There Are Three Primary Categories Of Medications To Treat Motor Symptoms Of Parkinsons:
- Dopaminergic medications for movement
- Dopaminergic medications replace lost dopamine and can be used to treat tremor, stiffness, slowness and problems walking. These medications may also have a beneficial impact on non-motor symptoms of Parkinson’s related to sleep, mood and cognition. Dopaminergic medications, such as carbidopa-levodopa , make up the majority of medicines used to treat Parkinson’s and can sometimes be used in combination with each other because of how they impact the body. As Parkinson’s progresses and more of these dopaminergic medications are needed to address symptoms, you may experience motor fluctuations and frustrating side effects of the added or increased medication, like dyskinesia. Dyskinesia is uncontrollable, jerky movements of the arms and legs caused long-term use of levodopa.
Parkinsonian Tremor: The Most Common Form Of Resting Tremor
Some patients have a predominant postural tremor in addition to their rest tremor. This form is uncommon and has been considered to be a combination of an ET with PD although the relation between postural tremor that is phenomenologically similar to ET and PD has not been well defined. Further studies are needed to define the relation between ET and other tremors, including PD and other task specific tremors.
Box 3 Clinical Features Suggestive Of Psychogenic Tremor73
Tremor increases with attention, and lessens with distractibility
Responsive to placebo
Absence of other neurological signs
Spontaneous remissions or cures of symptoms
No evidence of disease by laboratory or radiological investigations
Employed in allied health professionals
Litigation or compensation pending
Presence of psychiatric disease
Reported functional disturbances in the past
Commonly, patients with psychogenic tremor often undergo a large number of diagnosis and therapeutic procedures before the final diagnosis is established. A review of medical history in these patients usually shows multiple functional somatic or psychosomatic illnesses. Once the diagnosis is made, most patients continue to have a fluctuating or constant course, followed by improving and progressive periods suggesting the prognosis is far from benign. The therapeutic success is also variable, but the treatment approach should include various combinations of psychotherapy as well as drugs, such as mild anxiolytics and antidepressants. While pharmacological treatment in organic tremor may reduce amplitude, but does not change the tremor frequency, the effect of treatment in psychogenic tremor usually varies from total suppression of tremor, especially when associated with the suggestion of a “cure” to no benefit.26 Interestingly, most of successfully treated patients were young.63
Beyond Dopamine Does Pd Effect Other Neurotransmitters
Trends in PD research are showing that in addition to Parkinson’s impact on the neurotransmitter dopamine and the dopamingeric system, the neurotransmitter acetylcholine and the brain’s cholingeric system are also impacted.
This post reviews recent research , and discusses how two vitamins/supplements may impact Parkinson’s disease. This should not be considered medical advice. Always consult your doctors and pharmacist about any vitamins or supplements that you are taking or considering.
Exhibit A: Yale Study challenges assumptions about PD and acetylcholine
Several weeks ago, a Yale study challenged a long held assumption about Parkinson’s effect on a neurotransmitter other than dopamine. The loss of dopamine leads to slower movements, resting tremors, and other symptoms that worsen over time. To help these symptoms, doctors prescribe treatments that increase dopamine levels in the striatum, a portion of the brain that is responsible for motor learning. However, medical treatments do not consider the effects of Parkinson’s on another neurotransmitter, acetylcholine.
The Yale research argues that dopamine deficiency reduces acetylcholine, and suggests that treating Parkinson’s may require targeted therapies that restore the balance between these two chemicals, instead of focusing solely on dopamine, said the researchers.
More on this Yale study:
Exhibit B: Mayo research commentary on Vitamin B-12
Exhibit E : CDP Choline and PD Study from 1990
What Are The Different Categories Or Types Of Tremor
Tremor is most commonly classified by its appearance and cause or origin. There are more than 20 types of tremor. Some of the most common forms of tremor include:
Essential tremor is one of the most common movement disorders. The exact cause of essential tremor is unknown. For some people this tremor is mild and remains stable for many years. The tremor usually appears on both sides of the body, but is often noticed more in the dominant hand because it is an action tremor.
