Neurological and Neuropsychological Dysfunction in CFS

CFS patients have subtle problems in neuropsychological processing particularly in motor speed (Busichio, Tiersky, DeLuca, and Natelson 2004). A premovement readiness potential is reduced in CFS (Gordon, Michalewski, Nguyen, Gupta, and Starr 1999) and in addition, brain activity during performance of a motor task is significantly greater than that for controls. We did functional imaging in a group of patients with no measurable cognitive deficit and asked them to perform a relatively simple cognitive task: their brains showed the same pattern of activation as seen in healthy subjects given a much more difficult task (Lange et al. 2005).

In another brain imaging study, CFS patients with no psychiatric comorbidity had a significantly higher rate of brain MRI abnormalities than normals (67% versus 30%; Lange, DeLuca, Maldjian, Lee, Tiersky, and Natelson 1999). For the most part, these were small areas of T-2 uptake in frontal white matter. Data exist to support our interpretation that these abnormalities may play a role in the symptom complex of CFS in that patients with MRI abnormalities reported poorer functional status than those with normal MRI studies (Cook, Lange, DeLuca, and Natelson 2001). Stratifying patients based on presence or absence of psychiatric comorbidity is important because psychiatric illnesses such as depression are known to produce similar small lesions.

Two groups have noted decreased gray matter volume in CFS patients compared to controls (De Lange, Kalkman, Bleijenberg, Hagoort, van der Meer, and Toni 2005; Okada, Tanaka, Kuratsune, Watanabe, and Sadato 2004) although they did not agree on the areas affected. This has prompted studies of cerebral perfusion, which might account for a reduction in brain volume. Early studies using SPECT (single photon emission computed tomography) done in nonstratified patient samples revealed global decreases in cerebral flow (Ichise et al. 1992; Schwartz et al. 1994), but this result was not confirmed in later studies using selected patients without psychiatric comorbidity (Costa, Tannock, and Brostoff 1995; Fischler et al. 1996; Lewis et al. 2001; MacHale et al. 2000) or in twins where one twin had CFS (Lewis et al. 2001). Our own studies of absolute brain blood flow did find wide reductions in regional flow bilaterally in CFS (Yoshiuchi, Farkas, and Natelson 2006). Importantly, one of the previous SPECT studies did find actual increases in thalamic flow (MacHale et al. 2000); these could reflect local increases in metabolism at this site. Of interest is another study reporting increased metabolism in basal ganglia, which connect directly to thalamus (Chaudhuri, Condon, Gow, Brennan, and Hadley 2003).

Two groups have used positron emission tomography (PET) to evaluate the metabolism of the brain in CFS patients free of psychiatric disorders (Siessmeier, Nix, Hardt, Schreckenberger, Egle, and Bartenstein 2003; Tirelli et al. 1998). The first found normal metabolism in half their subjects but hypometabolism in cingulate and adjacent mesial cortical areas (Siessmeier et al. 2003). The second study found reduced metabolism in brain stem, thus supporting the earlier SPECT study, which had noted reduced flow there (Tirelli et al. 1998).

Table 19.1. Poly graphic characteristics of healthy people and CFS patients during their second night in the sleep lab._

Healthy (n = 15)

CFS (n = 13)

Total sleep time (min)

376 ± 42

347 ± 40*

Sleep efficiency (%)

87.3 ± 6.8

80.0 ± 7.0*

Sleep latency (min)

16 ± 16

17 ± 12

Total duration (min) of:


40 ± 30

71 ± 29*

 Stage 1

53 ± 14

61 ± 28

 Stage 2

213 ± 37

194 ± 25

 Stage 3

28 ± 17

33 ± 27

 Stage 4

4 ± 10

3 ± 5

 Stages 3/4

32 ± 25

35 ± 30

 Stage REM

77 ± 18

57 ± 26

Values are mean ± SD. Sleep efficiency is the percentage of time asleep relative to the

time spent in bed. REM, rapid eye movement. *Significantly (P < 0.05) different from healthy people.

time spent in bed. REM, rapid eye movement. *Significantly (P < 0.05) different from healthy people.

We have performed lumbar punctures on 44 CFS patients and 13 healthy controls. Although none of the controls had elevations in cell counts or spinal fluid protein levels, 30% of the patients did. The patient group with abnormal spinal fluid had increased levels of IL-10, an anti-inflammatory cytokine.

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