Morphometric and Microstructural Alterations Differ with Age of Onset in Patients with Essential Tremor

Essential tremor (ET) is typically characterized with postural and kinetic tremor generally in upper distal limbs and head. Due to the heterogeneity of the disease, possibly different set of risk factors, pathophysiological mechanisms and clinical course affect structural architecture based on the onset of the disease. In this sense, we restricted genetic effect by recruiting early- and late-onset ET patients who were homozygous and heterozygous for the HTRA2 p.G399S gene mutation, respectively. A detailed analysis of how ET onset could affect the structural brain architecture is lacking in the literature. In this sense, brain morphometry and white matter microstructural integrity were assessed to investigate the effect of the onset of the disease on brain architecture in early- and late-onset ET patients using magnetic resonance imaging. Our results showed disruptions in late-onset ET was closely specific to motor areas including both cortical and subcortical structures, whereas affected areas in early-onset ET were more extensive in frontal, parietal and occipital areas. Results of our study indicate different brain structures and possibly different functions could be affected based on the onset of ET. Our findings highlight the potential role of age onset on structural cortical and subcortical architecture.