SYSTEM AND METHOD FOR ASSESSING ADVANCED KINETIC SYMPTOMS

Abstract

A method of determining a state of progression in a subject of a disease or treatment having motion symptom comprises obtaining a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during usual activities of the subject; processing the motion data to produce a plurality of measures of kinetic state of the subject 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; determining a measure of dispersion of the measures of kinetic state; combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and generating an output indicating the selection score.

Claims

1. A method of determining a state of progression in a subject of a disease or treatment having motion symptoms, the method comprising; obtaining a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during usual activities of the subject; processing the motion data to produce a plurality of measures of kinetic state of the subject 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; determining a measure of dispersion of the measures of kinetic state; combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and generating an output indicating the selection score.

2. The method according to claim 1, including the step of generating an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and generating an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

3. The method according to claim 2, wherein the measure of dispersion is one of: a measure of the numerical distance between a high and low percentile of the measures of kinetic state; a measure of the interquartile range of the measures of kinetic state; a measure of the variance of the measures of kinetic state; and at least one of a measure of the standard deviation of the measures of kinetic state, an indicator of the variability of the measures of kinetic state, an indicator of the scatter of the measures of kinetic state, and an indicator of the spread of the measures of kinetic state.

4. (canceled)

5. (canceled)

6. (canceled)

7. The method according to claim 1, wherein the at least one other data characteristic comprises one or more of: a probabilistic measure of bradykinesia; a probabilistic measure of dyskinesia; a median or mean DK score in a period where the subject is off; minutes OFF, being the number of minutes during an observation period when the subject was not dyskinctic or when dyskinesia was below a threshold; minutes in dyskinesia, being the number of minutes during an observation period when the subject was dvskinetic or when dyskinesia was above a threshold; minutes in bradvkinesia, being the number of minutes during an observation period when the subject was bradvkinetic or when bradvkinesia was above a threshold; the proportion of time immobile (PTI) or amount of time immobile (ATI); a measure of tremor derived from the motion data; BKS.sub.IOR, being die interquartile range of BK scores: a measure of the number of windows of time throughout the observation period in which at least 5 out of 7 DK scores exceed the 75th percentile; a measure of the number of windows of time throughout the observation period in which at least 5 out of 7 BK scores exceed the 75th percentile.

8. The method according to claim 7 wherein the probabilistic measure of bradykinesia comprises one or more of: a mean or median value of a time series of individual measures of bradykinesia obtained throughout an observation period; and a percentile value of a time series of individual measures of bradykinesia; and a 75.sup.th percentile value of a time series of individual measures of bradykinesia.

9. (canceled)

10. (canceled)

11. (canceled)

12. The method according to claim 7 wherein the probabilistic measure of dyskinesia comprises one or more of: a mean or median value of a time series of individual measures of dyskinesia obtained throughout an observation period; a percentile value of a time series of individual measures of dyskinesia; and a 75.sup.th percentile value of a time series of individual measures of dyskinesia.

13. (canceled)

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. The method according to claim 1 further including combining the measure of dispersion with at least one other data characteristic, to produce the selection score; and wherein the at least one other data characteristic comprises a dosage measure.

20. The method according to claim 19 wherein the dosage measure comprises a number of medication reminders prescribed for that subject during a period of interest.

21. (canceled)

22. (canceled)

23. (canceled)

24. (canceled)

25. (canceled)

26. The method according to claim 1 wherein the motion data is obtained only during waking hours.

27. The method according to claim 1 wherein each measure of kinetic state comprises both a measure for bradykinesia and a measure for dyskinesia.

28. The method according to claim 27 wherein each measure of dispersion is produced as a weighted sum of a measure of the dispersion of the measures for bradykinesia and a measure of the dispersion of the measures for dyskinesia.

29. The method according to claim 1 wherein the measure of dispersion is produced by summing each measure of bradykinesia with a contemporaneous measure of dyskinesia to produce a combined measure of kinetic state, and determining the measure of dispersion from the dispersion of the combined measures of kinetic state.

