HAM is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic
cord. Tissue damage is attributed to the cellular immune response to HTLV-1 infected
lymphocytes. Using a specific 18KDa Translocator Protein ligand, [
11
C] PBR28, T1-weighted
and Diffusion Weighted magnetic resonance imaging, the brains of HTLV-1 infected patients,
with and without HAM but no clinical evidence of brain involvement, were examined.
Methods: Five subjects with HAM and two HTLV-1 asymptomatic carriers (AC) were
studied. All underwent clinical neurological assessment including cognitive function and
objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood
mononuclear cells and HLA DR expression on circulating CD8+ lymphocytes. [
11
C] PBR28
PET and MRI were performed on the same day. [
11
C]PBR28 PET total volume of distribution
(VT) and distribution volume ratio (DVR) were estimated using 2-tissue compartment
modelling. MRI data was processed using tools from the FMRIB Software Library (FSL) to
estimate mean diffusivity (MD) and grey matter (GM) fraction changes. The results were
compared with data from age matched healthy volunteers.
Results: Across the whole brain the VT for the subjects with HAM (5.44±0.84) was
significantly greater than those of AC (3.44±0.80). The DVR of thalamus in patients with
severe and moderate HAM were higher compared to the healthy volunteers suggesting
increased TSPO binding (z>4.72). Subjects with more severe myelopathy and with high DR
expression on CD8+ lymphocytes had increased DVR and MD (near-significant correlation
found for the right thalamus MD: p=0.06). On the T1-weighted MRI scans, the GM fraction
of the brain stem was reduced in all HTLV1-infected patients compared to controls
(p<0.001), whilst the thalamus GM fraction was decreased in patients with HAM and
correlated with the disease severity. There was no correlation between neurocognitive
function and these markers of CNS inflammation.
3

Conclusions: This pilot study suggests that some patients with HAM have asymptomatic
inflammation in the brain which can be detected and monitored by [
11
C]PBR28 PET together
with structural and diffusion-weighted MRI.