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  • 3.5% population >55
    • Prevalence increases with age

Risk factors

  • Age, family history (genetic susceptibility)
  • Smoking decreases risk
    • Therefore we are trying out nicotine as a possible therapy
  • May have an addictive personality factor
  • Coffee/ibuprofen?
  • No strong evidence for antioxidants, fats


  • Parkinson’s has a severe impact on activities of daily living and family
    • Often can result in depressive symptoms
  • Main risk factor is age


  • $7000/ year living in the community
    • direct and indirect costs = $16000/year
  • indirect: eg: carers, early retirement

Scenario video

  • Suffered Parkinson’s for 13 years
    • Began with a right leg tremor
      • Progressed to a right arm tremor
  • Initial diagnosis
    • 1st neurologist – no tests, straight diagnosis and given drugs
      • simply trusted the specialist, didn’t question
    • dyskinesia – wouldn’t go outside, voice was bad
      • got worse if thought about people watching, brought on by anxiety
    • Psychiatrist
      • Suggested shock treatment – too expensive, no
    • 2nd neurologist – 15 tablets, drugged badly + bad side effects
    • GP – trusted and liked – went to different neurologist
      • Notes weren’t transferred, many things were not explained properly, felt left out of the loop
    • Deep brain stimulation
      • Conscious, deep brain stimulators inserted
      • Alleviated symptoms
      • Had lots of family support
      • Recovered activities of daily living in response to dbs
  • ARx: lumps and bumps on head, and her medications have reduced her from 16 pills per day to 3 pills per day

Professor Colebatch

Parkinson’s disease

  • Basal ganglia – PD thought to be the archetypal disease; thus “paralysis agitans” – but “paralysis” is a very late feature however. Movement disorder not initially one of paralysis.
  • DBS – needs careful selection
  • 1813 – shaking palsy, James Parkinson, a movement disorder
    • long held to be a clear example of basal ganglia disease
    • 2nd most common disease of neurodegeneration
    • prevalence about 2% at age 70
  • Diagnosis and assessment remain mostly clinical


  • Most cases are idiopathic
    • 11 genetic abnormalities lead to susceptibility
      • eg: alpha synuclein and mitochondria
  • Age – failure of cellular energy production
    • PD can be the end product of a variety of insults
  • Arises in the substantia nigra, innervates the striatum etc
    • VTA projects to the frontal cortex which causes symptoms
  • Presymptomatic phase may be 5 years long
    • Lewy bodies – pathological indicators of Parkinson’s
    • Substantia nigra – loss of black substance
  • The cause of the common (idiopathic) disease remains unclear, although senescence and failure of cellular energy production (mitochondria) are likely to be important – genetic contributions appear to be small in most (MPTP)

Genetic causes of parkinsonism

  • Park1 A.D. Alpha synuclein
  • Park 2 A.R.(?) Parkin (most common cause of very early onset < 30 yrs old)
  • Park 3 A.D. gene unknown
  • Park 4 A.D. Alpha synuclein gene dup, trip
  • Park 5 A.D. ubiquitine C term hydrolase L1
  • Park 6 A.R. PINK1
  • Park 7 A.R. DJ-1
  • Park 8 A.D. LRRK2
  • Park 9 A.R. ATP13A2
  • Park 10 A.D. (?) gene unknown
  • Park 11 A.D. (?) gene unknown

Consider if: family history or early onset.

  • Main input for Parkinson's is striatum (putamen + caudate), main output is globus pallidus
  • Niagro-striatal dopamine pathway is damaged (reduced striatal dopamine due to substantia nigra problems)
    • Lewy bodies in substantia nigra, loss of pigmented cells
  • There is a lot of niagral reserve, so a fair amount of degeneration (5-10 years) before symptomatic
    • A good goal = stop the disease early (detect it early). What is initially easy treatment becomes more difficult with time.

Pathology of PD

  • Braak et al.:
    • α synuclein deposition occurs widely, initially (Stage 1) in anterior olfactory structures and dorsal motor nucleus of the vagus (X). (Indeed, effects start in the olfactory area and spread up the brainstem, but later on once the substantia nigra (particularly vulnerable) is involved, then the PD symptoms become clear. This makes it clearer why dementia is often a complication).
    • Only in (their) stage 3 does the process affect the midbrain and forebrain. Lewy neuritis and Lewy bodies appear in the pars compacta of the substantia nigra.
  • Recurrence of Lewy bodies occurs in grafted patients
  • Brundin et al. (2008) reported Lewy bodies in 3 of 8 grafted patients
    • Something in the milieu of these patients causes the disease
  • Similar to prion-based diseases (e.g. CJD), there is an intercellular transmissibility due to alpha-synuclein

Clinical assessment

  • Examination
    • Gait and expression
    • Speech, monotonal + characteristics (later may develop hesitant/festinant/repetitive qualities). Festinant = rushed. If they concentrate enough on speech/movement, it can almost become normal, but when they relax it returns to the diseased state
  • History
    • Writing
    • Difficulty getting out of chairs/bed (when bilateral)
    • Clumsiness
    • Paralysis
    • Swallowing problems (bulbar palsy - serious)
  • Examination
    • Review treatments
    • Tremor, tone, weakness
    • Increased muscle tone - cogwheeling/rigidity
    • Weakness, if present, is mild
    • Bradykinesia - slowness of movement. Critical in diagnosis.
    • Postural changes/gait changes
    • Severity - Hoehn and Yahr scale (I-IV)

