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Title:
PORTABLE WIRELESS ELECTRONIC SYSTEM FOR THE DIAGNOSIS, THE MONITORING AND/OR THE THERAPY OF DYSKINESIA OR RLS
Document Type and Number:
WIPO Patent Application WO/2006/105621
Kind Code:
A1
Abstract:
The present invention is related to an electronic system for the diagnosis, the monitoring and/or the treatment of dyskinesia or RLS comprising: - a measuring unit (1) with sensors to be applied upon a human body patient, - a Master Unit (2), - a video recorder (9), - a software platform (8), - a memory device (6), - and a drug delivery device (7) to be applied upon the human body patient.

Inventors:
MANTO MARIO (BE)
Application Number:
PCT/BE2006/000029
Publication Date:
October 12, 2006
Filing Date:
April 03, 2006
Export Citation:
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Assignee:
UNIV BRUXELLES (BE)
MANTO MARIO (BE)
International Classes:
A61B5/00; A61M5/14
Foreign References:
US6356784B12002-03-12
US20050080463A12005-04-14
Other References:
SHERRILL D M ET AL: "Advanced Analysis of Wearable Sensor Data to Adjust Medication Intake in Patients with Parkinson s Disease", NEURAL ENGINEERING, 2005. CONFERENCE PROCEEDINGS. 2ND INTERNATIONAL IEEE EMBS CONFERENCE ON ARLINGTON, VIRGINIA, USA MARCH 16-19, 2005, PISCATAWAY, NJ, USA,IEEE, 16 March 2005 (2005-03-16), pages 202 - 205, XP010785295, ISBN: 0-7803-8710-4
KEIJSERS N L W ET AL: "ONLINE MONITORING OF DYSKINESIA IN PATIENTS WITH PARKINSON'S DISEASE", IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE, IEEE SERVICE CENTER, PISACATAWAY, NJ, US, vol. 22, no. 3, May 2003 (2003-05-01), XP001195953, ISSN: 0739-5175
Attorney, Agent or Firm:
Van Malderen, Joëlle (Avenue Josse Goffin 158, Brussels, BE)
Download PDF:
Claims:
CLAIMS
1. An electronic system for the diagnosis, the monitoring and/or the treatment of dyskinesia or restless legs syndrome (RLS) comprising a measuring unit (1, 1' or 1") with sensors to be applied upon a human body patient, a Master Unit (2) , a video recorder (9) , a software platform (8) , a memory device (6) , and a drug delivery device (7) to be applied upon the human body patient.
2. The electronic system according to the claim 1, wherein the master unit is connected to the drug delivery device and controls the administration of the drug according to data collected from the measuring unit (1, 1' or 1") from the video recorder (9) and possibly from data collected in the memory device (6) .
3. The electronic system according to the claim 1 or 2 , which comprises at least two measuring units (1, 1' or 1") with sensors to be applied upon a human body patient .
4. The electronic system according to the claim 3, which comprises at least two measuring units (1, 1' and 1") with sensors to be applied upon the limbs of the human body patient.
5. The electronic system according to the claim 4 , wherein a measuring unit is applied upon : two arms , two arms and one leg, two legs and one arm, or two legs and two arms .
6. The system according to the claims 1 to 5, wherein the measuring unit (1) comprises inertial and muscle sensors .
7. The system according to the claim 6, wherein the inertial sensors are selected from the group consisting of gyroscopes (10) and accelerometers (11) .
8. The system according to the claim 6, wherein the muscle sensors are electromyographic sensors (40), electroencephalographic sensors or cortical sensors.
9. The system according to the claims 6 to 8, wherein the sensors are able to operate in a frequency range between about 0.05 Hz and about 30 Hz, preferably between about 0.05 Hz and about 18 Hz and more preferably between about 0.05 Hz and about 14 Hz.
10. The system according to any of the preceding claims 6 to 9 , wherein the inertial and muscular sensors of the measuring unit, are attached by means to the human body patient, preferably to the human body limbs.
11. The system according to the claim 10, wherein the means include the drug delivery device (7) possibly the master unit (2), the software platform (8), and/or the memory device (6) .
12. The system according to the claim 10 or 11, wherein the means are a textile carried by the human patient, preferably a neoprene textile.
13. The system according to the claims 10 to 12, wherein the means allow movement of the inertial and/or muscular sensors along the limbs of the patient.
14. The system according to the claim 13, wherein the movement of the inertial and/or muscular sensors is controlled by the master unit (2) according to a measurement obtained from a measuring unit (1, 1', 1" ) .
15. The system according to any of the preceding claims, wherein the Master Unit (2) comprises a microcontroller (3) , a visualisation unit (5) such as a LCD display and possibly a battery (4) .
16. The system according to any of the preceding claims, wherein the memory device (6) is a detachable memory stick or a detachable memory card.
17. The system according to any of the preceding claims, wherein the software platform (8) is integrated in a personal computer, a notebook or a handheld computer device.
18. The system according to any of the preceding claims, wherein the software platform (8) is connected to the master unit (2) to receive and record the set of data by the measuring unit (1) and transmitted by the master unit (2) .
19. The system according to any of the preceding claims, wherein the drug delivery device (7) is a subcutaneous pump placed on a limb and/or in the abdomen of the human body patient and able to deliver a drug at a given rate.
20. The system according to any of the preceding claims, wherein the measuring unit (1) comprises four sensors, two surfaces electromyographic sensors (12) and two tridimensional (triaxial) gyroscopes sensors (10) .
Description:
PORTABLE WIRELESS ELECTRONIC SYSTEM FOR THE DIAGNOSIS, THE MONITORING AND/OR THE THERAPY OF DYSKINESIA OR RLS

