A device for predicting the wearing-off state in patients with Parkinson's disease.

Abstract

A device for predicting a wearing-off state of a patient suffering from Parkinson's disease, comprising: an electrodermal sensor (2) arranged to detect an electrical quantity associated with the patient's skin conductance and to generate a corresponding measurement signal; an electronic control unit (3) connected to the electrodermal sensor (2) for receiving the measurement signal and arranged to obtain a value of a physiological parameter (PF) representative of the skin conductance at the patient's skin; and a communication unit (4) operatively connected to the electronic control unit (3) and activatable by the electronic control unit (3) to generate an off notification signal. The electronic control unit (3) comprises a processing module (7) arranged to detect an overall time variation of the physiological parameter (PF) indicative of an increase in skin conductance within a movable time window (FT) and to compare this overall time variation with a certain threshold value (VS), thereby controlling the communication unit (4) to allow a suitable operation by allowing a pre-warning of a possible upcoming confirmation of wearing-off.

Description

【Technical Field】 【0001】 The present invention relates to a device for predicting the off-state of a patient suffering from Parkinson's disease. 【0002】 This device is classified in the field of biomedical devices, particularly available in the field of neurology, and is for detecting a specific clinical condition (referred to as the off-state) of a subject suffering from Parkinson's disease. 【0003】 Specifically, this device is adapted to be worn by a patient so as to predict in advance the onset of the off-state of the patient and enable the use of suitable intervention means, and is advantageously intended to be used both in a hospital or a rehabilitation environment (such as a hospital, a nursing facility, etc.) and in a home or public environment. 【Background Art】 【0004】 In the fields of psychiatry or neurology, or in the field of the overall clinical condition of the central nervous system, there is a particular need to identify objective biomarkers for fluctuations in the clinical condition of patients. Such a need is particularly important in both the field of clinical trials and the treatment regimens applied to patients suffering from pathologies of the central nervous system. 【0005】 In recent years, wearable electronic devices have been developed, which enable the detection of specific biomarkers (such as heart rate, movement state, respiratory rate, etc.) and the collection in digital format in order to enable the analysis of the detected data. 【0006】 Specifically, in the research and treatment of Parkinson's disease, it is particularly important to detect biomarkers that enable the monitoring of movement disorders caused by degeneration of the central nervous system, which are involved in such diseases (such as tremors or states of motor block). 【0007】 However, in addition to motor symptoms, there are other very strong symptoms, which are also related to a more or less precise response to drug treatment. These manifest as a wide range of symptoms, including cardiovascular disorders, sweating, motor impairment, pain, and sleep disturbances. 【0008】 Even if therapeutic measures (e.g., levodopa-based) have been developed to achieve initial symptom control, patients often develop complications over several years due to the need to cope with the wearoff of the effect, as well as due to drug-induced involuntary movements or motor abnormalities. 【0009】 Specifically, certain symptoms experienced by patients with Parkinson's disease are linked to the onset of what is known as the "wearing-off" state. 【0010】 This wearing-off state is a clinical stage that generally occurs after complications in the advanced stages of the disease, in which the patient suffers relatively long-lasting motor blocks, even with well-adjusted medication. Symptoms may include tremors, rigidity or dullness of movement, difficulty initiating movement, involuntary movements, motor abnormalities, and ataxia, which may be accompanied by psychosomatic symptoms such as anxiety, fatigue, mood swings, difficulty thinking, and agitation. 【0011】 With current technology, monitoring and studying the aforementioned wearing-off state is conducted through the analysis of self-assessment questionnaires collected from patients. However, these raise reliability issues related to the patients' own subjective evaluations (e.g., due to the placebo effect). 【0012】 It is also known that monitoring is performed using a wearable electronic device (of the type described above) equipped with an accelerometer adapted to detect the patient's movement in order to perform an assessment of tremors and wearing-off block (significant reduction in movement) of motor abnormalities. Several examples of this type of device are described in U.S. Patent No. 9,393,418 and U.S. Patent No. 9,602,046. 【0013】 Nevertheless, these known types of devices allow for the performance of assessments that focus solely on the detection and quantification of motor symptoms by measuring the patient's movement. In particular, such solutions are available only for monitoring function, but do not allow for the acquisition of any information useful for identifying symptoms that predict wearing-off states. 