30. The method according to claim 1 further comprising recording a value of the selection score as determined on different occasions in order to monitor progression of the selection score, for example over the course of hours, days, weeks, months or years: and optionally, monitoring a rate of change in the selection score over time to project or predict disease progression towards a threshold at which advanced therapies may become appropriate.

31. (canceled)

32. The method according to claim wherein the monitoring of the selection score during progression of a disease is used as a basis to indicate which therapy, of a plurality of available progressions in therapy, is suitable for that particular subject.

33. The method according to claim 1 further comprising one or more of: aggregating selection scores obtained for a plurality of subjects in order to assess a state or progression of disease or treatment of the group; combining the measure of dispersion with at least one other data characteristic not derived from motion data, to produce the selection score, wherein the at least one other data characteristic is selected from the group including: number of medication reminders provided to a subject: dosage acknowledgements by the subject; years with motion disease; subject's cognitive state; subject's age: blood pressure; impulsivity; and apathy; and automatically generating a subject specific report based on a report module containing instructions executable by a processor receiving at least the motion data, wherein the report module populates fields of a report template with the selection score and clinical observations derived front the motion data.

34. (canceled)

35. (canceled)

36. The method according to claim wherein the report template includes fields selected from the group including: a subject identifier; referring clinician; duration of data collection; dates of data collection; dosage acknowledgements by the subject; therapies prescribed to the subject; dosage reminders provided to the subject; summary of kinetic behaviour during data collection (including one or more of bradykinetic, dyskinetic and tremor motion); summary of kinetic behaviour response to medication; and summary of clinical findings based on at least one of the motion data and measures of dispersion and selection score calculated by the processor.

37. A non-transitory computer readable medium for determining a state of progression in a subject of a disease or treatment having motion symptoms, comprising instructions which, when executed by one or more processors, causes performance of the following: obtaining a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during everyday activities of the subject; processing the motion data to produce a plurality of measures of kinetic state of the subject 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; determining a measure of dispersion of the measures of kinetic state; combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and generating an output indicating the selection score.

38. A non-transitory computer readable medium according to claim 37 comprising instructions which cause performance of the step of generating an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and generating an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

39. A system for determining a state of progression in a subject of a disease or treatment having motion symptoms, the system comprising: a motion detector configured to be worn on an extremity of the subject and to output a time series of motion data over an extended period; and a processor configured to receive the motion data and to process the motion data to produce a plurality of measures of kinetic state of the subject 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; the processor further configured to determine a measure of dispersion of the measures of kinetic state; the processor further configured to combine the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and the processor further configured to generate an output indicating the selection score.

40. The system according to claim 39 wherein the processor is configured to generate an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and to generate an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

41. (canceled)

42. A method for automated screening of a subject to determine clinical readiness to receive advanced therapy for a disease having motion symptoms, the method comprising: obtaining at a processor a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during usual activities of the subject; the processor calculating from the motion data a plurality of measures of kinetic state of the subject 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; the processor determining a measure of dispersion of the measures of kinetic state; and the processor combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and the processor generating an output indicating one or more of clinical readiness for advanced therapy when the selection score is greater than a threshold; and clinical unreadiness for advanced therapy when the selection score is less than the threshold.

43. The method according to claim 42, wherein the threshold is selected from the group including: (i) a median level of the selection score for subjects having received advanced therapy; (ii) the 75th percentile level of the selection score for subjects having received advanced therapy; and (iii) a scalar, logarithmic or exponential variant derived from such values in (i) or (ii).

44. The method according to claim 42, further including the step of automatically determining a subject's readiness to receive an advanced therapy selected from the group including: deep brain stimulation (DBS), apomorphine and levodopa-carbidopa (duodopa), wherein the subject's readiness to receive the selected advanced therapy is automatically determined by (he processor when (he selection score is greater than a threshold determined by a median level of the selection score for subjects having received the selected advanced therapy, or the 75th percentile level of the selection score for subjects having received the selected advanced therapy or an aggregate of these, or a scalar, logarithmic or exponential variant derived from such values.

