PRE2019 3 Group1

Group 1

Group members	Student number	Study	Email
C.C. Vreezen	1011476	Medical science and technology	c.c.vreezen@student.tue.nl
J. Voet	1386794	Psychology and Technology	j.voet@student.tue.nl
F.W.H.M. Ligtenberg	1237054	Biomedical engineering	f.w.h.m.ligtenberg@student.tue.nl
J.A. van Leeuwen	1261401	Applied Physics	j.a.v.leeuwen@student.tue.nl
P. Gort	1253042	Applied Physics	p.gort@student.tue.nl

Introduction

There are many neurodegenerative disorders that have one main occurring symptom in common, tremors. A tremor is an involuntary, rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. These tremors most of the time have an unknown cause, like in for example Parkinson’s disease, paraneoplastic syndrome, extrapyramidal syndrome and Idiopathic parkinson. It is very difficult to determine which disorder is related to which type of tremor. A recent report of the Public Health England shows trends in death numbers of neurological diseases in England between 2001-2014. Mortality associated with Parkinson’s disease and other similar neurodegenerative disorders has increased substantially between 2001-2014. (Darweesh et al., 2018) Since neurodegenerative diseases significantly decrease the quality of life and the incidence is high and still rising, helping these patients becomes of increasing importance for our society.

These neurodegenerative disorders cause tremors with different stages and different rates that affects a patient in their everyday life. Tremors can be caused by different malfunction in the neurons in the part of the brains. This causes difficulties in controlling movements. Tremors worsen because of stress or anxiety and can also cause Bradykinesia; slowed movements, which can cause feelings of tiredness and weakness. This causes a shuffling way of walking and falling since they cannot adjust their footing quickly enough. Moreover, this causes difficulty when buttoning clothes, brushing their teeth or typing something. They can suffer from decreased movement and range of motion due to muscle stiffness, which causes discomfort. Determining the disease is of high importance, since the health risks of each disorder differs. Also a lot of these disorders have serious tremors that contribute to difficulties in maintaining everyday life activities.

Problem statement

The user problem we want to solve is that it is very difficult for doctors to distinguish between tremor diseases, especially in their beginning stages. Since determining a correct diagnosis is a lengthy process, patients with an undiagnosed tremor diseases need to be in and out of the hospital often and undergo all kinds of testing. Some medical examinations like MRIs also can really add up in price. With a quicker and more accurate diagnosis, patients can spare their energy, fuel used for travelling to and from the hospital, their time and their money. On top of that, a wrong diagnosis could lead to the doctors prescribing wrong or temporary, only slightly effective medicine to the patients. This leads to frustration on the side of the patient and could even lead to undesired health consequences from either medicine side effects or from not treating the correct illness and thus decreasing the health of the patient.

When a correct diagnosis cannot be determined, patients will frequently come back to their family medicine doctor to get referred to other specialists in order to find the correct diagnosis. This leads to the doctor having less time to spend on other patients. Moreover, the doctor gets frustrated since he cannot give the patient the correct diagnosis, which might lead to official complaints against his practice. With our band, family medicine doctors can help these patients more efficiently, with the tests just taking a couple of minutes of the doctors' and patients' time. The doctor can then take a day to evaluate the data of the tremor frequency and amplitude to make sure the diagnosis agrees with the data. This also leads to less frustration on the side of the doctor and more free time to see other patients.

Validation of the product

When interviewing Irene Gort-Vos, a basis physician at the Albert Schweitzer hospital in Dordrecht, the relevancy and necessity of our product has become clear.

Willingness to wear the band

The interviewee pointed out that Parkinson patients in the beginning stages of the disease are, in her experience, a well-motivated, cooperative patient group. She thus expects that Parkinson patients will be more than willing to wear our product, if this means it can help with diagnosis and treatment and the band itself is not restrictive. This is because patients in the beginning stages of Parkinson are still cognitively well off and still have a great life to live.

Relevancy and necessity of the band

While frequency and amplitude can be measured in the hospital using several sensors, a family medicine doctor cannot do this in his/her practice. Our product can aid the family doctor in diagnosing a patient by analyzing data of the frequency and amplitude of the tremors. This is a very useful tool for family medicine doctors. Data should be interpreted in context with the complaints the patient expresses or that which the doctor can see in the moment, like when the tremors occur and other specific characteristics of tremor diseases. This context can be found partly by the tests that are performed when implementing the band, and partly by the questions a family medicine doctor always asks the patients as a routine during their appointments.

Objectives

- Support and help general practitioners in diagnosing the disease of a patient correctly without the help of specialists.

- Make the diagnosis of tremor diseases quicker and easier.

- The band is user-friendly to the patient and the general practitioner.

- The band is easy to use for every age.

State of art

Today a lot of tremor types are known, but still, there is a lot to investigate about these tremors. There are a lot of causes of tremors: neurological disorders, neurodegenerative disorders and disorderly conditions that include damage to the brain (e.g. stroke). Other causes are drugs, alcohol, smoking, overactive thyroid or liver failure, lack of sleep, lack of vitamins, increased stress or a cold. Moreover, magnesium and thiamine deficiency can cause tremors. (Chen et al, 2017 & Marshall et al, 1956). Unless there is an underlying issue that causes the tremors, for example, cancer or drug-related tremors, there aren’t any specific medical tests to diagnose for a lot of the diseases that cause these tremors. The most prominent examples of this are Parkinson’s disease (PD) and Essential tremor. A neurologist diagnoses a patient with tremors by holding an anamnesis, looking at clinical characteristics and neurological examination. (Federation of Medical specialists, 2020) In case of suspicion of a certain disease, there are tests that can help support this suspicion. For example, in the case of PD, a dopamine transporter scan can be made. This process to get to a diagnosis is done by ruling out other diseases. Not all causes, frequencies and amplitudes of all existing tremors are clear. However, in order to try and distinguish between tremor diseases, specific frequencies for some disease tremors have been determined. These frequencies can then be related to certain tremor types and therefore also certain diseases.

However, a tremor frequency can vary over time in some diseases. (Hellwig et al, 2009) In Parkinson’s disease and Essential tremor the instantaneous tremor frequency can change by fractions of 1 Hz over a period of seconds, either spontaneously or during voluntary paced contraction of another limb. In psychogenic tremors, tremors in all involved limbs appear to have a common oscillator. By revealing frequency dissociation among physically contracting muscle groups, a feature difficult to detect in clinical examination, multi-limbed recording in both spontaneous and paced conditions help in distinguishing psychogenic tremor from non-psychogenic tremors. (O’Suilleabhain, 1998). Still, there is a lot of missing information about the exact frequencies of certain tremors under certain conditions.

So far there are few techniques on the market which can measure kinematic movement of tremulous activity, but these stay within boundaries. With a tremor stability index, for example, Parkinson’s disease tremor can be discriminated from essential tremor with high diagnostic accuracy. (Di Biase et al., 2017) The tremor stability index is derived from kinematic measurements of tremulous activity. This sensor consists of an accelerometer to measure the linear acceleration caused by the vibrations and a gyroscope which determines the angular position. The data of these two components is used to continuously measure the position of the limb and can be mapped out to create a frequency and amplitude spectrum of the tremors of a patient. However, there is not yet a product on the market that can really measure the differences between multiple tremors, instead of just distinguishing two tremors. More investigation into frequencies and amplitudes of each of the tremor types is needed for writing an algorithm of such a product. Also, very accurate machinery is needed to finetune measuring tremors frequencies.

Users

Primary users

The primary users are family medicine doctors. We want to make it easier for them with our device. Through our device they do not need medical tests to identify tremor-related diseases, these tests are mostly not available for family medicine doctors. It is not always clear what disease a patient may have when they are in the beginning stages. Now they have to work with symptom-based judgement, even though the main symptom that they are looking at is the same: Involuntary limb movements. Our device can distinguish between these different illnesses based on the tremors. The types of medication for tremor diseases differ from disease to disease. Our device will help to come to the right diagnosis right away. With the help of the band, the family medicine doctors have an additional measuring tool to help determine the right diagnosis.

The second primary users are the patients that suffer from an early stage tremor-related disease. As said previously, the band is useful in getting to the right diagnosis. This prevents cases of misdiagnosis which would result in taking the wrong medication. Taking the wrong medication can be very bad for someone’s general health and it can also cause tedious side effects. Furthermore, the band prevents having to go to a specialist. This can save a lot of money and time of the patient as well as the specialists, who can treat more patients when the band is in use.

Secondary users

Secondary users of the band are the companies that create the product. Eventually, if there is a high enough demand for the product, companies will be producing the band. New technologies such as the band may create good business opportunities for both well-established companies and for newer companies.

Another type of secondary users are insurance companies. The purchase of the product will most likely end up being for insurance companies. Hospitals get financed by health insurers. The main option to make it more attractive for the health insurers to finance the product for the hospitals is to be as cheap as possible. So for them, it needs to be of low cost.

Tertiary users

The tertiary users are the neurologists. In case of suspicion with a disease caused by a neurological issue, the patient is normally sent to a neurologist. The goal of the band is that family doctors would already be able to accurately diagnose patients with tremors that result from neurological causes without the help of neurologists. This has positive and negative impacts on neurologists as in this case they would lose a portion of their patients, but they would also have more time to treat other patients that need it. This makes for shorter waiting lists or more time that can be spent on one patient.

Product

The product we developed to aid the user problem is a band. The working mechanism of the band consists of a gyroscope, an accelerometer, and an Arduino. The band uses a model to process the data of the tremors and converts it into a frequency and amplitude spectrum. The band gives a broader insight in determining a tremor disease. It will make the life of patients way easier, if a person experiences tremor in the beginning stadium they can go to a general practitioner just like you would with any other non-life-threatening ailments. There is no need to go to a specialist, e.g. a neurologist. A band that is easy to use can be recommended by a doctor to run tests for determining the disease that causes the tremor. The test consist of a couple of minutes of exercises that are easy to execute and that can be done in the general practice room under the supervision of a doctor or an assistant. While the exercises are executed by the patient, the data is processed and sent to the doctor's computer system. A doctor is guided by the data and the general observations from which he can subsequently draw a conclusion for a disease type. This way the diagnosis is less time consuming for the patient and doctor. Following this, correct medication or further trials can be prescribed. The band will be made as reliable as possible to reduce the risk of wrong diagnosis.