【0014】 Several studies in the biomedical field (for example, the article "Prediction of Freezing of Gait in Parkinson's From Physiological Wearables: An Exploratory Study" by Mazilu et al., IEEE Journal of Biomedical and Health Informatics, Vol. 19, No. 6) have shown that observing fluctuations in skin conductance can characterize the so-called freezing state (or freezing of gait) experienced by people with Parkinson's disease. More specifically, the freezing state manifests as a temporary, uncontrolled inability to perform short periods of movement (from a few seconds to a few minutes). Such symptoms often occur suddenly, especially while walking, but can also affect movements for speaking, writing, and opening the eyes. 【0015】 Nevertheless, since the freezing state has completely different clinical characteristics from the aforementioned wearing-off state, they are unlikely to provide useful indicators for identifying symptoms that predict such a wearing-off state. 【0016】 European Patent No. 3076868 discloses a known type of device for monitoring burnout and / or chronic fatigue syndrome stages by detecting skin conductance. In detail, such a device is adapted to calculate characteristics of the skin conductance signal that are interrelated with signal peaks, such as rising slope, rising time, peak height and number. 【0017】 European Patent No. 1519679 describes a known type of device for monitoring the autonomic nervous system of a patient in a sedated state. In detail, such a device provides the detection of information about the nervous system based on the number and frequency of signal peaks occurring within a specific time period. 【0018】 However, even the latter type of device, which is a well-known type, cannot provide useful information for identifying symptoms that predict the wearing-off state. [Prior art documents] [Patent Documents] 【0019】 [Patent Document 1] U.S. Patent No. 9,393,418 [Patent Document 2] U.S. Patent No. 9,602,046 [Patent Document 3] European Patent No. 3076868 [Patent Document 4] European Patent No. 1519679 [Non-patent literature] 【0020】 [Non-Patent Document 1] "Prediction of Freezing of Gait in Parkinson’s From Physiological Wearables: An Exploratory Study" by Mazilu et al., IEEE Journal of Biomedical and Health Informatics, Vol. 19, No. 6 【Summary of the Invention】 【Problems to be Solved by the Invention】 【0021】 In this situation, the main object of the present invention is to overcome the drawbacks represented by known solutions by providing a device for predicting the off - wearing state of patients suffering from Parkinson's disease. The device can predict the onset of the off - wearing state in a reliable way in advance. 【0022】 Another object of the present invention is to provide a device for predicting the off - wearing state of patients suffering from Parkinson's disease that enables warning another subject in advance regarding the onset of the patient's off - wearing state. 【0023】 Another object of the present invention is to provide a device for predicting the off - wearing state of patients suffering from Parkinson's disease that the patient can wear comfortably and easily, especially enabling him / her to continue using his / her hands. 【0024】 Another object of the present invention relates to a device for predicting the off - wearing state of patients suffering from Parkinson's disease with a reduced size. 【Means for Solving the Problems】 【0025】 The technical features of the present invention are clearly found in the content of the claims described below in accordance with the above - mentioned objects. Their advantages will become more apparent from the following detailed description with reference to the accompanying drawings, which show merely exemplary and non - limiting embodiments of the present invention. [Brief explanation of the drawing] 【0026】 [Figure 1] This diagram illustrates possible body positions where the device may be worn by a patient. [Figure 2] This figure shows an example of an embodiment of the device adapted to be worn on the arm or wrist. [Figure 3] This is a simplified block diagram of the device, which is the objective of this invention. [Figure 4] This graph records the time course of a first clinical case of physiological parameters (given by skin conductance) detected over a specific time period (20 hours) using the device described in this invention, which is the objective of this invention. [Figure 5] These are two graphs relating to the first example mentioned above. The upper graph shows the time course of skin conductance as illustrated in Figure 4 (the values ​​of such parameters are standardized according to specific factors, and the isotonic component of skin conductance is superimposed), and the second graph shows the measurements detected by this device representing the patient's movement over the same time period. [Figure 6] These are two graphs relating to the second clinical case. The upper graph shows the time course of skin conductance over a specific 13-hour period (the values ​​of such parameters are standardized according to specific factors, and the isotonic component of skin conductance is superimposed), and the second graph shows the measurements detected by this device representing the patient's movement over the same period. [Modes for carrying out the invention] 【0027】 Referring to the attached figure, reference numeral 1 overall shows a device for predicting the wearing-off state in a patient with Parkinson's disease, which is the objective of the present invention. 【0028】 Device 1 is intended to be worn by the user in a specific position on the body and is intended to detect the patient's wearing-off state a short time before it begins (e.g., 10-30 minutes). 【0029】 As is known, the wearing-off state in patients with Parkinson's disease is characterized by relatively prolonged generalized motor blocks (which can manifest as tremors, rigidity or dullness of movement, difficulty initiating movement, involuntary movements, dyskin, and ataxia), and it can occur even in the presence of well-adjusted medication. 