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CNS findings in chronic fatigue syndrome and a neuropathological case report
  1. Kimberly Ferrero1,
  2. Mitchell Silver1,
  3. Alan Cocchetto2,
  4. Eliezer Masliah3,
  5. Dianne Langford1
  1. 1Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
  2. 2State University of New York at Alfred, Engineering Technologies, Alfred, New York, USA
  3. 3University of California San Diego, La Jolla, California, USA
  1. Correspondence to Dianne Langford, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB 750, Philadelphia, PA 19140, USA; tdl{at}


Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS. Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia. Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.

  • Nervous System Diseases
  • Neurodegenerative Diseases
  • Brain Diseases

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  • Contributors DL conducted experiments, analyzed data, and wrote the manuscript. MS assisted with data generation and edited the manuscript. AC assisted with data collection and manuscript preparation. EM reviewed all neuropathological findings, analyzed the slides, and assisted with writing the manuscript.

  • Funding This work was supported by funding from the National Chronic Fatigue and Immune Dysfunction Syndrome Foundation to DL.

  • Competing interests None declared.

  • Ethics approval Temple University IRB Human Subjects Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.