Pro’s:

-Band is easy to use.

-Band comes with an instruction manual, which explains feasible and short exercises.

-Band can be used in general practice.

-Band gives the doctor helpful insights in determining a tremor disease.

-Band gives the doctor calculated data live.

-Doctor can determine disease fast.

-Doctor prescribes correct medication or other further steps.

Con’s:

-The doctor is still reliable for errors.

-Might bring the risk of incorrect diagnosis if data is processed incorrectly.

With the use of a good manual, the cons of the product are mostly non-existent. There are only two cons, and both are related to mistakes of the user, not the product itself.

Requirements

Requirements for family doctors

• The band needs to be able to accurately measure the frequency of the tremors

• The band needs to be able to accurately measure the amplitude of the tremors

• The band needs to be able to use sensor data to compute a model

• The band needs to be able to send data wirelessly to the computer or phone of the doctor via an app

• The product needs to come with a good manual

Requirements for patients

• The band needs to be easy to equip

• The band needs to be comfortable (e.g. by size, weight and feeling)

• The band needs to increase the chance of a correct diagnosis

• The band needs to make the process of diagnosis faster

Requirements for producers

• Cheap to produce

Requirements for insurance companies

• Cheap

• Using it needs to be of low risk

• Long lifetime

Approach

From the beginning of the project, a literature study was performed to investigate the current state of the art of exoskeletons and flexoskeletons for revalidation of tremor-related diseases. From the literature study, a problem statement has been derived to answer the main question for designing a band. For solving the problem statement, objectives have been determined to set guidelines for the realization of a band.

Further, literature study was done to deepen into different user perspectives and different tremor-related diseases. Also, the literature study was needed to deepen into the design of the product and the ethical considerations it gives within the usage of the product. By this, the design of the product needs to take different factors into account. Firstly, a functioning working model of the band has to be designed and incorporated into the system of the band. Secondly, a clear manual has to be set up and written down. Thirdly, a fluently working app has to be designed and created for both the general practitioner.

To finalize the project, interviews with general practitioner were scheduled to derive some different perspectives for human factors of the band. These interviews should enlight the project about user perspective and discover human factors that come with the usage of the band. Without interviews, human factors would have stayed unfound. Besides, the interviews would give more insight into user perspective and into the functionality and specific needs for the design. Also, the general practitioner has more practical information in the medical practice of the band and the exercises that come with the usage of the band. This will give more information to progress changes in for example the manual, design and app of the band to change existing exercises, to finetune the product before realizing it. Finally, for obtaining one of the most important human factors answers, the general practitioner is asked to give reasons if they would like to use the product or not. This is a very important note for realizing the band into a successful project.

Deliverables

- Wiki page

- Model

- A prototype band

- Presentation

Progress of Project

This project started with developing a soft skeleton to help the physically disabled. Feedback on this was that this subject was too broad for the scope of this class, and not focused on a relevant user problem. The focus then shifted from doing literature research on exoskeletons to finding an important and interesting user problem that we can try to find a solution for. Soft exoskeletons can be used for extra stabilization and support, which is how we thought about Parkinson’s disease.

The most well-known symptom of Parkinson’s disease is tremors, mostly of the arms, which proves to be the most bothersome when performing daily tasks. (National Tremor Foundation, 2020) However, for this only the arms need to be stabilized, so we realized an exoskeleton was not necessary for our demographic. Then we thought about creating a band which would counteract tremors, thus reducing them. However this seemed too difficult to do in this course. Through further literature study on Parkinson’s disease, it was discovered that diseases with tremors as a symptom are very difficult to distinguish from each other. (Thenganatt & Louis, 2012) To diagnose such a patient correctly takes multiple trips to the hospital, MRI scans and other tests. (Nederlandse Huisartsen Genootschap, 2020) Tremor diseases are found to be distinguishable from each other by the amplitude and frequency, and this can be used to diagnose these diseases correctly. This diagnosis can be made faster and more efficient by our band.

Diagnosis

Protocol of diagnosing tremor disease

The current order for medical practitioners is followed to identify which tremor disease is involved when a patient is indicating complaints about tremors:

1. Are essential tremors involved?

2. If the disease belongs to Parkinsonism.

3. Diagnosing if the tremor is a non-neurological tremor (e.g. medication use or an overactive thyroid gland).

Diagnosing Parkinson's disease

Parkinson's disease can be diagnosed by the occurrence of observation of four main symptoms, following the anamnesis protocol:

1. Is there a rest tremor occurring?

2. What is the rigidity?

3. Which kind of kinesia: Akinesia, hypokinesia, bradykinesia?

4. Are there interrupted posture and posture reflexes occurring?

For Parkinson's disease, a clinical diagnosis is needed for a typical presentation no additional research is further needed. Some more supportive characteristics of Parkinson’s disease, to help indicate the diagnosis by further observation of the disease, are:

• Is there asymmetry?

• Is there a typical ‘count tremor’?

• Is there a good response to dopamine medication?

• Is there a slowly progressive course?

Mainly by observations, a medical practitioner will identify which tremor disease is involved. Further explorations, will cost more time, more hospital visits and more visits to the local general practitioners.

Current treatments

A medical practitioner finds a suitable wat to treat patients with Parkinson's disease, mainly by diagnosing the symptoms from which the patients experience the most hindrance, the side effects and the stadium of the disease.

Drug treatment of Parkinson's disease

The cause of Parkinson's disease is the loss of neurons in the neurons in the substantia nigra (where dopamine is produced), resulting in a decrease in dopaminergic compounds. All of Parkinson's disease treatments are symptomatic. Still, there has been no demonstration of the neuroprotective effect of the medication. With relatively mild symptoms, treatment is started with amantadine or an MAO-B inhibitor. If the tremor is prominent, an anticholinergic or propranolol is prescribed as medication. In case of clear functional nuisance (motor main symptoms), dopaminergic medication prescribed. That is almost always levodopa with a decarboxylase inhibitor. During the progression of the disease, the duration of action of the medication decreases and the response follows the pattern of the concentration in the blood. During peaks, that means just after ingestion, excess movements occur (dyskinesias) and at the end of the medication period when it has largely disappeared from the body, the hypokinesia complaints occur again. These response fluctuations are called “on-off periods”. As these periods are less imaginable and therefore less effective with the medication, brain surgery may be considered or a continuous form of administration of dopaminergic stimulation in the form of apomorphine subcutaneously (injections or infusion into the skin) or with levodopa via an intestinal pump infusion (in which it passes directly into the intestines continuously).

Tremor symptoms	Medication
Motoric main symptoms	Activation of the Dopamine-2-receptor is most important. By Levodopa, a dopamineprecursor, in combination with a periphery decarboxylase inhibitor. Decarboxylase converts Levedopa into dopamine. The inhibitor causes that the conversion does not only happens in the body, but also in the brain. Dopamine itself does not go direclty through the brain-barrier, but Levodopa does.
Tremor	Thrihexyfenidyl Propranolol, a betablocker
Motoric response fluctuations	COMT-inhibitor: entacapon MAO-B-inhibitor: selegilini, rasagiline (by starting therapies) Amantadine (by starting therapies)
Psychose hallucinations	Clozapine, an atypical antipshychotium
Cognitive disorders	Ricastigmine
Depression	Citalopram Amitriptyline, an antidepresivum
Urinating problems	Oxybutynine, inhibits bladder spasms.

Alternative treatments

Operations

Operations are done in patients who respond well to treatment, but who suffer from response fluctuations. Patients should generally be <70 years of age, demonstrate a good response to levodopa and do not have severe cognitive impairment or psychiatric symptoms. During the procedure, electrodes are placed at certain places, which there stimulate the areas electrically. The procedure does not affect the progression of the disease.

Physiotherapeutic

Physiotherapeutics can be given with specific treatments for freezing and posture exercises for reflexes. By this falling can be prevented.

Logopedics

Logopedics are used when swallowing disorders and drooling are occurring.

Ergo therapeutics

Ergo therapeutics are used with advises for living at home and freezing and falling.

Tremor related diseases

Essential tremor (ET)

ET is a progressive neurological disorder that usually starts between the 10th and 20th or 60th and 70th year of life. ET causes an involuntary rhythmic pure action tremor, and as such no tremors are experienced while in rest. ET can affect the whole body but it occurs most often in the hands. Due to the lack of medical tests for this disease, the diagnosis is at first based on the symptoms. When one has the symptoms of ET, the medical history and family history of the patient is reviewed. ET is autosomal dominant, which means that a child of a patient with ET has a 50% chance to inherit it.

Essential tremor signs and symptoms:

• Begin gradually, usually more prominently on one side of the body

• Worsen with movement

• Usually occur in the hands first, affecting both hands

• Can include a "yes-yes" or "no-no" motion of the head

• May be aggravated by emotional stress, fatigue, caffeine or temperature extremes

A patient with ET can be prescribed multiple types of medication. Firstly, one of these medications is Betablockers, these normally are used for treating high blood pressure but also tend to reduce the tremors of patients. Secondly, anti-seizure medication is often a replacement for people who do not respond to betablockers. Lastly, tranquilizers are anti-anxiety medications for patients whose ET is affected by their emotional state. These are addictive.

Parkinson’s disease (PD)

PD is a neurodegenerative disorder that is the second most prevalent in America today, only surpassed by Alzheimer disease. (Marshall & Hale, 2020) 500.000 people have been diagnosed with PD in the United States, but it is believed that this number would be nearing a million if we allowed for misdiagnosed or undiagnosed cases. It is considered a disease that comes with old age. Costs for treatment are high, around $14 billion, and there is no cure as of now.

