Basal ganglia inflammation in children with neuropsychiatric symptoms

Objectives Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections is associated with obsessive-compulsive disorder and motor tics following group-A β-hemolytic streptococcal infections. However, this disorder remains controversial and many still consider it as a part of Tourette syndrome (TS) spectrum. We applied PET scanning with ¹¹C-[R]-PK11195 (PK) to detect potential neuroinflammation in children with clinically-diagnosed PANDAS and TS.

Methods Seventeen children with PANDAS (mean age: 11.4±2.6 years; 13 males), 12 with TS (mean age: 11.0±3.0 years; 10 males) and 15 normal adults (mean age: 28.7±7.9 years; 8 males) underwent dynamic PK-PET imaging and binding potential (BP), a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus, using reference tissue model and cluster analysis.

Results BP values were found to be increased in bilateral caudate (p=0.004 for left and 0.03 for right side) and bilateral lentiform nucleus (p=0.09 (a trend) and 0.002 for the left and right lentiform nucleus, respectively) in PANDAS group and in bilateral caudate nuclei only (p=0.06 (a trend) and 0.03 in the left and right caudate, respectively) in the TS group, compared to control group. BP values for bilateral basal ganglia and thalamus, except for left caudate, was found to be inversely related to the duration of illness in the PANDAS group (decreasing BP values with increasing duration); on the other hand, BP values appeared to be directly related to the duration of illness in the TS group (increasing BP values with increasing duration of illness) [Figure].

Conclusions Our findings suggest increased activated microglial cells, suggesting underlying neuroinflammation, in bilateral caudate nuclei in children with PANDAS and TS and in bilateral lentiform nuclei in PANDAS patients only. These differences in the pattern and extent of neuroinflammation signify a possible difference in pathophysiological etiology between PANDAS and TS.

Research Support The study was supported by grants/funding from 'Mental Illness Research Association (MIRA)' and 'Baiardi Family Foundation, Inc'.