© 2007 American Academy of Neurology Practice Parameter: Diagnosis and Prognosis of New Onset...

© 2007 American Academy of Neurology

Practice Parameter: Diagnosis and Prognosis of New Onset

Parkinson Disease (An Evidence-Based Review)

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


Presentation Objectives

• To define key issues in the diagnosis of Parkinson’s disease (PD)

• To define features influencing progression

• To make evidence-based recommendations


Overview

• Background/Epidemiology

• Gaps in PD care

• AAN guideline process

• Diagnosis of PD

• Prognosis of PD

• Summary

• Recommendations for Future Research


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


Descriptive Epidemiology of Parkinson Syndrome

• Incidence 13/100,000

(Van Den Eeden et al. Am J Epidemiol 2003;1015-22)

• Prevalence– 300/100,000 (Strickland & Bertoni, 2004)– Prevalence of PS/PD rising slowly with aging

population


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)


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


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


American Academy of Neurology Guideline Process

Clinical Question

Evidence

Conclusions

Recommendations


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


Literature Search/Review: Rigorous, Comprehensive,

Transparent

Search

Review abstracts

Review full text

Select articles

Relevant

Complete


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


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


Clinical Questions

1. Which clinical features and diagnostic modalities distinguish PD from other parkinsonian syndromes?

2. Which clinical features predict rate of disease progression?


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


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


Literature Search/Review: Diagnosis of PD

31 articles

176 articlesExclusion criteria:

-Studies not including at least 10 subjects with PD and 10 in the comparison group

-Articles that were off topic

-Review articles


Literature Search/Review: Prognosis of PD

7 articles

59 articlesExclusion criteria:

-Articles published before 1990 because of changes in the case definition of PD

-Articles that were off topic

-Review articles


Diagnosis of PD


Clinical Question 1

Which clinical features and diagnostic modalities distinguish PD from other Parkinsonian syndromes?


Diagnosis of PD

• Categories: – Clinical– Acute challenge testing– Radiological evaluation– Neurophysiological testing– Biochemical testing– CSF examination– Olfactory testing


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


Diagnosis of PD: Clinical Examination

Author Type Cohort Size

Spectrum Diagnostic Predictor

Reference Standard for

PD

Colosimo et al 1995

Case control Class 3

MSA(16); PD(20); PSP(16)

Narrow Rapid progression; symmetry; no tremor; poor response to dopa; autonomic dysfunction

Autopsy

Jankovic et al 2000

Retrospective cohort Class 2

800 (DATATOP cohort)

Narrow Poor response to levodopa, atypical clinical features

Clinical assessment (up to 6 yrs), autopsy, imaging


Diagnosis of PD: Clinical Examination

Author Type Cohort Size

Spectrum Diagnostic Predictor

Reference Standard

for PD

Wennings et al 2000


MSA(38); PD (100)

Broad Clinical exam, med side effects

Autopsy

Wennings et al 1999


MSA(15); PD(11); DLB(14); PSP(24); CBD(13)

Broad Time to onset of falling from onset of symptoms

Autopsy


• 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)

Recommendation for Diagnosis of PD


Diagnosis of PD: Clinical Features

• Longitudinal follow-up important – Lack of autonomic, oculomotor, cognitive

abnormalities at 5 years supports PD


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



• 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



Author Type Cohort Size Diagnostic Predictor

Reference Standard

for PD

Specificity Sensitivity

Rossi et al 2000

cohort survey Class 2

PD(83);MSA(28);PSP(6);unknwn(17)

UDPRS change after apomorphine challenge 1.5 or 4.5 mg or dopa 25/250

dopa apo 1.5mgapo 3apo 4.5

71%66% 64% 67%

77% 71% 77% 77%

Merello et al 2002

cohort survey Class 1

PD(55);nonPD(27--VP(5),MSA(4);ET(4);drug-induced(3); PSP(3);CBD(3); unknwn(3);DLB(3))

30% improve on UPDRS 3 after dopa 25/250 f/u of 24 mos for clinical diagnosis and chronic response to dopa

81% 71%


Recommendation for Levodopa/Apomorphine Challenge

• Both levodopa and apomorphine challenge tests should be considered when diagnosis of PD in doubt (Level B)


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


Diagnosis of PD: Olfaction

• Olfaction frequently impaired in PD

• Three Class II studies identified


Diagnosis of PD: Olfactory Testing

Author Class Cohort Size

Test Results

Doty et al, 1993

II PSP (21)

PD (21)

NC (21)

UPSIT PSP similar to NC

PD abn (p<0.001)

Mueller et al, 2002

II PD (37)

MSA, PSP, ET (13)

Sniffin Sticks

PD had anosmia

Wenning et al, 1995

II PD (118)

MSA (29)

PSP (15)

CBD (7)

NC (123)

UPSIT PD>MSA>PSP/CBD/NC

Sensitivity 77%

Specificity 85%


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


Diagnosis of PD vs. Other Parkinsonisms

• Not useful (Level C)• GH stimulation by clonidine• Electro-oculography• SPECT scanning


Diagnosis of PD vs. Other Parkinsonisms

• Insufficient Evidence (Level U)• Urodynamics • Autonomic testing• Urethral/anal EMG• MRI, FDG PET, brain sonography


Prognosis of PD


Clinical Question 2

Which clinical features predict the rate of disease progression?


Prognosis of PD

• Prognostic factors examined:– Age at disease onset– Sex– Cognitive and motor symptoms

• Seven studies– Six Class II– One Class III


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



• Predictors of faster rate of motor progression (Level C):– Postural instability/gait difficulty – Male sex – Presence of associated comorbidities

• Stroke, visual, auditory



• Predictors of earlier nursing home placement and decreased survival (Level C)– Older age at onset– Dementia– Poor responsiveness to dopaminergic

meds



• Predictors of earlier cognitive decline and dementia (Level B):– Older age at onset

– Initial hypokinesia/rigidity



• Tremor as a presenting symptom may be used to predict a more benign course and longer therapeutic benefit to levodopa (Level C)


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


Summary

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


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


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)


Recommendations for Future Research

• Methods for presymptomatic testing to identify patients at risk of developing PD

• Knowledge of disease progression


Questions, Comments?


Thanks for your participation!

© 2007 American Academy of Neurology Practice Parameter: Diagnosis and Prognosis of New Onset...

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