This is a mechanism of disease flowchart for Parkinson disease and other types of parkinsonism, covering the etiologies, pathophysiology, and manifestations of these diseases.
ADDITIONAL TAGS:
Pharmacology / toxicity
Infectious / microbial
Biochem / molecular bio
Neurotransmitter imbalance
Signs / symptoms
Labs / tests / imaging results
Parkinson disease
Core concepts
Social determinants of
health / risk factors
Neuron malfunction
Genetics / hereditary
Inflammation
Pathophysiology
Etiology
Manifestations
Dopaminergic neuron degeneration (50%) in substantia nigra
Dopamine deficiency at the striatum
Interrupted transmission to thalamus and motor cortex
Serotonin and norepinephrine depletion in the raphe nuclei
Acetylcholine excess in the nucleus basalis of Meynert
Dyskinesia (jerking, twitching, tics)
Idiopathic
Mutations (including duplication / triplication) of α-synuclein (SCNA) → Lewy bodies
Dardarin (LRRK2) mutation (dominant)
Parkin (PARK2) mutation (recessive)
Glucocerebrosidase (GBA) mutation (most common)
Altered phosphorylation of target proteins and lysosomal dysfunction
Impaired turnover and clearance of mitochondria
altered autophagy and lysosomal function
Impairment of α-synuclein clearance
Viral (HSV, HIV)
Bacterial (T pallidum, M tuberculosis)
Parasites (T gondii, Plasmodium)
Prion (Creutzfeldt-Jakob disease)
Antidopaminergic meds: haloperidol, metoclopramide, amiodarone, valproate, Li
Illicit drug MPTP → metabolite MPP+
Toxins: CO, carbon disulfide, manganese
Secondary parkinsonism
Advanced Huntington disease
Wilson disease
Hemochromatosis
Niemann Pick
Cardio- / cerebrovascular risk factors
Subcortical arteriosclerotic encephalopathy
Lewy body deposits in the autonomic nervous system
Apathy
Impulsive, irritable
Fatigue
Poor sleep
↓ sense of smell
Depression
↓ attention
↓ concentration
↓ memory
↓ executive function
Neuropsych
Urinary urgency → incon
Orthostatic hypotension
Oily skin
Impaired sex function
Autonomic
Motor
Early symptoms:
-constipation
-sleep problem: REM disorder, daytime sleepiness, RLS
-low sense of smell
-mood: depress, anxiety, apathy
Syndrome of parkinsonism (TRAP)
Tremor: resting (4-6Hz), pill-rolling, ↓ w voluntary movements, ↑ w stress
Rigidity: high and persistent resistance to passive joint movement. Tremor + tonus = cogwheel rigidity
Akinesia: no or ↓ movement; freezing; low arm swing → short steps with shuffling gait (5-8 to turn around) → parkinsonian gait
Postural instability: imbalance + impaired righting reflex → tendency to fall; + pull test
Dystonia: sustained muscle contraction → involuntary fixed posture
Increased axial muscle flexion → stooped posture
Shrinking handwriting (micrographia)
Decreased facial expressions (hypomimia)
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Негізгі бет Parkinson disease, parkinsonism (mechanism of disease)
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