Parkinson Disease

SOURCE

Source: Chen JJ, Dashtipour K. Parkinson disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=134127873.

DEFINITION

• Progressive, chronic disorder of central nervous system (CNS) characterized by impaired muscular coordination and tremor.

ETIOLOGY

• Unknown; likely result of interactions between aging, genetic constitution, and environmental factors.

PATHOPHYSIOLOGY

• Loss of neurons and presence of Lewy bodies in substantia nigra pars compacta.

• Degree of nigrostriatal dopamine loss correlates directly with severity of motor symptoms.

• Reduced activation of dopamine-1 and dopamine-2 receptors results in greater inhibition of thalamus.

• Loss of presynaptic nigrostriatal dopamine neurons inhibits thalamic activity and reduces activation of motor cortex.

EPIDEMIOLOGY

• Affects up to 1 million individuals in United States.

• Annual incidence ranges from 10 to 120 per 100,000 persons depending on age.

• Affects 0.5% of people in their sixties and 2.5% of those older than age 80.

• Usual age at diagnosis is 55–65 years.

RISK FACTORS

• Increasing age.

• Male sex.

• Heredity (close relative with disease)

• Toxin exposure (eg, herbicides, pesticides)

CLINICAL PRESENTATION

SIGNS AND SYMPTOMS

• General features.

  • Resting tremor.

  • Muscular rigidity.

  • Bradykinesia (usually asymmetric)

  • Postural instability in advanced disease.

• Motor symptoms.

  • Decreased manual dexterity.

  • Difficulty arising from seated position.

  • Diminished arm swing during ambulation.

  • Dysarthria.

  • Dysphagia.

  • Festinating gait.

  • Flexed posture.

  • “Freezing” at initiation of movement.

  • Hypomimia.

  • Hypophonia.

  • Micrographia.

• Autonomic and sensory symptoms.

  • Bladder and anal sphincter disturbances.

  • Constipation.

  • Diaphoresis.

  • Fatigue.

  • Olfactory impairment.

  • Orthostatic blood pressure changes.

  • Pain.

  • Paresthesias.

  • Paroxysmal vascular flushing.

  • Seborrhea.

  • Sexual dysfunction.

  • Sialorrhea.

• Mental status changes.

  • Anxiety.

  • Apathy.

  • Bradyphrenia.

  • Cognitive impairment.

  • Depression.

  • Hallucinosis/psychosis (typically drug-induced)

  • Sleep disorders.

DIAGNOSIS

MEANS OF CONFIRMATION AND DIAGNOSIS

• Bradykinesia and at least one of the following:

  • Restring tremor.

  • Rigidity.

  • Postural instability.

• Exclude other types of parkinsonism or tremor disorders (see Differential Diagnosis)

• Presence of at least three supportive positive criteria:

  • Asymmetry of motor signs/symptoms.

  • Unilateral onset.

  • Progressive disorder.

  • Resting tremor.

  • Excellent response to carbidopa/L-dopa.

  • L-dopa response for 5 years or longer.

  • Presence of L-dopa dyskinesias.

LABORATORY TESTS

• None available to diagnose Parkinson disease.

IMAGING

• Neuroimaging may be useful for excluding other diagnoses.

DIFFERENTIAL DIAGNOSIS

• Essential tremor.

• Pharmaco toxicity (drug-induced)

  • Antiemetics (metoclopramide, prochlorperazine)

  • Antipsychotics (chlorpromazine, fluphenazine, haloperidol, olanzapine, risperidone, thioridazine)

  • Other drugs (α-methyldopa, cinnarizine, flunarizine, tetrabenazine)

• Environmental toxicity (manganese, organophosphates)

• Infections (HIV, subacute sclerosing panencephalitis)

• Metabolic disorder (hypothyroidism, parathyroid abnormalities)

• Neoplasms, strokes, traumatic lesions involving the nigrostriatal pathways.

• Normal-pressure hydrocephalus.

• Parkinsonism with other neuronal system ...