INTRODUCTION

Parkinson disease (PD) is the most common cause of parkinsonism, a syndrome manifested by rest tremor, rigidity, bradykinesia, and postural instability. The disorder was first described by James Parkinson in his 1817 Essay on the Shaking Palsy. Although it has been proposed that PD emerged as a result of the industrial revolution, there is some evidence that a disease known as "kampavata", consisting of shaking (kampa) and lack of muscular movement (vata), existed in ancient Indian medical system, Ayurveda, as long as 4500 years ago [1]. The Mucuna pruriens plant was used in ancient times to treat the symptoms, and was later discovered to contain levodopa [2].

The pathology of PD was not well understood until the early 20th century, when the German pathologist Frederick Lewy in 1912 reported neuronal cytoplasmic inclusions in a variety of brain regions. In 1919, Tretiakoff observed that the most critical abnormality in PD was the loss of neurons in the substantia nigra pars compacta of the midbrain. In the 1950s, investigators discovered the importance of dopamine and its depletion from the basal ganglia as the key to understanding the pathophysiology and pathologic biochemistry of PD [3].

While the cause of PD is still unknown, remarkable advances have been made in understanding the possible underlying mechanisms [4]. This extraordinary progress has been fueled by new discoveries about the anatomy and function of the basal ganglia, improved characterization of neuropathologic and neurochemical abnormalities in PD, and by studies of genetic and experimental forms of parkinsonism.

This topic will review the etiology and pathogenesis of PD. Clinical issues related to PD are discussed separately. (See "Clinical manifestations of Parkinson disease" and "Diagnosis of Parkinson disease" and "Pharmacologic treatment of Parkinson disease".)

PATHOPHYSIOLOGY

Dopamine depletion from the basal ganglia results in major disruptions in the connections to the thalamus and motor cortex, and leads to parkinsonian signs such as bradykinesia.