State-of-the-Art: Peripheral neuropathy is a common problem in aged populations leading to increased risk of falls, injury and poor quality of life. Moreover, peripheral neuropathy constitutes a frequent finding in PD patients, but its impact on gait and balance or on the risk of falling in this population remains largely unexplored. The underlying pathogenic mechanisms are unclear and most likely heterogeneous (eg, neurodegeneration; levodopa-induced; vitamin deficiency) . Therefore, unravelling the role of peripheral neuropathy and its causes in gait and balance disturbances in PD could have an impact in the diagnosis and clinical approach of these patients in particular and the aged population in general.

Approach: We will perform a cross sectional study to determine the presence of peripheral neuropathy in our ongoing cohort of 300 well-characterised PD patients as well as in matched controls. For that purpose we will use standardised clinical assessment (Neuropathy Impairment Score), Unified PD Rating Scale, neurophysiological conduction studies, quantitative sensory assessment comprising small, large and autonomic fiber function (Quantitative Sensory Testing), assessment of personal and environmental parameters, and an exhaustive wearable sensor-based gait and balance assessment. This will allow us to define the diagnosis and stratify study participants by severity of sensory, motor and dysautonomic modalities. Videotape recording of all participants will be performed, and independently reviewed by two neurologists, blinded to the patient’s ON or OFF medication condition. Based on such a comprehensive approach we will be able to determine, based on the ICF model, whether the presence of peripheral neuropathy influences gait and balance, and elaborate a composite score to assess the risk of falls. Importantly, to investigate the etiology of peripheral neuropathy we will run an extensive blood biochemical and immunological screen, together with neuropathological ultra-structural analysis (skin biopsy to investigate unmyelinated nerve fibers and nerve biopsies in a subset of participants).