Parkinson Disease

• PD is a neurodegenerative disorder occurring due to the loss of dopaminergic cells from the substantia nigra
• The most common cause of parkinsonism: a syndrome of motor symptoms that involves bradykinesia plus at least one of; rigidity, tremor or postural instability
• Dopamine is produced in the substantia nigra within the basal ganglia
• Loss of dopaminergic neurons results in a reduction in the action of the direct pathways of the basal ganglia and a resultant increase in the antagonistic indirect pathway = restrictive action on movement
• Formation of Lewy bodies (protein clumps) within the remaining neurons
• Risk factors:

  ·       Idiopathic

  ·       First-degree family history

  ·       Male sex

  ·       Increasing age (over 55)
• Symptom history:

  ·       Motor symptoms: slowness of movement, stiffness, tremor (resting), instability or falls, reduced dexterity

  ·       Autonomic: constipation, light-headedness on standing, excessive salvation or sweating, urinary dysfunction and sexual dysfunction

  ·       Mood/cognitive symptoms

  ·       Sleep disturbances and daytime sleepiness

  ·       Anosmia – loss of smell

  ·       Cognitive decline

  ·       REM sleep behaviour – punching, kicking or shouting during sleep

  ·       Altered handwriting – micrographia
• Clinical exam:

  ·       Full neurological exam

  ·       Bradykinesia – tested using finger taps which are slow with progressive fatiguing and decrease in amplitude

  ·       Tremor- typically a ‘pill-rolling’ tremor of the hands at rest

  ·       Rigidity

  ·       Abnormal gait- shuffling, festinating (progressive acceleration of stride alongside with a reduction of stride length), reduced arm swing, freezing

  ·       Postural instability- tested using the pull test

  ·       Forehead tapping test
• Motor features usually begin unilaterally but will progress to become bilateral. The side affected first continues to be worse causing persistent asymmetry.
• General exam:

  ·       Hypomimia- decreased facial expression

  ·       Postural hypotension

  ·       Confusion

  ·       Reduced dexterity- struggles fastening buttons
• Other causes of parkinsonism:

  ·       Lewy body dementia

  ·       Multiple system atrophy – unsteadiness, falls and autonomic dysfunction

  ·       Progressive supranuclear palsy – unsteadiness, dysphagia and gaze palsies

  ·       Vascular parkinsonism – cerebrovascular disease along with a sudden onset of symptoms

  ·       Drug induced parkinsonism:

  -          Any drug that blocks dopamine or increases its breakdown

  -          Antipsychotics e.g. haloperidol

  -          Antiemetics

  -          Symptoms are more likely to be bilateral
• Investigations for PD:

  • L/S BP - postural hypotension
  • Cognitive assessment
  • Confusion screen - FBC, electrolyte derangement, hepatic encephalopathy, CRP, diabetes, hypothyroidism, hypo/hypercalcaemia
  • DaT scan
• Diagnosis:

  ·       A movement disorder/PD specialist should make the formal diagnosis

  ·       Refer promptly to specialist clinic

  ·       Key diagnostic features are bradykinesia plus one of: rigidity, tremor or postural instability
• There is no cure for PD and current treatment does not halt or reverse the progression of the disease

  ·       Treatment aims to reduce symptoms by replacing dopamine or reducing dopamine breakdown
• Offer levodopa to people in the early stages of Parkinson’s disease whose motor symptoms impact on their quality of life – Levodopa is a precursor is dopamine and is therefore metabolised into dopamine
• Levodopa taken with carbidopa to reduce metabolism into dopamine before crossing the blood-brain barrier and also reduces side effects such as nausea and vomiting
• Monoamine oxidase-B inhibitors (MOA-B inhibitors) e.g. selegiline block the breakdown of dopamine
• Catechol-O-methyl transferase (COMT) inhibitors e.g. entacapone decrease dopamine breakdown and prolong the action of levodopa
• Anti-parkinsonian medications are time critical medications. Patients who miss doses or receive late doses could experience freezing. Suddenly stopping PD meds may also cause neuroleptic malignant syndrome which can be life-threatening.
• Complications of PD:

  ·       Poor mobility can lead to increased falls and resultant injuries

  ·       Risk of dementia is significantly higher- dementia with Lewy Bodies and Parkinson’s dementia

  ·       Hallucinations are a common complication – patients can develop paranoia

  ·       Aspiration pneumonia is frequently seen in end-stage PD as a complication of dysphagia
• In Parkinson’s disease dementia, cognitive symptoms develop more than a year after the onset of movement symptoms
• PD typically presents in those above 55 years old. Higher prevalence in men.
• Parkinson’s disease occur due to the loss of dopaminergic neurons in the nigrostriatal pathway, a motor control pathway that originates in the substantia nigra and terminates in the striatum
• Physiologically, dopamine (an excitatory neurotransmitter) acts to upregulate the thalamus and ultimately the motor cortex via the direct pathway of the basal ganglia. This results in increased movement.
• Any drug which acts by blocking dopamine or increasing its breakdown can cause parkinsonism:

  • Antipsychotics - more commonly first generation such as haloperidol
  • Antiemetics - prochlorperazine, metoclopramide
• Symptoms are more likely to be bilateral in drug induced parkinsonism than in Parkinson Disease
• The antiemetics prochlorperazine and metoclopramide should not be used in patients with Parkinson disease as they block dopamine and therefore worsen motor symptoms
• Response to medication deteriorates with time and side effects may be seen such as dyskinesias (typically seen soon after taking medications due to overstimulation) or re-emergence of symptoms as each dose wears off. With disease progression and increased loss of dopaminergic cells, increasing doses of medication are needed, leading to an increased risk of side effects.
• Parkinson’s disease occur due to the loss of dopaminergic neurons in the nigrostriatal pathway, a motor control pathway that originates in the substantia nigra and terminates in the striatum.
• Although motor symptoms are the diagnostic features of parkinsonism, non-motor features may precede motor symptoms by years in PD.
• smoking is thought to be protective for PD