A Transdiagnostic Structural Brain Signature of Parkinsonian and Essential Tremor

BackgroundParkinsons disease (PD) and Essential Tremor (ET) are heterogeneous, yet distinct disorders. At the same time, PD and ET show overlapping features such as phenotypes with predominant tremor. These heterogeneities and overlaps pose challenges for clinical management and research and may indicate transdiagnostic, shared mechanisms for tremor. ObjectivesTo test the hypothesis that MRI may reveal structural brain changes related to tremor phenotypes rather than diagnoses in PD and ET patients. For this, we compared regional brain volumes between three patient groups with overlapping phenotypes and distinct diagnoses: ET, PD with tremor-dominant phenotype (PD-T), and PD with non-tremor-dominant phenotype (PD-nT). MethodsWe studied 164 patients (18 ET, 38 PD-T, 108 PD-nT) who were evaluated for deep brain stimulation. All patients underwent structural MRI, and standardized assessment of motor symptoms. We compared regional brain volumes between groups. ResultsVolumes of the thalamus, pallidum, and pre-cerebellar and upper brainstem (midbrain, pons, superior cerebellar peduncle) differed across groups and were smallest in ET, intermediate in PD-T, and largest in PD-nT. Differences reached significance when comparing ET or PD-T with PD-nT but not ET with PD-T. Thalamic and brainstem volumes correlated with more severe and less levodopa-responsive tremor in PD. In contrast to the subcortical findings, cortical thickness in frontal and parietal regions was thinner in PD-nT compared to PD-T patients. ConclusionsWe identified tremor-related volume loss in cerebellothalamic and interconnected regions (pallidum), potentially suggesting shared mechanisms of tremor in PD and ET and pointing towards a transdiagnostic structural brain signature of tremor.