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Reduced cortical thickness in patients with Sickle Cell Disease and a high pain burden: baseline results from the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) trial

Reduced cortical thickness in patients with Sickle Cell Disease and a high pain burden: baseline results from the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) trial
Reduced cortical thickness in patients with Sickle Cell Disease and a high pain burden: baseline results from the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) trial
Background: Sickle cell anaemia (SCA) is associated with frequent episodes of vaso-occlusive pain crises, but many patients also experience chronic daily pain, which may be due to avascular necrosis of joints, bone infarction, osteomyelitis or due to intractable chronic pain without obvious pathology2 or neuropathic pain3. Not all patients experience a significant chronic pain burden4. The impact of chronic sickle cell pain on the brain is not yet clear; a recent resting-state fMRI study showed a correlation between functional connectivity of the default-mode network and number of hospitalizations for pain5. In other chronic pain conditions, reduced grey matter volume has been noted in various cortical regions involved in pain processing such as the anterior6 and posterior7-9 cingulate cortex (ACC and PCC, respectively), primary motor cortex9 (M1), primary somatosensory cortex5,6 (S1) and insula cortex. The aim of this study is to investigate the relationship between daily pain and a priori selected grey matter regions.

Methods: As part of the baseline assessments for the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) phase-II trial, 52 children and adults recorded baseline daily pain and underwent neuropsychological testing and MRI in the 14 days prior to randomisation. Daily pain was recorded on a numerical scale 0-10 for 14 days. Patients were split into "Low-Pain" group (50% of recorded days in pain). Neuropsychological assessment was carried out using: Wechsler full-scale IQ (FSIQ), working memory index (WMI) and processing speed index (PSI), Delis-Kaplan Executive Function System Tower and Sorting subtests. Patients underwent MRI on a 3T Siemens Prisma that included T2-weighted sequences to diagnose silent cerebral infarction and a 3D T1-weighted MPRAGE. Cortical parcellation was carried out using Freesurfer. A model was fitted to the imaging data variables to investigate differences between low-pain and highpain groups, controlling for age, gender and presence of SCI and socioeconomic status10 (Index of Multiple Deprivation decile by UK postcode).

Results: Five children were excluded from analysis (poor quality data or braces artefact). The final sample was 47 children and adults with SCA. There was a significant correlation with percentage of days in pain and age (r = 0.53, p = 0.0001). In the low-pain group, 11 patients reported no pain during the recorded days. High-pain patients had significantly lower WMI and a trend for lower FSIQ, PSI, Sorting-correct sorts and Sorting-free sorting description. High-pain patients had significantly reduced cortical thickness in the mean cortex of the left and right hemispheres, and significantly thinner cortex in the bilateral precuenus, bilateral PCC, left M1 and right caudal ACC. There was a trend for positive correlation between average pain and right-hemisphere rostral ACC thickness.

Conclusion: This study is the first to describe structural brain abnormalities in patients with high burden of sickle cell pain. These patients are part of a 6-month randomised controlled trial of overnight respiratory support with cognitive and pain endpoints as well as repeat MRI; this study may provide structural biomarkers that may parallel amelioration of chronic daily pain.
Delis Kaplan Executive Function System, adult, artifact, assisted ventilation, brace, brain infarction, chronic pain, cingulate gyrus, clinical trial, congenital malformation, controlled clinical trial, controlled study, diagnosis, disease model, female, gender, gray matter, human, human tissue, imaging software, insula, major clinical study, male, morbidity, nuclear magnetic resonance imaging, phase 2 clinical trial, prevention, primary motor cortex, primary somatosensory cortex, randomization, right hemisphere, sickle cell anemia, social status, thickness, thinner, velocity, working memory
0007-1048
Kawadler, J
7d035760-69ea-4b6c-8a7a-771b73453db8
Liossi, C.
fd401ad6-581a-4a31-a60b-f8671ffd3558
Inusa, B.
34506234-2179-4399-b3ea-5e8ea164ef59
Clark, C.
ce59cb73-a993-43b6-854d-84ab33e787d6
Rees, D.
664d494e-f853-4ed4-9abb-337a7f991559
Pelidis, M.
8dcd6334-d986-4097-b4a2-e46656001b39
Chakravorty, S.
9f43bc47-7778-4320-a552-5aec14ddcb60
Kirkham, F.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Kawadler, J
7d035760-69ea-4b6c-8a7a-771b73453db8
Liossi, C.
fd401ad6-581a-4a31-a60b-f8671ffd3558
Inusa, B.
34506234-2179-4399-b3ea-5e8ea164ef59
Clark, C.
ce59cb73-a993-43b6-854d-84ab33e787d6
Rees, D.
664d494e-f853-4ed4-9abb-337a7f991559
Pelidis, M.
8dcd6334-d986-4097-b4a2-e46656001b39
Chakravorty, S.
9f43bc47-7778-4320-a552-5aec14ddcb60
Kirkham, F.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58

Kawadler, J, Liossi, C., Inusa, B., Clark, C., Rees, D., Pelidis, M., Chakravorty, S. and Kirkham, F. (2017) Reduced cortical thickness in patients with Sickle Cell Disease and a high pain burden: baseline results from the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) trial. British Journal of Haematology, 176 (S1). (doi:10.1111/bjh.14613).

