RECENT DIAGNOSIS

  • Clinicopathological studies that 25% of cases have different diagnosis.
  • Special proteins like tau,alpha synnuclein play a major role.
  • Immunohistochemistry:LEWY BODIES –hallmark of parkinsonism

TAU PROTEIN DEPOSITS

  • Hereditary factors : 13 different loci have been associated.
  • Oxidative stress,impairment in mitochondrial complex 1 are also responsible.

SITE OF FIRST PATHOLOGICAL CHANGE.

  • OLFACTORY NUCLEUSà
  • VAGUS NERVE à
  • LOWER BRAINSTEM NUCLEIà
  • AMYGDALAà
  • SUBSTANTIA NIAGRAà
  • TEMPORAL LOBE

POSSIBLE GENETIC BASIS.

  • 3 MAIN GENES ARE RESPONSIBLE
  • GENE FOR SYNUCLEIN: shows amino acid substitution àaccumulation of this protein in LEWY BODIES àTissue destruction
  • PARKIN GENE:Showing homozygous deletion.
  • GENE FOR UBIQUITIN: missense mutations.

TREATMENT

  • SURGERY
  • STEM CELL CULTURE
  • GENE THERAPY
  • DRUGS

SURGERY

  • PALLIDOTOMY by thermoregulation.
  • THALOTOMY
  • SUBTHALOTOMY
  • DEEP BRAIN STIMULATION using a quadripolar electrode(100-180Hz)

STEM CELL TREATMENT

  • First neurodegenerative disorder in which this technique was tried
  • Aborted foetal cells were being transplanted
  • Also porcine foetal cells were also being incorporated.
  • DRAWBACKS: Immunoincomptability,ethical issues.

GENE THERAPY

  • Cells like fibroblasts etc are modified.
  • With the help of adeno associated vectors DOPAMINE inducing enzymes are incorporated into the modified cells.
  • These are incorporated into the basal ganglia.

NEWER MEDICATIONS

  • DOPAMINE AGONISTS:
  • Not just as an adjuvent anymore.
  • Neuroprotection of dopaminergic neurons as monotherapy.
  • Egs; Bromocriptine,pergolide,mirapex,ropinerole

RULES

  • Use only one at a time.
  • Start at a lower dose.
  • Evenly spaced 3 doses at a time.
  • Slowly titrate the dose by doubling lowest dose no faster than every 1-2 weeks till beneficial effects/ intolerable side effects are seen.
  • If dementia prexists Ropinerole

  • COMT INHIBITORS
  • Increases ½ life of L-Dopa,bioavailability.
  • Egs;Tolacapone Entacapone.

Dopamine dysregulation syndrome.

  1. Seen in a subgroup of people taking additional quantities of drug well beyound their dose.
  2. This led to some behavioural changes &motor changes.