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American Academy of Neurology Quality Standards Subcommittee

American Academy of Neurology Quality Standards Subcommittee. O. Suchowersky, MD; S. Reich, MD; J. Perlmutter, MD; T. Zesiewicz, MD; G. Gronseth, MD; W.J. Weiner, MD. Practice Parameter: Diagnosis and Prognosis of New Onset Parkinson Disease (An Evidence-Based Review).

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American Academy of Neurology Quality Standards Subcommittee

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  1. American Academy of Neurology Quality Standards Subcommittee O. Suchowersky, MD; S. Reich, MD; J. Perlmutter, MD; T. Zesiewicz, MD; G. Gronseth, MD; W.J. Weiner, MD Practice Parameter: Diagnosis and Prognosis of New Onset Parkinson Disease (An Evidence-Based Review)

  2. The AAN develops these presentation slides as educational tools for neurologists and other health care practitioners. You may download and retain a single copy for your personal use. Please contact guidelines@aan.com to learn about options for sharing this content beyond your personal use.

  3. Presentation Objectives • To define key issues in the diagnosis of Parkinson’s disease (PD) • To define features influencing progression • To make evidence-based recommendations

  4. Overview • Background/Epidemiology • Gaps in PD care • AAN guideline process • Diagnosis of PD • Prognosis of PD • Summary • Recommendations for Future Research

  5. Background • PD a neurodegenerative disorder • Caused by a loss of dopaminergic neurons in the substantia nigra and other dopaminergic and nondopaminergic areas of the brain

  6. Descriptive Epidemiology of Parkinson Syndrome • Incidence • 5–24/105 worldwide (ref) • 20.5/105 USA (ref) • Prevalence • 57–371/105 worldwide (ref) • 300/105 USA/Canada (Strickland & Bertoni, 2004) • Prevalence of PS/PD rising slowly with aging population

  7. Gaps in PD Care • PD is a complex disease and hard to diagnose clinically, especially in the early stages • No simple diagnostic test available • About 5-10% of patients with PD misdiagnosed (Hughes et al., 1992)

  8. Gaps in PD Care • Up to 20% of patients have alternative diagnoses at autopsy • Multiple system atrophy (MSA) • Progressive supranuclear palsy (PSP) • Alzheimer disease-type pathology

  9. Seeking Answers • How do we find the answers to the questions that arise in daily practice? • In order to keep up to date, need to read 29 articles a day, 365 days a year (Didsbury, 2003) • Or find someone who has found and summarized the relevant data for you

  10. American Academy of Neurology Guideline Process Clinical Question Evidence Conclusions Recommendations

  11. Clinical Question • Question should address an area of quality concern, controversy, confusion, or variation in practice • Question must be answerable with sufficient scientific data • Potential to improve clinical care and patient outcomes

  12. Complete Search Review abstracts Review full text Select articles Relevant Literature Search/Review: Rigorous, Comprehensive, Transparent

  13. AAN Level of Recommendations • A = Established as effective, ineffective, or harmful for the given condition in the specified population • B = Probably effective, ineffective, or harmful for the given condition in the specified population • C = Possibly effective, ineffective, or harmful for the given condition in the specified population • U = Data is inadequate or conflicting; given current knowledge, treatment is unproven

  14. AAN Level of Recommendations • A = Requires two consistent Class I studies • B = Requires one Class I study or two consistent Class II studies • C = Requires one Class II study or two consistent Class III studies • U = Studies not meeting criteria for Class I through Class III

  15. Clinical Questions • Which clinical features and diagnostic modalities distinguish PD from other parkinsonian syndromes? • Which clinical features predict rate of disease progression?

  16. Methods • Literature Search: • MEDLINE, EMBASE, CINHAL, and Cochrane Database of Systematic Reviews (1997-2002) • Only articles written in English included • Second MEDLINE search (1966 through Aug. 2004) • Another search using the bibliographies of retrieved articles and knowledge of the expert panel extending to January 2005

  17. Methods • At least two authors reviewed each paper • Risk of bias determined using the classification of evidence for each study (Class I–IV) • Strength of practice recommendations linked directly to level of evidence (Level A–U) • Conflicts of interests disclosed

  18. 176 articles 31 articles Literature Search/Review: Diagnosis of PD Exclusion criteria: -Studies not including at least 10 subjects with PD and 10 in the comparison group -Articles that were off topic -Review articles

  19. 59 articles 7 articles Literature Search/Review: Prognosis of PD Exclusion criteria: -Articles published before 1990 because of changes in the case definition of PD -Articles that were off topic -Review articles

  20. Diagnosis of PD

  21. Which clinical features and diagnostic modalities distinguish PD from other Parkinsonian syndromes? Clinical Question 1

