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

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS. We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFS Fukuda ), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFS ICC ), and 25 healthy controls (HC). Group comparisons with HC detected extensive differences in subfield volumes in ME/CFS ICC but not in ME/ CFS Fukuda . ME/CFS ICC patients had significantly larger volume in the left subiculum head (p < 0.001), left presubiculum head (p = 0.0020), and left fimbria (p = 0.004). Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFS ICC than in ME/CFS Fukuda patients. In ME/CFS Fukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume. In ME/CFS ICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume.Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head). Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFS ICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFS ICC patients.

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis

“…Similar disrupted patterns of resting state FC have been observed to correlate with levels of fatigue and pain [41][42][43]. Imaging studies have also revealed abnormalities in brain structure and regional volumes [44][45][46][47][48], intra brainstem connectivity [49], (and cortical hypoactivation during resting EEG [50], including grey matter and white matter changes [45][46][47][50][51][52]. In a study of cortical autonomic network connectivity, 'reduced higher-order homeostatic regulation and adaptability in ME/CFS' was observed [53], which, if confirmed, would suggest the CHN as a potential therapeutic target for managing patient symptoms.…”

Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome

“…A recent PET study has reported underlying severe and extensive hypometabolism in the cerebellum region in patients with long-lasting ME/CFS ( Sahbai et al, 2019 ). A recent study reported that memory deficits in ME/CFS patients were associated with hippocampal volume changes ( Thapaliya et al, 2022 ). Another study in ME/CFS patients detected diffusion deficits in the fronto-pontine tract ( Thapaliya et al, 2021 ), supporting a role for the pontine nucleus and cerebellum in motion execution, relating it to impaired motor response preparation for some tasks ( Paul et al, 2008 ; Rasouli et al, 2017 ).…”

“…Magnetic resonance imaging (MRI) studies have been used to study structural and functional changes in ME/CFS patients. Anatomical anomalies have been reported in cortical and subcortical regions ( Buchwald et al, 1992 ; Okada et al, 2004 ; de Lange et al, 2005 ), with a significant reduction in cortical volume and thickness and an increase in hippocampal and brainstem volumes in ME/CFS patients when compared with healthy controls (HCs) ( Thapaliya et al, 2022 ). Moreover, Thapaliya et al (2020) reported significantly higher signal intensities in the white matter and basal ganglia regions using the ratio of T1 weighted-T2 weighted images in ME/CFS patients.…”

Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism

“…Saury JM et al believes that the hippocampus plays an important role in the pathogenesis of CFS, and the trigger factors of CFS will also affect the hippocampus, leading to neurocognitive defects and disorders in the regulation of the pressure system and pain perception, which will further affect the hippocampus and trigger a vicious cycle of increased disability ( Saury, 2016 ). There is a negative correlation between fatigue and hippocampus volume in CFS patients ( Thapaliya et al, 2022 ). In addition, the prefrontal cortex has been identified as critical to fatigue ( Ifuku et al, 2014 ).…”