Note: Descriptions are shown in the official language in which they were submitted.
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MOVEMENT DISORDER MONITORING
TECHNICAL FIELD
The present invention relates in general to the field of assistance devices
and
methods for persons having fluctuating movement disorder diseases, and in
particular to monitoring devices and methods for collecting data associated
with fluctuating movement disorder.
BACKGROUND
Parkinsonian patients under treatment typically present a short-term
fluctuation of disease status. "Short-term" is in the present disclosure
intended to indicate changes occurring within a couple of hours. Within a
period of a few hours, a patient can experience sub periods of an "off' state,
where the patient is stiff and slow in his movements and sometimes presents
shaking motions. Within the same period, the patient may also have sub
periods of "normal" state, where the patient responds more or less as a non-
parkinsonian person. Finally, also during the same period, the patient can
have sub periods of "dyskinetic" state, where involuntary movements and
abnormal softness is experienced. The patient changes between these states
depending on e.g. amount and type of medication, physical activity, mental
activity and food intake. The response to medication is extremely individual,
and any tuning of the amount and type of medication as well as the means
for distribution, has to be performed on a case-by-case basis. A general
object of the medication is typically to give the patients as long "normal"
periods as possible, minimizing both "dyskinetic" and "off' periods.
There are a number of different prior-art methods for testing patients with
movement disorders, for example advanced parkinsonian patients. Motor
tests for parkinsonian symptoms focus, as the name indicates, on a motion
pattern of a patient. Different approaches have been proposed, e.g. using
accelerometers, specialised hardware, standard keyboard tapping and spiral
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drawing on a graphic tablet connected to a PC. The different approaches
have been developed to be applied for testing different aspects of the
disease.
As an example, in [1] motor tests, such as motor speed tests, finger tapping
tests etc are disclosed. In [2], motor disorders of patients, for instance
parkinsonian patients, are examined by e.g. a spiral test, where a patient is
requested to follow a spiral by the finger.
Cognitive impairment is common in movement disorders and will be given
high weight in the coming version of the Unified Parkinson's Disease Rating
Scale (UPDRS). As an example, in [3], apparatuses and methods for cognitive
tests aimed for neurological diseases such as Alzheimer's disease are
disclosed. A small portable unit is controlled by a keyboard, mouse, joystick
etc., to enable inputs from a patient on cognitive tests. These investigations
could be used for diagnosing neurological pathology, as well as for
monitoring recovery from or maintenance or progression of neurological
pathology.
Patient home diaries, both on paper and palmtop computers, have been
successfully used with fluctuating parkinsonian patients in clinical studies.
A patient is requested to continuously fill in a patient diary by answering a
set of questions concerning his conditions. One study is presented in [4].
Compliance with paper diaries have been shown extremely low in pain
patients, see [5]. Another study [6] showed good compliance with an
electronic diary for Parkinson patients.
Determining treatment outcome and follow-up of patients is a complicated
task. Long-time progression can be tracked in non-fluctuating patients by
repeating single measurements or observations, such as indicated e.g. in [3].
However, short-term fluctuations ruin the accuracy of such approaches. In
general, single or a few scattered observations will not give full information
on what state a patient is normally in, how much the state varies and how
much time that is spent in different states. Continuous observations by
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medical staff require hospitalisation which is expensive and may not be
representative to the condition in the home environment.
Moreover, further analysis of the data in [6] has revealed that the diary
answers did not correlate with motor ratings performed hourly by
neurologists. Thus, there are aspects of the state which are not captured by
the diaries.
SUMMARY
A general problem with prior art methods and devices for monitoring of
neurological diseases is that they are not particularly well adapted to the
particular needs for patients exhibiting short-term fluctuating movement
disorder. A further problem is that measurements performed by different
approaches do not generally correlate. Follow-up with diary only will be
biased
by cognitive and emotional conditions, as well as changed expectations and
memory problems. Follow-up with motor tests only will be biased by
motivation, learning effects and a large variation of test scores between
individuals in the normal population, unrelated to disease state
An object of the present invention is to provide devices and methods for
improving monitoring of fluctuating movement disorders. A further object of
the present invention is to provide devices and methods enabling monitoring
of short term fluctuations. Another further object of the present invention is
to
provide devices and methods giving a more general description of a patient
having fluctuating movement disorder. A yet further object is to provide an
improved evaluation approach for spiral tests. It is also a further object of
the
present invention to provide for evaluation of effects of events such as
medicine doses, food intake, exercise etc. It is also yet a further object of
the
present invention to provide for possibilities of individual calibration of
test
results.