45. (canceled)

46. The method according to claim 42 , further comprising automatically generating a subject specific report based on a report module containing instructions that are executable by the processor, wherein the report module populates fields of a report template with the selection score and clinical observations derived from the motion data.

47. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0074] An example of the invention will now be described with reference to the accompanying drawings, in which:

[0075] FIG. 1 is a diagrammatic view of a means for detection of various Parkinsonian clinical states in accordance with an embodiment of the invention;

[0076] FIGS. 2a-2c illustrate a system for kinetic state monitoring and reporting in accordance with one embodiment of the invention. FIG. 2d is an example of a report template that in some embodiments, may be populated automatically with meaningful clinical information and summaries;

[0077] FIG. 3 gives an example of DK and BK scores output from one day of wrist-worn data logger motion recording from a patient;

[0078] FIGS. 4-6 illustrate the classification efficacy of a selection score in accordance with one embodiment of the invention;

[0079] FIG. 7 illustrates the classification efficacy of a selection score in accordance with another embodiment of the invention;

[0080] FIG. 8 illustrates the classification efficacy of a selection score in accordance with a further embodiment of the invention;

[0081] FIG. 9 illustrates steps in a method of determining a state of progression in a subject of a disease or treatment having motion symptoms according to embodiments of the invention; and

[0082] FIG. 10 illustrates a general-purpose computing device that may be used in an exemplary system for implementing the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0083] FIG. 1 is a diagrammatic view of apparatus for detection of various Parkinsonian or kinetic states in accordance with an embodiment of the invention. The apparatus 115 comprises three elements for obtaining movement data of a limb of a person to determine a state of progression of the disease or treatment. The apparatus 115 comprises a motion monitor 121 in the form of an accelerometer, an assessor 122 for analysis of the motion monitor data in a manner that provides an objective determination of bradykinesi a and dyskinesia, and an output means 123 for outputting objective determination of bradykinesia or dyskinesia over time periods so as to allow a clinician to prescribe medications or to allow the person to better understand their own kinetic state. Typically, the objective determination is in the form of a selection score.

[0084] The motion monitor 121 is a light weight device which is intended to be worn on the most affected wrist of the person to provide a sufficiently accurate representation of the kinetic state of the whole body 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. The motion monitor may be disposable.

[0085] The motion monitor 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 motion monitor 121 typically has 1 GB or more of storage so as to allow data collected by the device over an extended period of 6, 7. 8, 9 or 10 or more days to be stored, after which the data can be downloaded and analysed. Data may be downloaded from the motion monitor 121 via a physical connection such as a USB connector or other standard or bespoke means, or by a wireless interface as would be understood by one of skill in the art.

[0086] Data may be collected by the motion monitor 121 for a finite assessment period of e.g. 6, 7, 8, 9 or 10 or more days, or it may be collected for analysis by assessor 122 on an ongoing basis, indefinitely, with the motion data being periodically downloaded for evaluation. Periodical removal of the motion monitor 121 from the wearer for download of data also provides an opportunity for the motion monitor 121 to be recharged.

[0087] The output means 123 is typically remote from the motion monitor 121 and may be provided in concert with the assessor 122 (as shown by broken line 124) to provide evaluation and selection scores and reports to clinicians. It is to be understood, however, that in some embodiments the motion monitor 121, assessor 122 and optionally the output means 123 may be provided in a single body-worn device.

[0088] FIGS. 2a-2c illustrate a system 215 for kinetic state monitoring and reporting in accordance with one embodiment of the invention. Referring first to FIG. 2a, a patient 212 is wearing the motion monitor 121 of FIG. 1 which is typically in the form of an accelerometer data logger. The motion monitor 121 logs accelerometer data and communicates it to a central computing facility 214. The computing facility 214 analyses the data to produce an output comprising kinetic state reporting, indicating whether motion symptoms are at an initial stage or an advanced stage. The output is reported to a neurologist or physician 216 who is typically located remotely from the central computing facility 214. Thus, the neurologist/physician may receive the kinetic state reporting by email or by being made available on a website or portal on the Internet or other communication network, in a format which can be rapidly interpreted by the neurologist to ensure efficient use of the neurologist's time. The neurologist 216 then interprets the report and updates the patient's medication or prescription or therapy so that it is optimised according to the objective clinical information contained in the report. Additionally or alternatively the neurologist may make recommendations, based on the report, for further evaluation using the inventive system or method e.g. to determine if the patient 212 is a candidate for a particular advanced therapy.

