DEVELOPMENT OF A HAND TREMOR QUANTIFICATION ......Development of a Hand Tremor Quantification Device...

DEVELOPMENT OF A HAND TREMOR QUANTIFICATION DEVICE FOR THE MEASUREMENT OF PATHOLOGICAL TREMOR

Sonja Markez

A thesis submitted in conformity with the requirements for the degree of Master of Health Science,

Institute of Biomaterids and Biomedical Engineering, University of Toronto

O Copyright by Sonja Markez 2000

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Development of a Hand Tremor Quantification Device for the Measurernent of Pathologieal Tremor

Sonja Markez

Institute of Biomateriais and Biomedical Engineering University of Toronto

2000

ABSTRACT

Hand tremor is the most cornmon and visible symptom of a variety of neurological

disordea, including Parkinson's disease. Consequently, the seventy of tremor is oflen

used as an aid in diagnosis and a gauge to assess the eficacy of treatment.

A hand tremor quantification device, the miniBIRDTM/Tremor Quantifer system, was

designed with the electromagnetic tracker, miniBIRDm fiom Ascension Technology, and

customized software. The miniBtRDm's sensor is affixed to the finger and data are

acquired through a host computer. The system is set to rneasure the three main types of

tremor associated with Parkinson's disease: resting, postural, and intention. Frequency,

amplitude, and area of displacement of tremor (an indication of power) are determined

for each set of data,

The system was tested to a positional accuracy of (0.031 + 0.132) cm averaged over a specified range. The fiequency measurements were tested against those an

accelerometer and found to be comparable.

Development of a Hand Tremor Quantincation Device for the Measraement of Pathological Tremor ii

The timely completion of this project memt a great deal to me and I appreciate the

contribution of those who helped to make it possible. The following acknowledges their

contributions but 1 hope that my personal expressions of thanks have already done so.

Thank you to Dr. Tony Easty and Joe C d ~ o who gave me their tirne, support, and

guidance. Tony, 1 value the trust that you implied with your patience and support. Joe, it

has been my privilege to work under your supervision for al1 these years.

Thank you to Jack Lam whose assistance cannot be quantified. 1 think that 1 have leamed

more 'engineering' from you than I have in six years of univenity.

1 am fortunate to have been surrounded by good enginees and colleagues.

Many thanks to:

Rich Leask for his help, advice, and technical support. Th appreciate his kindness nonetheless.

ough it is his nature. 1

Rob Ebetsch for his proof-reading, sense of humour, and being a great person to talk to.

Des Campbell for his fme craftsmanship and fnendly smile.

John Leung for his generosity in Iending me his digital carnera.

Dave Brewin for not steaiing my chair.. . and for al1 his logistical help.

Katina Di Biase for her humour and niendship.

Thank you to my colleagues Sonia Pinkney and Vicky Young, without whose fnendship I

surely would have jumped ship a long t h e ago.

Most of all, thank you to my family: John, Frank, and Alenka Markez. Needless to Say

there would be no Master's if it were not for your patience and support.

Devetopment of a Hand Tremor Quantification Device for the Meamment of Pathologicai Tremor iii

TABLE OF CONTENTS

.................................................................................. ABSTRACT ................................................................ ACKNû WLEDGEMENTS

................................................................... TABLE OF CONTENTS ........................................................................ LIST OF FIGURES

LIST OF TABLES ........................................................................... ............ ......................... Chapter 1: INTRODUCTION ......................

............................................................ Chapter 2: BACKGROUND ............................................................. . 2 t Parkinson's Disease ............................................................ 2.1.1 Symptoms

2.1.1.1 Resting Tremor .......................................... 2.1.1.2 Postural Tremor .......................................... 2.1 . 1.3 Intention Tremor ......................................... 2.1.1.4 Cogwheel Phenomenon .................................

............................................................ 2.1.2 Treatment 2.1.2.1 Anticholinergic Drugs ................................... 2.1 2 .2 Antidepressants .......................................... 2.1.2.3 Levodopa (L-dopa) ...................................... 2.1.3.4 Sinemet .................................................... 2.1 .2.5 Dopaminergic Agonists ................................. 3.1 .3.6 Beta-Adrenergic Blocken .............................. 2.1.2.7 Thalamotomy .............................................

...................................................... 2.2 Classification of Tremor ............................................................... Etiology

Amplitude. Waveforrn. Frequency ................................ Pharmac olo gicd Response ........................................ Appearance and Behavioural C haract e ristics ....................

2.2.4.1 Resting Trernor .......................................... 2 . 2.4.2 Action Tremor ............................................ 2.2.4.3 Postural Tremor .......................................... 2.2.4.4 Kinetic Tremor ........................................... 2.2.4.5 Intention Tremor ......................................... 2.2.4.6 Task-Specinc or Occupational Kinetic Tremor ...... 2.2.4.7 Isometric Tremor ......................................... 2.2.4.8 Essential Tremor ......................................... 2.2.4.9 Static Tremor .............................................

................................. Chapter 3: MEASUREMENT OF TREMOR .... ........................................................... 3.1 Review o f Literature

............................................. 3.1.1 Subjective Assessrnent 3.1.1.1 Tremor Rating Scdes ....................................

.............................................. 3.1.2 Objective Assessrnent 3.1.2.1 Tambour ...................................................

.......................................... 3.1.2.2 Optical Methods 3.1.2.3 Accelerornetry ........................................... 3.1.2.4 Digitizing Tabtets .......................................

Page . . 11

iii iv vi ... vlrl

1 3 3 4 4 6 7 7 8 8 9 9 10 10 10 10 11 12 12 13 14 14 14 14 15 15 15 15 15 15 17 17 17 17 20 20 20 21 22

Development of a IIand Tremor Quantification Device for the Measurement of Pathologicai Tremor iv

3.1.2.5 Optoelectric Imaging Systems ......................... 3.1.2.6 Surface Electromyography ..............................

3.2 Tremor C haracteristics ......................................................... 3.2.1 Wavefonn ............................................................

............................................................ 3 2 .2 Frequency 3.2.3 Amplitude ............................................................ 3.2.4 Long-Term Tremor Measurement ................................

3.3 Selection of a Measurement Device ......................................... 3.3.1 RingMouse .......................................................... 3.3.2 Accelerometers ........................ .. ............................ 3.3.3 Electromagnetic Tracking ..........................................

Chapter 4: METHODOLOGY .......................................................... 4.1 Description of Technology: m i n i B I R D T M ...................................

................................................................. 4.2 Serial Interface 4.3 Hardware Configuration ...................................................... 1.4 Software Description ..........................................................

................................................... Chapter 5: SYSTEM EVALUTION

................................................... 5.1 System Evaluation Resuits 5.1.1 Test of Positional Accuracy .......................................

5.1.1.1 Position Accuracy Test - Part One ..................... .................... 5.1.1.2 Position Accuracy Test - Part Two

5.1.2 Test of Frequency Measurement .................................. 5.1.2.1 Frequency Measurement Test - Part One ............. 5.1 2 .2 Frequency Measurement Test - Part Two ............

................................. Chapter 6: DISCUSSION AND CONCLUSIONS ..................................................................... 6.1 Introduction

............................................................... 6.2 System Strengths . . ............................................................ 6.3 S ystem Limitations ............................................................... 6.4 Tremor Examples ............................................................. 6.4 C M c d Relevance

6.5 Conclusions ..................................................................... 6.6 Future Work ..................................................................... ....................................................................................... Glossary

.................................................................................... References .... Appendix A: Hoehn and Yahr Scale of Clinical Stages of Parkinson's Disease

Appendix B: miniBIRDm Specifications .......... .... .............................. Appendix C : FASTRAKfM S pecifications Compared to rniniBIRDTM ............... Appendix D: S tatic Position Test Data - Part One ...................................... Appenduc E: Static Position Test Data - Part Two ...................................... Appendix F: Entran@ Accelerometer Specincations - Model EGAX-F ............ Appendix G: Frequency Test Data With 'Oscillator'. ...................................

Development of a Hand Tremor Quantification Device for the Mea~ufement of Pathological T m o r v

LIST OF FIGURES

Figure 2.1 Figure 3.1 Figure 3.2 Figure 3.3 Figure 3.4 Figure 3.5 Fi-me 3.6 Figure 4.1 Figure 4.2 Figure 4.3 Figure 4.4 Figure 4.5 Figure 4.6 Figure 4.7 Figure 4.8 Figure 1.9

Figure 4.10

Figure 4.1 1

Figure 4.12 Figure 4.1 3

Figure 4.14

Figure 4.1 5

Figure 4.16 Figure 4.17 Figure 4.18 Figure 4.19 Figure 4.20 Figure 4.21 Figure 4.22 Figure 4.23

Figure 4.24 Figure 4.25 Figure 4.26 Figure 5.1 Figure 5.2 Figure 5.3

Tremor classification by appearance and behavioural characteristics . .......................................................... Pegasus RingMouse

Close-up of Entran EGAX-F uniaxial accelerometer .................... miniBIRDTM h m Ascension Technology ................................ FASTRAKTM fiom Poihemus Inc .......................................... miniBIRDTM versus FASTRAKfM .......................................... miniBIRDm sensor: mode! 800 versus model 500 ...................... Screen shot of Tremor @anrifer ........................................... Movement of hand in x direction of intention test ........................ Movement of hand in y direction of intention test ........................ Movement of hand in z direction of intention test ....................... LabVIEWTM sequence used to subtract mean fiom data ................ Movement of hand in x direction of intention test centred about zero Movement of hand in y direction of intention test centred about zero Movement of hand in z direction of intention test centred about zero Movement of hand in x direction of intention test centred about zero

......................................................... and hi&-pass filtered Movement of hand in y direction of intention test centred about zero

......................................................... and hi&-pass filtered Movement of hand in z direction of intention test centred about zero

........................................................ and high-pass filtered ........................... LabVIEWTM Auto Power Spectnim fûnction

X direction motion of sample tremor and corresponding power ........................................................................ spectnim

Y direction motion of sample tremor and corresponding power spectnun ........................................................................ Z direction motion of sarnple tremor and corresponding power spectrum ........................................................................