PD is caused by a malfunction in the neurons in the part of the brain that produces dopamine. Because of this, it becomes harder to control movement. The cause for this degeneration is still unknown. The greatest risks for PD are old age, genetics or prolonged exposure to toxins such as pesticides. PD can come with both motor and nonmotor symptoms, however motor symptoms are most common. These symptoms can affect one side of the body and then later also affect the other side. Tremors most often occur at rest and subside when the patient performs purposeful movements. They worsen because of stress or anxiety. It can also cause Bradykinesia; slowed movements, which can cause feelings of tiredness and weakness. This causes a shuffling way of walking and falling since they cannot adjust their footing quickly enough. Other motor symptoms include: freezing, sudden stopping, slurred speech and stammering. An issue is that the symptoms do not always show up in the same order. Some patient may only perceive a slight tremor at first while others start with other symptoms such as hypokinesia without any form of a tremor.

The most commonly prescribed medication for PD is Levodopa. Levodopa is processed in the brain, which turns it into dopamine. As PD affects the dopamine production, this is the best medication to help control the symptoms slow movements and stiff body parts. Levodopa is often taken along with Carbidopa, as Carbidopa increases the effectiveness of Levodopa. This results in smaller doses of Levodopa, which reduces the negative side effects. Other types of medication are dopamine agonists. These mimic the effects of dopamine, while they are not as effective as dopamine. Furthermore, anticholinergics have often been used in the past. These block involuntary movements to some degree. However, it is not often used anymore due to its side effects. Amantadine is also used for PD. This increases the availability of dopamine. Lastly, both MAO B inhibitors and COMT inhibitors block the enzyme which is responsible for the breaking down of dopamine in the brain.

Essential tremor vs Parkinson’s disease

ET is occasionally confused with Parkinson’s disease but there are some key differences. ET only causes tremors and there are no other health issues, whereas PD may shorten a patients' lifespan as it causes issues within the brain. Moreover, the tremor affected parts of the body differ. ET involves the hand, head and the voice, while PD cannot be involved with the voice but can be involved with other body parts. Furthermore, ET is a pure action tremor whereas PD is more often a (pure) resting tremor. Lastly, there are differences with the timing of the tremors. ET tremors tend to be of a lower magnitude and with a higher frequency than PD tremors.

Different forms of Parkinsonism

PD is not the only form of Parkinsonism. These other diseases are all similar to PD and therefore difficult to diagnose. The issue here is that not all of these diseases react the same to the normal PD treatments.Generally, the other forms than PD have in common that: - The decline is faster - The life expectancy is shorter - Other neurological phenomena occur - React less to dopamine treatments

Progressive Supranuclear Palsy

Mainly, people have problems with walking and will unexpectedly fall down. Later, vision issues will occur. Sight might get blurry and the movements of the eye become slower. This is most commonly the point where PSP is able to be diagnosed. Vertical Canine Pareses comes after this. If a patient is asked to move the eyes vertically, the patient will experience saccades, which are rapid eye movements to find a new fixation point. In a later stage, one may not be able to move the eyes vertically at all.

Multiple System Atrophy

This disease affects the body's autonomic involuntary actions. The first symptoms may be: males may get impotent, bladder issues and orthostatic hypotension, which is that the blood pressure lowers while standing up. Other symptoms may involve slurred speech and issues with swallowing.

Vasculair Parkinsonism

This is a form of Parkinsonism that is induced by cerebral infarction. The symptoms are mostly walking based. Patients have issues with their balance and generally walk very slowly in small steps. The symptoms are often barely noticeable in the upper body region and as such it is sometimes called lower-body Parkinsonism. The normal PD dopamine treatments are not very effective for this type of Parkinsonism

Dystonia

The cause of most cases of Dystonia are not currently known. However, in some cases it may be acquired due to brain damage or genetics. Dystonia can occur at any age but it typically starts at an early age. It is characterized by involunatary muscle contractions, causing slow repetitive movements and tremors. Dystonia may affect all parts of the body. There are currently no treatments that can prevent dystonia or slow its progress.

However, there are treatments that can lessen the symptoms. The most effective treatment is botulinum toxin. These injections are put in the affected muscles to prevent muscle contractions and also decreases muscle spasms. One injection can last for multiple months. Other drugs that are used as medication are anticholerinic agents. These block involuntary movements, however due to side effects aren’t used as often. Another type of drugs are GABAergic agents. These drugs regulate the GABA neurotransmitter. Lastly, Dopaminergic agents can be used. These act on the dopamine system which helps the control of muscle movement.

Cerebellar tremor

This type of tremor is caused by damage to the cerebellum and its pathways, which may be the result of a stroke, a tumor, alcoholism, or a disease. It is characterized by slow tremors with a high amplitude.

The tremors always occur in the extremities such as the hands or legs. Cerebellar tremors are currently not effectively treated with the use of medications.

Psychogenic tremor

These tremors are caused by some sort of psychiatric disorder such as PTSD. Its tremors can be all types of tremors but are characterized by a few things: Its onset is always very sudden and may affect any part of the body. It is also affected by stress levels.

(Enhanced) Physiologic tremor

Any human has a small tremor in their hands and fingers. This is a physiologic tremor. Physiologic tremor is not related to a disease but rather a human phenomenon. This tremor can be temporarily enhanced however due to drugs, drug withdrawal and some medical conditions.

Tremor types	Cause	Effect	Frequency
Cerebellar tremor	Damage to cerebellum, chronic alcoholism, overdose on medication.	A slow, broad tremor of the extremities that occurs at the end of a purposeful movement	<5 Hz
Dystonic tremor	Dystonia	Sustained involuntary muscle contractions cause twisting and repetitive motions or painful and abnormal postures or positions	7 Hz
Essential tremor/benign essential tremor	Neurodegenerative disorder	Although the tremor may be mild and nonprogressive in some people, in others, the tremor is slowly progressive, starting on one side of the body but affecting both sides within 3 years.	4-8 Hz (Severity differs on age, emotion stress, fever, physical exhaustion)
Orthostatic tremor	Neurodegenerative disorder	Rhythmic muscle contractions that occur in the legs and trunk immediately after standing. Cramps are felt in the thighs and legs and the patient may shake uncontrollably when asked to stand in one spot.	>12 Hz
Parkinsonian tremor	Damage to structures within the brain that control movement.	resting tremor: hands, may also affect the chin, lips, legs, and trunk, can be markedly increased by stress or emotion. The movement starts in one limb or on one side of the body and usually progresses to include the other side.	4-6 Hz
Physiological tremor	Strong emotion, physical exhaustion, hypoglycemia, hyperthyroidism, heavy metal poisoning, stimulants, alcohol withdrawal or fever.	Rarely visible	0.1-10 Hz
Enhanced physiological tremor	Reaction to certain drugs, alcohol withdrawal, or medical conditions including an overactive thyroid and hypoglycemia	a strengthening of physiological tremor to more visible levels	10 Hz
Psychogenic tremor/hysterical tremor	Conversion disorder or psychiatric disease.	Characteristics of this tremor may vary but generally include sudden onset and remission, increased incidence with stress, change in tremor direction or body part affected, and greatly decreased or disappearing tremor activity when the patient is distracted.	Unknown
Rubral tremor	Conditions that affect the red nucleus in the midbrain, classically unusual strokes.	coarse slow tremor which is present at rest, at posture and with intention.	Unknown
Alcoholism	Kill certain nerve cells	Asterix	Unknown
Peripheral neuropathy	Nerves that supply the body's muscles are traumatized by injury, disease, abnormality in the central nervous system, or as the result of systemic illnesses.	Affect the whole body or certain areas, such as the hands, and may be progressive. Resulting sensory loss may be seen as a tremor or ataxia (inability to coordinate voluntary muscle movement) of the affected limbs and problems with gait and balance.	Unknown
Tobacco withdrawal	Smoking	-	Unknown
Panic	Stress	-	Unknown

Design

Band

If a patient experiences tremor symptoms, they pay a visit to the family doctor. Their doctor can then prescribe them to wear this band according to the instruction manual. This band then collects data about the amplitude and frequency of the tremors of the patient.......

In order for the band to be easily put on by tremor patients, the band needs to have as little fastenings, zippers or buttons as possible. (Parkinson's News today, 2020) Patients can use force, however they just cannot complete actions that require detailed movement. Preferred is loose fitting clothing for easy removal. However, our band needs to stay in place, so making the band very loose would cause a hazard in case the band falls off of their arm. An elastic band that is not uncomfortably tight would be the best fit, since this band will stay in place, while the patients are able to put on or remove the band themselves without help. The desired elasticity can be compared to that of a sweatband. To cover the fragile hardware (Arduino etc.) that will be put inside the band it is important to add soft, shock absorbing material to cover these parts. These soft materials can also function in making the device more comfortable to use. Eventually all of the hardware needs to be safely concealed for the eye of the user to make the device more approachable. The size of the band needs to be 10cm making it possible that all materials can fit in, mostly concerning that the biggest piece of hardware, the Arduino, is 7.5cm.

Instruction manual

This instruction manual will be given to the general practitioner in the form of a small booklet. He/she will then instruct the patient where to put on the band and how to perform the tests properly within his/her practice.

For the most accurate test results of time varying tremor parameters, the band should be worn on the forearm, close to the wrist on one arm. This is because: (Gallego, Rocon, Roa, Moreno, & Pons, 2010)

• Tremors are more prominent at joint farther away from the torso

• Wrist tremors are the largest contributors to disability

• Together with tremors of the finger, wrist tremors are studied the most in clinical literature

Four tests need to be performed, that are all relevant from a usability or clinical analysis standpoint. (Gallego, Rocon, Roa, Moreno, & Pons, 2010) The first three tests are also employed by neurologists to activate and analyze different types of tremors, the fourth test tests the ability of a patient to perform daily life activities. (Grimaldi & Manto, 2008)(Belda-Lois et al., 2004) All tests are done in 30 seconds or under, but can be extended to one minute, if within the patients abilities, to acquire more data. Even though test time is short, enough data is acquired within these 30 seconds. Tests can also be repeated if more data is desired.