Field of the invention [0001] The present invention is related to a portable wireless electronic system for the diagnosis, the monitoring and/or the therapy of various diseases or disorders, such as dyskinesia, especially human dyskinesia, or restless legs syndrome (RLS) (including leg cramps and leg movements at bedtime) .

Background of the invention

[0002] Human dyskinesia constitutes an asymmetric abnormal movement, which interferes heavily with the activities of daily living. This irregular and uncontrollable movement affects a different part of the body.

[0003] Burkhard et al . (Mov. Disord. 1999, vol. 14, p. 754-763) describes three types of dyskinesia : choreic, dystonic and mixed dyskinesia which may have various origins . [0004]

1) Parkinson disease : dyskinesia appears among 30% of the patients receiving levodopa after five years of treatment (Derkinderen et al . Rev. Neurol. Paris 2002, vol. 158, p. 92-101 and Schrag et al . Brain 2000, vol. 123, p. 2297 - 2305) and among more than 50 % of the patients after ten years of treatment (Poewe et al . Movement disorders, Watts and Roller Edition, Mac Graw Hill, 1997, p. 2001-2019) .

[0005] Various risk factors have been identified : the early development of Parkinson disease, a disease having severe effects or the administration of high level of levodopa to the patient . [0006] Furthermore, survival curves show that Parkinson disease having started in a patient before, or at 50 years, combined with an initial dose of levodopa higher than 600 mg/day is associated with a high risk of dyskinesia (p < 0.05) (Grandas et al . J. Neurol. 1999, vol. 246, p. 1127 - 1133). For these patients, dyskinesia presents an important biphasic character, which means that such dyskinesia appears at the begin of the administration and in the end of the administration, or can be present during the peak dose administration (peak dose dyskinesia) . [0007] These dyskinesia are preferably present upon the body side firstly affected when early symptoms are discovered (Grandas et al . 1999).

[0008] During the evolution of the Parkinson disease, the distinction between the various type of dyskinesia is more difficult, because an overlap exists with other detected abnormal movements (myoclonus, akathisia and pseudoakathisia) (Derkinderen et al . 2002, Havaki-Kontaxahi et al . Eur. Neuropsychopharmacol . 2000, vol. 10, p. 333-336) . [0009] Pulsate stimulation of Dopaminergic nerves can also generated dyskinesia (Jenner Neurology 2004, vol. 62, p. 47-55) .

[0010] Furthermore, preliminary studies upon primates show that the addition of small doses of levodopa to a COMT (cathechol-o-methyl transferase) inhibitor (such as entacapone) or to a dopaminergic agonist can avoid dyskinesia in toxic models of Parkinsonism (Jenner 2004) .

[0011]

2. Multi-systemic atrophy : dyskinesia appears earlier than with Parkinson disease.

[0012]

3. Schizophrenia : dyskinesia appears spontaneously or following the administration of neuroleptics (McCreadie et al. Br. J. Psychiatry 2002, vol. 181, p. 135-137) .

[0013] The natural evolution is not well known because patients can also suffer from akathisis or pseudo- akathisis. Pseudoakathisis is present in about 5% of schizophrenic patients (Havaki-Kontaxaki et al . 2000) . [0014] Natural evolution of this pseudo akathisis is not well known. Among patients receiving a poly-therapy treatment, dyskinesias are often detected after complex clinical studies and are usually not well characterized from these clinical analyses.

[0015] Furthermore, classical neuroleptics (such as Haloperidol) are usually associated with a higher incidence of diskinesia than recently developed anti-psychotic drugs

(such as Risperidone) . However, further studies are required upon these new compounds . [0016]

4. CO Intoxication : dyskinesia usually disappears after 8 weeks after the diagnosis (Choi et al . Eur. Neurol. 1999, vol. 42, p. 141-144) .

[0017] More rarely, Parkinson disease can also be associated with a dysfunction of a neuro-muscular junction, coupled with clinical lesions of the central neuronal system and the peripheral neuronal system (Ueno et al .