Hoehn and Yahr Scale (1967)

Note we get concerned when presentation is atypical, because there are other diseases that can produce similar symptoms but are not amenable to treatment

  • Stage I: unilateral involvement only
  • Stage II: bilateral but balance normal
  • Stage III: impaired postural reflexes
  • Stage IV: need help to dress and feed, still able to walk unaided
  • Stage V: unable to walk without assistance – (Va – can transfer, Vb unable to transfer)

Clinical Assessment of PD - 3

  • Make specific note of:
    • eye movements pursuit and saccades
    • evidence of autonomic involvement (postural bp) – pyramidal/cerebellar/sensory changes
    • cognitive impairment
    • (myoclonus, “alien limb”)
    • postural stability
    • (a)symmetry of signs (good indicator of it being PD and not atypical disease)
  • Atypical features may indicate presence of a “Parkinson’s Plus” or other syndrome (inc. MSA – autonomic involvement, PSP – eye movement changes, DLB – fluctuation, early dementia).

Clinical Signs of PD - Tremor

  • Tremor:
    • typically unilateral upper limb
    • a “resting” alternating tremor, may occur on holding an object or when walking, easily abolished by making a movement
    • classically said to be “pill rolling” but not always so.
  • Recordings show that when a voluntary movement is asked to be done, the tremor is removed.

Clinical Signs of PD - Rigidity

  • Rigidity=increase in passive muscle tone, appreciated by examiner
    • typically best appreciated at the wrists, but may be present at any muscle joint (shoulder, knees)
    • present with even slow movements, throughout range of movement thus “lead-pipe”, persistent muscle activity
    • limb does not resume original position if displaced
    • tendon reflexes are not enhanced
    • may be interrupted = “cogwheel”

Clinical Signs of PD - Bradykinesia

  • Arguably the most important sign of PD
    • Related: akinesia (inability to initiate movement; very late sign), hypokinesia (reduced movement), bradykinesia (slowness of movement)
    • typically tested using repeated fine movements of the fingers e.g. pinch, tapping, writing (micrographia)
    • test the feet – tapping, alt heel/toe movements
    • observe the speed of movement and “fatiguability”
    • with sufficient effort or if startled, may move almost normally – greater “effort” is required

Movement disorder of PD

  • movement of small muscles (eg interossei) more severely affected than large ones (Wilson, 1925)
  • often run better than walk (Parkinson)
  • role of cues – auditory or visual
  • greater deficits when attempting to do two movements simultaneously (Schwab et al., 1953)
  • no true apraxia – able to select and contract the desired muscle(s) (Wilson, 1925) – selection and relative timing of different muscle groups is normal.

Schwab et al., 1954, Case 1

  • 58M, described an episode:..walking across the hotel lobby in front of the usual number of strangers to pay his bill, he reached into his inside pocket with his left hand to get his wallet. At once he stopped walking, standing immobile..he then resumed walking but his left hand remained in his inside pocket, suggesting perhaps a planned holdup.

Slowness of Movement in PD

  • CD Marsden (1989) factors:
    • rigidity (not sole cause),
    • delayed simple reaction time,
    • impaired prediction of targets, dependence upon visual information,
    • prolonged movement times for simple movements,
    • additional difficulty with simultaneous or sequential movements.

Clinical Signs of PD – Posture

  • Gait said to be “festinating” (= hurry) but this is rarely seen in its strict sense
  • Gait more commonly consists of small steps and reduced armswing
  • Patient is typically flexed
  • Test postural stability using the “pull back” test


  • Medical oral: L-dopa/decarboxylase inhibitors, dopa agonists, entacapone, selegiline
  • Medical – parenteral (apomorphine)
  • Surgical – deep brain stimulation (DBS) – subthalamic nucleus (STN) is usual target
    • Good candidates - dyskinesia, responsive to L-Dopa

Prognosis/Current outlook

  • Sydney Multicentre Study (Hely M et al.)
    • initially designed to compare L-dopa treatment with bromocryptine (n=136)
    • has become a very useful source of information about current prognosis
    • 20 year follow up recently published.

==Sydney Multicenter Follow Up==

  • At 20 years:
    • 100/136 dead (76%) – higher than standardised rate for age
    • most problems related to non-levodopa responsive features of the disease
    • dementia present in 83% of survivors
    • only one patient was living independently
      • falls(87%), freezing(81%),sleepiness(70%)
      • hallucinations(74%)
    • Represents progression of the disease up the brainstem and higher
  • First 5 years of the disease, management is relatively simple. After that, things become more grim.


  • Slow gait, flexed, bradykinesia, upper limb tremor
  • Arm stops swinging when you walk - affects balance
  • Some have very pronounced dyskinesias, particularly upper limb/head