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The above objects are achieved by devices and methods according to the
enclosed patent claims. In general words, a test battery comprises both a
motor test section and a p atient diary collection s ection. The motor test
section is arranged for supporting motor tests and for collecting data
representing results of the motor tests. The patient diary collection section
is
arranged for collecting data representing patient subjective experiences. The
test battery further comprises a scheduler, which is arranged to restrict
operation of the motor test section and the patient diary collection section
to a
multitude of predetermined limited time intervals. This restriction in time
provides an association in time between the two types of tests, as well as a
possibility for timing the test intervals dependent on e.g. the medication
schedule or the daily activity schedule. The limited time intervals are
preferably shorter than or equal 'to one hour, and preferably there is at
least
one limited time interval each 24 hours. For parkinsonian patients, at least
four limited time interval each 24 hours are to prefer. The predetermined
limited time intervals can preferably be event driven, i.e. the intervals can
be
pre-defined relative to a certain event, such as e.g. medicine or food intake,
physical exercise etc. In preferred embodiments, the test battery also
comprises cognitive test means and/or psychometric measurement means.
The test battery is preferably implemented as a portable device, enabling
monitoring under home environment conditions.
In further preferred embodiments, the test battery comprises test evaluation
means arranged to evaluate the results of the motor tests. Over each test
period, a summary of how much time that has been spent in different states
and how the states varied is presented. The test battery may also comprise
data processing means arranged to classify a momentary state of a patient
performing the motor tests and providing the patient subjective experiences,
preferably implemented as a fuzzy rule-based expert system,. e.g. a Sugeno-
style fuzzy inference system [11]. The data processing means may also
comprise means for calibrating the classification for each patient
individually,
by utilising calibration sessions, where test results can be correlated with a
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gold standard classification of motor state, e.g. using adaptive neuro-fuzzy
technology [12].
Spiral test evaluation is preferably performed utilising entropy values of
drawing velocities. Multi-Scale Entropy analysis (MSE) with a Sample Entropy
(SampEn) measure is one preferred evaluation [8], [9].
One advantage with the present invention is that the combination of patient
diary and motor tests and possibly also cognitive tests and/or psychometric
measurements gives new possibilities for interpreting evolution of data,
which cannot be provided by each test separately. The time synchronization
of the test ensures that the same state of disease is monitored. Other
advantages with the present invention is that the scheduling of preferably
several pre-planned test occasions daily gives a reliable tool to follow even
short-term fluctuations, thereby evaluating e.g. different treatments.
Advantages of this test setup are that it enables provision of information
about different states in.short -term fluctuating patients in order to:
1. Evaluate effects of different treatments in clinical practice and
research.
2. Follow up treatments and disease progression.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention, together with further objects and advantages thereof, may best
be understood by making reference to the following description taken together
with the accompanying drawings, in which:
FIG. 1A & B are block schemes of data processing and communication
systems in which devices according to the present invention advantageously
can be used;
FIG. 2 is a block scheme of main parts of an embodiment of a device
according to the present invention; and
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FIG. 3A & B are flow diagrams of main steps of embodiments of
methods according to the present invention.
DETAILED DESCRIPTION
The present invention as claimed does not concern any diagnosing method.
The patients that are subjects for the present invention are already
diagnosed having a fluctuating movement disorder, and typically receive
medication therefore. The presence of such a disorder is instead a
prerequisite
of the need of the present invention. The present invention as claimed does
neither comprise any method of treatment, since there is in the present claim
no subject matter connected to any definite decisions about treatment. The
main part of the present invention instead concerns the procedure of
obtaining different measures possible to be associated with patient states,
i.e.
a pure data collection procedure ensuring the quality of the measurement&. In
one aspect of the invention, a subsequent primary evaluation gives data that
indeed may be used for differing purposes. One possible use is pure
monitoring of a patient progression, a "surveillance". This surveillance may
comprise provision of processed data supporting evaluation of different
treatments and doses in a certain patient. Another possible use can be
collection of statistics for scientific purposes, whereby the collected data
is not
used at all in connection with the targeted patient in any respect. A third
use
could be as a decision support for selecting suitable candidates for certain
treatments, which are to be further investigated and evaluated. The methods
and devices of the present invention can also be used to provide feed-back
information to the patient, e.g. as an objective indication of the actual
result of
a single medication dose.
Prior-art methods for providing test results have been shown to present
results of different kinds that not always are well correlated to each other.
Typically, most motor tests are relatively well compatible with each other,
but when e.g. comparing with diary questions, the results are not obvious to
incontestably analyse and explain. Possible reasons can be several.
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One possible explanation is that the different types of tests target different
aspects of a patient. Motor test have in general a more objective appearance,
being connected to physiological functioning of a patient. Diary questions are
instead targeting more subjective aspects of a human being. Here, an
intrinsic discrepancy may occur, since the physical and mental condition
may not always be in perfect agreement with each other. Motor tests are
believed to be more insensitive e.g. to environmental conditions such as if
the test is performed at home or at a hospital. However, different levels of
mental stress or motivation may indeed influence the test results.