【0030】 Referring to the application example in Figure 1, the device 1, which is the object of the present invention, can be positioned to be applied to multiple possible parts of the patient's body, such as the arm, wrist, fingers, waist, chest, shoulder, and neck. 【0031】 For example, if device 1 is positioned to be applied to the wrist or arm, device 1 is configured in a bracelet shape and intended to be applied around such a part of the body. 【0032】 Referring to the illustrative diagram in Figure 3, device 1 comprises a skin potential sensor 2 intended to be placed on the patient's skin. Such a skin potential sensor 2 is placed to detect at least one electrical quantity associated with the patient's own skin conductance and to generate a corresponding measurement signal (preferably of electrical type). 【0033】 In addition, device 1 includes an electronic control unit 3, which is operably (preferably electrically) connected to the skin potential sensor 2 to receive the aforementioned measurement signals and is positioned to obtain from the skin sensor 2 the time course of the value of the physiological parameter PF, which represents skin conductance in the patient's skin. 【0034】 More specifically, such physiological parameters PF represent information related to skin potential in the patient's skin, and favorably correspond to the same skin conductance. 【0035】 One example of the physiological parameter PF obtained by the electronic control unit 3 over time is illustrated in the graph in Figure 4 and will be explained in detail below. 【0036】 Device 1 also includes a communication unit 4 operably connected to an electronic control unit 3. The electronic control unit 3 is positioned to be controlled on such a communication unit 4 and emits an off notification signal to indicate that the patient's wearing-off state is approaching. 【0037】 Advantageously, device 1 comprises one or more connecting elements 5, preferably made of a flexible material, and is positioned to press against a corresponding part of the patient's body (such as an arm, wrist, fingers, or chest). 【0038】 For example, the connecting element 5 can be shaped into a band or belt that can be wrapped around and tightened around a part of the body where device 1 is to be positioned. 【0039】 More specifically, referring to the embodiment in Figure 1, the connecting element 5 comprises a flexible band that is closed or can be closed as a loop and is intended to be tightened around a part of the patient's body, such as an arm or wrist. 【0040】 Preferably, the device 1 comprises a support body 6, which is fixed to and positioned to support a connecting element 5, and advantageously includes a skin potential sensor 2, an electronic control unit 3, and a communication unit 4. 【0041】 Advantageously, the skin potential sensor 2 is positioned to be placed in contact with the patient's skin in order to detect electrical quantities, thereby enabling the derivation of skin potential, particularly skin conductance. 【0042】 For example, the skin potential sensor 2 comprises two electrodes intended to be placed in contact with two spaced-out positions on the skin, and a DC voltage generator adapted to apply a predetermined voltage between these two electrodes, so that a current acts on a skin zone between the two electrodes. 【0043】 Since the intensity of such a current depends on skin resistance (and therefore skin conductance), by detecting this current, the skin potential sensor 2 is adapted to detect an electrical measurement related to the patient's skin conductance. 【0044】 For example, the skin potential sensor 2 can be realized using one or more conductivity measuring instruments. 【0045】 Naturally, such a skin potential sensor 2 can also be implemented using a resistance sensor or, more generally, an electrical quantity sensor capable of detecting an electrical quantity related to skin conductance. In detail, the skin potential sensor 2 may be of a capacitive type. 【0046】 As is well known, the skin's electrical potential (particularly skin conductance) changes in response to the state of the skin's sweat glands, and the function of the sweat glands is controlled by the autonomic nervous system. More specifically, active autonomic nervous system activity corresponds to active sweat gland activity, which in turn increases skin conductance, and vice versa. 【0047】 Typically, skin conductance is used to analyze an individual's emotional behavior in different environments. 【0048】 Surprisingly, it was confirmed that the assessment of the wearing-off state in Parkinson's disease patients is preceded by a sustained, significant increase in the overall progression of skin conductance, at least several minutes (particularly 10–30 minutes). For example, in the graph in Figure 4, it is possible to identify multiple peaks in the progression of skin conductance that precede the corresponding wearing-off period in the patient. In detail, such peaks indicate a sustained, significant increase in skin conductance in their elevated sections, which is maintained for at least several minutes. 【0049】 Therefore, it has been demonstrated that the physiological activity of the autonomic nervous system fluctuates particularly before the wearing-off state (detectable from peaks in skin conductance), thereby enabling prediction of the wearing-off state with appropriate advance notice (e.g., about 10-30 minutes). 【0050】 More specifically, as can be seen in the example graph in Figure 4, the time course of the physiological parameter PF (in this case, composed of skin conductance) has a peak period PP, where the value of the physiological parameter PF increases relative to the baseline value obtained when the patient is at rest in a substantially normal state. 