.................... LabVIEWRn Power & Frequency Estimate function ....................................... Deviation From Mean @FM) c w e

............... Deviation From Mean (DFM) curve for intention tremor ...................... High-pass Ntered DFM cuve for intention tremor

.................. DFM curve with area of displacement of tremor of 6.9

................. DFM curve with area of displacement of tremor of 1.4 ................... Deviation From Mean @FM) plot for sample tremor

Signed Deviation From Mean (SDFM) plot for the same tremor displayed in Figure 4.22 ......................................................

................... SDFM curve and accornpanying frequency spectrum ..................... DFM curve and accompanying kquency spectnim

.................................. Sample printout fiom Tremor Quuntij?er .......................................... Plexiglass grid: position test setup

..................... miniBIRDfM sensor in plexiglass position test sehip ... Close-up of plexiglass position test setup with miniBIRDm sensor

DeveIopment of a Hmd Tremor Quantification Device for the Measurement of Paihological Tremor vi

Figure 5.4

Figure 5.5 Figure 5.6

Figure 5.7 Figure 5.8 Figure 5.9 Figure 5.10 Figure 6.1 Figure 6.2 Figure 6.3 Figure 6.4

Cornparison of tolerance of plexiglass grid and miniBIRDTM pubfished error ................................................................ Distribution of position error ................................................ Mean error and standard deviation of measurement readings fiom

............................................................... the miniBIRDTM Entran accelerometer next to d I R D m sensor ........................ Frequency test setup with accelerometer and miniBIRDa sensor ..... Accelerometer and rniniBIRDTM sensor on tip of 'oscillator'. ...........

............. m i n i B I R D T M sensor and accelerometer mounted on &ger

............. Tremor Quantifier screen shot of simulated resting tremor ............ Tremor Banrifer screen shot of simulated postural tremor .......... Tremor Quantifier screen shot of simulated intention tremor

Tremor Quantijer screen shot of simulated intention tremor - SDFM high-pass filtered ...................................................

Devdopment of a Hand Tremor Quantification Device for the Meamremnt of Pathological Tremor vii

LIST OF TABLES

Table 2.1

Table 3.1 Table 3.2 Table 3.3 Table 5.1 Table 5.2 Table 5.3 Table 5.4

Table 5.5 Table 5.6

Table 5.7 Table 6.1

Classification of common tremors by fiequency and behavioural ..................................................................... appearance

Webster Scde for parkinsonian tremor .................................... ............................ Unifïed Rating Scale for parkinsonian fremor

........................................... Rathg scale for essential tremor Sarnple static position test data - Part one ................................. Descriptive statistics on position enor ..................................... Enor associated with measurement of various distances ................ Frequency measurements ushg miniBIRDTM and accelerometer on

....................................................................... 'oscillator' ....................... Pair t-test results for frequency test on 'oscillator'.

Frequency measurements using miniBIRDm and accelerometer on ........................................................................... finger

.......................... Paired t-test results for fiequency test on h g e r Strengths and limitations of miniBIRDm/Tremor Quantifier system

Page

13 18 18 19 70 72 76

82 83

85 85 89

Development of a Hand Tremor Quantification Device for the Measurement of Paihological Tremor viii

Chapter 1 Introduction

Chapter 1 INTRODUCTION

Hand tremor is the most common and visible symptom of Parkinson's disease. As a

result, its severity is ofien used as an indication of the ihess' stage of progression. It cm

aiso be used to assess the efncacy of phamiacological or surgical treatment.

Attempts to quanti@ the characteristics of hand tremor have occupied researchen for

over a century and although there are a number of systems that can quantiq tremor, each

saers fiom its own shortcomings whether it be prohibitive cost, insunicient accuracy,

unwieldy hardware, etc.

In 1989, Dr. Peter Ashby a neurologist at the University Health ~etwork ' approached Dr.

Tony Easty, Director of Medical Engineering, requesting a low-cost systern that could be

used to measure hand tremor in Parkinson's patients. The project was taken on by

Elizabeth Sheil, a graduate student at the institute of Biomatenals and Biomedical

~ng ineer in~~ , University of Toronto. Her Master's thesis, entitied 771e Quantification of

Hmd Tremor in Clinical Newological Assessment (1991), descnbes the construction of a

video imaging system that used CCD cameras to track the motion of an ÙiFared LED.

This motion was then analyzed with custom-written software. The system was M e r

improved by Joseph Cafazzo in his Master's thesis: Development of a Hand Tremor

Quantiifier for Chical Neurological Assessment ( 1 992).

Although the video imagîng system fÙI.filled al1 technical requirements it was comprised

of a large amount of bulky hardware including two CCD cameras, two moniton, a large

1 Toronto Western Hospital ï hen caiied the Iastitute of Biomedical Engineering

Development of a Hand Tremor Quantification Device for the Mea~urement of Pathological Tremor 1

Chapter I Introduction

box area for testing, and a cornputer. As a result of its relative non-portability it was

never implemented clinically.

This project is an attempt to revisit this clinical need by developing a relatively low-cost,

portable hand tremor quantification device that can measure pathological tremor.

Although the project specifications are identical to those of the previoiis two atternpts, the

technology applied is completely different. An electromagnetic tracking device,

miniBIRDTM fiom Ascension ~ e c h n o l o ~ ~ ' , dong with the custom-designed sohare ,

Tremor Quantzfzer. is used to measure the fiequency, amplitude, and area of displacement

of resting, postural, and intention tremor.

I Ascension Technology Corporation PO Box 527 Burlington, Vermont, USA 05402 www.ascension- tech.com

DeveIopment of a Hand Tremor Quantincation Device for the Measurement of Pathologid Tremor 2

Chapter 2 Background

Chapter 2 BACKGROUND

2.1 Parkinson's Disease

Parkinson's disease is by no means the only source of pathological tremor, but it is a

major one. It is also the quest to quanti@ parkinsonian tremor that has initiated and

driven this project. As a tesult, the system presented here has been tailored to masure

three types of tremor commonly associated with Parkinson's disease (resting, postural,

and intention) and as such it is helpful to have some general background on the disease.

Parkinson's disease is a degenerative, neurological affliction that usually occurs in later

life although occasionally may affect people as young as 30 years of age. One of the first

people to recognize parkïnsonian symptoms as a related collective group was James

Parkinson. In his 18 17 An Essay on the Shaking Palsy he describes the disease, which

now bears his name, as:

"hvoluatary tremulous motion, with lessened muscular power, in parts not

in action and even when supported; with a propensity to bend the trunk

fonvard, and to pass fiom w&g to a running pace: the senses and

intellects being uninjured." p. 1

Pathologically, Parkinson's is characterized by the deterioration of the nuclear masses in

the extrapyramidal system. It is a disorder of the basal nuclei involving degeneration of

fibres fitom the sustantia nigra. Clinical symptoms include: tremor of resting and

activated muscles, mask-like facies (Parkinson's facies), slowing of voluntary

movements, festinating gai% peculiar posture, and muscular weakness.

DeveIopment of a Hand T m o r Quantincation Device for the Mea~urernent of Pathological Tremor 3


2.1.1 Symptoms of Parkinson's Disease

The symptoms of Parkinson's disease appear g r a d d y and progress slowly. Tremor is

the most common and visible symptom of the disease. However, other symptoms can be

more disabling. For example, hypokinesia (reduced movement) or a feeling of

sluggishness may make it difficult for the penon to initiate movement such as getting up

out of a chair or rnoving fiom a standing position to walking. However, once the person

is in motion he/she is generaliy able to walk for a prolonged penod of t h e . The gait is

often shunling and there is involuntary acceleration as the penon seeks to readjust his or

her centre of gravity. Rigidity is another symptom and often strikes in the muscles of the

arms, legs, and face as the tone of skeletd muscles increases. #en this occurs in the

facial muscles it causes a charac:eristic 'rnask-like' expression. Despite the fact that

Parkinson's disease stems fiom a degeneration of brain tissue it does not adversely affect

mental cognitive capacity.