A combination of diary questions and motor tests will therefore not only
provide more data to analyse, but will also, as a synergetic effect, give
inputs
for a cross evaluation. A high score at a motor test, when at the same time
having a low own state assessment, may be evaluated in a different manner
compared to the same score made when the own assessment was high. By
co-evaluating results of both diary questions and motor tests, completely
different analyses may be performed compared to performing the two test
types just side by side, more or less independently from each other. The
combination of the test methods thus provides a synergetic effect compared
with a pure addition of the individual benefits.
By such evaluation, other effects may also be taken into account. In the case
of certain motor tests, repeated tests comprising the same type of tasks will
eventually give a learning effect to the patient. It is thus natural that
results
of a motor test improve by time, even if the actual physiological status is
unchanged, just by a simple learning procedure. In other tests, the demands
on the patient to always improve the results may instead lead to the opposite
result. Such effects are typically not of primary interest when evaluating
e.g.
the result of a medication, and may be reduced by co-processing motor test
results to answers on diary questions.
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Most patients have a tendency to increase their expectations e.g. at the
beginning of a new medication. This may lead to answers to the diary
questions that are more positive than motivated physiologically. For
instance, when starting a medication, every small improvement may be
experienced by the patient as a huge relief, rating the condition much higher
than what is objectively motivated. However, with time, the patient gets used
to the medication and its effects, and the expectations may be damped with
time. A correlation with e.g. motor tests may in such cases give indications
on such adjustments of subjective reference level.
By this, it is obvious that both motor tests and diary questioning are
advantageous to perform, substantially at the same time, or at least during
the same disease state. At the same time, 'the time dimension is also of
crucial importance, since long-term trends in the relations between motor
test results and diary question answers may reveal systematic errors as well
as completely new information. A problem when predicting outcome for
treatments using statistical methods based on baseline levels is the
regression
to the mean [10]. To avoid this, repeated baseline measurements are required
and this can be accomplished with the test battery of the present invention.
In the general field of neurological diseases, many different test methods are
proposed. However, diseases presenting short-term fluctuations of movement
disorder, such as e.g. advanced Parkinson's disease, put further restrictions
to the test methods. This means that tests operable on general neurological
diseases will not be the optimum choice when focussing on short-term
fluctuations of movement disorders. The most obvious characteristic is the
time scale of the fluctuations. A parkinsonian patient may very well pass all
three states of "off', "normal" and "dyskinesia" within a few hours. It is
therefore crucial that all tests are performed essentially at the same time,
so
they reflect the same state of the patient. It is also of crucial importance
that
a suitable phase of the fluctuation is targeted. Such timing is typically very
dependent on the type of evaluation that is going to be performed.
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The fluctuations of the state of movement disorder of e.g. Parkinson's disease
may depend on many things. The type and timing of medication will of course
influence the patient state considerably, as well as the method for
distributing
the medicament. In a typical case, a patient will be "off' before the
medication
occasion, while the highest probability of a "dyskinesia" state, will be at a
certain time after the medication took place. There are also unpredictable
fluctuations. The results of tests will therefore be highly dependent on the
actual occasion when it was performed. The patient state may also be strongly
affected by mental and/or physical activity or simply by the daily routines,
e.g.
food intake. It is therefore of crucial importance that the test occasions are
appropriately selected. Events can be documented in the test battery and
trigger a test sequence.
One possibility is to connect the test occasion to a certain time of the day.
For
instance, tests may be performed between 08:00-09:00, 12:00-13:00, 16:00-
17:00 and 20:00-21:00, respectively, every day. Another possibility would be
to perform the tests event-triggered, i.e. at times which are pre-determined
relative to some other event. One example would be to perform the tests one
hour after each medication occasion. In this case, the invention could be used
to assess the impact of each event.
The schedule of testing may be planned depending on the purpose of the
investigation. If a mean response or a long-time stability to a certain
medication is to be investigated, a few tests every day during one or a couple
of weeks may be appropriate. However, if the short-term (within-day)
fluctuations are to be investigated, frequent measures have to be performed.
A possible schedule could e.g. be once every 15 minutes during the first two
hours after each medication occasion.
According to the present invention, devices and methods are presented,
which ensures an appropriate timing of motor tests and diary questions. In
the described embodiments, a portable test battery device is presented as an
example of the implementation.
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Fig. 1A illustrates an embodiment of a data handling system 1 in which a
device according to the present invention can be used. A central data server
2 is connected to a number of terminals 3. The central data server 2 may be
implemented as one device or may be implemented in a distributed manner.
The terminals 3 are available for physicians, researchers or other persons
involved in taking care of the patients having fluctuating movement
disorders. The terminals 3 can be used to access software 5 for evaluation of
tests and a central database 6 of the central data server 2. The information
concerning test programs, such as instructions about time schedules can be
provided to the central data server 2, and data associated with results of
patient tests can be retrieved from the central database 6.