[0089] 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.

[0090] The system 215 is shown in more detail in FIG. 2b. A nurse 210 or clinician may pre-screen candidates with reference to whether age is appropriate, cognitive impairment, and whether oral therapy (levodopa) is optimised. To undertake screening for advanced therapy according to embodiments of the invention, the nurse uses a tablet or similar device 220 having a processor executing a suitable application to configure the wrist worn motion monitor 121. Typically this involves the application executed by the device 220 receiving as inputs one or more of: a patient identifier, that patient's medication type and times, session coding details, and the like. The application creates a session key for encryption and decryption of data generated and transmitted through the system. The wrist worn motion monitor 121 is worn during typical daily activities of that patient 212, and during this period reminds the patient when to take medication, and in a preferred embodiment, receives patient input indicating when doses are taken. The motion monitor 115 may be removed when bathing (although a water resistant device is contemplated and within the scope of this disclosure) or sleeping or for recharging, then use may continue.

[0091] When the use session ends (typically after an extended period of 6 to 10 days or more), the motion monitor 115 is coupled with dock/charge station 222 and interfaced with a tablet or similar device 220 executing a suitable application for data retrieval from the docked motion monitor. The data is secured passed and (via wired or wireless means) to a clinic server or equivalently to the central computing facility 214 where patient specific data is retrieved by a processor of the central computing facility and analysed for calculation by the processor of a selection score according to embodiments of the present invention.

[0092] An example of the process 240 of data analysis undertaken by the inventive system 215 to produce the selection score (as may be included in a work product 225) is illustrated in FIG. 2c. As shown, an acceleration time series is used to derive DK and BK scores as described in WO 2009/149520.

[0093] In some embodiments, the central computing facility 214 further generates reports providing a more detailed interpretation of the retrieved and analysed data that is specific to the patient and provides clinical detail as to the factors underpinning the selection score as determined by the inventive system and method. The work product 225 generated by a processor of the central computing facility 214 or equivalent processer/server may include e.g. a PKG 226 and report 228 in PDF or other suitable file format readable by the clinician 216. An example of a work product 225 populated with meaningful clinical information is provided in FIG. 2d, Here, the work product template 225 includes a field for a PKG 226 of the patient (being a chart of data extracted from the motion monitor) and a report 228 including fields automatically populated by the system. Such fields may include but are not limited to: a patient identifier; referring clinician; duration of data collection; dates of data collection; dosage reminders provided to the subject; dosage acknowledgements (of medication dosages consumed) by the subject; therapies prescribed to the subject; summary of kinetic behaviour during data collection (including one or more of bradykinetic, dyskinetic and tremor motion); selection score as calculated by the system; summary of kinetic behaviour response to medication and in particular, evidence from the motion monitor data that the subject did or did not respond to medications such as levodopa based medications (or other medications); summary of clinical findings based on at least one of the motion data and measures of dispersion and selection score calculated by the processor. Advantageously, summary of kinetic behaviour response to medication including specific evidence from the motion monitor data that the subject did or did not respond to medications such as levodopa based medications (or other medications) is clinically valuable since levodopa responsiveness is a criteria for selection for advanced therapy.

[0094] In some embodiments, the system is configurable to collect data and/or populate fields in the work product template 225 representing metrics for clinical scales collected through the inventive system. These may include for example, cognitive measures or other measures including blood pressure, age, duration of disease, impulsivity or apathy. Such information may be collected via a patient portal provided by a device such as a tablet or mobile phone or other device operated by the patient or carer. Typically, the inventive system prompts the patient or carer to provide such information to the device. In some embodiments, the system is configurable to receive or prompt the patient or carer for further patient motion inputs pertaining to, for example, gait, as may be determined by the motion monitor or another body-worn device, or supplied by a nurse or clinician.

