Parkinson Disease

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites.

Essential update: Biomarkers in CSF may diagnose and predict progression of Parkinson disease
In the “Parkinson’s Progression Markers Initiative” cross-sectional study of 63 drug-naive patients with early-stage PD and 39 healthy controls, the combination of the Alzheimer’s biomarkers ?-amyloid 1-42 (A?1-42), total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and ?-synuclein — all measured in the CSF — were lower in the drug-naive patients than in the controls. A?1-42 and P-tau 181 were significant predictors of Parkinson’s disease, and T-tau and ?-synuclein were associated with the severity of motor dysfunction. In particular, lower A?1-42 and P-tau181 concentrations were associated with the postural instability–gait disturbance–dominant PD phenotype, but were not associated with the tremor-dominant or intermediatephenotypes.[1, 2]

Signs and symptoms.
Initial clinical symptoms of Parkinson disease include the following:

Tremor
Subtle decrease in dexterity
Decreased arm swing on the first-involved side
Soft voice
Decreased facial expression
Sleep disturbances
Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
Decreased sense of smell
Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
A general feeling of weakness, malaise, or lassitude
Depression or anhedonia
Slowness in thinking
Onset of motor signs include the following:

Typically asymmetric
The most common initial finding is a resting tremor in an upper extremity
Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
Axial posture becomes progressively flexed and strides become shorter
Postural instability (balance impairment) is a late phenomenon
Nonmotor symptoms
Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.

Diagnosis
Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.

Clinical diagnosis requires the presence of 2 of 3 cardinal signs:

Resting tremor
Rigidity
Bradykinesia

Management.

The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.

Symptomatic drug therapy

Usually provides good control of motor signs of Parkinson disease for 4-6 years
Levodopa/carbidopa: The gold standard of symptomatic treatment
Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only
Treatment for nonmotor symptoms

Sildenafil citrate (Viagra): For erectile dysfunction
Polyethylene glycol: For constipation
Modafinil: For excessive daytime somnolence
Methylphenidate: For fatigue (potential for abuse and addiction)
Deep brain stimulation

Surgical procedure of choice for Parkinson disease
Does not involve destruction of brain tissue
Reversible
Can be adjusted as the disease progresses or adverse events occur
Bilateral procedures can be performed without a significant increase in adverse events
See Treatment and Medication for more detail.