Parkinson disease

Last updated: September 28, 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. PD is predominantly considered an idiopathic disease but genetic factors play a role in approx. 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 a common finding in later stages of PD. Parkinsonism that results from medication, intoxication, or traumatic brain injury is referred to as secondary parkinsonism. Parkinsonism due to neurodegenerative disorders other than PD is called atypical parkinsonism and 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. The diagnosis is clinical; diagnostic testing may be considered to rule out alternative diagnoses. There is currently no cure for PD. Symptomatic treatment includes physical therapy and, depending on patient factors and individual symptoms, certain medications (e.g., levodopa, dopamine agonists). Deep brain stimulation surgery may be beneficial in specific cases.

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

References:[3][5]

Overview

  • 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 syndrome comprising bradykinesia and either resting tremor or rigidity (or both) and 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: 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 patients with PD
        • 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

Approach [8][9][10]

  • Consider PD in patients with parkinsonism.
  • Perform a thorough clinical evaluation.
  • Consider diagnostic testing to:
    • Provide diagnostic certainty if a diagnosis cannot be made based on clinical features alone
    • Help rule out alternative diagnoses of parkinsonism
  • Refer to a neurologist or movement disorder specialist for diagnostic confirmation.

Parkinson disease is a clinical diagnosis. A definitive diagnosis requires postmortem confirmation of Lewy bodies.

Clinical evaluation [10][11]

Supportive features [11]

Atypical features

Consider other causes of parkinsonism if any of the following are present :

If patients have atypical features for PD, evaluate for secondary parkinsonism or atypical parkinsonian syndromes.

Diagnostic testing

Imaging [13] [14]

Imaging is not routinely required for diagnosis but can be considered under specialist guidance if the diagnosis is unclear.

Ancillary tests

Ancillary tests are not routinely used but can support the diagnosis.

  • Levodopa challenge test: performed to support the diagnosis of PD or as part of the evaluation prior to implantation of a deep brain stimulator
  • Olfactory testing: to test for hyposmia [8][9][16][17]
  • MIBG myocardial scintigraphy: to test for cardiac sympathetic denervation

Differential diagnoses of Parkinson disease [5][11][18][19][20]
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 [21]
  • 6–9 years
  • 5–8 years
  • ∼ 7 years
First symptoms
  • Gait impairment
Parkinsonism
Symmetricity
  • Asymmetric
  • Symmetric
  • Limited to lower limbs
  • Symmetric
  • Usually symmetric
  • Markedly asymmetric
Tremor
  • 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
Rigidity
  • 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
Imaging
  • No specific signs
  • Asymmetric cortical atrophy (mostly parietal)

The differential diagnoses listed here are not exhaustive.

General principles [13][17][22]

  • Offer supportive care to all patients.
  • Initiate pharmacotherapy when symptoms start to cause functional impairment.
  • Consult a neurologist or movement disorder specialist before initiating or changing treatment.
  • Manage associated symptoms (e.g., major depressive disorder, dementia) as necessary.

Pharmacotherapy does not alter the disease trajectory in PD; initiate when symptoms interfere with quality of life.

Supportive care [10]

Treatment [10][24][25]

Choose initial therapy based on individual patient factors (e.g., motor symptoms, age, comorbidities). To delay levodopa-based treatment for as long as possible, various age thresholds were previously recommended. [25]

  • Commonly used options for initial monotherapy include levodopa, a dopamine agonist, or an MAO-B inhibitor.
  • Risk factors for levodopa-induced dyskinesia include: [24]
    • Young age
    • Low body weight
    • Female sex
    • Severe disease
  • In patients with refractory symptoms or intolerable adverse effects that require dose reduction, consider:
    • Switching monotherapy
    • Combination therapy
  • Avoid abrupt discontinuation or sudden changes in medication.
  • Consider enteral infusion of levodopa or deep brain stimulation for patients with advanced disease and severe motor fluctuations.
  • See “Medication for Parkinson disease for additional information on mechanisms of action and adverse effects.

Levodopa is the most effective treatment for motor symptoms in PD but is associated with time- and dosage-dependent increase of dyskinesia.

Avoid abrupt discontinuation or sudden changes in medication. Consult a specialist if such changes are necessary.

Pharmacological treatment

Pharmacological treatment for PD [10][22]
Agents Indications Important considerations
Levodopa
  • Initial treatment option for most patients
  • Preferred initial treatment for older patients
  • Most effective treatment for motor symptoms
  • Higher risk of dyskinesia than other agents
  • Honeymoon period: beneficial effect in early phase of treatment
Nonergot dopamine receptor agonists
MAO-B inhibitors
Anticholinergics
NMDA antagonist
COMT inhibitors

Anticholinergics and levodopa/carbidopa can increase intraocular pressure; avoid in patients with glaucoma.

Ergot dopamine agonists (e.g., bromocriptine) have mostly been replaced by nonergot agonists because of significant side effects (e.g., pulmonary fibrosis).

