Parkinson disease

Last updated: May 9, 2022

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Parkinson disease (PD) is a neurodegenerative condition that involves the progressive depletion of dopaminergic neurons in the basal ganglia, particularly the substantia nigra. The disease most commonly manifests at approx. 60 years of age. Although PD is considered an idiopathic disease, genetic factors play a role in about 10–15% of cases and, accordingly, familial clustering has been observed. A core clinical feature of PD is parkinsonism, a syndrome that comprises bradykinesia along with resting tremor and/or rigidity. Postural instability is another frequent finding in PD. Parkinsonism that results from medication, intoxication, or head trauma is referred to as secondary parkinsonism. Parkinsonism due to neurodegenerative disorders other than PD is considered atypical parkinsonism, which manifests with features that are not characteristic of PD such as vertical gaze palsy in progressive supranuclear palsy, and apraxia and agnosia in corticobasal degeneration. There is currently no cure for PD. Symptomatic treatment includes physical therapy and, depending on patient age and individual symptoms, various medications (e.g., levodopa, dopamine agonists). In specific cases, deep brain stimulation surgery may be beneficial.

Epidemiological data refers to the US, unless otherwise specified.

Parkinson disease

  • Idiopathic
  • Contributing genetic factors include:
    • α-Synuclein (SNCA)
    • Glucocerebrosidase (GBA): A mutation in the GBA gene (the same gene associated with Gaucher disease) is the most common genetic risk factor for PD. GBA mutations are associated with altered autophagy and lysosomal function, potentially resulting in impairment of α-synuclein clearance.
    • Dardarin (LRRK2): A mutation in LRRK2 gene is the most common cause of dominantly inherited PD.
    • Parkin (PARK2): A mutation in PARK2 gene is the most common cause of recessively inherited PD.

Secondary parkinsonism



  • Signs of PD gradually progress over time: The course is usually > 10 years.
  • Motor signs are unilateral at onset but may progress to the contralateral side.
  • Motor signs are asymmetrical (i.e., more pronounced on one side than on another).
  • Preclinical (prodromal) stage with nonmotor signs may precede the onset of motor signs (clinical phase).

Preclinical stage [6]

Clinical stage

Motor signs [7]

  • Parkinsonism: a triad of signs (bradykinesia, rigidity, and resting tremor) that is consistent with impairment of the extrapyramidal system
    • A core feature of PD
    • Can be also seen in a variety of other disorders, e.g. multiple system atrophy, corticobasal degeneration (see “Atypical parkinsonism”)
    • Bradykinesia: slowed movements in combination with decreased amplitude/speed when moving
    • Resting tremor (4–6 Hz)
      • Pill-rolling tremor that subsides with voluntary movements but increases with stress
      • Most common in the hands but may involve the legs, jaw, lips, and tongue
    • Rigidity: increased and persistent resistance to passive joint movement that is independent of speed
      • Froment maneuver: The patient is asked to perform repetitive movements in the contralateral extremity (e.g., opening and closing of the left fist if the right side is examined) → subclinical rigidity becomes more pronounced and may be detected.
      • Cogwheel rigidity
        • A phenomenon caused by the overlay of increased muscle tonus and resting tremor in PD patients.
        • It may manifest before tremor becomes clinically apparent.
        • Muscles in an extremity (most commonly the arms) are passively stretched, eliciting a jerking-like motion.
        • Muscle tone should be tested with at least two joints.
  • Postural instability
    • Imbalance and tendency to fall
    • Evaluated with the pull test
  • Gait abnormalities
    • Parkinsonian gait: shuffling gait with quickened and shortened steps
    • Freezing: sudden inability to start or continue movements
    • Festination: gait pattern characterized by small, increasingly quick steps
    • Propulsion: forward-leaning gait with a risk of a patient falling forward
    • Decreased arm swing
  • Other motor findings
    • Unhabituated glabellar reflex
    • Signs of dystonia
    • Stooped posture
    • Abnormal flexor posturing of hands and feet (i.e., striatal deformities)
    • Micrographia: size of handwriting is reduced
    • Hypomimia: low degree of facial expression

Parkinsonism is required for the diagnosis of Parkinson disease. Unilateral onset is characteristic of Parkinson disease.

Parkinsonism TRAPs the patient: Tremor, Rigidity, Akinesia, and Postural instability.

Nonmotor signs

  • Autonomic symptoms
  • Neuropsychiatric symptoms
    • Depression
    • Cognitive problems, e.g., decreased attention and concentration, executive dysfunction, impaired memory (Parkinson dementia): develop in advanced disease [5]
    • Apathy
    • Behavioral changes (e.g., irritability, impulsivity)
  • Disordered sleep (sleep fragmentation, vivid dreams)
  • Fatigue
  • Hyposmia, anosmia


  • PD diagnosis is based on the presence of typical parkinsonian features (see “Clinical features” above).
  • Criteria from the Movement Disorder Society criteria, such as absolute exclusion criteria, red flags, and supportive criteria, can be used to facilitate the diagnosis. [8]
  • Additional tests, including imaging, are not routinely required for diagnosis but should be considered in an atypical presentation or to rule out other underlying disorders.
  • Definitive diagnosis can only be made upon postmortem examination showing the typical Lewy pathology (see “Pathology” below).

Parkinson disease is a clinical diagnosis.

