Am Fam Physician. 2007;75(6):922-924
Guideline source: American Academy of Neurology
Literature search described? Yes
Evidence rating system used? Yes
Published source: Neurology, April 2006
Parkinson's disease is the second most common neurodegenerative disease and is characterized by bradykinesia; tremor at rest; rigidity; and abnormalities of balance, posture, and gait. Its etiology remains unknown in most patients. Recommendations from the Quality Standards Subcommittee of the American Academy of Neurology (AAN) discuss the following aspects of this condition in a collection of articles in the April 2006 issue of Neurology: diagnosis and prognosis; neuroprotective strategies and alternative therapies; treatment; and evaluation and treatment of depression, psychosis, and dementia in patients with Parkinson's disease.
An accurate diagnosis of Parkinson's disease is challenging in the early stages of the disease. Long-term follow-up and clinical examination may be the best way to confirm the diagnosis during the lifetime of the patient.
The presence of the following clinical fetures distinguishes Parkinson's disease from other parkinsonian syndromes: falls at presentation and early in the disease; poor response to levodopa (Larodopa); symmetric motor signs at onset; rapid progression (to Hoehn and Yahr stage 3 in three years); lack of tremor; and early dysautonomia.
When the diagnosis is questionable, levodopa and apomorphine (Apokyn) challenge should be considered for confirmation. Also, olfaction testing should be considered to distinguish Parkinson's disease from corticobasal degeneration and progressive supranuclear palsy, but not to distinguish Parkinson's disease from multiple system atrophy. However, there is insufficient evidence to determine whether levodopa and apomorphine challenge and olfaction testing are more accurate than clinical diagnostic criteria for Parkinson's disease.
Growth hormone stimulation with clonidine, electro-oculography, and single-photon emission computed tomography may not be useful in distinguishing Parkinson's disease from other parkinsonian syndromes. Also, there is insufficient evidence to support or refute the use of autonomic testing, brain parenchyma sonography, fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, urethral or anal electromyography, or urodynamics to make this distinction.
Factors that predict a more rapid rate of progression of Parkinson's disease include older age at onset (defined as age 57 to 78 years) and rigidity/hypokinesia as a presenting symptom. Male sex, features of postural instability, gait disorder, and comorbidities for Parkinson's disease (e.g., auditory defects, stroke, visual impairments) also may predict a more rapid rate of motor progression of Parkinson's disease.
Tremor at the initial presentation appears to predict slower progression and a longer response to levodopa therapy. Older age at onset and initial manifestations of hypokinesia/rigidity probably predict earlier development of cognitive decline and dementia.
Dementia, older age at onset, and decreased dopamine responsiveness are factors that may predict an increased risk of placement in a nursing home and a shorter survival rate.
Motor Fluctuations and Dyskinesia
For the treatment of motor features of tremor, bradykinesia, and rigidity associated with Parkinson's disease, dopaminergic therapies (e.g., levodopa) are initially effective; however, motor fluctuations eventually complicate therapy and can cause significant disability and impair quality of life. Sustained-release carbidopa/levodopa (Sinemet) and bromocriptine have not been found to reduce off time.
Risk factors for motor complications include disease severity, younger age at onset of Parkinson's disease, high levodopa dosage, and longer disease duration. The motor fluctuations usually are addressed with levodopa adjustments as well as adjunctive medications or surgery as discussed below.
Entacapone (Comtan) and rasagiline (Azilect) can be recommended to reduce “off” time for patients with Parkinson's disease who have motor fluctuations. Pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), and tolcapone (Tasmar) may also be considered to reduce off time. However, tolcapone and pergolide require monitoring, and it is recommended that they be used with caution.
Other drugs to reduce off time include apomorphine, cabergoline (Dostinex), and selegiline (Eldepryl).
Although ropinirole has been recommended over bromocriptine (Parlodel) for reducing off time, there is not enough evidence to recommend one agent over another.
Motor fluctuations and dyskinesia can be resistant to medical therapy, which has led to an increase in surgical approaches for medically refractory disabilities. Deep brain stimulation (DBS) is the most common surgery for Parkinson's disease in North America.
Deep Brain Stimulation
DBS uses an implanted electrode connected to an implantable pulse generator to deliver electrical current to targeted nuclei—ventral intermediate nucleus of the thalamus, globus pallidus interna, and the subthalamic nucleus—in the brain.