Neurology 1987, vol. 37, p. 832-833).

[0018] Furthermore, a motricity asymmetry (hemibody chorea and weakness of lateral control of the hemibody) can be the initial manifestation of a dysfunction in a neuro-

muscular junction, such as myasthenia) (Ong et al . Singapore Med. J. 1993, vol. 34, p. 60-61) .

[0019] At the present time, various techniques are used for the detection and the analysis of dyskinesia :

A clinical quantification can be obtained upon the graduations of the severity of a dyskinesia starting from score 0 up to score 4 (Burkhard et al . , Mov. Disord. 1999, vol. 14, p. 754-763) . These graduations take into account a left-right asymmetry (they can be more present upon one side) and the type of dyskinesia. However, these graduations are subjective and their reproducibility depends upon the experience of the clinician.

- A quantification by videos requires well trained users. However, reproducibility between different clinicians is not adequate .

- A quantification by "accelerometry" requires the use of different "accelerometers" having various technical drawbacks that do not provide information upon muscular activity patterns associated with dyskinesia or concerning the motor behaviour during the evolution of the disease. [0020] Furthermore, there is no monitoring of this disease following the administration of therapeutical products, such as dopaminergic agonist levodopa or continuous administration of drugs, such as Apomorphine that requires a sub-cutaneous administration by a pump) . The flow and the concentration of these drugs require a monitoring following a clinical evaluation of the dyskinesia (Poewe et al . 1997). [0021] Furthermore, if the detected dyskinesia has a biphasic character, the administration of apomorphine by a sub-cutaneous way is realised in bolus (Poewe et al . 1997) .

[0022] It is also known that peripheral nerve stimulation by an electrical or magnetic stimulus induces modulation of electromyographic activity and muscular response. This stimulus can be administrated at different frequencies and at different intensities allowing an index of muscular response synchronisation. However, the effects of these repetitive electrical stimuli upon kinematic and electromyographic activities with dyskinetic patients are not well known. [0023] Furthermore, it seems that the restless legs syndrome (RCS) is present in an important percentage of the population (up to 10% of the US population) and is characterized by various sensations, such as creeping, itching, pulling, creezy-crowly, tugging and gnawing. [0024] The cause of restless legs syndrome (RCS) is unknown in most patients. However, RLS has been associated with pregnancy, obesity, smoking, iron deficiencies and anaemia, nerve diseases, heavy metal toxicity, toxins and many other conditions . [0025] However, up to now, the diagnosis of such syndrome and the screening of compounds for its treatment still needs improvements.

State of the art [0026] The publication of Sherrill DM et al . (Neural Engineering 2005, Conference proceedings. 2 nd International IEEE EMBS Conference on Arlington, Virginia, USA, March 16- 19, 2005) discloses an electronic system for diagnosis, monitoring and treatment of dyskinesia comprising a measuring unit with sensors to be applied upon a human body patient, a master unit, a video recorder, a software platform and a memory device.

[0027] However, this document does not disclose a system which allows simultaneous administration of a

medicament to the patient by a drug delivery device to be applied upon the human body patient.

[0028] The US patent 6 356 784 describes a method for treating movement disorders by electrical stimulation and/or implantable pump and catheters for drugs infusions.

[0029] The device described in said document incorporates electrical stimulation and/or drug infusion techniques to directly or indirectly influence the PPN

(pedunculopontine nucleus) . One or more of these electrodes or catheters are implanted into the brain so that the stimulation or infusion portion leads within or in combination with predetermined portions of the brain. [0030] However, until now, it has not been proved that electrical stimulation or drug therapy influences the PPN to achieve a desired result and reduce movement disorders .

[0031] Furthermore, in this prior art disclosure, the drug delivery device applied in a specific portion of the brain requires complicated and expensive devices that can create a trauma to a patient.

[0032] Furthermore, such device is not adapted for the monitoring and/or the therapy of RLS that is present in a patient at bedtime.

Aims of the invention

[0033] The present invention aims to provide a new system, which does not present the drawbacks of the device of the state of the art and especially improves the detection, the monitoring and possibly the simultaneous treatment of patients suffering from various diseases or disorders, especially dyskinesia or restless legs syndrome

(RLS) .

[0034] Another aim of the present invention is to provide such system which does not present the drawbacks of

the system of the state of the art, in particular, which is portable, wireless and which can be used directly by various clinicians, or patients suffering from this disease and which is particularly adapted to be carried upon limbs of the patient, especially during their sleeping.

[0035] A further aim of the present invention is to propose such system which does not induce trauma to the patients, especially psychological trauma due to the presence of connection between the device or which does not require invasive, intra-cerebral administration of compounds .

