Heart rate variability and sympathetic skin response for the assessment of autonomic dysfunction in leucine-rich repeat kinase 2 associated Parkinson's disease

• Published in: Neurophysiologie clinique 2022-02, Vol.52 (1), p.81-93
• Main Authors: Nasri, Amina, Kacem, Imen, Farhat, Nouha, Gharbi, Alya, Sakka, Selma, Souissi, Amira, Zidi, Sabrina, Damak, Mariem, Bendjebara, Mouna, Gargouri, Amina, Mhiri, Chokri, Gouider, Riadh
• Format: Article
• Language: English
• Subjects: Age; Autonomic; Autonomic nervous system; Basal ganglia; Central nervous system diseases; Cross-Sectional Studies; Dysautonomia; Female; G2019S mutation; Gender; Genetic; Heart Rate; Heart rate variability; Humans; Leucine - genetics; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; LRRK2; LRRK2 protein; Male; Movement disorders; Mutation; Neurodegenerative diseases; Parasympathetic nervous system; Parkinson Disease; Parkinson's disease; Phenotypes; Primary Dysautonomias - complications; Skin; Sympathetic nervous system; Sympathetic skin response; Tremor
• ISSN: 0987-7053; 1769-7131
• DOI: 10.1016/j.neucli.2021.12.007

We aimed to assess and compare autonomic function in Parkinson's disease (PD) associated with the leucine-rich repeat kinase (LRRK2) G2019S mutation (LRRK2-PD) and non-LRRK2 PD, by the study of heart rate variability (HRV) and sympathetic skin responses (SSR). In a cross-sectional three-year study, fifty LRRK2-PD and fifty clinically matched non-LRRK2 PD patients were included. Cardiac parasympathetic functions were assessed using heart rate variation to deep breathing (HR-DB), to the Valsalva maneuver (HR-V) and to standing (HR-S) and the sympathetic autonomic system by sympathetic skin responses (SSR). Neurophysiological, parasympathetic and sympathetic dysautonomia were found in 78%, 69% and 37% of all PD patients respectively. Rates of dysautonomia in the LRRK2-PD and non-LRRK2 PD patient subgroups were 76% vs 80% (p = 0.405) for neurophysiological, 62% vs 76% (p = 0.123) for parasympathetic and 38% vs 36% (p = 0.500) for sympathetic dysautonomia. HR-S was the most frequently altered parameter in both groups, and was significantly associated with the tremor-dominant (TD) motor phenotype of PD in the total cohort (p = 0.004) and in LRRK2-PD (p = 0.015). In LRRK2-PD patients, female gender was associated with parasympathetic dysfunction (p = 0.024), and with altered HR-DB (p = 0.022). Early-onset parkinsonism was also significantly associated with preserved neurophysiological autonomic functions (p = 0.044) in LRRK2-PD. In non-LRRK2 PD patients, male gender was associated with early parasympathetic (p = 0.043) and sympathetic dysfunction (p = 0.007). Our study showed a roughly similar neurophysiological autonomic profile in non-LRRK2 PD and LRRK2-PD. The latter had some peculiarities with more marked parasympathetic dysfunction and more altered HR-DB in females, more altered HR-S in the TD-motor phenotype, and preserved autonomic functions in early-onset parkinsonism. These preliminary findings would require further investigations on larger genetically homogeneous cohorts to explore the multiple facets of autonomic dysfunction in PD.