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

Deep brain stimulation (DBS) [13][26]

  • Indications
    • Severe motor symptoms or refractory tremor
    • Decrease in dosage of medication because of adverse effects
  • Procedure
  • Complications
    • Infection
    • Hemorrhage
    • Breakage or displacement of electrodes or leads

Treatment of associated symptoms [13][22]

Under specialist guidance, carefully consider the risks and benefits of pharmacological treatment of nonmotor symptoms.

While improvement of nonmotor symptoms is often crucial for quality of life, treatments often worsen other clinical features of PD.

  1. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017; 3 (1). doi: 10.1038/nrdp.2017.13 . | Open in Read by QxMD
  2. Connolly BS, Lang AE. Pharmacological Treatment of Parkinson Disease. JAMA. 2014; 311 (16): p.1670. doi: 10.1001/jama.2014.3654 . | Open in Read by QxMD
  3. Grimes D, Fitzpatrick M, Gordon J, et al. Canadian guideline for Parkinson disease. Can Med Assoc J. 2019; 191 (36): p.E989-E1004. doi: 10.1503/cmaj.181504 . | Open in Read by QxMD
  4. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease. JAMA. 2020; 323 (6): p.548. doi: 10.1001/jama.2019.22360 . | Open in Read by QxMD
  5. Allen NE, Schwarzel AK, Canning CG. Recurrent Falls in Parkinson’s Disease: A Systematic Review. Parkinsons Dis. 2013; 2013 . doi: 10.1155/2013/906274 . | Open in Read by QxMD
  6. Pringsheim T, Day GS, Smith DB, et al. Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary. Neurology. 2021; 97 (20): p.942-957. doi: 10.1212/wnl.0000000000012868 . | Open in Read by QxMD
  7. Susan H. Fox, Regina Katzenschlager, Shen-Yang Lim, Brandon Barton, Rob M. A. de Bie, Klaus Seppi, Miguel Coelho, Cristina Sampaio. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. Movement Disorders. 2018; 33 (8): p.1248-1266. doi: 10.1002/mds.27372 . | Open in Read by QxMD
  8. Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848307/. Updated: April 28, 2016. Accessed: March 29, 2017.
  9. Lorraine V Kalia, Anthony E Lang. Parkinson's disease. The Lancet. 2015; 386 (9996): p.896-912. doi: 10.1016/s0140-6736(14)61393-3 . | Open in Read by QxMD
  10. Daroff RB, et al.. Bradley's Neurology in Clinical Practice. Elsevier
  11. The prevalence of Parkinson's disease: A systematic review and meta-analysis. http://onlinelibrary.wiley.com/doi/10.1002/mds.25945/abstract?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+30th+July+2016+from+08:00-11:00+BST+/+03:00-06:00+EST+/+15:00-18:00+SGT+for+essential+maintenance.Apologies+for+the+inconvenience.. Updated: June 28, 2014. Accessed: March 29, 2017.
  12. A systematic review of the worldwide prevalence and incidence of Parkinson's disease. https://www.ncbi.nlm.nih.gov/pubmed/21696087. Updated: June 1, 2011. Accessed: March 29, 2017.
  13. Kasper DL, Fauci AS, Hauser S, Longo D, Jameson LJ, Loscalzo J . Harrisons Principles of Internal Medicine . McGraw-Hill Medical Publishing Division ; 2016
  14. Shin HW, Chung SJ. Drug-Induced Parkinsonism. J Clin Neurol. 2012; 8 (1): p.15-21. doi: 10.3988/jcn.2012.8.1.15 . | Open in Read by QxMD
  15. Ropper A, Klein J, Samuels M. Adams and Victor's Principles of Neurology 10th Edition. McGraw-Hill Education / Medical ; 2014
  16. Halli-Tierney AD, Luker J, Carroll DG. Parkinson Disease.. Am Fam Physician. 2020; 102 (11): p.679-691.
  17. Homayoun H. Parkinson Disease. Ann Intern Med. 2018; 169 (5): p.ITC33-ITC48. doi: 10.7326/aitc201809040 . | Open in Read by QxMD
  18. Postuma RB, Berg D, Stern M et al. Clinical Diagnostic Criteria for Parkinson's Disease. Movement disorders. 2015; 30 (12): p.1591-1599. doi: 10.1002/mds.26424 . | Open in Read by QxMD
  19. Saranza G, Lang AE. Levodopa challenge test: indications, protocol, and guide. J Neurol. 2020 . doi: 10.1007/s00415-020-09810-7 . | Open in Read by QxMD
  20. Booth TC, Nathan M, Waldman AD, Quigley AM, Schapira AH, Buscombe J. The Role of Functional Dopamine-Transporter SPECT Imaging in Parkinsonian Syndromes, Part 1. American Journal of Neuroradiology. 2015; 36 (2): p.229-235. doi: 10.3174/ajnr.A3970 . | Open in Read by QxMD
  21. 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
  22. Doty RL. Olfactory dysfunction in Parkinson disease. Nature Reviews Neurology. 2012; 8 (6): p.329-339. doi: 10.1038/nrneurol.2012.80 . | Open in Read by QxMD
  23. 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
  24. 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
  25. 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
  26. 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
  27. Pahwa R, Factor SA, Lyons KE et al. Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review). Neurology. 2006; 66 (7): p.983-995.
  28. 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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