Summary of the invention

[0036] The present invention is related to a portable wireless electronic system for detecting, monitoring and/or (simultaneously) treating various diseases or disorders, especially human dyskinesia or restless legs syndrome (RLS) , said system comprising at least the following elements : a master unit, a measuring unit, preferably at least two measuring units, a video or any other image recorder, a software platform, a (preferably detachable) memory device, and, possibly, a drug delivery device (allowing an administration to a patient according to the values measured by the measuring unit or the disorders recorded by the video recorder) and. - Possibly, batteries for maintaining the system portable .

[0037] Advantageously, the combination of a master unit and a measuring unit and a drug delivery device allows simultaneously a detection and possibly a monitoring of such disease or syndrome and at the same time a treatment of said disease or syndrome. Such monitoring can be done easily by clinicians or patients for whom the treatment can be adapted, according to the data obtained from the measuring unit .

[0038] Furthermore, the master unit of the system according to the invention could also perform an immediate release of a drug by the drug delivery device according to the data (detected value, importance of the recorded disorder, ...) obtained from the measuring unit, the video recorder and possibly the data collected on the memory device. This immediate treatment is obtained in a few milliseconds, preferably, in a time of less than 1 second.

[0039] The present invention is therefore related to a system for computer aided, detection of various diseases but also simultaneously delivery of drugs to a patient, wherein the master unit is connected to the measuring unit to the video or any other image recorder to a memory device and to the drug delivery device. Said master unit is controlled by a software platform which may comprise a graphic user interface to display different views of the system and to accept an user imput and wherein this interface is used to link the master unit and the drug delivery device and to link the master unit to specific view display by the graphical user interface. The computer aid delivery of drugs is ....??? obtained by a cession controller arranged to carry out modelling of drugs administration and arranged to run a first procedure and possibly to dynamically adapt said first procedure and/or to select and run this procedure or another procedure based upon data obtained from the measuring unit, the video or

another image recorder and possibly a data collected in the memory device; each of this data being specific of the patient to be treated and submitted to this diagnosis and/or treatment . [0040] Furthermore, said procedure could be also adapted according to other sensor outputs and/or observations from a clinician.

[0041] Furthermore, the system may also comprise a second interface linking a cession controller to this view displayed by the graphical user interface, in order to follow a specific protocol .

[0042] Advantageously, the system also comprises either a processor or a drug delivery cession manager that integrates the graphic user interface, the master unit and the cession controller.

[0043] The system may also comprise a set of configurable written procedure or protocol to steer drugs delivery, wherein said procedures are adapted to the type of treatment to be applied to the patient, adapted to the patient physical conditions and adapted to the type of drugs to be administrated to the patient and possibly adapted by specific tools and theoretical models already used for the treatment of said disease or disorder.

[0044] The characteristics related to the patient physical conditions are for example : the age, the sex, the weight and the general physical conditions of the patient.

[0045] The system according to the invention can also contain a set of configurable written procedures or protocols, established by experience of one or more clinicians upon different subjects submitted to .the same treatment. Therefore, this set of procedures which reflect the knowledge and expertise of varied experienced clinicians is put at the disposition of the user (other clinicians, nurses or assistants in charge who are not

obliged to follow the procedure blindly and which allow a reversion to a manual mode, if possible at any time.

[0046] However, the advantages of this system is that an immediate administration of a drug could be applied to the patient according to the data collected from the measuring unit, the video and other image recorder and possibly the data collected in the memory device.

[0047] However, the level of experience of the person in charge or the user, determines whether he or she will be allow to configure models or adapt any of the written procedure and/or may only be allowed to make use of existing procedure without the possibility of changing anything to the system.

[0048] Therefore, different levels of competence or experience could be applied for different sets of procedure. These procedures are also adapted according to known pharmacokinetic and pharmacodynamic and/or posology models of known drugs.

[0049] Other requirements for such procedure are the condition of use (material configuration, type of treatment, type of patient) and the elementary task to perform such drug delivery and registering of vital parameters of the patient.

[0050] Advantageously, the drug delivery device is adapted for intravenous, intradermal or subcutaneous administration of a drug, preferably in the limb of the patient .

[0051] Advantageously, the system according, to the invention comprises at least two measuring units which could be applied upon different parts (limbs) of a human body. [0052] Preferably, the measuring unit comprises sensors, more preferably inertial or muscular sensors.

Inertial sensors are preferably selected from the group

consisting of gyroscopes and/or accelerometers . Muscular sensors are preferably electromyographic (EMG) sensors, electroencephalograph^ (EEG) sensors or cortical sensors. [0053] Preferably, these sensors are able to operate in a frequency range between about 0.01 Hz and about 30 Hz, preferably between about 0.05 Hz and about 18 Hz, more preferably between about 0.5 Hz and about 14 Hz . [0054] Furthermore, the sensors may incorporate a band-pass filtering (about 0.3Hz to about 25 Hz) ; the sensor gain can be adapted to render 1,5V at maximum angular velocity (about 300deg/s) .

