Q&A: Pathophysiology Of Parkinson's Disease

Parkinsonism is a clinical syndrome presenting with any combination of bradykinesia, rest tremor, rigidity, and postural instability. The most common form of parkinsonism is Parkinson disease (PD), a chronic, progressive disorder caused by degenerative loss of dopaminergic neurons in the brain and characterized clinically by asymmetric parkinsonism and a clear, dramatic, and sustained benefit from dopaminergic therapy.

This article is for Medical Students & Professionals

This is a Question & Answer revision article designed for medical students and professionals preparing for the PLAB, MRCP or USMLE examinations. They are based on actual questions from these examinations. You may find the Parkinson's Disease article more useful, or one of our many articles on Diseases & Conditions, Medical Syndromes, Health & Wellness or Home Remedies.

In this article:
A. Sub-Heading A
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Sub-Heading A

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 (SNc) 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.

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. A number of compensatory mechanisms may operate to mask or reduce the deleterious effects of dopamine depletion, particularly in the presymptomatic phase of PD, but they are eventually overwhelmed by disease progression.

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

MCQ exam: clinical scenario

An elderly man with Parkinson's disease presents with his daughter who is very worried about him. She noticed a deterioration in his movement whilst away in the UK for a family reunion. He also had a fall during the night and banged his head. On examination, his dopamine concentration was found to have decreased to 20% of the normal level since his last check up. You also observe severe symptoms of bradykinesia.

What is the least probable reason leading to the premature death of dopaminergic neurons?

a). Brain damage
b). Genetic predisposition
c). Accelerated aging
d). Toxic factors
e). Proteolytic stress

MCQ exam: answer

The correct answer is A.

MCQ exam: explanation

Progressive loss of 6-8% of dopamine concentration every 10 years is a physiological finding attributed to age. However, when it decreases to 20% of the normal level, symptoms such as bradykinesia, cogwheel rigidity, resting tremor and postural reflex impairment appear. The severity of these symptoms can be measured according to the Hoehn and Yahr Scale.

Probable reasons leading to the premature death of dopaminergic neurons are genetic predisposition, accelerated aging, toxic factors, specific and non-specific central nervous system inflammations, chronic inflammatory reaction of the neuroglia, oxidative stress and protein metabolism disturbances leading to so called proteolytic stress. Although some studies have shown dopamine transporter loss, it is still the least probable cause as most of these studies have not been conducted on humans.

Reference(s)
1). UpToDate: Etiology and pathogenesis of Parkinson disease. Available online: https://www.uptodate.com/contents/etiology-and-pathogenesis-of-parkinson-disease