What is bradykinesia

Bradykinesia means slowed movement or slowness of movement. Hypokinesia refers to small amplitude movements, particularly with repetitive movements  ¹. Akinesia means absence or poverty of expected spontaneous voluntary movement including slow reaction time ². Bradykinesia is one of the clinical hallmarks of Parkinson’s disease and atypical Parkinsonian syndromes ³. Bradykinesia makes simple tasks difficult and time-consuming. Your steps may become shorter when you walk. Bradykinesia can make it difficult to get out of a chair. People with bradykinesia may drag their feet as they try to walk.

In Parkinson’s disease, bradykinesia happens in different ways:

• Reduction of automatic movements (such as blinking or swinging your arms when you walk)
• Difficulty initiating movements (like getting up out of a chair)
• General slowness in physical actions
• The appearance of abnormal stillness or a decrease in facial expression

This translates into difficulty performing everyday functions, such as buttoning a shirt, cutting food or brushing your teeth.

Bradykinesia can be particularly frustrating because it is often unpredictable. One moment you can move easily, while in the next moment you may need help.

Dopamine is a chemical messenger (neurotransmitter) that is primarily responsible for controlling movement, emotional responses and the ability to feel pleasure and pain. In people with Parkinson’s disease, the cells that make dopamine are impaired. As Parkinson’s disease progresses, more dopamine-producing brain cells die. Your brain eventually reaches a point where it stops producing dopamine in any significant amount. This causes increasing problems with movement.

Symptoms generally develop slowly over years. The progression of symptoms is often a bit different from one person to another due to the diversity of the disease. People with Parkinson’s disease may experience:

• Tremor, mainly at rest and described as pill rolling tremor in hands. Other forms of tremor are possible
• Bradykinesia
• Limb rigidity
• Gait and balance problems

There is no single test or scan for Parkinson’s disease, but there are three telltale symptoms that help doctors make a diagnosis:

1. Bradykinesia
2. Tremor
3. Rigidity

Bradykinesia plus either tremor or rigidity must be present for a Parkinson’s disease diagnosis to be considered ⁴.

Another movement symptom, postural instability (trouble with balance and falls), is often mentioned, but it does not occur until later in the disease progression. In fact, problems with walking, balance and turning around early in the disease are likely a sign of an atypical parkinsonism.

Clinical ratings scales and technology-based assessments have been developed to measure bradykinesia. Bradykinesia is effectively measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) and Movement Disorder Society revision of the UPDRS, the MDS-UPDRS, and the clinical exam remains the gold standard for evaluation of Parkinsonian patients ³. An additional scale, the Modified Bradykinesia Rating Scale for Parkinson’s disease ⁵ has also been used in clinical practice, though the gold standard for assessment of bradykinesia remain the Unified Parkinson’s Disease Rating Scale (UPDRS) and Movement Disorder Society revision of the UPDRS, the MDS-UPDRS. These scales have also been effectively applied to atypical Parkinsonian syndromes such as progressive supranuclear palsy. Technology-based tools are aimed at quantifying bradykinesia objectively to increase diagnostic accuracy and to help monitor subtle clinical changes when therapies are initiated. To date, no new treatment has received regulatory approval based on use of technology-based objective measures of bradykinesia or any other objective measure of parkinsonism.

There are currently no blood or laboratory tests that diagnose sporadic Parkinson’s disease. Therefore the diagnosis is based on medical history and a neurological examination. In some cases Parkinson’s disease can be difficult to diagnose accurately early on in the course of the disease. Early signs and symptoms of Parkinson’s disease may sometimes be dismissed as the effects of normal aging. Doctors may sometimes request brain scans or laboratory tests in order to rule out other disorders. However, computed tomography (CT) and magnetic resonance imaging (MRI) brain scans of people with Parkinson’s disease usually appear normal. Since many other diseases have similar features but require different treatments, making a precise diagnosis is important so that people can receive the proper treatment.

