What Is The Difference Between Bradykinesia And Dyskinesia
Bradykinesia may appear as a reduction in automatic movements such as blinking or swinging of arms while walking, or it may manifest as trouble initiating intentional movements or just slowness of actions. The second movement problem is dyskinesia, in which people have involuntary, erratic, writhing movements.
Box 1classification Of Levodopainduced Dyskinesias
- Peak dose dyskinesia
- On state dystonia
- Peakdose dyskinesiasThese are the most common forms of LID and are related to peak plasma levels of levodopa. They involve the head, trunk, and limbs, and sometimes respiratory muscles. Dose reduction can ameliorate them, frequently at the cost of deterioration of parkinsonism. Peakdose dyskinesias are usually choreiform, though in the later stages dystonia can superimpose.
- Diphasic dyskinesiasThese develop when plasma levodopa levels are rising or falling, but not with the peak levels. They are also called DID . DID are commonly dystonic in nature, though chorea or mixed pattern may occur. They do not respond to levodopa dose reduction and may rather improve with high dose of levodopa.
- Off state dystoniasThese occur when plasma levodopa levels are low . They are usually pure dystonia occurring as painful spasms in one foot. They respond to levodopa therapy. Rare forms of LID include on state dystonias and yoyo dyskinesia .
What Do Off Times Look Like
OFF times look different for everyone. For some people with Parkinsons, OFF presents as slowed movement, reduced mobility, increased tremor, muscle cramping, rigidity, balance issues, stiffness, shortness of breath, and/or swallowing issues. OFF isnt always a visible state it can be a period when your non-motor symptoms increase, and you experience fluctuations in cognition, attention, anxiety, depression, and apathy. OFF can also cause a person with Parkinsons to experience increased sweating, lightheadedness, abdominal pain, bloating, urinary issues, visual disturbances, pain, dysesthesia, akathisia, and/or restless legs syndrome.
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Potential Molecular Mechanisms Underlying Dystonia And Dyskinesia
Figure 1. Schematic diagram of corticostriatal synapse in healthy condition and in patients with PARKIN mutations . The figure shows the interaction of parkin with KAR and NMDAR and potential changes induced by loss of PARKIN function.
The molecular signatures that have recently emerged as key signals in LIDs are ERK1/2 phosphorylation , abnormal activation of mitogen- and stress-activated protein kinase-1 , and phosphorylation of histone H3 . The final result of this chain of events is a change in the molecular make-up of MSNs due to alterations in gene expression and protein synthesis that might account for maladaptive morphological plasticity at the corticostriatal synapse . Morphological examination of MSNs in dopamine-depleted animals and in autopsy specimens from iPD patients has revealed dendrite atrophy, truncated dendrites, and decreased spine density . These functional and morphological changes in the corticostriatal synapses are believed to result in dyskinesias .
Understanding The Levodopa Side Effect
If you have Parkinsons disease, there is a good chance that youve been, or will be taking medication containing levodopa. Levodopa is administered in combination with the drug carbidopa . This drug combination is considered standard treatment for Parkinsons disease symptoms such as tremor, muscle stiffness, and slowness of movement. A side effect of long-term use of levodopa is dyskinesia. Below, you will learn about dyskinesia, what causes it, how it can be managed, and some basic coping strategies.
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What Is The Difference Between Tardive Dyskinesia And Dystonia
Tardive dyskinesia refers to uncontrollable mouthing and lip-smacking grimaces that develop following the long-term use of neuroleptics. Dystonia refers to abnormal muscle tone resulting in muscle spasms or abnormal postures.
Tardive dyskinesia is always caused by the long-term use of neuroleptics. However, various factors such as different drugs, neurodegenerative diseases and traumatic damages to central nervous system can cause dystonia. Moreover, dystonias include a variety of movement disorders that occur due to various reasons while tardive dyskinesia is only a subgroup of primary dystonias.
