Peripheral neuropathy in Parkinson's disease

Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.