F016 Cerebrospinal fluid cell count in the Hdclarity registry indicates a transient inflammatory response in late premanifest Huntington’s disease

<h3>Background</h3> An inflammatory response is present in Huntington’s Disease (HD) brains. Cerebrospinal fluid (CSF) cell count (CC) is a commonly used inflammatory CSF biomarker. <h3>Aims</h3> Whether CSF-CC changed in HD. <h3>Methods</h3> Average CSF-CCs per first CSF sample from each HDClarity participant was analyzed together with corresponding Enroll-HD data. <h3>Results</h3> Median CSF-CC in all premanifest and manifest HD gene carriers [HD-GC, median 0.67/µl (interquartile range 0.0–1.33/µl), N=346] was significantly higher than in control participants [CP, 0.0(0.0–1.0)/µl, N=98, Mann-Whitney U test, p=0.0291]. When the HD-GCs were grouped as early premanifest (epreHD-GC), late premanifest (lpreHD-GC), early HD (eHD) or moderate/advanced HD (m/aHD) according to the HDClarity protocol, only lpreHD-GCs [1,00/µl (0,33–1,33/µl), N=98] had a higher CSF-CC compared to CPs (Kruskal-Wallis with Dunn’s posttests, p=0.0006). lpre-HD-GC CSF-CC was higher than in epreHD-GCs [0,00 (0.00–1.00)/µl, N=49; p=0.0104), eHD [0.33(0.00–1.25)/µl, N=176, p=0.0417] and m/aHD [0.00(0.00–0.67)/µl, N=23, p=0.0038). A CSF-CC&gt;0.33/µl separated lpreHD-GC best from CPs with a sensitivity and specificity of 71% and 61%, respectively. Upon multiple logistic regression analysis adjusting for age and sex, CSF-CC&gt;0.33/µl showed an odds ratio of 3.4 (95%CI 1.6–7.4) for lpre-HD-GC compared to epreHD-CC and manifest HD (p=0.001). Neither the HD-ISS nor identification of lpreHD by PINHD score separated a HD-GC population with increased CSF-CC as good as the disease burden score (DBS) of ≥250 in HDClarity did. <h3>Conclusion</h3> There seems to be transient CSF inflammation in HD-GC just before manifestation of HD. Why this HD-GC population is best captured by DBS ≥250 but not PINHD or HD-ISS remains to be explored.