Bradykinesia causes

Bradykinesia is one of the clinical hallmarks of Parkinson’s disease and atypical Parkinsonian syndromes ³. Parkinson’s disease is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.

The cause of Parkinson’s disease remains largely unknown.

Parkinson’s disease occurs when nerve cells, or neurons, in the brain die or become impaired. Although many brain areas are affected, the most common symptoms result from the loss of neurons in an area near the base of the brain called thesubstantia nigra. Normally, the neurons in this area produce an important brain chemical known as dopamine. Dopamine is a chemical messenger responsible for transmitting signals between the substantia nigra and the next “relay station” of the brain, the corpus striatum, to produce smooth, purposeful movement. Loss of dopamine results in abnormal nerve firing patterns within the brain that cause impaired movement. Studies have shown that most people with Parkinson’s have lost 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra by the time symptoms appear, and that people with Parkinson’s disease also have loss of the nerve endings that produce the neurotransmitter norepinephrine. Norepinephrine, which is closely related to dopamine, is the main chemical messenger of the sympathetic nervous system, the part of the nervous system that controls many automatic functions of the body, such as pulse and blood pressure. The loss of norepinephrine might explain several of the non-motor features seen in Parkinson’s disease, including fatigue and abnormalities of blood pressure regulation.

The affected brain cells of people with Parkinson’s disease contain Lewy bodies—deposits of the protein alpha-synuclein. Researchers do not yet know why Lewy bodies form or what role they play in the disease. Some research suggests that the cell’s protein disposal system may fail in people with Parkinson’s disease, causing proteins to build up to harmful levels and trigger cell death. Additional studies have found evidence that clumps of protein that develop inside brain cells of people with Parkinson’s disease may contribute to the death of neurons. Some researchers speculate that the protein buildup in Lewy bodies is part of an unsuccessful attempt to protect the cell from the toxicity of smaller aggregates, or collections, of synuclein.

Genetics

Scientists have identified several genetic mutations associated with Parkinson’s disease, including the alpha-synuclein gene, and many more genes have been tentatively linked to the disorder. Studying the genes responsible for inherited cases of Parkinson’s disease can help researchers understand both inherited and sporadic cases. The same genes and proteins that are altered in inherited cases may also be altered in sporadic cases by environmental toxins or other factors. Researchers also hope that discovering genes will help identify new ways of treating Parkinson’s disease.

Environment

Exposure to certain toxins has caused parkinsonian symptoms in rare circumstances (such as exposure to MPTP, an illicit drug, or in miners exposed to the metal manganese). Other still-unidentified environmental factors may also cause Parkinson’s disease in genetically susceptible individuals.

Mitochondria

Several lines of research suggest that mitochondria may play a role in the development of Parkinson’s disease. Mitochondria are the energy-producing components of the cell and abnormalities in the mitochondria are major sources of free radicals—molecules that damage membranes, proteins, DNA, and other parts of the cell. This damage is often referred to as oxidative stress. Oxidative stress-related changes, including free radical damage to DNA, proteins, and fats, have been detected in the brains of individuals with Parkinson’s disease. Some mutations that affect mitochondrial function have been identified as causes of Parkinson’s disease.

While mitochondrial dysfunction, oxidative stress, inflammation, toxins, and many other cellular processes may contribute to Parkinson’s disease, the actual cause of the cell loss death in Parkinson’s disease is still undetermined.

Who gets Parkinson’s disease?

Estimates suggest that about 50,000 Americans are diagnosed with Parkinson’s disease each year, although some estimates are much higher. Getting an accurate count of the number of cases is difficult because many people in the early stages of the disease may assume their symptoms are the result of normal aging and do not seek medical attention. Diagnosis is sometimes complicated by the fact that other conditions may produce symptoms of Parkinson’s disease and there is no definitive test for the disease. People with Parkinson’s disease may sometimes be told by their doctors that they have other disorders, and people with Parkinson’s disease-like diseases may be incorrectly diagnosed as having Parkinson’s disease.

