Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach.

Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration. ET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinical-demographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested. Twenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters, two independent groups were identified: cluster "A" (N = 15) and cluster "B" (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes. The presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration.

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