The key feature of essential tremor is a tremor in both hands and arms, which is present during action and when standing still. Additional symptoms may include head tremor without abnormal posturing of the head and a shaking or quivering sound to the voice if the tremor affects the voice box. The action tremor in both hands in essential tremor can lead to problems with writing, drawing, drinking from a cup, or using tools or a computer.
Tremor frequency may decrease as the person ages, but the severity may increase, affecting the person’s ability to perform certain tasks or activities of daily living. Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremor and/or increase its severity. Though the tremor can start at any age, it most often appears for the first time during adolescence or in middle age . Small amounts of alcohol may help decrease essential tremor, but the mechanism behind this is unknown.
Tremor: Sorting Through The Differential Diagnosis
PAUL CRAWFORD, MD, and ETHAN E. ZIMMERMAN, MD, Mike O’Callaghan Military Medical Center, Nellis Family Medicine Residency, Nellis Air Force Base, Nevada
Am Fam Physician. 2018 Feb 1;97:180-186.
Patient information: A handout on tremors, written by the authors of this article, is available.
Tremor is an involuntary, rhythmic, oscillatory movement of a body part and is the most common movement disorder encountered in primary care practices.1–3 Aside from careful clinical examination and imaging when needed, there is no standard test to distinguish between common types of tremor, which can make the evaluation challenging. However, establishing the underlying cause is important because prognosis and specific treatment plans vary considerably. The most common tremors in patients presenting to primary care physicians are enhanced physiologic tremor, essential tremor, and parkinsonian tremor.1,3–6 All tremors are more common in older age.7
SORT: KEY RECOMMENDATIONS FOR PRACTICE
A resting tremor is usually caused by parkinsonism.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
A resting tremor is usually caused by parkinsonism.
Causes Of Resting Tremors In Parkinson’s Disease
Resting tremors are among the most noticeable features of Parkinson’s disease .?? The tremors are believed to be caused by complex interactions between a number of factors. Alterations in the activity of several areas of the brain including the substantia nigra, the basal ganglia, and the thalamus, as well as changes in the level and action of the neurotransmitter dopamine, are all related to each other and to the production of the tremors.
Other Movement Symptoms Of Parkinsons Include:
- Reduced manual dexterity, making everyday tasks like buttoning a shirt difficult
- Severe muscle cramping
- Pain without an obvious cause
Learn more about how to evaluate your walking-related motor symptoms and how to manage them with our .
Parkinson’s slows you down, but staying active, like riding my bike, keeps me limber and moving and improves my outlook. It’s really important not to give up on doing the things you like. —Robert
Tremors Not Associated With Parkinsons Disease
There are different types of tremors, of which not all are associated with Parkinson’s disease, and they vary slightly in terms of how, when and where they manifest in the body. They include essential tremor and dystonic tremor and may be associated with other conditions and genetic mutations, although a specific gene has not been identified.
A patient with a Parkinson’s tremor typically will find that their symptoms worsen and spread to other parts of the body over time. Generally, the tremor starts in one hand and can progress to the arm and foot on the same side of the body, and then eventually to the other side of the body. In severe cases, tremors also can affect the jaw or lips.
Which Body Parts Do Parkinsons Tremors Affect
There are five main places you’ll have Parkinson’s tremors:
1. Hands. Parkinson’s disease tremors often start in the fingers or hands with what’s called a pill-rolling motion. Imagine holding a pill between your thumb and index finger and rolling it back and forth.
2. Foot. A Parkinson’s foot tremor is more likely to happen while you’re sitting or lying down with your feet at rest. If the tremor moves into your thigh muscles. It could look like your whole leg is shaking.
Foot tremors disappear when you stand or walk because those are active movements. A foot or leg tremor while you’re standing may be another condition.
3. Jaw. This is common in people with Parkinson’s. It may look like you’re shivering. It can become bothersome if the tremor makes your teeth chatter. If you wear dentures, it could make them shift or fall out.
Chewing eases the tremor, so gum might help.
4. Tongue. It’s rare, but a tongue tremor can cause your entire head to shake.
5. Internal. Some people with Parkinson’s say they can feel a shaking sensation in their chest or abdomen. But can’t be seen from the outside.
