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Am J Transl Res 2013;5(1):53-68
Original Article
A Chronic Fatigue Syndrome (CFS) severity score based on case des-
ignation criteria
James N Baraniuk, Oluwatoyin Adewuyi, Samantha Jean Merck, Mushtaq Ali, Murugan K Ravindran, Christian R
Timbol, Rakib Ray-han, Yin Zheng, Uyenphuong Le, Rania Esteitie, Kristina N Petrie
Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA; School of
Medicine, University of Pennsylvania, Philadelphia, PA, USA; Internal Medicine Residency Program, 1415
Woodland Ave, Suite 140, Des Moines, IA 50309, USA; Department of Internal Medicine, Norwalk Hospital,
Norwalk, CT, USA; School of Medicine, Georgetown University, Washington, DC, USA; School of Medicine
University of South Florida, Tampa, FL, USA
Received November 25, 2012; Accepted January 3, 2013; Epub January 21, 2013; Published January 30, 2013
Abstract: Background: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective,
nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes),
cognitive dysfunction, sleep and exertional exhaustion. Methods: Subjects self-reported symptoms using an
anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of
3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested
as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure
categorization as healthy or CFS subjects. Results: Fatigued subjects were divided into CFS with ≥4 symptoms or
Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a
threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include
Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls
(HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS–Like With
Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R2=0.977; Cronbach’
s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4
clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from
cerebrospinal fluid. Conclusions: Plotting Fatigue severity versus Sum8 produced an internally consistent
classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their
pathophysiological mechanisms. (AJTR1211008).
Keywords: Fatigue, pain, fibromyalgia, myalgic encephalomyelitis, proteomics
Address correspondence to: Dr. James N Baraniuk, Georgetown University Medical Center, Division of
Rheumatology, Immunology and Allergy, Room 3004F, 3rd Floor PHC Building, 3800 Reservoir Road, NW
Washington, DC 20007-2197, USA. Phone: 202-687-2906; Fax: 202-687-9886; E-mail: baraniuj@georgetown.edu
Original Article
A Chronic Fatigue Syndrome (CFS) severity score based on case des-
ignation criteria
James N Baraniuk, Oluwatoyin Adewuyi, Samantha Jean Merck, Mushtaq Ali, Murugan K Ravindran, Christian R
Timbol, Rakib Ray-han, Yin Zheng, Uyenphuong Le, Rania Esteitie, Kristina N Petrie
Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA; School of
Medicine, University of Pennsylvania, Philadelphia, PA, USA; Internal Medicine Residency Program, 1415
Woodland Ave, Suite 140, Des Moines, IA 50309, USA; Department of Internal Medicine, Norwalk Hospital,
Norwalk, CT, USA; School of Medicine, Georgetown University, Washington, DC, USA; School of Medicine
University of South Florida, Tampa, FL, USA
Received November 25, 2012; Accepted January 3, 2013; Epub January 21, 2013; Published January 30, 2013
Abstract: Background: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective,
nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes),
cognitive dysfunction, sleep and exertional exhaustion. Methods: Subjects self-reported symptoms using an
anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of
3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested
as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure
categorization as healthy or CFS subjects. Results: Fatigued subjects were divided into CFS with ≥4 symptoms or
Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a
threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include
Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls
(HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS–Like With
Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R2=0.977; Cronbach’
s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4
clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from
cerebrospinal fluid. Conclusions: Plotting Fatigue severity versus Sum8 produced an internally consistent
classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their
pathophysiological mechanisms. (AJTR1211008).
Keywords: Fatigue, pain, fibromyalgia, myalgic encephalomyelitis, proteomics
Address correspondence to: Dr. James N Baraniuk, Georgetown University Medical Center, Division of
Rheumatology, Immunology and Allergy, Room 3004F, 3rd Floor PHC Building, 3800 Reservoir Road, NW
Washington, DC 20007-2197, USA. Phone: 202-687-2906; Fax: 202-687-9886; E-mail: baraniuj@georgetown.edu
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