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Parkinsonism and Other Neurodegenerative Diseases

PARKINSONISM:
PARKINSON DISEASE
  • Clinical Features: 
    • Cardinal: Tremor, Bradykinesia, Rigidity, Postural Instability
    • Motor: See Below in Movement D/O in PD
    • Non-motor:  Anxiety (Even Panic), Inner Restlessness (Akathasia), Extreme Apathy, Depression, Insomnia, 
    • Pathophysiologically
      • Dopaminergic Clinical Features 
      • Non-Dopaminergic Clinical Features 
  • Diagnosis: Clinical
    • Rest Tremor, Asymmetry, Good Response to Levodopa (99% Correct Pathologically)
    • 2 of the 3 (Tremor, Rigidity, Bradykinesia; 22% error on autopsy)
  • Rx:
    • Dopaminergic Agents (for Tremor, Bradykinesia, Rigidity):
      • Carbidopa-Levodopa (is still the best)
        • Anti-PD effect occurs in 2 patterns
          • Long-Duration Response (First several years on treatment)
          • Short-Duration Response (SDR) (Response mirror the LD concentration in circulation; occurs after several years of treatment)
            • SDR Dose adjustment based on TWO concepts (Similar to Furosemide and Morphine)
              • Is does enough to capture the optimum peak effect? (Larger dose does not last much longer)
              • Assess duration of response (Do not worry about number of doses per day; there is no cumulative toxicity)
                • Watch for "wearing off"
        • Always check orthostatics BP before and after starting
          • BP fluctuates with different times of the day (as much as 90/60)
        • Space from meal (1 hr before or 2 hr after)
    • Non-dopaminergic agents (solely or primarily for tremor reduction)
      • COMT Inhibitor (Entacapone): Blocks COMT outside the BB
        • Can Increase Levodopa Dyskinesia
        • Helps to amplify the potency of CP-LD
    • Insomnia: Common due to akathisia, stiffness, cannot turnover in bed
      • Bedtime LD-CD will help
      • If they wake up in middle of the night, LD-CD may need to be given
      • Insomnia also responds in ALL-or-NONE fashion, if under treated even potent sleep aid medications will be ineffective
    • Nausea: 
      • LD effect at Brain-Stem N/V Center will cause N
      • Avoid anti-dopaminergic anti-emetics (Metoclopramide, Prochlorperazine - Compazine); Ondansetron can be used.
    • Hallucinations and Delusions
      • Drugs for the treatment of PD can cause these symptoms especially Dopamine agonists than LD-CD (50% dose reduction is reasonable)
      • Avoid anti-psychotic agents (all most all will block Dopamine); Exception: Quetiapine (can be started at 25 mg)
      • Often they act out their dreams (REM Behavior). Do not confuse this with Hallucinations
    • Pain
      • Directly due to PD (painful leg cramps, toe curling, dystonic limbs): Highly responsive to treatment with LD
      • Pain from other source are worse in LD worn off state, and pain threshold reduced and severity enhanced if undertreated
    • Dyskinesia (Chorea like; LD Excess) and Dystonia (Low LD)
    • Anxiety: Is also ALL-OR-NONE phenomenon
  • References
Freezing of Gait
Movement Disorders in patient with PD (details in movement disorder: see below): 
Pre-diagnosis : 
Restless Leg Syndrome, 
Dystonia (Task-specific, Exertion-induced), 
Inner sense of Tremor
Akathisia
At Diagnosis: 
Resting / Action Tremor, 
Akinesia / Bradykinesia, 
Postural Instability
Post-Diagnosis:  Two Concepts
Levodopa Dyskinesia (Chorea, Choreo-Dystonia)
  • Excessive Levodopa Effect
  • Usually "short duration" effect
  • Related to individual dose and not cumulative dose
  • Decreasing the dose to the level that prevents dyskinesia is the simple strategy
  • AMANTADINE reduces dyskinesia. Usually added if dose reduction of LD-CD leads to Parkinsonism symptoms.
    • Amantadine can induce hallucinations esp in higher dose
Levodopa MOTOR FLUCTUATIONS Pure Dystonia (especially if painful), Akathisia(restlessness)
  • Due to Levodopa Insufficiency
  • Distinguish it from Levodopa excess effect as above
  • Somewhat similar to pre-diagnosis stage (which has dopa insufficiency)






ATYPICAL PARKINSONISM
Other Myoclonos
Additional Resources on PD and Pharmacology
Levodopa for the Treatment of Parkinson’s Disease 
Advances in the Pharmacologic Management of Early Parkinson Disease 
Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review) (2006, American Academy of Neurology) 
Parkinson's Disease (Medical Letter)

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