Definition

Parkinson disease (PD) is a chronic, progressive neurodegenerative disease. On pathologic examination, it is characterized by prefential degeneration of dopaminergic neurons in substantia nigra pars compacta and the presence of cytoplasmic inclutions known as Lewy bodies; clinically, it is characterized by a resting trmor, bradykinesia, and rigidity. It is important to distinguish PD from the disorders that are known collectively as Parkinson-plus syndromes. These are relatively rare disorders that share some of the features of PD, such as rigidity and bradykinesia. However, the Parkinson-plus syndromes do not respond to medical treatment and have some unique clinical features as well.

The prevalence of PD, in industrialized countries, is estimated at 0,3% of the entire population and 1% of the population older than 60 years. PD is clearly an age-related disease. Studies show that the prevalance of PD increase up to the ninth decade (ages 80 to 89 years) of life. Reliable information about prevalence of PD beyond the ninth decade is not available. Some studies have reported a higher incidence of PD in men than in women, although other studies have refuted this finding.

Symptoms

The most common initial manifestations of PD are rest tremor and bradykinesia. Less common presenting complaints include hypophonia, gait difficulty, and fatigue. It is not uncommon for one of these features to be present for months or even years before others develop.

Pain also a part of PD. An aching pain in the initially affected limb may first be attributed to bursitis or arthritis. Additional symptoms, seen early in the course of PD, include a resting tremor is suppressed by either purposeful movement or sleep and exacerbated by anxiety. The sensation of stiffness occurs in the affected arm or leg and may be accompanied by the perception that one is slow with movement.

As the disease progress, there is marked difficulty in both initiating and terminating movement. There is difficulty in rising from a seated position, particularly when one is seated in a sofa or chair without armrest. Hand-writing becomes smaller and more difficult to read. Friends and family members often complain that the patients speech is more difficult to understand, particularly on the telephone. The symptom of a softer voice a decline in enunciation is known as hypophonia.

Physical Examination

The most distinctive clinical feature is the rest tremor. It is typically present in a single upper extremity early in the course of the disease. As the disease progresses, the resting tremor may spread to both the ipsilateral lower limb and the contralateral limbs. Examination of motor tone reveals cogwheel rigidity in the affected limb. Motor strength, however, remains unaffected.

Additional features that must be evaluated in an examination include rapid, repetitive limb movements and gait. Examination of repetitive movements of the fingers or entire hand will reveal bradykinesia in the affected limb. Examination of gait wiil reveal decreased arm swing on the affected side, smaller steps, and an inability to pivot turn. Typically, patients make several steps to complete a turn because of some degree of postural instability. Deep tendon reflexes and sensation are not affected in PD.

In advanced PD, loss of postural reflexes becomes evident. Individuals are unable to maintain balance when turning. Other manifestations of advanced PD include freezing episodes and dysphagia.

In examination of someone who is talking medication for PD, it is important to record the time at which the last dose of medication was taken relative to the time at which the examination occurs. Medications for PD are particularly in the early stages of the disease. Typically, the rest tremor will subside for 1 to 3 hours after the last dose of medication. Other features, such as reduced arm swing, hypophonia and loss of postural reflexes, do not respond to oral medication.

Functional Limitations

Functional limitations depend on which symptoms are most prominent in a particular patient. Early in the course of PD, the sole limitation may be in ones ability to write legibly. Affected individuals are still able to perform activities of daily living, although the rest tremor may result in a feeling of self-consciousness as it is suppressed with purposeful movement.

As the disease progress, the ability to perform fine motor skills decline, and difficulty with standing and gait develops. An individual will have difficulty in buttoning a shirt or tying shoelaces. More time will be required to stand and initiate gail. Postural instability with a tendency to retropulse also develops. Thus, patients have difficulty in climbing stairs and walking safely and quickly. Slowed reaction times may also affect ones ability to drive safely. Decisions about whether someone should drive are often difficult and must be made on an individual basis. Marked hypophonia may make speaking on the telephone difficult as well. As the voice becomes more affected, dysphagisa is likely to develop.

One aspect of PD that has historically gotten little attention from medical professionals is the effect it has on sexual activity. According to the National Parkinson Foundation, almost 81% of men and 43% of women with PD report experiencing diminished sexual activity. Men may experience a declining interest in sexual activity, abnormal sexual arousal, or reduced orgasm.

In end-stage PD, limitations include marked dysphagia and severe abnormalities of gait that require both devices and one or two person for assistance. At this stage, help is necessary for all activities of daily living as well.

Diagnostic Studies

PD is clinical diagnosis. Conventional laboratory investigations do not contribute to the diagnosis or management of PD. Computed tomography and magnetic resonance imaging scans of the brain do not reveal any consistent abnormalities. Positron emission tomography with use of 6-[18F] flurolevodopa reveals reduced accumulations of radioisotope in the striata. There is greater loss contralateral to the side that is most affected clinically. These findings are consistent with the reduction of dopamine that occurs in PD. However, positron emission tomography remains an experimental rather than a diagnostic tool.

