Tag: parkinsonism

Etiopathologenesis

Loss of Dopaminergic neurons from SUBSTANTIA NIGRA (Parkinson disease).

Destruction of SN neurons due to exposure to MPTP (1 METHYL 4 PHENYL 1,2,3,6 TRIHYDRO PYRIDINE) – contaminant of illicit opioids. (Acute Parkinsonian syndrome)

Gut-Brain hypothesis (enteric NS to medulla)

Clinical features

• Triad (all motor – due to SN involvement)
  • Tremor (pill rolling tremor)
  • Rigidity
  • Bradykinesia
• Responds to L-Dopa.
• Appearance:
  • Masked face – less expression
  • Stooped posture
  • Slowing of voluntary movement (Bradykinesia)
  • FESTINATING gait

Pathology

Protein accumulation in cytoplasm, mitochondrial damage, lysosomal dysfunction (a/w Gaucher disease).

Diagnostic hallmark: Alpha Synuclein: Major component of Lewy body.
Encoded by SCNA gene.
Effect like Alzheimer’s (ABeta) – forms deposits.
Propogates like Prion (PrPsc).
Other proteins: DJ1, PINK1, PARKIN. These are involved in Mitochondrial dysfunction.

Morphology

SN – Pallor. (White)
Neuronal loss + reactive gliosis
Lewy bodies – eosinophilic irregular multiple cytoplasmic inclusions with halo.
Densely packed filaments of alpha synucelin.