[0055] Preferably, said measuring units are applied upon different parts of a human body, preferably upon the limbs of a human body (arms and/or legs) . [0056] Preferably, the system also comprises means for applying this measuring unit upon the limbs of a human body. Preferably, said means are a textile, wherein the connexion required by the sensors will be established underneath this textile. [0057] Furthermore, this textile may consist of elastic elements, preferably made in a textile (neoprene) , that should be elastic with a high flexion coefficient, respecting the skin and ensuring a good fitting and reliable measurements . [0058] Furthermore, said textile also allows various connections between the measuring units and the master unit (which could be also integrated into the textile) and the software platform, and possibly the memory device. Preferably, said textile also allows a movement of -the various sensors of the measuring unit (movement of the inertial sensor and possibly movement of the muscular sensor) . Movements of the inertial sensor, means an axial displacement of this initial sensor along the main axis of a limb. A movement of the initial sensor can be obtained

from a first reference location (for example : defined by a bone position of the body patient) to a second reference location (defined by a second bone position of the body patient) .The displacement of these sensors is controlled by the master unit. The movement of a first measuring unit applied upon a first limb of a human patient could modify the position of a second sensor applied upon another limb of the human patient; the movement coordination is controlled by the master unit . The induced displacement can also modify the administration of the drug by the drug delivery device to the patient (reducing or improving the doses, ...)

[0059] Furthermore, the means for applying the measuring unit upon a part of the human body could also comprise a drug delivery device, such as a subcutaneous pump placed in a limb or in the abdomen of the human body patient and able to deliver a drug or combination of drugs at a given rate.

[0060] In the system according to the invention, the master unit comprises a micro-controller, possibly a battery and a visualisation unit (such as a LCD display) .

Advantageously, the detachable memory device is a memory stick or a memory card.

[0061] In the system of the invention, the software platform is connected to a personal computer or a notebook, or a handheld computer device and is connected to the master unit to receive and record the set of data by the measuring unit transmitted by the master unit .

[0062] Preferably, the drug delivery device is a subcutaneous pump to be placed in the abdomen, or on a limb of the patient, and able to deliver a therapeutical or prophylactic drug at a given rate, preferably automatically. Said drug being a drug able to treat or prevent diseases inducing these human dyskinesia or prevent

symptoms induced by this disease or to treat or prevent other diseases or syndromes including RLS.

[0063] According to a preferred embodiment of the present invention, the system according to the invention comprises a measuring unit with at least four sensors, preferably two surface electromyographic EMG sensors (to be placed over the flexor and extensor muscles) and two triaxial gyroscope sensors (to be placed over the third metacarpal and over the edge of the forearm) . [0064] A textile may consist basically of an elastic shirt made on neoprene . The fabric should be elastic and with a high friction coefficient (i.e. neoprene) with respect to skin to ensure a good fitting and reliable measurements. The sensors are placed on the top of the shirt . The conductors are placed underneath the fabric in a sandwich-like approach. Sensors are clamped to the conductors through the layers of the textile substrate so that it is not possible to have an access to the conductors without dismantling the shirt. The conductors have a flat profile in order to achieve the better possible integration.

[0065] This configuration is used in order to avoid the destruction of connexions by the patient or develop any stress or trauma to the patient (that may induce a strangulation by the patient) that may affect the measures realised by the connexion between the master unit and the measuring unit. All connexions between the master unit, measuring unit, drug delivery device, video recorder, software platform and detachable memory device could be done by cable or preferably by means of a wireless communication network (given the high risk of using cables in psychiatric patients, who could for instance make a suicide attempt with cables, or patients suffering from RLS) .

[0066] A last aspect of the present invention is related to a method for detecting, monitoring and/or possibly treating human dyskinesia or RLS, by using the portable wireless electronic system according to the invention upon a patient, especially for the screening of drugs that could be used for the treatment and/or the prevention of these diseases (human dyskinesia or RLS) .

[0067] Such method comprises the step of using the system according to the invention upon a patient, possibly suffering from these syndromes or diseases or the step of administrating one or more compounds at different concentrations and different time and monitoring the effects of such drugs upon these diseases or syndromes.

Short description of the drawings [0068] Fig. 1 represents schematically the system according to the invention.

[0069] Fig. 2_ represents a solid model representation of the forearm.

[0070] Fig. 3 represents a biochemical parameter per segment for the biochemical model and design of the upper limb.

[0071] Fig . 4 represents pressure turn-around threshold map .

[0072] Fig . 5 represents physiological warms . [0073] Fig . 6 represents possible positioning for tri-dimensional gyroscope present in the system according to the invention .

[0074] Fig . 7 represents tri-dimensional gyroscope sensor of the system according to the invention . [0075] Fig . 8 represents the overall schematic representation of a preferred embodiment of the system according to the invention applied upon a human body .