Parkinson’s disease affects about 50 percent more men than women, and the reasons for this discrepancy are unclear. While Parkinson’s disease occurs in people throughout the world, a number of studies have found a higher incidence in developed countries. Other studies have found an increased risk in people who live in rural areas with increased pesticide use. However, those apparent risks are not fully characterized.

One clear risk factor for Parkinson’s disease is age. The average age of onset is 60 years, and the incidence rises significantly with advancing age. However, about 5 to 10 percent of people with Parkinson’s disease have “early-onset” disease that begins before the age of 50. Some early-onset cases are linked to specific gene mutations such as parkin. People with one or more close relatives who have Parkinson’s disease have an increased risk of developing the disease themselves, but the total risk is still about 2 to 5 percent unless the family has a known gene mutation for the disease. An estimated 15 to 25 percent of people with Parkinson’s disease have a known relative with the disease.

In very rare cases, parkinsonian symptoms may appear in people before the age of 20. This condition is called juvenile parkinsonism. It often begins with dystonia and bradykinesia, and the symptoms often improve with levodopa medication.

Bradykinesia symptoms

Bradykinesia is slowness of movement, which is one clinical hallmarks of Parkinson’s disease. There is no single test or scan for Parkinson’s disease, but there are three telltale symptoms that help doctors make a diagnosis:

1. Bradykinesia. This slowing down of spontaneous and automatic movement is particularly frustrating because it may make simple tasks difficult. The person cannot rapidly perform routine movements. Activities once performed quickly and easily—such as washing or dressing—may take much longer. There is often a decrease in facial expressions.
2. Tremor. The tremor associated with Parkinson’s disease has a characteristic appearance. Typically, the tremor takes the form of a rhythmic back-and-forth motion at a rate of 4-6 beats per second. It may involve the thumb and forefinger and appear as a “pill rolling” tremor. Tremor often begins in a hand, although sometimes a foot or the jaw is affected first. It is most obvious when the hand is at rest or when a person is under stress. Tremor usually disappears during sleep or improves with intentional movement. It is usually the first symptom that causes people to seek medical attention.
3. Rigidity. Rigidity, or a resistance to movement, affects most people with Parkinson’s disease. The muscles remain constantly tense and contracted so that the person aches or feels stiff. The rigidity becomes obvious when another person tries to move the individual’s arm, which will move only in ratchet-like or short, jerky movements known as “cogwheel” rigidity.
4. Postural instability. Postural instability, or impaired balance, causes affected individuals to fall easily.

Bradykinesia plus either tremor or rigidity must be present for a Parkinson’s disease diagnosis to be considered ⁴.

Parkinson’s disease does not affect everyone the same way, and the rate of progression and the particular symptoms differ among individuals.

Parkinson’s disease symptoms typically begin on one side of the body. However, the disease eventually affects both sides. Even after the disease involves both sides of the body, the symptoms are often less severe on one side than on the other.

Friends or family members may be the first to notice changes in someone with early Parkinson’s disease. They may see that the person’s face lacks expression and animation (known as “masked face”) or that the person moves more slowly.

Early symptoms of Parkinson’s disease may be subtle and occur gradually. Affected people may feel mild tremors or have difficulty getting out of a chair. Activities may take longer to complete than in the past and individuals may note some stiffness in addition to slowness. They may notice that they speak too softly or that their handwriting is slow and looks cramped or small. This very early period may last a long time before the more classical and obvious motor (movement) symptoms appear.

As the disease progresses, the symptoms of Parkinson’s disease may begin to interfere with daily activities. Affected individuals may not be able to hold utensils steady or they may find that the shaking makes reading a newspaper difficult. People with Parkinson’s disease often develop a so-called parkinsonian gait that includes a tendency to lean forward, taking small quick steps as if hurrying (called festination), and reduced swinging in one or both arms. They may have trouble initiating movement (start hesitation), and they may stop suddenly as they walk (freezing).