Other Types Of Dyskinesia In Parkinson’s Disease
PD patients on treatment with levodopa may also have other types of dyskinesia including stimulation-induced dyskinesia and graft-induced dyskinesia . SID has been reported in patients who receive subthalamic nucleus -deep brain stimulation surgery. SID is considered to be a good prognostic sign for optimal lead placement. Usually, SID occurs within 1 month after surgery. In one study, 40 contacts of 16 electrodes causing SID were analyzed. Most common site of dyskinesia was contralateral lower limb and dystonia was commonly reported. In another study, 4 of 179 STN-DBS patients had SID. This type of dyskinesia was also labeled as brittle STN-associated dyskinesia. Interestingly, none of 75 patients undergoing globus pallidus interna -DBS developed SID. One STN-DBS patient, who developed SID, underwent GPi-DBS and his SID was successfully reversed. GID is an abnormal dyskinetic movement in off state seen in PD patients receiving transplantation of fetal tissues. Serotonergic neurons are considered to mediate the GID. In one study, systemic administration of 5-HT1A agonist, buspirone, completely suppressed the GID.
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Medications And Supplements Used To Treat Tardive Dyskinesia
A number of medications and supplements have been identified that ameliorate TD symptoms.
Cholingergic Agents.
Cholinergic agents are used as muscle stimulants to diagnose myasthenia gravis and to treat glaucoma. These agents can also improve the Parkinsonian features of TD. Donepezil, a reversible acetylcholinesterase inhibitor, is currently the only cholinergic medication that has shown benefit against TD. Overall, however, cholinergic agents are not a widely accepted treatment for TD as sufficient evidence is lacking to suggest they are more helpful than other treatments.
Clozapine, Quetiapine, Olanzapine, and Apomorphine.
Clozapine, a serotonin and dopamine receptor antagonist, is an atypical APD used to treat schizophrenia. Clozapine is the best current medication recommended for patients who require antipsychotics and simultaneously have TD, as clozapine has been reported to reverse TD symptoms., Clozapine has been linked to TD however, the incidence is much lower compared to other atypical APDs. Drugs with similar mechanisms of action such as quetiapine, a weak striatal dopamine antagonist, and olanzapine, a dopamine and serotonin receptor antagonist, have also been shown to be effective in ameliorating TD symptoms. Apomorphine, a dopamine receptor antagonist, can be given in conjunction with L-DOPA to decrease dyskinesias.
Tetrabenazine Analogs.
Antioxidant Medications and Supplements.
Whats The Main Difference Between Tremor And Dyskinesia
Tremor seen in Parkinsons disease is one of the hallmark features of the condition. Its one of the motor symptoms of Parkinsons that shows improvement with medication.
On the other hand, dyskinesia tends to show up later in the course of the disease as a long-term side effect of medications used to treat Parkinsons. Sometimes it can be a bit hard to tell whether the abnormal movements are tremor or dyskinesia.
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Pharmacologic Strategies To Directly Address The Incidence Of Dyskinesias
Restoration of striatal dopaminergic stimulation is the goal in the treatment of parkinsonian motor symptoms. Levodopa provides the greatest benefit for treating parkinsonian motor dysfunction, but because its use is associated with the development of motor complications, one of the great unmet needs for the treatment of PD is a medication that will match the efficacy of levodopa but not cause motor complications. Until such a medication is available, it is useful to identify treatment strategies that can provide adequate efficacy while minimizing motor complications.
The short half-life of levodopa and the resultant pulsatile dopaminergic stimulation appear at least in part to be responsible for the development of motor complications . Therefore, CDS may delay the onset of dyskinesias in early disease and alleviate dyskinesias in advanced disease.
Rating Scales For Dyskinesia
Different scales and instruments have been used to provide objective assessment of LID and its impact on overall quality of life. UPDRS is helpful in assessment of different aspects of dyskinesia, but it does not include the anatomical distribution of dyskinesia in different body parts. There are other scales used to assess LID, including the Rush Dyskinesia Rating Scale , Unified Dyskinesia Rating Scale, and Clinical Dyskinesia Rating Scale . There are different instruments to measure quality of life, including 39-item Parkinson’s Disease Questionnaire and Parkinson’s Disease Quality of Life Scale. Patients self-evaluation diaries such as Hauser diary have been used to know the effect of drugs used to treat LID, but the compliance to diary completion and accuracy is extremely challenging. Several quantitative instrumental techniques have been developed to quantify dyskinesia including wearing devices, accelerometers, and position transducers.