[0076] Fig. 9 represents a textile carried by a patient and comprising sensors.

[0077] Fig. 10 represents a preferred embodiment of the system according to the invention which comprises three measuring units applied upon the human body limbs.

[0078] Fig. 1_1 represents schematically the different steps for performing an analysis and possibly a treatment of a patient by the system according to the invention.

Detailed description of the invention.

[0079] The system according to the invention is an (preferably portable and wireless) electronic system for analysing human dyskinesia made of six components. [0080] As shown in fig. 1 or fig. 8, the proposed system comprises a measuring unit (1) comprising a set of sensors. These sensors are preferably inertial sensors, such as gyroscopes (10) or accelerometers (11) able to measure all the aspects of the 3 D cinematic activity of the upper limb of a body, preferably a human body. [0081] The other types of sensors possibly comprised in the system of the invention are electromyography (EMG) sensors (40) , electroencephalography (EEG) sensors or cortical sensors able to measure electrical activities of the upper limb muscles of the body, preferably a human body. These sensors take preferably the form of electrodes, such as surface electrodes or needle or fine-wire electrodes .

[0082] The both type of sensors above described (inertial and muscle sensors) should be able to operate in a frequency range, approximately comprised between about 0.01 Hz and about 30 Hz, preferably between about 0.05 and about 18 Hz, preferably between about 0.5 and about 14 Hz.

[0083] The system according to the invention also comprises a master unit (2) connected to the measuring unit

(1) and collecting the data from each sensor of the measuring unit (1) . The master unit (2) treats the collected data and performed four different tasks with the treated data :

- generates command signals in order to control the device (7) responsible for a drug delivery;

- provides the relevant information regarding a human body upon which the sensors are applied and directly available to a clinician;

- transmit the acquired data to a software platform

(8) ;

- save the acquired data or processed information in a memory device (6) (such as a memory card or memory stick) .

[0084] The communication between the master unit (2) and the other elements comprised in the system is implemented by cables or preferably by means of a wireless communication network (3) using (for example, the Bluetooth technology, HomeRF, the WiFi technology or the IrDA technology well known by the person skilled in the art) .

[0085] The master unit (2) of the system according to the invention is an electronic board with a microcontroller (Atmega 128, Atmel Inc) connected to a LCD display (5) (o column x 2 lines character display) and a Bluetooth module. There are 8 ADC channels for each sensor. One of them is shared with the battery level meter. The resolution of each channel is up to 10 bits.

[0086] The system uses the wireless Bluetooth technology to communicate between the different units, the platform and the video-recorder. This Bluetooth technology

is an open specification for short-range wireless communication between electronic devices. This system uses a Bluetooth module (Bluegiga Wrap Thor) in each unit . Medical telemetric device avoid problems with a cable. A wireless network could be established using this technology.

[0087] The master unit (2) further comprises a visualization unit (5) , such as a LCD display screen, which is able to present on demand relevant information to the clinician (such as data obtained from sensors signals, details regarding the drug delivery device (7) performance or the status of the communication between the master unit (2) and the drug delivery device (7)) . [0088] In addition, the master unit (2) further contains a detachable memory device (6) (such as a memory card or a memory stick) which comprises data collected from the measuring unit (1) and data collected from the signals generated to control the device (7) responsible for the drug delivery. These data are stored for future analysis in a software platform (8) , installed preferentially in a personal computer, a notebook or a handheld computer device .

[0089] A memory stick used is for instance a SanDisk 256 MB Memory Stick (SDMS-256-822) . The video camera used is preferably a video Canon NTSC ZR 40. The

Electromyographic sensor used can be an active

Electromyographic sensor or amplifier, like the 2.1 Delsys surface electrode.

[0090] The base unit preferably also comprises a Bluetooth mode to establish a wireless link with the master unit. This system is powered by lithium ion batteries (CGA- 7/102F, 3.7V, 900 MaH, Matsushita Inc.).

[0091] The master unit (2) is also connected to an external digital video recorder (9) , preferably via a wireless communication network and is responsible for the generation of synchronization signals in order to synchronize the acquisition of the digital video recorder

(9) and the measuring unit (1) .

[0092] The power supply of the master unit (2) and its components (1,9,7,8) is provided by batteries (4) in order to maintain the system portable and independent . [0093] The proposed system also comprises a software platform (8) which is optionally connected to the master unit (2) for receiving and recording the set of data collected by the measuring unit (1) and transmitted by the master unit (2) . The software platform collects, treats and presents the data result under an appropriate form to a clinician, preferably upon the visualization unit (5) , such as the LCD display."