Additional movement symptoms

• Cramping (dystonia): sustained or repetitive twisting or tightening of muscle.
• Dizziness or Fainting
• Drooling (sialorrhea): while not always viewed as a motor symptom, excessive saliva or drooling may result due to a decrease in normally automatic actions such as swallowing.
• Dyskinesia: involuntary, erratic writhing movements of the face, arms, legs or trunk.
• Dystonia. The rigidity and lack of normal movement associated with Parkinson’s disease often causes muscle cramps, especially in the legs and toes. Massage, stretching, and applying heat may help with these cramps. Parkinson’s disease can also be associated with dystonia—sustained muscle contractions that cause forced or twisted positions. Dystonia in Parkinson’s disease is often caused by fluctuations in the body’s level of dopamine. Management strategies may involve adjusting medications.
• Festination: short, rapid steps taken during walking. May increase risk of falling and often seen in association with freezing.
• Freezing: gives the appearance of being stuck in place, especially when initiating a step, turning or navigating through doorways. Potentially serious problem as it may increase risk of falling.
• Masked face (hypomimia): results from the combination of bradykinesia and rigidity.
• Micrographia: small, untidy and cramped handwriting due to bradykinesia.
• Postural Instability (trouble with balance and falls)
• Rigidity (Stiffness)
• Shuffling gait: accompanied by short steps and often a stooped posture.
• Soft speech (hypophonia): soft, sometimes hoarse, voice that can occur in Parkinson’s disease.
• Stooped Posture
• Trouble Moving or Walking

Non-movement symptoms

In addition to motor symptoms such as bradykinesia (slowness of movement), tremor, stiffness and postural instability, most people develop other health problems related to Parkinson’s disease. These symptoms are diverse and collectively known as non-motor symptoms.

While family and friends may not be able to see these symptoms, it is important to realize that non-motor symptoms are common and can be more troublesome and disabling than motor symptoms. Some symptoms, such as loss of smell, constipation, depression and REM sleep behavior disorder can occur years before the diagnosis of Parkinson’s disease.

Non-motor symptoms can include:

