What Causes Dyskinesia In Parkinson’s

Dyskinesia And Wearing Off

If youve been taking a Parkinsons drug that contains for example, co-beneldopa or co-careldopa for some time, you may develop motor fluctuations, wearing off and dyskinesia. These are side effects that can affect your movement.

Dyskinesia is muscle movements that people with Parkinsons cant control. They can include twitches, jerks, twisting or writhing movements. Dyskinesia can affect various parts of the body such as the arms, legs and torso.

There are different types of movements, and when and how often they appear can be different for each person with Parkinsons. Some people can have dyskinesia for most of the day. Others may only experience it after taking their medication or just before the next dose is due.

People with Parkinsons can also experience this side effect when levodopa is at its highest level in the bloodstream , and the dopamine levels in their brains are at their highest. Dopamine is a chemical messenger made in the brain. The symptoms of Parkinson’s appear when dopamine levels become too low.

Because dyskinesia causes people to move around so much it can sometimes cause weight loss. If youre worried about this, speak to your GP, specialist or Parkinsons nurse. They can refer you to a dietitian, who will be able to help you maintain a healthy weight.

If you go from having good control of your movement symptoms to having less control, its called a motor fluctuation. This change can happen slowly or quickly.

Dystonia Vs Dyskinesia In Parkinson’s Disease

Claudia Chaves, MD

Claudia Chaves, MD, is board-certified in cerebrovascular disease and neurology with a subspecialty certification in vascular neurology. She is an associate professor of neurology at Tufts Medical School and medical director of the Lahey Clinic Multiple Sclerosis Center in Lexington, Massachusetts.

and dyskinesia are movement problems that commonly occur in Parkinsons disease . You may experience one or both of them, particularly in late-stage PD. Dystonia is muscle stiffening caused by PD, while dyskinesia is a type of muscle twisting caused by some PD medications.

Dystonia and dyskinesia can both cause distress, and they are distinguished from each other based on their visible features. They can be managed with medication or surgery, typically with a moderate improvement of symptoms.

PD is characterized by four primary symptoms:

• Resting tremor
• Postural instability
• Rigidity

While they can fluctuate in severity, the primary symptoms of PD tend to be present most of the time.

Dystonia and dyskinesia are recurrent, abrupt, and short-lived muscle movements. Not everyone who has PD experiences dystonia and dyskinesia. If they do, the symptoms they experience can be telling.

• Affects large muscle groups

• Smooth, repetitive movement often described as a rolling or writing motion

• Can begin suddenly and stop after several minutes

• Not typically painful

• More likely to occur when PD medication effects are at their peak

How Does Levodopa Work In Parkinson’s Disease

Levodopa is the gold standard treatment for Parkinson’s and works by temporarily replacing dopamine in the brain. In the nervous system, dopamine is a chemical messenger released by neurons to send signals to other neurons about movement. In Parkinson’s, the dopamine-producing brain cells are lost and dopamine levels decrease, leading to Parkinson’s disease symptoms. Levodopa effectively treats motor symptoms such as tremor, bradykinesia , and muscle stiffness by crossing into the brain through what is referred to as the blood/brain barrier. It is combined in medications with carbidopa, which slows the breakdown of levodopa in the bloodstream so more medication can reach the brain. While effective at managing some symptoms, it does not slow or stop disease progression or treat non-motor symptoms like sleep issues and depression.

As Parkinson’s disease progresses, more levodopa tends to be needed in order to continue managing symptoms. Patients may experience what is referred to as “off” time, when medication wears off before it’s time for another levodopa dose. “Off” time can lead to motor fluctuations as well as the return of other symptoms.

Are There Ways To Manage Dyskinesia

Once dyskinesia has started it is difficult to treat. However, there are several ways to delay it from starting or reduce it once it has begun.

Supplemental or alternative treatment options

Things you can do on your own

• Keep a diary that logs the time and frequency of dyskinesia, which will help your doctor assess if your medications are working and help you schedule daily activities when mobility is better.
• Physical activity, including mild aerobic exercise such as walking, dancing, and swimming, will help keep the body strong and prevent muscle weakening.
• Stress can make dyskinesia symptoms worse, so find ways to reduce stress and try to keep a positive attitude.
• Poor sleep at night is associated with dyskinesia. Aim for good sleep quality and try to experiment with different positions in bed that will help you relax and sleep better.

