Parkinson’s Disease

Introduction

Parkinson’s disease (PD) has highly characteristic neuropathologic findings and a clinical presentation, including motor deficits and, in some cases, mental deterioration.

• Two hallmark features in the substantia nigra pars compacta are loss of neurons and presence of Lewy bodies. The degree of nigrostriatal dopamine

loss correlates positively with severity of motor symptoms.

• Reduced activation of dopamine1 and dopamine2 receptorsresults in greater inhibition of the thalamus and reduced activation of the motor cortex. Clinical improvement may be tied to restoring activity more at the dopamine2 receptor than at the dopamine 1 receptor.

Morbidity And Mortality

• PD develops insidiously and progresses slowly. It is relatively asymptomatic until profound depletion (70%–80%) of substantia nigra pars compacta neurons has occurred.
• Initial symptoms may be sensory, but as the disease progresses, one or more classic primary features presents (e.g., resting tremor, rigidity, bradykinesia, and postural instability that may lead to falls).
• Resting tremor is often the sole presenting complaint. However, only two thirds of PD patients have tremor on diagnosis, and some never develop this sign. Tremor is present most commonly in the hands, often begins unilaterally, and sometimes has a characteristic “pill-rolling” quality.

Resting tremor is usually abolished by volitional movement and is absent during sleep.

• Muscular rigidity involves increased muscular resistance to passive range of motion and can be cogwheel in nature. It commonly affects both upper and lower extremities, and facial muscles may be affected.
• Intellectual deterioration is not inevitable, but some patients deteriorate in a manner indistinguishable from Alzheimer’s disease.

Clinical Presentation

• A diagnosis of PD can be made with a high level of confidence when there is bradykinesia (along with resting tremor and/or rigidity), prominent asymmetry, and a positive response to dopaminergic medication.
• Other symptoms may include: decreased dexterity, difficulty arising from a chair, postural instability, festinating gait, dysarthria, difficulty swallowing, reduced facial expression, freezing at initiation of movement, hypophonia, micrographia, bladder disturbances, constipation, blood pressure changes, dementia, anxiety, depression, sleepiness, insomnia, obstructive sleep apnea.
• Several other conditions must be excluded,such as medication-induced Parkinsonism (e.g., induced by antipsychotics, phenothiazine antiemetics, or metoclopramide), essential tremor, corticobasal ganglionic degeneration, multiple system atrophy, and progressive supranuclear palsy.

Diagnosis

• Goals of Treatment: The goals of treatment are to minimize symptoms, disability, and side effects while maintaining quality of life. Education of patients and caregivers, exercise, and proper nutrition are essential

Treatment

General Approach : Monotherapy usually begins with a monoamine oxidase-B (MAO-B) inhibitor.

• Consider addition of a catechol-O-methyltransferase (COMT) inhibitor if motor fluctuations develop to extend l-dopa duration of activity. Alternatively, consider addition of an MAO-B inhibitor or dopamine agonist.
• For management of l-dopa-induced peak-dose dyskinesias, consider addition of amantadine.

Pharmacologic Therapy

Benztropine, Starting dose 0.5–1, Maintenance dose 1–6

Carbidopa/l-dopa , Starting dose 100–300c, Maintenance dose 300–1,000c

Apomorphine, Initail dose1–3, Maintenance dose 3–12

Entacapone, Starting dose 200–600, Maintenance dose 200–1,600

Selegiline, initial dose 5–10, Maintenance dose 5–10

Amantadine, Initial dose 100, Maintenance dose 200–300