• Anxiety
• Apathy
• Breathing and respiratory difficulties
• Cognitive changes: problems with attention, planning, language, memory or even dementia. Some people with Parkinson’s disease may develop memory problems and slow thinking. Cognitive problems become more severe in late stages of Parkinson’s disease, and a diagnosis of Parkinson’s disease dementia (Parkinson’s diseaseD) may be given. Memory, social judgment, language, reasoning, or other mental skills may be affected. There is currently no way to halt Parkinson’s disease dementia, but drugs such as rivastigmine, donepezil, or memantine may help. The medications used to treat the motor symptoms of Parkinson’s disease may cause confusion and hallucinations.
• Constipation and nausea
• Depression. This common disorder may appear early in the course of the disease, even before other symptoms are noticed. Some people lose their motivation and become dependent on family members. Fortunately, depression typically can be treated successfully with antidepressant medications such as amytriptyline or fluoxetine.
• Early satiety: feeling of fullness after eating small amounts
• Emotional changes. Some people with Parkinson’s disease become fearful and insecure, while others may become irritable or uncharacteristically pessimistic.
• Excessive sweating, often when wearing off medications
• Fatigue and loss of energy. Many people with Parkinson’s disease often have fatigue, especially late in the day. Fatigue may be associated with depression or sleep disorders, but it may also result from muscle stress or from overdoing activity when the person feels well. Fatigue may also result from akinesia—trouble initiating or carrying out movement. Exercise, good sleep habits, staying mentally active, and not forcing too many activities in a short time may help to alleviate fatigue.
• Increase in dandruff (seborrheic dermatitis)
• Hallucinations and delusions. Hallucinations, delusions, and other psychotic symptoms can be caused by the drugs prescribed for Parkinson’s disease. Reducing Parkinson’s disease medications dosages or changing medications may be necessary if hallucinations occur. If such measures are not effective, doctors sometimes prescribe drugs called atypical antipsychotics, which include clozapine and quetiapine. The typical antipsychotic drugs, which include haloperidol, worsen the motor symptoms of Parkinson’s disease and should not be used.
• Lightheadedness (orthostatic hypotension): drop in blood pressure when standing
• Loss of sense of smell or taste
• Mood disorders, such as depression, anxiety, apathy and irritability
• Orthostatic hypotension. Orthostatic hypotension is a sudden drop in blood pressure when a person stands up from a lying-down or seated position. This may cause dizziness, lightheadedness, and, in extreme cases, loss of balance or fainting. Studies have suggested that, in Parkinson’s disease, this problem results from a loss of nerve endings in the sympathetic nervous system that controls heart rate, blood pressure, and other automatic functions in the body. The medications used to treat Parkinson’s disease may also contribute to this symptom. Orthostatic hypotension may improve by increasing salt intake. Physicians treating the disorder may also reduce anti-hypertension drug dosage or by prescribing medications such as fludrocortisone.
• Pain. Many people with Parkinson’s disease develop aching muscles and joints because of the rigidity and abnormal postures often associated with the disease. Treatment with levodopa and other dopaminergic drugs often alleviates these pains to some extent. Certain exercises may help.
• Sexual problems, such as erectile dysfunction. Because of its effects on nerve signals from the brain, Parkinson’s disease may cause sexual dysfunction. Parkinson’s disease-related depression or use of certain medications may also cause decreased sex drive and other problems. People should discuss these issues with their physician as they may be treatable.
• Skeletal and bone health. Rigidity, weakened muscles and involuntary muscle contractions (dystonia) can cause painful deformities for people with Parkinson’s disease. A tilted or twisted spine also can throw a person off balance and increase the risk of falling.
• Skin changes. In Parkinson’s disease, the skin on the face may become oily, particularly on the forehead and at the sides of the nose. The scalp may become oily too, resulting in dandruff. In other cases, the skin can become very dry. Standard treatments for skin problems can help.
• Sleep disorders, such as insomnia, excessive daytime sleepiness, REM sleep behavior disorder, vivid dreams, Restless Legs Syndrome
• Speech changes. About half of all individuals with Parkinson’s disease have speech difficulties that may be characterized as speaking too softly or in a monotone. Some may hesitate before speaking, slur, or speak too fast. A speech therapist may be able to help these individuals reduce some of these problems.
• Swallowing and chewing problems. Muscles used in swallowing may work less efficiently in later stages of the disease. Food and saliva may collect in the mouth and back of the throat, which can result in choking or drooling. These problems may also make it difficult to get adequate nutrition. Speech-language therapists, occupational therapists (who help people learn new ways to perform activities of daily living), and dieticians can often help with these problems.
• Urinary urgency, frequency and incontinence
• Vertigo and dizziness
• Vision problems, especially when attempting to read items up close
• Weight loss

Bradykinesia test

The Unified Parkinson’s Disease Rating Scale

The Unified Parkinson’s Disease Rating Scale (UPDRS) was developed to assess Parkinson’s disease function, and bradykinesia is rated by observation of several tasks, each scored using five options from normal (0) to severe impairment (4). Eleven of the total 27 objective ratings measure bradykinesia through finger taps, hand movements, rapid alternating movements of the hands, leg agility, arising from a chair, gait, and body bradykinesia and hypokinesia. The factor structure and internal consistency has been studied in 294 Parkinson’s disease patients in the “on” state, that is during the period of the day when they experience positive dopaminergic medication effects. Factor structure analysis was performed and six factors were obtained which accounted for approximately 78% of the sample variance. Three of these six factors concerned bradykinesia. Items assessing axial function, balance, and gait clustered together into one factor. Two additional distinct factors, right side extremity and left side extremity bradykinesia were also identified. There was no correlation between bradykinesia testing on the right and left sides. These Unified Parkinson’s Disease Rating Scale (UPDRS) measures of bradykinesia correlated well with other measures of Parkinson’s disease disability, i.e., Hoehn and Yahr (HY) staging and Schwab and England ADL scale (SE) ⁶.

