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The relationship of microglial activation and multiple sclerosis-associated fatigue: a [F-18]PBR06 PET study
Author(s): ,
T. Singhal
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology
,
K. O`Connor
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology
,
H. Pan
Affiliations:
Functional Neuroimaging Laboratory, Department of Psychiatry
,
S. Dubey
Affiliations:
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology
,
S. Cicero
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology
,
S. Hurwitz
Affiliations:
Department of Medicine
,
S. Tauhid
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology
,
M. Kijewski
Affiliations:
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology
,
D. Silbersweig
Affiliations:
Functional Neuroimaging Laboratory, Department of Psychiatry
,
E. Stern
Affiliations:
Functional Neuroimaging Laboratory, Department of Psychiatry; Department of Radiology, Brigham and Women`s Hospital, Harvard Medical School, Boston, MA, United States
,
R. Bakshi
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology; Department of Radiology, Brigham and Women`s Hospital, Harvard Medical School, Boston, MA, United States
H.L. Weiner
Affiliations:
Partners Multiple Sclerosis Center, Laboratory for Neuroimaging Research, Ann Romney Center for Neurologic Diseases, Department of Neurology
ECTRIMS Online Library. Singhal T. Oct 12, 2018; 228147
Tarun Singhal
Tarun Singhal
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Abstract: P1769

Type: Poster Sessions

Abstract Category: N/A

Introduction: Fatigue is a disabling symptom in most multiple sclerosis (MS) patients but its underlying mechanism is unclear. Microglial activation may play a role in the pathogenesis of MS but it has not been systematically studied in relation to MS-associated fatigue (MSAF). [F-18]PBR06 is a second-generation, longer half-life positron emission tomography (PET) radioligand, targeting the 18kDa-translocator protein for noninvasive assessment of cerebral microglial activation. Our aim is to assess the role of microglial activation in MSAF using [F-18]PBR06 PET.
Methods: Fatigue severity was measured using modified fatigue impact scale (MFIS) in twelve MS subjects [7 relapsing-remitting and 5 secondary progressive] who underwent [F-18]PBR06 PET. Standardized Uptake Value (SUV) 60-90 minute frame PET maps were co-registered to 3T MRI. Atlas-based regional analyses (using Automated Anatomical Labeling template and Hammers atlases) and voxel-by-voxel analysis using statistical parametric mapping (SPM) were performed. SUV ratios (SUVRs) were global brain-normalized.
Results: There were significant correlations between MFIS scores and SUVRs in the substantia nigra (SN) (r=0.76, p=0.004), right parahippocampal gyrus (R PHG) (r=0.75, p=0.005), right precuneus (r=0.66, p=0.02), and left putamen (r=0.61, p=0.03). The cognitive fatigue subscale of MFIS showed a significant correlation with SUVRs in the SN (r=0.71, p=0.009), R PHG (r=0.67, p=0.02), and right precuneus (r=0.71, p=0.009); the physical fatigue subscale showed significant correlations with SUVRs in the SN, R PHG, thalamus, and left putamen (r=0.77, 0.77, 0.58, 0.66; p= 0.003, 0.003, 0.04, 0.02, respectively). The psychosocial fatigue subscale significantly correlated with R PHG SUVR (r=0.66, p=0.02). On SPM analysis, additional clusters of voxels in juxtacortical white matter, cerebellar vermis and hypothalamus demonstrated significant correlations with MFIS (all p< 0.05).
Conclusion: Our data suggests that microglial activation across key brain regions represents a unifying mechanism for MSAF. Microglial activation may represent a therapeutic target for MSAF and further evaluation of neuroimmunological basis of MSAF is warranted.
Disclosure: H.L.W. has received consulting fees from Biogen, Nasvax, Novartis, Merck-Serono, and Teva Neurosciences and has received grant support from Merck-Serono and Sanofi-Genzyme. R.B. has received consulting fees from EMD Serono, Genentech, Guerbet, Sanofi- Genzyme, and Shire and research support from EMD Serono and Sanofi- Genzyme. T. Singhal: nothing to disclose. K. O´Connor: nothing to disclose. H. Pan: nothing to disclose. S. Dubey: nothing to disclose. S. Hurwitz: nothing to disclose. S. Cicero: nothing to disclose. S. Tauhid: nothing to disclose. M. Kijewski: nothing to disclose. D. Silbersweig: nothing to disclose. E. Stern: nothing to disclose.
The authors received research grants from Nancy Davis Foundation´s “Race to Erase MS” program and Harvard Neuro Discovery Center for support of this work.

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