Pathophysiology of Parkinson’s Disease
Parkinson’s disease is a neurodegenerative disease marked by:
1) progressive slowing of all voluntary movements
2) muscular “cogwheel” rigidity
3) tremors at rest
4) mask-like facies
5) emotional lability
Signs and Symptoms
1) tremors disappear with voluntary movement
2) drooling
3) dementia (15%)
4) depression
5) micrographia
6) “pill rolling”
7) hesitancy when rising from chair
8) short shuffling gait
9) decreased blink rate
10) diminished arm swing
11) stooped posture
12) loss of postural righting reflexes
13) autonomic problems (constipation, impotence, hypotension, impaired thermoregulation
14) loss of smell (anosmia) oftern first presenting sign
15) can present with unilateral motor symptoms
Histology and Gross Pathology
1) loss of dopaminergic neurons in basal ganglia, substantia nigra, and locus ceruleus
2) eosinophilic sphere-shaped inclusions in cytoplasm (Lewy bodies)
3) end stage of disease – destruction of dopaminergic nigrostriatal pathways in striatum and putamen
Associated Conditions
1) reported to have occurred after ingestion of MPTP
2) some physicians report Parkinson-like symptoms with tick borne infections such as Lyme Disease
Biochemistry
1) possibly related to damage to cells in substantia nigra during auto-oxidation of catecholamines during the synthesis of melanin (increased oxidative stress)
2) defects in the mitochondrial electron transport of affected cells have been described
Inheritance and Epidemiology
1) affects 2% of North Americans
2) most common onset is 50-80 years
3) no race or sex predilection
4) a few cases have autosomal dominant, early-onset inheritance (point mutation on chromosome 4 for the alpha-synculein gene
5) a few cases have an autosomal recessive inheritance (defects in the gene parkin that lack Lewy bodies)
Treatment
1) mainstay is palliative treatment with levodopa (carbidopa given concurently to increase absorption and decrease nausea)
2) aim is to delay levodopa as long as possible as the effectiveness wanes
3) other drugs used – selegiline (neuroprotective), Artane and Cogentin (anticholinergics), bromocriptine and ropinirole (dopamine agonists), amantadine (antiviral)
4) some physicians who treat Lyme patients use Lyme medication and herbal treatment protocols to treat patients with clinical symptoms resembling Parkinson’s disease in the theory that Parkinson’s disease is misdiagnosed Borrelia infection
5) surgical treatment – thalamotomy, implantation of fetal nigral tissue, implantation of brain stimulators
6) acupuncture has been shown to be helpful in reducing symptoms in anecdotal reports
Tips for USMLE
1) Parkinson’s disease is largely a motor disease and not associated with large sensory disturbances
2) substantia nigra is par of the extrapyramidal system involved in dopaminergic synapses; hence Parkinson’s disease is an extrapyramidal disorder
3) clinical hallmarks are bradykinesia and either tremors at rest or cogwheel rigidity
4) pathological hallmarks of Parkinson’s disease are Lewy bodies and degeneration of dopaminergic neurons of substantia nigra
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