  22. Diagnosis of PD • Categories: • Clinical • Acute challenge testing • Radiological evaluation • Neurophysiological testing • Biochemical testing • CSF examination • Olfactory testing

  23. Diagnosis of PD: Clinical Features • Four articles that addressed the diagnostic accuracy of clinical features helpful in distinguishing PD from other forms of parkinsonism • Three class II studies • One class III study

  24. Diagnosis of PD: Clinical Examination

  25. Diagnosis of PD: Clinical Examination

  26. Recommendation for Diagnosis of PD • Factors that predict against PD and are supportive of other parkinsonian syndromes in early stages of disease (Level B) • Symmetry of motor signs • Lack of tremor • Poor response to levodopa • Falls early in course • Dysautonomia early in course • Rapid progression (to H & Y III within 1 year)

  27. Diagnosis of PD: Clinical Features • Longitudinal follow-up important • Lack of autonomic, oculomotor, cognitive abnormalities at 5 years supports PD

  28. Diagnosis of PD: Levodopa/Apomorphine Challenge • Response to chronic levodopa therapy an important factor in distinguishing PD from a parkinsonian syndrome • Acute dopaminergic challenge may have similar predictive value • Levodopa • Apomorphine

  29. Diagnosis of PD: Levodopa/Apomorphine Challenge • Two articles that addressed the predictive value of levodopa/apomorphine challenge in distinguishing PD from other forms of parkinsonism • One class I study • One class II study

  30. Diagnosis of PD: Levodopa/Apomorphine Challenge

  31. Recommendation for Levodopa/Apomorphine Challenge • Both levodopa and apomorphine challenge tests should be considered when diagnosis of PD in doubt (Level B)

  32. Diagnosis of PD:Levodopa/Apomorphine Challenge • 30% false positive and negative rates • Acute levodopa challenge response a reliable predictor of chronic response to levodopa • Pretreatment with domperidone* in drug naïve patients recommended * domperidone is not available in the United States

  33. Diagnosis of PD: Olfaction • Olfaction frequently impaired in PD • Three Class II studies identified

  34. Diagnosis of PD: Olfactory Testing

  35. Recommendation for Olfactory Testing • Olfaction testing should be considered to distinguish PD from PSP and CBD (Level B) • UPSIT or “Sniffin’ Sticks tests • Differences between PD and MSA not as pronounced

  36. Diagnosis of PD vs. Other Parkinsonisms • Not useful (Level C) • GH stimulation by clonidine • Electro-oculography • SPECT scanning

  37. Diagnosis of PD vs. Other Parkinsonisms • Insufficient Evidence (Level U) • Urodynamics • Autonomic testing • Urethral/anal EMG • MRI, FDG PET, brain sonography

  38. Prognosis of PD

  39. Which clinical features predict the rate of disease progression? Clinical Question 2

  40. Prognosis of PD • Prognostic factors examined: • Age at disease onset • Sex • Cognitive and motor symptoms • Seven studies • Six Class II • One Class III

  41. Recommendations for the Prognosis of PD • In patients with newly diagnosed PD, the following should be used to predict more rapid rate of motor progression (Level B): • Older age at onset as an initial symptom • Rigidity/hypokinesia as an initial symptom

  42. Recommendations for the Prognosis of PD • Predictors of faster rate of motor progression (Level C): • Postural instability/gait difficulty • Male sex • Presence of associated comorbidities • Stroke, visual, auditory

  43. Recommendations for the Prognosis of PD • Predictors of earlier nursing home placement and decreased survival (Level C) • Older age at onset • Dementia • Poor responsiveness to dopaminergic meds

  44. Recommendations for the Prognosis of PD • Predictors of earlier cognitive decline and dementia (Level B): • Older age at onset • Initial hypokinesia/rigidity

  45. Recommendations for the Prognosis of PD • Tremor as a presenting symptom may be used to predict a more benign course and longer therapeutic benefit to levodopa (Level C)

  46. Summary • Improving accurate diagnosis • Clinical features predictive of other forms of parkinsonism: • Early falls • Poor response to levodopa • Symmetry of motor manifestations • Lack of tremor • Early autonomic dysfunction

  47. Summary • Levodopa or apomorphine challenge and olfactory testing may be helpful in distinguishing PD from other forms of Parkinsonism

  48. Summary • Predictive factors for more rapid motor progression, nursing home placement, and shorter survival time • Older age at onset of PD • Associated comorbidities • Presentation with rigidity and bradykinesia • Decreased dopamine responsiveness

  49. Recommendations for Future Research • Other techniques to improve diagnostic accuracy and address disease progression (neuroimaging, levodopa challenge tests) • Long term follow-up and autopsy confirmation to determine accuracy of new diagnostic tests (genetic screening)

  50. Recommendations for Future Research • Methods for presymptomatic testing to identify patients at risk of developing PD • Knowledge of disease progression

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