Using Catecholomethyl Transferase Inhibitors

The inhibitors of the enzyme catecholOmethyl transferase extend the halflife of levodopa. Entacapone and tolcapone are two such agents used in clinical practice. Tolcapone has been associated with significant hepatotoxicity, necessitating regular monitoring of liver function tests. In an animal study using rats, coadministration of entacapone with levodopa attenuated all kinds of dyskinesia when compared to levodopa monotherapy. Stalevo , a commercially available formulation, combines levodopa, dopadecarboxylase inhibitor carbidopa and entacapone in a single tablet. It is hoped that early use of Stalevo might reduce the incidence of dyskinesia.

Continuing Education / Review Questions

• The inter-relationships of tardive dyskinesia, parkinsonism, akathisia and tardive dystonia: the Curaçao Extrapyramidal Syndromes Study II.van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS. Schizophr Res. 1997 Aug 29; 26:235-42.
• Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and chronic akathisia in schizophrenic patients.Spivak B, Mester R, Abesgaus J, Wittenberg N, Adlersberg S, Gonen N, Weizman A. J Clin Psychiatry. 1997 Jul; 58:318-22.
• The nosology of tardive syndromes.Frei K, Truong DD, Fahn S, Jankovic J, Hauser RA. J Neurol Sci. 2018 Jun 15; 389:10-16. Epub 2018 Feb 6.
• Review Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia.Barnes TR, McPhillips MA. Int Clin Psychopharmacol. 1998 Mar; 13 Suppl 3:S49-57.
• Review Clinical relationship of extrapyramidal symptoms and tardive dyskinesia.Andrew HG. Can J Psychiatry. 1994 Nov; 39:S76-80.

What Are Dyskinesias And How Can I Manage Them

Dyskinesias are abnormal, involuntary movements that occur in response to repeated dopamine-replacement therapy . Sometimes, they can be debilitating. These motor complications are typically choreiform. Chorea comes from the Greek word meaning to dance, so the dyskinesias looks similar to dance-like, constant writhing or wriggling movements of the arms, legs, trunk, and sometimes even facial muscles. However, dyskinesias can also be dystonic , or myoclonic or other movement disorders, and can become progressively more severe with increasing duration of treatment . Sometimes, with advancing disease, it becomes increasingly difficult to find a dose of levodopa that provides symptom relief while avoiding dyskinesia.

Wake Forest Baptist Multidisciplinary Approach

The treatment of movement disorders at Wake Forest Baptist is a collaborative effort between neurologists and neurosurgeons.

Quality of life is further enhanced by the participation of physical, occupational and speech therapists, and otolaryngologists who have special expertise in speech and swallowing difficulties.

Dyskinesia Is A Debilitating Side Effect Of Parkinsons Medications That Can Significantly Impact On Quality Of Life In This Post We Find Out Why Medications Like Levodopa Cause This Side Effect And How Serotonin Signalling Is Involved

Nov 6, 2017

Parkinsons can cause an array of physical symptoms that include tremor, rigidity and stiffness, as well as non-motor symptoms such as memory problems and anxiety. Despite huge improvements in the medications that are available today, it is not just the symptoms of Parkinsons that impact on quality of life, the drugs that are used to manage the symptoms of Parkinsons can cause terrible side effects.

Involuntary movements, called dyskinesia, which are different to a Parkinsons tremor, are experienced by many people with Parkinsons as a side effect of their medication. These often quick, jerky or twitchy movements can affect various parts of the body, such as the arms, legs and upper half of the body and have a major impact on quality of life.

It makes eating very difficult. And walking is almost impossible.

They are intrinsically linked to the medications used to help manage the condition a side effect, not a symptom and are mostly associated with levodopa based medications, however dopamine agonists can also cause dyskinesia. While they can be present early in the condition, they often become more problematic in the later stages of Parkinsons when people have been taking Parkinsons medications for several years.

Even though I take Amantadine to control the dyskinesia, I still have involuntary movement like right now and it is exhausting. It is also embarrassing in public when I cant control it.

What Is Parkinsons Disease Dyskinesia

Dyskinesia literally means abnormal movement. Parkinsons Disease Dyskinesia, often referred to as levodopa-induced dyskinesia, can be described as uncontrolled jerking, dance-like or wriggling movements. Symptoms range from minor tics to full-body movements. It can be a stand-alone condition; however, in people with Parkinsons, it is most often associated with long-term use of levodopa, a drug that increases levels of dopamine in the brain.

What Is Dyskinesia In Parkinsons Disease

Dyskinesia is predominately a side effect of a medication called levodopa thats used to treat Parkinsons disease.

To the trained eye, dyskinesias look quite different , says Herrington. Dyskinesias are not rhythmic they have a more writhing quality.

