Method and system for assessing motion symptoms
10736577 ยท 2020-08-11
Assignee
Inventors
Cpc classification
G16H20/30
PHYSICS
A61B5/4076
HUMAN NECESSITIES
A61B5/4082
HUMAN NECESSITIES
G16H20/70
PHYSICS
A61B5/7275
HUMAN NECESSITIES
A61B5/16
HUMAN NECESSITIES
International classification
A61B5/11
HUMAN NECESSITIES
G16H20/30
PHYSICS
A61B5/16
HUMAN NECESSITIES
G16H50/30
PHYSICS
Abstract
A state of progression in an individual of a disease or treatment having motion symptoms is determined. A time series of accelerometer data is obtained from an accelerometer worn on an extremity of the person, over an extended period during everyday activities of the person. The accelerometer data is processed to produce a plurality of measures of kinetic state of the individual at a respective plurality of times throughout the extended period, each measure of kinetic state comprising at least one of: a measure for bradykinesia, and a measure for dyskinesia. A measure of dispersion of the measures of kinetic state is determined. An output is generated, indicating that motion symptoms are at an initial stage if the measure of dispersion is less than a threshold, or indicating that motion symptoms are at an advanced stage if the measure of dispersion is greater than the threshold.
Claims
1. A method of determining a state of progression in an individual with Parkinson's disease, the method comprising: receiving a time series of accelerometer data obtained from an accelerometer of a wrist-mounted device worn on a wrist of the individual over an extended period of time during everyday activities of the individual; determining, by a processor and based on the time series of accelerometer data, a plurality of measures of kinetic state of the individual at a plurality of times throughout the extended period of time, each measure of kinetic state comprising a measure for bradykinesia and a measure for dyskinesia; determining, by the processor, a measure of dispersion of the measures of kinetic state including a measure of dispersion of the measure for bradykinesia and a measure of dispersion of the measure for dyskinesia; calculating, by the processor, a Fluctuation Score using a function including a weighted sum of the measure of dispersion of the measure for bradykinesia and the measure of dispersion of the measure for dyskinesia; responsive to the Fluctuation Score being less than a threshold, displaying, by a display device, a first output indicating that Parkinson's disease is at an initial stage to assess treatment thereof; and responsive to the Fluctuation Score being greater than the threshold, displaying, by the display device, a second output indicating that Parkinson's disease is at an advanced stage to assess treatment thereof.
2. The method of claim 1, wherein the measure of dispersion comprises a measure of an interquartile range of the measures of kinetic state.
3. The method of claim 1, wherein the measure of dispersion comprises a measure of a standard deviation of the measures of kinetic state.
4. The method of claim 1, wherein the measure of dispersion comprises a measure of a variance of the measures of kinetic state.
5. The method of claim 1, wherein the extended period of time comprises more than one day.
6. The of claim 5, wherein the extended period of time comprises 10 days.
7. The method of claim 1, wherein during the extended period of time, the accelerometer data is obtained only when the individual is awake.
8. The method of claim 1, wherein the weights are equal.
9. The method of claim 1, wherein the measure of dispersion is determined by summing each measure of bradykinesia with a contemporaneous measure of dyskinesia to produce a combined measure of kinetic state, and the Fluctuation Score is determined from the dispersion of the combined measures of kinetic state.
10. The method of claim 1, wherein the method is used to obtain Fluctuation Scores for a plurality of individuals, and further comprising aggregating a plurality of measures of dispersion in order to assess a state or progression of Parkinson's disease or treatment therefor, for the group of individuals.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) An example of the invention will now be described with reference to the accompanying drawings, in which:
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DESCRIPTION OF THE PREFERRED EMBODIMENTS
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(16) The device 115 is a light weight device which is intended to be worn on the most affected wrist of the person throughout waking hours. The device is mounted on an elastic wrist band so as to be firmly supported enough that it does not wobble on the arm and therefore does not exaggerate accelerations. The device is configured to rise away from the person's wrist by a minimal amount so as to minimise exaggeration of movements.
(17) The accelerometer 121 records acceleration in three axes X, Y, Z over the bandwidth 0-10 Hz, and stores the three channels of data in memory on-board the device. This device has 1 GB of storage so as to allow data to be stored on the device for up to 10 days, after which the data can be downloaded and analysed.
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(19) In this embodiment algorithms are applied to the obtained data by a central computing facility 214 in order to generate both a dyskinesia score and a bradykinesia score for every 2 minute window of data, in the manner taught by WO 2009/149520.
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(21) The present embodiment recognises that dispersion, or greater fluctuations, in the DK scores 306 and/or BK scores 308 over an extended period, is a useful predictor of whether motion symptoms have progressed to an advanced stage.
(22) A study was conducted in which patients wore the device of
(23) a) the interquartile range of all DK scores 306 was determined from the 10 days data set;
(24) b) the interquartile range of all BK scores 308 was determined from the 10 days data set;
(25) c) the results of steps (a) and (b) were summed together to produce the fluctuation score.