The symptoms of Parkinson's rnay hclude al1 types of tremor (Fhdley 1996) but is

mostly characterized by four types (Findley et al. 198 1 ):

1. resting tremor

3. postural tremor

3. intention tremor

4. cogwheel phenornenon

2.1.1.1 Resting Tremor

Considered to be the hallmark symptom of Parkinson's disease, resting tremor affects

about 75% of ali patients (Elble and Kolier, 1990 p.118). The tremor is observed when

Devetopmwt of a Hand Tremor Quantification Device for the Measuremeot of Pathologicd Tremor 4

Chapter 2 Back-ground

the muscles are not voluntarily activated and the body part is supported agauist gravity.

For example, in a classic display of resting tremor, the patient is seated with hisfher arm

resting on the legs and a distinct tremor begins to manifest itself.

Resting tremor usually begins on one side of the body in an upper limb before spreading

to the same-side leg d e r about 2 years (Findey 1996). The tremor can remah on this

side of the body for a number of years before the other side is affected (Findley 1996).

Manifestation is most common in the distal muscles of extremities, such as the hands and

fingers, but rnay also occur in the arms, legs, lips, tongue or jaw. Resting tremor rarely

effects the head and this distinguishes it fiom other disorders such as essential tremorl

(Findley 1996).

h its early stages, resting tremor c m usually be inhibited by voluntary activation of

afTected muscles. For example, patients may disguise resting tremor in the hand by

performing a purposehl action such as touching the head or picking up a pen. However,

this technique usually works o d y with mild tremor. As resting tremor progresses, it

becomes more continuous and does not disappear with voluntary muscle activation.

Resting tremor is most pronounced during periods of mental or physical stress and also

seerns to increase in the upper extremities when the patient is waking. In gened, tremor

is worsened by actions which distract the patient's attention.'

' Essential tremor is an idiopathic, heterogeneous group of movernent disordm or tremon. That is, the cause is unknown and this tremor is not related to other pathological tremors such as that of Parkinson's disease. This unqlained symptorn is not necessady a firnction of disability, pathophysiology, or hmdity (FindIey 1996) although 30-50% of patients have a history of essentid tlmor in tbeir f d e s ( M e , 1995 p. 165). - The physician may induce a high-stress state by asking the patient to perform a mentally chaiienging task such as counting backwards from 100 by a prime number.

Development of a Hand Tremor Quantif?caiion Device for the Measurement of Pathologicai Tremor 5


A particular form of resting tremor termed the pill-rolhg tremor is pathognomonic of

Parkinson's. A patient with this characteristic tremor can be seen rhythmically extending

and flexing hisher wrist with a grasping movement of the k g e s and a superimposed

rotational movement produced by rhythmic pronation-supination of the forearm (Elble

and Kolier, 1990, p. 1 18).

Resting tremor has been characterized by diierent sources as having a fiequency of:

4 to 7 Hz (Webster, 1968)

4 to 5.3 Hz (Findley et al., 198 1, Findley and Gresty, 1984, p. 295)

4 to 5 Hz (Capildeo and Findley, 1984, p.7)

4 to 6 Hz (Jankovic, 1987, p. 109)

3 to 5 Hz (Elble and Koller, 1990, p. 1 18)

4 to 5.5 Hz (Buckwell and Gresty, 1995, p. 148)

2.1.1.2 Postural Tremor

Postural tremor is also a very common symptom of Parkinson's disease, usually occurrîng

in the upper extremities. This tremor has a higher fiequency than resting tremor with

reported ranges of:

5.5 to 8 Hz (Findley and Gresty, 1984, p. 297)

5 to 8 Hz (Jankovic, 1987, p. 109)

5 to 12 Hz (Elble and Koller, 1990, p. 1 19)

6 to 8 Hz (Buckweil& Gresty, 1995, p. 148)

However, postural tremor usuaiiy has a smder amplitude (Findley and Gresty 1984, p.

295) than resting tremor. Its fkquency makes postural tremor dEcul t to distinguish

fkom essential trernor, which hm a range of 4 to 12 Hz (Elble and Koller 1990 p. 61), and

Development of a Hand Trexuor Quantification Device for the Measuremeat o f f athological Tremor 6


the 8- 12 Hz cornponent of nomial, always-present physiologie tremor. Postural tremor is

a symptom in 60% of Parkinson's patients and if this is the first manifestation of

Parkinson's disease without other significant symptoms it can easily be misdiagnosed as

essential tremor (Elble and Koller 1990, p. 1 1 9). Elble and Koiier ( 1 990, p. 1 19) report

than in 10 - 20% of Parkinson patients postural tremor is the only form of trernor

exhibited in the course of illness.

2J.1.3 Intention Tremor

Intention tremor, sometimes called temiinal or cerebellar tremor, occurs towards the end

of goal-directed movement. For example, in a 'touch-the-target' test the finger begins to

oscillate with increasing amplitude as it approaches its target. This type of tremor is not

exclusive to Parkinson's disease as it manifests as the result of various cerebellar injuries.

It rnay even be diagnosed as a unique and rare inherited disorder (McDowell 1971, p.

170). However, as a symptom of Parkinson's disease it may be more disabling than rest

tremor because it is caused, as opposed to calmed, by muscle activation. The tremor is

usually contùied to the han& and arms and has approximately the sarne fiequency as rest

tremor (Webster, 1968), or 3-5 Hz (Jankovic and Fahn 1980).

2.1.1.4 Cogwheel Phenornenon

A rhythmicai, repetitive alteration in resistance during passive movement of a limb about

a joint is temed the "cogwheel phenornenon". Cogwheeling has been reported to

manifest itself in two distinct fiequencies: 6 Hz and the 8 to 9 Hz band (Findey et al.

198 1). Because the upper range is similar to the fkquency range of postural tremor some

- - -

Development of a Hand Tremor Quantincation Device for the Measurement of Pathologicai Tremor 7


researchers believe that the two tremor mechanisms are related (Elble and Koler, 1990,

p. 119) while others daim a relationship to exaggerated physiologic tremor (Webster,

1968). Although cogwheel tremor is often observed in Parkinson's patients, it is not

exclusive to the disease and therefore cannot be used as the definitive evidence for a

Parkinson diagnosis.

2.1.2 Treatmeut

Pathologically, parkinsonism (the symptom complex associated with Parkinson's disease)

is the result of the stopping or slowing down of dopamine activity in the corpus striatum

of the brain. This results fiom degeneration that occurs in the dopaminergic nigrostriatal

pathway. Normally, the two opposing neurotransmitters, dopamine and acetylcholine,

are balanced, but when dopamine is depleted, the overactivity of acetylcholine produces

the symptoms of Parkinson's disease.

2.1.2.1 Anticholinergic Dnigs

For mild symptoms in patients with minor fùnctional impairment, anticholinergic dmgs

such as trihexylphenidyl (Artane) or antihistamines with anticholinergic properties, such

as diphenhydramine (Benadryl), c m be used effectively. These types of agents block the

muscarinic effects of acetylcholine in the central nervous system.

Cornmon side effects of anticholinergics include: dry mouth, constipation, paralysis of

accommodation in the eye, and urinary retention. Less cornmon but more severe

reactions may include memory loss and serious states of confusion in elderly patients,

particularly those with dementia (Elble and Koller, 1 990: 1 27). These side effects usually

disappear within several days of treatment termination.

-- --

Development of a Hand Tremor Quantifidon Device for the Measiwment of Paîhological Tremor 8


Most patients receive anticholinergic dmgs early in their treatment, foilowed eventually

by levodopa or dopaminergic agonists. Cessation of antichoiinergic treatrnent should be

done by tapering the dosage as opposed to rapid withdrawal because this can result in

M e r exacerbation of symptoms, especially tremor (Elble and Koller, 1990).

2.1.2.2 An tidepressants

Tricyclic antidepressants such as imipramine or amitriptyline cm also be effective for the

treatment of mild Parkinson symptoms because they block the re-uptake of dopamine

fiom the nerve synapses and also have anticholinergic effects. However, it is not ciear if

these drugs improve motor signais directly or only have an indirect effect through the

treatment of aaviety and depression.

2.1.2.3 Levodopa (L-dopa)

In patients with more severe symptoms, the augmentation of dopamine levels in the brain

is required. This is often done with the dmg levodopa (L-dopa), a breakthrough in the

treatment of Parkinson's disease. Levodopa crosses the blood-brain barrier and is

converted to dopamine by decarboxylation, thus partially correcting the dopaminergic

deficit within the striatum. Levodopa is the most effective treatment for the entire range

of Parkinson symptoms. However, it does not always produce consistent results,

sometimes entirely suppressing tremor in one patient but not another without apparent

explanation. It has a particulariy bad track record for easing resting tremor.

The decarboxylation reaction may also occw in penpheral tissues causing adverse

reactions such as cardiac stimulation (tachycarida and arrhythmias), confusion, nausea

and vomiting.

Development of a Hand Tremor Quantincation Device for the Measurement of PathoIogical Tremor 9


2.1.2.4 Sinemet

A newer d m g than levodopa, called Sinemet, combines the chemical carbidopa with

levodopa. Carbidopa works to inhibit production of dopamine outside of the brain thus

lessening the side effects associated with the use of levodopa alone. Sinemet

occasionally has only a limited span of effectiveness in some patients and hence is

usuaiiy reserved for severe cases.

2.1.2.5 Dopaminergic Agonists

Dopaminergic agents such as bromocriptine, pergoiide, and lisuride are also used to treat

Parkinson's disease. Although these drugs have not been shown to be any more effective

than levodopa for resting tremor, occasionally a patient responds dramatically to this type

of dmg.

