RELATIONSHIP OF BRAIN MRI ABNORMALITIES AND
PHYSICAL
FUNCTIONAL STATUS IN CHRONIC FATIGUE
SYNDROME
----------------------------------------------------
By:
Cook, D. B., Lange, G., Deluca, J., Natelson, B.
H.,
International Journal of Neuroscience,
0020-7454, March 1, 2001, Vol.
107, Issue 1/2
(Received 10 February
2000)
Chronic Fatigue Syndrome (CFS) is an
unexplained illness that is characterized by severe fatigue. Some have suggested
that CFS is a "functional somatic syndrome" in which symptoms of fatigue are
inappropriately attributed to a serious illness. However, brain magnetic
resonance imaging (MRI) data suggest that there may be an organic abnormality
associated with CFS. To understand further the significance of brain MRI
abnormalities, we examined the relationship between MRI identified brain
abnormalities and self-reported physical functional status in 48 subjects with
CFS who underwent brain MR imaging and
completed the Medical Outcomes Study
SF-36. Brain MR images were examined for the presence
of abnormalities based on 5 general categories previously shown to be sensitive
to differentiating CFS patients from healthy controls. There were significant
negative relationships between the presence of brain abnormalities and both the
physical functioning
(PF) (?3D -.31, p 3D .03), and
physical component summary PCS (? 3D -.32, p 3D .03) subscales of the SF-36. CFS
patients with MRI identified brain abnormalities scored significantly lower on
both PF (t1,46 3D 2.3, p 3D .026) and the PCS (t1,41 3D
2.4, p 3D .02) than CFS subjects without an identified brain abnormality. When
adjusted for age differences only the PF analysis remained significant. However,
the effect sizes for both analyses were large indicating meaningful differences
in perceived functional status between the groups. These results demonstrate
that the presence of brain abnormalities in CFS are
significantly related to
subjective reports of physical function and that CFS subjects with MRI brain
abnormalities report being more physically impaired than those patients without
brain abnormalities.
Chronic Fatigue Syndrome (CFS) is an unexplained
illness characterized by severe fatigue with infectious, rheumatological and neuropsychiatric symptoms (Fukuda, Strauss, Hickie, Sharpe, Dobbins and Komaroff, 1994). Barsky and Borus (1999) posit that CFS is one of a
group of
functional somatic syndromes in which symptoms are
"exacerbated by a self-perpetuating, self-validating cycle in which common,
endemic, somatic symptoms are incorrectly attributed to a serious abnormality,
reinforcing the patient's belief that he or she has a serious disease."
Contrary to the somatic amplification hypothesis driving this analysis are
two studies from our laboratory in which we found a higher frequency of abnormal
brain magnetic resonance images (MRI) in CFS patients compared to healthy
controls (Lange, DeLuca, Maldjian, Lee and Tiersky, 1999;
Natelson, Cohen, Brassloff
and Lee, 1993). A critical question
regards the significance of these
abnormalities. Are they nonspecific findings or do
they relate in some way to the illness itself? If CFS were a functional somatic
illness without any organic basis, then brain abnormalities would not be related
to the patient's functional status.
On the contrary, we report data here
that demonstrate a relationship between the presence of
brain MRI abnormalities and diminished physical functional status in CFS
patients.
