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Parkinson’s disease etiopathogenesis

Classification of PD

Classification into three types based on etiopathogenesis

  1. Idiopatic PD (95%)
    1. ENVIRONMENTAL FACTORS – OVER 50s
  2. Familial PD (5%)
    1. GENETIC FACTORS – youngers
    2. Proteins preventing mitochondrial dysfunction (PINK-1; DJ-1)
    3. Proteins involved in the recycling of vesicles (α-synuclein)
    4. Proteins involved in the degradation pathway (parkin, UCH-L1)

Parkinsonism can be induced by:

  • Pharmacological onset (drugs): antipsychotics, antiemetics eg. metoclopramide (Plasil®), antiseizures eg. ethosuximide (Zarontin®) or calcium antagonists eg. flunarizine (Sibelium®).
  • Toxicological onset: methamphetamine, pesticides eg. fluocianbenpirazole (Fipronil®), herbicides.
    • METHAMPHETAMINE is uptaken inside the neurons by DAT
    • Outflow of DA from synaptic vesicles
    • MAOB-dependent oxidation of DA and production of free radicals
    • Production of toxic free radical MAOB non dependent
    • LOSS OF STRIATAL DOPAMINERGIC TERMINALS
  • Post infective onset: encephalitis
  • Post traumatic onset:
  • Parkinson-Plus-Disease: eg. Wilson’s disease (hepatolenticular degeneration); Fahr’s disease (basal ganglia calcification).

Cardinal symptoms of PD

Parkinson is a chronic neurodegenerative disease whose cardinal features are:

  1. Bradykinesia (slowness of movement)
  2. Muscular rigidity
  3. Resting tremor (which usually abates during voluntary movement)
  4. Impairment of postural balance (leading to disturbances in gait and falling)

They are expression of the extrapyramidal motor system i.e. basal ganglia and related thalamic and brainstem nuclei.

Hallmarks of PD neurodegeneration

(detected by striatal fluorodopa – PET which measure the integrity of nigrostriatal system)

  • DA: Degeneration of DOPAMINERGIC NEURONS [DOPAC + H2O2 (HYDROGEN PEROXYDE IS TOXIC)] in the SUBSTANTIA NIGRA PARS COMPACTA (SNc)
  • Reduced striatal dopamine
  • Intracytoplasmatic proteinaceous inclusions (LEWIS BODIES) can affect
    1. Ach: CHOLINERGIC NEURONS of the NUCLEUS BASALIS O MEYNERT
    2. NE: NOREPINEPHRINE NEURONS of the LOCUS CERULEUS (LC)
    3. 5-HT: SEROTONIN NEURONS in the RAPHE NUCLEI OF THE BRAINSTEM (RN)

PD onset phases

  1. Peripheral autonomic nervous system
  2. Olphactory system
  3. Dorsal motor nucleus of vagus (in the lower brainstem)

THAN SPREAD IN SEQUENTIAL MANNER TO AFFECT

  1. Cerebral emispheres
  2. and in the mid-stage are affected DA NEURONS
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