Parkinson’s disease (PD; paralysis agitans) is a neurodegenerative disease of the substantia nigra (an area in the basal ganglia of the brain). The disease was first discovered and its symptoms documented in 1817 (An Essay on the Shaking Palsy) by the British physician Dr. James Parkinson; the associated biochemical changes in the brain of patients were identified in the 1960s. Some genes were identified only recently; others remain unknown.

The disease involves a progressive movement disorder of the extrapyramidal system, which controls and adjusts communication between neurons in the brain and muscles in the human body. It also commonly involves depression and disturbances of sensory systems.

In the United States, the prevalence of Parkinson’s disease is 1 per 625 people, though this increases with age, as indicated by the mean onset of 55 years of age. Symptoms usually begin in the upper extremity, and are usually unilateral (one-sided) or asymmetrical at onset.


The cause of Parkinson’s disease is not known. Geneticists have since 1997 found nine different specific genetic defects, each of which causes the disease in one or a few families with extraordinarily high incidences of the disease, but such families are rare. While a strong inheritance pattern occurs in only a very small percentage of cases, an affected individual is three to four times more likely than an unaffected individual to have a close relative with Parkinson’s. Having a parent with Parkinson’s raises one’s lifetime risk of developing the disorder threefold, from the general population’s figure of 2% to about 6%. Genes that have been identified include SNCA (protein alpha-synuclein), UCHL1 (protein ubiquitin carboxy-terminal hydrolase L1), PARK2 (protein parkin), and PARK7 (protein DJ-1). Indeed, recent linkage studies excluded most of the above gene defects from consideration in the causation of sporadic (i.e. non-familial) Parkinson’s disease, which constitutes more than 95% of cases. Most recently, a new gene was identified, ND5, mutation in which is thought to account for a vast majority of sporadic PD cases (see below).

A prevalent theory holds that the disease might result in most cases from the combination of a subtle genetically-determined vulnerability to environmental toxins along with even limited exposure to those toxins. This is consistent with the fact that Parkinson’s disease is not distributed homogenously throughout the population, rather incidence varies geographically. The toxins most strongly suspected at present are certain pesticides and industrial metals. MPTP is used as a model for Parkinson’s as it can rapidly induce parkinsonian symptoms in patients/animals of any age. Other toxin-based models employ paraquat (an herbicide), rotenone (an insecticide), maneb (a fungicide), or [(2-4D)] (a pesticide). Studies have consistently found an increase in PD in persons exposed to these agricultural chemicals; the risk apparently rises with exposure. Although family history of the disease and (especially) multiple episodes of head-trauma-induced unconsciousness increase risk more as isolated factors than does pesticide exposure, the ubiquity and insidious nature of agricultural chemical exposures makes it difficult to gauge the true extent of the problem.


Differential diagnosis

The differential diagnosis for a patient presenting with Parkinsonian symptoms is:

* Idiopathic Parkinson’s disease
* Essential tremor
* Parkinson plus syndromes (see below)
* Secondary parkinsonism due to drugs, toxins, stroke, head trauma, or hydrocephalus

Parkinson’s tremors differ from essential tremors in that the latter are posture or action tremors, have bilateral tremors involving the hands, head and voice, and are alcohol responsive. In contrast, Parkinson’s tremors are rest tremors, and usually start unilaterally.


SPECT with ([123I]FP-CIT) or PET with 18F-fluorodopa are the two imaging modalities used to assess dopamine transporter density and the integrity of nigrostriatal pathways in the central nervous system. Currently (2005) FP-CIT is widely used in Europe for the diagnostic workup of Clinically Uncertain Parkinsonian Syndromes; although it is not available in the United States.


The treatment of Parkinson’s disease mainly relies on replacing dopamine with levodopa (L-DOPA) or mimicking its action with dopamine agonists such as pramipexole, ropinirole, pergolide or bromocriptine. Discovered as a Parkinson’s treatment by Arvid Carlsson, levodopa is a dopamine precursor that is transfomed into dopamine by the brain. Levodopa is almost always supplemented with carbidopa or benserazide, drugs which prevent levodopa from being metabolized in the gut, liver and other tissues, thus allowing more levodopa to reach the brain and allowing for a reduced dosage, thus reducing some of the side effects. The most frequent side effects of these dopaminergic drugs are nausea, sleepiness, dizziness, involuntary writhing movements and visual hallucinations. Often times, the treatment of the Parkinson’s patient with these two drugs can result in them very much “coming back to life” in the eyes of their family and doctors, to the point of them appearing to not have any disease at all. However, the drugs are not effective forever. Sometimes a point is reached where the drugs only work for a few hours, or become completely ineffective (“off periods”).

As in many other diseases, the therapy requires a continuing regimen of medicines, the dosage of which has to be specifically calculated for each single case and might vary during the evolution of the disease. The treatment is complex and usually consists of a mixture of drugs (basically focused on levodopa), some of which compensate for the side effects of others. Amantadine hydrochloride, anticholinergics and COMT inhibitors tolcapone or entacapone are sometimes prescribed. Tolcapone should be used with extreme caution because of the possibility of liver failure. However entacapone has not been shown to cause significant alterations of liver function. Foods rich in proteins can reduce the uptake of levodopa, because the same uptake system is used both by certain amino acids and levodopa. However, this can usually be dealt with by redistributing meal times: in many cases it is advisable to move the consumption of proteins towards the evening, so to have symptoms appearing when the patient has less need of mobility. While these therapies are a good attempt at treating the symptoms, they are not a cure–they do not attack the underlying cause of the disease which is a loss of dopamine producing neurons.

Regular physical exercise and/or therapy are beneficial to the patient and essential for maintaining and improving mobility, flexibility, balance and a range of motion, and for a better resistance against many of the secondary symptoms and side effects. There is increasing evidence that exercise is both neuroprotective against the development of Parkinson’s disease, and also ameliorative of both severity of symptoms, and also possibly of progression. “Alternative” exercise modalities such as yoga, tai chi, and dance may also hold particular promise as rehabilitation therapies, due to their integration of movement, thought, feeling, and sensory experience