METHODS
We examined 48 chronic fatigue
syndrome (CFS) patients (38.0 B1 9.4 yrs) who completed the Medical Outcomes
Study SF-36 (Stewart, Hayes and Ware, 1988) and underwent brain MRI testing. The
SF-36 is a vehicle with well established psychometric properties and it has been
shown to be a highly reliable and valid tool in assessing functional status in a
wide range of medical and psychiatric illnesses including CFS (Buchwald,
Pearlman, Umali, Schmaling and Katon, 1996; McHorney, Ware, Lu and Sherbourne,
1994). Because our a priori hypothesis was that the presence of MRI
abnormalities would correlate with diminished physical function, we confined our
analysis to the physical functioning (PF) subscale and to the physical component
summary (PCS) comprised of the following
subscales: PF, role physical,
bodily pain, and general health. Lower scores on these measures are
representative of greater functional impairment. All subjects signed a consent
form approved by the review board at the Veterans Administration (VA)
Brain MR images were obtained with a 1.0 Tesla magnet (Picker HPQ,
brainstem
hyperintensities; (4) cerebral atrophy; and (5)
left-right cerebral hemisphere asymmetries. MR abnormalities were identified as
part of a separate study (Lange et al., 1999) in which two neuroradiologists separately reviewed these films as well as
those of
healthy controls with no information as to group membership. Films
were then dichotomized using the above criteria as normal or abnormal depending
on the absence or presence of any MR abnormalities.
RESULTS
CFS
subjects (n 3D 25) classified as having an MRI identified brain abnormality were
significantly older (43.0 B1 9.7 yrs) than those CFS subjects (n 3D 23) without
an abnormality (33.5 B1 6.5 yrs) [t1,46 3D 4.0, p < .001]. Spearman's
correlations revealed significant negative relationships between the presence of
brain abnormalities and
PF (? 3D -.31, p 3D .03), and PCS (? 3D -.32, p 3D
.03), indicating that brain abnormalities were associated with self reports of
poor physical function. Independent samples t-tests revealed that CFS patients
with an MRI identified brain abnormality scored significantly
lower on both
PF (tl,46 3D 2.3, p 3D .026) and the PCS (t1,41 3D 2.4,p 3D .02) than CFS
subjects without an identified brain abnormality (See Fig. 1). Analysis of
covariance with age entered as the covariate increased the probability values
for both the PF (F1,46 3D 4.0, p 3D
.05) and PCS
(Fl,41 3D 3.6, p 3D .066) analyses, and only the analysis of physical
functioning remained significant at the .05 level. However, Cohen's effect size
d was large for both the differences in PCS and PF scores indicating a
meaningful difference in perceived physical functional status between the two
groups, and suggesting that a larger
sample would have resulted in a
significant difference in the PCS subscale of the
SF-36.
DISCUSSION
These results demonstrate that the presence of
brain abnormalities are significantly related to subjective reports of physical
function in CFS, and underscore the importance of the patient's subjective
experience in clinical assessment. Moreover, CFS patients with MRI brain
abnormalities report being more physically impaired (lower scores on the PF
subscale of the SF-36) than those patients without brain abnormalities even
after accounting for the age differences observed between the two groups. It
should be pointed out that abnormalities,
specifically small punctate white matter hyperintensities are rarely observed in people less than 60
years of age (our sample averaging only 43 yrs) (Schmidt, Fazekas, Kapeller, Schmidt and
Hartung, 1999; Schmidt, Hayn, Fazekas, Kapeller and Esterbauer, 1996;
Tupler, Coffey, Logue, Djang
and Fagan, 1992). Moreover, identified lesions in healthy elderly individuals
are not normally associated with functional impairment (Schmidt et al., 1999;
Schmidt et al., 1996; Tupler et al., 1992). This
suggests that the abnormalities observed in CFS are functionally significant as
has been shown in the case of multiple sclerosis (Rao,
Leo, Haughton, St. Aubin-Faubert and Bernardin, 1989).
The present results support our
hypothesis that some CFS patients have an identifiable organic component
responsible for their illness and indicate that CFS is not purely due to
psychological factors. To our knowledge, this is the first study to examine the
significance of brain abnormalities in CFS on physical functional status.
Importantly, since not all CFS patients have identifiable brain abnormalities,
the presence of such abnormalities may be useful in differentiating subsets of
CFS patients whose pathophysiology may be different.
This approach may serve to decrease some of the heterogeneity inherent in this
unexplained
illness. More research is needed to delineate further the
significance of these brain abnormalities and to rule out other potentially
confounding variables (e.g., symptom severity, disease duration,
etc.).