Differential Diagnosis

The differential diagnosis includes several diseases known collectively as the Parkinson-Plus syndromes. Multiple system atrophy in addition to bradykinesia and rigidity multiple system atrophy is characterized by ataxia and autonomic dysfunction that typically is manifested as episodes of flushing or palpitations. Progressive supranuclear palsy in addition to bradykinesia, rigidity and rest tremor. Progressive supranuclear palsy is characterized by the inability to voluntarily move the eyes upward and frequent falls that occur relatively early in the course of the disease. Corticobasal degeneration in addition to bradykinesia and rigidity corticobasal degeneration is characterized by a loss of the ability to coordinate specific purposeful movement of the limbs (apraxia) and a sensation that ones limbs are not ones own (alien-limb syndrome). Essential tremor: Essential tremor is an involuntary, rhythmic tremor of a body part. Essential tremor most commonly affects the arms and hands but can also involve the head voice, tongue, trunk, or legs.

Treatment

Initial

The decision to initiate medical treatment is based on the degree of disability and discomfort that the patient is experiencing. Six classes of drugs are used to treat PD (summarized in Table 132-1). The selection of a particular drug depends on the patients main complaint, which is usually either a rest tremor or bradykinesia. There is no evidence to suggest that expediting or delaying the onset of treatment for PD has any effect on the overall course of the disease. However, it is clear that those who do not receive treatment and are bradykinetic are at greater risk of failing and injuring themselves.

Anticholinergic agents are oldest class of medications used in PD. They are the oldest class of medications used in PD. They are most effective in reducing the rest tremor and rigidity associated with PD. However, the side effects associated with anticholinergic agents typically limit their usefulness. Amntadine is also used in the treatment of PD. Amantadine produces a limited improvement in akinesia, rigidity, and tremor.

Dopamine replacement remains the cornerstone of antiparkinson therapy. Levodopa is the natural precursor to dopamine and is converted to dopamine by the enzyme aromatic amino acid decarboxylase. To ensure that adequate levels of levodopa reach the central nervous system, levodopa is administered simultaneously with a peripheal decarboxylase inhibitor is carbidopa. Levodopa is most effective in reducing tremor, rigidity, and akinesia. The most common side effect, seen with the onset of treatment, are nausea, abdominal cramping, and diarrhea. Long-term treatment with levodopa is associated with three types of complications: hourly fluctuations in motor state, dykinesias, and a variety of psychiatric complaints including hallucinations and confusion. However, it is not clear whether the motor fluctuation are due to the levodopa treatment alone, the disease progression alone, or a complex interplay of imperfect dopamine replacement and the inexorable progression of disease. In summary, current evidence supports the use of dopamine replacement as soon as the symptoms of PD become troublesome to the individual patient. There is no evidence that support withholding of treatment to minimize long-term motor complications.

Dopamine agonists, which directly stimulate dopamine receptors, are also used in the treatment of PD. These agents can be used either as an adjunct to levodopa therapy or as monotherapy. The older dopamine agonist, which are relatively nonspecific and exert their effects at both D1 and D2 receptors, are bromocriptine and pergolide. In comparison to the side effects seen with levodopa, there is a lower frequency of dyskinesias and a higher frequency of confusion and hallucinations. The newer dopamine agonists pramipexole and ropinirole are more specific for D2 receptors. These newer agents have been reported to cause excessive lethargy and sleep attacks. All dopamine agonist can cause orthostatic hypotension, particularly when they are first introduced. It is best to start with a small dose of medication at bed time and then slowly increase the total daily dose

Inhibitors of dopamine metabolism are also used in the medical treatment of PD. Both selegiline and rasagiline inhibit monoamine oxidase B, which metabolizes dopamine in the central nervous system. Thus, inhibitors of monoamine oxidase B are thought to improve an individuals response to levodopa by alleviating the motor fluctuations that are seen with long-term levodopa treatment. Another agent that inhibits the metabolism of dopamine is entacapone. Entacapone inhibits catechol O-methyltransferase in the periphery. Entacapone is administered in conjunction with levodopa and, by inhibiting peripheral catechol O-methyltransferase activity, increases the amount of levodopa that reaches the central nervous system. The benefit of entacapone treatment include a reduction in total daily levodopa dose and an improvement in the length of time of maximum mobility.

Constipation is a frequent complaint. Treatment includes increase in physical activity; discontinuation of anticholinergic drugs; and maintenance of a diet with intake of adequate fluids, fruit, vegetables, fiber, and lactulose (10 to 20 g daily).