Parkinson's Disease

Parkinson's disease is a movement disorder characterised by: tremor at rest, rigidity, bradykinesia

Aetiology

Risk factors

  • Advancing age is the greatest risk factor
  • Positive family history
    • Early onset (below 40 years) increases probability of genetic cause
  • Male gender
  • Environmental factors e.g. pesticide exposure, prior head injury, rural living, beta blocker use
  • Genetic link - monogenetic forms have been identified e.g. LRRK2 and PARKIN

Pathophysiology

Pathological hallmarks

  • Sections through the brainstem reveals loss of the normally dark black pigment in the substantia nigra and locus coeruleus
  • Pigment loss correlates with dopaminergic cell loss
  • A neurohistological hallmark of PD are Lewy bodies
notion image

Subtypes of PD

  • Motor features in PD are heterogenous, but there are broadly 2 subtypes:
    • Tremor dominant PD (with relative absence of other motor symptoms)
    • Non-tremor dominant PD (such as akinestic-rigid syndrome and postural instability gait disorder)
    • Mixed/indeterminate phenotype
  • Course and prognosis differ with the tremor-dominant subtype being associated with slower rate of progression and less functional disability

Clinical presentation

Motor symptoms

  • Bradykinesia - slowness of movement with progressive loss of amplitude or speed during attempted rapid alternating movement of body segments
  • Resting tremor - rhythmic oscillatory involuntary movement of affected body part at rest
    • Often described as pill-rolling because the patient appears to be rolling something between thumb and forefinger
  • Rigidity - stiffness on passive limb movement is described as ‘lead pipe’, as it is present throughout the range of movement and, unlike spasticity, is not dependent on speed of movement
    • When stiffness occurs with tremor (not always visible), a ratchet-like jerkiness is felt, described as ‘cogwheel’ rigidity
  • Postural and gait impairment
    • Stooped posture owing to impaired postural reflexes (major contributor to falls risk)
    • Gait gradually becomes shuffling

Non-motor symptoms

  • Sleep disorders
  • Hallucinations
  • GI dysfunction
  • Depression
  • Cognitive impairment/dementia
  • Anosmia
  • Issues with speech and swallowing
    • Speech becomes quiet, indistinct and flat
    • Drooling
    • Swallowing difficulty is a late feature that may eventually lead to aspiration pneumonia as a terminal event

Investigations

Supportive features of a diagosis of Parkinson's

  • Essential (Parkinsonism) - bradykinesia and one or more of the following:
    • Resting tremor
    • Rigidity (cogwheel or lead-pipe)
    • Postural instability
  • Additional motor features
    • Stooped posture
    • Dystonic postures
    • Hypomimia ('masked' face)
    • Shuffling
    • Short-stepped gait +/- festination
  • Additional non-motor features
    • Late onset hyposmia
    • Depression and anxiety
    • Constipation
    • Bladder problems
    • Pain
    • Subtle mental or cognitive impairment

Confirmation of diagnosis

  • Parkinsonism
  • No alternative explanation for presentation
    • Rule out treatable conditions of asthenia (hypothyroidism, anaemia)
  • Dopamine responsiveness
  • Diagnostic tests not usually needed, structural brain involvement and SPECT can be helpful

Management

Pharmacological management of motor symptoms

  • To date there are no available neuroprotective or disease modifying drugs for PD
  • Symptomatic treatments enhance intracerebral dopamine concentrations or stimulate dopamine receptors
    • These symptomatic drugs include levodopa, dopamine agonists, monoamine oxydase type B inhibitors, and less commonly amantadine
  • Tremor is inconsistently responsive to dopamine replacement therapy, especially in lower doses; anticholinergic agents, trihexyphenidyl, or clozapine, can be effective for tremor

Phamacological manangement of non-motor symptoms

  • Treat non-motor symptoms accordingly e.g. dopamine agonist, SSRIs for depression, osmotic laxitives for constipation etc.