【0051】 It was found that patients experienced a wearing-off state after the elevated section of the peak period PP (usually 10-30 minutes later). Therefore, the aforementioned peak period PP in the time course of the physiological parameter PF is due to an increase in autonomic nervous system activity related to the subsequent wearing-off state. 【0052】 According to the fundamental concept of the present invention, the electronic control unit 3 comprises a processing module 7 which is configured to define a specific movable time window FT lasting for 30 seconds or more in the aforementioned continuous values ​​of the physiological parameter PF. 【0053】 The processing module 7 is also configured to periodically update such a movable time window FT by advancing the physiological parameter PF along a continuous value of the physiological parameter PF. 【0054】 In detail, for each newly acquired measurement signal from the skin potential sensor 2, and therefore for the subsequent calculation of new values ​​of the physiological parameter PF over time, the processing module 7 is configured to add one or more physiological parameters PF at the beginning of the time window FT. Accordingly, to remove one or more values ​​at the end of the time window FT, the time window FT is moved forward along the time course of the values ​​while maintaining the same size of the time window FT. 【0055】 For each update of the time window FT, processing module 7 is configured to calculate the overall time variation of the physiological parameter PF, which indicates an increase in skin conductance (intended to be a positive increase) within the time window FT itself. The aforementioned overall time variation is calculated by processing the elapsed values ​​contained within the time window FT, thereby identifying clear increases in the physiological parameter PF within such a time window FT and executing a specific calculation algorithm. Several examples of this are provided below. 【0056】 Additionally, processing module 7 is positioned to compare the overall temporal variation of physiological parameters with a specific threshold VS, thereby detecting significant increases in the value of such physiological parameters PF (particularly skin conductance) over time. This can be used to display an evaluation of the wearing-off state. 【0057】 In detail, such a significant increase in the physiological parameter PF, distinguished based on the aforementioned threshold VS, detects peaks in the magnitude and duration of skin conductance as an indicator of the closest assessment of the wearing-off state. 【0058】 The electronic control unit 3 is configured to transmit a control signal SC to the communication unit 4, which is adapted to enable the electronic control unit 3 to issue a corresponding off notification signal, when the overall time variation in the value of the physiological parameter PF within the time window FT is greater than the threshold VS (i.e., when a significant increase is identified). 【0059】 Therefore, such off-notification signals allow for alerting a third party or the patient themselves to the nearest possible wearing-off, thereby enabling appropriate action (e.g., appropriate support intervention or therapeutic action). 【0060】 More specifically, as described above, significant increases (indicating the peak period PP over time of the physiological parameter PF) are distinguished according to the magnitude of such increases (greater than the threshold VS) and their duration (determined by the time window FT). 【0061】 Such parameters (threshold VS, time window FT) allow us to identify continuous fluctuations in the overall progression of the physiological parameter PF. The mean slope of such fluctuations is large enough to indicate reaching a peak in the physiological parameter PF prior to the wearing-off state. 【0062】 In effect, the overall temporal variation of the physiological parameter PF represents a distinct variation, and the progression of such a physiological parameter PF is affected within all time windows FT (i.e., from the start to the end of such a time window FT). 【0063】 Advantageously, the overall temporal variation of the physiological parameter PF is obtained as the ratio between the increase in the value of the physiological parameter PF detected in the time window FT and the time over which such variation occurs, given by the duration of the time window FT. 【0064】 In detail, the overall temporal variation of the physiological parameter PF is essentially a representation of the slope at which the progression of the physiological parameter PF itself occurs, primarily within the time window FT. Essentially, if such a major slope is greater than the threshold VS, it indicates a significant increase in the physiological parameter PF, which can precede the patient's wearing-off state. 【0065】 Advantageously, the overall temporal variation of the physiological parameter PF depends on both local increases and local decreases that can be observed within the time window FT. 【0066】 Advantageously, processing module 7 is positioned to determine the overall time variation of the physiological parameter PF based on the time derivative of the physiological parameter PF itself, which is calculated within the time window FT. 【0067】 More specifically, the time derivative of the physiological parameter PF can be calculated by using all or only some of the values ​​of the physiological parameter PF within the time window FT. 