The central data server 2 is connected to a communication system 4, capable
of transmitting data to and from a number of terminals 10'. ' In this
embodiment, the communication system 4 comprises an Internet network
30, to which a number of patient servers 31 are connected. The terminals 10
communicate with the patient servers 31, e.g. via wireless communication 32
such as IR communication or Bluetooth. The communication between the
terminal 10 and the patient server 31 may also be provided by cables 33. In
such a manner, the terminals 10 are able to communicate with the central
data server 2. Typically, the terminals 10 receive instructions about test
scheduling, which is discussed more in detail below. The terminals 10
typically report test results, e.g. periodically to the central data server 2.
The
results may be intermediately stored at the patient server 31, and at least
parts of evaluation procedures on the test results may be performed at the
terminal 10 itself or at the patient server 31. The central data server may in
other embodiments be the sole responsible for data evaluation and
processing.
Fig. 1B illustrates an alternative embodiment of a data handling system 1 in
which a device 10 according to the present invention can be used. Here the
communication system 4 comprises a cellular communication system 40, in
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which base stations 41 are in radio contact 42 with the terminals 10. Anyone
skilled in the art realises that the above systems are just two non-exclusive
examples of possible configurations, and other variants are of course also
possible to use. The scope of the present invention should therefore not be
constricted to the particular embodiments.
Fig. 2 illustrates an embodiment of a device for monitoring of fluctuating
movement disorder according to the present invention. The device 10
consists in the present embodiment of a palmtop computer which presents a
patient interface 11. The patient interface 11 comprises in this embodiment
a touch screen 12 and a stylus 13. The palmtop computer typically further
comprises a processor 14 having software code implementing test
functionality. Alternatively, or complementary, the processor 14 is arranged
for interacting with the central data server 2 or the patient server 31, if
any,
to load test configuration data into the palmtop via computer communication
arrangements, discussed in more detail further below. The test configuration
data may comprise a configuration file or a data base table that is used to
determine which test that is going to be performed. Texts of questions and
answer alternatives as well as degree of difficulty in motor tests, cognitive
tests etc can be provided. Also, as further described below, scheduling of the
test can also be provided this way.
A motor test portion 15 of the processor 14 provides test configurations to
the patient via the touch screen 12. The patient responds to the test
configurations by touching the touch screen 12 in certain positions with the
stylus 13. The position of the contact is interpreted as a test result by the
motor test portion 15. The test results are stored in a local storage 16,
waiting for further transmission to a central data base, c.f. Fig. 1. A motor
test section 17 of the device 10 of the present embodiment comprises thereby
the motor test portion 15 of the processor 14, the touch screen 12 and the
pointer rod 13. The motor test section 16 is thereby arranged for supporting
motor tests and for collecting data representing results of the motor tests.
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A diary question section 18 of the processor 14 provides diary questions to
the patient via the touch screen 12. The patient responds to the diary
questions by touching the touch screen 12 in certain positions with the
stylus 13. The position of the contact is interpreted as an answer by the
diary question section 18. The answers are also stored in the local storage
16. A patient diary collection section 19 of the device 10 of the present
embodiment comprises thereby the diary question section 18 of the processor
14, the touch screen 12 and the stylus 13. The patient diary collection
section 19 is thereby arranged for collecting data representing patient
subjective experiences.
The patient diary collection section 19 and the motor test section 17 comprise
a patient interface 11. In the present embodiment, both sections 17, 19
utilise the same patient interface 11. However, anyone skilled in the art
realises that the motor test section 17 may utilise one patient interface and
the patient diary collection section 19 another.
The patient interface 11 comprises in the present embodiment a touch screen
12 and a stylus 13. However, other types of patient interfaces can also be
used. For the diary questions, a screen showing the questions could be
combined with physical button, used for inputting the patient answers.
Alternatively, the questions could even be provided to the patient in an audio
manner, e.g. by retrieving a voice question through the loudspeakers. The
patient interface for the motor tests can also be implemented differently and
any prior-art approaches, such as using physical buttons to press or using a
joy stick may be utilised also together with the present invention. Also for
the
motor tests, instructions may be given by a voice via the loudspeaker. The
alternatives of this section are only intended as non-exclusive examples of
possible configurations of usable patient interfaces. Therefore, the scope of
the
invention should not be restricted thereto.
The device 10 further comprises, according to the present invention, a
scheduler 20. In the present embodiment, the scheduler 20 is implemented in
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the processor 14. The scheduler 20 controls the time intervals, during which
the motor test section 17 and the patient diary collection section 19 can be
accessed. The scheduler 20 is thereby arranged to restrict operation of the
motor test section and the patient diary collection section to a multitude of
predetermined limited time intervals. These predetermined limited time
intervals can be event driven, i.e. determined relative a certain event, such
as
a time of medication, food intake, exercise etc. Such event driven time
intervals will also be discussed further below.
The device 10 comprises also communication arrangements, in the present
embodiment in the form of a transmitter 21 and an antenna 22 as well as a
data communication interface 23. These communication arrangements are
used for transmitting the collected data to a database server (c.f. Fig. 1)
e.g.
via a mobile communication network and/or via data communication cables.