Attention: The band needs to calibrate for 10 seconds before every use in order to receive accurate data. Let the patient assume the rest position for 10 to 15 seconds before performing a test, and do this for every new task that is performed.

Patients remain seated during testing, both of their arms resting comfortably on their laps as a starting position. The tests include:

• Outstretched arms: Stretch your arms out if front of you and hold them in the air with your fingers abducted (spread out) during 30 seconds.
  • This test typically activates postural tremors.

• Finger to nose: Alternate between touching your nose and knee with your finger during 30 seconds, holding your finger on the nose or knee for a few seconds each.
  • This test typically activates kinetic tremors.

• Rest: Stay in the starting position of sitting down, both arms resting on your lap comfortably during 30 seconds. Make sure your elbow is in about a 90° angle.
  • This test typically activates rest tremors.

• Pouring water into glass: Pour 20 cl of water from a bottle into a glass. It is not of importance how you choose to hold the glass or the bottle.
  • This test is used as a functional and usability analysis.

If you still have questions regarding the use of this product, you can call +31612345678 (fake number, will be changed by the real phone number of costumer service of the manufacturers in the actual instruction manual) from 8 am to 6 pm every day of the week.

Model

For our product we used a Arduino Uno and the MPU6050 which contains a gyroscope and accelerometer. To make it function as intended, we need to write a code for the Arduino. For our product we need to have as output the relative X,Y and Z positions. After some research online, code was written that fulfilled the requirements of the product. It now correctly puts out the relative X, Y and Z components. It appears however that the device needs about 10 seconds to calibrate its position. So this needs to be taken into account, we can only start measuring after those 10 seconds. The Arduino measures about 120 per second, meaning about 0.0083 seconds between measurements. Therefore the data we acquire is really accurate. The data is presented to us in the serial monitor, to do further research on this data we copied it into excel and after that into Matlab. The following code is used to analyze. We put a fast Fourier transform over the data and it puts out a graph where the amount of acceleration is plotted against the frequency. We can then see which frequency is the dominant one. This code is an example for the X direction. We need to also look at the Y and Z direction. We then look at these different axis to determine which has the highest frequency and amplitude and we select this axis to determine what the dominant frequency and amplitude is.

    fs = 1/0.1; % sampling frequency
    LL = length(X_vect1);
    N=1024;  % Block size
    f = fs/2*linspace(0, 1, N/2+1);  % Frequency values
    subplot(311)
    X = fft(X_vect1, N)/LL;          % Accel. along X axis
    plot(f, 2*abs(X(1:N/2+1)));  grid on; 
    title('One-sided Amplitude Spectrum') , shg
    figure(2)
    plot(f, 2*abs(X(1:N/2+1)), 'r');  grid on; 
    xlabel('f, frequency, [Hz]')
    legend('Acc X ')
    title('One-sided Amplitude Spectrum') , shg
    https://nl.mathworks.com/matlabcentral/answers/460422-fft-on-data-acquired-from-an-accelerometer

App

Data of the band can be sent to an app on the phone of the doctor using an HC06 module. (Electronoobs, 2020) This allows for the sending of data via a Bluetooth connection between the HC06 module and the phone. The app shows a graph of the data, normalized using a Fourier transform (Ik weet niet of ik dit zo goed zeg, normaliseert een Fourier transform, of is het meer een filter ofzo?), from which the doctor can clearly read out the amplitude and frequency of the tremors of the patients.

By using this app, the doctor can examine the data on his own time and call the patient back later in the day with the results. This saves a lot of back and forth to the hospital for the patient to be examined by a neurologist or other specialists. Misschien kunnen deze laatste twee zinnen beter bij het stukje over hoe een neuroloog nu een diagnose stelt voor een tremorziekte, om te zeggen dat onze manier dus veel sneller en efficienter is etc.

Costs

Material	costs
Arduino Uno R3 compatible	7.00 euro
MPU-6050	5.00 euro
DuPont Jumper cable male-male	3.50 euro
Wrist band	4.75 euro
Soft material	0.25 euro
Printer cable	2.50 euro
Total	23 euro

Concessions

Due to the limited time for this assignment, concessions have been made to make sure that everything done within this project would be achievable.

• The first concession is that the prototype will have limited functions.

The most notable functions that the final product should have that the prototype will not have is a Bluetooth connection via which the band is able to send data wirelessly to a mobile device or computer through an app. This app would be the interface of all the data from the band and is used by the doctors to assess the data. Moreover, because of time constraints, only a mock-up of the app can be shown, not a working app.

• This also results partly in the second concession: the prototype is very cheap and in no way reflects the price of the final product.

The material that is used for the prototype is rather basic and as mentioned before the prototype has limited functions. This makes it hard to determine a clear, definite cost of the final product.

• The last concession that was made is related to the starting idea of the product.

It was decided that the main goal of the band would be to assist the doctors with a diagnosis instead of actually letting the band make the final diagnosis. This is to avoid the ethical complications that would come with letting a robot make decisions that impact a human life, because who is then to blame when a wrong diagnosis is determined? People generally do not like it when a technology has a final say in any important matter, hence the final call should be made by a person. The fact that people do not trust a technology as much as an educated person is even more true for the elderly. Subsequently, most cases of tremor-related diseases are with elderly people making this an even bigger issue. This led to the decision that the band should merely assist in the final say of a diagnosis instead of having the final say.

Marketing

Medical

It is challenging to distinguish between Parkinson’s disease and other diseases with tremor symptoms like essential tremor, both in the beginning and progressing stages of the diseases. (Thenganatt & Louis, 2012) Both essential tremor and Parkinson’s disease show tremor types like rest, postural, kinetic an intention tremors. Both diseases could even coexist in the same patient. Now, the diagnosis is determined by looking at things like tremor frequency and amplitude and associated neurological findings. Laboratory testing may also aid in differentiating these two diseases. Tests like this include: “accelerometry and surface electromyography, spiral analysis, dopamine transporter imaging, olfactory testing and, eventually, postmortem histopathology. These tests have limitations and their diagnostic utility requires additional study.” (Thenganatt & Louis, 2012) This difficulty with diagnosis shows the practicality of a model that could acquire data from which the doctor could determined the correct diagnosis, thus bypassing extensive clinical testing.

Frustration

PD patients get frustrated when they are dependent on partners or carers for performing daily tasks. (National Tremor Foundation, 2020) They often lack necessary confidence when these helpers are not there. Simple household tasks like cleaning and cooking are really difficult or even impossible. Carrying lightly weighted objects makes these tremors even worse. (Robakis & Louis, 2014) An early and correct diagnosis is thus very important to improve the quality of life of patients with tremor symptoms.

Expected impacts

User perspective

• To improve the precision of the diagnosis.

• To improve the life of patients, by correct medical prescriptions.

• To improve the durability of the patient's diagnosis trail.

• To improve the workflow of the doctor.

• To improve the life quality of patients.

• To improve the relationship and trust patients have with their family medicine doctors.

Society perspective

• To decrease medical costs for other medical trials for society.

• To decrease the pressure on the healthcare system.

Entrepreneur perspective

• To gain financially (e.g. entrepreneurs).

Ethical considerations

It is of utmost importance to pay attention to the balance between benefiting the patients’ quality of life, and avoiding damage, risk or injury. (Bulboacă, Bolboacă, & Bulboacă, 2017)

Most concerns around electronic health records (EHRs) like the data the model will calculate and store are around privacy, confidentiality and the jeopardization of autonomy. (Ozair, Jamshed, Sharma, & Aggarwal, 2015) EHRs are massively being implemented because of their several advantages over paper records, since they increase healthcare access, decrease costs and improve care quality. Autonomy can be taken away from patients if their data is shared without their knowledge. Because of this, a patient might choose to withhold important information in fear of their data being leaked. This can cause suboptimal treatment plans with undesired outcomes. Following privacy and confidentiality guidelines, information about a patient can only be shared with third parties with the patients’ consent. Clinical data is confidential and must always be safeguarded. When this patient cannot give informed consent because of mental capacity or old age, this decision falls upon their guardian or legal representative. Data leaks violate a patients’ privacy and thus damage trust in the health care system as a whole. The fact that the privacy and autonomy of patients can be compromised when collecting data from them in a clinical setting is an ethical question that needs to be at the forefront of the development of this band .

Moreover, when can a doctor decide if this band should be worn by a patient? Under which conditions should the band be applied? What should a patient expect from the band? These conditions should be determined before usage to avoid conflict. Little guidance exists in health care, which results in competing pressures and affects the way that the band is put into practice. (Foye et al, 2002)

Beyond conflicts also the clinical reasoning process is being affected by reimbursement or money issues and this raises significant concerns about the way in which we assess the quality of the provided services of the band. If the band is not in the family medicine budget, it will not see the light of day. If the patient needs to buy it to own it and be able to use it, they will only do so if the symptoms become severe. By this time, treatment could have been started way earlier, combating these symptoms. This product needs to not become a product only the rich can afford.

Another closely related issue that arises is that the patient will get less attention from health care professionals compared to now. This can feel less personal, so patients might not feel like they get the care they deserve, even though this model makes the diagnosis more accurate and faster.

Interview

The interview was done with the dutch basis physician Irene Gort-Vos, and therefore has been done in dutch.

Question 1:

Hoe complex is het om een ziekte met tremors/trillingen in de beginfase te diagnosticeren? En is het moeilijk om verschillende ziektes met tremors te onderscheiden?

Answer:

Dit kan beide vrij complex zijn, aangezien er veel bewegingsstoornissen zijn die met tremoren gepaard kunnen gaan. Toch kun je op basis van andere bijkomende kenmerken en de aard van de tremor, onderscheid tussen deze ziekten maken. Enkele oorzaken van tremoren zie je in onderstaande tabel (sommige staan dus dubbel, omdat het dan niet typisch in rust of bij beweging optreedt).

