Somatosensory processing in asymptomatic PINK1- and PARKIN-mutation carriers

Introduction: Sensory symptoms are not uncommon in Parkinson's disease (PD). It is unclear whether these symptoms are primary or secondary due to pathophysiological changes occurring in PD. Mutations in the PINK1 (PARK6) and PARKIN gene have been identified as one cause of recessively inherited PD with early onset. Asymptomatic carriers of PINK1 and PARKIN mutations represent individuals at risk who may develop PD later in life and can be identified by molecular genetic testing. Therefore, they may serve as a model to detect sensory abnormalities before subjects show pronounced clinical signs of PD. This might shed light on the pathomechanisms related to sensory abnormalities in patients with the more frequent idiopathic PD.

Methods: Fourteen family members with PINK1 mutation (3 homozygous, 11 heterozygous) as well as 9 family members with PARKIN mutation and their healthy age-matched controls were examined clinically, with nerve conduction studies and a shortened form of the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS). The QST protocol included perception thresholds for warm, cold, cold pain, heat pain, mechanical and painful mechanical stimuli, vibration and pain pressure.

Results: Nine PINK1 and 3 PARKIN mutation carriers showed signs of PD (affected) whereas 5 PINK1 and 6 PARKIN mutation carriers did not (unaffected). Thresholds for mechanical detection, mechanical pain and pain pressure were higher not only in affected homozygous but also in heterozygous PINK1 mutation carriers compared to controls, but they did not differ from controls in unaffected PINK1 mutation carriers. In contrast, parameters of PARKIN mutation carriers did not differ from controls. Comparison of age-matched asymptomatic PINK1 and PARKIN mutation carriers revealed higher thresholds of cold detection, cold pain and pressure pain on the hands as well as higher thresholds of cold pain and mechanical pain on the feet in PINK1 mutation carriers with a trend towards higher thresholds of all parameters in PINK1 mutation carriers.

Conclusion: These data suggest (1) that PINK1-associated PD is linked with primary somatosensory changes,(2) that even heterozygous PINK1 mutations might play a role in the pathophysiology of sensory abnormalities associated with PD and (3) that different aetiologies of PD might lead to different somatosensory abnormalities in PD patients.