Central Nervous System


What is Parkinson's Disease?

It is a neurodegenerative disease that develops slowly but progressively, principally involving certain functions, such as control of movements and balance. The disease belongs to a group of diseases that are known as "Movement Disorders," and is the one with the highest incidence. The symptoms of Parkinson's disease have most likely been known for thousands of years.
But it is named after James Parkinson, a 19th century apothecary and surgeon from London, who first described most of the symptoms of the disease in his famous "An Essay on the Shaking Palsy."
The disease is recorded worldwide and in all ethnic groups. It develops in both sexes with a slight prevalence in males. The mean age of onset is around 58-60 years but about 5% of patients may develop it between the age of 21 and 40 years. It is extremely rare in subjects aged under 20 years. It affects 1-2% of the population over 60 years of age, while the percentage rises to 3-5% in subjects over 85.

Body structures involved in Parkinson's Disease

Body structures involved in Parkinson's Disease are located in the deep regions of the brain, known as basal ganglia (caudate nucleus, putamen and globus pallidus), which participate in the correct execution of movements (and much more, besides). Parkinson's Disease develops when dopamine production in the brain undergoes a considerable reduction. The low levels of dopamine are caused by neuronal degeneration in a region called Substantia Nigra (with a loss of cells in excess of 60% at the onset of symptoms). Build-up of the protein alpha-synuclein can be noticed from bone marrow to brain. Perhaps this is the protein that disseminates the disease in the entire brain. The duration of the preclinical phase (period of time between the start of neuronal degeneration and the onset of motor symptoms) is not known but some studies record it as about 5 years.

The principal motor symptoms of Parkinson's Disease

The principal motor symptoms of Parkinson's Disease are tremors during rest, rigidity, bradykinesia (slow automatic movements) and, in the late stage, postural instability (loss of balance). These symptoms present asymmetrically (one side of the body is more concerned than the other).

Tremors are not observed in all patients. Very often symptoms are not immediately recognised at the onset of the disease because they manifest subtly and inconstantly, and progression of the disease is typically slow. At times relations and friends are the first to notice that "something is wrong," and encourage the patient to see a doctor.

Other motor symptoms that can be associated with the above ones include: walking disorder, hunching, voice, swallowing, excessive salivation.

"Non motor" symptoms are also important in Parkinson's Disease

Parkinson's Disease might also present non-motor symptoms that can develop several years before the onset of motor symptoms. They are often noticed during the early stages of the disease and record the highest incidence in the late stages. Non-motor symptoms observed most often include: abnormal vegetative functions (e.g. constipation, urinary disorders, sexual dysfunction, skin disorders and perspiration), smell, sleep, mood (depression) and cognitive function disorders, fatigue and pain.

Late stage motor signs and symptoms

After a variable number of years, treatment with Levodopa is unable to ensure stable motor control, and patients start experiencing the end of the effect of one oral administration of Levodopa. The condition is known as "wearing off."

The late stage of Parkinson's Disease presents motor symptoms that are distinguished into involuntary movements or dyskinesia and motor fluctuations.

Dyskinesia is a frequent complication of dopaminergic therapy that is developed by the major part of patients after 10 years of treatment. Several factors have been considered associated with dyskinesia, including Levodopa dosage, gravity of the disease and age of onset.

They are divided into two groups: a) peak dose dyskinesia, thus defined because they develop at the peak plasma concentration of Levodopa, and are characterised by involuntary movements that involve several parts of the body (head, limbs, trunk, respiratory muscles); b) dysphasic dyskinesia, namely involuntary movements (choreoathetosic) that manifest during the on-off transition phase (and the reverse); they can be variable in intensity; c) 'plateau' dyskinesia, which are involuntary movements that manifest during the motor 'on' period.

Motor fluctuations manifest as increased latency on reaching the "on" phase, the impossibility to reach the "on" phase (no-on phase) and the predictable end-dose deterioration (wearing-off). It also includes nocturnal akinesia and waking akinesia, and unpredictable motor "off" phases.