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Parkinson's Disease
Overview
Parkinson's disease is a disease of asymmetric stiffness and slowness of movement (bradykinesia, muscle rigidity); tremor; frequent falls; and difficulty with sudden changes in movement that can develop over two decades or more.
The pathological hallmark of PD is loss of dopaminergic cells in the substantia nigra pars compacta, within the midbrain and the build-up of Lewy bodies – abnormal neuronal inclusions of alpha-synuclein.
Clinical Manifestations
Rigidity
Movements are essentially frozen, rigid, and slowed.
- Masked facies refers to the wide-eyed stare and immobility of facial muscles with little emotional play.
- Also known as bilateral mimetic (aka emotional) facial palsy.
- Failure of Glabellar tap to disappear (normally disappears after 4 — 5 taps)
- Lead-pipe rigidity describes the constant/persistent resistance to passive movement.
- Bradykinesia describes slowness of movement, delay in initiation, minimal spontaneity.
- Rare blinking (“serpentine stare”)
- Cogwheeling refers to the ratchet-like starting and stopping when a limb is moved (think of it as a tremor within the rigid movement).
- There are alternating agonist/antagonist contractions.
- You can feel a catch in the alternation (Negri’s sign), most easily at the wrist.
- Micrographia refers to small handwriting that gets progressively smaller during the writing process.
Speech
Speech is hypophonic (soft) and rapid (once initiated) and there is associated drooling.
Tremor
Asymmetric rest tremor is a 4-6 hz oscillatory tremor that can involve the elbow (flexion/extension); the forearm (pronation/supination); the fingers (pill-rolling).
- It is prominent at rest but extinguishes with action, which distinguishes it from essential tremor, which is absent at rest but prominent with action.
- Tremor can also manifest in the head (vertical head tremor).
Hyperkinetic movements
Dyskinesias and dystonia are potential features in Parkinson's disease.
- Dyskinesia is excessive movement that typically occurs with treatment.
- Dystonia is involuntary sustained muscle contractions with abnormal posturing.
Gait
The Parkinsonian gait has multiple signature characteristics and falls are a common and serious consequence of Parkinon's disease. See Gait Abnormalities
- There is ignition failure.
- Prominent rigidity (the elbows and wrists are in flexion).
- Shuffling, short-stepped gait.
- Turn en-bloc describes the restricted gait and the inching movements required for a turn.
- There is also a "start-up" phenomenon in which patients are slow to initiate gait but once moving having difficulty stopping.
- Freezing when passing through a doorway.
Pathology
There is dropout of dopaminergic neurons in the substantia nigra, pars compacta in the midbrain. It is characteristically pale and degenerated (asymmetrically).
See the Parkinson's Disease whiteboard tutorial for discussion of Lewy bodies and Lewy neurites.
Genetics
Idiopathic PD stems from a combination of numerous genetic and environmental effects. Less than 30% of PD patients claim a familial history of PD but idiopathic PD can still come from spontaneous AD gene mutations. Siblings of patients with PD have at least a 6-fold risk of developing the disease; those with early-onset PD are at greater risk than those with late-onset.
See the Parkinson's Disease whiteboard tutorial for discussion of key genetic causes of PD.
Pharmacotherapy
Levodopa is used in conjunction with carbidopa, which provides peripheral DOPA decarboxylation inhibition (we don't want peripheral dopaminergic excitation). Carbidopa increases the circulating concentration of L-DOPA in the brain where it's intended.
Levodopa (and other PD meds) primarily act stimulate D2 receptors within the basal ganglia (there are two main classes: D1 (direct pathway) and D2 (indirect pathway), which we address in the basal ganglia physiology tutorial).
The following are some of the central effects of dopamine, which will help us remember the side effects of the various PD meds.
- Psychosis (meaning delirium, hallucinations, confusion), we can remember this if we remember that in schizophrenia there is excess dopamine.
- Dyskinesias, meaning excess movement (think about the excess movement in Huntington's chorea, for instance).
- Paradoxically, there are also akinesias (freezing episodes), which is characteristic of late-stage treatment of Parkinson's disease: fluctuations in the fluidity of movement.
- Cardiac arrhythmias.
- Blood pressure dysregulation. Dopamine can produce hypertension or, paradoxically, orthostasis.
- Nausea and vomiting (which is one of the most common symptoms).
- Rare ocular manifestations of mydriasis and glaucoma can also occur.
Atypical Parkinsonian Syndromes
Atypical Parkinsonian Syndromes
- Progressive supranuclear palsy (PSP), which involves early gait instability and falls.
- Multiple systems atrophy (MSA), which involves autonomic, extrapyramidal, and cerebellar disease.
- Corticobasal degeneration (CBD), which involves cerebrocortical and basal ganglia degeneration.
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