The transmitter 21 is thereby arranged to allow for transfer of data, e.g.,
data
temporarily stored in the storage 16, over e.g. a radio communication system.
Such a system could e.g. be based on a mobile telephony standard or on
Bluetooth technology. The data communication interface 23 is arranged for
allowing the collected data to be transferred by cable, e.g. using standard
USB
technology.
The communication arrangements can also be utilised for providing the device
with input data. The data communication interface 23 can for instance be
used e.g. as a staff interface to assign patients and possibly for period
identification, i.e. setting the scheduler 20 to provide an appropriate set of
predetermined limited time intervals. A trained physician or nurse may
thereby remotely specify at what occasions the tests are going to be
performed. Also test definitions and question texts can be provided this way.
The communication arrangements are also suitable for providing feed-back
information to the patient. Patients are typically very curios about their
state
and may be very eager to know e.g. what the last test period results were. In
particular, where the main evaluation is performed at the central data
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server, it is useful to provide some feed-back data to the patient, for
knowing
e.g. if the last medicine dose had the intended effect.
In more elaborate systems, e.g. where medication distribution is controlled
by some electronic device, such medication equipment may communicate
data concerning medication times and amounts of medication to the device
10, using the communication arrangements or any separate external interface
27. This can e.g. serve as input data for setting event driven predetermined
limited time intervals. Such relative test periods can be utilised when
evaluating the medication effects on individual medication events.
When starting the device 10 by an on j off button 24, a first screen in the
test
display of the touch screen is presented. This appearance of the first screen
may also be provided automatically at the start of a predetermined limited
time interval, preferably connected with e.g. some sound signal to catch the
attention of the patient. The screen presents a button icon with the text
"start
diary" appears. This button is only active during the multitude of
predetermined limited time intervals, as controlled by the scheduler 20. When
the "start diary" button is pressed, a number of diary questions are
presented,
on which the patient is supposed to answer. One example of a typical question
that has been used in [7] is "Have you had difficulty walking about 100 meters
during the last four hours?". A number of answering alternatives are
presented, such as "not able at all", "difficult", "with efforts", "pretty
well",
"without problems". The patient touches the touch screen, preferably by the
stylus 11 at the appropriate choice. A new question is then shown, e.g. "Have
you been "off' (stiffness/slowness/shakings) during the last four hours?".
Answering alternatives could then be "all the time", "most of the time", "half
of
the time", "a smaller part of the time" and "not at all". Alternatively, the
patient
could be given a graphical representation of the four hours and be asked to
divide the representation into three parts, representing the amount of "off'
time, "dyskinetic" time and "normal" time. To catch the momentary perceived
state, a question such as "How are you feeling right now?" can be used.
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Answering alternatives could be "very off', "moderately off, "slightly off,
"quite
well", "slightly dyskinetic", "moderately dyskinetic" and "very dyskinetic".
A number of such questions, typically seven selected questions and one or two
questions on mental mood are presented to the patient. Typically, 5
alternatives are given for the answers or the patient could himself make an
indication on a scale. However, the questions appearing in the diary part of
the tests are only possible to be answered once in each time interval. So,
when
all questions have been answered, it is no longer possible to activate any
"start
diary button" again until next time interval. There is also preferably a
timeout
functionality if a sequence of questions has not been completed. When all
questions are answered, the screen instead presents a "start motor test"
button, or alternatively automatically switches to the motor tests.
A first example of a motor test can be a standard tapping test. The screen
presents two coloured squares and the patient is instructed to tap on the
squares in an alternating manner as fast as possible during e.g. 60 seconds.
The areas corresponding to the squares are then active for registering taps
during 60 seconds from the first tap. Absence of audio or visual triggers
assures that pure motor function is measured. Estimates of speed (number
of taps/min), rhythmicity (standard deviation of tap times) and spatial
accuracy (number or missed or double clicked squares) are calculated and
stored.
A second example is tapping with increasing speed. In such a test, two
squares are presented at the screen, one red and one grey. The colour
switches according to a predetermined schedule having an increasing speed.
The patient is instructed to tap the squares alternately when the red
colouring shifts. Also this test is performed e.g. during 60 seconds. There
will
possibly be a sound connected to movement of the red colouring, e.g. by
means of a loudspeaker 25. The patient should try to tap all red squares.
Number of correct and incorrect taps are calculated and stored. Possibly, a
break-point in the relation speed vs. proportion of incorrect taps could be
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recorded. Another alternative is to record an n:th failure time, i.e. the time
to
the n:th incorrect tap.
A third example is a random chase test. A screen with four squares is
presented. One of the squares is red and the colouring shifts in a random
manner between the squares. The patient is instructed to tap all red squares
as fast as possible. The test starts when the first red button is tapped and
continues for e.g. 60 seconds. When a red button is tapped, another button
(randomly selected) will turn red. The same data as in the standard tapping
test is calculated and stored, preferably together with an identification of
the
square that was tapped. This is a semi-cognitive test which will assess the
function between eye and hand.
