Definitions of the classification of diagnostic evidence (Class I–IV), classification of prognostic evidence (Class I–IV), and strength of recommendations (A, B, C, U) are provided at the end of the "Major Recommendations" field.
Which Clinical Features and Diagnostic Modalities Distinguish Parkinson Disease (PD) From Other Parkinsonian Syndromes?
Recommendations
Determining the presence of the following clinical features in early stages of disease should be considered to distinguish PD from other parkinsonian syndromes: 1) falls at presentation and early in the disease course, 2) poor response to levodopa, 3) symmetry at onset, 4) rapid progression (to Hoehn and Yahr stage 3 in 3 years), 5) lack of tremor, and 6) dysautonomia (urinary urgency/incontinence and fecal incontinence, urinary retention requiring catheterization, persistent erectile failure, or symptomatic orthostatic hypotension) (Level B).
Levodopa and apomorphine challenge should be considered for confirmation when the diagnosis of PD is in doubt (Level B).
Olfaction testing should be considered to differentiate PD from progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), but not PD from multiple system atrophy (MSA) (Level B).
There is insufficient evidence to determine whether levodopa and apomorphine challenge or olfaction testing have any advantage over the clinical diagnostic criteria of PD (Level U). Additionally, there is insufficient evidence to determine the optimal combination or sequence of these tests (Level U).
The following may not be useful in differentiating PD from other parkinsonian syndromes: growth hormone (GH) stimulation with clonidine, electrooculography, and single photon emission computed tomography (SPECT) scanning (Level C).
There is insufficient evidence to support or refute the following as a means of distinguishing PD from other parkinsonian syndromes: urodynamics, autonomic testing, urethral or anal electromyography (EMG), magnetic resonance imaging (MRI), brain parenchyma sonography, and 18F fluorodeoxyglucose positron emission tomography (FDG PET) (Level U).
Which Clinical Features Predict Rate of Disease Progression?
Recommendations
In patients with newly diagnosed PD, older age at onset and rigidity/hypokinesia as an initial symptom should be used to predict more rapid rate of motor progression (Level B).
The presence of associated comorbidities (stroke, auditory deficits, and visual impairments), postural instability/gait difficulty (PIGD), and male sex may be used to predict faster rate of motor progression (Level C).
Tremor as a presenting symptom may be used to predict a more benign course and longer therapeutic benefit to levodopa (Level C).
Older age at onset and initial hypokinesia/rigidity should be used to predict earlier development of cognitive decline and dementia (Level B).
Older age at onset, dementia, and decreased dopamine responsiveness may be used to predict earlier nursing home placement as well as decreased survival (Level C).
Definitions:
Classification of Evidence for Diagnostic Articles
Class I: Evidence provided by a prospective study in a broad spectrum of persons with the suspected condition, using a reference (gold) standard for case definition, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy. All patients undergoing the diagnostic test have the presence or absence of the disease determined.
Class II: Evidence provided by a prospective study of a narrow spectrum of persons with the suspected condition, or a well designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy.
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where the reference standard, if not objective, is applied by someone other than the person that performed the test.
Class IV: Any design where test is not applied in an independent evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls).
Classification of Evidence for Prognostic Articles
Class I: Evidence provided by a prospective study of a broad spectrum of persons who may be at risk of developing the outcome (e.g. target disease, work status). The study measures the predictive ability using an independent gold standard for case definition. The predictor is measured in an evaluation that is masked to clinical presentation and the outcome is measured in an evaluation that is masked to the presence of the predictor. All patients have the predictor and outcome variables measured.
Class II: Evidence provided by a prospective study of a narrow spectrum of persons at risk for having the condition, or by a retrospective study of a broad spectrum of persons with the condition compared to a broad spectrum of controls. The study measures the prognostic accuracy of the risk factor using an acceptable independent gold standard for case definition. The risk factor is measured in an evaluation that is masked to the outcome.
Class III: Evidence provided by a retrospective study where either the persons with the condition or the controls are of a narrow spectrum. The study measures the predictive ability using an acceptable independent gold standard for case definition. The outcome, if not objective, is determined by someone other than the person who measured the predictor.
Class IV: Any design where the predictor is not applied in an independent evaluation OR evidence provided by expert opinion or case series without controls.
Classification of Recommendations:
Level A = Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)
Level B = Probably effective, ineffective, or harmful for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.)
Level C = Possibly effective, ineffective, or harmful for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
Level U = Data inadequate or conflicting; given current knowledge, treatment is unproven.