Record type: Meeting abstract

Abstract

Background: Sickle cell anaemia (SCA) is associated with frequent episodes of vaso-occlusive pain crises, but many patients also experience chronic daily pain, which may be due to avascular necrosis of joints, bone infarction, osteomyelitis or due to intractable chronic pain without obvious pathology2 or neuropathic pain3. Not all patients experience a significant chronic pain burden4. The impact of chronic sickle cell pain on the brain is not yet clear; a recent resting-state fMRI study showed a correlation between functional connectivity of the default-mode network and number of hospitalizations for pain5. In other chronic pain conditions, reduced grey matter volume has been noted in various cortical regions involved in pain processing such as the anterior6 and posterior7-9 cingulate cortex (ACC and PCC, respectively), primary motor cortex9 (M1), primary somatosensory cortex5,6 (S1) and insula cortex. The aim of this study is to investigate the relationship between daily pain and a priori selected grey matter regions.

Methods: As part of the baseline assessments for the Prevention of Morbidity in Sickle Cell Anaemia (POMS2b) phase-II trial, 52 children and adults recorded baseline daily pain and underwent neuropsychological testing and MRI in the 14 days prior to randomisation. Daily pain was recorded on a numerical scale 0-10 for 14 days. Patients were split into "Low-Pain" group (50% of recorded days in pain). Neuropsychological assessment was carried out using: Wechsler full-scale IQ (FSIQ), working memory index (WMI) and processing speed index (PSI), Delis-Kaplan Executive Function System Tower and Sorting subtests. Patients underwent MRI on a 3T Siemens Prisma that included T2-weighted sequences to diagnose silent cerebral infarction and a 3D T1-weighted MPRAGE. Cortical parcellation was carried out using Freesurfer. A model was fitted to the imaging data variables to investigate differences between low-pain and highpain groups, controlling for age, gender and presence of SCI and socioeconomic status10 (Index of Multiple Deprivation decile by UK postcode).

Results: Five children were excluded from analysis (poor quality data or braces artefact). The final sample was 47 children and adults with SCA. There was a significant correlation with percentage of days in pain and age (r = 0.53, p = 0.0001). In the low-pain group, 11 patients reported no pain during the recorded days. High-pain patients had significantly lower WMI and a trend for lower FSIQ, PSI, Sorting-correct sorts and Sorting-free sorting description. High-pain patients had significantly reduced cortical thickness in the mean cortex of the left and right hemispheres, and significantly thinner cortex in the bilateral precuenus, bilateral PCC, left M1 and right caudal ACC. There was a trend for positive correlation between average pain and right-hemisphere rostral ACC thickness.

Conclusion: This study is the first to describe structural brain abnormalities in patients with high burden of sickle cell pain. These patients are part of a 6-month randomised controlled trial of overnight respiratory support with cognitive and pain endpoints as well as repeat MRI; this study may provide structural biomarkers that may parallel amelioration of chronic daily pain.

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More information

e-pub ahead of print date: 15 March 2017
Published date: March 2017
Additional Information: Special Issue: Abstracts of the 57th Annual Scientific Meeting of the British Society for Haematology, 27–29 March 2017, Brighton, UK
Venue - Dates: 57th Annual Scientific Meeting of the British Society for Haematology, United Kingdom, 2017-03-27 - 2017-03-29
Keywords: Delis Kaplan Executive Function System, adult, artifact, assisted ventilation, brace, brain infarction, chronic pain, cingulate gyrus, clinical trial, congenital malformation, controlled clinical trial, controlled study, diagnosis, disease model, female, gender, gray matter, human, human tissue, imaging software, insula, major clinical study, male, morbidity, nuclear magnetic resonance imaging, phase 2 clinical trial, prevention, primary motor cortex, primary somatosensory cortex, randomization, right hemisphere, sickle cell anemia, social status, thickness, thinner, velocity, working memory

Identifiers

Local EPrints ID: 430150
URI: http://eprints.soton.ac.uk/id/eprint/430150
ISSN: 0007-1048
PURE UUID: ca8cb74f-76bd-4668-9c34-ccbf13a797ab
ORCID for C. Liossi: ORCID iD orcid.org/0000-0003-0627-6377
ORCID for F. Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

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Date deposited: 15 Apr 2019 16:30
Last modified: 07 Oct 2020 01:52

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