In order to confirm that the statistic stability of the Unified Parkinson’s Disease Rating Scale (UPDRS) factor structure across different groups of patients with varying levels of Parkinson’s disease impairment, a subsequent analysis was performed with Parkinson’s disease patients in the off state, that is when medication effects were not apparent. In a sample of 200 patients examined in the off state, with identical analytic methods used in the prior publication, six factors were again identified and accounted for approximately 70% of the variance, three of which related to bradykinesia. All assessments of axial function, speech, facial expression, balance, and gait clustered together into one factor. Again, two additional distinct factors assessing bradykinesia affecting the extremities were identified, right and left. There was no correlation between bradykinesia testing on the right and left sides. There was a significant relationship between the individual factors assessing bradykinesia from the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr stage. The results were highly consistent between the two studies, confirming the reliability and validity of the Unified Parkinson’s Disease Rating Scale (UPDRS) as a scale for assessment of bradykinesia in Parkinson’s disease both when patients are experiencing medication benefit and when they are not ⁷.

The Unified Parkinson’s Disease Rating Scale (UPDRS) has also been applied to the evaluation of parkinsonian syndromes outside of Parkinson’s disease. Progressive Supranuclear Palsy (PSP) shares some clinical features with Parkinson’s disease and is the most common and best recognized condition among the atypical parkinsonian syndromes. A study analyzing the factor structure of Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Examination in 175 PSP patients revealed five factors which accounted for approximately 64% of the sample variance, two of which assess bradykinesia. Items assessing axial bradykinesia and gait clustered into one factor, and items assessing bradykinesia of the extremities, right and left combined, clustered into a separate factor. There was no correlation between these two factors, and each of the factors assessing bradykinesia was significantly related to Hoehn and Yahr (HY) stage. No side-to-side difference in bradykinesia was found in the factor analysis for Progressive Supranuclear Palsy (PSP) patients, which follows the typical clinical presentation of Progressive Supranuclear Palsy (PSP) as a symmetrical illness in contrast with the asymmetry of typical Parkinson’s disease. These results support the validity and reliability for the use of the motor scale of the Unified Parkinson’s Disease Rating Scale (UPDRS) in measuring bradykinesia for patients with Progressive Supranuclear Palsy (PSP) ⁸.

The movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale

The Movement Disorder Society revision of the UPDRS, the MDS-UPDRS is a revision of the original Unified Parkinson’s Disease Rating Scale (UPDRS), aimed at retaining the strengths of the original scale and resolving some of the ambiguities and identified weaknesses. In regards to bradykinesia, the main addition to the MDS-UPDRS involves toe tapping. Conceptually, the Unified Parkinson’s Disease Rating Scale (UPDRS) and the MDS-UPDRS are not identical, as the new scale was designed specifically to detect very mild changes not captured in the original scale. As such, the five options for each item are “normal,” “slight,” “mild,” “moderate,” and “severe” impairment whereas the original scale focused more on advanced disease. Thus for most items, and specifically the bradykinesia items, direct item-to-item mapping is not possible between the two scales. The factor structure of the MDS-UPDRS was evaluated in a study of 877 native English-speaking Parkinson’s disease patients of diverse race/ethnicity representations. Exploratory and confirmatory analysis of the individual parts of the MDS-UPDRS identified a factor structure that was statistically consistent and clinically meaningful for all parts. Eigenvalues and scree plots informed the exploratory factor analysis which determined the number of factors that best represented the data. Confirmatory analysis was used to assess dimensionality, with a comparative fit index (CFI) greater than or equal to 0.90 as an acceptable fit. For the Motor Examination the CFI = 0.91, and seven factors were identified, four of which pertained to bradykinesia (midline function, bradykinesia right upper extremity, bradykinesia left upper extremity, lower limb bradykinesia, including both right and left legs). Further, there was a strong concurrent validity based on high correlations between the MDS-UPDRS and the UParkinson’s diseaseRS Part III (r = 0.96). These results support the reliability and validity of the MDS-UPDRS in Parkinson’s disease patients. This has led to an increasing trend in the field to adopt this newer scale as the “gold standard” ⁹.

