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Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome1

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Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. ORIGINAL R Right Arcuate Fasciculus ESEARCH Abnormality in Chronic Fatigue n Syndrome1 NEURORADIOLOGY Michael M. Zeineh, MD, PhD Purpose: To identify whether patients with chronic fatigue syndrome James Kang, MD (CFS) have differences in gross brain structure, micro- Scott W. Atlas, MD scopic structure, or brain perfusion that may explain their Mira M. Raman, MS symptoms. Allan L. Reiss, MD Jane L. Norris, PA Materials and Fifteen patients with CFS were identified by means of Ian Valencia, BS Methods: retrospective review with an institutional review board– Jose G. Montoya, MD approved waiver of consent and waiver of authorization. Fourteen age- and sex-matched control subjects provided informed consent in accordance with the institutional review board and HIPAA. All subjects underwent 3.0-T volumetric T1-weighted magnetic resonance (MR) imag- ing, with two diffusion-tensor imaging (DTI) acquisitions and arterial spin labeling (ASL). Open source software was used to segment supratentorial gray and white matter and cerebrospinal fluid to compare gray and white matter volumes and cortical thickness. DTI data were processed with automated fiber quantification, which was used to compare piecewise fractional anisotropy (FA) along 20 tracks. For the volumetric analysis, a regression was per- formed to account for differences in age, handedness, and total intracranial volume, and for the DTI, FA was com- pared piecewise along tracks by using an unpaired t test. The open source software segmentation was used to com- pare cerebral blood flow as measured with ASL. Results: In the CFS population, FA was increased in the right ar- cuate fasciculus (P = .0015), and in right-handers, FA was also increased in the right inferior longitudinal fasciculus (ILF) (P = .0008). In patients with CFS, right anterior arcuate FA increased with disease severity (r = 0.649, P = .026). Bilateral white matter volumes were reduced in CFS (mean 6 standard deviation, 467 581 mm3 6 47 610 for patients vs 504 864 mm3 6 68 126 for control subjects, P = .0026), and cortical thickness increased in both right arcuate end points, the middle temporal (T = 4.25) and precentral (T = 6.47) gyri, and one right ILF end point, the occipital lobe (T = 5.36). ASL showed no significant differences. 1 From the Department of Radiology, Lucas Center for Conclusion: Bilateral white matter atrophy is present in CFS. No dif- Imaging, Stanford University School of Medicine, 1201 ferences in perfusion were noted. Right hemispheric in- Welch Rd, Room P271, Stanford, CA 94305-5488. Received creased FA may reflect degeneration of crossing fibers or May 7, 2014; revision requested June 10; revision received strengthening of short-range fibers. Right anterior arcuate July 4; accepted July 16; final version accepted July 29. FA may serve as a biomarker for CFS. Supported by the Division of Infectious Disease CFS Fund. M.M.Z. supported by GE Healthcare. Address correspon- q dence to M.M.Z. (e-mail: [email protected]). RSNA, 2014 q RSNA, 2014 Online supplemental material is available for this article. Radiology: Volume 274: Number 2—February 2015 n radiology.rsna.org 517 NEURORADIOLOGY: Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome Zeineh et al hronic fatigue syndrome (CFS) is has been explored across a variety of none of these patients were excluded. a debilitating disorder character- neurodegenerative disorders. White More than 300 control subjects from a Cized by 6 or more months of per- matter microstructure may be altered database of volunteers were examined sistent or relapsing fatigue without any in CFS as a consequence of inflamma- to find age-matched (within 1 year) associated medical or psychiatric disor- tion (12) or as part of the neurocog- and sex-matched participants without der (1). The high prevalence of 2–4 per nitive physiology of fatigue (13), but it any history of major depression, CFS 1000 people in the United States (2,3), has not been investigated to date with or chronic fatigue, or substance abuse combined with the profound disability DTI. in the past year; 28 eligible volunteers (4) and poor prognosis (5), motivates The purpose of this study was to (a) were contacted, and 14 chose to par- urgent scientific investigation. Brain identify differences in gross brain struc- ticipate and underwent MR imaging. imaging could aid in diagnosis and ture in CFS by using T1-weighted gray Control subjects provided informed prognosis. However, structural imaging and white matter volumetric analysis, consent in accordance with the insti- findings have been inconsistent: Three (b) detect microstructural abnormal- tutional review board and the Health voxel-based morphometry studies dem- ities underlying CFS by using DTI, and Insurance Portability and Accountabil- onstrated gray matter atrophy in