Dopaminergic agonists are often used in combination with levodopa and produce similar

side effects as those associated with levodopa.

2.1.2.6 Beta-Adrenergic Blocken

Many patients with Parkinson's disease experience postural trernor that can be treated

with beta-adrenergic blockers such as propranolol or nadolol.

2.1.2.7 Thalamotomy

Thaiamotomy is a stereotactic surgicd operation that destroys specinc ceils in the brain

whose degeneration is Linked to Parkinson's disease.

-- pp

Development of a Hmd Tremor Quantification Device for the Measurement of Pathologicai Tremor 1 O


Thalamotomy is usually perfomed unilaterally and produces a reduction in resting

tremor in the contralateral extremities. The complications of thalamotomy include

hemiparesis (partiai paralysis on one side), seizures, dysarthna (imperfect articulation of

speech), dystonia (sustained muscle contractions), limb ataxia (failure of muscuiar

coordination), confusion and hemidysesthesia (disorder of sensation affecthg only one

side of the body). Bilateral thalamotomy has the increased risk of postoperative

confusion and disorientation and also may result in dysarthria, hypophonia (weak voice)

and dysphagia (difficulty swallowing) (Goldman and Kelly, 1 995 p. 554).

2.2 Classification of Tremor

Tremor is simpl y defïned as an involuntary , approximatel y rhythmic, oscillatory

movement of a body part The amplitude of tremor is often so srnaIl that it cm only be

measured with a highly responsive sensor. In other cases, such as with Parkinson's

disease, tremor may be quite prominent.

Tremor can be divided into two very basic groups: physiological and pathological.

Physiological tremor is a ubiquitous, asymptomatic (normal) shaking that affects

everyone and results fiom the activity in individual motor units. It is generally a low

amplitude (< 0.5 mm peak-to-peak, Elble et al. 1990), hi& fiequency movement

(between 8 and 12 Hz, Findley 1996) that is barely visible to the eye. People are rarely

aware of this tremor and it may only become noticeable when tryhg to complete a fine

motor task such as threading a needle. In certain cases such as fear or excitement, the

tremor might increase in amplitude to such a degree that it interferes with simple actions

such as writing or holding a cup (Findley, 1996).

- -- -- -

Development of a Hand Tremor Quantincation Device for the Measurement of Pathological Tremor 1 1


Pathological tremor, on the other hand, is that which arises as a result of a disease or

disorder, usually of the central or peripheral nervous system. Generally, if a tremor is

clinically visible and persistent it is consider pathological (Findley, 1996). Tremor itself

is not a disease, but rather a symptoml. These tremors always involve rhythmical

contractions of muscle groups (Findey, 1996 j which manifest in periodic, that is, roughly

sinusoidai, movement about an axis.

2.2.1 E tiology

Tremor c m be organized or classified according to a number of criteria. It has been

suggested that it would be useful to group tremor according to etiology. However, it is

very difficult to associate a specific type of tremor with a particular disease because many

tremors resulting fiom different diseases exhibit similar characteristics. Furthemore, a

disease of the nervous system may result in more than one type of tremor.

2.2.2 Amplitude, Waveform, Frequency

The rhyihmic nature of tremor suggests characterization by amplitude, waveform or

fiequency. Amplitude, while important in tems of syrnptoms, does not provide enough

unique information for categorization. Amplitude of tremor c m be influenced by a wide

range of physiological, psychological, and environmental factors and even under

controiled conditions displays considerable variability (Findley 1996). Tremor waveform

is also not very useful since there is no waveform that is unique to a paaicular disease.

' Essentiai tremor is an exception. --

Development of a Hand Tremor Quantincation DeMce for the Measurement of Pathotogicai T m o r 12


Frequency of tremor is its most stable parameter (Buckwell and Gresty, 1995: 148) and is

often used for general classifications as can be seen in Table 2.1.

Table 2.1 Classification of common tremors by fiequency and behavioural appearance Frequency Disease processAocus of lesion Behavioural characteristics

1 2.5 -3 -5 Cerebellarhrainstem P o s ~ e t i c

Multiple sclerosis PostutaVkinetic Alcoholic degeneration PostutaVkUietic Post-braumatic PosturaVkinetic

4 - 5 Parkinson's disease Rest Cerebellar disease PosturaVkinetic Rubral Rest/posture/movement/kinetic Drug induced Rest

5.5 - 7.5 Essential tremor PosturaVkinetic Clonus Parkinson's disease Drug induced PosturaVkinetic

8 - 12 Enhanced-physiological tremor Postural/kinetic Drug intoxications Essential tremor Cerebrocortical

Source: Fuidey 1996

However, although certain fiequencies are more typical of individual diseases than

others, there is considerable overlap and that makes classification by fiequency difficult.

2.2.3 Pharmacological Response

Another attempt to classify tremor is based on pharmacological response. Some diseases

respond particularly well to specifk dnig therapies. For example, Parkinson's disease

responds weli to dopaminergic dmgs and a response to smaii amounts ofalcohol is faKly

indicative of essential tremor (Findley 1996). However, most dmgs used to treat tremor

lack specinci~ (Findley 1996). AU dmgs with sedative action will dampen tremor to

Developlnent of a Hand Tremor Quantincation Device for the Measurement of Pathologicai Tremor 13


some degree. As a result, characterization by h g response is not specific enough to be

particularly useful.

2.2.4 Appearance and Behavioural Characteristics

The lack of any other clear distinguishing feahire leads the way for the most commonly-

used classification systern for tremor: a basic system that categorizes tremor based on its

a p p e m c e and behavioural characteristics. The most cornmon tremors are described

below. These definitions were drafted at the initiai meeting of the Tremor Investigation

Group (TRIG) in Houston, Texas, in December 1990 as reported in FUidley & Koller,

1995 (p. 1 - 2) and Findley, 1996.

2.2.4.1 Resting Tremor

This tremor is defhed as that which occurs when the muscles are not voluntarily

activated and the body part is supported against gravity.

2.2.4.2 Action Tremor

This is tremor that occurs on the voluntary contraction of muscles and includes postural,

kinetic, and isometric trernor.

2.2.4.3 Postural Tremor

Men voluntariIy maintaining position against gravity the tremor that may result is

termed postural tremor. This type of tremor can be seen when the arm is held in an

outstretched position. That is, the muscle must be activated in order to keep the ann in

this position.

Development of a Hand Tremor Quantikation Device for the Measurement of Pathologicai Tremor 14


2.2.4.4 Kinetic Tremor

This is the tremor that occurs during any sort of movement. Two subsets of b e t i c

tremor include intention tremor and task-specific kinetic tremor.

2.2.4.5 Intention Tremor

Also temed 'terminal tremor', intention tremor exhibits progressive wonening towards

the end of a goal-directed movement such as touching a target.

2.2.4.6 TaskSpecific or Occupational Kinetic Tremor

This tremor occurs or wonens during the carrying out of a highly specific, skilled

movement. An example of this would be writing tremor.

2.2.4.7 Isometric Trernor

Isometric tremor is exhibited as a result of muscle contraction against a @id, stationary

object.

2.2.4.8 Essential Tremor

This is an idiopathic, heterogeneous group of movement disorders or tremors. That is,

the cause is unknown and this tremor is not related to other pathological tremors such as

those of Parkinson's disease. This unexplained symptom is not necessarily a fûnction of

disability, pathophysiology, or heredity. (Findley 1996)

2.2.4.9 Static Tremo r

Static tremor is a confushg t e m as it is used by different researchers to denote either

resting or postural tremor. It WU not be used in this text.

Deveiopment of a Hand Tremor Quantification Device for the Measurenient of Paîhologicai Tremor 15


1 Physiological 1 1 I

i 1 j Pathological 1 1

Figure 2.1 Tremor classification by appearance and behaviourai characteristics

Development of a Hand Tremor Quantification Device for the Measurement of Pathological Tremor 16

Chapter 3 Measurement of Tremor

Chapter 3

MEASUREMENT OF TREMOR

3.1 Review of Literature

Tremor lends itself well to measurement because of its rhythmic and oscillatory

characteristics. An ideal tremor measuring device would be a low-cost, accurate,

electronic device that quantifies tremor characteristics such as fiequency and amplitude.

Several different electronic sensors are used for this purpose but since none have been

perfected, subjective rating scaies are still widely used in place of quantitative

measurements.

3.1.1 Subjective Assessrnent

3.1.1.1 Tremor Rating Scales

A number of tremor rating scaies have been developed and used but none has become a

univenally accepted standard. The sensitivity of these scales is insufficient to mesure

slight changes in tremor amplitude or fiequency. Nevertheless, because of their

simplicity these tests continue to be widely used in the clinical assessrnent of tremor

symptoms.

A few of the most common scales are listed in Table 3.1 - 3.3. '

' Note tfiat one of the most popuiar rating scales for Parkinson's disease, the Hoehn and Yahr Scale, îs not included because it is not specific to the measurement of tremor but instead rates the severity of the disease as a whole. This sale can be found in Appendix A.