【0068】 Preferably, according to a particular embodiment of the present invention, within the aforementioned time window FT, the processing module 7 is adapted to calculate the time variation of the physiological parameter PF according to the difference between at least one maximum and minimum value of the physiological parameter PF detected within the time window FT. 【0069】 For example, the overall time variability can be calculated as the difference between the maximum and minimum values ​​of the physiological parameter PF within the time window FT, relative to the time interval (within the time window FT) that exists between the maximum and minimum values. 【0070】 According to different embodiments, the overall time variation is obtained from the average value of the time derivative at the physiological parameter PF within the time window FT. 【0071】 Advantageously, the time window FT is about 5 minutes or less, preferably consisting substantially of 1 to 3 minutes, for example, 2 minutes. 【0072】 More specifically, such values ​​of the time window FT allow for the identification of substantially continuous temporal variations in the physiological parameter PF over a time period large enough to represent an assessment of the peak period PP of skin conductance. It is an indication of the assessment of the nearest wearing-off state. 【0073】 As shown above, time variations occurring during the time window FT are selected as significant increases if they are greater than the aforementioned threshold VS. 【0074】 In detail, in this explanation, the values ​​and variability of the physiological parameter PF are intended as absolute values. This is because such values ​​of the physiological parameter PF may be positive or negative depending on the specific physiological parameter PF (for example, when considering skin resistance rather than skin conductance). 【0075】 In any given case, the time variation of the physiological parameter PF represents a positive increase in the patient's skin conductance (i.e., a specific variation in which the overall slope of the progression of the physiological parameter PF increases). For example, if the physiological parameter PF coincides with skin conductance, the time variation will be positive. However, if the physiological parameter PF coincides with skin resistance, the time variation will be negative. 【0076】 In general, the values ​​obtained from the physiological parameter PF (especially skin conductance), both in terms of peak and baseline values, as well as the magnitude and rate (slope) of significant increases, may vary from patient to patient. Additionally, such values ​​may also vary depending on the part of the body to which the skin potential sensor 3 is positioned. Therefore, the threshold VS and time window FT are determined in accordance with these applicable factors, particularly based on the measurements of the physiological parameter PF performed on such patients. 【0077】 Advantageously, the threshold VS is determined according to the peak value detected at least partially over time in the value of the physiological parameter PF. 【0078】 Preferably, the electronic control unit 3 is configured to be set in a calibration state, where the electronic control unit 3 determines the threshold VS based on the value obtained at a specific calibration time interval IT over time of the physiological parameter PF. 【0079】 For example, the electronic control unit 3 can be set in the initial stage of its operation to a calibration state, for example, after being first applied to a specific patient. 【0080】 Preferably, the calibration time interval IT during which the electronic control unit 3 operates in a calibration state has a duration of several hours, for example, 3 to 6 hours. 【0081】 In detail, during calibration, the processing module 7 is configured to detect the peak value (or maximum value) in the sequence of values ​​of the physiological parameter PF evaluated over the aforementioned calibration time interval IT, and calculates a threshold VS according to this peak value. 【0082】 More specifically, in the calibration state, the processing module 7 is configured to determine at least one rest reference value (VPR) corresponding to the time-lapse values ​​detected outside the peak period PP, where the physiological parameter PF remains substantially stable near the baseline value when the individual is not subjected to conditions and / or activities (in addition to the wearing-off state) that would cause significant fluctuations in skin sweating (which typically vary depending on the subject). 【0083】 For example, the values ​​used to determine the baseline value are selected based on whether they fall below the upper limit and / or have a variation (derived from) a specific judgment value. 【0084】 Additionally, in the calibration state, the processing module 7 is configured to determine the peak reference value VRP according to the evaluated peak value during the peak period PP, i.e., the period during which the physiological parameter PF has increased significantly relative to the baseline value. 【0085】 In detail, the static reference value VRR and the peak reference value VRP can be obtained by applying a processing function (filtering, averaging, etc.) to the time-dependent values, which is adapted to remove minor values ​​such as noise, faults, and spurious vibrations. 【0086】 For example, the static baseline VRR is obtained as the mean value of the physiological parameter PF outside the PP period, excluding any further strong deviations from the baseline due to possible factors (usually irregular) that are not related to the wearing-off state. 【0087】 For example, the peak reference value VRP is obtained as the average of the maximum values ​​reached over multiple peak periods. 