Candidates considered for DBS treatment include non-demented, neuropsychiatrically intact, and levodopa-responsive patients who want to reduce their motor fluctuations, dyskinesia, and medication usage. It is recommended that physicians counsel patients on the risks and benefits of this procedure.
However, there is not sufficient evidence to clearly show the effectiveness of DBS for reducing motor complications or medication usage, or in improving motor function in patients with Parkinson's disease.
As the treatment of motor symptoms has improved, it has become increasingly clear that nonmotor features of Parkinson's disease (e.g., dementia, depression, psychosis) may result in significant disability.
Nonmotor symptoms in patients with Parkinson's disease include depression, anxiety, fatigue, sleep problems, and sensory disturbance, and may affect the autonomic, neuropsychiatric, and sensory domains. The prevalence of nonmotor symptoms is high, but physician recognition of these clinical features is relatively low.
Symptoms such as withdrawal, flattened affect, and decreased physical activity overlap with dementia and depression, making it much more difficult to identify these cognitive and behavior disorders.
Parkinson's disease remains a progressive disease with complex, long-term, nonmotor symptoms that often go unrecognized. The use of validated diagnostic questionnaires and rating scales is needed to identify the impact of depression, psychosis, and dementia in these patients.
The Beck Depression Inventory and the Hamilton Depression Rating Scale are recommended for depression screening in patients with Parkinson's disease. The Montgomery Asberg Depression Rating Scale also may be considered for depression screening.
The Mini-Mental State Examination and the Cambridge Cognitive Examination are recommended as screening tools for dementia in patients with Parkinson's disease.
Depression associated with Parkinson's disease can be treated with amitriptyline. However, it is not necessarily the first-line treatment. There is insufficient evidence to recommend other treatments for depression in patients with the disease.
Clozapine (Clozaril) is recommended as a drug treatment for patients with Parkinson's disease who also have psychosis. Physicians must monitor the absolute neutrophil count because the drug's use with agranulocytosis could be fatal.
Quetiapine (Seroquel) also is recommended, but olanzapine (Zyprexa) should not be routinely considered.
Rivastigmine (Exelon) can be recommended for the treatment of dementia in patients with Parkinson's disease, although the benefit is modest and the use of this medication may cause exacerbation of tremors. Donepezil (Aricept) also should be considered for the treatment of dementia in these patients. There is not enough evidence to refute or support the effectiveness of piracetam (Nootropil).
Patients with Parkinson's disease should not be treated with 2,000 units of vitamin E because this does not provide neuroprotection and will not delay the need for levodopa therapy. There is not enough evidence to recommend the use of amantadine (Symmetrel), riluzole (Rilutek), coenzyme Q10, pramipexole, ropinirole, rasagiline, or thalamotomy for neuroprotection. However, a modest benefit from riluzole and coenzyme Q10 cannot be ruled out.
Levodopa can be used for the initial treatment of Parkinson's disease because it doesn't accelerate the progression of the disease and is considered to be safe. There is not, however, any long-term evidence to recommend that levodopa be used for neuroprotection.
FOODS AND VITAMINS
Mucuna pruriens, or velvet bean, has been shown to contain levodopa. However, its benefit cannot be determined.
As mentioned above, vitamin E is ineffective for the treatment of Parkinson's disease. Neither vitamin C nor folic acid has been adequately studied, but vitamin C can increase levodopa levels.
As one of the most widely used treatment options in alternative medicine, acupuncture suggests that it has symptomatic benefits for motor and nonmotor symptoms of Parkinson's disease. However, no controlled studies exist to determine if acupuncture holds any benefit for patients with the disease.
MANUAL THERAPY AND EXERCISE
Chiropractic manipulation, osteopathic manipulation, and Trager therapy have been suggested to benefit patients with Parkinson's disease. No studies exist, however, to refute or confirm this position. The Alexander technique has shown some benefit and patient improvement has been noted in some studies.
Standard physical therapy, as well as occupational therapy, did result in improved functional outcomes, but the benefit was small and was not sustained when the exercise therapy stopped.
Patients with Parkinson's disease may develop dysarthria, and speech therapy is often used to treat it. Individual speech therapy that emphasizes prosodic features of pitch and volume may improve speech volume. Individual speech therapy aimed at maximizing phonatory efforts also may improve speech volumes, but there is not enough evidence to recommend one type of speech therapy over another.