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The Potential Role Of Parkin At The Corticostriatal Synapse
In vitro studies have revealed that parkin can localize at the pre-synapse, where it associates with the cytoplasmic surface of synaptic vesicles and binds to synaptotagmin-11, a pre-synaptic protein involved in synaptic vesicle formation, docking, and recycling . The loss of parkin function may inhibit endocytosis and the processes of vesicle replenishment and recycling, leading to as yet undefined changes in neurotransmitter release. Interestingly, the pre-synaptic functions of parkin resemble the function of synuclein, another key protein involved in PD pathogenesis and a regulator of pre-synapse size and synaptic vesicle pool organization , additionally, the roles of other PD genes such as DNAJC6, SYNJ1, SH3GL2, LRRK2, and VPS35 in the regulation of synaptic vesicle trafficking SVE are beginning to emerge .
This raises the possibility that parkin could be involved in D1 receptor hypersensitization after dopaminergic denervation, an important mechanism underlying the dyskinesia in iPD . Accordingly, a recent paper showed that parkin ubiquitinates and regulates the levels of STEP61, the striatal enriched protein tyrosine phosphatase, whereas clinically relevant parkin mutants fail to do so. Because STEP61 substrates include ERK1/2, it is conceivable that a parkin-induced increase in STEP61 might influence D1 signaling in MSNs .
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Acknowledgements And Conflict Of Interest Disclosure
RM acknowledges grants from the Spanish Ministries de EconomÃa y Competitividad and of Sanidad PolÃtica Social e Igualdad, ISCIII: BFU2010-20664, PNSD, CIBERNED ref. CB06/05/0055 and Comunidad de Madrid ref. S2011/BMD-2336, JRGM is supported by ICyTDF México MTH acknowledges the support by CIBERNED CB05/05/505, SAF2007-062262 and FIS PI10-02827. RH and KC were supported by the German Bundesministerium für Bildung und Forschung, Grant 01GN1006B. NS gratefully acknowledges Sardinia Regional Government for financial support . The authors have no conflicts of interest to declare.
All experiments were conducted in compliance with the ARRIVE guidelines.
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What Causes Dyskinesia
Dyskinesia is a side effect of levodopa that typically occurs four to 10 years after starting the drug. People with Parkinsons disease lose brain cells that produce the chemical dopamine. Levodopa is used to increase levels of dopamine in the brain. This helps to relieve Parkinsons symptoms like tremor or stiffness.
Not everyone with Parkinsons disease will develop dyskinesia. Were not entirely sure why dyskinesias occur in people with PD, Dr. OShea said. One potential explanation is related to the fluctuations in dopamine levels that occur when someone with Parkinsons is taking levodopa, she explained.
How Is It Treated
When dyskinesia is a direct result of taking levodopa, the treatment differs from person to person. Some treatment options may include:
- adjusting the dose of your levodopa to avoid large fluctuations in the amount of dopamine in your system
- taking levodopa in a continuous infusion or an extended release formulation
- taking amantadine extended release , which has been approved to treat dyskinesia
- taking levodopa in smaller doses more often
- taking Duodopa, a medication that helps stabilize the amount of dopamine in the blood, which may help with smoother motor functions
- undergoing deep brain stimulation, which is a surgical treatment for severe symptoms. Certain criteria must be met for this to be an effective treatment. Ask your doctor if this is an option for you. Deep brain stimulation is only done after other treatments have not worked.
As with any treatment, be sure to discuss all side effects with your doctor before deciding on the best treatment for you.