[0094] In other words, both the master unit (2) and the software platform (8) are able to perform the analysis of the data acquired by the measuring unit (1) . However, it is only the master unit (2) which is able to generate signals to control the drug delivery device (7) . [0095] In addition, the software platform (8) is a configuration tool, where the clinician could set up different parameters of the system according to the invention, such as the sampling frequency of the acquisition system or the characteristics of the signal used to obtain a synchronization of the video recorder system (9) with the acquisition system (measuring unit) . This configuration parameters are preferably transmitted to the master unit (2) .

[0096] In the system according to the invention, the drug delivery device (7) is responsible for a delivery of a drug to the body, preferably a human body. Such device is

for example a subcutaneous pump placed in the abdomen which delivers a drug at a given flow rate.

[0097] The video recorder (9) of the system according to the invention allows the assessment of the general neurological status of the patient, in particular the presence or the absence of involuntary movements in lower liτnbs and the awakeness of the patient during diagnosis and/or treatment (by the sensors of the measuring unit (1) and during drug delivery) .

Position of the sensors upon the human body

Biomechanical model and design of the upper-limb [0098] A biomechanical model of the upper arm is used to monitor and analyse the movements of a human arm. The biomechanical model built takes into account the Leva (Leva, 1996) corrections and the biomechanical tables of Zatsiorsky and Seluyanov (1990) , Zatsiorsky VM, Seluyanov V. The mass and inertia characteristics of main segments of human body. Proceedings of Biomechanics VII-A. Morecki A, Fidelus K (Ed) 1981; Leva P. Adjustments to Zatsiorsky- Seluyanovs's segment inertia parameters. J. Biomech 1996; 9: 1223-1230; Denavit J, Hartenberg RS. A kinematic notation for lower-pair mechanisms based on matrices. J. App. Mech. 1955; 77: 215-221. These tables are the most widely accepted within the field of biomechanics dynamic analysis; in particular, in sports and medical biomechanics. Leva adjustments are used to define accurately the anthropometric measurements required to obtain inertial parameters from Zatsiorsky tables. From these tables a forearm solid rigid model is built. This model has been parametrised using the Denavit-Hartenber approach (1995) . (references completes, svp) .

[0099] For a Denavit-Hartenberg parametrisation, four rigid segments are defined, in order to obtain analysis of all the recorded degrees of freedom. Each segment is responsible for a degree of freedom :

1. Elbow flexion-extension

2. Pronation-supination

3. Wrist flexion-extension

4. Wrist deviation

Two of these segments are virtual (with no mass and no length) and each segment has attached its own reference system (plus a coordinate frame for all of them) (see fig. 5 representing the coordinate frame defined and the degree of freedom represented for each system) .

[0100] The Denavit-Hartenberg parameters are also present in the following table 1 in reference to figure 2.

[0101] For rotary elements, the parameter θ determines the position of the joint. Therefore, in this table, it is indicated the relationship between the parameter and the physiological measured angle represented by the letter β.

Table 1

(F L means forearm length and H L means hand length. a = Angle between Zi to Zi +1 measured about Xi a = Distance from Zi and Zi +1 measured along Xi d = Distance from Xi-χ and Xi measured along Zi θ = Angle between Xi_i and Xi measured about Zi

[0102] Furthermore, biomechanical parameters per segment have to be obtained from Leva (1996) . Segment 1 and segment 3 are virtual . They are only defined to manage the degree of freedom of elbow flexion-extension and wrist flexion-extension respectively. But when these segments are moved, they move the masses of the "real" segments. All inertial and mass parameters per segment are defined below. The following symbols of fig. 3 are used :

— B M : body mass

- F L : forearm length

- F M : forearm mass

- H L : hand length

— HM : hand mass

Biomechanial constrains

[0103] The sensor devices allocated on the upper limb jointly with the "sleeve" containing them comply with the biomechanical requirements for general upper limb textile. The following data represent the most important requirements related to pressure and physiological warns. [0104] For pressure tolerance threshold map of the upper-limb for textile design (it is necessary to take care of maximum pressure which is tolerated) . 15 = Low tolerance area (average near 45OkPa)

16 = Middle tolerance area comprised between 45OkPa and 95OkPa)

17 = High tolerance area (average near 95OkPa)

[0105] The map of fig. 4 gives maximum values of this pressure between the hand and the forearm of a human patient that needs to be avoided, in order to keep a comfortable design of the system.

[0106] The fig. 5 represents the physiological warns. These areas cannot be used to allocate sensors:

Physiological warns

21. Elbow movement area 27. Guyon tunnel

22. Medial epycondile 28. Carpal tunnel

23. Lateral epycondile 29. Thumb movement area

24. Wrist movement area 30. Fingers movement area

25. Radial styloid process 31. Cubital tunnel

26. Ulnar styloid process 32. Olecranon process

33. Metacarpal heads

The following measurements are obtained with the various sensors of the measuring unit :

a) for gyroscopes (10) : they are used to measure the speed of the three-dimensions in space. These speed values are collected and formed a vector which is the addition of the various absolute speeds. b) Cutaneous electromyographic sensors : they are used for collecting muscle activities (agonist, antagonist and synergic muscle activities) . c) Electromyographic needle electrodes : they are used to measure and collect motor unit activities as well as denervation signs such as fibrillations, detect and collect data related to the muscular activities.

