Influence of L-dopa on subtle motor signs in heterozygous Parkin- and PINK1 mutation carriers

Abstract Introduction A latent nigrostriatal deficit and its possible clinical consequences in asymptomatic heterozygous Parkin and PINK1 mutation carriers (AMC) have been a matter of investigation in recent years. Notably, mild Parkinsonian signs in heterozygous mutation carriers can be so subtle that they may be missed if not specifically investigated. Methods We studied 15 heterozygous Parkin and PINK1 AMC and 18 age- and sex-matched mutation-negative controls using a standardized video, instructing the probands to perform relevant parts of the UPDRS III to investigate fine motor movements at baseline and after first-time L-Dopa administration. Additionally, available UPDRS III scores of mutation carriers from the past ten years were reviewed. Results AMC showed a reduced number of fine motor movements per second compared to controls at baseline ( p  = 0.04). L-Dopa improved motor performance numerically but non-significantly in AMC (p = 0.2301), but significantly in healthy controls (p = 6.1·10–5). Although none of the AMC reported symptoms, nine showed rigidity, bradykinesia, tremor, and postural instability when the UPDRS III was applied. Mean UPDRSIII scores significantly decreased after L-Dopa administration (p = 0.005), but did not increase over the past ten years. Conclusions (i) Heterozygous AMC show subtle motor abnormalities when a detailed, specialized motor examination is applied and compared to mutation-negative matched control subjects. (ii) The mild motor deficit present in a subgroup of heterozygous Parkin and PINK1 AMC appears to be non-progressive and responsive to L-dopa administration. (iii) Evaluating motor changes, their progression, and treatment response in AMC can provide valuable insights into possible early disease stages and compensatory mechanisms.