brain abnormalities – Page 2 – American ME and CFS Society

Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging

Abstract:

BACKGROUND: Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI).

PURPOSE: To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics.

STUDY TYPE: Prospective.

POPULATION: Twenty ME/CFS patients and 23 healthy controls were recruited.

FIELD STRENGTH/SEQUENCE: Three-b value DWI (b-values = 0, 1000, and 2000 sec/mm2 ) and 3D T1 -weighted images were at 3.0T.

ASSESSMENT: Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated.

STATISTICAL TESTING: The two-sample t-test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups.

RESULTS: In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05).

DATA CONCLUSION: Right SLF abnormalities may be a diagnostic marker for ME/CFS.

LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Source: Kimura Y, Sato N, Ota M, Shigemoto Y, Morimoto E, Enokizono M, Matsuda H, Shin I, Amano K, Ono H, Sato W, Yamamura T. Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging. J Magn Reson Imaging. 2018 Nov 14. doi: 10.1002/jmri.26247. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30430664

Brain Science on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. A variety of studies have been performed to establish objective biomarkers of the disease, including positron emission tomography (PET) molecular imaging and neuro-functional imaging using magnetic resonance imaging (MRI) and magnetoencephalogram (MEG). In this chapter, we summarize the results from PET, MRI, and MEG imaging.

Regional cerebral blood flow and glucose utilization rates are decreased in patients with ME/CFS as compared with age- and sex-matched healthy subjects. Acetyl-L-carnitine uptake into the releasable pool of glutamate and serotonin transporters densities are decreased in a few specific brain regions, mostly in the anterior cingulate in the patients. Although it is hypothesized that brain inflammation is involved in the pathophysiology of ME/CFS, there was no direct evidence of neuroinflammation in patients.

Our recent PET study successfully demonstrated that neuroinflammation is present in widespread brain areas in ME/CFS patients, and is associated with the severity of neuropsychological symptoms. Evaluation of neuroinflammation in patients with ME/CFS may be essential for understanding the core pathophysiology, as well as for developing objective diagnostic criteria and effective medical treatments for ME/CFS. By using specific neurological features of these patients such as prefrontal cortical atrophies and the over-guarding phenomenon were found using MRI and functional MRI, respectively. We here describe related pathophysiological findings and topics in order to aid in the development of future therapies for ME/CFS patients.

Source: Watanabe Y. Brain Science on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Nerve. 2018 Nov;70(11):1193-1201. doi: 10.11477/mf.1416201164. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/30416112

The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy

Abstract:

The underlying pathophysiology of chronic fatigue syndrome remains incompletely understood and there are no curative treatments for this disorder at present. However, increasing neuroimaging evidence indicates that functional and structural abnormalities exist in the brains of chronic fatigue syndrome patients, suggesting that the central nervous system is involved in this disorder and that at least some chronic fatigue syndrome patients may have an underlying neurological basis for their illness.

In the present paper, we speculate that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome. We further postulate that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain.

Although recent evidence indicates that at least some chronic fatigue syndrome patients may benefit from cerebrospinal fluid drainage, further studies are needed to confirm this finding and to determine whether this can be attributed to enhancement of glymphatic fluid flow and interstitial fluid clearance. If confirmed, this could offer promising avenues for the future treatment of chronic fatigue syndrome. Clearly, given the relative invasive nature of cerebrospinal fluid diversion, such procedures should be reserved for chronic fatigue syndrome patients who are severely debilitated, or for those with severe headaches. Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.

Source: Wostyn P, De Deyn PP. The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy. Med Hypotheses. 2018 Sep;118:142-145. doi: 10.1016/j.mehy.2018.07.007. Epub 2018 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/30037603

Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients

Abstract:

Chronic fatigue syndrome (CFS) is a disorder associated with fatigue, pain, and structural/functional abnormalities seen during magnetic resonance brain imaging (MRI). Therefore, we evaluated the performance of structural MRI (sMRI) abnormalities in the classification of CFS patients versus healthy controls and compared it to machine learning (ML) classification based upon self-report (SR). Participants included 18 CFS patients and 15 healthy controls (HC). All subjects underwent T1-weighted sMRI and provided visual analogue-scale ratings of fatigue, pain intensity, anxiety, depression, anger, and sleep quality. sMRI data were segmented using FreeSurfer and 61 regions based on functional and structural abnormalities previously reported in patients with CFS. Classification was performed in RapidMiner using a linear support vector machine and bootstrap optimism correction.