The enclosed fig. 6 represents a possible positioning for three-dimensional gyroscopes of the measuring unit. [0107] However, this measuring unit can also comprise other sensors, such as two surface EMG sensors (11) placed over the flexo and extensor muscles and two other sensors which are the two triaxial gyroscope sensors,

a first gyroscope (10A) placed over the third metacarpal placed while the gyroscope (10B) is placed over the edge of the forearm. The measurement of the wrist flexo/extension angular speed is therefore obtained by the subtraction obtained from gyroscope (10A) from gyroscope (10B) .

[0108] As shown in the fig. 7, the three-dimensional gyroscopes sensors (10) according to the invention, measure absolute angular velocity. [0109] Therefore, two of these gyroscopes are required to get a tremor contribution of each joint.

[0110] The sensor elements of the gyroscope sensors will just measure angular velocity in one axis. [0111] A tri-dimensional measurement of the movements is achieved based upon the use of three elements sensor mechanically placed orthogonally between them (see fig. 5) . The system may also include EMG sensors (40) as represented on figure 8.

[0112] As represented in the fig. 9, the patient will wire a textile, such as a neoprene shirt (41) with sensors. The connections (42) required for the sensors (40) are therefore incorporated into the textile element . Preferably, the sensors (41) are placed on top of the shirt while the conductors (42) are placed underneath the fabrics in a sandwich-like element. [0113] Sensors are clamped to the conductors through the layers of the textile element. Therefore, it is not possible to have an access to the conductors without dismantling the shirt (41) .

[0114] Preferably, the conductors (42) have a flat profile in order to achieve the better possible integration.

[0115] This type of textile is preferably used to avoid stress for the person during the diagnosis, the monitoring and/or the therapy of dyskinesia.

[0116] As represented in the enclosed figure 10, the patient could also wear a textile (such as neoprene) with elements of the system of the invention applied upon the patient's limbs (the two arms and one leg) . [0117] In the present case, the system comprises at least three different measuring units, possibly linked to a single master unit (not represented) .

[0118] Preferably, the textile comprises three measuring units (1, 1', 1") with inertial sensors (a gyroscope (52) and electromyographic sensors (51) ) .

[0119] Furthermore, the measuring units also comprise drug delivery devices which are preferably a subcutaneous pump (53) able to administrate a therapeutic or prophylactic drug at a given rate into the blood vessel of the patient .

[0120] Preferably, this administration from the subcutaneous pump (53) is controlled by a master unit (54) according to the detection obtained from one or more measuring unit (s) (1 , 1 ' , 1 ' ' ) . [0121] Furthermore, the measuring units can comprise means for allowing displacement of the gyroscope

(52) in different positions along the main axis (A) of the limb. These positions are selected and controlled by the master unit (54) according to the detection obtained from the measuring unit.

[0122] Therefore, a displacement of a first gyroscope (52) of a first unit (1) is controlled by the master unit (54) which defines its movement according to the measurements obtained from a second measuring unit (1') and a third measuring unit (1") .

[0123] Therefore, a coupling between these measuring units (1,1' ,1") could be done possibly through the master unit (54) .

[0124] Therefore, it is possible to use the system according to the invention for improving the diagnostic, the monitoring and/or the therapy of asymmetric dyskinesia resulting from Parkinson disease. [0125] The figure 11 represents schematically a flow chart with the different steps of a method controlling the device of figure 10. The steps of this method are:

A) Characterizing a first speed vector from a first measuring unit (1) ; B) Transmitting a first signal to the pump (53) of the first unit 1 (drug A of concentration A) to the pump of a second unit 1' (drug B of concentration A) and to the pump of a third unit 1" (drug B of concentration B) ; C) Starting infusion;

D) Collecting of second speed vector value (s) from a measuring unit (1, 1' or 1") ;

E) Correcting a possible detected value allowing a blocking of step B; F) Collecting an unexpected or impossible value;

G) Modification of the administration mode of the pump of each unit.

H) Modification of one or more gyroscope sensors (52) included in the unit 1, unit 1' and/or unit 1" .

I) Characterisation of speed vectors for each unit, but adapted according to the results obtained from the other units.

These steps are also based upDn a ponderation factor which indicates to the user, which gyroscope sensors introduced into the unit 1 and the unit 1' or unit 1" have detected unexpected or impossible values, but that are specific of a

disease to be detected. Furthermore, a definition of the speed vector value for each unit will be taken into consideration for couples of units (unit 1 and 1', unit 1 and unit 1" , unit 1' and unit 1", units 1, 1' and 1").