Clinical diagnostic criteria for Parkinson disease

Imaging [9][10]

Imaging is not routinely required for diagnosis but should be considered in an atypical presentation or to rule out other underlying disorders.

Differential diagnoses of Parkinson disease [5][8][11][12][13]
Characteristics Parkinson disease Vascular parkinsonism Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration
Usual onset age
  • ∼ 60 years
  • > 70 years
  • 50–55 years
  • 60–70 years
  • 50–70 years
Average survival
  • > 10 years
  • 3–5 years [14]
  • 6–9 years
  • 5–8 years
  • ∼ 7 years
First symptoms
  • Gait impairment
  • Asymmetric
  • Symmetric
  • Limited to lower limbs
  • Symmetric
  • Usually symmetric
  • Markedly asymmetric
  • Absent
  • Usually absent
  • Postural or kinetic tremor if present
  • Absent
  • Usually absent
  • High amplitude rest or kinetic tremor if present
Postural instability
  • Late
  • Early
  • Early
  • First symptom
  • Early
  • Can be combined with spasticity, but rigidity predominates
  • Less prominent in predominantly cerebellar type compared to predominantly parkinsonian type
  • Marked
  • Axial more prominent than limb
  • Marked
  • Limb more prominent than axial
Other clinical signs
Eye movements
  • Typically none
  • Vertical supranuclear gaze palsy
  • Decreased velocity of saccades
  • Square wave jerks
  • Reducing blinking
Bulbar dysfunction
  • Uncommon
Other specific features
  • No specific signs
  • Asymmetric cortical atrophy (mostly parietal)

The differential diagnoses listed here are not exhaustive.

General measures

Medical therapy


For details on therapeutic effects, administration, and side effects, see “Medication for Parkinson disease.”

  • Drug classes for initial treatment of motor symptoms in Parkinson disease include nonergot dopamine agonists, MAO-B inhibitors, and levodopa combined with carbidopa.
  • Although levodopa is the most effective drug for the management of motor symptoms in Parkinson disease, its use is associated with unavoidable motor complications.
    • There is usually a dramatic beneficial effect of levodopa in the early phase of treatment ("honeymoon period").
    • All patients treated with levodopa eventually develop drug-related motor fluctuations (see “Side effects” in “Medication for Parkinson disease”).
  • Since levodopa is associated with inevitable motor complications that require treatment modification, younger (< 65 years) patients might benefit from initial treatment with dopamine agonists.

Overstimulation of D2-receptors by levodopa or dopamine agonists may induce psychosis and hallucinations, especially in elderly patients with concurrent dementia or other psychiatric disorders.

Levodopa can increase intraocular pressure, therefore it is not recommended in patients with glaucoma.

Patients < 65 years with no significant comorbidities

Administration of anticholinergics may worsen existing psychiatric symptoms (particularly dementia). There is also a risk of ischuria.

Patients > 65 years or multimorbid patients of any age

Patients with severe motor fluctuations

Treatment of associated symptoms

Deep brain stimulation (DBS) [16]

  • Indication: primarily recommended for patients with severe motor symptoms who respond to levodopa treatment but are not sufficiently controlled by it (or if a decrease in dosage is necessary due to side effects) [16][17]
  • Targets: subthalamic nucleus or internal globus pallidus
  • Adverse effects: infections, hemorrhages, breakage or displacement of electrodes or the leads

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  4. A systematic review of the worldwide prevalence and incidence of Parkinson's disease. Updated: June 1, 2011. Accessed: March 29, 2017.
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  10. Booth TC, Nathan M, Waldman AD, Quigley AM, Schapira AH, Buscombe J. The Role of Functional Dopamine-Transporter SPECT Imaging in Parkinsonian Syndromes, Part 2. American Journal of Neuroradiology. 2015; 26 (2): p.236-244. doi: 10.3174/ajnr.A3971 . | Open in Read by QxMD
  11. A. B. Deutschländer, O. A. Ross, D. W. Dickson, Z. K. Wszolek. Atypical parkinsonian syndromes: a general neurologist's perspective. European Journal of Neurology. 2017; 25 (1): p.41-58. doi: 10.1111/ene.13412 . | Open in Read by QxMD
  12. McFarland NR. Diagnostic Approach to Atypical Parkinsonian Syndromes. CONTINUUM: Lifelong Learning in Neurology. 2016; 22 (4): p.1117-1142. doi: 10.1212/con.0000000000000348 . | Open in Read by QxMD
  13. Korczyn AD. Vascular parkinsonism—characteristics, pathogenesis and treatment. Nature Reviews Neurology. 2015; 11 (6): p.319-326. doi: 10.1038/nrneurol.2015.61 . | Open in Read by QxMD
  14. Staszewski J, Piusińska-Macoch R, Brodacki B, Skrobowska E, Macek K, Stępień A. Vascular parkinsonism and vascular dementia are associated with an increased risk of vascular events or death. Archives of Medical Science - Atherosclerotic Diseases. 2017; 2 (2): p.16-23. doi: 10.5114/amsad.2017.68549 . | Open in Read by QxMD
  15. J. J. Ferreira et al.. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. European Journal of Neurology. 2012; 20 (1): p.5-15. doi: 10.1111/j.1468-1331.2012.03866.x . | Open in Read by QxMD
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