We compared ML classifiers based on (1) 61 a priori sMRI regional estimates and (2) SR ratings. The sMRI model achieved 79.58% classification accuracy. The SR (accuracy = 95.95%) outperformed both sMRI models. Estimates from multiple brain areas related to cognition, emotion, and memory contributed strongly to group classification. This is the first ML-based group classification of CFS. Our findings suggest that sMRI abnormalities are useful for discriminating CFS patients from HC, but SR ratings remain most effective in classification tasks.

Source: Sevel LS, Boissoneault J, Letzen JE, Robinson ME, Staud R. Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients. Exp Brain Res. 2018 May 30. doi: 10.1007/s00221-018-5301-8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29846797

Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by fatigue lasting for at least six months, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. ME/CFS has been a controversial illness because it is defined exclusively by subjective complaints. However, recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation – either inside or outside the brain – through release of inflammatory cytokines. In this review, we summarize potentially important recent findings on ME/CFS, focusing on objective evidence.

Source: Komaroff AL, Takahashi R, Yamamura T, Sawamura M. Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Brain Nerve. 2018 Jan;70(1):41-54. doi: 10.11477/mf.1416200948. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/29348374

VIDEO: Discovery Forum 2017 Highlights: ME/CFS and Gulf War Illness

The Solve ME/CFS Initiative presents highlights from Discovery Forum 2017 addressing the connections between Gulf War Illness and ME/CFS, featuring the presentation of Dr. Nancy Klimas of Nova Southeastern University. Dr. Klimas has more than 30 years of professional experience and has achieved international recognition for her research and clinical efforts in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Gulf War Illness (GWI).

Decreased connectivity and increased BOLD complexity in the default mode network in individuals with chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome / myalgic encephalomyelitis (CFS) is a debilitating disease with unknown pathophysiology and no diagnostic test. This study investigated the default mode network (DMN) in order to understand the pathophysiology of CFS and to identify potential biomarkers.

Using functional MRI (fMRI) collected from 72 subjects (45 CFS and 27 controls) with a temporal resolution of 0.798s, we evaluated the default mode network using static functional connectivity (FC), dynamic functional connectivity (DFC) and DFC complexity, blood oxygenation level dependent (BOLD) activation maps and complexity of activity. General linear model (GLM) univariate analysis was used for inter group comparison to account for age and gender differences. Hierarchical regression analysis was used to test whether fMRI measures could be used to explain variances of health scores.

BOLD signals in the posterior cingulate cortex (PCC), the driving hub in the DMN, were more complex in CFS in both resting state and task (P < 0.05). The FCs between medial prefrontal cortex (mPFC) and both inferior parietal lobules (IPLs) were weaker (P < 0.05) during resting state, while during task mPFC – left IPL and mPFC – PCC were weaker (P < 0.05). The DFCs between the DMN hubs were more complex in CFS (P < 0.05) during task. Each of these differences accounted for 7 – 11% variability of health scores. This study showed that DMN activity is more complex and less coordinated in CFS, suggesting brain network analysis could be potential used as a diagnostic biomarker for CFS.

Source: Shan ZY, Finegan K, Bhuta S, Ireland T, Staines DR, Marshall-Gradisnik SM, Barnden LR. Decreased connectivity and increased BOLD complexity in the default mode network in individuals with chronic fatigue syndrome. Brain Connect. 2017 Nov 20. doi: 10.1089/brain.2017.0549. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29152994

Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects

Abstract:

Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) have similar profiles of pain, fatigue, cognitive dysfunction and exertional exhaustion. Post-exertional malaise suggests exercise alters central nervous system functions. Lumbar punctures were performed in GWI, CFS and control subjects after (i) overnight rest (nonexercise) or (ii) submaximal bicycle exercise. Exercise induced postural tachycardia in one third of GWI subjects (Stress Test Activated Reversible Tachycardia, START). The remainder were Stress Test Originated Phantom Perception (STOPP) subjects. MicroRNAs (miRNA) in cerebrospinal fluid were amplified by quantitative PCR. Levels were equivalent between nonexercise GWI (n = 22), CFS (n = 43) and control (n = 22) groups. After exercise, START (n = 22) had significantly lower miR-22-3p than control (n = 15) and STOPP (n = 42), but higher miR-9-3p than STOPP. All post-exercise groups had significantly reduced miR-328 and miR-608 compared to nonexercise groups; these may be markers of exercise effects on the brain. Six miRNAs were significantly elevated and 12 diminished in post-exercise START, STOPP and control compared to nonexercise groups. CFS had 12 diminished miRNAs after exercise. Despite symptom overlap of CFS, GWI and other illnesses in their differential diagnosis, exercise-induced miRNA patterns in cerebrospinal fluid indicated distinct mechanisms for post-exertional malaise in CFS and START and STOPP phenotypes of GWI.

Source: James N. Baraniuk & Narayan Shivapurkar. Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects. Scientific Reports 7, Article number: 15338 (2017) doi:10.1038/s41598-017-15383-9 https://www.nature.com/articles/s41598-017-15383-9 (Full article)

Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: A magnetic resonance spectroscopy study at 7 Tesla

Abstract:

Background: Chronic fatigue syndrome (CFS) is a disorder characterized by prolonged physical and mental fatigue that cannot be explained by another established medical diagnosis. The anterior cingulate cortex (ACC) and putamen are two regions involved in frontal-striatal neural circuitry, which may be related to the pathophysiology of CFS. The aim of this study was to investigate the concentrations of neurometabolites, including glutamate, gamma-aminobutyric acid (GABA) and glutathione, in the ACC and putamen, using magnetic resonance spectroscopy (MRS) at 7 Tesla (7T). In addition, this study also aimed to evaluate resting-state functional connectivity in CFS with functional magnetic resonance imaging (fMRI).

Methods: This study involved 12 patients who met the Oxford criteria for CFS and 25 healthy controls. Participants rated themselves on the Chalder Fatigue Questionnaire (CFQ) and the Beck Depression Inventory (BDI). All participants had a single proton (1H) MRS and resting-state fMRI scan with a 7T Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32 channel receive array head coil. Spectra were measured from voxels in the ACC (20 × 20 × 20 mm), putamen (10 × 16 × 20 mm) and occipital cortex (20 × 20 × 20 mm). Spectra were analysed with LCModel to obtain absolute concentrations of the neurochemicals. Differences in functional connectivity between CFS and healthy participants were tested using multivariate exploratory linear optimized decomposition into independent components (MELODIC) and dual regression.

Results: Concentrations of putamen glutamate and glutamate+glutamine (Glx) were increased in CFS while that of ACC GABA was decreased. Putamen Glx and ACC glutamine were negatively associated with the severity of self-reported fatigue. There were main effects of CFS diagnosis on glutathione (GSH) and total creatine, indicating decreases of these neurometabolites in all the regions studied in CFS patients. In addition, the CFS patients demonstrated elevated functional connectivity between the default mode network and right supracalcarine cortex, precuneus cortex and dorsolateral prefrontal cortex.

Conclusions: The increased putamen glutamate, decreased ACC GABA and elevated resting state functional connectivity of the default mode network suggest a hyperactive brain status in CFS. The global decrease of GSH and total creatine also suggest that CFS patients may have an abnormal bioenergetic status with higher oxidative stress.

Source: Chi Chen. Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: A magnetic resonance spectroscopy study at 7 Tesla. Oxford University Research Archive. September 22, 2017. (Open access article) https://ora.ox.ac.uk/objects/uuid:60ff242e-2ccd-4f23-ac7d-16553d864e8b

Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study

Abstract:

OBJECTIVE: Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods.

METHODS: Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments.

RESULTS: Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe.

CONCLUSION: Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.

Source: Finkelmeyer A, He J, Maclachlan L, Watson S, Gallagher P, Newton JL, Blamire AM. Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study. Neuroimage Clin. 2017 Sep 28;17:24-30. doi: 10.1016/j.nicl.2017.09.024. ECollection 2018. https://www.ncbi.nlm.nih.gov/pubmed/29021956