A fourth example is a spiral test, which is found to be a test type giving
much useful information. A spiral is presented on the screen. The spiral is
preferably an Archimedes spiral following the definition of:
r=a=O
x = r =cos(a - r)
y=Y=sin(a=r)
in polar and Cartesian coordinates, where
r = x2 + y2
and
tan(o)=y.
x
The constant a defines the spiral and is adjusted such that the spiral fits
into the screen on three rounds about the origin. The patient is instructed to
follow the pre-drawn spiral from the centre outwards with the stylus as
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accurate and fast as possible. The position and times for the stylus are
recorded. For calculations, original coordinates are transformed to polar
form with the origin placed in the centre of the spiral. The drawing velocity
in
r, O, x and y directions are obtained by differentiation. In a standard
evaluation of the result, the drawing velocities in different directions are
Fourier transformed and frequency-filtered to detect involuntary movements
of different frequencies as described in [13]. This test will thus mainly
assess
involuntary movements such as high frequency (5-10 Hz) tremor and lower
frequency (1-5 Hz) dyskinesias. Standard deviations of frequency filtered
drawing velocities could also be of use as well as average of corresponding
mean accelerations for each direction.
Quality validation of drawn spirals is preferably done according to the
following rules:
1. The number of coordinates must be larger than some threshold
value.
2. Maximum radial distance must be larger than some threshold
value.
3. Maximum gap length between consecutive turns must be smaller
than some threshold value.
4. The mean square deviation from the pre-drawn spiral must be
smaller than some threshold value.
We have found that spiral test also advantageously can be evaluated using
entropy approaches. Preliminary work indicates that entropy is lower in
shaky spirals. Entropy values of drawing velocities are preferably calculated
with use of the Multi-Scale Entropy (MSE) method with the sample entropy
(SampEn) measure.
Motor tests and diary questions target different aspects of a patient. In
order
to assess validity of self assessments in the diary section, cognitive tests
could also be of use. Cognitive tests as such are available in prior-art.
Perception, attention and concentration are the main subjects for cognitive
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tests. Disability in these aspects is related to some movement disorders,
such as Parkinson's disease, and cognitive test results will provide useful
background information on how to interpret diary answers. There are many
cognitive test suites on the market and any type of tests would be possible to
incorporate in the test battery of the present invention. For instance, the
Mini Mental State Exam, which is frequently used to test dementia in
elderly, has one test where the test person is asked to draw the hands on a
clock so it shows ten past ten. This test can be generalised and added to the
present test battery such that the hands of a clock can be moved. by the
patient, e.g. by pointing by the stylus on the touch screen presenting a
clock,
to indicate different times. A text or voice asks the patient to set the clock
to
indicate a certain time. The time to be set is randomly changed each time the
test is performed.
Another widely used cognitive test is pattern matching. This is implemented
in the present battery such that the screen shows a selection of different
symbols in one or two rows. One of these symbols is shown again in a box
below and the patient is asked to tap the matching symbol in a row above.
The symbol in the box will be randomly selected each time the test is
performed. The device registers preferably question identification, time,
given
answer and correct answer.
Since perception, attention and concentration in many cases also influence
motor test results as well as answers to diary questions, cognitive test
results can advantageously be used in an integrated analysis with motor
tests and diary questions. Cognitive test results may e.g. also contribute to
interpret long-term variations as described more in detail above.
The motivation of a patient may also influence the test results. Observations
concerning mental mood and attitude can thereby give additional
information about how to interpret the results of other tests. Questions
about mental mood at the time for performing test may e.g. be included in
the diary questions, as described further above. However, also other
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psychometric tests may be useful. A simple arrangement for measuring the
skin resistance may for instance give indications of stress levels of the
patient.
The MSE method is also advantageously applied for evaluation of the motor
tests as well as of psychometric measurements and diary answers for the
whole period.
When the tests and questions are performed, the results have to be compiled
and processed. Such tasks can be performed at different stages in the
system. A first compilation of test results is preferably performed already in
the portable palmtop computer. Compilation and evaluation can also be
performed at different stages in the communication chain to the central data
server, e.g. at a patient server (c.f. Fig. 1A) or at the central data server.
If
compilation and/or evaluation is performed early in the reporting chain, the
amount of data that is necessary to transmit will be decreased. However, it is
also possible that the device collecting the data sends all primary data
directly to the central data server before any data treatment at all is
performed.
