Chapter 58: Parkinson Disease

INTRODUCTION

• Parkinson disease (PD) has highly characteristic neuropathologic findings and a clinical presentation, including motor deficits and, in some cases, mental deterioration.

PATHOPHYSIOLOGY

• Its true etiology is unknown. Reduced activation of dopamine₁ and dopamine₂ receptors results in greater inhibition of the thalamus and reduced activation of the motor cortex. Clinical improvement may be tied to restoring activity more at the dopamine₂ receptor than at the dopamine₁ receptor. Antagonism of adenosine A_2A receptors located in GABAergic neurons can prolong dopaminergic action.

• Two hallmark features in the substantia nigra pars compacta are loss of neurons and presence of Lewy bodies. The degree of nigrostriatal dopamine loss correlates positively with severity of motor symptoms.

CLINICAL PRESENTATION

• PD develops insidiously and progresses slowly over many years.

General Features

• Bradykinesia (slowness of movements) and at least one of the following: resting tremor, rigidity, or postural instability.

Motor Symptoms

• Only two-thirds of patients with PD have tremor on diagnosis, and some never develop this sign. Tremor in PD is present most commonly in the hands, sometimes with a characteristic pill-rolling motion. Motor features may be asymmetric.

• Hypokinetic movements, decreased manual dexterity, difficulty arising from a seated position, diminished arm swing during ambulation, dysarthria (slurred speech), dysphagia (difficulty with swallowing), festinating gait (tendency to pass from a slow to a quickened pace), flexed posture, “freezing” at the initiation of movement, hypomimia (reduced facial animation), hypophonia (reduced voice volume), and micrographia.

Autonomic and Sensory Symptoms

• Bladder dysfunction, constipation, diaphoresis, fatigue, olfactory impairment, orthostatic intolerance, pain, paresthesia, paroxysmal vascular flushing, seborrhea, sexual dysfunction, and sialorrhea (drooling).

Mental Status Changes

• Anxiety, apathy, bradyphrenia (slowness of thought processes), cognitive impairment, depression, and hallucinosis/psychosis.

Sleep Disturbances

• Excessive daytime sleepiness, insomnia, obstructive sleep apnea, and rapid eye movement (REM) sleep behavior disorder.

DIAGNOSIS

• The clinical diagnosis of PD is outlined in Table 58-1.

• Laboratory or genetic testing, cannot diagnose PD. Neuroimaging may be useful for excluding other diagnoses.

• Obtain a medication history to rule out medication-induced parkinsonism.