Seasonal variation in hemorrhage and focal neurologic deficit due to intracerebral cavernous malformations

Flemming, Kelly D.; Brown, Robert D.; Link, Michael J.

doi:10.1016/j.jocn.2015.01.007

Cited by 15 publications

(9 citation statements)

References 14 publications

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“…Since it is known that vitamin D levels can vary seasonally [14], one might expect a seasonal variation in hemorrhagic presentation with CM. Our group previously reported a higher likelihood of hemorrhagic presentation during fall and winter months (October-March) in our retrospective CM cohort supporting this theory [15]. However, we did not see a seasonal variation in the current, prospective cohort.…”

Section: Discussionsupporting

confidence: 78%

Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level

et al. 2020

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Background: Cavernous malformations (CM) are angiographically occult vascular malformations that may be incidental or present with intracerebral or spinal hemorrhage, seizures, or nonhemorrhagic focal neurologic deficit (FND). Recently in vitro data have suggested vitamin D may play a role in stabilizing CCM2 endothelial cells. Little is known about the effect of vitamin D in human CM disease. Methods: Beginning in 2015, consecutive patients at our institution with radiologically confirmed CM were recruited to participate in a prospective clinical registry as well as 25-hydroxy-vitamin D study. A structured interview, survey, and examination were performed at baseline. Medical records and magnetic resonance imaging studies were reviewed and data collected included comorbid conditions, medication use, and location of CM. Standard definition of clinical hemorrhage, FND, and seizures was used. Univariate and multivariate logistic regression models were used, and OR, 95% CIs, and likelihood-ratio p values were calculated to de-

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Section: Discussionsupporting

confidence: 78%

Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level

et al. 2020

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“…Overall, genetic and nongenetic determinants of vitamin D status are significant predictors of its health outcomes, and may have an important impact on susceptibility to various human diseases. Indeed, there is already clear evidence that both seasonal variations and genetic modifiers of vitamin D metabolism and functions are independently associated with inter-individual variability with regard to the risk of developing cardiovascular disorders, including severe cerebrovascular diseases [117,118], as described in more detail below.…”

Section: Determinants Of Vitamin D Status and Related Health Outcomesmentioning

confidence: 99%

Vitamin D Deficiency and the Risk of Cerebrovascular Disease

Kim

Perrelli

Ragni³

et al. 2020

Antioxidants

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Vitamin D deficiency has been clearly linked to major chronic diseases associated with oxidative stress, inflammation, and aging, including cardiovascular and neurodegenerative diseases, diabetes, and cancer. In particular, the cardiovascular system appears to be highly sensitive to vitamin D deficiency, as this may result in endothelial dysfunction and vascular defects via multiple mechanisms. Accordingly, recent research developments have led to the proposal that pharmacological interventions targeting either vitamin D deficiency or its key downstream effects, including defective autophagy and abnormal pro-oxidant and pro-inflammatory responses, may be able to limit the onset and severity of major cerebrovascular diseases, such as stroke and cerebrovascular malformations. Here we review the available evidence supporting the role of vitamin D in preventing or limiting the development of these cerebrovascular diseases, which are leading causes of disability and death all over the world.

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“…However, analysis of existing patient records may yield indirect evidence of inflammation during disease progression. One such study tracked symptom onset in a small population of patients and found that over 60% of patients presented with symptoms during the fall and winter flu season, suggesting the possibility that sub-clinical viral infection could create the appropriate cellular context for disease progression (Flemming et al, 2015). Alternatively, the authors of this study suggested that the correlation could be caused by vitamin D deficiency, a potent antioxidant, during cloudy winter months, particularly intriguing given that vitamin D reduces lesion burden in mouse models of CCM (Gibson et al, 2015).…”

Section: Role Of Inflammation In Ccm Pathogenesismentioning

confidence: 99%

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

Retta

Glading

2016

The International Journal of Biochemistry & Cell Biology

110

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Graphical abstractTowards a unifying mechanism for CCM disease pathogenesis and treatment.CCM proteins play pleiotropic roles in distinct redox-sensitive pathways by modulating the fine-tuned crosstalk between redox signaling and autophagy. Effective autophagy removes ROS-generating cellular trash, including damaged mitochondria, to rejuvenate cell environment, thus serving a cytoprotective function for the maintenance of endothelial cell monolayer integrity and functionality and blood–brain barrier (BBB) stability even under adverse stress conditions. Loss-of-function of a CCM protein (e.g., KRIT1) causes defective autophagy and altered redox signaling, affecting BBB stability and sensitizing endothelial cells to local oxidative stress and inflammatory events, which may act as key pathogenic determinants of focal formation and progression of CCM lesions. The common capacity to modulate the interplay between autophagy and redox signaling reconciles the distinct pharmacological approaches proposed so far for CCM disease prevention and treatment.

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Seasonal variation in hemorrhage and focal neurologic deficit due to intracerebral cavernous malformations

Cited by 15 publications

References 14 publications

Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level

Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level

Vitamin D Deficiency and the Risk of Cerebrovascular Disease

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

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