TY - JOUR

T1 - Age-related decline in cerebral oxygen consumption in multiple sclerosis

AU - Knudsen, Maria H.

AU - Vestergaard, Mark B.

AU - Lindberg, Ulrich

AU - Simonsen, Helle J.

AU - Frederiksen, Jette L.

AU - Cramer, Stig P.

AU - Larsson, Henrik B.W.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

AB - Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

KW - Aging

KW - cerebral metabolism

KW - magnetic resonance imaging

KW - multiple sclerosis

KW - oxygen extraction fraction (OEF)

U2 - 10.1177/0271678X231224502

DO - 10.1177/0271678X231224502

M3 - Journal article

C2 - 38190981

AN - SCOPUS:85181758883

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

ER -