Parkinson's Disease:etiology and pathophysiology

Parkinson's Disease (PD) - named after the discoverer James Parkinson.
Parkinson's Disease is a common chronic neuro-degenerative disease, characterised by rigidity,tremors,bradykinesia and postural instability.



Epidemiology:
It affects almost 2% of population within 50 -60 years of age.Men and women are affected equally.

Etiology:
1:Parkinson's disease is also known as 'paralysis agitants' and 'shaking palsy'
 It occurs due to damage to the substantia nigra and nigro strial pathway in the basal ganglia.
 It has two groups based on predominant features:
- Postural instability gait disturbed(PIGD) where the posture and gait are highly affected.
 -Tremor predominant, where tremors are a primary symptom.

2:Secondary parkinsonism: This includes the following types
-Post-infectious parkinsonism eg influenza epidemics of encephalitis lethargica.
-Toxic parkinsonism due to industrial poisons and chemicals like manganese, carbon disulfide,cyanide, methanol,etc.
-Drug induced Parkinsonism  due to drugs that interfere with dopaminergic mechanisms .For instance, chlorpromazine , haloperidol,amoxapine,methyldopa, reserpine. The effect of these drugs can be reversed as they only mimic the signs of PD.
-:Metabolic causes ,occurs in rare cases of metabolic conditions like hypothyroidism,hyperparathyroidism,hypoparathyroidism,wilson's disease.

3:Parkinson-plus syndromes :
 The parkinson-plus syndromes typically do not show improvement from the administration of anti-parkinson medication like levo-dopa.This is a differentiating factor between the two.
These are also neurodegenerative diseases that affect the substantia nigra and hence produce symptoms similar to PD.
These include:
-Striatonigral degeneration(SND) ,
-Progressive supranuclear palsy,
-Shy-Drager syndrome,
-Alzhimer's disease ,
-Wilson's disease,
-Diffuse lewy body disease, etc.

Pathophysiology
PD is associated with degeneration of neurons that produce Dopamine.
They have their cell bodies located in substantia nigra, of the basal ganglia.
The clinical features begin to appear with 30-60% degeneration of neurons.
To understand the pathophysiology of PD , we need to have a basic understanding  basal ganglia ,and its functions.


Basal ganglia (BG) is a collection of nuclear masses of grey matter deep within the brain.
It's made up of caudate and putamen together known as striatum.And also the globus pallidus, subthalamic nucleus,and substantia nigra.
BG  controlls the planning and programming of the movements by regulating the levels of kinetic activity , muscle tone and force.It translates thoughts into willed movements.
BG gets its input from the striatum from all the parts of cerebral cortex and substantia nigra.
Output is channelized by globus pallidus, substantia nigra to thalamus and back to cortex.

Direct pathway :here, the BG gives a direct output to thalamus and motor areas of cortex.
Indirect pathway :it suppresses some of the movements by not inhibiting the subthalamic nucleus.

Now, depletion of dopamine may result into the following:
-Overactive indirect pathway : which leads to akinesia and rigidity as it suppresses the movements.
-Underactive direct pathway: which leads to bradykinesia.
-Underactive indirect pathway: leads to hyperkinesia, chorea , hemiballismus.
-Overactive direct pathway : leads to dyskinesia,athetosis or dystonia.
-Loss of inhibition over BG explains tremors.