Primary Motor Symptoms Of Parkinsons Include:
- Tremor: a rhythmic shaking in your arms, legs or chin. Most people with Parkinson’s who experience tremor that is worse when relaxing and resting have rest tremor. Others experience active tremor, which means their shaking worsens when trying to do something, like drinking out of a cup of coffee or eating with a spoon.
- Rigidity: painful stiffness, often in the arms, legs, neck or back muscles.
- Akinesia, Bradykinesia, Hypokinesia:Akinesia and bradykinesia refer to the reduction of movement, slowness of movement, and sometimes even complete lack of movement that can be caused by Parkinson’s. Hypokinesia refers to a loss of momentum or force in movement that can come with Parkinson’s, usually in connection with akinesia, bradykinesia, or both. The small, cramped handwriting that some people with Parkinson’s experience is thought to be some combination of akinesia and hypokinesia.
- Postural Instability: balance problems caused by a loss of reflexes that help you stay upright. This can cause challenges with general balance as well as walking . Sometimes postural instability brings the tendency to fall backward, called retropulsion.
Early motor symptoms can also include a mask-like face or loss of facial expression, small, cramped handwriting , and decreased natural arm swing.
People often complain of a heaviness feeling, dragging of one side, or cramping in certain muscles. Speech can become softer and more difficult as Parkinson’s progresses and swallowing can also be affected.
Box 1 Clinical Criteria For Essential Tremor2
Definite essential tremor
Postural tremor of moderate amplitude is present in at least one arm
Tremor of moderate amplitude is present in at least one arm during at least four tasks, such as pouring water, using a spoon to drink water drinking water, finger-to-nose manoeuvre, and drawing a spiral.
Tremor must interfere with at least one activity of daily living.
Medications, hypothyroidism, alcohol, and other neurological conditions are not the cause of tremor.
Probable essential tremor
Tremor of moderate amplitude is present in at least one arm during at least four tasks, or head tremor is present.
Medications, hyperthyroidism, alcohol, and other neurological conditions are not the cause of tremor.
Monoamine oxidase inhibitors
ET is believed to be of a central nervous system origin, but a reproducible neuropathology has not been described. A central aetiology was partly supported by the beneficial effect of thalamotomy, thalamic deep brain stimulation , and drugs that act centrally. Numerous experimental physiological and functional imaging studies have also implicated dysfunction in brain stem structures, including the inferior olive, locus coeruleus, red nucleus, thalamus, but cerebellum seems to be a prime candidate for the site of dysfunction in ET.23–25 It is probable that ET occur as a result of an abnormal oscillator of a CNS “pacemaker” in a currently unknown exact location that can be increased or suppressed by reflex pathways.
What Are The Motor Symptoms Of Parkinsons
Parkinson’s is officially classified as a movement disorder because it involves damage to the areas of the brain, nerves and muscles that influence the speed, quality, fluency and ease of movement. Motor symptoms are usually the most visible elements of Parkinson’s. Motor symptoms of Parkinson’s also respond well to Parkinson’s medications.
Although motor symptoms of Parkinson’s often get the most attention and treatment, researchers estimate motor symptoms don’t actually appear in most people until around 60?80% of the nerve cells in the brain that make dopamine have stopped working because of Parkinson’s.
In this article, we will help you identify and learn about the various motor symptoms of Parkinson’s so you can be proactive in the management of your symptoms.
The impacts of Parkinson’s on movement are called motor symptoms.
Strategies To Help Manage Tremor Include:
- Take your medication on time! This helps minimize off times that can make tremor worse.
- Streamline your focus to reduce multitasking. Rest your elbow on the table when taking a drink to stabilize yourself or sit down when you button your shirt to concentrate more intently on the task at hand.
- Reduce stress. Nerves and feeling stressed, in general, can make tremor worse, as can fatigue.
- Consider adaptive technologies and products designed to make everyday tasks easier, such as specially-designed razors, pens, keyboards, utensils, cups and dishes.