[0095] FIG. 3 gives an example of the output from one day of wrist-worn motion monitor recording from a patient who was prescribed 6 doses of levodopa per day. The upper set of data points 306 represent the dyskinesia scores (DK scores) produced from each 2 minute window of data, and the lower set of data points 308 represent the bradykinesia scores (BK scores) produced from each 2 minute window of data. DK scores are plotted only on or above the midline 300 of FIG. 3, while BK scores are plotted only on or below the midline 300 of FIG. 3. Greater severity of dyskinesia is represented by increasing distance of the DK scores 306 upwards from the midline, while greater severity of bradykinesia is represented by increasing distance of the BK scores 308 downwards from the midline. The horizontal lines indicate the respective median, 75th percentile and 90th percentile of controls, for both DK and BK scores, controls being subjects not having a neurodegenerative disorder. The six vertical lines, of which two are indicated at 302, indicate the times at which medications were prescribed, and the diamonds 304 represent when the taking of medication was acknowledged by the patient.

[0096] 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.

[0097] A study was conducted in which patients were monitored using the apparatus of FIG. 1 for 10 days, and all data was collected. 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.

[0098] A measure of dispersion was computed in accordance with the fluctuation score taught by WO 2015/131244, the content of which is incorporated herein by reference. As noted in that disclosure a fluctuation score threshold of 7.7 is optimal under those study/population conditions. Using only the fluctuation score and a threshold of 7.7 gives rise to Sensitivity of 83%, selectivity of 47%, Fishers exact=p=0.078 and Kappa=0.304, while modifying the weights of the fluctuation score can provide an optimised fluctuation score having Sensitivity 84%: selectively 58% Fishers exact=p=0.038 and Kappa=0.364. However, the present invention recognises that the approach of the present invention can significantly improve the identification of DBS candidates.

[0099] 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.

[0100] FIG. 4 illustrates classification efficacy of a selection score in accordance with one embodiment of the present invention. In this embodiment, the Selection Score was derived from the following inputs:

Selection Score=5.86*FDS+0.981+7.113K50+8,9* DK 506.913KS.sub.IQR+8.8*Minutes_Under+4.04 *Minutes_Over+7.7*Reminder_Count>5+0.4*over count+0.07*under count+0.4*tremor+0.8*PTI+0.5*BK75.

[0101] Or, expressed in code form:

bin_score(n, bins)=findfirst(x>n<x, [bins . . . ,Inf])1dbss_a(x)=5.863*bin_score(x[TDS], [7.7, 9.4, 11.7])+7.136*bin_score(x[:BK_50], [22.0, 25.0, 31.0])+8.921*bin_score(x[:DK_50], [ 1.3, 3.0, 6.5])+6.957*bin_score(x[:BK_75]x[:BK_25], [16.2, 19.1, 20.4])+8.805*bin_score(x[:Minutes_Under], [188, 288, 420])+4.041*bin_score(x[:Minutes_Over], [26, 95, 135])+7.737*bin_score(x[:Reminder_Count], [5])+0.842*(x[:Minutes_Immobile]>z=54?1:(x[:Minutes_Immobile]<=27?1:0))+0.433*x:[Over_Count]+0,072*x:[Under_Count]+0,400*x[:Minutes_Tremor]

[0102] In FIG. 4 the first cluster of dots (I) represents patients who have a selection score above the threshold designated by line A and so have motion symptoms that are at an advanced stage. Here, line A is the best separation using ROC (other horizontal bars represent median, 25.sup.th and 75.sup.th percentiles for each group). The inventive system may therefore designate patients in the first cluster I as ready for an advanced therapy or as candidates for selection for advanced therapy. The second cluster of dots (II) represents patients who have a selection score near or below the threshold designated by line A and so have motion symptoms that are at an initial stage. The inventive system may therefore designate these patients as not ready for advanced therapy. This embodiment achieves high Sensitivity of 95% indicating that this selection score and system should identify most DBS candidates. This embodiment also provides high Specificity of 87.5%, showing that this method and system can tolerate false positives but increase specialty work load. This embodiment further provides a Fishers exact=p<0.0001 and Kappa=0.74.

