Parkinson hastalığı ve atipik parkinsonizm sendromlarında periferik nöropatik ağrının multimodal incelenmesi

Abstract

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system that is mostly idiopathic and may also occur due to monogenic mutations in 5% of the patients. Multiple system atrophy (MSA) is one of the atypical parkinsonism syndromes that may present with parkinsonism as well as autonomic dysfunction, cerebellar and pyramidal signs. Peripheral neuropathic pain may be present in all of these disease forms at different frequencies. This study aims to determine the frequency of peripheral neuropathic pain and evaluate morphology and functions of small fibers in idiopathic PD, hereditary PD and MSA patients. Twenty idiopathic, fourteen hereditary PD patients with five different mutations and six MSA patients were included in the study. Disease severity was evaluated by Hoehn-Yahr stage, Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS part Ⅲ), non-motor symptoms were detected by using non-motor symptom scale (NMSS), pain in particular was interrogated by King's PH pain scale, DN4 and painDETECT questionnaires. Hot and cold sensation thresholds were measured by quantitative sensory test (QST) to evaluate the small fiber functions. Subsequently, skin punch biopsies were performed from 10 cm above the lateral malleolus and the thoracic skin area of T8-10 dermatome. The biopsy samples were immunostained with panaxonal marker protein gene product 9.5 (PGP9.5) antibody and intraepidermal nerve fiber density (IENFD) was determined. Peripheral neuropathic pain was detected in 15% of idiopathic PD and 14.2% of hereditary PD patients by pain scales whereas none of MSA patients reported peripheral neuropathic pain. Distal IENFD was found to be higher in the MSA patients compared to idiopathic (p = 0.04) and hereditary PD patients. Moreover, distal IENFD was lower than proximal IENFD in all disease groups (p <0.001). Abnormal thermal sensation was detected in 13.3% of the idiopathic PD and in 30.8% of the hereditary PD patients but thermal sensation thresholds were within the normal limits in MSA patients. However, it was noticed that patient cooperation to QST was limited in all disease groups. No relation between disease duration or severity and IENFD loss was detected. In conclusion, our study showed that the frequency of neuropathic pain, as well as, the loss and dysfunction of small fibers were common in patients with idiopathic and hereditary PD compared to patients with MSA. Considering recent knowledge that small fiber loss occurs due to pathological α-synuclein accumulation, the immunohistochemical staining of phosphorylated α-synuclein in small fibers, especially in a larger group of hereditary PD patients, can provide additional information about the PD pathogenesis and the development of new diagnostic tools.