Rigidity refers to muscle stiffness and tightness associated with Parkinson’s. Like tremor, rigidity usually appears first on one side of the body and spreads to both sides over time. Occasionally, rigidity can go unrecognized as a symptom of Parkinson’s, instead of being attributed to past injuries or old age.
Muscle stiffness associated with Parkinson’s can make movement difficult and can also impact how you walk . Stiff muscles combined with slowed, smaller movements particularly increases the risk of falling.
Rigidity usually responds well to Parkinson’s medications, especially dopaminergic medications such as carbidopa-levodopa . Regular exercise, seeing a physical therapist and complementary therapies such as acupuncture and massage can all help manage rigidity.
Learn more about Bradykinesia and Rigidity
Learn more about Bradykinesia and Rigidity
When To Be Concerned About Hand Tremors
Someone with a severe tremor can have their hands shaking uncontrollably. Fact is, everybody has the potential to experience tremors in some form. Dr. Tom Miller talks with movement disorder specialist Dr. Lauren Schrock about the two main types of tremors and how to identify the differences between them, possible causes, and when to be concerned.
May 20, 2014
What Treatments Are There For Tremors
Parkinson’s tremors cannot be cured. However, there are several options to manage them.
Many of the typical Parkinson’s drug treatments are associated with a reduction in tremors, including levodopa and dopamine agonists. A surgical procedure called deep brain stimulation also may be offered to control unmanageable tremors.
Physical therapy can help some patients control their tremors better, as can reducing the intake of substances such as caffeine, which can induce tremors. Many patients experience an increase in the severity of their tremors when they are stressed. Therefore, trying to reduce sources of anxiety and engaging in complementary therapies may help some patients.
Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
What Looks Like Parkinsons But Isnt
Dr. Fernandez describes two main Parkinson’s mimics:
Essential tremor. Also known as benign essential tremor or familial tremor, this movement disorder causes brief, uncontrollable shaking.
It most often affects your hands, but can also affect your head and neck, larynx and other areas. In rare cases, it affects your lower body as well.
But one clue can help distinguish essential tremor from Parkinson’s.
“This is not an absolute rule, but if shaking occurs at rest, it often is Parkinson’s. And if shaking occurs in action, such as when you’re writing or eating, it is essential tremor,” Dr. Fernandez says.
About half of those with essential tremor have a family history of the condition.
Unlike Parkinson’s, essential tremor is generally not perceived as a progressive disorder, and, if mild, may not require treatment.
Doctors can prescribe medications to reduce shaking, but they are not the same drugs used to treat Parkinson’s, he says.
Drug-induced Parkinson’s. Along with shaking, this condition may cause many symptoms similar to Parkinson’s disease, including stiffness, slow movement, a decrease in facial expression and a change in speech.
As the name suggests, taking certain drugs, most commonly antipsychotics and mood stabilizers, can trigger this condition. How long it takes to develop can vary greatly, depending on which drug you’re taking, how long you take it and the dosage.
Environmental Factors And Exposures
Exposure to pesticides and a history of head injury have each been linked with PD, but the risks are modest. Never having smoked cigarettes, and never drinking caffeinated beverages, are also associated with small increases in risk of developing PD.
Low concentrations of urate in the blood is associated with an increased risk of PD.
How Are Parkinsons Tremors Treated
Tremor can be unpredictable. Some experts say it’s the toughest symptom to treat with medication. Your doctor may prescribe medication for your tremors:
- Levodopa/carbidopa combination medicines . This treatment is a type of medication called a dopamine agonist. It’s usually the first treatment for Parkinson’s.
The Tremors Of Parkinson’s Disease
The distinction between these different tremors is not always visible to the naked eye. For example, resting tremor can re-emerge during postural holding, making it difficult to clinically distinguish it from essential tremor. This distinction can be made by focusing on the delay between adopting a posture and the emergence of tremor: in essential tremor there is no delay, while Parkinson’s disease resting tremor re-emerges after a few seconds . Since the frequency of re-emergent and resting tremor can be similar, it has been hypothesized that both tremors share a similar pathophysiological mechanism. One interesting patient with Parkinson’s disease had no resting tremor, but a marked 3–6 Hz postural tremor that occurred after a delay of 2–4 s following postural holding , thus resembling re-emergent tremor. Such observations point to heterogeneity in the circumstances under which the classical Parkinson’s disease ‘resting’ tremor occurs.