(26) The interquartile range for both the DK and BK scores is defined as the difference between (a) the value below which 75% of all data points fall and (b) the value below which 25% of all data points fall.
(27) The median BK scores correlate with contemporaneously obtained clinical ratings using the Unified Parkinson's rating Scale part III (UPDRS3), and the median DK scores correlate with clinically obtained ratings using the modified Abnormal Involuntary Movement Score (AIMS) rating. The fluctuation score was tested in a group of people with Parkinson's who were categorised by a neurologist as either being fluctuators (at an initial disease state) or non fluctuators (at an advanced disease state), as reflected in
(28) This fluctuation score was then further examined in relation to patients already having received advanced interventions, including DBS, Amantadine and Apomorphine (
(29) TABLE-US-00001 TABLE 1 Statistics for DBS See FIG. 2B Fluctuation UPDRS 3 AIMS-R AIMS-A score before after before after before After before after Me- 26 10.5 4.5 0 8 0.5 38.9 21.7 dian IQR 14.5 11.5 7.75 1 9.5 1 45.85 9.55
(30) The fluctuation score thus detects changes produced by advanced therapies.
(31) To investigate how the fluctuation score changes over the course of progression of disease, the fluctuation score was assessed in 30 people with Parkinson's with various durations since diagnosis (
(32) To investigate how the fluctuation score changes in relation to candidates for advanced therapy, consulting neurologists were asked to classify patients into three categories: i) those who are likely to be candidates for advanced therapies in the next 12-18 months, ii) those who are now candidates for advanced therapy but have not yet commenced treatment, and iii) subjects who should/could have advanced therapy on motor grounds but who have chosen against it or are excluded by other non-motor grounds. Also, subjects who had PD for 0-3 years as plotted in
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(34) Thus the fluctuation score could be used to identify candidates for advanced therapies. When the fluctuation score of a PD patient increases from the low values typical of the 0-3 year cohort and enters the region between the median and 75th percentile response to DBS it may be an indication that the patient is or soon will be a candidate for advanced therapies (see
(35) The ability of the fluctuation score to map the transition of a patient from non-fluctuator to fluctuator was examined in further detail. In this further study the fluctuation score was determined as above, and is referred to as a fluctuation score (FS). The FS of subjects at various stages of PD was compared, as shown in
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(37) This was further examined in 177 subjects (
(38) TABLE-US-00002 TABLE 2 AIMS >2 2-5 6-9 2-9 >10 No. of subjects 96 25 16 41 34 25% Percentile of FS 6.8 8.8 8.1 8.5 12.2 Median of FS 8.0 9.8 9.4 9.7 14.6 75% Percentile of FS 9.7 14.7 12.6 14.3 20.3 P = 0.6 <0.0001 Mann Whitney P < 0.005
(39) The median FS of those cases with an AIMS of 1 or 0 was 8.0 and 65% of FS were below the FT: most likely the higher FS were due to variation in the bradykinesia score. There was no statistical difference in the FS's of subjects with AIMS between 2-5 and 6-9 so these were pooled (see 2-9 column) and were statistically different to those with higher (>10) or lower AIMS. Broadly, subjects with AIMS of 2 or less, between 2-9 and greater than 10 approximated the FS below the FT, within the RCMS and above the RCMS (respectively).
(40) Without intending to be limited by theory, it is to be anticipated that subjects in their first years of disease will reveal two broad pathways: one consistent with fluctuations (path A in
(41) In summary, we propose that an FS derived from the variation in the BKS and DKS of a movement symptoms data series has the potential to be used as a tool for choosing and optimising therapies for patients with PD.
(42) The combination of a falling fluctuation score and asymmetry between the fluctuation score in the left and right side (by equipping the patient with a suitable accelerometer data gathering device on each wrist) will detect people with early motor symptoms.
(43) It is thus proposed that the size of the Interquartile Range (IQR) of the BKS and DKS provided by the presently proposed fluctuation score or FS reflects the extent of fluctuations. To further investigate this proposition, the IQR of the BKS and DKS (BKS.sub.IQR and DKS.sub.IQR) were extracted from 527 patients' recordings and the combined IQR (IQR.sub.C) for each patient was calculated. The BKS.sub.IQR and DKS.sub.IQR for each patient was plotted against the IQR.sub.C (
(44) The validity of these IQR measures was first tested against a small sample of subjects with (n=5) and without (n=7) fluctuations. Their classification was blinded while the IQR measurements were applied (
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(47) Although the IQR.sub.C does appear to distinguish fluctuators from non fluctuators, the weighting given to each of the BKS.sub.IQR and DKS.sub.IQR was investigated. Thus a general formula was introduced:
Fluctuation Score=sBKS.sub.IQR+tDKS.sub.IQR where s and t were independent weightings applied to BKS.sub.IQR and DKS.sub.IQR.