Compilation of test and question data is preferably performed by applying a
scaling of measurements of each test parameter. There might be different
optimal scales for the answers/results in different tests. The single question
answers and test results can then be weighted together, e.g. using a fuzzy
logic inference system to a common scale, in the Parkinson case e.g. having
the grades [-3,+3], where -3 represents severe off, 0 is normal and +3 is
severe dyskinesia. The limits for the classification based on e.g. "high",
"low"
etc. are to a high degree "fuzzy". Fuzzy classification of test parameters can
be utilised by use of fuzzy logic membership functions. The meaning of
"high", "low" etc. will then be defined e.g. after finding a distribution of
test
results for reference sample groups of patients and healthy individuals of the
typical age.
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Multivariate scaling of test parameters can also be applied, i.e. more than
one test result may be utilised when determining the value of a parameter. A
combination of e.g. answers to diary questions and motor test can easily be
performed already in the compilation step. For instance, a"bad" test result
may be caused either by an "off' condition or a"dyskinetic condition. If a
bad test result, e.g. low tapping speed, occurs when the patient is
"dyskinetic", the multivariate parameter could be set to +2, while the -2 is
reserved for a low tapping speed test result occurring when the patient is
"off' according to his own assessment. The compilation of individual test
results to more global state variables is preferably performed using a fuzzy
rule-based expert system, preferably a Sugeno type fuzzy inference system
(FIS) [ 11 ] using expert rules.
In a preferred embodiment of the present invention, the compiled and
evaluated test results are further processed for classifying a momentary state
of the patient performing the tests. Such processing is preferably performed
utilizing an adaptive neuro-fuzzy inference system (ANFIS) [12]. This requires
a calibration period with gold standard classification e.g. on the [-3, +3]
scale.
Various aspects of patient state are preferably specified and assessed, e.g.
in
the following state variables:
- Overall Patient State (OPS) based on diary questions and motor tests (and
further on psychometric measures and cognitive tests, if any);
- Perceived State (PS) based on diary questions only;
- Motor Test State (MTS) based on motor tests only;
- Cognitive State (CS) based on cognitive tests only;
- Mental Mood & Attitude (MMAS) based on diary question and psychometric
measurements;
These state variables can be assessed at different time scales, e.g. per
occasion (j=1,m); per day (i=1,n) and per assessment period (e.g. week, n=7).
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When assessment is performed per test occasion, m per day, this leads to
the following set of momentary states:
OPS(i,j), PS(i,j), MTS(i,j), CS(i,j), MMAS(i,j); i=1, n and j=1,m.
For typical values m=4 and n=7 there will be mxn=28 values for each of the
state variables.
The momentary states are calculated e.g. as:
OPS = Fops (all test parameters)
PS = Fps (diary question 1; diary question 2; ...)
MTS = FMTS (tap speed; rhythmicity; proportion of correct taps; break-
point; failure time; MSE values; area; drawing velocities and
accelerations)
CS = Fcs (proportion of correct matches; ...)
MMAS = FMMAS (diary question; psychometric measures)
The various 'functions' FoPs Fps FMTs Fcs FmMAs can be expressed by Sugeno
type FISs [11] defined in consensus with expert physicians.
The primary momentary OPS, PS, and MTS state variables can be expressed
on the scale [-3, +3] where:
-3 is 'very off
-2 is 'moderately off
-1 is 'slightly off
0 is 'normal function'
1 is 'slightly dyskinetic'
2 is 'moderately dyskinetic'
3 is 'very dyskinetic'
Examples of using a zero-order Sugeno style FIS:
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If tapping_speed is HIGH and proportion_missed is LOW then MTS is 0
If tapping_speed is VERY LOW then MTS is -3
If spiral_entropy is VERY_LOW then MTS is +3
Antecedents of all these rules will get a truth value between 0 and 1. 'And'
and 'or' operators can be compiled using 'min' and 'max' membership values,
respectively.
The end result will be a weighted average:
MTS = sum (truth_value(rule(i))*MTS(rule(i))) / sum (truth_value(rule(i)))
i=1,2, ... all rules.
This MTS value is then rounded to nearest integer
For OPS we take diary answers into account:
If sign(MTS) = sign(PS) then
OPS=weighted_average (MTS,PS)
else
flag conflict
end if
(An alternative is to use a FIS even in this case).
When assessment is performed per day, m occasions, this leads to the
following set of 'daily' states:
dOPS(i) _ OPS(i, j), i = 1, n
j=1,m
dPS(i) PS(i, j), i=1, n
j=1,m
dMTS(i) =Y, M?'S(i, j), i= l, n
j=1,m
dCS(i)=yCS(i, j), i= l, n
j=1,m
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dMMAS(i) MMAS(i, j), i=1, n
j=1,m
Y, stands for a combination of the m momentary state values, for instance, in
the Parkinson case, calculated fraction off-time / good time / dyskinetic
time, mean squared deviations, maximum, median and minimum values,
frequencies of each state [-3, +3] The off-time can e.g. be defined as time
spent in -3 and -2 states, the good time as time spent in -1, 0 and +1 states
and the dyskinetic time as time spent in +2 and +3 states.
