Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline

Abstract

Background and Purpose Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in MS patients contributing to cognitive impairment. We sought to localize perfusion distribution differences in relapsing-remitting MS patients with and without cognitive impairment, and healthy controls. Materials and Methods 39 relapsing-remitting MS patients (20 cognitively impaired, 19 non-impaired) and 19 age and gender-matched healthy controls underwent a neurocognitive battery and MRI scanning. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. Results Adjusting for localized volumetric differences in the right frontal, temporal and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for cognitively impaired patients compared to unimpaired patients and controls. Compared to healthy controls, reduced CBF was present in the limbic regions of cognitively impaired patients and reduced CBV in the right middle frontal gyrus of cognitively impaired and temporal gyrus of non-impaired relapsing-remitting MS patients. Conclusions Consistent regional frontal cortical perfusion deficits are present in relapsing-remitting MS patients, with more widespread hypoperfusion in cognitively impaired patients, independent of structural differences indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS.

Local functional connectivity of patients with acute and remitting multiple sclerosis

“…[ 34 , 35 ] A previous study reported a significant hypoperfusion area was found for MS in the superior frontal gyrus, suggesting superior frontal gyrus has tissue damage. [ 36 ] The similar alteration was also reported in other previous perfusion study, [ 37 ] which showed a progressive cerebral blood flow and cerebral blood volume deficits present in the superior frontal gyrus for RRMS patients. Another study using echo planar spectroscopic imaging showed abnormal metabolite such as decreased NAA and Glx were predominantly tested in gray matter within prefrontal cortices in MS patients.…”

Enrichment of disease-associated genes in cortical areas defined by transcriptome-based parcellation

“…36,37 The enrichment of genes associated with multiple sclerosis in the inferior frontal gyrus might explain reductions in blood flow and activation correlated with cognitive impairments in affected patients. 38,39 Lastly, the enrichment of genes associated with neuralgia and migraine in the midcingulate cortex is in accordance with a recently characterized pathway from the area to the posterior insula that supports the development of chronic hypersensitivity to pain. 40 Limitations arising from different sources need to be considered.…”

Cortical and Deep Gray Matter Perfusion Associations With Physical and Cognitive Performance in Multiple Sclerosis Patients

“…In similar manner, hypoperfusion of the thalamus, a deep gray matter (DGM) region highly implicated in MS, has been associated with worse disability and composite clinical scores (8). Lastly, MS patients with cognitive impairment demonstrate greater cortical perfusion deficits despite any evidence of structural abnormalities or significant brain atrophy (9). The changes in DSC and ASL-based perfusion measures within the cortical and DGM in MS patients and their association with clinical outcomes have been recently reviewed elsewhere (6).…”