(48) A family of Fluctuation Scores (FS) were produced by independently and serially varying s and t from 0.1 to 5.0. Each FS was used to produce a p value by comparing the early PD and those on the DBS waiting list (in
(49) Inspection of
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(51) It is to be appreciated that patients may be grouped by clinic as shown in
(52) Some portions of this detailed description are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is here, and generally, conceived to be a self-consistent sequence of steps leading to a desired result. The steps are those requiring physical manipulations of physical quantities. Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated. It has proven convenient at times, principally for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, or the like.
(53) As such, it will be understood that such acts and operations, which are at times referred to as being computer-executed, include the manipulation by the processing unit of the computer of electrical signals representing data in a structured form. This manipulation transforms the data or maintains it at locations in the memory system of the computer, which reconfigures or otherwise alters the operation of the computer in a manner well understood by those skilled in the art. The data structures where data is maintained are physical locations of the memory that have particular properties defined by the format of the data. However, while the invention is described in the foregoing context, it is not meant to be limiting as those of skill in the art will appreciate that various of the acts and operations described may also be implemented in hardware.
(54) It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. Unless specifically stated otherwise as apparent from the description, it is appreciated that throughout the description, discussions utilizing terms such as processing or computing or calculating or determining or displaying or the like, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.
(55) The present invention also relates to apparatus for performing the operations herein. This apparatus may be specially constructed for the required purposes, or it may comprise a general purpose computer selectively activated or reconfigured by a computer program stored in the computer. Such a computer program may be stored in a computer readable storage medium, such as, but is not limited to, any type of disk including floppy disks, optical disks, CD-ROMs, and magnetic-optical disks, read-only memories (ROMs), random access memories (RAMs), EPROMs, EEPROMs, magnetic or optical cards, or any type of media suitable for storing electronic instructions, and each coupled to a computer system bus.
(56) The algorithms and displays presented herein are not inherently related to any particular computer or other apparatus. Various general purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct more specialized apparatus to perform the required method steps. The required structure for a variety of these systems will appear from the description. In addition, the present invention is not described with reference to any particular programming language. It will be appreciated that a variety of programming languages may be used to implement the teachings of the invention as described herein.
(57) A machine-readable medium includes any mechanism for storing or transmitting information in a form readable by a machine (e.g., a computer). For example, a machine-readable medium includes read only memory (ROM); random access memory (RAM); magnetic disk storage media; optical storage media; flash memory devices; electrical, optical, acoustical or other form of propagated signals (e.g., carrier waves, infrared signals, digital signals, etc.); etc.
(58) Turning to
(59) In
(60) The hard disk drive 27, magnetic disk drive 28, and optical disk drive 30 are connected to the system bus 23 by a hard disk drive interface 32, a magnetic disk drive interface 33, and an optical disk drive interface 34, respectively. The drives and their associated computer-readable media provide nonvolatile storage of computer readable instructions, data structures, program modules and other data for the personal computer 20. Although the exemplary environment shown employs a hard disk 60, a removable magnetic disk 29, and a removable optical disk 31, it will be appreciated by those skilled in the art that other types of computer readable media which can store data that is accessible by a computer, such as magnetic cassettes, flash memory cards, digital video disks, Bernoulli cartridges, random access memories, read only memories, storage area networks, and the like may also be used in the exemplary operating environment.
(61) A number of program modules may be stored on the hard disk 60, magnetic disk 29, optical disk 31, ROM 24 or RAM 25, including an operating system 35, one or more applications programs 36, other program modules 37, and program data 38. A user may enter commands and information into the personal computer 20 through input devices such as a keyboard 40 and a pointing device 42. Other input devices (not shown) may include a microphone, joystick, game pad, satellite dish, scanner, or the like. These and other input devices are often connected to the processing unit 21 through a serial port interface 46 that is coupled to the system bus, but may be connected by other interfaces, such as a parallel port, game port or a universal serial bus (USB) or a network interface card. A monitor 47 or other type of display device is also connected to the system bus 23 via an interface, such as a video adapter 48. In addition to the monitor, personal computers typically include other peripheral output devices, not shown, such as speakers and printers.
(62) The personal computer 20 may operate in a networked environment using logical connections to one or more remote computers, such as a remote computer 49. The remote computer 49 may be another personal computer, a server, a router, a network PC, a peer device or other common network node, and typically includes many or all of the elements described above relative to the personal computer 20, although only a memory storage device 50 has been illustrated. The logical connections depicted include a local area network (LAN) 51 and a wide area network (WAN) 52. Such networking environments are commonplace in offices, enterprise-wide computer networks, intranets and, inter alia, the Internet.
(63) When used in a LAN networking environment, the personal computer 20 is connected to local network 51 through network interface or adapter 53. When used in a WAN networking environment, the personal computer 20 typically includes modem 54 or other means for establishing communications over WAN 52. The modem 54, which may be internal or external, is connected to system bus 23 via the serial port interface 46. In a networked environment, program modules depicted relative to the personal computer 20, or portions thereof, may be stored in the remote memory storage device. It will be appreciated that the network connections shown are exemplary and other means of establishing a communications link between the computers may be used.
(64) It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.