An Overview PARKINSON PRIMER
Overview of Parkinson Disease
Parkinson disease (PD) was first described in 1817 by Dr. James Parkinson, a British physician, for whom the disease was named. It is a disease that is characterized by four major features:
Rest tremor of a limb (shaking with the limb at rest)
Slowness of movement (bradykinesia)
Rigidity (stiffness, increased resistance to passive movement) of the limbs or trunk
Poor balance (postural instability)
When at least two of these symptoms are present, and especially if they are more evident on one side than the other, a diagnosis of PD is made, unless there are atypical features that suggest an alternative diagnosis. Patients may first realize something is wrong when they develop a tremor in a limb; movements are slowed and activities take longer to perform; or they experience stiffness and have balance problems. Initially, symptoms are a variable combination of tremor, bradykinesia, rigidity and postural instability. Symptoms typically begin on one side of the body and spread over time to the other side.
Changes occur in facial expression, so that there is a certain facial fixity (blank expression showing little emotion) or a staring appearance (due to reduced frequency of eye blinking). Complaints of a frozen shoulder or foot drag on the affected side are not uncommon. As symptoms come on gradually, older patients may attribute these changes to aging. The tremor is thought to be œshakiness,? bradykinesia is regarded as normal œslowing down,? and stiffness is attributed to arthritis. The stooped posture, common to PD, may be attributed to age or osteoporosis. Both younger and older patients may experience initial symptoms for a year or more before seeking medical evaluation.
Parkinson disease affects 1 in 100 people over the age of 60, with the average age of onset being 60 years. It can also affect younger people. Young-onset Parkinson disease (onset at age 40 or younger) is estimated to occur in 5 “ 10% of patients with PD.
After Alzheimer™s disease, Parkinson disease is the most common neurodegenerative disease.
It is a chronic, progressive disease that results when nerve cells in a part of the midbrain, called the substantia nigra, die or are impaired. These nerve cells produce dopamine, an important chemical messenger that transmits signals from the substantia nigra to another part of the brain called the corpus striatum. These signals allow for coordinated movement. When the dopamine-secreting cells in the substantia nigra die, the other movement control centers in the brain become unregulated. These disturbances in the control centers of the brain cause the symptoms of PD. When 80% of the dopamine-producing cells in the substantia nigra are depleted, symptoms of PD develop.
Initially the symptoms are mild, usually on one side of the body, and may not require medical treatment. Rest tremor is a major characteristic of PD, and the most common presenting symptom, but some patients never develop it. Tremor may be the least disabling symptom, but is often the most embarrassing to the patient. Patients may keep their affected hand in their pocket, behind their back, or hold something to control the tremor, which may be more psychologically distressing than any physical limitation that it imposes.
Over time, initial symptoms become worse. A mild tremor becomes more bothersome and more noticeable. Difficulties may develop with cutting food or handling utensils with the affected limb. Bradykinesia (slowness in movement) becomes a significant problem and the most disabling symptom. Slowness may interfere with daily routines; getting dressed, shaving or showering may take much of the day. Mobility is impaired and difficulty develops in getting into or out of a chair or a car, or turning over in bed. Walking is slower and there is a stooped posture, with the head and shoulders hanging forward. The voice becomes soft and monotonous. A disturbance of balance may lead to falls. Handwriting becomes small (œmicrographia?) and illegible. Automatic movements, such as arm swing when walking, are reduced.
Symptoms may originally be restricted to one limb, but will typically spread over time to the other limb on the same side. They eventually progress to the other side of the body. Generally this progression is gradual, but the rate of progression varies in different patients. As symptoms progress, it is important for patients to talk with their physicians so that optimal treatment can be established. The goal of treatment is not to abolish symptoms, but rather to help the patient manage their symptoms, function independently, and make the appropriate adjustments to a chronic illness. The illness will not go away, but management of its symptoms can be successful in reducing disability or other handicap.
Patients are aware of the progressive nature of the illness and this may become a source of much anxiety. It is not uncommon for patients to over-monitor themselves and their symptoms, compare themselves to other Parkinson disease patients whom they may meet (length of diagnosis, level of symptoms, etc.), and avoid situations such as support groups, where they may see patients who are worse off than they are. Concern about the progression of the disease and the ability to continue working is frequently voiced.
It is not possible to predict with any confidence the likely course of the disease in an individual patient. The rate of progression and resulting level of disability vary in different patients. Some guide to the likely outcome in individual patients is provided by the course of the illness since diagnosis, but this is no more than suggestive.
When the disorder is such that normal activities of daily living are impaired, at least to some extent, symptomatic treatment is begun.
Is PD Inherited?
There is a family history of Parkinson disease in 5-10% of patients. It may affect people of the same generation (e.g., a brother or sister) or in two generations, such as a father and son. Environmental toxins such as manganese, carbon monoxide, and, rarely, certain pesticides cause diseases that resemble PD. However, most people with Parkinson disease have not been exposed to these toxins. In less than 1% of cases, PD is clearly familial. Several gene mutations have been shown to cause Parkinson disease in a few families, but these have not been found in most individuals with PD. Studies of identical twins in which one twin was known to have PD showed no increase in the incidence of PD in the other twin compared to the general population of patients over the age of 60 years. However, among identical twins younger than 50, if one member of the twinship has Parkinson disease, there is an increased risk of PD in the other twin. This indicates heredity may play a role in young-onset cases. Currently, researchers suspect that the cause of Parkinson disease in most individuals reflects a combination of genetic factors and environmental exposures.
What Else Could It Be?
There are many causes of tremor other than Parkinson disease, and it generally requires examination by a neurologist to distinguish between them.