When assessment is performed per assessment period (n days, e.g. one week
with nxm momentary states), this leads to the following set of 'period'
states:
pOPS = EdOPS(i)
f=1,n
pPS dPS(i)
i=1,n
pMTS = E dMTS(i)
e=l,n
pCS = EdCS(i)
i=1,n
pMMAS dMMAS(i)
i=1,n
where E stands for a combination of the n'daily' state values.
Following storage in the database, a server program presents summaries for
the whole test period:
- Overall Patient State (pOPS)
- Perceived State (pPS)
- Motor Test State (pMTS)
- Cognitive State (pCS)
- Mental Mood 8s Attitude State (pMMAS)
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with calculated values of "fraction good time", "fraction off-time", "fraction
dyskinetic time", Mean Squared Deviation, and median, maximum,
minimum values.
Options for further display and inspection by physicians and nurses:
1) Daily and momentary patient state values;
2) Summaries for questions in
- histograms with "fraction time" or frequency of answers (e.g. scale 1-
5) for the whole period, or for each occasion j=1,m such as 'morning'
state etc. over the whole period;
- time series of all answers (e.g. scale 1-5) for the whole period, with
results of ANOVA (within-day, between-day and total variation) and of
Multiscale Entropy analysis;
3) Median, max and min values, and frequency histograms for:
- test completion time;
- speed, rhythmicity and accuracy of the tapping tests;
- number of correct and incorrect taps and time to failure for the speed
tapping test;
- scores for tremor and dyskinesia, or MSE curve profiles, according to
the spiral test;
4) Summaries of number of completed and expected test sequences,
numbers of valid and invalid spirals, and numbers of correct and incorrect
answers to cognitive tests;
These summaries are tabulated and presented in graphical form comparing
different treatment periods in a web interface for treating staff.
The data processing preferably comprises functionality for individual
calibration. The purpose of calibration is to acquire a test result that can
be
comparable between patients. Since different patients experience symptoms
differently, answers on diary questions may differ significantly between
patients. Some patients have a high tolerance level and always give answers
close to a medium value. Other patients react very much on every tendency
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of symptoms, and will often indicate extreme answers. Also motor tests are
somewhat influenced by individual patient response. Some patients may
cover symptoms in a more efficient manner than other patients. In order to
compare results from different patients, some sort of calibration is
preferred.
With use of a built-in camera 26, (Fig. 2) of the hand-computer or an
external camera, film sequences may be recorded while the patient performs
well defined motor exercises, e.g. walking. These recordings could then be
transmitted to a central server and rated by a trained physician or nurse in
order to obtain some kind of pragmatic calibration standard. Such rated film
recordings performed during an initial period of calibration in direct
connection before or after the various tests could then be used to establish a
multivariate calibration function, to be used for transformation of the set of
motor function test parameters from each test occasion into a provisional
gold standard score value, e.g. on the [-3, +3] treatment response scale (TRS)
[7].
The calibration function can be established with use of e.g. Adaptive Neuro-
Fuzzy Inference Systems (ANFIS), (also known as Adaptive-Network-Based
Fuzzy Inference Systems) training of the already defined FISs. An alternative
to video-recording in the home could be to use the test battery at the
hospital at the same time as when doing gold standard ratings on the TRS
scale. These measures are then used as gold standards for an individual
calibration.
In Fig. 3A, a flow diagram of main steps of an embodiment of a method for
collecting data associated with fluctuating movement disorder according to the
present invention is illustrated. The procedure starts in step 200. In step
210,
a multitude of predetermined limited time intervals are determined. Answers
of diary questions are collected in step 220. In step 230, motor tests are
performed and in step 232, results of the motor tests are collected. In step
240, cognitive tests are performed and in step 242, results of the cognitive
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tests are collected. Finally, psychometric measurements are performed in step
250. The procedure ends in step 299.
In Fig. 3B, a flow diagram of main steps of an embodiment of a method for
provision of data supporting evaluation of treatment of fluctuating movement
disorders according to the present invention is illustrated. The procedure
starts in step 300. In step 310, data are collected according to the procedure
illustrated in Fig. 3A. In step 320, a multitude of momentary states of a
patient are classified, based on data representing results of the data
collected
in step 310. In step 330, a compilation of the classified results is provided.
The
procedure ends in step 399.
The embodiments described above are to be understood as a few illustrative
examples of the present invention. It will be understood by those skilled in
the
art that various modifications, combinations and changes may be made to the
embodiments without departing from the scope of the present invention. In
particular, different part solutions in the different embodiments can be
combined in other configurations, where technically possible. The scope of the
present invention is, however, defined by the appended claims.
REFERENCES
[1] US 2004/0229198
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[3] EP 1 122 679
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[5] A.A. Stone, S. Shiffman, J.E. Schwartz, J.E. Broderick, M.R. Hufford,
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[10] A.G. Barnett et el. "Regression to the mean: what it is and how to deal
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