(Plaatje 1)

Belangrijke aspecten om op te letten indien een patiënt zich presenteert met tremoren: - Moment van optreden (rust of juist bij actie, zoals het aannemen van een nieuwe houding of tijdens beweging). - De frequentie (langzaam <3 Hz, gemiddeld 5-8Hz, snel >10Hz) - Waar in het lichaam de tremor zichtbaar is en of hierin een asymmetrie geldt - Of er wel of geen andere verschijnselen zijn (met name bradykinesie, dystonie of ataxie).

Voor jou is het denk ik het meest relevant om te weten dat indien een patiënt zich presenteert met als klacht ‘tremoren’, je als dokter dan wil onderscheiden of er sprake is van 1) een essentiële tremor, 2) een ziekte behorend tot de groep van Parkinsonisme of 3) een niet-neurologische tremor (dus bijvoorbeeld ten gevolge van een te snel werkende schildklier of medicatiegebruik).

Klinische verschijnselen bij essentiële tremor:

Deze ziekte erft vaak autosomaal dominant over; waarbij navraag of het voorkomt binnen de familie dus van aanvullende waarde kan zijn. Deze ziekte komt veel vaker voor dan de ziekte van Parkinson en is eigenlijk de meest voorkomende bewegingsstoornis! De tremor begint vaak tussen het 10e en 20e jaar of tussen de 60e-70e jaar. Kenmerkend voor de tremor bij dit ziektebeeld is dat het een frequentie heeft van 6-9 Hz en dat het vooral optreedt bij houdingsveranderingen en bewegingen; het is niet of nauwelijks aanwezig in rust (dit in tegenstelling tot de typische rusttremor bij de ziekte van Parkinson). De tremor treft met name de handen, maar ook het hoofd en de stem kunnen meedoen. De tremor aan de handen is altijd dubbelzijdig, maar er kan wel asymmetrie in ernst zijn. Problemen ontstaan bijvoorbeeld met schrijven, een kopje naar de mond brengen, sleutel in sleutelgat willen steken, etc. Dit noemen we een ‘intentietremor’. Veel patiënten merken een afname van de tremor door alcoholgebruik en juist een toename bij emoties, spanningen of vermoeidheid. De diagnose wordt gesteld op basis van het klinisch beeld.

Klinische verschijnselen ziekte v. Parkinson:

Motorische verschijnselen: Bij de ziekte van Parkinson is het begin en het beloop van de ziekte sterk variërend. Bij sommige patiënten begint de ziekte met een rusttremor en blijven de andere hypokinetische klachten (rigiditeit, akinesie/hypokinesie/bradykinesie, gestoorde houding en houdingsreflexen) lange tijd op de achtergrond en komen pas in het verdere beloop van de ziekte tot uiting. Soms bestaat de ziekte van Parkinson juist alleen uit een langzaam progressief hypokinetisch-rigide syndroom, zonder bijkomende rusttremor. De tremor bij de ziekte van Parkinson is wel kenmerkend: de tremor treedt alleen op in rust met een frequentie van 4-6 Hz in handen, voeten, kin en soms het hoofd en de tremor verdwijnt bij activiteit of het veranderen van houding. De tremor neemt in amplitude toe bij spanning of emotie en tijdens het lichamelijk onderzoek valt de tremor het beste op als je de patiënt laat lopen. De hypokinesie bij de ziekte van Parkinson begint met verminderde armswing van één of beide armen tijdens het lopen en een verminderde mimiek (‘maskergelaat’). De stem wordt zachter en monotoner. De vaardigheid vermindert en mensen krijgen een kleiner handschrift (micrografie). Bij het lopen loopt de patiënt gebogen met kleine passen. Soms kan het lopen niet afgeremd worden (propulsie). De houding verandert geleidelijk met een meer gebogen rug en een flexieneiging van armen en benen. Wat vrij typisch is voor de ziekte van Parkinson en ook bij veel patiënten in een vroeg stadium al tot uiting komt, is problemen met het omdraaien in bed. Door gestoorde houdingsreflexen kunnen kleine balansverstoringen ook leiden tot gemakkelijk vallen. In het latere beloop kan ‘freezing’ optreden. Hierbij wordt de beweging van de voeten tijdens lopen of draaien plots geblokkeerd, waarbij de patiënt dan wel aan de grond vastgelijmd lijkt te zitten dan wel op zijn plaats blijft dribbelen. Dit wordt met name uitgelokt door draaien.

Niet-motorische verschijnselen: veel patiënten worden initiatiefloos en emotioneel vlak. Typisch is ook een verminderde reuk (echter, dit is ook weer weinig specifiek, aangezien reuk ook afneemt met het ouder worden). Het kan moeilijker zijn om de urine op te houden, er is vaker sprake van obstipatie en er kunnen slaapstoornissen zijn (REM-slaap stoornissen). In de loop van de ziekte komt vaak een subcorticaal dementiesyndroom voor.

Diagnose stelling: Voor de diagnose van de ziekte van Parkinson moeten ten minste drie van de volgende vier hoofdsymptomen aanwezig zijn:

1. Rusttremor

2. Rigiditeit

3. Akinesie, hypokinesie, bradykinesie

4. Gestoorde houding en houdingsreflexen

Zoals je ziet, zijn dit allemaal kenmerken die je met je anamnese en lichamelijk onderzoek kan vaststellen. Aanvullend onderzoek is dus niet noodzakelijk om de ziekte van Parkinson te stellen. Kortom: de ziekte van Parkinson is een klinische diagnose en bij een typische presentatie is geen aanvullend onderzoek nodig.

Ondersteunende kenmerken voor de ziekte van Parkinson zijn dus:

- Asymmetrie in klachten (vaak treedt de tremor initieel aan één zijde op. Indien het aan beide kanten ontstaat, dan blijft vaak één kant erger aangedaan).

- Typische ‘geld tel tremor’.

- Goede reactie op dopaminerge medicatie.

- Langzaam progressief beloop.

Naast de ziekte van Parkinson, bestaan er nog andere ziekte die tot ‘Parkinsonisme’ behoren, zoals multisysteematrofie, progressieve supranucleaire paralyse, corticobasaal syndroom en vasculair parkinsonisme. Deze ziektebeelden lijken dus op de ziekte van Parkinson en hebben bepaalde overeenkomsten, maar ook verschillen en soms typische klachten die je enkel bij dat ziektebeeld ziet. Bij vasculair parkinsonisme staan loop- en balansstoornissen op de voorgrond, vaak met freezing en vallen. De bradykinesie (traag bewegen) en rigiditeit aan de armen kunnen heel erg meevallen. Het wordt daarom ook wel ‘lower body parkinsonism’ genoemd, omdat het dus met name aan de benen optreedt.

In vergelijking met de ziekte van Parkinson is bij de andere parkinsonismen het tempo van achteruitgang hoger, de levensverwachting korter, de reactie op dopaminerge medicatie minder of afwezig en zijn er vaak neurologische verschijnselen die bij de ziekte van Parkinson niet voorkomen. Toch kan het in de eerste ziektejaren lastig zijn om deze klinische beelden te onderscheiden van de ziekte van Parkinson; ook is soms in het begin onduidelijk om welk type parkinsonisme het gaat. Vanwege deze diagnostische onzekerheid worden de patiënten vaak aanvankelijk met dopaminerge medicatie behandeld, waarbij het uitblijven van een respons het vermoeden op een andere ziekte dan die van Parkinson kan versterken (progressieve supranucleaire paralyse reageert bijvoorbeeld niet op dopaminerge medicatie).

Onderstaande kenmerken doen juist wijzen op een andere ziekte dan de ziekte van Parkinson, waarbij je dus moet denken aan een ander ziektebeeld binnen de Parkinsonismen:

- Verticale blikparese 🡪 dit is typisch voor progressieve supranucleaire paralyse, welke je bij lichamelijk onderzoek kan aantonen: initieel begint dit met saccaden als je vraagt of de patiënt in verticaal vlak zijn ogen kan bewegen; in een later stadium van de ziekte kan de patiënt niet naar boven of beneden kijken.

- Autonome functiestoornissen vroeg in het beloop 🡪 kenmerkend voor multisysteem atrofie (bij nauwkeurig navragen zullen dit vaak de eerste uitingen zijn van de stoornis van multisysteem atrofie, waarbij patiënten klachten krijgen van erectiestoornissen, plasklachten (incontinentie, incomplete blaaslediging, verhoogde aandrang) en orthostatische hypotensie (= het dalen van de cerebrale bloeddruk bij opstaan; met name bij ouderen; het kenmerkende ‘zwart voor je ogen worden’ als je te snel opstaat).

- Piramidale verschijnselen 🡪 passend bij multisysteematrofie (verhoogde reflexen bijv. past hierbij).

- Vroeg optreden van spraak- en slikstoornissen 🡪 passend bij multisysteematrofie.

- Cerebellaire ataxie 🡪 kenmerkend voor multisysteem atrofie.

- Vallen vroeg in het beloop optredend 🡪 dit is typisch voor progressieve supranucleaire paralyse, waarbij patiënten met name achterover vallen.

Question 2:

Aan de hand van welke factoren bepaalt een arts de geschikte manier van het behandelen van Parkinson?

Answer:

Met name door welke symptomen er op de voorgrond staan, waar de patiënt de meeste hinder van ondervindt (zie tabel onderstaand), de bijwerkingen van medicatie en het stadium van de ziekte.

Medicamenteuze behandeling: De oorzaak van de ziekte van Parkinson is het verlies van neuronen in de substantia nigra (waar dopamine wordt geproduceerd), met een afname van de dopaminerge verbindingen als gevolg. Alle behandelingen bij de ziekte van Parkinson zijn symptomatisch; er is geen neuroprotectief effect van medicatie aangetoond.