Herrington points out that you can see an example of dyskinesia if you look at videos of Michael J. Fox. Usually, he says, when is on camera, he has some dyskinesia, or extra movements that are involuntary.

How Prominent Is The Problem Of Pd

The prevalence rate of PD was estimated a few years ago to be between 100 to 200/100,000 population , with an incidence rate of 10 to 20/100,000 population . However, the number of PD cases is increasing and will have grown from 10 million worldwide in the late 1980s to 40 million in 2020 due mainly to the aging population. While most patients with PD are diagnosed after the age of 55 , about 10% of patients are diagnosed before the age of forty and characterized as ‘young-onset PD’ . While most young-onset patients exhibit typical parkinsonian symptoms , they appear to display slower disease progression and show a tendency for increased prevalence and severity of motor fluctuations and dyskinesia with prolonged L-3,4-dihydroxyphenylalanine therapy . Early onset of motor complications may be especially relevant in these patients as they will live with the disease for longer periods with a diminished quality of life and impaired social and economic productivity .

Causes And Risk Factors For Tardive Dyskinesia

Tardive dyskinesia is mainly caused by an older class of drugs used to treat psychiatric disorders. These antipsychotic medications, also called neuroleptic drugs, are generally prescribed to treat psychiatric disorders. They work by blocking receptors in the brain. Dopamine is a that helps control the brains reward and pleasure centers. It also plays a major role in motor functioning.

Its not clear why or how tardive dyskinesia symptoms begin, but theyre thought to be related to the chronic blocking of these receptors.

Newer antipsychotic drugs are less likely to cause the syndrome, but still may trigger symptoms.

Other drugs that can cause the problem include:

• , which treats gastroparesis

Journal of Neurological Sciencespeople with schizophrenia

What Makes Dyskinesia Worse For Members

People with Parkinsons disease lose brain cells that produce the chemical dopamine. Levodopa therapy relieves Parkinsons symptoms by temporarily replacing dopamine, but fluctuating levels of levodopa cause dyskinesia as a side effect. This is believed to contribute to the motor complications that characterize dyskinesia.

Dyskinesia can occur or worsen at two different points. One is when dopamine levels are at their highest, called peak-dose dyskinesia, usually one or two hours after medication is taken. The other is when dopamine levels drop, called diphasic dyskinesia.

I start to feel dyskinesia about a half-hour to an hour after my morning dose, said one member, whose symptoms subside after two hours. Mine hits whenever the meds are wearing off and can last up to two hours a stretch, explained another. My symptoms are worse in the afternoon and evening , said one member.

Some members of MyParkinsonsTeam said dyskinesia lessened or stopped when their neurologists reduced their levodopa dosage or prescribed a drug approved by the U.S. Food and Drug Administration to treat it such as, an extended-release formulation of the drug amantadine.

When my doctor lowered the dose of , the dyskinesia disappeared, said one member. We reduced my wifes dose and the dyskinesia virtually disappeared, agreed another.

Treating Dystonia In Parkinsons

Treatment options for dystonia include:

• Dopaminergic medication adjustment as discussed above
• Botulinum toxin injections of the affected muscles
• Physical therapy to loosen and strengthen the dystonic body part
• Trying other medications that target the dystonia directly such as muscle relaxants or anti-cholinergic medications
• Use of a device to provide a sensory trick*.
• Deep brain stimulation can be considered in difficult-to-treat situations

*To minimize their dystonia, some people have success using an interesting tactic called a sensory trick. A sensory trick is defined as a physical gesture that mitigates the production of the dystonia. For example, touching the eyebrow may help keep the eyes open, or touching the chin may keep the neck from twisting. In my clinical practice, one woman wears metals rings on her dystonic fingers to help them assume a more normal position. Another man wears 5-toed shoes to prevent dystonic toe curling

Use Of Controlledrelease Preparations Of Levodopa

The standard preparation of levodopa with a short halflife has the potential for pulsatile stimulation of the postsynaptic receptors. It was hoped that a controlledrelease formulation with a longer halflife would obviate this problem. However, a study comparing standard formulation of levodopa with a controlledrelease type in early Parkinson’s disease showed no difference in the frequency of LID after 5 years of followup. However, the controlled release formulation has variable absorption and it was administered in a twicedaily regimen. This could have accounted for the failure to achieve continuous dopaminergic stimulation.