[0103] To further investigate efficacy of the Selection Score, the Selection Score was calculated on motion monitor data obtained from 33 people with Parkinson's (PwP) from four Australian centres, before (pre DBS) and six months after DBS (post DBS) as shown in clusters III and IV. Using the cut off threshold A, the Specificity in the cohort of cluster III was 90% and the Selectivity was 87.5%. It is relevant that one of the subjects with the lowest Selection Score was eventually diagnosed with multiple system atrophy (MSA) and should not in fact have been a DBS candidate. Furthermore the mean Selection Score fell by 25 points (p<0.0001, t-test) following DBS. As well there was broad tendency for those with the highest Selection Score to have the biggest improvement (FIG. 5).

[0104] Table 1 summarises the improved results delivered by the Selection Score as compared to two versions of the earlier Fluctuation Score (FS).

TABLE-US-00001 TABLE 1 Sensitivity Selectivity Fisher's Kappa Standard FS 83% .sup.47% p = 0.078 0.304 Modified FS 84% .sup.58% p = 0.038 0.368 Selection Score (FIG. 4) 95% 87.5% <0.0001 0.74 Re test of Selection 90% 87.5% NA NA Score (cluster III)

[0105] The next step was to use the study data set (FDS, BKS, DKS scores etc.) to train a decision system to predict which of the Australian PwP should have DBS. The system was again about 90% accurate (very similar to the Selection Score)

[0106] FIG. 6 further illustrates performance of the embodiment of FIGS. 4-5,

[0107] Thus it can be concluded that the Selection Score of this embodiment strongly predicts which patients require DBS,

[0108] Other embodiments of the Selection Score can be envisaged and are within the scope of the present invention.

[0109] FIG. 7 illustrates an alternative embodiment of the invention, in which the Selection Score is determined from the following inputs:

Selection Score=6.8*FS+80*Reminder_Count>5+0.5*Minutes_Under+3.0*over count

[0110] Or, expressed in code form:

dbss_b(x)=7.071*bin_score(x[:BK_50], [22.0, 25.0, 31.0])+14.481*bin_score(x[:DK_50], [1.3, 3.0, 6.5])+8.462*bin_score(x[:BK_75]x[:BK_25], [16.2, 19.1, 20.4])+7.655*bin_score(x[:Minutes_Under], [188, 288, 420])+4.307*bin_score(x[:Minutes_Over], [ 26, 95, 135])+4.106*bin_score(x[:Remincler_count], [5 ])+0.272*x[:Over Count]0.420*x[:Minutes_Tremor]

[0111] FIG. 8 illustrates another alternative embodiment of the invention, in which the Selection Score is determined from the following inputs:

Selection Score=0.7.5*FDS+0.981*DK_50+0.202*BKSIQR+2.885*Minutes_Under+1.743 Minutes_Over+1.154*Reminder_Count>5]

[0112] Or, expressed in code form:

dbss_s(x)=(x[:FDS]>6.8?100:0)+(x[:Reminder_Count]>5.0?70:0)+x[:Minutes_Under]*0.5+x[:Over_Count]*3.0

[0113] FIG. 9 illustrates schematically steps in a method 900 for method of determining a state of progression in an subject of a disease or treatment having motion symptoms, In a step 902 a processor obtains a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during usual activities of the subject. In a step 904 the processor processes the motion data to produce a plurality of measures of kinetic state (905) of the subject 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. The processor also determines at least one other data characteristic (907) determined from the motion data. In a step 908 the processor determines a measure of dispersion of the measures of kinetic state and in a step 908 combines the measure of dispersion with the one or more other data characteristic to produce a selection score (909). In some embodiments, the processor generates an output indicative of the selection score (909). In some embodiments, in a step 910 the processor generates an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and generating an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

[0114] In summary, it is proposed that a Selection Score derived from dispersion, and also from other data characteristics of a movement symptoms data series, has the potential to be used as an improved tool for choosing and optimising therapies for patients with motion disorders including PD. This invention recognises that in the conventional approach to advanced therapy, an experienced clinician assesses several symptoms to recognise a suitable DBS candidate based on their experience and knowledge. These symptoms might include overall level of bradyki nesi a and dyskinesia, the amount of time spent in dyskinesia and bradykinesia, the number of medication doses, cognition and the variability of kinetic state.