(*) This work was supported by NIH
AI-32247.
GRAPHS: FIGURE 1 Bar graphs (mean B1
SE) demonstrating greater
impairment among the CFS subjects who exhibited an
MRI brain
abnormality. PF 3D physical function; PCS 3D
physical component
summary *p <
.05.
References
Barsky, A. J. & Borus, J. F.
(1999) Functional somatic syndromes,
Annals of
Internal Medicine, 130, 910-921.
Buchwald, D., Pearlman, T., Umali, J., Schmaling, K. & Katon, W.
(1996) Functional
status in patients with chronic fatigue syndrome,
other fatiguing illnesses,
and healthy individuals, American Journal of
Medicine, 101,
364-370.
Fukuda, K., Strauss, S. E., Hickie, I., Sharpe, M. C., Dobbins, J.
G. & Komaroff, A.
(1994) Chronic fatigue syndrome: a comprehensive
approach to its
identification and study, Annals of Internal Medicine,
121,
953-959.
Lange,
G., DeLuca, J., Maldjian, J.
A., Lee, H.-J., Tiersky, L.
A.
& Natelson, B. H. (1999) Brain MRI abnormalities exist in a
subset of
patients with chronic fatigue syndrome, Journal of the
Neurological
Sciences, 171, 3-7.
McHorney, C. A., Ware, J. E., Lu, J. F. R. & Sherbourne, C. D.
(1994) The MOS 36-item short-form
health survey (SF-36): III. tests of
data quality,
scaling assumptions, and reliability across diverse
patient groups, Medical
Care, 32, 40-66.
Natelson, B. H., Cohen, J. M., Brassloff, I. & Lee, H.-J. (1993) A
controlled study of brain magnetic resonance imaging in patients with
the chronic fatigue syndrome, Journal of the Neurological Sciences, 120,
213-217.
Rao, S. M., Leo, G. J., Haughton, V. M., St. Aubin-Faubert, P. &
Bernardin, L. (1989) Correlation of magnetic resonance
imaging with
neuropsychological testing in multiple sclerosis, Neurology,
39,
161-166.
Schmidt, R., Fazekas,
F., Kapeller, P., Schmidt, H. & Hartung,
H.-P.
(1999) MRI white matter hyperintensities. Three year follow-up of
the Austrian stroke
prevention study, Neurology, 53, 132-138.
Schmidt, R., Hayn, M., Fazekas, F., Kapeller, P. & Esterbauer, H.
(1996) Magnetic resonance imaging
white matter hyperintensities in
clinically normal
elderly individuals, Stroke, 27,
2043-2047.
Stewart, A. L., Hays, R. D.
& Ware, J. E. (1988) The MOS
short-form general health survey:
reliability and validity in a patient
population, Medical Care, 26,
724-735.
Tupler,
L. A., Coffey, C. E., Logue, P. E., Djang, W. T. &
Fagan,
S. M. (1992) Neuropsychological importance of subcortical white matter
hyperintensity, Archives of Neurology, 49,
1248-1252.
By D. B. Cook, Department of Neurosciences, Department
of
Anesthesiology,; G. Lange, Department of
Psychiatry, Department of
Radiology Address for correspondence: Department
of Psychiatry,
UMDNJ-New Jersey Medical School, 30 Bergen St., ADMC 1410,
University
Heights, Newark, NJ 07107-3000. Fax: (973) 972-8305, e-mail:
langegu@umdnj.edu; J. Deluca, Department of
Neurosciences, Department of
Physical Medicine and Rehabilitation, UMDNJ-New
Jersey Medical School,
Newark, NJ 07103, USA and B. H. Natelson, Department of
Neurosciences
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Source: International Journal of Neuroscience, 2001,
Vol.
107 Issue 1/2, p1, 6p, 1 graph.