PARKINSON’S

Hypokinesis

Parkinson’s Disease is the major hypokinetic movement disorder. The triad of Parkinson’s is hypokinesis, lead pipe rigidity and resting tremors. Hypokinesis refers to the difficulty initiating and sustaining movement. Their postural muscles are rigid, producing a hunched posture. The limbs are also rigid, producing “lead pipe rigidity” and a shuffling gait (festinating gait). If you try to move their arm for them, they will tense and jerk throughout their range of motion (cogwheel rigidity). The facial muscles become less expressive, giving them a stony and stern expression (mask-like facies). 

There is a unique tremor with Parkinson’s called the resting “pill rolling” tremor. Their hands quiver in such a way that it makes it look like they’re rolling a small object between their index finger and thumb. 

Due to some mild cortical atrophy, psychiatric symptoms like depression, apathy and memory loss will occur after a few years (if dementia dominates the clinical picture, consider Lewy Body Dementia). 

Pathophysiology?

Their brain doesn’t make enough dopamine. Dopamine is made by a cluster of neurons in the brainstem, called the substantia nigra, which degenerates in Parkinson’s disease. We don’t know the cause, but it’s usually seen around ages 50-60. There is one rare cause -- MPTP is an impurity that can occur when you try to cook up homemade synthetic heroin, which can cause Parkinson’s!

What does dopamine do? 

Dopamine in the brain = movement in the body. Dopamine binds to D1 and D2 receptors in the basal ganglia through the nigrostriatal path. Both D1 and D2 use different mechanisms, but overall they both favor movement. Acetylcholine is dopamine’s mortal nemesis. Within the basal ganglia, ACh does the opposite of Dopamine.  So in Parkinson’s, the scales of power have tipped, and there is more ACh than Dopamine.

Diagnosis?

The diagnosis is clinical, but an MRI would show degeneration of the substantia nigra. 

Treatment?

For decades the only drug around was L-DOPA, a notoriously fickle drug. It was hard to maintain the right dose (very narrow therapeutic window), and often the side effects (mania and hyperkinesis) are worse than Parkinson's itself. Nowadays we have a few other adjunctive treatments, but the mainstay remains L-DOPA. Now we add Carbidopa to prevent L-DOPA from breaking down before the blood brain barrier. When and if L-DOPA stops working, COMT inhibitors and MAO-B Inhibitors are added. For young patients, AChE inhibitors help with mild symptoms, and is the preferred drug because L-DOPA’s side effects can be sorta permanent. Many neurologists hold off on giving L-DOPA until a patient reaches old age, because in many cases the drug stops working after ~10 years (and won’t ever work again).