In the following sections, we will mainly focus on the classic resting tremor in Parkinson’s disease. We will first describe the clinical and cerebral differences between patients with tremor-dominant and non-tremor Parkinson’s disease. Then we will detail how these differences may inform us about the causes and consequences of Parkinson’s disease resting tremor.
The Right Diagnosis Can Save Time
Because the symptoms of Parkinson’s vary and often overlap other conditions, it is misdiagnosed up to 30% of the time, Dr. Fernandez says. Misdiagnosis is even more common in the early stages.
Patients who don’t know where to turn may make appointments with a rheumatologist, or an orthopaedic or heart specialist, and undergo MRIs, EMGs and other expensive tests.
But only a neurologist can distinguish Parkinson’s from essential tremor, drug-induced Parkinson’s and Parkinson’s plus syndromes, he says.
“If patients come to us with typical signs of Parkinson’s, we don’t need to order expensive tests,” he says.
Instead, neurologists base their diagnosis on a detailed patient exam and medical history, along with other information from the patient, family members or caregivers.
“That’s all stirred into the pot,” he says. “Sometimes we can diagnose Parkinson’s with one visit. Other times, several follow-up visits are necessary.”
Can Essential Tremor Be Inherited
Dr. Miller: Wow, that would be very difficult to live with, I would think. Do essential tremors travel in families? Are they associated with a family history? Because many of my patients will say, “Yeah, I really haven’t worried about it because I knew my dad had it and his mother had it.”
Dr. Schrock: Yes. It’s very common to see essential tremor strongly travel in families. In medical school, we’re taught that it’s what they call autosomal dominant disorder, so that each child has a 50 percent chance of getting the gene.
Dr. Miller: Is that still true? Does that hold?
Dr. Schrock: I would say there’s definitely a sub-group where you definitely see that, but as I mentioned before, essential tremor probably includes many different tremors, some of them where you see clear family inheritance and others where you actually don’t.
Where Can I Get More Information
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute’s Brain Resources and Information Network at:
Office of Communications and Public LiaisonNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda, MD 20892
NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.
What Age Do You Get Hand Tremors
Dr. Miller: What about the age difference when these tremors might develop? Does the Parkinson’s tremor occur a little bit later, that pill rolling tremor you described? Is that a little bit later on in life, or essential tremor earlier in life?
Dr. Schrock: On average, when you look at the large groups, you will see that essential tremor comes on a little bit earlier than Parkinson’s disease. However, even within a single family who has multiple family members with this essential tremor, you may have one family member who has the onset at age 20 and another family member at age 75. There really is not a clear indicator of what your diagnosis is based on the age of onset.
In Parkinson’s disease, the large majority of patients have their onset in their 60s, 70s. However, there is a small subset of patients who can have early onset Parkinson’s disease. A great example of that would be Michael J. Fox who had his onset around age 30.
Dr. Miller: Also, tremors are related to certain drugs, I think. A lot of us think about people who maybe are withdrawing from alcohol having a tremor. Is that actually a tremor? Is that something that is separate from what we’ve been talking about?
What Is The Physiological Tremor
Tremor is a common side effect of many drugs . Various drugs and toxins can cause all types of tremor known clinically although increased physiological tremor is most commonly seen. Tremor is the dose limiting side effect of the ?2 adrenergic agonists, salbutamol and terbutaline, used to treat obstructive airway diseases. Tremor is usually seen within a month of starting valproic acid treatment and is more evident when a dose is >750 mg/day although it can also occur when the dose is within therapeutic range. It is the most common tremorogenic drug among anticonvulsants, affecting up to 25% of patients.53 Intention tremor may occur in patients on lithium. The occurrence rate increases with increasing serum lithium levels and manifests almost 100% in patients with lithium toxicity.54 Tardive tremor, a rare disorder, represents a separate entity in which, by definition, is caused by exposure to a dopamine receptor blocking agent within six months of the onset of symptoms and persisting for at least one month after stopping the offending drug.55 It is usually static in nature but can occur at rest and on intentional movements, such as eating and writing. Tremor can also occur as a toxic reaction to marijuana, and 3,4-methylene-dioxymethamphetamine or ecstasy.56
Other Tremors And How It Differs
A Parkinsonian tremor has a few distinct characteristics, though it may be easy to confuse with other types of tremors depending on the other symptoms a person shows. Doctors will look for and rule out other types of tremors to confirm their diagnosis.
