Parkinson’s Disease.

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s.

ETIOLOGY/ PATHOGENESIS

  • Average age of onset is 45-65 years old, with more men than women affected (3:2).
  • Cause is a combination of poorly understood genetic and environmental factors.
  • Genetics: can be due to autosomal dominant (α-synuclein gene mutations, duplications, triplications; LARK2 mutations) or Autosomal recessive (parkin, DJ-1, PINK-1).
  • Pathologic hallmarks: neuronal loss with depigmentation of the substania nigra and the presence of Lewy-bodies.
  • Dopamine depletion due to degeneration of dopaminergic neurons in the substania nigra which produces an imbalance of dopamine and acetylcholine.

 PERTINENT HISTORICAL FINDINGS/ CLINICAL SYMPTOMS

  • Gradual onset with patients complaining of problems related to slow movements, difficulty arising from seated position, trouble with activities of daily living such as dressing, personality changes, autonomic dysfunction, or cognitive impairment.
  • Typically, the motor symptoms begin in one limb.

 PERTINENT PHYSICAL EXAM FINDINGS

  • Motor Symptoms: bradykinesia, cog-wheel rigidity, resting tremor/ pill-rolling, postural instability, loss of fine motor movements, shuffling gait with short steps & decreased arm swing, flexed posture.
  • Non-motor Symptoms: dysarthria or drooling, cognitive impairment, masked facies with infrequent blinking, micrographia, Difficulty initiating movements and freezing of motion.
  • Autonomic dysfunction: orthostatic hypotension, respiratory dysregulation, flushing, constipation.
  • Neurobehavioral Dysfunction: apathy, lack of confidence, fearfulness, anxiety, social withdrawal, emotional liability, Dementia.

 DIFFERENTIAL DIAGNOSIS

  • Multi-system atrophy
  • Progressive supranuclear palsy
  • Corticobasal degeneration
  • Vascular parkinsonism
  • Dementia with Lewy Bodies
  • Alzheimer’s Disease
  • Normal-pressure hydrocephalus
  • Drug-induced parkinsonism

DIAGNOSTIC EVALUATIONS

  • Diagnostic evaluation focuses on ruling out other causes of parkinsonism.
  • Young-onset patients should have 24-hour urine copper and serum ceruloplasmin to rule out Wilson’s disease.
  • MRI: Usual normal in Parkinson’s disease.
  • Transcranial ultrasound: increased echogenicity in the SNc of the midbrain.

MEDICAL MANAGEMENT

  • No medical treatment has been proved to modify the progression of the disease.
  • Anticholinergics (benztropine, trihexyphenidyl): early treatment for tremor in young patients. Contraindicated in the elederly and those with cognitive disturbances. Peripheral and central side effects.
  • Amantadine: Early treatment; later for dyskensias. Side effects: confusion, hallucinations.
  • Dopamine agonist (Bromocriptine, Pergolide): early and adjunctive therapy. Can be used in patients that are cognitively intact, younger than 65 and are without other medical problems. Side Effects of Dopamine Agonist:  excessive sleepiness, leg edema, “impulse control disorders” and hallucinations. If a full dose of a dopamine agonist does not provide adequate clinical benefit or has intolerable side effects, levodopa should be initiated.
  • Monoamine Oxidase B Inhibitors (Selegiline, Zydis, Rasagiline): Early mild disease. The selective monamine oxidase B (MAO-B) inhibitor selegiline may exert a mild neuroprotective effect and there may be a disease modifying effect with the newer MAO-B inhibitor rasagiline and coenzyme Q10.
  • Dopamine precursor (Levodopa/ carbidopa): Most effective treatment for Parkinson’s disease. Side effects: peripheral and central dopaminergic side effects including: nausea, vomiting, orthostatic hypotension, dyskinesias, psychiatric disturbances, motor fluctuations.
  • Non-ergot derivative (Ropinirole, Pramipexole): Effective as firstline therapy and adjunctive therapy. Associated with less motor complications than with levodopa. Similar peripheral and central dopaminergic side effects to those of ergot derived dopamine agonists.
  • Catechol O-mrthyltransderase inhibitors (Tolcapone, Entacapone: Indicated for motor fluctuations.Effects of levodopa accentuated
  • Aytipical Neuroleptics (Clozapine, Quetiapine): Indicated for drug resistant tremor and levodopa-induced dyskinesias. Side effects: agranulocytosis, sedation, hypotension
  • Acetylcholinesterase Inhibitors (Donepezil, Rivastigmine): Indicated for dementia nd possibly effective for psychotic symptoms. Peripheral cholinergic side effects.

 SURGICAL MANAGEMENT

  • Deep brain stimulation of the subthalmic nucleus improves symptoms and permits lower dosing of medications.
  • The best predicator of a good response to deep brain stimulation is the patient’s on-going clinical response to levodopa.
  • The typical best candidate: healthy, relatively young, cognitively and psychiatrically intact patient who responds well to levodopa but suffers from disabling motor fluctuations and dyskinesias.

 EMERGENCY MANAGEMENT (when applicable)

  • Not applicable

PATIENT EDUCATION/ MAINTENANCE – PREVENTION

  • Early treatment in patients with little disability includes: education, psychological support, encouragement to remain active and become involved in an exercise program.
  • Support for family members and care-takers is important.
  • Address patient safety issues.

 https://www.youtube.com/watch?v=jyBakRkzswU

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 Dr. Zachary M. Lahlou

 

One thought on “Parkinson’s Disease.

  1. Pingback: Parkinson’s Disease. | Dr. Zachary Lahlou

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