Talk To Your Doctor About Continuous Drug Infusion

One way to potentially avoid fluctuations in medication delivery and dopamine levels is through a continuous drug delivery system such as duodenal infusion, in which the medication travels through a tube directly into the intestine. Another option is continuous subcutaneous apomorphine infusion, in which a small device similar to an insulin pump is clipped to the clothing, according to the Parkinsons Foundation. A wire then enters the skin to deliver a steady dose of the medication apomorphine , a dopamine agonist, which may reduce the “off” periods, when levodopa stops working, and may minimize dyskinesia symptoms.

Epidemiology And Risk Factors

The reported incidence rates of LID show a wide range, from 980%., This is unsurprising as the risk of developing LID depends on age of onset and severity of Parkinson’s disease, dose and duration of levodopa therapy, and possibly on some hitherto unknown factors. Moreover, methodological differences in the reporting of LID and lack of a universally agreed assessment scale may account for the differences among studies. The earlier reports of higher rates as compared to the significantly lower rates observed in later studies could be explained on the basis of introduction of levodopa at high dosage in relatively advanced stage of Parkinson’s disease in the immediate postlevodopa era.

The dose of levodopa is important in the production of LID. In the DATATOP study, at the same followup time, a mean daily levodopa dose of 338 mg was not associated with LID, while LID developed at a mean daily dose of 387 mg. Larger doses of levodopa are associated with prolonged dyskinesias. When used in very high doses, levodopa can produce dyskinesias in normal monkeys. LID do not appear early in the course of therapy. Most studies have reported an increase in the frequency of LID with increasing period of followup., Recently, an association of LID with weight loss has been reported.

Initiating Therapy With An Agonist And Adding Levodopa When Necessary

Animal data suggest that pulsatile stimulation with short-acting agents is the driving force in the genesis of dyskinesias . Conversely, these short-acting agents do not induce dyskinesias when given in a continuous fashion . In drug-naive, MPTP-lesioned monkeys, the administration of longer-acting dopamine agonists results in significantly less dyskinesia than does levodopa . However, once a long-acting agonist is administered to animals already primed to exhibit dyskinesias with levodopa, the resultant dyskinesias are comparable to those seen in the levodopa group . An MPTP-marmoset study evaluating the combination of ropinirole, a long-acting agonist, plus levodopa showed that the levodopa-dominant group had increasingly intense dyskinesias as the study progressed, whereas the ropinirole-dominant combination produced no greater intensity of dyskinesias than was produced by ropinirole alone.

Clinical studies randomly assigning patients to initial treatment with a dopamine agonist or levodopa have shown a lower risk for dyskinesias in the agonist-treated groups . Retrospective analyses have demonstrated that once levodopa is added, the rate of development of dyskinesias is the same regardless of whether or not the patient was already taking a dopamine agonist . Therefore, it appears that the benefit of initial treatment with a dopamine agonist in lowering the incidence of dyskinesias is related to the ability of the agonist to delay the need for levodopa .

Talk To Your Doctor About Changing Your Medication Dosage

is more likely to cause side effects like dyskinesia when its taken in higher doses. “More than 600 milligrams a day in the long run is associated with a greater incidence of dyskinesia,” says Dr. Pantelyat. Thats why its important to find the lowest dose that will still control your symptoms. Your doctor will work to do this by starting you on a low dose and gradually increasing it as needed.

When Do You Get Dyskinesia

Most people are on levodopa for 5 to 10 years before they notice dyskinesia. And it usually starts when Parkinson’s is under good control. This is called peak dyskinesia because it happens when your dopamine levels are highest. After a while, symptoms may start sooner and last longer than this peak time.

But they still happen when levodopa is keeping your symptoms in check. Your doctor may call this being âonâ with dyskinesia.

Dyskinesia is sometimes lumped together with a problem called motor fluctuations. But theyâre not the same thing. Motor fluctuations are when Parkinson’s symptoms come back during times your meds arenât working. This can happen if levodopa wears off before you take your next dose or a new dose doesnât kick in right away.

If Levodopa Causes Dyskinesia Then Why Should I Take It

At present, treatment with levodopa is the most effective way to relieve tremor, stiffness, and slow movement associated with Parkinsons. In the early stage of Parkinsons, levodopa may not be necessary and there are other medications available to treat this stage of the disease. However, as the disease progresses and begin to interfere with daily living, your doctor will prescribe levodopa.

