Parkinson Disease

GENERAL PRINCIPLES

• Parkinson disease (PD) is a chronic, progressive neurodegenerative disease characterized by at least two of three cardinal features: resting tremor, bradykinesia, and rigidity.

• The neurologic examination remains the gold standard diagnostic test for PD.

• Cognitive dysfunction and dementia are common in PD (one-third of patients in most studies; six times higher than age-matched controls). Considerable overlap can occur between AD and PD.

๎ One-third of PD patients are depressed.

๎ Olfactory dysfunction, autonomic dysfunction, and sleep disorders are also common in PD and have a significant impact on quality of life.

Epidemiology

Approximately 1 million people in the US have been diagnosed with PD. Usually, the age at diagnosis is older than 50 years. Approximately 1% of the population older than 50 years has the disorder.

DIAGNOSIS

Clinical Presentation

• The parkinsonian tremor is a resting pill rolling tremor (3-7 Hz) that is often asymmetric.³²

• Bradykinesia is characterized by generalized slowness of movement, especially in finger movement dexterity and gait (often shuffling).

• Cogwheel rigidity is often observed with a ratchety pattern of resistance and relaxation as examiner moves limbs (“cog wheeling” is due to the rigidity with a superimposed tremor).

• Postural instability can be assessed by the “pull” test, where the examiner pulls the patient by the shoulders while standing behind the patient, assessing the patient's ability to recover.

• Other signs that are often associated but not required for diagnosis include masked-like facies, decreased eye blink, increased salivation, hypokinetic dysarthria, micrographia, and sleep disorders, particularly rapid eye movement (REM) sleep behavior disorder.

• Dementia seen with PD is typically subcortical with psychomotor retardation, memory difficulty, and altered personality.

Differential Diagnosis

See Table 27-10.

TABLE 27-10

DIFFERENTIAL DIAGNOSIS OF PARKINSON DISEASE

• Essential tremor

๎ Action tremor

• Dementia with Lewy bodies

๎ Visual hallucinations, fluctuating cognition, sensitivity to neuroleptics

• Corticobasal degeneration

• Multiple system atrophy

• Progressive supranuclear palsy

• Alzheimer disease

• Frontotemporal dementia

๎ Changes in personality

• Huntington disease

• Wilson disease and other neurodegenerative disorders with metal accumulation

• ToxicZiatrogenic

๎ Carbon monoxide, manganese, neuroleptics, other dopamine receptor antagonists

Diagnostic Testing

MRI of the brain (or head CT with contrast in patients unable to undergo MRI) should be performed to exclude specific structural abnormalities.

TREATMENT

Medications

• PD patients should not be given neuroleptics or any dopamine-blocking medications under any circumstances (e.g., prochlorperazine, metoclopramide) because this can have devastating consequences ranging from worsening PD symptoms to death.³³ If a neuroleptic is absolutely necessary, quetiapine and clozapine are the safest, but the risk/benefit profile needs to be considered. Pimavanserin has also been approved specifically for PD psychosis.

• Treatment of PD can be divided into neuroprotective and symptomatic therapy.

• Initiation of symptomatic treatment for a PD patient is determined by the degree to which the patient is

functionally impaired.

FIRST LINE

• Carbidopa-Ievodopa (Sinemet, CD-LD) is the most effective symptomatic therapy for PD and is often considered when both the patient and the physician decide that quality of life of the patient is being affected by PD.

• Dopamine agonists (i.e., pramipexole, ropinirole) can be used as monotherapy or in combination with other PD medications.

• Many patients can be managed with CD-LD alone without the need for agonist therapy.

SECOND LINE

• Amantadine and catechol-O-methyl transferase inhibitors can help supplement the effects of dopamine replacement therapy and are beneficial with regard to the dyskinesias and fluctuations, respectively, commonly experienced by patients.

• Anticholinergic drugs are used only in younger patients in whom tremor is the predominant symptom.

THIRD LINE

Deep brain stimulation and Duodopa (intestinal infusion of carbidopa/levodopa gel) have benefit in PD patients who progress to develop motor fluctuations and dyskinesias unresponsive to oral medications. It is important to note that advanced therapies are not a cure for PD and patients will continue to progress.

Complications

• Patients can develop neuroleptic malignant syndrome (NMS) after sudden withdrawal of levodopa or dopamine agonists and following exposure to neuroleptics or other antidopaminergic drugs.

• Serotonin syndrome can occur when monoamine oxidase inhibitors (MAOIs) are combined with TCAs or SSRIs.