMD in East Asian, is a susceptible gene for ICAS confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). Method: We analyzed 532 consecutive patients with ischemic events within the MCA distribution and relevant stenotic lesion on distal ICA or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed in 370 (69.5%) patients, and HR-MRI in 283 (53.2%). Results: Based on angiographic and HR-MRI findings, 234 patients were diagnosed as ICAS, and 288 as MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients as well as 119 (69.1%) MMD patients. The RNF213 variant was observed in 25.2% (33 of 131) of patients with HR-MRI confirmed ICAS. Similarly, 15.8% (6 of 38) of ICAS patients in whom MMD was excluded by angiography had this variant. Among ICAS patients, RNF213 variant carriers were younger and more likely to have family history of MMD than non-carrier. Multivariate testing showed that age of ICAS onset was independent associated with RNF213 variant (odds ratio, 0.97; 95% CI, 0.944-0.99). Other clinical characteristics including vascular risk factors and HR-MRI findings were not different between them. Conclusions: RNF213 is susceptible gene not only for MMD but also for ICAS in East Asians. Further studies are needed on non-p.Arg4810Lys RNF213 variants in ICAS patients outside East Asian populations.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.47.suppl_1.tp123
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 6
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    Predicting Collateral Status With Magnetic Resonance Perfusion Parameters : Probabilistic Approach With a T max-Derived Prediction Model
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. 10 ( 2015-10), p. 2800-2807
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 10 ( 2015-10), p. 2800-2807
    Abstract: Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion–weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Methods— Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s T max strata to the entire hypoperfusion volume ( T max≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each T max strata proportion and cerebral blood volumes. Results— Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe T max delays ( T max 16–18 s , T max 18–22 s , T max 22–24 s , and T max 〉 24 s ) were associated with poor collaterals. The probability equation model using T max strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682–0.9924). The probability score was negatively correlated with the volume of infarct growth ( P =0.030). Conclusions— Collateral status is associated with more severe T max delays than previously defined. The present T max severity–weighted model can determine good collaterals and subsequent infarct growth.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.115.009828
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 7
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    Image_1.pdf
    Frontiers Media SA ; 2019
    In:  Frontiers in Neurology Vol. 10 ( 2019-7-16)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 10 ( 2019-7-16)
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2019.00765
    DOI: 10.3389/fneur.2019.00765.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
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  • 8
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    Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study
    SAGE Publications ; 2022
    In:  Cephalalgia Vol. 42, No. 7 ( 2022-06), p. 570-578
    Details
    In: Cephalalgia, SAGE Publications, Vol. 42, No. 7 ( 2022-06), p. 570-578
    Abstract: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. Methods In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. Results The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3–14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). Conclusions The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    URL: Article
    DOI: 10.1177/03331024211067784
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2019999-5
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  • 9
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    Temporal changes of circadian rhythmicity in cluster headache
    SAGE Publications ; 2020
    In:  Cephalalgia Vol. 40, No. 3 ( 2020-03), p. 278-287
    Details
    In: Cephalalgia, SAGE Publications, Vol. 40, No. 3 ( 2020-03), p. 278-287
    Abstract: To investigate the temporal changes of circadian rhythmicity in relation to the disease course in patients with cluster headache. Methods In this multicenter study, patients with cluster headache were recruited between September 2016 and July 2018. We evaluated the patients for circadian rhythmicity and time of cluster headache attacks in the current bout and any experience of bout-to-bout change in circadian rhythmicity. We analyzed the patterns of circadian rhythmicity in relation to the disease progression (the number of total lifetime bouts, grouped into deciles). Results Of the 175 patients in their active, within-bout period, 86 (49.1%) had circadian rhythmicity in the current bout. The prevalence of circadian rhythmicity in the active period was overall similar regardless of disease progression. Sixty-three (46.3%) out of 136 patients with ≥2 bouts reported bout-to-bout changes in circadian rhythmicity. The most frequent time of cluster headache attacks was distributed evenly throughout the day earlier in the disease course and dichotomized into hypnic and midday as the number of lifetime bouts increased ( p = 0.037 for the homogeneity of variance). When grouped into nighttime and daytime, nighttime attacks were predominant early in the disease course, while daytime attacks increased with disease progression (up to 7th deciles of total lifetime bouts, p = 0.001) and decreased in patients with the most advanced disease course ( p = 0.013 for the non-linear association). Conclusions Circadian rhythmicity is not a fixed factor, and changes according to the disease course. Our findings will be valuable in providing a new insight into the stability of functional involvement of the suprachiasmatic nucleus in the pathophysiology of cluster headache.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    URL: Article
    DOI: 10.1177/0333102419883372
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 10
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    Abstract 110: Caveolin-1 and Arterial Remodeling in Adult Moyamoya Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. suppl_1 ( 2017-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: Background and purpose: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease that is characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that caveolin-1, a protein that controls the regulation of endothelial vesicular trafficking and signal transduction, is associated with negative remodeling in MMD. Methods: We prospectively recruited 77 consecutive patients with MMD (49 bilateral and 28 unilateral MMD) diagnosed by conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. Distal ICA outer diameters were examined with high-resolution MRI. We evaluated whether the degree of negative remodeling in MMD patients was associated with RNF213 polymorphism, caveolin-1 levels, or various clinical and vascular risk factors. Results: The RNF213 variant was observed in 49 (63.6%) patients with MMD. The serum caveolin-1 (ng/mL) level was lower in MMD patients than in controls (0.47±0.29 vs. 0.86±0.68, P =0.034). The mean ICA diameter was 2.48±0.98 mm (range 0.00-4.76) for the 126 affected distal ICAs in MMD patients and 3.84±0.42 mm for asymptomatic ICAs in controls. After adjusting for possible confounders, male sex (coefficient, 0.396; P =0.029), clinical presentation with ischemic stroke (coefficient, -0.733; P 〈 0.001), and caveolin-1 level (coefficient, 1.018; P 〈 0.001) were independently associated with distal ICA diameter in MMD patients. Conclusion: Our findings suggest that caveolin-1 may play a major role in arterial negative remodeling in MMD patients. Future studies exploring caveolin-1 as a therapeutic target in MMD are warranted.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.48.suppl_1.110
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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