【0088】 Advantageously, the processing module 7 is adapted to calculate the threshold VS according to the difference (particularly the absolute value of that difference) between the static reference value VRR and the peak reference value VPR. 【0089】 For example, the aforementioned difference between the static reference value VRR and the peak reference value VPR (and therefore favorably the threshold VS) is at least at the level of microsiemens, and in particular, it consists of a level between a few microsiemens and a level of tens of microsiemens. 【0090】 Preferably, the threshold VS is proportional to the aforementioned difference (due to a specific fixed or variable factor), and preferably less than this difference. 【0091】 In detail, the threshold VS is comprised of approximately 1 / 3 to 1 / 7 of the difference between the static baseline VRR and the peak baseline VRP. 【0092】 For example, the threshold VS can be obtained as follows: VS = (VRP - VRR) / 5 【0093】 Alternatively, for example, before performing the calibration, the threshold VS can be set based on different criteria, such as values ​​derived from the target material. 【0094】 Advantageously, the electronic control unit 3 of device 1 comprises an electronic processor (preferably a microprocessor) which is suitably programmed to perform the functions described above. 【0095】 Preferably, the processing module 7 of the electronic control unit 3 is integrated with the aforementioned electronic processor and executed using a specific program installed on such an electronic processor. Of course, alternatively, the processing module 7 can also be executed using hardware components different from the aforementioned electronic processor. 【0096】 Advantageously, the communication unit 4 of device 1 includes a wireless communication module (such as a wireless transmitter) that can transmit an off notification signal to a remote unit adapted to receive such a signal and arrange for a warning signal to a third party. Such a remote unit includes, for example, a portable device (such as a smartphone, people finder, or suitable receiver), a computer in a control station, or an electronic device that can be used by a person such as a medical practitioner, nurse, or relative, so that they can make appropriate preparations considering the patient's nearest possible wearing-off state. 【0097】 Preferably, in certain embodiments, device 1 includes a signal transmitting unit connected to (and possibly integrated with) a communication unit 4. It can emit an acoustic, visual, or tactile signal to alert the patient or a nearby person after receiving an off notification signal. 【0098】 According to another specific embodiment, the communication device 4 is arranged to transmit signals to a device adapted to coordinate the administration of one or more drugs to a patient according to a specific drug therapy. 【0099】 For example, in the embodiment illustrated in Figure 2, the processing module 7 and the communication unit 4 are mounted close together, for example, on the support body 6 of the device 1. 【0100】 According to an alternative embodiment, the processing module 7 and the communication unit 4 are mounted remotely to a remote processor (such as a server). Device 1 includes a transmitter, which is connected to an electronic control unit 3 adapted to transmit a series of electrical measurements and / or physiological parameters PF to the remote processor, enabling the processing module 7 and the communication unit 4 to complete their functions remotely as described above. 【0101】 Preferably, the hardware and software of device 1, which are used to detect the value of the physiological parameter PF during the calibration state and subsequent operation, are installed in the same support body 6. 【0102】 Alternatively, the hardware and software of device 1 used to detect the value of the physiological parameter PF during the aforementioned calibration state are located in a separate unit of device 1. 【0103】 Advantageously, device 1 comprises at least one inertial sensor 8, which is intended to be applied to a patient and is adapted to measure the kinematic variables of the patient's own body in order to generate a corresponding detection signal. 【0104】 Preferably, the inertial sensor 8 can be attached to the support body 6 of the device 1 and may include, for example, an accelerometer or a gyroscope. 【0105】 The inertial sensor 8 is operably connected to the electronic control unit 3 to transmit the aforementioned detection signal to the electronic control unit 3, from which the electronic control unit 3 can obtain information regarding the frequency, intensity, and type of movement performed by the patient. 【0106】 Such information can be favorably correlated with the time course of these physiological parameters PF in order to identify specific interactions between them. 【0107】 For example, the graph in Figure 4 shows an example of a test showing the time course of the physiological parameter PF (corresponding to skin conductance in this case) obtained based on measurements detected by the skin potential sensor 3 over a 20-hour period. 【0108】 The same graph is shown in the upper part of Figure 5 (with standardized values ​​of skin conductance), while another graph is shown in the lower part of Figure 5, which shows the time course of measurements representing the frequency and intensity of exercises detected by the inertial sensor 3 and completed by the patient during the same aforementioned time period. 【0109】 The graph in Figure 6 shows the aforementioned information derived from different patients in the second clinical case. 