-- -

Development of a Hand Trernor Quantification Device for the Measunment of PaîhoIogical Tremor 17

Chapter 3 Measurernent of Tremor

Table 3.1 Webster Scale for ~arkinsonian tremor 1 O = 1 No detectable tremor found. 1

1 =

2 =

Table 3.2 Unified Ratine Scale for ~arkinsonian tremor' Version 2.0 - Decernber 1985

Less than 1 inch of peak-to-peak tremor movement observed in lirnbs or head at rest or in either hand while waiking or during h g e r to nose testing. Maximum tremor envelope fails to exceed 4 inches. Tremor is severe but not constant, and ~atient retains some control of the hands.

3 =

- -- - - -- -

Tremor (as art of assessrnent of Activities of Daiiv Living)

Tremor envelope exceeds 4 inches and is constant. Tremor is constant and severe. Patient cannot get free of tremor while awake unless it is a pure cerebellar type. Writing and feeding are impossible.

O = Absent 1 = Slight and infrequently present 2 = Moderate; bothersome to patient 3 = Severe; interferes with many activities 4 = Marked; interferes with most activities

Tremor at Rest (as Motor Examination)

Source: Webster 1968

O = Absent 1 = SLight and aequently present 2 = Mild in amplitude and persistent; or moderate in amplitude but only

intermittentiy present 3 = Moderate in amplitude and present most of the t h e 4 = Marked in amplitude and present most of the time

Action or Postural Tremor of Hands (as Motor Examination) O = Absent 1 = Siïght; present with action 2 = Moderate in amplitude; present during action 3 = Moderate in amplitude with posture holding as well as action 4 = Marked amplitude; interferes with feeding

Source: Koller 1 987 : 482-485 N e w versions of this rating scde are termed: Unifïed Parkinson's Disease Rathg S d e (LTPDRS)

- - - - - - -

~ e v e l o ~ m ~ of a Hand Tremor Quantification Device for the Measurement of Pathological Tremor 18


Table 3.3 Rating scale for essential tremor

1 Right Leît Hand: resting

postural kinetic intention

Finger (iso lated) Arm Les

Jaw

Voice

Tremor scale: O = absent: 1 = mild; 2 = moderate: 3 = severe

Head no-no yes-yes cornplex

Source: Elble and Koller 1990, p. 12

C h c a l assessrnent of tremor using these scales, before and after treatment, can be used

to determine whether the therapy has been successful in calming the tremor.

Other methods of measuring tremor include rating tasks such as handwriting and drawing

Archimedes spirals'. Handwriting samples are ranked on the basis of clarity and

smoothness and spirals are ranked according to tremor amplitude and time taken to

accomplish the task. These evaiuation protocols s a e r fiom the fact that they require the

subject to hold a pen in hiskier hand. Only tremor that is superimposed on hand motion

during the act of writing or drawing can be measured. This precludes the ability to

rneasure the most common tremon of Parkinson's disease: resting, postural, and

intention.

m e r general testing protocols for measuring band tremor include assessing the ability to

drink fiom a g las without spilling, timed h g e r tapping, and pegboard tasks (Elble &

Koiler 1990, p. 1 1- 12). The difliculty with these action tests, aside fiorn their

' Archimedes spiral:

pppppp

Development of a Hand Tremor Quantification Device for the M m e n t of Pathologid Tremor 19


subjectiveness, is that they may require excessive rnotor and cognitive ninction. As a

result they may not be a pure measure of tremor. (Elble & KolIer 1990, p. 1 1)

3.1.2 Objective Assessrnent

The diniculties inherent in subjective assessrnent of tremor intensity have led researchers

to many attempts at evaluating tremor in some objective, quantifiably measurable

manner.

3.1.2.1 Tambour

The earliest attempts to measure tremor made use of a tambour applied to a Limb. The

limb movement resulted in displacement of this receiving tambour which was affixed to

the limb under investigation. The receiving tambour was commonly attached via mbber

to a second recording tambour whose lever was connected to a rotating cim. A pen set

against the d m made a record of the limb movement. Several early researchers

describe the set-up of their experiments used to investigate muscle contraction and tremor

(Horsley & Schafer 1886, Wolfenden & Williams 1888, Eshner 1897).

This early method was satisfactory in many respects, particularly in its tirne. However,

the sensitivity and accuracy of a variety of newer technologies greatly surpasses that of

the ancient tambour.

3.1.2.2 Optical Methods

Other early researchers opticdy magnined the displacement of light caused by iimb or

finger movement. This Somat ion was transduced by a photo-electric cell and

Development of a Hand Tremor Quantincation Device for the Measurement of Pathological Tremor 20

Chapter 3 Mesurement of Tremor

amplined. The output of this was then fed to a moving-coii pen or oscilloscope (Jasper

and Andrew 1938, Graham 1945, Cooper et al. 1957).

Because these methods could only record srnall movements within a lirnited space

restriction they were only used for poshiral and resthg tremor.

By far, the most widely used method of quantifjmg hand tremor is accelerometry. Many

researchers, dathg back over a hundred years, have used this rnethodology to measure a

variety of body tremors (Boshes 1966, McAllister et al. 1985, Ghika 1993, Timmer et ai.

1996). Uniaxial or triaxial accelerometers are widely available. Tremor is rarely, if ever,

a unidirectional movement (Elble & Koller, 1990) and since uniaxial accelerometers only

measure tremor in one dimension they have serious limitations Triaxial accelerometers

are now becoming more popular as their cost and size decrease. Despite this, the

majority of researchers in this particular field have used uniaxial accelerometers with

only a few using multidimensional sensors (Jankovic and Frost, 198 1, Salzer, 1972).

With respect to measuring tremor, miniature accelerometers have the advantage of being

quite srnall and iight-weight so they do not have a dampening affect on the trernor. In

addition, the sampling rates offered by some accelerometers are far greater than one

would even need to measure motion up to 20 Hz. Furthemore, accelerometers are much

more sensitive to high fiequency vibrations than displacement tramducers (Scholz &

Bacher, 1995, p. 295, Gresty and Findey, 1984 p. 17).



These attributes suppori the use of accelerometers for determining the fiequency

component of tremor. However, there are a number of chical tests that require

information about the position of the hand. For example, a patient may be asked to trace

a certain shape with a sensor on hisher hger . Amount of deviation fiom the trace shape

indicates severity of tremor. Positional information is oot easily obtained fiom

acceierometer data. The amplitude of tremor cannot be determined and it has been noted

that the tremor a m p h d e denved fiom acceleration does not correlate well with the

functional disability experienced by the patient (Spyers-Ashby, 1997, p. 36). On the

other hand, absolute amplitude of tremor and the impairment and disability it can cause

are of interest to the patient and clinician (Biickwell and Gresty, 1995, p. 148).

3.1.2.4 Digitizing Ta blets

Digitizing tablets have also been used by researchers (Elble et al. 1990, Pullman 1998) to

quanta trernor. In this approach, a digitking tablet is normally linked to a computer via

an RS232 serial connection and specimens of handwriting or Archimedes spi& are

analyzed. What was on paper a subjective judgement of clarity and smoothness, can now

be quantified in the extracted amplitude and fiequency information of the superimposed

tremor. Commercial digitizen can have resolutions that range fhm 78.7 to 787 ünes per

centimetre (0.127 mm to 0.0 12 mm), accuracies of 0.25 mm, and data rates of 200 points

per second (Elble et al., 1990). These tablets are a good alternative to subjective rating

scales because they provide some quantitative rneasure of tremor at a relatively low cost'.

However, they can only be used to measure the tremor that accompanies tasks such as

' As of this writing a 4" x 5" Wacom Intuos digitking tablet was priced at $200 US [Accuracy: iO.25 mm, Resolution: 200 Lines per mm, Max data rate: 200 points per second)

Development of a Hand Tremor Quantincation Device for the Measurement of Pathologicai Tremor 22


writing or drawing with a pen in hand. Resting tremor, which is the most prevalent

symptom of Parkinson's, cannot be measured in this manner.

3.1.2.5 Optoelectric Imaging Systems

The gold standard of three-dimensional position tracking devices are optoelectric irnaging

systems, such as the OPTOR4K (Northem ~igital)', which use CCD c m n s to

determine the location of h f k e d markers (LEDs). The OPTOTRAK in particular

provides an accuracy of 0.1 mm and a sampiing rate of up to 3500 Hz. Three CCD

cameras with Light sensitive pixels measure the amount of energy striking each pixel to

determine the position of the light source. Although the accuracy of these systems is

enviable, their price tag makes them out of reach for the individual clinician. The cost

range of such systems is in the tens of thousands of dollars. In addition, the equipment is

fairly large (the CCD unit stands about a metre high) and a direct line-of-sight must be

maintained between the idiared LED and the cameras.

3.1.2.6 Surface Electromyography

Surface electromyography @MG) quantifies the muscular activity causing tremor. As

such, it is not a direct measure of tremor itself and is most ofien combined with another

measurement device (e.g. accelerometer) in order to investigate the way in which motor

unit activity and tremor are related.

' Nonhem Digital hc 103 Randaii Dr. Waterloo, Ontario, Canada N2V lC5 www.ndigital.com Development of a Hand Tremor Quantification Device for the Measurement of Pathological Tremor 23


3.2 Tremor Characteristics

In order to choose an appropriate measurement device it is important to understand the

characteristics of what is king measured. For example, when measuring kinetic tremor a

device is required that is sensitive to both tremor and voluntary motion. However, when

mesuring resthg tremor, voluntary movement is not important. The best recording

device is that which has signal-response characteristics that are similar to the signal

properties of the tremor.