[0115] The present invention provides for collection and machine analysis of one or more of several other data characteristics, such as number of minutes during an observation period when the patient was not dyskinetic or when dyskinesia was below a threshold and when the subject was not bradykinetic or when bradykinesia. was below a threshold, as well as other patient data such as years with PD or other motion disorder, cognitive state, blood pressure, impulsivity, apathy and the like to produce a robust selection score indicative of the stage of progression of the disease or therapy. The selection score of the present invention is particularly effective as it objective and accommodates more than one kinetic symptom, and gathers much more detailed and accurate kinetic state data than patient diaries.

[0116] 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.

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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.

[0121] 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.

[0122] Turning to FIG. 10, the invention is illustrated as being implemented in a suitable computing environment. Although not required, the invention will be described in the general context of computer-executable instructions, such as program modules, being executed by a personal computer. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Moreover, those skilled in the art will appreciate that the invention may be practiced with other computer system configurations, including hand-held devices, multi-processor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, mainframe computers, and the like. The invention may he practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote memory storage devices.

[0123] In FIG. 10 a general purpose computing device is shown in the form of a conventional personal computer 20, including a processing unit 21, a system memory 22, and a system bus 23 that couples various system components including the system memory to the processing unit 21. The system bus 23 may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. The system memory includes read only memory (ROM) 24 and random access memory (RAM) 25. A basic input/output system (BIOS) 26, containing the basic routines that help to transfer information between elements within the personal computer 20, such as during start-up, is stored in ROM 24. The personal computer 20 further includes a hard disk drive 27 for reading from and writing to a hard disk 60, a magnetic disk drive 28 for reading from or writing to a removable magnetic disk 29, and an optical disk drive 30 for reading from or writing to a removable optical disk 31 such as a CD ROM or other optical media.

[0124] 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 solid state drives (SSDs) 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.

[0125] 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.

[0126] 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.

[0127] 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.

[0128] Also described herein is a method of determining a state of progression in a subject of a disease or treatment having motion symptoms, the method comprising:

[0129] obtaining a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during usual activities of the subject;

[0130] processing the motion data to produce a plurality of measures of kinetic state of the subject 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;

[0131] determining a measure of dispersion of the measures of kinetic state;

[0132] combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and

[0133] generating an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and generating an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

[0134] Also described herein is a non-transitory computer readable medium for determining a state of progression in a subject of a disease or treatment having motion symptoms, comprising instructions which, when executed by one or more processors, causes performance of the following:

[0135] obtaining a time series of motion data from a motion detector worn on an extremity of the subject, over an extended period during everyday activities of the subject;

[0136] processing the motion data to produce a plurality of measures of kinetic state of the subject 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;

[0137] determining a measure of dispersion of the measures of kinetic state;

[0138] combining the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and

[0139] generating an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and generating an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

[0140] Also described herein is a system for determining a state of progression in a subject of a disease or treatment having motion symptoms, the system comprising:

[0141] a motion detector configured to be worn on an extremity of the subject and to output a time series of motion data over an extended period; and

[0142] a processor configured to receive the motion data and to process the motion data to produce a plurality of measures of kinetic state of the subject 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; the processor further configured to determine a measure of dispersion of the measures of kinetic state; the processor further configured to combine the measure of dispersion with at least one other data characteristic determined from the motion data, to produce a selection score; and the processor further configured to generate an output indicating that motion symptoms are at an initial stage if the selection score is less than a threshold, and to generate an output indicating that motion symptoms are at an advanced stage if the selection score is greater than the threshold.

[0143] 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.