【0110】 The vertical lines further illustrate the moment when the wearing-off state occurred in the patient. 【0111】 To enable detection, the wearing-off state was evaluated after the value of the physiological parameter PF of the corresponding peak period PP increased, particularly during the downward phase of such a peak period PP. 【0112】 Additionally, as can be demonstrated in the graphs below Figures 5 and 6, at the moment of wearing off, the measurements detected by the inertial sensor 8 are substantially at their lowest point, and there is no peak representing patient movement. Therefore, demonstrating the absence of substantial patient movement is consistent with the existence of a wearing-off state. 【0113】 Advantageously, the electronic control unit 3 comprises an electrical sensor 3 and a tuning module for signals 9, preferably connected to an inertial sensor 8. This is for receiving the measurement signal and the detection signal, respectively, generated by such sensors 3 and 8. Such a tuning module 9 is arranged to process such measurement / detection signals in particular to remove spurious components (e.g., noise, faults, etc.) by specific processing for processing and / or transforming the signals, such as filtering, interpolation, and smoothing operations. 【0114】 The adjustment module 9 is connected to the electrical control unit 3 to transmit measurement / detection signals to the electrical control unit 3, which have been adjusted in a manner that facilitates accurate processing of the included data by the electrical control unit 3 itself. 【0115】 Advantageously, device 1 includes a power supply unit 10, such as a battery, which is electrically connected to an electronic control unit 3, a skin potential sensor 2, a communication unit 4, and preferably an inertial sensor 8, to provide electrical energy (preferably DC current) suitable for operation. Such a power supply unit 10 is installed, for example, within the support body 6 of device 1. 【0116】 The following describes how to operate the aforementioned type of device 1. 【0117】 In the following, even though this method must be intended to be applicable to adjustment devices possessing all the features considered above, for the sake of brevity, we will refer to the same names as those introduced so far. 【0118】 This method of operation applies the skin potential sensor 2 to the patient's skin, particularly by having the patient wear device 1 themselves. Preferably, the skin potential sensor 2, and especially its electrodes, are positioned in contact with the skin. 【0119】 The skin potential sensor 2 is activated to detect at least one electrical quantity associated with the patient's skin conductance in a manner that generates a corresponding measurement signal transmitted to the electronic control unit 3. 【0120】 Therefore, the electronic control unit 3 receives a measurement signal from the skin potential sensor 2 and obtains the time course of the physiological parameter PF, which represents the skin conductance of the patient's skin, from it. 【0121】 The electronic control unit 3 controls the communication unit 4 according to the value of the physiological parameter PF to emit at least one off notification signal indicating the closest assessment of the patient's wearing-off state. 【0122】 In this operation method, the processing module 7 of the electronic control unit 3 defines a specific movable time window FT in the elapsed time of the value of the physiological parameter PF, which is 30 seconds or more, preferably less than about 5 minutes, and particularly consists of a duration of about 1 to 3 minutes. 【0123】 Following the acquisition of a new measurement signal by the skin potential sensor 2 (and the acquisition of a corresponding new value for the physiological parameter PF), the module update proceeds in accordance with the time course of the value obtained for the physiological parameter PF, as already explained above, and the time window FT update operation is repeated. 【0124】 Through all update operations of the time window FT, processing module 7 calculates within the time window FT itself the overall time variation of the physiological parameter PF, which indicates the increase in skin conductance within the time window FT. Such calculations are obtained by processing the elapsed time values ​​contained within the time window FT. 【0125】 Advantageously, the time variation of the aforementioned physiological parameter PF can be obtained by the time derivative of the physiological parameter PF within the time window FT, in particular, as explained above. 【0126】 According to this method, the processing module 7 compares the overall time variation of the physiological parameter PF with a specific threshold VS, and if this overall time variation is greater than this threshold VS, it sends a control signal SC to the communication unit 4, enabling the communication unit 4 to emit an off notification signal, thereby allowing the nearest wearing-off state to be warned to the patient or a third party (as described above). 【0127】 Advantageously, the method for operating device 1 is preferably performed when device 1 is first applied to the patient, so as to provide a calibration step and set the threshold VS. 【0128】 More specifically, in this calibration step, the electronic control unit 3 determines a threshold VS based on the value of the physiological parameter PF obtained over time at a specific calibration time interval IT, as described above. In the aforementioned calibration state, the electronic control unit 3 is set by, for example, a preferred control that can be made by the user. 【0129】 Thus, it is considered that the present invention has achieved its predetermined objectives.