Bradykinesia treatment

Levodopa combined with carbidopa is the medication most commonly given to control the movement symptoms of Parkinson’s disease. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of parkinsonian cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity. Other drugs, such as bromocriptine, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. In May 2006, the U.S. Food and Drug Administration (FDA) approved rasagiline to be used along with levodopa for patients with advanced Parkinson’s disease or as a single-drug treatment for early Parkinson’s disease. In March 2017, the FDA approved safinamide tablets as an add-on treatment for individuals with Parkinson’s disease how are currently taking levodopa/carbisopa and experiencing “off” episodes (when the person’s medicatins are not working well, causing an increase in Parkinson’s disease symptoms).

Table 1. Medications to treat the motor symptoms of Parkinson’s disease

Category	Generic	Brand name
Drugs that increase brain levels of dopamine	Levodopa/carbidopa	Parcopa, Sinemet
Drugs that mimic dopamine (dopamine agonists)	Apomorphine Pramipexole Ropinirole Rotigotine	Apokyn Mirapex Requip Neupro
Drugs that inhibit dopamine breakdown (MAO-B inhibitors)	Rasagiline Selegiline (deprenyl)	Azilect Eldepryl, Zelapar
Drugs that inhibit dopamine breakdown (COMT inhibitors)	Entacapone Tolcapone	Comtan Tasmar
Drugs that decrease the action of acetylcholine (anticholinergics)	Benztropine Ethopropazine Trihexyphenidyl	Cogentin Parsidol Artane
Drugs with an unknown mechanism of action for PD	Amantadine	Symmetrek

Dopamine agonists, MAO-B inhibitors, and amantadine can also be used alone or in combination with other medications to improve slowness, as well as stiffness and tremor.

Dopamine agonists. These drugs, which include apomorphine, pramipexole, ropinirole, and rotigotine, mimic the role of dopamine in the brain. They can be given alone or with levodopa. They are somewhat less effective than levodopa in treating Parkinson’s disease symptoms, but work for longer periods of time. Many of the potential side effects are similar to those associated with the use of levodopa, including drowsiness, sudden sleep onset, hallucinations, confusion, dyskinesias, edema (swelling due to excess fluid in body tissues), nightmares, and vomiting. In rare cases, they can cause an uncontrollable desire to gamble, hypersexuality, or compulsive shopping.

MAO-B inhibitors. These drugs inhibit the enzyme monoamine oxidase B, or MAO-B, which breaks down dopamine in the brain. MAO-B inhibitors cause dopamine to accumulate in surviving nerve cells and reduce the symptoms of Parkinson’s disease. Studies supported by the NINDS have shown that selegiline (also called deprenyl) can delay the need for levodopa therapy by up to a year or more. When selegiline is given with levodopa, it appears to enhance and prolong the response to levodopa and thus may reduce wearing-off. Selegiline is usually well-tolerated, although side effects may include nausea, orthostatic hypotension, or insomnia. It should not be taken with the antidepressant fluoxetine or the sedative meperidine, because combining selegiline with these drugs can be harmful. The drug rasagiline is used in treating the motor symptoms of Parkinson’s disease with or without levodopa. Whether rasagiline slows progression of Parkinson’s disease is still controversial.

COMT inhibitors. COMT stands for catechol-O-methyltransferase, another enzyme that breaks down dopamine. The drug entacapone and tolcapone prolong the effects of levodopa by preventing the breakdown of dopamine. COMT inhibitors can decrease the duration of “off periods” of one’s dose of levodopa. The most common side effect is diarrhea. The drugs cause nausea, sleep disturbances, dizziness, urine discoloration, abdominal pain, low blood pressure, or hallucinations. In a few rare cases, tolcapone has caused severe liver disease, and people taking tolcapone need regular monitoring of their liver function.

