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White matter damage relates to oxygen saturation in children with sickle cell anemia without silent cerebral infarcts

White matter damage relates to oxygen saturation in children with sickle cell anemia without silent cerebral infarcts
White matter damage relates to oxygen saturation in children with sickle cell anemia without silent cerebral infarcts

BACKGROUND AND PURPOSE: Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation.

METHODS: A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested.

RESULTS: Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum.

CONCLUSIONS: These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

Adolescent, Anemia, Sickle Cell, Cerebral Infarction, Child, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Oxygen, White Matter, Young Adult, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
0039-2499
1793-1799
Kawadler, Jamie M.
7d035760-69ea-4b6c-8a7a-771b73453db8
Kirkham, Fenella J.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Clayden, Jonathan D.
1f384d07-9591-4dd4-80e0-50244283d314
Hollocks, Matthew J.
37782979-571e-4d5e-95a3-ca8380da6bf7
Seymour, Emma L.
16cbd22f-2d2b-4d2a-a595-5038315b72d7
Edey, Rosanna
0b456f97-aedb-4e55-82b5-d40a1f6a1924
Telfer, Paul
4f57150d-6011-4689-82ab-d32aa65f32c7
Robins, Andrew
a0bfbeab-581e-4803-a897-d0c2200f4453
Wilkey, Olu
adb1eb81-8a3f-4966-820e-2d4d2d78a476
Barker, Simon
4ec1e930-ec52-4154-a7aa-537ff4785607
Cox, Tim C.S.
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Clark, Chris A.
2aa6957f-c5e9-4cdc-ac2d-7565e8c6eae8
Kawadler, Jamie M.
7d035760-69ea-4b6c-8a7a-771b73453db8
Kirkham, Fenella J.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Clayden, Jonathan D.
1f384d07-9591-4dd4-80e0-50244283d314
Hollocks, Matthew J.
37782979-571e-4d5e-95a3-ca8380da6bf7
Seymour, Emma L.
16cbd22f-2d2b-4d2a-a595-5038315b72d7
Edey, Rosanna
0b456f97-aedb-4e55-82b5-d40a1f6a1924
Telfer, Paul
4f57150d-6011-4689-82ab-d32aa65f32c7
Robins, Andrew
a0bfbeab-581e-4803-a897-d0c2200f4453
Wilkey, Olu
adb1eb81-8a3f-4966-820e-2d4d2d78a476
Barker, Simon
4ec1e930-ec52-4154-a7aa-537ff4785607
Cox, Tim C.S.
5fd0a6c2-fcdf-400f-86b8-dcfda1dd4e35
Clark, Chris A.
2aa6957f-c5e9-4cdc-ac2d-7565e8c6eae8

Kawadler, Jamie M., Kirkham, Fenella J., Clayden, Jonathan D., Hollocks, Matthew J., Seymour, Emma L., Edey, Rosanna, Telfer, Paul, Robins, Andrew, Wilkey, Olu, Barker, Simon, Cox, Tim C.S. and Clark, Chris A. (2015) White matter damage relates to oxygen saturation in children with sickle cell anemia without silent cerebral infarcts. Stroke, 46 (7), 1793-1799. (doi:10.1161/STROKEAHA.115.008721).

Record type: Article

Abstract

BACKGROUND AND PURPOSE: Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation.

METHODS: A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested.

RESULTS: Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum.

CONCLUSIONS: These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

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More information

Accepted/In Press date: 14 April 2015
e-pub ahead of print date: 12 May 2015
Published date: July 2015
Additional Information: © 2015 American Heart Association, Inc.
Keywords: Adolescent, Anemia, Sickle Cell, Cerebral Infarction, Child, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Oxygen, White Matter, Young Adult, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 420602
URI: https://eprints.soton.ac.uk/id/eprint/420602
ISSN: 0039-2499
PURE UUID: a8f5e61b-5bb7-4091-bee2-dad0e6c9943d

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Date deposited: 10 May 2018 16:31
Last modified: 13 Mar 2019 18:42

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Contributors

Author: Jamie M. Kawadler
Author: Fenella J. Kirkham
Author: Jonathan D. Clayden
Author: Matthew J. Hollocks
Author: Emma L. Seymour
Author: Rosanna Edey
Author: Paul Telfer
Author: Andrew Robins
Author: Olu Wilkey
Author: Simon Barker
Author: Tim C.S. Cox
Author: Chris A. Clark

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