RELATIONSHIP
OF BRAIN MRI ABNORMALITIES AND PHYSICAL
FUNCTIONAL STATUS IN CHRONIC FATIGUE SYNDROME
----------------------------------------------------
http://freespace.virgin.net/david.axford/update18.htm
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) Hospital of East Orange, New Jersey.
Brain MR images were obtained with a 1.0 Tesla magnet (Picker HPQ, Highland Heights, Ohio). Serial slices were obtained at a thickness of 5 mm with an interslice gap of 1.5 mm. Brain abnormalities were classified into 5 general categories:
(1) lateral ventricular enlargement; (2) subcortical white matter
hyperintensities; (3) grey matter and/or
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