The Case of the Frozen Addict

(Nova, 2/18/86, copyright PBS)

1. drug-induced Parkinsonism
   1. synthetic heroin ("designer drugs") - at this time, small changes in the chemical structure of an illegal substance could make it a "street-legal" drug (this loophole in the law has since been plugged)
   2. treated with l-dopa (the standard treatment for Parkinson's disease)
      1. replaces missing dopamine in the brain (l-dopa is the precursor for dopamine)
      2. without dopamine, thoughts of movement cannot be translated into the movements themselves
   3. contaminants in the synthetic drug (produced through sloppy basement chemistry) had destroyed the dopamine neurons in the substantia nigra, producing an advanced Parkinsonian state overnight
      1. MPPP (synthetic heroin)
         1. injected rats freeze up
         2. but only temporarily
      2. MPTP (the contaminant)
         1. injected rats are unaffected
         2. injected monkeys develop Parkinsonism
   4. revitalized research into Parkinson's disease
2. Parkinson's disease
   1. a disease of old age characterized by:
      1. fine tremor, especially noticeable in the hands when at rest
      2. cogwheel rigidity
      3. difficulty initiating voluntary movements
      4. masked face
      5. shuffling gait
   2. l-dopa therapy
      1. oftentimes must be taken every few hours, even during the night
      2. side effects - writhing movements (athetosis) and hallucinations; sometimes schizophreniform psychosis
   3. severe cases (drug-induced) have been misdiagnosed as hysterical paralysis and as catatonic schizophrenia
   4. causes: environmental toxins are suspected
      1. substantia nigra cells die off gradually with aging
      2. if exposure to a toxin kills off large numbers of the cells, then subsequent cell death with aging results in Parkinson's disease
      3. 80% of nigral dopamine neurons must die before symptoms become evident
3. possible toxins
   1. MPTP is converted to MPP+ (Cyperquat) in the brain by MAO
   2. this product is related to chemical herbicides (Cyperquat, Paraquat)
   3. incidence of Parkinson's disease is highest in agricultural areas and areas with pulp and paper mills (according to a Canadian study cited in the video--a subsequent study done in the midwestern US has found the same pattern, but this study was not mentioned in the video)
   4. MPTP-like substances (pyridines) are widespread in the environment
   5. the MAO-blocking drug pargyline prevents the MPTP-induced Parkinsonism and prevents cell death in the substantia nigra
   6. PET scanning can detect those at risk for Parkinson's disease--someday it may be possible to do a routine brain scan on middle-aged people; those with abnormally low nigral cell counts may then be put on MAO blockers to prevent further nigral cell deterioration
4. some new findings since this video was made
   1. MPTP has become a major research tool in the study of Parkinsonism in animal models
   2. a Parkinsonian-like state has now been produced in rats
   3. some research suggests that the toxin binds to a pigment molecule in the substantia nigra called neuromelanin (it is neuromelanin that gives the substantia nigra its dark appearance in primates; rats have very little pigmentation in the substantia nigra, which may be why they are less susceptible to the toxin)

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