• It typically doesnt develop immediately Its important to note that there is usually a time lag of roughly 4 to 10 years from the start of treatment with levodopa to when dyskinesia emerges, and its severity will vary among different individuals.
• Younger people are at a greater risk People who get Parkinsons in their later years may not show signs of dyskinesia or may have only mild symptoms within their lifetime. Being diagnosed with Parkinsons at a younger age is associated with a greater chance of developing dyskinesia.
• As with every aspect of Parkinsons, there is variability in dyskinesias Some do notdevelop dyskinesias at all. For those who do get them, not all experience them the same. Dyskinesia inits milder form may not be bothersome, and the mobility afforded by taking levodopa may be preferable to the immobility associated with not taking levodopa. People with Parkinsons must weigh the benefits from using levodopa versus the impact of dyskinesia on their quality of life.

Is Tardive Dyskinesia A Symptom Of Parkinsons Disease

Tardive dyskinesia is not a symptom of Parkinsons disease. Its a separate movement disorder caused by long-term use of anti-psychotic medications. 

In addition to being a side effect of different medications, tardive dyskinesia also has its own set of symptoms. The movements associated with tardive dyskinesia tend to be more fluid in appearance compared with Parkinsons dyskinesia.

Drugs that most often cause tardive dyskinesia include: 

• Chlorpromazine
• Thioridazine

Finding Humor In Dyskinesia

Despite the challenges of coping with dyskinesia, some members of MyParkinsonsTeam find healing humor in their condition.

• I make the greatest milkshakes.
• If anyone needs a strobe light, just hand me a flashlight.
• I do a good imitation of an electric toothbrush.
• If the power went out, you could hook up my legs to an electric generator.

What Causes Dyskinesia And Dystonia

Dyskinesia is a common side effect of the Parkinsons drug levodopa. This drug is used to help increase the level of dopamine in the brain, alleviating symptoms of the disease. However, levodopa is taken intermittently throughout the day, causing dopamine levels to rise and fall over time. These fluctuations are thought to be the cause of dyskinesia. There are two types of dyskinesia:

• Peak-dose dyskinesia, which occurs when the level of levodopa is at its highest
• Diphasic dyskinesia, which occurs when levels of levodopa are rising or falling

While can be a symptom of Parkinsons disease itself, it can also be caused by levodopa treatment, similar to dyskinesia. Dystonia symptoms occur when there is a decrease in brain dopamine levels, which can occur before medication is taken in the mornings or as it is wearing off during the day. This off and on dystonia can be addressed by taking an extended-release form of levodopa, or increasing the number of doses taken per day.

Dystonic dyskinesia can occur when the movements caused by levodopa are more sustained and twisting than in typical dyskinesia. When this occurs, it is important to determine the cause whether the movement occurs at peak-dose levels of dopamine or it is off and on dystonia.

Drugs Acting On Nmda Receptors

Based on the importance of overexpression of NMDA receptors in LID, NMDA antagonists have been tried as potential treatment for LID. In monkeys with MPTPinduced lesions, Papa et al reported useful antidyskinetic effects using an experimental selective NMDA antagonist. In humans, amantadine can reduce dyskinesias without worsening parkinsonian symptoms. The antidyskinetic effect of amantidine is mediated via the inhibition of NMDA receptors. In a randomised, doubleblind, placebocontrolled study of 18 consecutive Parkinson’s disease patients, amantidine reduced the duration of LID by 60%. A recent evidencebased review supports the use of amantidine in LID. Tachyphylaxis can be a limiting factor in its use.

Other Surgical Methods For Parkinsons

There are a few other surgical procedures that may also be considered for the management of the LID. These procedures do not involve the implantation of a stimulator; they involve creating a lesion in one of the regions of the brain that is responsible for either Parkinsons symptoms or the dyskinesias.

Typically, lesional surgeries also target the globus pallidus or the subthalamic nucleus, and they may involve both sides if necessary. These procedures are, like DBS, considered safe and effective. If you are a candidate for DBS surgery, then it is very likely that your medical team will be discussing several surgical options with you, in addition to DBS.

Advanced Disease: Reducing Or Eliminating Established Dyskinesias

PD patients eventually need levodopa to help alleviate parkinsonian motor features. When dyskinesia emerges, one strategy is to dose levodopa so that it peaks just below the dyskinesia threshold and administer it frequently enough to avoid wearing off. This typically amounts to administering levodopa in smaller doses more often, which may be inconvenient and result in reduced compliance. At the extreme, liquid levodopa can be used to deliver very small doses of levodopa very frequently ; however, patients usually find this very inconvenient.

Another strategy is to use higher doses of a dopamine agonist to reduce both the total daily levodopa dose and its frequency or to gradually substitute a dopamine agonist for levodopa . Unfortunately, these strategies rarely work and typically reduce dyskinesias at the expense of less satisfactory control of parkinsonian symptoms.