3.2.1 Waveform

Tremor lends itself well to measurement because it is a roughly penodic, sinusoicial

signal. Although the system presented here investigates motion in three dimensions it is

instrumental to consider the one-dimensional characteristics of tremor. In its shplest

form, a tremor can be expressed as:

d = ~ s i n ( 0 t ) [Eqn. 3.11

Where d = positional displacement; A = peak amplitude; t = tirne and o = firequency of

oscillation (rads). Although tremor is never perfectly shusoidai, the Fourier theorem

states that the signal c m be analyzed into a series of sine waves of appropriate amplitudes

and fiequencies.

The first derivative of equation 3.1 provides the velocity of movement:

v =Aocost [Eqn. 3-21

Note that the peak velocity (when cos t = 1) is simply the peak amplitude of displacement

multiplied by the fkquency of oscillation in radians per second.

Development of a Hand Tremor QuantiiIcation Device for the Measurement of PathoIogical Tremor 24


The second derivative of equation 3.1, or the Est derivative of equation 3.2, provides the

acceleration of movement:

[Eqn. 3.31

3.2.2 Frequency

Although there is some debate about whether it is possible to distinguish between

physiological and pathological tremor based on fiequency alone, there is no doubt that

fiequency is one of the most important measures of tremor (Deusch1 et al. 1996).

Although the fkequency ranges for pathological and physiological tremor overlap, some

conclusions can be inferred fkom a given fiequency measurement. Ln 1996, Deuschl et al.

measured the fkequency distribution of hand tremor for normal controls, patients with

Parkinson's, and patients with essential tremor. Their work showed that physiological

tremor clearly fits between 6 and 11 Hz, whereas pathological tremor (essential and

parkinsonian) have significantly lower peak fiequencies between 4 and 10 Hz.

Regarding the 6 Hz breakpoint, almost none of the normal subjects exhibited a tremor of

under 6 Hz; 25% of patients with essential tremor exhibited a peak fiequency of 6 Hz or

under; and 65% of Parkinson's patients had a tremor equal to or lower than 6 Kz. The

conclusion fkom this is that although fiequency may not be enough to completely

distinguish between pathological and physiological tremor it plays a signincant role and

is therefore an important panuneter of tremor.

The issue in terms of assessing the benefit of treatment (i.e. phannacologicd or surgical)

is whether it subdues the tremor and by how much. In this instance it is not a matter of

diagnosing an illness or type of tremor. Thus the question related to kquency is: Has

- -

Development of a Hand Trenior Quantification Device for the Measunment of Pathological Tremor 25


the fiequency of the tremor become more 'normal'? That is, has the Wemor nequency

moved up into the 6-1 1 Hz band?

Although tremor fiequency does fluctuate within the penod of a day (see Section 3.2.4

below) it does not appear to fluctuate over moderate periods of t h e . That is, al1 things

being equai ie.g. level of stress, rime of day, amount of cafi?eine consumedj a person's

tremor does not change sigmfïcantly ftom day to day. Data taken over a 3-&y period

have shown that tremor fiequency is stable in patients with Parkinson's disease and over a

penod of 5 years there is only a slight decrease in tremor fiequency of less than 2 Hz

(Deuschl et al. 1996). As a result, a change in fiequency of tremor after surgical or

pharrnacological treatment wouid Likely be an indication of a treatmeot's efficacy.

3.2.3 Amplitude

The amplitude of tremor is not appreciably helpful in differentiating between various

types of pathological tremor but can distinguish between pathological and physiological

tremor. Patients with pathologicd tremor generally have much higher tremor amplitudes

than nomal subjects. Furthemore, the absolute amplitude of tremor and the impairment

that accompanies it can be a very important factor for both clinician and patient

(BuckweLl and Gresty, 1995, p. 118).

3.2.4 Long-Term Tremor Measurement

Most of the studies conducted to measure pathological tremor have concentrated on

tremor exhibited within a very short tirne frame, usually a few minutes. However, it

pp -- - - - - - - - -- -

Developrnent of a Hand Tremor Quantification Device for the Measurement of Pathologicai Tremor 26

Chapter 3 Measmement of Tremor

should be noted that trernor amplitude does undergo diunial fluctuations (Elble and

Koiler, 1990, p. 24).

Without takllig into consideration tremor fluctuations over the course of a day, it is

àiflicult to assess the true disabling nature of the tremor. Mild tremor that is consistent

over the course of the day cm be as debilitating as severe tremor that oniy manifests itself

occasionally. In order to account for these variables, some researchers require subjects to

peIform trernot enhancing tasks (e.g. mental arithmetic, "Stroop" test1) in order to record

the maximum amplitude tremor possible (Elble and Koller, 1 990).

ûther researchers have attempted to measure tremor over extended periods of time in

order to more accurately assess disability (Smeja et al. 1999, Spieker et al. 1998).

Because d ima l fluctuations are so difficult to measure, their effect should be taken into

account by experimental control: taking measurements for the same length of time and at

the same time of day.

3.3 Selection of a Measurement Device

The eventuai choice of Ascension's mlliiBIRDm electromagnetic tracking system for the

application of hand tremor quantification came only after the evaluation of a number of

different systems. The technologies considered are bnefly descnbed below.

' h the Stroop test the patient is presented with words - names of common colours (mi, yeilow, green, blue). Each word is printed in a coloured ink that ciiffers tiom the word-name. For exampIe, the word "Yellow" might be printed in blue ink The patient is asked to name the colour of the inks in which each word is wina.. This requires an inîeUectu;al effort because reading is a more over-Iearned response than colour naming and therefore the patient has to inhibit the dominant tendency to say the word (Gresty et al. 1984, p. 323).

- - - - -- -

Developrnent of a Hand Tremor Quantification Device for the Measmernent of Pathologiçal Tremor 27


Interest in revisiting the idea of developing a hand tremor quantification system came

with the accidental discovery of a wireless, 3D tracbg RingMouse. See Figure 3.1.

Figure 3.1 : Pegasus RingMouse

This product is made by Pegasus Technologies ~ t d ' . (Holon, Israel) which markets the

device as a wireless joystick (the RingMouse is mounted in a handle) for use in computer

games such as Doomm or QuakeTM. It generates x, y, z coordinates in real time using

bot , &ed and ultrasonic signals. Two ASICs (Application Specific Integated

Circuit) are incorporated into a receiving unit that is mounted on the computer monitor.

The first ASIC includes signai processing software aigorithms and performs reai-tirne

' Pegasus Technologies Ltb MerkaPm 2000. 5 Hazoref St Hoion, h e l , 58856,. www.pegatecbcom Development of a Hand Trernor Quantification Device for the Measurement of Paîhological Tremor 28


calculations while the other contains condensed signal processing hardware. Ultmonic

signals are transmitted fiom the wireless, mobile RingMouse to the receiving mit. Using

DTO A (DifTerential Times Of Amval) technology, the receiving unit calculates the

location of the RingMouse by use of tnangulation calculations. The buttons on the

RingMouse transmit information to the receivuig imit via infriired signals. In addition,

because the system's power supply is less than 10 mA, power can be drawn directly fiorn

the cornputer's serial port and no extemal power supply is required.

The RingMouse appeared to be an excellent option because of its low cost (475 US),

light weight, and accuracy. However, it had a maximum sampling rate of 50Hz

according to the manufacturer's specifications. Furthemore, practical experimentation

was only able to c o n h a sampling rate of 20 to 30 Hz. This is inadequate for

measuring signals up to 20 Hz. Initial communication with Pegasus regarding a

customized version of the RingMouse with a higher sampling rate appeared promising.

However, the pnce for the design alterations as quoted by Pegasus was prohibitive and

the idea was abandoned.

Mer the RingMouse technology was deemed unsuitable, an investigation was launched

into alternative measurement systerns. As mentioned earlier, the majority of the work

done in haod tremor quantification has used accelerometrîc technology. An extensive

literature review was undertaken concurrently with a survey of miniature, triaxial

accelerometers on the market. Two Merent accelerometea were brought into the lab for

Development of a Hand Tremor Quantification Device for the Measurement of Pathologicai Tremor 29


assessment: Brüel & Kjær's model 4507 and Entran's model EGAX-F. The Entran

accelerometer is shown in Figure 3.2.

Figure 3.2: Close-up of Entran EGAX-F miaxial accelerometer

Both accelerometers were uniaxial but gave an idea of the accelerorneters' response. In

the case of the Entran EGAX-F, two uniaxial accelerometers were mounted perpendicular

to each other to obtain information about the motion in both the x and y directions. The

accelerometers' response was excellent and the decision appeared only to hinge on the

choice of a suitable Light-weight, miniature, triaxial accelerometer that met al1

requirements. However, in the end this approach was also abandoned. This decision was

dtimately made based on the accelerometer's data output. Although accelerometers

- - --

Development of a Hand Tremor Quantification Device for the Measurement of Pathologicd Tremor 30


provide excellent and accurate acceleration data, which is sufncient to obtain tremor

fiequency, the amplitude provided is that of acceleration. Amplitude of acceleration is

not a usehi parameter in measuring tremor. Amplitude of tremor, a required parameter,

c m be theoretically, but not practicaiiy integrated fiom acceleration data.

