Negative correlation of glucose metabolism and microglial activation in multiple system atrophy in the lentiform nucleus – a PET study

Background: Multiple System Atrophy (MSA) is an atypical Parkinsonian Syndrome of unknown etiology. This neurodegenerative disorder has been found to be associated with microglial activation [1] but the exact role and time course of these neuroinflammatory changes are still largely unclear.

[11C](R)-PK11195 Positron Emission Tomography (PET) can image activated microglia in vivo [2]. We have used [11C](R)-PK11195 and FDG in a dual tracer PET-study in order to elucidate the relationship between neuroinflammatory and metabolic changes in MSA.

Methods: 6 patients diagnosed with MSA- P (parkinsonian type) with a mean age of 55 years (range 45–71) and a mean clinical disease duration of 3.7 years (range 2–5) were examined with [11C](R)-PK11195 and FDG PET. Parametric maps of binding potential values (PK-PET) and CMRGlu were transformed into MNI space using SPM99 and regional values were sampled using a detailed anatomical template [3]. Basal ganglia, brainstem and cerebellar values of the two modalities were correlated (Pearson correlation, two tailed).

Results: Increases in PK11195 binding potential correlated with decreases in regional glucose metabolic rate in the putamen (r=-0.58; p=0.048) and pallidum (r=-0.652, p=0.022) while correlations for the other regions investigated failed to reach significance (p<0.05).

Conclusion: In MSA levels of microglial activation remain high in regions that are especially targeted by the disease process even at a time when impairment of cell function and probably also cell death has already taken place. This is further evidence that microglial activation is an ongoing feature of the pathological changes in MSA that seems to be present throughout the disease.

References

1. Ishizawa, K., et al., Microglial activation parallels system degeneration in multiple system atrophy. J Neuropathol Exp Neurol, 2004. 63(1): p. 43–52.

2. Gerhard, A., et al., [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology, 2003. 61(5): p. 686–689.

3. Hammers, A., et al., Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp, 2003. 19(4): p. 224–47.