CFS/FM: Recent Research Progress. Benjamin H. Natelson, MD Professor of Neurosciences, UMDNJ-New Jersey Medical School. =. Level of Activity. 0. 1. 2. 3. 4. 5. 6. Duration of Fatigue (mo.). CDC CFS case definition. CFS subset of prolonged fatigue > 1 month duration.
Benjamin H. Natelson, MD
Professor of Neurosciences,
UMDNJ-New Jersey Medical School
1994 Prevalence: ~0.4% of general population F>M
Percent reporting each symptom
Memory-concentration 92 96
Unrefreshing sleep 89 100
Post-exertional fatigue 81 98
Muscle pain 77 100
Weakness 69 96
Headache 46 89
Joint pain 39 87
Swollen lymph nodes 31 87
Sore throat 23 89
Feverishness 23 89
Patients with milder CFS (i.e., ‘94 but not ‘88) appear to be less likely to have had an infectious trigger and/or a continuing immunological problem.
Brimacombe et al. J Clin Psychol Med Settings, 9:309, 2002
Diagnosis given to patients varies with referral process. Flu-like malaise is CFS. Diffuse pain is FM. Sensitivity to odors is MCS. Bowel complaints are IBS. All these OVERLAP!
(163 consecutive female patients with CFS)
CFS CFS/MCS CFS/FM CFS/FM/MCS
# Axis I Dx
0 35/62 (56%) 14/31 (45%) 17/44 (39%) 4/26 (15%)
1 18/62 (29%) 4/31 (13%) 13/44 (30%) 8/26 (31%)
>1 9/62 (15%) 13/31 (42%) 14/44 (32%) 14/26 (54%)
Ciccone et al. Psychosom Med, 65:268, 2003
CFS without other medically unexplained illnesses may be a different process than CFS with comorbid illness syndromes.
Critical to repeat with an FM alone group
One argument is that CFS is a variant of depression. However, post-exertional fatigue, although common in CFS, is not seen in depression.
Pre-treadmill Post-treadmill Pre-treadmill Post-treadmill
Sisto et al. QJM, 91:365, 1998
Ottenweller et al., Neuropsychobiol 43:34, 2001.
LaManca et al. AJM 105:59S, 1998
LaManca et al. Psychosom Med., 63:756, 2001
Could be responsible in part for post-exertional symptom worsening.
Could aggregate over entire day to produce longer lasting symptoms.
Could CFS be a chronobiological disorder – i.e., chronic internal desynchronization or a disorder of entrainment?
* P<0.05 from controls; ** P<0.05 from active CFS with
t-test (variance controlled) for the mean and F-test for the S.D..
Ohashi et al. Physiol & Behav.77:39, 2002
Ohashi et al. Physiol. Behav. 77:39, 2002
Sleep is further disturbed by vigorous exertion to alter circadian phase
Johnson et al. J. Affective Dis 39:21, 1996
CFS is probably not a variant of major depression
25 CFS Subjects
+ Symptom of
– Symptom of
– Symptom of
Sirois et al. J Rheum 28:126, 2001
1Wallace et al. CDLI 6:216, 1999
2Natelson et al. CDLI 9:747, 2002
Johnson et al., Psychosom Med 58:50,1996
Some CFS patients may have an occult encephalopathy despite having no neurological findings other than occasional balance problems
If this dysfunction were relevant to the symptom complex of CFS, it should relate to functional status. If it is an epiphenomon, its presence should not relate to functional status
PLAN: Evaluate relation between presence of neuropsych abnormalities and physical function on the SF-36
0 1 >=2
Number of Failing Test Scores JNNP, 64:431, 1998
Lange et al. J. Neurol. Sci.171:3-7, 1999.
If these lesions were relevant to the symptom complex of CFS, they should relate to functional status. If they are epiphenoma, their presence should not affect functional status
PLAN: Evaluate relation between presence of abnormalities and physical function on the SF-36
NJ Case Definition for “Severe” CFS(Modification of 1988 CDC case definition)
Natelson et al. Clin. Infec. Dis. 21:1204-10, 1995
in subcortical white matter of frontal lobes
Supports conclusion that some CFS patients may have underlying encephalopathy
Examination of spinal fluid
Thus 30% of taps were outside of nl range!!
Natelson et al. CDLI, 12:53, 2005
Cook et al., J. Rheumatology, in press.
Lange et al, JNNP, in press.
Look at the heart and determine if abnormalities exist and, if present, if they relate to any index of brain dysfunction
Do radionucleid MUGA study to evaluate cardiac function during exercise stress; EF should increase
Are CNS lesions secondary to perfusion problem or primary?
Data collected to this point supports our major hypothesis that CFS is for some a neurological disorder; the pathophysiological role of the heart is under active investigation
Dr. Michael Brimacombe
Dr. Kim Busichio
Dr. Don Ciccone
Dr. Helena Chandler
Dr. Neil Cherniack
Dr. Dane Cook
Dr. John DeLuca
Dr. Drew Helmer
Dr. Susan Johnson
Dr. Gudrun Lange
Dr. John LaManca
Dr. John Ottenweller
Dr. Arnold Peckerman
Dr. Karen Quigley
Dr. Rick Servatius
Dr. SueAnn Sisto
Dr. Lana Tiersky
Dr. Chin-Lin Tseng
Dr. Yoshi Yamamoto
Dr. Kazu Yoshiuchi
Dr. Shelley Weaver
Dr. Quan Wu ZhangCFS/FM Center Researchers