Parkinson's Disease

Key Facts

Degenerative movement disorder caused by a REDUCTION IN DOPAMINE IN THE SUBSTANTIA NIGRA

Characterised by the triad of - rigidity, bradykinesia (slow to execute movement), resting tremor

Epidemiology

Peak age of onset in 55-65 yrs

More common in MALES

Increasing prevalence with age

Aetiology

Drug induced

Combination of:

Idiopathic

Parkinson's genes - mutation in Parkin gene and alpha-synuclein gene

Oxidative stress and mitochondrial dysfunction

Environmental factors - pesticides, MPTP - found in illegal opiates

Risk Factors

Increasing age

Family history

Male

Being a non-smoker have a higher risk of Parkinson's

Pathophysiology

Results from mitochondrial dysfunction and oxidative stress

This results in the progressive degeneration of DOPAMINERGIC NEURONS from the pars compact of the substantia nigra in the midbrain that project to the striatum (caudate and putamen) of the basal ganglia

This results in reduced striatal dopamine levels due to the loss of dopaminergic neurones

Less dopamine means that the thalamus will be inhibited resulting in a DECREASE IN MOVEMENT and thus the symptoms of Parkinson's

Clinical Presentation

Speech becomes quiet indistinct and flat

Characteristic Parkinson's gait - stooped posture, small shuffling steps, reduced arm swing, narrow base

Drooling of saliva and swallowing difficulty is a late feature

Depression is common

Difficulty with fine movements e.g. doing up buttons

Constipation is common

Before motor symptoms develop (can be 7 years prior) - anosmia, depression/anxiety, aches, REM sleep disorders, urinary urgency, hypotension and constipation

Increased urinary frequency

Onset is ASYMMETRICAL - ONE SIDE ALWAYS WORSE THAN OTHER

CLASSIC TRIAD

Onset of symptoms is gradual and commonly presents with impaired dexterity or unilateral foot drop

Rigidity - since Parkinson's is extrapyramidal lesion

Bradykinesia/hypokinesia

Tremor

Improved by voluntary movements and made worse by anxiety

Worse at rest and often ASYMMETRICAL

Limbs resists passive extension throughout movement

Increased tone and thus rigidity over entire radius of joint movement

Increased tone in the limbs and trunk

Can cause pain and problems with turning in bed

Slow to initiate movement and flow, low-amplitude excursions in repetitive actions

Gait - narrowed

Differential Diagnosis

Benign essential tumour (more common) - worse on movement and rare whilst at rest - treat with beta blockers, or anti-seizure/anti-epileptics

Multiple cerebral infarcts, Lewy body dementia, drug-induced, Wilson's disease, trauma and all dopamine antagonists

Treatment

Diagnosis

Can confirm by response to LEVODOPA

MRI head - initially normal but will show atrophy, also used to exclude tumours or normal pressure hydrocephalus (forget how to walk, enlarged ventricles, dementia)

Diagnosis is CLINICAL, based on history and examination

If any of these are present in EARLY PARKINSON's, they are a sign that they aren't Parkinson's

  • Dementia
  • Incontinence
  • Symmetry
  • Early falls

The GOLD STANDARD treatment is ORAL LEVODOPA given alongside a decarboxylase inhibitor

Physical activity is beneficial and should be encouraged

Balance problems, speech and Gai disturbance do not respond to medication thus physiotherapy is the mainstay treatment for these

Dopamine agonists

Monoamine Oxidase B (MAO-B) inhibitors

Catechol-O-methyl transferase (COMT) inhibitors

Explain that the disease is slowly progressive and although incurable is amenable to palliation

Main treatment aim is to compensate for the loss of dopamine

Deep brain stimulation may help those who are partly-dopamine responsive

Surgical ablation of overactive basal ganglia circuits e.g. sub thalamic nuclei