Claims

[Claim 1] A device (1) for predicting the wearing-off state in a patient suffering from Parkinson's disease, A skin potential sensor (2) is intended to be placed on the patient's skin, positioned to detect at least one electrical quantity associated with the patient's skin conductance, and to generate a corresponding measurement signal. To receive the measurement signal, an electronic control unit (3) is operably connected to the skin potential sensor (2) and is configured to obtain from the measurement signal the time course of a physiological parameter (PF) representing skin conductance in the patient's skin. A communication unit (4), which is operably connected to an electronic control unit (3) arranged to control the communication unit (4) in order to emit at least one off notification signal, Equipped with, The electronic control unit (3) comprises at least one processing module (7), and the processing module (7) is In the time course of the physiological parameter (PF) value, define a movable time window (FT) of the characteristic having a duration of 30 seconds to 5 minutes, and The time window (FT) is updated by advancing the value along the aforementioned time progression. They are arranged, For each update of the aforementioned time window (FT), the processing module (7) Within the time window (FT), the overall time variation of the physiological parameter (PF) that indicates an increase in skin conductance within the time window (FT) is calculated by processing the time-elapsed values ​​included in the time window (FT). The overall time variation is compared to a specific threshold (VS), Using the overall time variation which is greater than the threshold (VS), at least one control signal (SC) is transmitted to the communication unit (4) which is adapted to enable the communication unit (4) to emit the off notification signal. Device (1) is positioned. [Claim 2] The device (1) according to claim 1, characterized in that the processing module (7) is arranged to determine the overall time variation according to the time derivative of the physiological parameter (PF) in the time window (FT). [Claim 3] The device (1) according to claim 1 or 2, wherein the processing module (7) is arranged to determine the overall time variation according to the average value of the time derivative of the physiological parameter (PF) calculated within the time window (FT). [Claim 4] The device (1) according to claim 3, characterized in that the time window (FT) is composed of 1 to 3 minutes. [Claim 5] The device (1) according to any one of claims 1 to 4, characterized in that the processing module (7) is arranged to determine the time variation according to the difference between at least one maximum value and a minimum value of the physiological parameter (PF) in the time window (FT). [Claim 6] The device (1) according to any one of claims 1 to 5, characterized in that the threshold (VS) is determined according to the peak value of the physiological parameter (PF) over the course of time. [Claim 7] The device (1) according to claim 6, wherein the electronic control unit (3) is arranged to be set to a calibration state, and in a specific calibration time interval (IT), the processing module (7) is arranged to detect the peak value of the value over the time elapsed and to calculate the threshold value (VS) according to the peak value. [Claim 8] The device (1) according to claim 7, characterized in that the threshold (VS) is a function of at least one mean value of the peak values ​​detected in the calibration time interval (IT). [Claim 9] The aforementioned time course includes a peak period (PP), during which one or more of the aforementioned peak values ​​are included. The device (1) according to claim 7 or 8, wherein in the calibration state, the processing module (7) is configured to determine at least one static reference value (VRR) according to the elapsed time outside the peak period (PP), and at least one peak reference value (VRP) according to the peak value, and to calculate the threshold value (VS) according to the difference between the peak reference value (VRP) and the static reference value (VRR). [Claim 10] The device (1) according to claim 9, characterized in that the threshold (VS) is composed of 1 / 3 to 1 / 7 of the difference between the static reference value (VRR) and the peak reference value (VRP). [Claim 11] The device (1) according to any one of claims 1 to 10, characterized in that the overall temporal variation of the physiological parameter (PF) is obtained as a ratio between the increase in the value of the physiological parameter (PF) detected in the time window (FT) and the duration of the time window (FT). [Claim 12] The device (1) according to any one of claims 1 to 11, characterized in that the overall time variation of the physiological parameter (PF) shows a slope in which the progression of the physiological parameter (PF) mainly advances within all of the time windows (FT).

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