Bij relatief lichte symptomen beginnen we meestal met amantadine of een MAO-B-remmer. Indien de tremor op de voorgrond staat, dan een anticholinergicum of propranolol. Bij duidelijke functionele hinder (motorische hoofdsymptomen) wordt begonnen met dopaminerge medicatie (vrijwel altijd levodopa met een decarboxylaseremmer). In verloop van de ziekte neemt de werkingsduur van de medicatie af en gaat de respons het patroon volgen van de concentratie in het bloed: tijdens pieken (dus net na inname) treden er overtollige bewegingen op (= dyskinesieën) en aan het einde van de medicatieperiode, als het grotendeels uit het lichaam is verdwenen, treden weer de hypokinesie klachten op. Deze responsfluctuaties worden “on-off-perioden” genoemd. Naarmate deze perioden minder voorstelbaar zijn en je hier dus met je medicatie minder goed op in kan spelen, kan een hersenoperatie worden overwogen of een continue vorm van toediening van dopaminerge stimulatie in de vorm van apomorfine subcutaan (injecties of infusie in de huid) of met levodopa via een intestinale pompinfusie (waarbij het direct continue in de darmen terecht komt).

(Plaatje 2)

Het voert te ver om bovenstaande middelen allemaal te bespreken. Indien je ze op wil zoeken, is dit hiervoor de beste site: https://www.farmacotherapeutischkompas.nl/. Hier kan je denk ik ook nog wel goede informatie vinden over Parkinsonisme behandeling.

Operaties: dit wordt gedaan bij patiënten die goed op de behandeling reageren, maar veel last hebben van responsfluctuaties. Patiënten moeten in het algemeen <70 jaar zijn, een goede reactie op levodopa tonen en geen ernstige cognitieve stoornissen of psychiatrische verschijnselen hebben. Bij de ingreep worden op bepaalde plaatsen elektrodes geplaats welke daar de gebieden elektrisch stimuleren. De ingreep heeft geen invloed op progressie van de ziekte.

Andere behandelingen:

- Fysiotherapie: specifieke behandelingen bij freezing en oefeningen voor houding(sreflexen), zodat valpartijen voorkomen kunnen worden.

- Logopedie: bij slikstoornissen en kwijlen.

- Ergotherapeut: adviezen in thuissituatie voor (hulpmiddelen bij) bevriezen en vallen.

Question 3:

Is het nuttig voor artsen om data te krijgen over de amplitude en frequentie van de trillingen van Parkinson patiënten?

Answer:

Ja, met name de frequentie kan als hulpmiddel gebruikt worden indien het onvoldoende duidelijk is wat de oorzaak is van de tremor (essentiële tremor <> Parkinsonisme etc.). Dit wordt ook in de praktijk gedaan, maar is nooit een waterdicht diagnosticum en moet je interpreteren in de context (wanneer treedt de tremor op, zijn er andere klachten die bijv. passen bij een Parkinsonisme en zijn er daarin weer specifieke kenmerken voor een bepaalde ziekte binnen de groep van Parkinsonismen).

Question 4:

Denkt u dat Parkinsonpatiënten bereid zijn om een handschoen of sleeve (denk aan 1 dag per week) te dragen voor medische doeleinden?

Answer:

Ligt eraan hoe beperkend dit is en wat je ‘medische doeleinde’ betreft. Zoals ik eerder schreef, is de achteruitgang in vaardigheid bij Parkinson patiënten een probleem. Ik kan me voorstellen dat een handschoen deze vaardigheid niet ten goede komt 😉. Ook vraag ik me af wat de meerwaarde is; wat is je doel voor de handschoen/sleeve: het vaststellen van de frequentie (🡪 dit kan namelijk op een gemakkelijkere en goedkopere manier door patiënt sensoren op te plakken tijdens een onderzoek in het ziekenhuis), vaststellen van hoe vaak het voorkomt (🡪 dit kan je vaak met je anamnese wel filteren) of vaststellen of het in rust of beweging optreedt (🡪 dit kan je vaak met je anamnese en lichamelijk onderzoek of het onderzoek met sensoren vaststellen)? Parkinsonpatiënten zijn aan het begin van de ziekte – waarin ze cognitief vaak nog hartstikke goed zijn en nog een behoorlijk leven voor zich hebben liggen – wel een goed gemotiveerde, coöperatieve patiëntengroep, dus daarin verwacht ik wel bereidheid.

Literature study

Femke

This article talks about the implications with on the one side the increasing acceptance of disability, and on the other side the rapid scientific developments in the medical field. If you could just function as a non-disabled person again with the help of an exoskeleton, would you still be able to choose to not use this medical advancement? Would you still have a free choice in this, or are you frowned upon when you do not want to “fix” your disability? (Tesconi., 2019) https://app.knovel.com/web/toc.v/cid:kpWESDCA03/viewerType:toc//root_slug:wearable-exoskeleton-systems?kpromoter=marc)

This website states the ethical codes for computing machinery. Exoskeletons would violate some of these codes, such as 1.1 "Be fair and take action not to discriminate" and 1.4 "Contribute to society and human well-being" (Breen., 2015) https://doi.org/10.1080/09687599.2015.1085200

This article talks about ethical implications such as financial availability (with exoskeletons costing as much as a luxury car), and the dehumanization of soldiers or workers using these exoskeletons (overworking employees and dehumanizing warfare and the humans that fight in that war). (Association for Computing Machinery., 2020) https://www.acm.org/: https://www.acm.org/code-of-ethics

This research paper talks about the importance of, aside from existing ethical guidelines, complementing this with an analysis of the social impact of this exoskeleton technology. They studied the opinions of factory workers (so people who are more at risk of physical injuries) and people outside this environment. (Maurice et al., 2018) https://hal.archives-ouvertes.fr/hal-01826487/document

This research paper evaluates some ethical questions about the domestic use of a robotic exoskeleton (ReWalk Robotics) for gait assistance in patients with a spinal cord injury. “This device is presently FDA and EC market approved and it is now available”. It talks about ethical concerns like financial coverage because of personal resources, but learning to walk again is of high priority for patients (Bissolotti et al., 2018) https://www.frontiersin.org/articles/10.3389/fnins.2018.00078/full

Bibliography

Tesconi, M. (2009). A Wearable System for Lower Limb Movement Analysis. Weinheim, Duitsland: Beltz Verlag. https://app.knovel.com/web/toc.v/cid:kpWESDCA03/viewerType:toc//root_slug:wearable-exoskeleton-systems?kpromoter=marc)

Breen, J. S. (2015). The exoskeleton generation – disability redux. Disability & Society, 30(10), 1568–1572. https://doi.org/10.1080/09687599.2015.1085200 https://www-tandfonline-com.dianus.libr.tue.nl/doi/full/10.1080/09687599.2015.1085200

Association for Computing Machinery (ACM). (2020, 02 04). code-of-ethics. Opgehaald van https://www.acm.org/: https://www.acm.org/code-of-ethics

Greenbaum, Dov., 'Ethical, Legal and Social Concerns Relating to Exoskeletons.' ACM SIGCAS Computers and Society 45, no. 3 (2015): 234-239. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2843109

Pauline Maurice, Ludivine Allienne, Adrien Malaisé, Serena Ivaldi. Ethical and Social Considerations for the Introduction of Human-Centered Technologies at Work. IEEE Workshop on Advanced Robotics and its Social Impacts (ARSO), 2018, Genova, Italy. hal-01826487 https://hal.archives-ouvertes.fr/hal-01826487/document

Bissolotti, L., Nicoli, F., & Picozzi, M. (2018). Domestic Use of the Exoskeleton for Gait Training in Patients with Spinal Cord Injuries: Ethical Dilemmas in Clinical Practice . Frontiers in Neuroscience , Vol. 12, p. 78. Retrieved from https://www.frontiersin.org/article/10.3389/fnins.2018.00078

Pim

One yet existing exoskeleton is the RUPERT (Robotic upper extremity repetitive trainer). This device has 5 actuated degrees of freedom which are driven by compliant and safe pneumatic (operated by air or gas under pressure.) muscle actuators. This helps with shoulder elevation, elbow extension, forearm supination (turning your arm outwards) and humeral external rotation. There is no gravity compensation for this exoskelet. The system is lightweight and uses a PID-based controller combined with an ILC (iterative learning controller) controller. (Balasubramanian, 2008) https://ieeexplore.ieee.org/document/4625154

The state of the art of currently available lower limb assistive exoskeletons is presented in this paper. The functional abilities and the mechanism designs are described. In conclusion, there is still a lot to improve on assistive exoskeletons like choosing the proper and effective tools methods, developing user friendly interfaces and making the devices more affordable. (Kapsalyamov, 2019) https://ieeexplore.ieee.org/abstract/document/8759880

To operate a robotic exoskeleton a control system is needed to monitor an output of electrical activity sensors which are disposed on the human operator. The control system reacts automatically an the step the human makes, choosing from a plurality of different modes. Eventually the operating mode selected will determine the response the system will have to make. (Wilkinson, 2014) https://patents.google.com/patent/US9339396B2/en

The lower-limb exoskeleton is designed to provide weight-bearing assistance for strength and endurance augmentation. It has 10 degrees of freedom. A trajectory learning scheme based on RL (reinforcement learning) and DMP (dynamic movement principles) is present to give assistance to human walking. A two-level plan is presented, the first one concerns the ZMP (zero-moment-point) within the ankle joint for the supported leg. For this purpose the inverted pendulum approximation is utilized, this is done with the so called locomotion parameters. The second level models the joint trajectories learned by the DMP. The RL is now adopted to learn these trajectories so that it can eliminate all the uncertainties in the joint space. The experiments show that it is an effective method for minimizing disturbances and uncertainties. (Yuan, 2019) https://dr.ntu.edu.sg/handle/10356/88973

The robots used for physical rehabilitation allow the patient a compliance and a quantitative, more accurate monitoring of the performance of the patient. However when the patients go back home, it is logistically not possible to keep this same kind of support. Recent research in soft materials for designing robotic devices can make this possible. These are made of fabric and elastomers, is a promising way of delivering power and being ergonomic. Features like assisting the elbow joint and compensating the gravitational forces with a controller are developed and evaluated. It is tested on both the kinetics and kinematics of healthy people. (Xiloyannis, 2019) https://ieeexplore.ieee.org/abstract/document/8718029

Bibliography

Balasubramanian, S. (2008). RUPERT: An exoskeleton robot for assisting rehabilitation of arm functions. Vancouver, BC, Canada: IEEE.