dif- (c) detect global alterations in brain ity Act. The 20-item Multidimensional fering locations when specified (6–8), perfusion by using pseudocontinuous Fatigue Inventory (MFI-20) was ad- while one study in which cerebrospinal arterial spin labeling (ASL). ministered to each subject, which has fluid was segmented yielded no atrophy been validated as a reproducible in- (9). Brain perfusion studies have shown strument for the identification of CFS inconsistent decreases (10), with a Materials and Methods (14–17). The MFI-20 score is used to well-controlled study of monozygotic assess general, physical, and mental twins showing no differences (11). No Subjects fatigue, as well as reduced motivation technique has provided either a patho- This study began in June 2011, and and activity; higher MFI-20 scores in- physiological understanding of the dis- follow-up was completed in November dicate increased severity. Subjects order or served as a biomarker. 2013. Institutional review board ap- completed an expanded Edinburgh With diffusion-tensor imaging (DTI), proval with a waiver of consent and a handedness inventory (http://www. the random motion of water is used to waiver of authorization were obtained, brainmapping.org/shared/Edinburgh. demonstrate brain microstructure and and a retrospective review was con- php), with scores thresholded at 48 ducted from 2008 to the present for Advances in Knowledge patients evaluated in the university CFS n Patients with severe chronic clinic. Inclusion criteria were (a) the Published online before print fatigue syndrome (CFS) have clinical criteria for CFS (fatigue for a 10.1148/radiol.14141079 Content codes: duration of 6 months or longer, along increased fractional anisotropy Radiology 2015; 274:517–526 (FA) in the anterior right arcuate with having at least four of the eight Abbreviations: fasciculus when compared with Fukuda symptoms: impaired memory ASL = arterial spin labeling control subjects (P = .0015), with or concentration, sore throat, tender lymph nodes, headaches, muscle pain, CFS = chronic fatigue syndrome most right-handed patients CI = confidence interval joint pain, unrefreshing sleep, and having maximal FA in the ante- DTI = diffusion-tensor imaging rior 10% of the arcuate of higher postexertional malaise) and (b) ongoing FA = fractional anisotropy than 0.6, while in the same memory and concentration symptoms ILF = inferior longitudinal fasciculus MFI-20 = 20-item Multidimensional Fatigue Inventory region, most right-handed con- that cause a severe enough impairment that the physician determined clinical ROC = receiver operating characteristic trol subjects have an FA of less ROI = region of interest than 0.6. magnetic resonance (MR) imaging was appropriate to exclude other diagnoses. Author contributions: n The right hemisphere in younger All patients with CFS except one were Guarantors of integrity of entire study, M.M.Z., J.K., J.G.M.; patients with CFS exhibits evaluated by one clinician (J.G.M., with study concepts/study design or data acquisition or data regions of cortical thickening that 10 years of experience with CFS). No analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all are connected via the right ar- other inclusion or exclusion criteria authors; approval of final version of submitted manuscript, cuate fasciculus, specifically in were used for patients with CFS. Among the right middle temporal and all authors; agrees to ensure any questions related to the 259 charts reviewed, 15 patients were work are appropriately resolved, all authors; literature precentral gyri. identified who met these criteria, and research, M.M.Z., J.K., J.G.M.; clinical studies, M.M.Z., J.K., n White matter volumes are lower S.W.A., J.L.N., I.V., J.G.M.; experimental studies, M.M.Z., in patients with CFS compared J.K., A.L.R., I.V.; statistical analysis, M.M.Z., J.K., A.L.R.; with control subjects (467 581 Implication for Patient Care and manuscript editing, M.M.Z., J.K., S.W.A., A.L.R., I.V., J.G.M. mm3 6 47 610 vs 504 864 mm3 6 n Right anterior arcuate FA may be 68 126, P = .0026). a biomarker for CFS. Conflicts of interest are listed at the end of this article. 518 radiology.rsna.org n Radiology: Volume 274: Number 2—February 2015 NEURORADIOLOGY: Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome Zeineh et al and higher. Four subjects declined this proton-density image, and imaging time volumes were excluded from analysis. inventory and simply described them- of 4 minutes 50 seconds). One patient Data were corrected for motion with a selves as left-handed, right-handed, or with CFS did not undergo ASL imaging rigid-body transformation and aligned ambidextrous. Left-handed and ambi- because of a technical error. to the b of 0 mm/sec2 image, which was dextrous subjects were pooled as non– then aligned to the T1-weighted vol- right-handed subjects. Segmentation: Volumetry ume in anterior commissure–posterior A FreeSurfer pipeline analysis con- commissure space.
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