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Current Therapeutic Strategies For Td In Older Patients
The first step in developing the optimal treatment strategy for TD is timely diagnosis, which requires the clinician to be routinely vigilant.67 Diagnosis is based on history of exposure to DRBAs, and a minimum duration of only 1 month of AP exposure is required to diagnose TD in individuals aged 60 years, compared with 3 months in younger adults.2,7,60
An early strategy to mitigate TD symptoms involves modification of the existing AP medication regimen if clinically feasible.68 However, success with this approach is often limited.23,68,69 Two vesicular monoamine transporter 2 inhibitors, valbenazine and deutetrabenazine, have been approved by the US FDA to treat TD.68,70,71 Recent guidelines for the treatment of schizophrenia recommend VMAT2 inhibitors as first-line therapy for patients who have moderate to severe or disabling TD or for patients with mild TD on the basis of such factors as patient preference, associated impairment, or effect on psychosocial functioning.72 In two recent studies of subjects aged 55 years who had participated in clinical trials conducted by the manufacturer, Sajatovic et al demonstrated that valbenazine and deutetrabenazine (mean age: 63.1 years, range: 5581 years are well tolerated in older individuals.73,74 Of note, VMAT2 inhibition manages the symptoms of TD but does not cure them dyskinetic movements generally return when the VMAT2 inhibitor is discontinued.75
Clinical Evidence For Dystonia And Dyskinesia In Parkin Patients
Since the first description of juvenile parkinsonism caused by mutations of the PARKIN gene in two families , dystonia has been proposed as a clinical hallmark of the disease . Recent literature reviews have reported that an overall, clinically typical form of PD with early onset, slow progression, and excellent response to levodopa treatment is frequently associated with dystonia and dyskinesia in patients with PARKIN mutations . Usually independent of levodopa intake, dystonia is described as the presenting symptom in a large percentage of PARKIN patients in whom it can be present in isolation for years before the appearance of parkinsonism . The reported phenotypic overlap between PD patients with PARKIN mutation and rare forms of dystonia-parkinsonism, such as levodopa-responsive dystonia , prompts screening for PARKIN mutations along with GTP cyclohydrolase 1 and tyrosine hydroxylase in clinically diagnosed DRD patients . To determine whether dystonia contributes to gait abnormalities in patients with PARKIN mutations, a recent study used a clinical computerized video motion analysis system to evaluate lower limb dystonia severity in 15 patients. Lower limb dystonia occurred in most PARKIN patients who displayed a specific, abnormal gait pattern that differed from the patterns observed in healthy controls independent of the OFF/ON state .
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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.
How Can I Manage Dyskinesia
Medication Adjustments
If you experience dyskinesias that are bothersome and/or present most of the time, one management strategy is to reduce your dosage of levodopa or other related Parkinsons medications. However, if doing so would adversely affect the control of your chief Parkinsons symptoms, your doctor may prescribe treatment to target the dyskinesia specifically. For example, the FDA has approved an extended-release formulation of amantadine to treat levodopa-induced dyskinesia in people with Parkinsons. Another option is to consider other forms of amantadine, which are approved to treat Parkinsons and may be prescribed off-label to treat dyskinesia.
Calming Activities
Many people with Parkinsons find that exciting and emotional settings, even positive and joyful ones, increase dyskinesia. Strong feelings of stress, anger, and happiness can trigger the release of the brain chemical norepinephrine , which increases involuntary movement. Calming activities such as meditation, yoga, tai chi, massage, and breathing exercises do the opposite. They lessen your sympathetic nervous systems responses to emotional situations. Incorporating these practices into your daily life can strengthen your inner peace and manage your dyskinesia.
Exercise Adjustments
Surgical Therapies
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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.
How Do You Calm Dyskinesia
Here are eight ways to manage dyskinesia.
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Tweak The Timing Of Your Medication
The timing of medication is also a consideration, because of “wearing off” phenomenon, in which some patients feel that the effects of the medication end about four hours after a dose. Your doctor may decide to split your daily medication into smaller, more frequent doses. Doing so may deliver a steadier amount of medication to the body, according to a 2016 research review in the European Medical Journal.
Your doctor may also suggest a switch to extended-release pills, which work in a similar manner. The downside to these formulations, however, is that they tend to require more of the drug to achieve the same result.