Correlation between corticospinal excitability and rigidity in individuals with parkinson's disease

Abstract

Parkinson's disease (PD) is a slow, chronic and degenerative pathology resulting from the reduction of dopaminergic synaptic efficacy in the negroestriatal pathway, resulting from neuronal death of the cerebral black substance, with consequent movement disorders1. PD it can be characterized by three motor signals, including rigidity2 that generates limitations in daily activities of life and reduced quality of life for patients3. In addition to clinical changes, PD alters the electrophysiological activity of the basal base cores and the cerebral cortex, with changes in the corticospinal excitability (CE) of the primary motor cortex (M1)4 that can be measured by transcranial magnetic stimulation single pulse (p-TMS), a safe and non-invasive method able to promote depolarization of neurons5. Despite this, the relation between such changes and the motor dysfunction presented by the patient, in this case, the stiffness, is still not clear. Therefore, the objective of this study is to investigate whether there is a relation between the rigidity and possible changes in cortical excitability (CE) in individuals with PD. MATERIALS AND METHODS: This is a transversal study (CAAE: 79597417.6.0000.5208; Clinical Trials: NCT03645538), which included 14 individuals, female and male, with PD, age ≥40 years old and a clinical diagnosis of PD provided by a neurologist, without cognitive decline (Montreal Cognitive Assessment (MoCA) ≥ 27 points), under regular antiparkinsonian pharmacological treatment and with staging from I to IV on the modified Hoehn & Yahr Scale (HY). Individuals with other neurological disorders, postural hypotension, vestibular, visual, cardiovascular or musculoskeletal disorders that affect the performance of the proposed tests were excluded; with other musculoskeletal or joint diseases in the lower limbs that interfere with the performance and the locomotion; submitted to previous surgical intervention for PD; or with contraindications for the application of TMS6. The rigidity of the hemibodies (right upper limb + right lower limb and left upper limb + left lower limb) was measured in the OFF state (without medication effect) through the score obtained in item 22 of session III of the Unified Parkinson’s Disease Rating Scale (UPDRS). In the beginning, magnetic pulses were administered over the motor cortex to determine the hot spot, the cortical representation area, a region in which the TMS evoke greater amplitudes of motor evoked potential (MEP), of the first interosseous dorsal muscle (FID). The evaluation of CE, also in the OFF state was given by the motor resting threshold (MRT), using the Motor Threshold Assessment Software, version 2.0 ( http://www.clinicalresearcher.org/software ), using as criteria for decision a motor evoked potential greater than or equal to 50µV. For the measurement of MRT, transcranial magnetic stimulation single pulse (p-TMS) of model 200² (Magstim, UK) was used, administered over the primary motor cortex of both hemispheres. Data analysis was performed considering both the most affected hemisphere and the least affected hemisphere, with the corresponding hemibody rigidity, so the sample was doubled. The normality of the data was verified using the Shapiro-Wilk test and the correlation analysis using the Spearman test, using a p-value <0.05. For the measurement of the correlation degree between the variables, the following values of correlation coefficient (r) will be taken into account: 0,26-0,49 = weak; 0,5-0,69 – moderate; 0,7-0,89 = strong; and 0,9-1,0 = very strong7. In addition, still in the correlation between rigidity and excitability, some control analyzes were done, dividing patients according to the factors (i) gender (male and female); (ii) age (≤60 and >60 years); (iii) time of diagnosis (≤5 and >5 years); and (iv) disease severity (mild and moderate to severe). For statistical analysis, SPSS software version 23.0 was used for Windows. RESULTS / DISCUSSION: The demographic and clinical characteristics of the 14 patients included in the sample are detailed in table 1. The Shapiro-Wilk test was used, and part of the data was found to be not normal. The Spearman test showed a significant correlation (p = 0.017) moderate and inversely proportional (r =-0.446) between the variables (figure 1)8. The control analysis showed a difference for the gender (male), age (≤60 years), and disease severity (moderate/severe) factors (table 2). Our findings suggest that patients with higher levels of rigidity have a lower motor threshold when compared to patients who have lower levels of stiffness, but a higher motor threshold. Mckay identified that lower limb stiffness, even with common risk factors, such as age, sex, and controlled UPDRS, is associated with patients' history of falls, negatively impacting their life quality9. A study also identified that rigidity is also one of the factors that impose limitations on the activities of daily living of these patients, with a consequent reduction in quality of life3. Although stiffness is a clinically relevant variable for the patient, so far, no other study has proposed to assess the relationship between cortical excitability and stiffness. The understanding of the relation between the clinical and electrophysiological findings of PD is essential both for the patient's assessment to be as detailed and assertive as possible and for the more targeted and effective use of neuromodulation in the treatment of PD. CONCLUSION: Cortical-spinal excitability is correlated with the degree of stiffness in patients with PD, since the results of the study suggests that the higher the MRT, the lower the stiffness score. This can be an important finding for whenever a clinical decision has to be taken in neuromodulation in the treatment of patients with PD.