Parkinson's disease (PD, aka hypokinetic rigid syndrome) is a degenerative disorder of the CNS, mainly affecting the motor system.
Patient information
What is Parkinson's disease?
It's a disease of the brain, that just gets worse. And worse. And worse.
Pathophysiology
Accumulation of alpha-synuclein into Lewy bodies, causing death of dopaminergic neurons in the substantia nigra, a region of the midbrain
The causes of this cell death are poorly understood
Many risks and protective factors have been investigated, the clearest evidence is for an increased risk of Parkinson’s disease in people exposed to certain pesticides and a reduced risk of tobacco smokers
Where the Lewy bodies are located is often related to the expression and degree of the Sx of an individual
Patient information
It doesn't sound to great... But what makes the brain just get worse?
Proteins in the nerve cells in the brain, clump up. They're called Lewy bodies. It particularly targets the nerve cells which make dopamine.
So Parkinson's disease is a disease of low dopamine?
Yeah. Basically.
Sx
Motor Sx, Parkinsonism (aka parkinsonian syndrome) are the main motor Sx, including:
Parkinsonian tremor (see page)
Shaking
Rigidity
Hypokinesia (slow movement)
Difficulty with walking and gait
Later, thinking and behavioral problems may arise
Depression is the most common psychiatric Sx
Other Sx include:
Sensory
Sleep
Emotional problems
Patient information
What happens if you have clumps in the brain causing low dopamine? What is dopamine?
Dopamine is used by the brain to send signals. It's particularly involved with preventing you from moving when you don't want to. So because it's low, you have these unwanted movements in Parkinson's. Shaking. Being rigid. Slow to move. Dopamine is also involved in the motivation system, so there can be behavioral and emotional problems too.
Classification
Primary, is referred to as idiopathic (having no known cause), although some atypical cases have genetic origin
Secondary, is due to known causes like toxins
Dx
Dx of typical cases is aminly based on Sx
Tests e.g. neuroimaging being used for confirmation
Tx
L-DOPA (Levodopa), which is the precursor to the catecholamines (dopamine, noradrenaline and adrenaline). The precursor is used rather than dopamine, because L-DOPA can cross the BBB, thereby increasing the doapmine concentration to Tx PD. Side effects are caused by conversion into dopamine in the peripheral PNS. This is countered by co-administering a peripheral DOPA decarboxylase inhibitor, which inhibits peripheral metabolism of L-DOPA, such that more of it will cross the BBB before conversion. Examples of inhibitors include:
Carbidopa, of which combinations of carbidopa+levodopa include Levocarb (Duodopa), Sinemet CR
Benserazide, of which combinations of carbidopa+benserazide include Madopar
Dopamine agonists
Patient information
What can you do about clumps in the brain causing low dopamine?
You can give dopamine. The only problem is that too much dopamine however, and you have schizophrenia. You go a bit looooopy. That's why in schizophrenia, you actually give a drug, which DECREASES dopaimne (which in turn, can cause Parkinsonian like problems!).
I heard that by giving dopamine, you can actually CAUSE a shake...?
Yeah you can. That's why we give a DOPA decarboxylase inhibitor. Basically, it helps prevent dopamine from being created throughout the body. It only creates dopamine in the brain, where you want it work. So it decreases the motor problems side effects of dopamine.
Epidemiology
Most commonly occurring in elderly Pt's, with most cases occurring after 50yo, when it is seen in young adults, it is called young onset Parkinson’s disease
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