Definition

Parkinson disease (PD) is a chronic, progressive neurodegenerative disease. On pathologic examination, it is characterized by preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta and the presence of cytoplasmic inclusions known as Lewy bodies. It is characterized clinically by a resting tremor, bradykinesia, and rigidity. It is important to distinguish PD from the disorders that are known collectively as the 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 has been estimated in more than 80 studies conducted around the world. The most consistent finding is that PD is an age-related disease. Between the ages of 50 and 59 years, the prevalence is estimated at 273 per 100,000, whereas between 70 and 79 years, the prevalence is estimated at 2700 per 100,000 [1]. Some studies have reported a higher prevalence of PD in men, whereas other studies have not.

The genetic contribution to the development of PD is an area of intense study. A variety of gene mutations that can cause PD have been identified in family studies [1]. However, their contribution to the development of PD in a larger population is not yet fully appreciated. Environmental risk factors are also thought to play a role in the pathogenesis of PD. Numerous studies have focused on the risk of pesticide and heavy metal exposure to the development of PD. Whereas the methodology varies in different studies, in those with an occupational exposure to pesticides or heavy metals, the data have been mixed, indicating either an increased risk for development of PD or no increased risk [1].

Symptoms

The most common initial manifestations of PD are rest tremor and bradykinesia. The resting tremor is suppressed by either purposeful movement or sleep and exacerbated by anxiety. The bradykinesia may produce a sensation of stiffness in the affected arm or leg. Pain is also a part of PD. An aching pain in the initially affected limb may first be attributed to bursitis or arthritis. Less common presenting complaints include gait difficulty and fatigue. It is not uncommon for one of these features to be present for months or even years before others develop.

As the disease progresses, 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 armrests. Handwriting becomes smaller and more difficult to read. Friends and family members often complain that the patient’s speech is more difficult to understand, particularly on the telephone. The symptom of a softer voice with 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 and decreased amplitude and accuracy of finger tapping or toe tapping movements in the affected limb. Examination of gait will 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. There is also a spectrum of cognitive impairment in PD, extending from minimal cognitive impairment to PD with dementia. Minimal cognitive impairment is defined as a gradual decline in cognitive function, identified by the patient or caregiver, that does not interfere significantly with functional independence [2]. PD with dementia is dementia with a slowly progressive course of cognitive impairment that most prominently affects attention, executive, and visuospatial functions [3].

In examination of someone who is taking 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 good at ameliorating the rest tremor and bradykinesia, 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 one’s ability to write legibly. Affected individuals are still able to perform activities of daily living, although they may prefer to use the unaffected limb for tasks such as shaving and dressing. Although the rest tremor may result in a feeling of self-consciousness or embarrassment, it does not affect one’s independence as it is suppressed with purposeful movement.

As the disease progresses, the ability to perform fine motor skills declines, 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 to initiate gait. 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 one’s 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, dysphagia is likely to develop.

One aspect of PD that has historically received little attention is the effect it has on sexual activity. Men may experience erectile dysfunction and difficulty with ejaculation as part of the autonomic dysfunction found in PD. Women may experience inadequate lubrication and a tendency to urinate during sex secondary to autonomic dysfunction. In both genders, hypersexuality may be seen as a side effect of treatment with dopamine agonists [4].

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

Diagnostic Studies

PD is a 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. A dopamine transporter radioligand has recently become available for clinical use, in single-photon emission computed tomography scanning, to assist in the evaluation of those with suspected PD. The scan is known as a DaTscan, and a recent analysis demonstrates that it does not provide greater accuracy than a clinical diagnosis based on history and examination of a patient [5].