3.3.3 Electromagnetic Tracking

Electromagnetic tracking technology proved to be the optimal solution to the hand tremor

measurement dilemma. The positional information of a small receiver unit with respect

to a magnetic coi1 transrnitter is relayed to an electronics system which is typically

comected to the cornputer via a s e r d port (RS232 comection). Two electromagnetic

tracking systems were evaiuated in this case. The first was the miniBIRD~1 by

Ascension ~ e c h n o l o ~ ~ ' (Figure 3.3) and the second was the FASTRAKm fiom

Poihemus hc2. (Figure 3.4).

The two systems use virtually identical technology and are very similar in physical

appearance. See Figure 3 S.

' See Appendk B for complete specifications. ' Polhemus hcorporated. 40 H d e s Drive P.O. Box 560 Colchester, VT, USA 05446 www.poihemus.com

- - . -. . - -

Development of a Hand Tremor Quantification Device for the Measurement of Pathological Tremor 3 1

Chapter 3 Measurerneut of Tremor

Figure 3.3 rniniBRDm fiom Ascension Technology

Figure 3.4 FASTRAKm fiom Poihemus Inc.

Development of a Hand Tremor Quantincation Device for the Mea~ufement of Pathological Tremor 32

Figure 3.5 : miniBIRDM venus FASTRAKTM

The main difference between the two systems is that the FASTRAKW is an AC system

whereas the miniBIRDm uses DC technology. A complete cornparison c m be found in

Appendix C. The critical differences between the two systems are sensor sue, sampling

Eequency, susceptibility to metdlic distortions, and cost.

The miniBIRD'sm 18mm x 8mm x 8mm receiver is smaller and lighter than that of the

FASTRAKT One of the major considerations in measuring tremor is that the sensor

size and weight not dampen the actual tremor. As such, it is important that the sensor be

as s m d and iight as possible. In addition, Ascension Technology is currently developing

an even smaller sensor (IOmm x 5mm x 5mm) in their miniBIRD~ model500 which

will be implemented into this system when in cornes on the market in the fd of 2000.

See Figure 3.6.

Development of a Hand Tremor Quantincation Device for the Measuremmt of Pathologicd Tremor 33


Figure 3.6: miniBIRDm sensor: model 800 versus model 500

Another technical consideration was the miniBIRD's maximum sampling rate of 144 Hz

which was supenor to the FASTRAK'sTM 120 Hz. Also, the DC magnetic technology

used in the rniniBLRDfM is reported to be Iess susceptible to metallic distortion than the

AC technology used in the FASTRAKTM (Milne et al. 1996). The final deciding factor

was price. At a cost of over one and a hdf times that of the miniBIRDTM, ihe

FASTRAKm was not priced competitively. Its higher pnce likely has to do with the four

channels that it provides versus the single channei that the miniBIRDfM offers. If four

channels were required it would defmitely be more cost effective to purchase a single

FASTRAKTM versus four single-channel miniBIRDsTM. However, this application only

requires one measurement channel and this is provided by the miniBIRDThf at a lower

cost.


Chapter 4 Methodology

Chapter 4

METHODOLOGY

4.1 Description of Technology : rniniBIRD-

The tracking device used to measure tremor motion is the miniBRDm Model 800 fiom

Ascension Technology. The rniniBLRDTM is based on the same technology as

Ascension's main product, the Flock of BudsTM (FOB), except that with sensor

dimensions of 18- x 8 mm x 8mm it is the smallest probe that Ascension makes' and

is specifically designed for biomedical applications.

The miniBIRDm memures the real-time position and orientation (6 degrees of fieedom)

of the receiver (sensor) with respect to a transrnitter using pulsed direct curent magnetic

fields. It is made up of four main components: the transmitter, receiver, electricai unit,

and power supply. See Appendk B for complete specifications. The transmitter contains

three coils mounted orthogondly about a cubic core. Electrical circuitry within the

transmitter sends puises of direct current ihrough each of the three tnuismitter coils in

tum and this generates an elecûomagnetic field. Each receiver also houes three

orthogonal coils which measure the respective components of the magnetic field in which

the receiver unit is placed.

Several researchers have tested Ascension's FIock of BirdsTM and concluded that it is

appropriate for various biomechanicai measurements (Mihe et al. 1996, Bottlang et al.

1998, Mesken et al. 1999, Bottlang et al. 2000).

Ascension Tecimology is ctarently working on the miniBIRDm Model 500 which wül have sensor dimensions of 10 mm x 5 mm x Smm (See Section 3 3 3 )

Development of a Hand Tremor Quantification Device for the Measurement of Paîhological remo or 35

Mihe et al. (1996) conducted an investigation into the accuracy of the Flock of BirdsTM

based on its optimal operating range and the degree to which metal interfered with the

electromagnetic signai. Their study concluded that the optimal operation zone (that

which exhibited the smaliest positional error: < 2%) was within a trammitter-to-receiver

separation range of 22.5 - 64.0 cm. In addition, for small step positional increments (<

2.5 cm) the device was sensitive enough to obtain a resolution of 0.25 mm. Angular

motion could be resolved to O. 1". These results were better or equai to the manufacturer's

daims of accuracies of 2.5 mm RMS and 0.5" RMS averaged over the translationai range

and resolutions of 0.75 mm and 0.10" at 30.5 cm.' Furthemore, it was shown that only

rniid steel (a cylindx-ical piece 12 mm in diameter and 125 mm in length) exhibited

significant intefierence on the data (other metals tested were titanium, stainless steel,

cobalt chrome, and aluminum), particulariy when placed next to the receiver (at 6 mm

from the edge). Overall, the device was deemed to be a useful tool for a variety of

muscuioskeletal research investigations.

Bull et al. (1997) repeated Milne et d.'s work co-g the optimal operating range but

claimed the positional accuracy to be an order of magnitude better at large step sizes.

Their explanation was the fact that the Flock of Birdsm maintains the strength of the

magnetic field at the receiver (sensor) by stepping up the trammitter power as the

receiver is moved m e r away fkom the transmitter. Transients during this process

adversely affect the system. However, by using a power supply with a higher ratiq than

' Note tha< the latest generation of b o t . the FOBW and the miniBIRDRL daim accuracies of 1.78mm 1 O.SO RMS and resolutions of 0.5 mm / 0.1" at 10.5 an

Development of a Hand Tremor Quantification Device for the Measurement of Pathoiogicai Tremor 36


that supplied by the vendor, Bull et al. were able to obtain smaller enors at the extreme of

transmitier to receiver separations.

Bottlang et al. (1 999) performed similar venfication tests with comparable results. They

determined that the main source of data distortion was randorn noise and not systernatic

error ( e g distortion &om ferromagnetic objects, calibration erron of the receiver coils).

ûther researchers, namely Meskers et al. (1999) and Bottlang et al. (2000), used the

Flock of B i r d s T M for upper body kinematics (shoulder and elbow motion respectively)

and concluded that it was a useful tool.

4.2 Serial Interface

A software handshaking RS232 cable is used to connect the miniBIRDm to the host

computer which captures the data acquired by the miniBirdTM. Only pins 2,3 , and 5 of

the 9-pin interface connector are required for communication.

Pin RS232 Siaa l Direction - Description 2 Receive Data BUd to Host Serial data output fiom the BW to the host 3 Transmit Data Hoa to Bird Serial data output fiom host to Bird 5 Signal Ground Signal Reference

4.3 Hardware Configuration

The host computer used in this setup has a Pentium II', 400 MHz processor with 64 MB

RAM, and the Microsoft Windows TM 952 operathg systern.

' Compaq Compter wwwcompaq.com ' Microsofi www.mic.rosofi.com

Development of a Hand Tremor Quantincation Device for the Meamment of Pathologicai Tremor 37


The miniBIRD'sTM dipswitchs are set to:

Dip Switch Position:

- - -- 1

Sets Baud aie to 19200 Sets address to "stand-alonel' mode "Fly"

1 12 on 1 o n

The "stand-alone" mode is used because there is oniy one m i n i B I R D T M in this

configuration (multiple miniBIRDsTM are required if more than one sensor is used to

track motion). The "Fly" mode (dipswitch 8 of€) sets the miniBIRDm to a state ready to

begin acquiring data. This is in contrast to the "Test" (dipswitch 8 on) mode that is used

to run specific manufacturer-designed tests on the mullBkdTM.

4.4 Software Description

The software T m o r Quczntifer was written by the author in LabVEWTM 5.1 (National

instruments, Austin, exa as') and custom designed to interface with the miniBIRD% It

has three display modes:

I ) Acquired Data (data acquired using the rniniBIRDRn)

2) Sample Data (previously recorded data)

3) Test Data (for illustrative and testing purposes)

Figure 4.1 is a shot of the main screen of Tremor Quantzifer.

