Parkinson’s Disease

Progressive chronic central neurological disorder that occurs due to degeneration of dopaminergic neurons in the substantia nigra, and is characterised by:

Epidemiology and Risk Factors

Prevalence:

  • Highly prevalent once over 50
    Lifetime risk:
    • Men: 2%
    • Women: 1.3%
  • Second-most common neurodegenerative condition
    Following Alzheimer disease.

Pathophysiology

Histologically characterised by:

  • Loss of dopaminergic neurons in the nigrostriatal system
    60-80% loss required for motor symptoms to be present.
  • Lewy bodies in brainstem

Aetiology

Multifactorial:

  • Genetic
    5-10%.
  • Environmental
    • Pesticides
    • Heavy metals
    • Well water
    • Woodworking
    • Head injury
    • Carbon monoxide

Clinical Manifestations

Four cardinal symptoms:

  • Tremor
    Rhythmic oscillation around a fixed point in the rest position.
    • Often first symptom
    • Usually a resting tremor
    • Characteristics include:
      • Asymmetrical
        Bilateral once deterioration occurs.
      • Supination/pronation
      • “Pill-rolling”
  • Rigidity
  • Bradykinesia
    Slowness of movement. May be:
    • Initiation
    • Continuation
  • Postural instability
    Balance dysfunction.
    • Major cause of falls, and subsequent injury and loss of independence

Secondary motor symptoms:

  • Dyskinesia
    Involuntary, prolonged muscle contractions with abnormal posturing.
    • Usually occurs when dopamine levels are low
      SUch as early morning.
  • Motor fluctuations
    Times of poor response to levodopa, and associated with advancing disease.
  • Reduced arm swing
  • ↓ blink rate
  • Masked facies
  • ↓ voice volume
  • Difficulty turning over

Non-motor symptoms may also fluctuate: * In off states: Poorer mood, and dysautonomia * In on states: Mania, agitation, delusions, paranoid, impulsivity

Autonomic dysfunction:

  • Orthostatic hypotension
  • Constipation
  • Incontinence
  • Nausea/Vomiting

Neuropsychiatric manifestations:

  • Mood disorders
    • Depression
    • Anxiety
    • Apathy
  • Impulse control
  • Psychosis
  • Hallucinations
  • Panic attacks
  • Executive dysfunction
  • Dementia

Diagnostic Approach and DDx

Remains a clinical diagnosis.

Investigations

Management

  • Therapy targeted to symptoms
  • Dopaminergic replacement when symptoms become bothersome
  • Surgical treatment is indicated when motor symptoms are unable to be ameliorated by medication

Medical

  • Levodopa
    Dopamine precursor.
    • Gold standard
    • Administered with a dopa-decarboxylase inhibitor (e.g. carbidopa) to reduce peripheral breakdown and nausea
      Variable preparations:
      • Immediate release
      • Extended release
      • Orally disintegrating tablet
      • Gel for PEG administration
    • Effective for rigidity and akinesia
    • Variable effects on tremor
    • Treatment does not worsen disease progression but high daily doses and long duration of disease is associated with motor fluctuations and dyskinesias
    • Benefit ↓ as disease worsens
      Reduced storage and release of dopamine limits utility of levodopa therapy.
  • Dopamine agonists
    Directly agonise receptors, bypassing degenerating dopaminergic neurones.
    • Used as monotherapy or adjuncts
    • Longer half-life
    • ↑ incidence of psychiatric side effects
    • Agents included:
      • Pramipexole
      • Ropinirole
      • Rotigotine
      • Apomorphine
        Rescue medication given subcutaneously.
  • COMT inhibitors
    Reduce levodopa breakdown.
    • Used in conjunction with levodopa
    • May ↑ dyskinesia
    • Include:
      • Entacapone
      • Tolcapone
  • MAO-B inhibitors
    Reduce levodopa breakdown.
    • Include:
      • Selegiline
        Selective, irreversible; used as an adjunct.
      • Rasagiline
        Monotherapy or adjunct.