Kapsalyamov, A. (2019). State of the Art Lower Limb Robotic Exoskeletons for Elderly Assistance. Nazarbayev: IEEE.

Wilkinson, L. J. (2014). Robotic exoskeleton multi-modal control system . US: Harris Corp.

Xiloyannis, M. (2019). Development and validation of a soft robotic exosuit for assistance of the upper limbs. Singapore: Nanyang Technological University.

Yuan, Y. (2019). DMP-based Motion Generation for a Walking Exoskeleton Robot Using Reinforcement Learning. Liverpool: IEEE.

Jan

The IHMC exoskeleton is a suit that can be used to gain more strength. The first prototypes were targeted for walking assistance for persons with lower paralysis. The goal is to successfully enable a person to walk a straight line of a distance of 15 feet without human assistance. (Hian., 2019) https://ieeexplore.ieee.org/abstract/document/5152394

In this paper the development of a lower limb exoskeleton is described. These twin legs are powered by pneumatic muscle actuators. These are low mass high power to weight and volume actuation system. These “muscles” being pneumatic means that a more natural muscle like feeling is achieved. This exoskeleton is mostly used for rehabilitation. (Costa., 2017) https://ieeexplore.ieee.org/abstract/document/1639137

CRUX: compliant robotic upper-extermity exosuit. This exosuit is a lightweight (1.3 kg), has flexible multi-joitn design for portable augmentation. The CRUX also maintains the ability to freely move why wearing it. Mostly used for physical therapy and in extreme environments. It is mostly used for people suffering from stroke. It can help these people with the rehabilitation. Most of these rehabiliations now a days succeed. CRUX can provide a solution for this. (Lessard., 2017) https://ieeexplore.ieee.org/abstract/document/8009482

In this article a exosuit is talked about that can help people with hip problems. It uses a backpack frame to connect to the torso. Beneftis of using this method is that exosuits eliminate the problem regarding the alignment of a rigid frame to the biological joints, furthermore the inertia of the joints can be extremely low, meaning less muscle power has to be used. A spooled-webbing of actuators is attached onto the back of the user. These actuators can assist the user. Due to this mechanics more torque is achieved which means that for the same movement 30% less power is needed. (Asbeck et al., 2015) https://www.sciencedirect.com/science/article/abs/pii/S0921889014002103

In this article the biomechanical and physiological effects of a multi-joint soft exosuit are assessed. This exosuit can apply a assisting torque to the hip and ankle joints during walking. This study has looked at the effects of the exosuit on the characteristics of the movement of humans. It appeared that the suit is able to support most of the power that is needed to walk. However there is a decline in kinematic performance with this suit on. This is technical limitation. (Panizzolo et al., 2016) https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-016-0150-9

'Bibliography

Jorn

A study performed in order to help, the ever-increasing amount of, paralysed patients to regain control over their limbs using a wearable exoskeleton. (Chen, 2017) https://doi.org/10.1016/j.jot.2017.02.007

Research for the application of a ‘muscle suit’ that will provide muscular support for manual workers. If the application in this scene will succeed then the muscle suit can be taken further to help the elderly or paralysed patients. But as these categories inquire more risks it is necessary to test it on manual workers beforehand. (Kobayashi et al., 2017) https://ieeexplore.ieee.org/document/4415104

This paper introduces a new orthotic system that supports people with lower-limb paralysis in their everyday life. (Auberger et al., 2018) https://ieeexplore.ieee.org/abstract/document/8488119

The paper briefly discusses the history of artificial limbs and describes present prosthetics, exoskeletons and robotic rehabilitation and the challenges in prosthetics and exoskeletons. (Dellon et Matsuoka., 2017) https://ieeexplore.ieee.org/abstract/document/4141030

This research tested if the HAL exoskeleton is safe and whether it improves functional mobility. The patient sample consisted of eight patients with chronic spinal cord injury. The results showed highly significant improvements to functional mobility without the exoskeleton in the end. (Aach et al, 2019) https://doi.org/10.1016/j.spinee.2014.03.042.

Bibliography

Chen, B (2017) A wearable exoskeleton suit for motion assistance to paralysed patients, Journal of Orthopaedic Translation, https://doi.org/10.1016/j.jot.2017.02.007

H. Kobayashi, H. Suzuki, H. Nozaki and T. Tsuji, "Development of Power Assist System for Manual Worker by Muscle Suit," RO-MAN 2007 - The 16th IEEE International Symposium on Robot and Human Interactive Communication, Jeju, 2007, pp. 332-337. https://ieeexplore.ieee.org/document/4415104

R. Auberger, C. Breuer-Ruesch, F. Fuchs, N. Wismer and R. Riener, "Smart Passive Exoskeleton for Everyday Use with Lower Limb Paralysis: Design and First Results of Knee Joint Kinetics," 2018 7th IEEE International Conference on Biomedical Robotics and Biomechatronics (Biorob), Enschede, 2018, pp. 1109-1114. https://ieeexplore.ieee.org/abstract/document/8488119

B. Dellon and Y. Matsuoka, "Prosthetics, exoskeletons, and rehabilitation [Grand Challenges of Robotics]," in IEEE Robotics & Automation Magazine, vol. 14, no. 1, pp. 30-34, March 2007. https://ieeexplore.ieee.org/abstract/document/4141030

M. Aach, O. Cruciger, M. Sczesny-Kaiser, O. Höffken, R. Ch. Meindl, M. Tegenthoff, P. Schwenkreis, Y. Sankai, T. A. Schildhauer, Voluntary driven exoskeleton as a new tool for rehabilitation in chronic spinal cord injury: a pilot study, The Spine Journal, Volume 14, Issue 12, 2014, Pages 2847-2853, ISSN 1529-9430, https://doi.org/10.1016/j.spinee.2014.03.042.

Chantal

The importance of the availability to drive after obtaining a physical impairment for SCI. Also driving is a very important factor for rehabilitation, but there are various reasons not for driving with a physical impairment. (Lee et al, 2017) https://doi.org/10.1186/s12889-020-8285-9

The importance of autonomy is a valuable asset in the lives of societies and individuals and is causing the problem of loneliness. There are multiple characteristics of psychological mechanisms accompanying the experience of loneliness by people with mobility disabilities. (Zuk et al. 2019) 12(1). https://doi.org/10.1186/s13104-019-4324-y

There are different difficulties, limits and capabilities of Mobility impaired people in normal daily lifestyle activities. (Plus, 2020) https://medlineplus.gov/disabilities.html

A research project examines a student perception of what it would be like to live with a physical or sensory impairment, and how adaptation influences health and quality of life. Mobility impairment is perceived to have the largest impact on health status. (Bray et al., 2019) https://www.ncbi.nlm.nih.gov/pubmed/31586975

Research to identify factors at the levels of the socio-ecological framework and their interaction, that influence the use of community assets among people with physical disabilities and community stakeholders. It calls for stronger enforcement of the existing legal framework through articulated work between different stakeholders, so that people with disabilities can enjoy community assets. (Hernandez et al., 2020) https://doi.org/10.1038/s41393-017-0034-2

Bibliography

Toro-Hernandez, M. L., Villa-Torres, L., Mondragón-Barrera, M. A., & Camelo-Castillo, W. (2020). Factors that influence the use of community assets by people with physical disabilities: results of participatory mapping in Envigado, Colombia. BMC Public Health, 20(1). https://doi.org/10.1186/s12889-020-8285-9

Bray, N., Edwards, R. T., Squires, L., & Morrison, V. (2019). Perceptions of the impact of disability and impairment on health, quality of life and capability. BMC Research Notes, 12(1). https://doi.org/10.1186/s13104-019-4324-y

Plus, M. (2020). Disabilities. Consulted on February 13th 2020, van https://medlineplus.gov/disabilities.html

Zuk, M. (2019). Autonomy - a way for loneliness. analysis of the experience of loneliness of people with physical disabilities. Autonomy, 1633-1640. https://www.ncbi.nlm.nih.gov/pubmed/31586975

Lee, R. C. H., Hasnan, N., & Engkasan, J. P. (2017). Characteristics of persons with spinal cord injury who drive in Malaysia and its barriers: a cross sectional study. Spinal Cord, 56(4), 341–346. https://doi.org/10.1038/s41393-017-0034-2

Planning

	What has to be done	Person(s)
Week 3	Tutor meeting 2 Review of previous week Starting on introduction Making the planning Contacting people for interviews Updating wiki Finishing self study Finishing literature	All All Femke Jan Pim Jorn Chantal, Jorn, Jan All
Week 4	Tutor meeting 3 Describe different users Explain why our project is relevant Explain what Parkinson is (finish introduction)	All Chantal, Jan Pim, Jorn Femke, Chantal, Jorn
Week 5	Tutor meeting 4 Start working on model Start working on design	All All All
Week 6	Tutor meeting 5 Finishing model Finishing design	All All All
Week 7	Tutor meeting 6 Putting everything on wiki Checking for fault on wiki	All All All
Week 8	Finshing the wiki Prepare presenation	All All

Time management

Week 1 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	hours
Jorn Voet	1386794	9 hours	Meeting (2 hrs), Literature research (6 hrs), Update wiki (1 hr)
Pim Gort	1253042	8 hours	Meeting (2 hrs), Literature research (6 hrs)
Femke Ligtenberg	1237054	9 hours	Meeting (2 hrs), Literature research (7 hrs)
C.C. Vreezen	1011476	8 hours	Meeting (2hrs), Literature research (6 hrs),

