Ritmos circadianos y cronodisrupción en la enfermedad de Parkinson

Résumé

BACKGROUND. Parkinson's disease (PD) is associated with several non-motor symptoms, which may precede its diagnosis and constitute an important source of fragility in this population. The digital era, incorporated into health care, is allowing a qualitative leap that surpasses the limitations of subjective assessment techniques in the assessment of PD. This is based on the use of new portable biosensors that allow frequent, quantitative, reliable and multidimensional measurements with minimum discomfort and inconvenience for patients. OBJECTIVES. This Thesis aims to develop a procedure based on ambulatory circadian monitoring (ACM), for the ambulatory, objective and non-invasive evaluation of the main motor and non-motor alterations in PD. In order to achieve this objective, the following specific objectives have been proposed: 1. To determine the validity of the distal peripheral temperature for the detection of autonomic alterations in PD. 2. To validate a device for ambulatory monitoring of circadian rhythms of different complementary variables, which inform from motor, autonomic and behavioral alterations, such as: skin temperature, acceleration, time in movement, body position and exposure to light. 3. To examine the usefulness of the ACM technique for the evaluation of motor, autonomic, sleep and chronodisruption alterations in patients with PD. 4. To determine if the ambulatory circadian monitoring device is valid for the detection of sleep-wake rhythm compared to the gold standard, polysomnography. 5.- To develop and patent a new device that allows the evaluation of environmental rhythms (noise, light and temperature) and variables associated with sleep (snoring, movement, temperature and humidity) without the need of any contact with the subject and at different temporal scales. METHODOLOGY. After thermographic validation of peripheral skin temperature as a reliable marker of disautonomy, cross-sectional studies were conducted to test an MCA device (Kronowise) placed on the wrist, combined with automatic learning techniques to detect alterations in the circadian rhythms of motor activity, skin temperature, light exposure and sleep which may be adequate for the objective and non-invasive evaluation of patients with PD. The skin temperature of the wrist, acceleration, movement time, position of the hand, exposure to light and sleep rhythms in patients with PD and healthy controls of the same age were continuously recorded for seven consecutive days. CONCLUSION. Our study demonstrates that the multichannel ACM (Kronowise) device is able to provide reliable and complementary information of motor functions (acceleration and time of movement) and non-motor (rhythms of temperature of the skin and sleep) more commonly affected in the PD. The acceleration during the day (A, as an index of motor impairment), the time of movement during sleep (T, representative of the fragmentation of sleep) and its relation (A/T) are the best indices to objectively characterize the most common symptoms of PD, which can be used as an objective index to evaluate the patients' condition. The chronodisruption indices, measured as intraday stability (IS), intraday variability (IV), day-night contrast (RA) and the integrated index, circadian function index (CFI), are directly related to a low A/T ratio. Our work opens a new way for the implementation of innovative technologies based on portable, multisensory, objective and easy-to-use devices, which would allow quantifying circadian rhythms in large groups of patients with PD for periods of prolonged time while, at the same time, controlling exposure to exogenous circadian synchronizers.