Amantadine. This antiviral drug can help reduce symptoms of Parkinson’s disease and levodopa-induced dyskinesia. It is often used alone in the early stages of the disease. It may also be used with an anticholinergic drug or levodopa. After several months, amantadine’s effectiveness wears off in up to half of the people taking it. Amantadine’s side effects may include insomnia, mottled skin, edema, agitation, or hallucinations. Researchers are not certain how amantadine works in Parkinson’s disease, but it may increase the effects of dopamine.

Anticholinergics. These drugs, which include trihexyphenidyl, benztropine, and ethopropazine, decrease the activity of the neurotransmitter acetylcholine and can be particularly effective for tremor. Side effects may include dry mouth, constipation, urinary retention, hallucinations, memory loss, blurred vision, and confusion.

If you experience “off” periods – changes in your ability to move, usually related to medication timing – when bradykinesia and other symptoms are worse, adjusting the dose or schedule of your medication could help. Talk to your healthcare provider before making any changes to your medications.

In addition to medications, exercise should be part of your treatment plan for all Parkinson’s symptoms.

Exercise. Exercise can help people with Parkinson’s disease improve their mobility and flexibility. Some doctors prescribe physical therapy or muscle-strengthening exercises to tone muscles and to put underused and rigid muscles through a full range of motion. The effects of exercise on disease progression are not known, but it may improve body strength so that the person is less disabled. Exercises also improve balance, helping people minimize gait problems, and can strengthen certain muscles so that people can speak and swallow better. Exercise can improve emotional well-being and general physical activity, such as walking, gardening, swimming, calisthenics, and using exercise machines, can have other benefit. A clinical trial demonstrated the benefit of tai chi exercise compared to resistance or stretching exercises ¹⁰. People with Parkinson’s disease should always check with their doctors before beginning a new exercise program. Other complementary and supportive therapies that are used by some individuals with Parkinson’s disease include massage therapy, yoga, hypnosis, acupuncture, and the Alexander technique, which optimizes posture and muscle activity.

Research also suggests that music therapy can reduce bradykinesia.

In some cases, surgery may be appropriate if the disease doesn’t respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In deep brain stimulation (DBS), electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. Deep brain stimulation can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. Deep brain stimulation requires careful programming of the stimulator device in order to work correctly.

Parkinson’s disease prognosis

The average life expectancy of a person with Parkinson’s disease is generally the same as for people who do not have the disease. Fortunately, there are many treatment options available for people with Parkinson’s disease. However, in the late stages, Parkinson’s disease may no longer respond to medications and can become associated with serious complications such as choking, pneumonia, and falls.

Parkinson’s disease is a slowly progressive disorder. It is not possible to predict what course the disease will take for an individual person. One commonly used scale neurologists use for describing how the symptoms of Parkinson’s disease have progressed in a patient is the Hoehn and Yahr scale.

Hoehn and Yahr Staging of Parkinson’s Disease

1. Stage one — symptoms on one side of the body only.
2. Stage two — symptoms on both sides of the body. No impairment of balance.
3. Stage three — balance impairment. Mild to moderate disease. Physically independent.
4. Stage four — severe disability, but still able to walk or stand unassisted.
5. Stage five – wheelchair-bound or bedridden unless assisted.

Another commonly used scale is the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). This four-part scale measures motor movement in Parkinson’s disease: non-motor experiences of daily living, motor experiences of daily living, motor examination, and motor complications. Both the Hoehn and Yahr scale and the MDS-UPDRS are used to describe how individuals are faring and to help assess treatment response.

References

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2. A clinical rating scale for progressive supranuclear palsy. Golbe LI, Ohman-Strickland PA. Brain. 2007 Jun; 130(Pt 6):1552-65.
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9. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N, Movement Disorder Society UPDRS Revision Task Force. Mov Disord. 2008 Nov 15; 23(15):2129-70.
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