Week 2 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	16 hours	Meeting (3 hrs), Literature research (7 hrs), Working on model ( 6 hrs)
Jorn Voet	1386794	14 hours	Meeting (3 hrs), Literature research (6 hrs), Research diseases (4 hrs)
Pim Gort	1253042	17 hours	Meeting (3 hrs), Literature research (6 hrs), researching forces and tremors parkinson (6 hrs), Contact for an interview (2 hrs)
Femke Ligtenberg	1237054	19 hours	Writing introduction (3 hrs), literature research (8 hrs), researching subject of project and relevance (5 hrs), meeting (3 hrs)
C.C. Vreezen	1011476	13 hours	Meeting (2hrs), Writing introduction (4hrs), Contact medics( 1hrs). Literature research (6 hrs),

Week 3 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	14 hours	Literature research ( 9 hrs), working on planning ( 2 hrs), meeting x2 ( 3 hrs)
Jorn Voet	1386794	16 hours	Literature research (9 hrs) Meeting x2 (3 hrs) Work on types of PD (4 hrs)
Pim Gort	1253042	18 hours	Literature research (8 hrs) collected data parkinson (2 hrs) mailing + calling (2 hrs) meeting 2x (3 hrs)
Femke Ligtenberg	1237054	18 hours	Literature research (8 hrs), worked on introduction (4 hrs), meeting x2 (4 hrs), working on records of meetings (2 hrs)
C.C. Vreezen	1011476	23 hours	Literature research (9 hrs), Working on the introduction (3 hrs), Meeting x2 (3hrs), Mailing State of the art (6 hrs), Adjusting introduction (2hrs)

Week 4 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	14 hours	Thinking about model, finding literature (6 hrs), meeting (2 hrs)
Jorn Voet	1386794	19 hours	Literature research (8 hrs) User analysis (6 hrs) Meeting x2 (4 hrs), Updating wiki (1 hr)
Pim Gort	1253042	20 hours	interview ( 2 hrs), model orientation (8 hrs), meeting 2x(4 hrs), Literature research on exercises Parkinson patients (6 hrs)
Femke Ligtenberg	1237054	22 hours	Literature research (8 hrs), working on the marketing of our product (3 hrs), meeting x2 (4 hrs), working on pitch (2 hrs), working on wiki page (5 hrs)
C.C. Vreezen	1011476	17 hours	Litarature research (8 hrs), Writing state of the art (4 hrs), Contacting for interviews(1 hr), meeting (2 hrs), Intervieuw questionaire (2hrs)

Week 5 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	17 hours	Meeting ( 3 hrs), compile parts of Arduino ( 8 hrs), Work on Arduino code ( 6 hrs)
Jorn Voet	1386794	19 hours	Rewriting state of the art ( 4 hrs), working out tremor-related diseases (8 hrs), Meeting (3 hrs), Updating users ( 4 hrs)
Pim Gort	1253042	17 hours	Meeting (3 hrs), compile parts of Arduino (8 hrs), Work on Arduino code (6 hrs)
Femke Ligtenberg	1237054	17 hours	Writing instruction manual based on literary research (6 hrs), writing progress of project (2 hrs), reading and checking wiki page (5 hrs), meeting (3 hrs), working on records of meeting (1 hrs)
C.C. Vreezen	1011476	20 hours	Rewrting state of the art (6hrs), Benefits of product (2hrs), Adjustment to introduction & contact with doctor (6hrs), Update wiki page (3hrs), meeting(1hrs),writing beyond state of art (2hrs)

Week 6 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	18 hours	Meeting ( 3 hrs), Working on fourier transform ( 8 hrs), Measurements with Arduino (7 hrs)
Jorn Voet	1386794	12 hours	Meeting (3 hrs), Updating users (2 hrs), Searching additional items for prototype ( 1 hr), Working out concessions ( 6 hrs)
Pim Gort	1253042	18 hours	Meeting (3 hrs), costs estimation product (3 hrs), worked on requirements and users (4 hrs), Testing with Arduino (8 hrs)
Femke Ligtenberg	1237054	16 hours	Meeting (3 hrs), working on problem statement (5 hrs), literature research (6 hrs), working on validation of the product (2 hrs)
C.C. Vreezen	1011476	16 hours	Meeting 2x (3 hrs), Working on the approach (4 hrs), Formatting the wikipage on literature study (1hrs), Interview writing in english (4hrs), Convert interview into wiki page (4hrs)

Week 7 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	hours
Jorn Voet	1386794	hours	Meeting (), Writing app interface ( 5 hrs)
Pim Gort	1253042	hours
Femke Ligtenberg	1237054	hours
C.C. Vreezen	1011476	3 hours	Meeting 2x (1hrs) Writing on the expected impacts (1hrs), Writing down for ideas of risks analysis and updating wiki on treatments (1hrs)

Week 8 log:

Name	Student number	Time spent	Break-down
Jan van Leeuwen	1261401	hours
Jorn Voet	1386794	hours
Pim Gort	1253042	hours
Femke Ligtenberg	1237054	hours
C.C. Vreezen	1011476	hours

References

Belda-Lois, J. M., Vivas, M. J., Castillo, A., Peydro, F., Garrido, J. D., Sanchez-Lacuesta, J., … Prat, J. (2004). Functional assessment of tremor in the upper limb. INTERNATIONAL JOURNAL OF REHABILITATION RESEARCH, 27, 62–63. LIPPINCOTT WILLIAMS & WILKINS 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA.

Bulboacă, A. E., Bolboacă, S. D., & Bulboacă, A. C. (2017). Ethical considerations in providing an upper limb exoskeleton device for stroke patients. Medical Hypotheses, 101, 61–64. https://doi.org/https://doi.org/10.1016/j.mehy.2017.02.016

Chu, C.-Y., & Patterson, R. M. (2018). Soft robotic devices for hand rehabilitation and assistance: a narrative review. Journal of NeuroEngineering and Rehabilitation, 15(1). https://doi.org/10.1186/s12984-018-0350-6 Darweesh, S. K. L., Raphael, K. G., Brundin, P., Matthews, H., Wyse, R. K., Chen, H., & Bloem, B. R. (2018). Parkinson matters. Journal of Parkinson’s Disease, 8(4), 495–498.

Electronoobs. (2020, 03 07). http://www.electronoobs.com/. Opgehaald van electronoobs.com: http://www.electronoobs.com/eng_arduino_tut20_1.php

Foye, S. J., Kirschner, K. L., Brady Wagner, L. C., Stocking, C., & Siegler, M. (2002). Ethical Issues in Rehabilitation: A Qualitative Analysis of Dilemmas Identified by Occupational Therapists. Topics in Stroke Rehabilitation, 9(3), 89–101. https://doi.org/10.1310/7824-1ae0-gff0-kt55

Gallego, A. J., Rocon, E., Roa, J. O., Moreno, C. J., & Pons, J. L. (2010). Real-Time Estimation of Pathological Tremor Parameters from Gyroscope Data. Sensors , Vol. 10. https://doi.org/10.3390/s100302129

Grimaldi, G., & Manto, M. (2008). Tremor: from pathogenesis to treatment. Synthesis Lectures on Biomedical Engineering, 3(1), 1–212.

Irene Gort-Vos, personal communication, March 14, 2020

Koh, T. H., Cheng, N., Yap, H. K., & Yeow, C.-H. (2017). Design of a Soft Robotic Elbow Sleeve with Passive and Intent-Controlled Actuation. Frontiers in Neuroscience, 11. https://doi.org/10.3389/fnins.2017.00597

Marshall, K., & Hale, D. (2020). Parkinson Disease. Home Healthcare Now TA - TT -, 38(1), 48–49. https://doi.org/10.1097/NHH.0000000000000844 LK - https://tue.on.worldcat.org/oclc/8492212894

National Tremor Foundation. (2020, 03 01). https://tremor.org.uk/orthostatic-tremor.html. Opgehaald van https://tremor.org.uk: https://tremor.org.uk/orthostatic-tremor.html

Nederlandse Huisartsen Genootschap. (2020, 03 02). https://www.nhg.org/standaarden/volledig/nhg-standaard-ziekte-van-parkinson? Opgehaald van https://www.nhg.org/: https://www.nhg.org/standaarden/volledig/nhg-standaard-ziekte-van-parkinson?tmp-no-mobile=1

Ozair, F. F., Jamshed, N., Sharma, A., & Aggarwal, P. (2015). Ethical issues in electronic health records: A general overview. Perspectives in Clinical Research, 6(2), 73–76. https://doi.org/10.4103/2229-3485.153997

Parkinson's News today. (2020, 03 06). https://parkinsonsnewstoday.com/. Opgehaald van Parkinson's News today: https://parkinsonsnewstoday.com/2018/01/18/18-tips-getting-dressed-easier-parkinsons-disease/

Robakis, D., & Louis, E. D. (2014). Another case of “shopping bag” tremor: a difficult to classify action tremor. Tremor and Other Hyperkinetic Movements (New York, N.Y.), 4, 269. https://doi.org/10.7916/D8PV6HVJ

Thenganatt, M. A., & Louis, E. D. (2012). Distinguishing essential tremor from Parkinson’s disease: bedside tests and laboratory evaluations. Expert Review of Neurotherapeutics, 12(6), 687–696. https://doi.org/10.1586/ern.12.49

Velandia, C. C., Tibaduiza, A. D., & Vejar, A. M. (2017). Proposal of Novel Model for a 2 DOF Exoskeleton for Lower-Limb Rehabilitation. Robotics , Vol. 6. https://doi.org/10.3390/robotics6030020

Yap, H. K., Lim, J. H., Nasrallah, F., & Yeow, C.-H. (2017). Design and Preliminary Feasibility Study of a Soft Robotic Glove for Hand Function Assistance in Stroke Survivors. Frontiers in Neuroscience, 11. https://doi.org/10.3389/fnins.2017.00547

Yap, H. Kai., Sebastian, Frederick., Wiedeman, Christopher., & Yeow, C.-H. (2017). Design and characterization of low-cost fabric-based flat pneumatic actuators for soft assistive glove application. 2017 International Conference on Rehabilitation Robotics (ICORR). https://doi.org/10.1109/icorr.2017.8009454\