Diffusion tensor imaging reveals neuronal microstructural changes in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a variety of physical and neurological complaints indicating the central nervous system plays a role in ME/CFS pathophysiology. Diffusion tensor imaging (DTI) has been used to study microstructural changes in neurodegenerative diseases. In this study, we evaluated DTI parameters to investigate microstructural abnormalities in ME/CFS patients. We estimated DTI parameters in 25 ME/CFS patients who met Fukuda criteria (ME/CFSFukuda), 18 ME/CFS patients who met International Consensus Criteria (ICC) (ME/CFSICC) only and 26 healthy control (HC) subjects. In addition to voxel‐based DTI‐parameter group comparisons, we performed voxel‐based DTI‐parameter interaction‐with‐group regressions with clinical and autonomic measures to test for abnormal regressions. Group comparisons between ME/CFSICC and HC detected significant clusters (a) with decreased axial diffusivity (p = .001) and mean diffusivity (p = .01) in the descending cortico‐cerebellar tract in the midbrain and pons and (b) with increased transverse diffusivity in the medulla. The mode of anisotropy was significantly decreased (p = .001) in a cluster in the superior longitudinal fasciculus region. Voxel‐based group comparisons between ME/CFSFukuda and HC did not detect significant clusters. For ME/CFSICC and HC, DTI parameter interaction‐with‐group regressions were abnormal for the clinical measures of information processing score, SF36 physical, sleep disturbance score and respiration rate in both grey and white matter regions. Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFSICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS.

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome

“…Importantly, a recent MRI study has suggested increased myelination in subcortical white matter regions in ME/CFS patients (Thapaliya et al, 2020). Moreover, an MRI diffusion study has shown that MD value was lower in the brainstem in ME/CFS ICC patients which is also consistent with increased subcortical myelination (Thapaliya et al, 2021). Collectively, these data suggest the fimbria volume was increased in ME/CFS ICC patients compared with HC.…”

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings

“…Also importantly, these MRI brain changes were associated with, and supported by, a wide range of clinical assessments, including the vital signs (36,38,43,46), sleep parameters (36,38,46), disease duration (36,37) and severity levels (37,39,41,42,44).…”

“…The studies pointed to a reduced WM volume (36)(37)(38)(39), impairments in myelination (36,38,40,43,46), reduced conduction (37,38,40,46), abnormal FC linking the brainstem and other brain regions (41,42,44), and compensatory brain changes (37,40). The research findings also demonstrated a linkage between brainstem abnormalities and other brainstem structures, highlighting myelination impairment and dysregulation underlying the disease (Table 2 and Figure 2).…”

“…Despite the widely available MRI technologies as applied in studying other clinical conditions (48), they have yet to be sufficiently employed in better understanding ME/CFS. For example, structural scans have only involved T1W and T2W sequences in investigating the brainstem, save for the most recent pioneer DTI work (46). Future research using different MRI techniques, including DTI and other advanced methods may help detect WM changes more sensitively.…”

“…First, the abnormal connectivity between RAS nuclei possibly lessened the cortical oscillatory coherence as they control the thalamocortical state between sleeping and wakefulness, which can consequently affect consciousness and cognitive function (19,20). Also, given the distribution of the RAS nuclei throughout the brainstem (11), their functions may be affected by the reduced WM volume and functional connectivity, and the suggested abnormal axon caliber and axonal/myelin density in the midbrain and pons (46). RAS dysfunction may lead to fatigue, impaired attention, short term memory, cognitive function, and sleep quality, all of which have been seen in the ME/CFS population (7,8).…”