3 off

' Nationai instruments Corporation 1 1500 N Mopac Ekpwy A- Texas, USA 78759-3504 www.ni.com


4 off

5 off

8 off

6 off

7 off


Figure 4.1 : Screen shot of Tremor Quantifier

Developrnent of a Hand Tremor Quantification Device for the Measrwment of Pathological Tremor 39

The prLnary mode is the acquisition and display of tremor data as obtained fiom the

miniBIRDfM. Upon depressing the 'Acquire Data' button the program:

1. Reads data fiom miniBIRDfM.

2. Decodes data to determine x, y, z coordinates of position.

The pro= - executes the remainine sequential actions regardless of the type of data

mode chosen:

3. Displays motion in each axis (x, y, z) with 3 options:

1) Raw data

2) Mean subtracted fiom data

3) Data passed through hi&-pass filter

4. Displays power spectrum for each mis.

5. Estirnates dominant fiequency in each a i s .

6. Calculates Deviation From Mean @FM) for each data point (x, y, z).

7. Detemiines peak and average amphde of tremor.

8. Determines area uademeath DFM plot per second.

9. Displays Signed Deviation From Mean (SDFM) c w e @FM cuve with direction

taken into account).

10. Displays power spectrurn of Signed Deviation From Mean (SDFM) data.

1 1. Estimates the dominant fkequency for overall tremor.

12. Provides option to store tremor information to file.

13. Provides option to export information to spreadsheet nle.

14. Provides option to load previously-stored data.

15. Provides option to print out &ta andysis dong with graphs.

This sequence of events is described in m e r detail below.

Development of a Hand Tremor Quanrification Device for the Mea~ufement of Pathological Tremor 40

1. Readine Data From miniBIRD-

The Tremor @anhifier executes the foilowing steps to read the data fiom the

rniniBIRûm:

1) Uutializes the serial port.

1 S t o ~ bits: 1 1 1

Port number: Baud rate: Data bits:

2) Writes to the serial port to set sampling rate.

Sends CHANGE VALUE command to miniRIRDm to set BIRD MEASUREMENT

RATE. The CHANGE VALUE comrnand must be issued to the minü3IRD'fM in the

followiag sequence:

O (Corn !) 19 200 8

1 BYTE # 1 1 t l 1 Command Bvte 1

The default rneasurement rate for the mllüBIRDm is 103 Hz. The steps to set the

rneasurement rate to 144 Hz are detailed below. This general procedure can be followed

to set the sampling rate to any other acceptable value (20 - 144 Hz). The program sends

four bytes of information to the miniBIRDfM:

Deveiopment of a Hand Tremor Quantiacation Device for the Mea~ucement of Pathoiogical Tremor 41

Byte # 1 2 3

Hex Value 50 07 00

Command Byte PARAMETERnumber PARAMETERdata LSByte

4 1 90 PARAMETERdata MSBvte " PARAMETERvalue


The CHANGE VALUE command is:

The CHANGE VALUE command allows for the changing of the m i n i B I R D T M system

parameter defined by the P.4,rtLWERnumber byte md the PAwIETLRvdue bytes

Command Byte

sent with the command:

1 Command Data 1 PARAMETERnumber 1 PARAMETERdata 1

ASCII P

The PARAMETERnumber for BIRD MEASUREMENT RATE is 7.

To CHANGE the BIRD MEASUREMENT RATE, the program sends the miniBIRDm

one word of PARAMETERdata correspondhg to: (measurement rate) x 256.

In order to set the BIRD MEASUREMENT RATE to 144 Hz consider:

HEX 50

144 x 256 = 36 864 (Decimal) = 9000 (Hexadecimal)

Thus the Hex version of the PARAMETERvalue is 9000. That is:

DECIMAL 80

MS Byte LS Byte 90 O0

BINARY 0101 O000

X LS Byte MS Byte

Therefore, the Hex command sent to the miniBIRDm to change the BIRD

MEASUREMENT RATE to 144 Hz is 50 07 00 90.

DeveIopment of a Hand Tremor Quantifidon Device for the M-ent of Pathologicai Tremor 42


CHANGE VALUE BIRD LS Byte of 9000 MS Byte of 9000 MEASUREMENT

RATE

3) Writes data acquisition command to serial port.

The Tremor Qumtz~er program sends the command IV@' to the miniBIRD~. ' Ibis

indicates a request to obtain POSITION information (x, y, z coordinates) in STREAM

mode.

J) Reads fiom serial port, 6 bytes at a time (each coordinate [x, y, z] has two bytes of information associated with it).

The program captures data for the time penod specified by the user. If the user chooses

to capture 5 seconds of data then the program will capture 720 data samples:

capture period [ s ] x sampling rate = No. of sarnples

samples 5 ~ x 1 4 4 = 720 samples

S

Since each sample contains 6 bytes of data this means that 4320 bytes of data are

collected:

bytes 720 samples x 6 = 4320 bytes samples

Development of a Hand Tremor Quantification Device for the Measmement of Pathological Tremor 43

2. Decoding data to determine x,va coordinates

The data read fkom the miniBRDm comes in the f o m of decimal nurnbers and is fed

into an amy. The information is arranged in the may in the following order:

Where Point O, Po = (h, y,, G) point 1, Pl =(xi, Yi, 21)

Although this is the order that the information comes in, it does not always begin with the

LS byte of an x coordinate. In order to identify the beginning of a sequence of data

representing a single point, the LS byte of every x coordinate is flagged with a leading '1'.

In order to furnish the LS byte of every x coordinate with this leading '1' the data is coded

LS Byte %

in a paaicular way. Therefore, the byte with the leading one must be f o n d and then

the bytes must be decoded. in order to do this the Tremor @unifier:

- - - * *

101 Pl Pl 131 141 Pl VI VI 181

MS Byte &

LS Byte Y0

1) converts the data into binary values

2) runs a search for the leading '1' and splits the array at this point, discarding

MS Byte Y0

every byte to the left of the byte with the leading '1' (note that at maximum

there can only be 5 bytes in the discarded array)

Mer catchhg the Ieading '1' the Tremor Quunt@er translates the bytes into actual x, y, z

coordinates by the foIlowing method:

LS Byte 4

3) shifts each LS byte Ief3 one bit

J) combines each MS byte/LS byte pair into data words (1 word = 2 bytes)

MS Byte 2,

5) shifts each word left one more bit

- * - - -

LS Byte ; : Yi : ...{

LS Byte XI

Deveiopment of a Hand Tremor Quantifkation Device for the Measmement of Paîhological Ttemor 44

MS Byte XI

Chapter 4 Methodology -- - -- - --

Then the program:

6) multiplies the decimal e q d e n t of the binary number by the position

36 constant - to obtain coordinates in inches

32768

7) multiplies the coordinate values by 2.54 to obtain values in centimetres

An example is used to illustrate this procedure:

The data that cornes fiom the bird is put into an array. A sample array rnay be as follows:

The value in position [l] has the leading '1' so this is the LS byte of the x coordinate.

Everything to the left of this is striped fiom the array. Now the array is:

LS byte MS byte g LS byte y. MS byte y. LS byte 2. MS byte z, ----- - LS byte --a----, xi 1 1 1 1 1 1000 ~00000111 10011 1001 10110 1 1 1 1 ~01100001 10111 1101 1 *-.*,---*.**--l ..*

PI [ I I PI i31 PI 153 FI

Al1 the LS bytes are shifted lefi by one bit:

The MS byte/ LS byte pairs are combined into a data word:

Development of a Hand T m o r Quantification Device for the Measirrement of Pathologicai Trernor 45


Values over 16 384 are in two's complement, indicating negative values. Thus, taking the

two's complement of those values:

Then, each word is shifted to the left one more bit:

x, YO

1 1 B inarv 1 Shifi Left One Bit 1 Decimal 1

36 Each value is multiplied by the position factor - to obtain coordinates in inches and 32768

Binary O000 11 11 11 10 O000 0110111101110010

multiplied again by 2.54 to obtain coordinates in centimetres:

Two's Complement

10010000~0001110

2*54 cm 1 y. = - 9.3 1 incher x 2S4cm 1 z, = - 1 .?7incher x 2.54 cm xo = 4.46 Niches x inch inch inch

Decimal 2 032 -4 238

36 .r, =4064x- inches 32768

Development of a Hand Tremor Quantification Device for the Measurement of Pathalogical Tremor 46

36 y, = -8476 x - inches

32768 36

z,=-1148~- inches 32768


3. Displaving: motion in each sKis

For illustrative purposes the Tremor Quantifer displays the motion of the tremor in each

of the three axes: x, y, and z. The pro- splits the data into separate x, y, z arrays and

then displays the data in one of three formats:

1. raw data

2. mean position over acquisition period subtracted from data

3. hi&-pass filtered data

1 . Raw Data

The K. y, z coordinates are graphed with respect to tirne. This gives an indication of what

the raw movement looks like in each axes. An exarnple of raw data c m be seen in

Figures 4.2 through 4.4 in which the raw data of an intention tremor test is graphed in

each axis. Note that the y-coordinate of the graphs represents distance (in cm) from the

miniBIRDTM transrnitter.

Figure 4.2: Movement of hand in x direction of intention test

- - - - - - - - -- - - -

Development of a Hand Tremor Quantification Device for the Measurement of Pathologicai Tremor 47

DEVELOPMENT OF A HAND TREMOR QUANTIFICATION ......Development of a Hand Tremor Quantification Device...

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