Parkinson Disease

Contributed by: Yasmin Qaseem, Baylor College of Medicine, 1 Baylor Plaza, Houston, Tx 77030

Overview

• Parkinson's Disease (PD) refers to a particular etiopathogenic cause of set of clinical features known as Parkinsonism, characterized by resting tremor, bradykinesia, rigidity, and gait instability. While a variety of insults can cause Parkinsonism, such as medications, PD refers to those pathologically associated with progressive loss of dopaminergic neurons in the midbrain with presence of intracytoplasmic inclusions known as Lewy Bodies that contain the protein alpha-synuclein. The prevalence of PD increases with age, commonly manifesting in the sixth decade, with a preponderance of cases in men.

Pathogenesis and Morphology

• The precise etiopathogenesis of PD remains unknown although given its largely sporadic nature, environmental factors are suspected. While these factors are unidentified, in the 1980s a small set of patients who injected heroine that contained the byproduct MPTP, developed a PD-like syndrome with damage to dopaminergic neurons. It should be noted that 10-15% of cases appear to be familial, although multiple mutations have been associated with the different families.
• The hallmark of PD is the loss of dopaminergic neurons in the basal ganglia, particularly in the substantia nigra. These neurons display characteristic intracytoplasmic inclusions known as Lewy Bodies that are composed of the protein alpha-synuclein. Interestingly, a small subset of familial cases are associated with mutations in the alpha-synuclein gene, supporting its role in PD�s etiopathogenesis. How accumulation of alpha-synuclein ultimately contributes to dopaminergic neuronal loss is still being investigated.

Clinical Manifestations

• Overview
• The diagnosis of PD is made clinically but is characterized by the hallmarks of resting tremor, bradykinesia, rigidity, and gait instability. Patients also display a number of cognitive and psychiatric sequelae.
• Tremor
• The tremor of PD is classically described as “pill-rolling” which occurs at rest but resolves with intentional movements.
• Bradykinesia
• Slowing of body movements is characteristic of PD and involves minimized facial expressions and blinking, otherwise known as “masked facies”.
• Rigidity
• Patient�s with PD display rigidity of the extremities and is manifest in the clinical exam “cogwheel rigidity” where intermittent rigidity is encountered when the upper extremity is over in a circle.
• Gait Instability
• Diminished reflexes and poor balance cause a stooped posture and “shuffling gait” with small slow steps.
• Cognitive/Psychiatric:
• Cognitive decline and dementia are common in PD patients, as well as depression, apathy, and anxiety.

Treatment

• Overview
• A variety of treatments are now available for PD. The mainstay of therapy remains levadopa, which acts to increase dopamine levels within the brain.
• Levadopa
• Levadopa is a precursor to dopamine that is able to cross the blood-brain barrier. It is generally administered with carbidopa, which inhibits DOPA decarboxylase and prevents the peripheral conversion of levodopa to dopamine. This increases the availability of levodopa in the brain.
• Dopamine Agonists
• Drugs such as bromocriptine, pramipexole and ropinirole stimulate dopamine receptors in the CNS. Pramipexole and ropinirole are especially helpful for improving motor symptoms.
• MAO-B inhibitors
• Selegiline and rasagaline inhibit the monoamine oxidase B enzyme, which normally degrades central dopamine, and thereby increase dopamine availability at the synapse.

• Amantadine
• Originally developed as an antiviral agent, the mechanism of action of amantadine is poorly understood. However it is generally thought to inhibit NMDA receptors centrally and may be useful for motor symptoms.
• Surgical Treatment
• Deep Brain Stimulators are now an increasingly common mode of treatment. Here electrodes are placed, typically within the subthalamic nucleus, and provide electrical stimulation of brain regions.

Further Reading

• Jankovic, Joseph. "Parkinson�s disease: clinical features and diagnosis." Journal of Neurology, Neurosurgery & Psychiatry 79.4 (2008): 368-376.
• Lee, Virginia M-Y., and John Q. Trojanowski. "Mechanisms of Parkinson's disease linked to pathological α-synuclein: new targets for drug discovery." Neuron 52.1 (2006): 33-38.
• Rao, Shobha S., Laura A. Hofmann, and Amer Shakil. "Parkinson�s disease: diagnosis and treatment." Am Fam Physician 74.12 (2006): 2046-54.

To cite this article

Qaseem, Y, “Parkinson Disease” in Pathway Medicine: An Introduction to Clinical Medicine, PathwayMedicine.org (2015).