Surgical

Deep Brain Stimulation:

  • Modulation of brain circuitry via electrical stimulation
  • Improves tremor, dyskinesia, and motor fluctuations

Anaesthetic Considerations

  • A
    • Potential difficult airway
      • Cervical spine rigidity
      • TMJ dysfunction
    • Aspiration
      • Bulbar dysfunction
      • Oesophageal dysfunction
        Bradykinesia and pharyngeal rigidity ↑ aspiration risl.
      • Gastroparesis
      • Sialorrhoea
  • B
    • Chest wall rigidity
      • Impaired secretion clearance
  • C
    • Autonomic instability
  • D
    • Parkinsonian medications
      Medication management is critical.
      • Continue anti-Parkinson’s drugs perioperatively
        • Give up to the time of surgery
          Except prior to deep brain stimulator placement.
        • Restart as soon as possible after surgery
      • Avoid dopamine antagonists
        • Metoclopramide
        • Typical antipsychotics
          Droperidol, haloperidol.
        • Phenothiazines
          Chlorpromazine.
      • MAO-I use
        Selegiline.
    • Deep brain stimulators
      Consist of electrodes implanted into brain parenchyma, a pulse generator located (usually) below the clavicle, and a wire connecting them.
      • Preoperatively
        Assess:
        • Model, location, last check, battery life
        • Severity of symptoms when disabled
        • How to use the patient programmer
          Particularly how to turn it on and off.
        • Discuss with patients neurologist about any post-operative checks required
        • Path of wires and location of device to avoid iatrogenic injury
      • Intraoperatively
        • Turn device off to minimise EMI
          Can turn off after induction if severe symptoms.
        • Regional anaesthesia may require ↑ sedation to control symptoms whilst off
        • Turn device on prior to emergence
        • Use bipolar diathermy in short bursts with lowest possible power
      • Post-operatively
        • Neurological examination to rule out adverse events
        • Device check by product representative or neurologist
    • Opioids
      • Muscle rigidity
      • Dystonic reactions
    • Dementia
  • E
    • Motor function

Marginal and Ineffective Therapies

Complications

Parkinson Hyperpyrexia Syndrome:

  • Potentially fatal complication of withdrawal of antiparkinsonian medications leading to sudden suppression of central dopaminergic activity
  • Additional precipitants include:
    • Neuroleptics
    • Dehydration
    • Hot weather
  • Presents 18-24 hours following the trigger
  • Clinical features include:
    • Initial tremor, rigidity, and leads to immobility
    • Later (24-72 hours) development of pyrexia and obtundation
    • Autonomic dysfunction
      Tachycardia, labile BP, fever.
  • Treatment recommendations include:
    • Replace antiparkinsonian medications
      • Premorbid levodopa dose
      • Dopamine agonists
    • Supportive therapy
      • HDU
      • Cooling
      • Consider dantrolene if rigidity not responding to other measures
  • Complications of the syndrome include:
    • Aspiration pneumonia
    • DVT/PE
    • DIC
    • Rhabdomyolysis
    • Seizures

Prognosis

Progression subdivided into three stages:

  • Preclinical phase
    Asymptomatic neurodegeneration.
  • Prodromal phase
    Symptoms present but insufficient for diagnosis.
  • Clinical phase
    Symptoms manifest and recognisable.

Key Studies

References

  1. Zesiewicz TA. Parkinson Disease. CONTINUUM: Lifelong Learning in Neurology. 2019 Aug;25(4):896.
  2. Newman EJ, Grosset DG, Kennedy PGE. The Parkinsonism-Hyperpyrexia Syndrome. Neurocrit Care. 2009;10(1):136-140. doi:10.1007/s12028-008-9125-4
  3. Yeoh, Tze Yeng, Pirjo Manninen, Suneil K. Kalia, and Lashmi Venkatraghavan. ‘Anesthesia Considerations for Patients with an Implanted Deep Brain Stimulator Undergoing Surgery: A Review and Update’. Canadian Journal of Anesthesia/Journal Canadien d’anesthésie 64, no. 3 (1 March 2017): 308–19. https://doi.org/10.1007/s12630-016-0794-8.