Parkinson Disease

Parkinson Disease

Parkinson’s disease is a progressive neurodegenerative disorder that results in abnormalities in movement, autonomic function and cognition. It is caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, a nucleus that is involved in the initiation of movements. Parkinson’s disease can be diagnosed clinically, especially in older patients.

Diagnosis requires two or more of the following, not explained by any other condition: resting tremor, rigidity and/or bradykinesia

Postural instability and inability to carry out ADLs are associated with severe disease.

The gold standard of treatment for parkinson’s disease is Levodopa/carbidopa. Therapy is usually tailored to the patient

The incidence of Parkinson’s disease increases with age, with an average age of onset of 60 years. It is uncommon under the age of 40 years.

• Patient history
  • Older patient
  • Asymmetric onset eventually spreading to other parts of the body in an unpredictable way
  • Restlessness during sleep and/or sleepwalking
  • Reduced sense of smell
• Signs and symptoms of Parkinson’s disease
  • Bradykinesia
    • Decreased speed of repetitive movements
    • Micrographia
    • Masked facies
    • Softer or quiet voice accompanied by poor articulation
    • Fenestrating gait
  • Resting tremor (commonly pill-rolling)
  • Rigidity (cogwheel rigidity noticed at the wrist)
  • Postural instability
  • Bradyphrenia (slow thinking)
  • Sleep disturbance
  • Autonomic dysfunction
    • Constipation
    • Sweating
    • Sexual dysfunction
• Differentials
  • Parkinson plus syndrome
    • Shy-Drager syndrome (Multiple system atrophy): Parkinsonian symptoms, severe autonomic instability, and gait disturbances. Presents with upper motor neuron symptoms (hyperreflexia, primitive reflexes) and cerebellar symptopms (nystagmus)
    • Progressive supranuclear palsy: most common. Parkinsonian symptoms and vertigal gaze palsy. Tremor is not as prominent
    • Lewy body dementia: parkinsonian symptoms and prominent dementia at or near onset of symptoms
    • Vascular parkinson (lower body parkinson): parkinsonia symptoms + wide-based gait and absence of tremors
  • Secondary parkinsonism
    • Normal pressure hydrocephalus: urinary incontinence, gait disturbances and dementia. Rule out with CT scan. Resolves with CSF drainage.
    • Essential tremor: usually hereditary tremor that resolves with alcohol consumption or with trial of propranolol
    • Huntington’s disease: early onset, personality changes, angedonia, ballismus, chorea. Autosomal dominant inheritance
    • Wilson’s disease: psychiatric disturbances, liver failure, Kaiser-Fleischer rings. Autosomal recessive inheritance
    • Postencephalitic parkinsonisms: signs and symptoms of parkinsonism following encephalitis
    • Adverse effects of antipsychotics (extrapyramidal side effect): especially first generation antipsychotics
• Investigations
  • CT or MRI of the brain: to rule out differentials in patients < 55 years or additional signs and symptoms not associated with Parkinson’s
    • Brainstem and cerebellar atrophy in Shy-drager syndrome
• Treatment
  • Levodopa/carbidopa: first-line for patients who cannot maintain ADLs
    • Levodopa is a dopamine precursor that is converted into dopamine in the CNS
    • Carbidopa prevents the degradation of levodopa in plasma
  • Anticholinergics (pramipexole, ropinirole, bromocriptine, trihexylphenidyl, benztropine):
    • Trihyexylphenidyl and benztropine are preferred for high-functioning patients < 60 years old
    • Since bromocriptine is an ergot that can cause cardiotoxicity it should be used with caution
    • Ropinirole and pramipexole can be used as adjunctive therapy with dopamine agonists to increase it effects
  • Amantadine: preferred in high-functioning older patients since the adverse effects of anticholinergics are undesirable in older patients
  • COMT inhibitors (entacapone, tolcapone): to reduce fluctuations and adverse effects of dopamine agonists. These do not relieve Parkinson symptoms
  • MAO-B inhibitors (selegiline, rasagiline): used for Parkinson’s disease that is resistant to levodopa/carbidopa
  • Domperidone: to manage nausea
  • Atypical antipsychotics (quiteapine): drug of choice fo patients with schizophrenia
  • Regular follow-up
  • Screen for depression and other mood disorders
  • Exercise and speech therapy to improve quality of life
• Adverse effects of dopaminergic drugs
  • Dyskinesia (abnormal movements)
  • Akathisia (restlessness)
  • Nausea:
  • Response fluctuation throughout the day (due to fluctuating drug levels)