White matter changes correlates of peripheral neuroinflammation in patients with Parkinsons disease

1. BackgroundThe evolving paradigm shift in the role of neuroinflammation in neurodegenerative disorders has led to observations that proved neuroinflammation to be a pivotal part of pathogenesis in Parkinson disease (PD).Neutrophil-lymphocyte ratio (NLR) has been a popular marker to measure peripheral inflammatory response. As CNS inflammation can only be proved through biopsy, studies have addressed NLR to differentiate between PD patients and controls or different subtypes of PD. Connectometry is a statistical approach based on diffusion tensor imaging with the ability to reveal white matter tracts with statistical significance to a variableof interest. Herein we implemented connectometry to find tracts in with decreased/increased quantitative anisotropy in patients with early Parkinson disease compared to controls. 2. Method Participants involved in this research were recruited from Parkinson’s Progression Markers Initiative (PPMI) (www.ppmi-info.org/data/). The diffusion data were reconstructed in the MNI space using q-space diffeomorphicreconstruction to obtain the spin distribution function. Diffusion MRI connectometry was used to study the effect of NLR. A multiple regression model was used to consider sex, age, H&Y, and NLR in a total of 39 subjects. The analysis was conducted using DSI Studio (http://dsi-studio.labsolver.org). Neutrophil and lymphocyte counts were determined using autoanalyser device on fresh whole blood samples of patients,preserved with EDTA. 3. ResultsThe connectometry analysis identified splenium of corpus callosum, bilateral cingulum, bilateral inferior longitudinal fasciculi (ILF), bilateral fornixes and right uncinate fasciculus with decreased connectivity related to NLR (false discovery rate=0.0554238).4. Conclusions Neuroinflammatory processes are proposed to contribute to PD. Activated microglia accumulate in areas of neurodegeneration, months before the onset of motor symptoms and CD4+ T-cells infiltrate the substantia nigra and cytokine levels increase in the affected areas in the substantia nigra. Neuroinflammation is now believed to be the common pathway by which mitochondrial dysfunction, environmental toxins and perhaps infections, i.e. peripheral inflammation, culminate to result in dopaminergic specific neural death. Our study revealed reduced white matter integrity in areas previously reported to be affected in PD, with NLR as a marker of peripheral inflammation. Cingulum is implicated in cognitive functions and is known to be implicated in PD loss of executive function and dementia. The ILF has an integrative function is visuospatial tasks and isdisturbed in PD patients with visual hallucinations and fornix is mandatory for preservation of memory and attention is these patients. Our observations suggest that white matter degeneration is early PD might have pathological instems in peripheral inflammation.