Other Parkinsonism Syndromes
The characteristic symptom-complex of Parkinson disease (tremor, rigidity, bradykinesia, postural instability) is termed parkinsonism. This is a general term and not all patients with parkinsonism have typical Parkinson disease. Early in the disease process it may be difficult to know whether a patient has typical Parkinson disease or a syndrome that mimics it. The development of additional symptoms and the subsequent course of the disease generally points to the correct diagnosis.
Recognizing other causes of Parkinsonism
A number of patients with parkinsonism do not have PD. One study of patients with parkinsonism found that 65% had PD, 18% had drug-induced parkinsonism, 7% had vascular parkinsonism (i.e. from blocking-up of the small blood vessels feeding the brain) and 10% had atypical parkinsonism. Atypical parkinsonism should be considered particularly in patients with poor dopaminergic responsiveness, early loss of balance, prominent intellectual changes (dementia), rapid onset or progression, conspicuous postural hypotension, and little or no tremor. The present of neurological findings not associated with classic Parkinson disease, such as myoclonic jerking (shock-like sudden muscle contractions), should also suggest other diagnostic possibilities. The autonomic nervous system regulates the œinvoluntary? internal functions of the body, such as blood pressure, heart rate, and bladder, rectum, and sexual function. It may be affected in certain atypical parkinsonian syndromes.
Although tremor and postural instability may be less prominent, this condition may be indistinguishable from Parkinson disease. Medications frequently associated with the development of parkinsonism include antipsychotics, metaclopramide, reserpine, tetrabenazine and some calcium-channel blockers (especially cinnarizine and flunarizine). The parkinsonism usually resolves within weeks to months after discontinuing the offending medication.
Progressive Supranuclear Palsy (PSP)
Early onset of imbalance, frequent falls, rigidity of the trunk, and (eventually) eye-movement problems characterize PSP. Symptoms usually begin after age 50 and progress more rapidly than with Parkinson disease. The most characteristic eye movement abnormality is a vertical gaze paralysis. Upgaze and downgaze are therefore limited. Patients may present with frequent falls while walking downstairs, because they cannot look down. Dementia develops later in the disease. There is no specific treatment for PSP. Dopaminergic treatment should be tried but often provides little benefit. Supportive measures such as speech therapy, physical therapy, and antidepressants may help.
Corticobasal Degeneration (CBD)
CBD is the least common of the atypical causes of parkinsonism. It often affects patients quite asymmetrically and progresses more rapidly than Parkinson disease. The initial symptoms of CBD usually develop after age 60 and include asymmetric bradykinesia, rigidity, limb dystonia (abnormal postures), postural instability, and disturbances of language (speech expression or comprehension). There is often marked and disabling apraxia, i.e., it becomes difficult or impossible to use the affected limb even though there is no weakness or sensory loss.
There is no specific treatment for CBD. Supportive treatment such as botulinum toxin for dystonia, antidepressant medications and speech and physical therapy may help. Levodopa and dopamine agonists seldom offer benefit.
Multiple System Atrophy (MSA)
MSA is a neurodegenerative disease of unknown cause. Initially it may be difficult to distinguish from Parkinson disease, but it is far less common and progresses more rapidly. The mean age of onset is in the mid-50s. Clinically, it presents with bradykinesia, poor balance, abnormal autonomic function, rigidity, difficulty with coordination, or a combination of these features. Abnormalities of autonomic function include impotence, low blood pressure upon standing, excessive or reduced sweating, and constipation. There are three subtypes of the illness, each affecting different systems.
Striatonigral degeneration (SND) is characterized by parkinsonism, but without much tremor and with poor response to Sinemet. In the Shy-Drager syndrome, parkinsonism and autonomic abnormalities are conspicuous. In olivopontocerebellar atrophy (OPCA), patients have lack of coordination and clumsiness which affect balance and gait.
As MSA progresses, other symptoms and signs develop that reflect involvement of a different system. Patients with the parkinsonian presentation typically have an asymmetrical tremor, bradykinesa, rigidity and postural instability. Men often develop impotence; both men and women often experience urinary urgency and incontinence. Patients with Shy-Drager syndrome present with more prominent symptoms of autonomic dysfunction.
Although 30% of patients with MSA obtain a definite but short-lived benefit from levodopa and dopamine agonists, the parkinsonism is typically poorly responsive to medications. Dyskinesias and dystonia emerge in half of treated patients. There is not much experience of using deep brain stimulators (DBS) for MSA, but some researchers have found a modest benefit of DBS that persisted for over two years in a few patients.
Multiple small strokes can cause parkinsonism. Patients with this disorder are more likely to present with gait difficulty than tremor and are more likely to have symptoms that are worse in the lower than upper limbs. Some will also report the abrupt onset of symptoms or give a history of step-wise deterioration (symptoms get worse, then plateau for a period). Treatment is the same as for Parkinson disease, but the results are often disappointing.
Dementia with Lewy bodies (DLB)
This disorder is characterized by early dementia, prominent hallucinations, fluctuations over the day in cognitive status, and parkinsonism. The neuropsychological profile is characterized by deficits in attention, executive function (problem solving, planning) and visuospacial function (the ability to produce and recognize figures, drawing or matching figures).
Treatment with cholinesterase inhibitors may reduce delusions, apathy, agitation and hallucinations. A severe reaction to antipsychotic medication is another feature of this disease. If behavioral problems do not respond to cholinesterase inhibitors, low-dose treatment with atypical antipsychotic medications (quetiapine, resperidone, or clozapine) may be considered. Although motor symptoms may respond to levodopa, hallucinations may become worse with its use.
The above information was contributed by Mariann Di Minno, RN, MA, and Michael J. Aminoff, MD, DSc, of the Parkinson™s Disease Clinic and Research Center at the University of California, San Francisco.