White matter lesion burden correlates with the free water distribution surrounding the lateral ventricle

Adult-onset Alexander disease (AOAD) is an autosomal dominant progressive astrogliopathy caused by pathogenic variants in glial fibrillary acidic protein (<i>GFAP</i>). Individuals with this disorder often present with a typical neuroradiologic pattern, including frontal white matter abnormality with contrast enhancement, atrophy and signal intensity changes of the medulla oblongata and upper cervical cord on MRI. Focal lesions are rarely seen in AOAD, which causes concern for primary malignancies. This study aimed to present the case of a 37-year-old male patient initially diagnosed with an astrocytoma in the lateral ventricle that was later identified as GFAP mutation-confirmed AOAD. <i>GFAP</i> sequencing revealed a heterogeneous missense mutation point c.236G>A. Hence, AOAD should be considered in patients with tumor-like lesion brain lesion in association with atrophy of medulla oblongata and upper cervical spinal cord, and frontal white matter abnormality with contrast enhancement.

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Changes in brain functional connectivity and cognition related to white matter lesion burden in hypertensive patients from SPRINT

Neuroradiology ◽

10.1007/s00234-020-02614-6 ◽

2021 ◽

Author(s):

Chintan Shah ◽

Dhivya Srinivasan ◽

Guray Erus ◽

James E. Schmitt ◽

Adhish Agarwal ◽

...

Keyword(s):

White Matter ◽

Functional Connectivity ◽

White Matter Lesion ◽

Hypertensive Patients ◽

Brain Functional Connectivity

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Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion

Experimental Biology and Medicine ◽

10.1177/1535370221989955 ◽

2021 ◽

pp. 153537022198995

Author(s):

Jian Huang ◽

Jun Yang ◽

Xingju Zou ◽

Shilun Zuo ◽

Jing Wang ◽

...

Keyword(s):

White Matter ◽

White Matter Lesion ◽

Neuroprotective Effect ◽

Precursor Cell ◽

Cerebral Hypoperfusion ◽

Ginkgolide B ◽

Oligodendrocyte Precursor Cell ◽

Learning Abilities ◽

Phosphorylated Akt ◽

Oligodendrocyte Precursor

White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats’ memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.

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Characterizing Extracellular White Matter Pathologies Using Free Water Imaging Across the Schizophrenia Illness Course: A Multi-Site Harmonized Diffusion MRI Study

Biological Psychiatry ◽

10.1016/j.biopsych.2021.02.226 ◽

2021 ◽

Vol 89 (9) ◽

pp. S85

Author(s):

Suheyla Cetin-Karayumak ◽

Ofer Pasternak ◽

Fan Zhang ◽

Johanna Seitz ◽

Doron Elad ◽

...

Keyword(s):

White Matter ◽

Diffusion Mri ◽

Free Water ◽

Mri Study

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Resistance Training and White Matter Lesion Progression in Older Women: Exploratory Analysis of a 12-Month Randomized Controlled Trial

Journal of the American Geriatrics Society ◽

10.1111/jgs.13644 ◽

2015 ◽

Vol 63 (10) ◽

pp. 2052-2060 ◽

Cited By ~ 37

Author(s):

Niousha Bolandzadeh ◽

Roger Tam ◽

Todd C. Handy ◽

Lindsay S. Nagamatsu ◽

Chun Liang Hsu ◽

...

Keyword(s):

Randomized Controlled Trial ◽

White Matter ◽

Resistance Training ◽

Older Women ◽

White Matter Lesion ◽

Controlled Trial ◽

Exploratory Analysis ◽

Randomized Controlled

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Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging

Fluids and Barriers of the CNS ◽

10.1186/s12987-021-00264-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Xinfeng Yu ◽

Xinzhen Yin ◽

Hui Hong ◽

Shuyue Wang ◽

Yeerfan Jiaerken ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Extracellular Fluid ◽

Free Water ◽

Inverse Correlation ◽

Brain Regions ◽

Fiber Density ◽

Four Levels

Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.

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Abstract TP201: The Relationship Between Chronic Kidney Diseases and the Presence of Cerebral Small Vessel Disease in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp201 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Kana Ueki ◽

Asako Nakamura ◽

Masahiro Yasaka ◽

Takahiro Kuwashiro ◽

Seiji Gotoh ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

White Matter Lesion ◽

Kidney Diseases ◽

Univariate Analysis ◽

Small Vessel ◽

Chronic Kidney Diseases ◽

History Of ◽

The Relationship

Introduction: Cerebral small vessel diseases (SVDs) i.e. white matter lesion and cerebral microbleeds (CMBs) are related to the patients with stroke more deeply than those without. In general population, in addition to age, hypertension, diabetes chronic kidney diseases (CKD) is well known to be related to SVDs, but it remains unclear in patients with stroke. We investigated the relationship between CKD and the presence of SVDs in patients with acute ischemic stroke. Methods: We enrolled 493 patients with acute ischemic stroke patients or transient ischemic attack patients (mean age 71; 60% male) who had undergone 1.5T MR imaging within a week of the index events from April 2013 to march 2015. We evaluated kidney function by estimated glomerular filtration rate (eGFR) with the modification of diet in Renal Disease. CKD was defined as an eGFR less than 60mil/min/1.73m 2 . CMBs were defined as focal areas of very low signal intensity smaller than 10mm. White matter lesion as Periventricular hyper intensity (PVH)>grade 2 and Deep and Subcortical White Matter Hyper intensity (DSWMH)> grade 2 were defied as advanced PVH and advanced DSWMH, respectively. We investigated relationship between CKD and CMBs, advanced PVH and advanced DSWMH using a logistic regression analysis. Results: We noted CMBs in 173 patients (35%), PVH in 81 (16%), and DSWMH in 151 (31%). An univariate analysis revealed that the age, CKD, history of stroke, and antiplatelet agents were associated with presence of CMBs, advanced PVH and severe DSWMH . The multivariate analysis revealed that CMBs, advanced PVH and advanced DSWMH were associated with age (CMBs: odds ratio(OR) ; 1.32 ; 95% confidence interval(CI), 1.10-1.60, p=0.004, advanced PVH : OR ; 3.00 ; 95% CI, 2.17-4.26, p<0.01, advanced DSWMH: OR ; 1.94; 95% CI, 1.56-2.45, p<0.01 ), history of stroke(CMBs : OR ; 2.01 ; 95% CI, 1.21-3.34, p=0.007, advanced PVH : OR ; 2.25 ; 95% CI, 1.18-4.27, p=0.01, advanced DSWMH: OR ; 1.78 ; 95% CI, 1.03-3.06, p=0.038). CKD was associated with CMBs (OR ; 1.62 ; 95% CI, 1.04-2.52, p=0.03), but PVH and DSWMH were not. Conclusions: It seems that age and history of stroke are related to CMBs, advanced PVH and advanced DSWMH, and that CKD is associates with CMBs but not with either advanced PVH or advanced DSWMH.

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