The National Institute of Neurological Disorders and Stroke notes that some common tremors include:
Dopamine is an important neurotransmitter that plays a critical role in a number of bodily functions, such as movement and coordination. People with Parkinson’s disease produce less dopamine, which may cause them to experience movement-related problems, such as rigidity, slowness of movement, poor balance, and tremors.
Low levels of dopamine may disrupt the way the brain processes movement, which can result in movement problems. Evidence suggests that many people with Parkinson’s disease lose 60–80% of dopamine-producing cells in the brain by the time they present symptoms.
Other causes of tremors unrelated to Parkinson’s disease can include:
- certain medications
Confusion With Essential Tremor
The tremor of Parkinson’s disease is often confused with the tremor of a condition called Essential Tremor, or Benign Familial Tremor . Katherine Hepburn had Essential Tremor, and was originally misdiagnosed with Parkinson’s. Ronald Reagan also had Essential Tremor. Both had a head tremor and a vocal tremor. In Essential Tremor, the hands are most commonly involved, followed by the head and then the voice. Essential Tremor can also cause the jaw to tremor, and it may be difficult to figure out if a jaw tremor is from Essential Tremor or Parkinson’s. Unfortunately, some people may have both disorders. Some authorities believe that there is, in fact, an increased association between the two conditions, so that more people with Parkinson’s disease have Essential Tremor than would be expected by chance alone, but this has not been established.
What Are The Symptoms Of Tremor
Symptoms of tremor may include:
- a rhythmic shaking in the hands, arms, head, legs, or torso
- shaky voice
- difficulty writing or drawing
- problems holding and controlling utensils, such as a spoon.
Some tremor may be triggered by or become worse during times of stress or strong emotion, when an individual is physically exhausted, or when a person is in certain postures or makes certain movements.
Can Essential Tremor Get Worse
Dr. Schrock: Essential tremor definitely can get worse. Really, when it comes down to it, probably two decades from now we’re going to find out there are many different types of essential tremors. There are a lot of varieties of the different severity of tremor, what part of the body it includes. Most commonly . . .
Dr. Miller: So it’s not just the hands?
Dr. Schrock: It’s not just the hands. Head tremor can be involved, head and voice tremor.
Dr. Miller: I’ve heard some people that sound like their voice is almost trembling when they talk, and you wonder if they’re anxious. Actually, it’s the essential tremor, that type of tremor at least, right?
Dr. Schrock: It definitely can be. There’s one other thing that can be mixed up or misdiagnosed as essential tremor, and that’s something that’s much more rare, so most people haven’t heard of it. It’s something called dystonic tremor, something when someone has dystonia, meaning abnormal spasm of a muscle that causes either pulling or abnormal postures.
Dr. Miller: Is essential tremor mostly in both hands, or is it usually in one?
Dr. Miller: But the essential tremor is a little finer tremor, it’s worse as you move towards something or try to do something. It’s a finer base tremor. I guess sometimes it can actually be a pretty marked tremor, depending on who has it.
Tremors And Parkinsons Disease
Tremors are a major symptom of Parkinson’s disease, presenting in about 75% of cases.
When a person has the disease, nerve cells in the basal ganglia begin to die, producing less dopamine.
The basal ganglia need dopamine to form connections between neurons. A reduction in this hormone leads to fewer connections and interrupted communication within the brain, meaning movements do not occur as smoothly in the body. Additionally, tremors and other movement symptoms, such as jerking, can develop.
While pill-rolling tremors may sometimes be a symptom of other neurological conditions, such as multiple sclerosis, they are almost always an indicator of Parkinson’s disease.