Approach
A thorough history and skilled clinical examination enable diagnosis of PD. No specific diagnostic tests are available.[1][67]
The history will contain symptoms suggestive of bradykinesia and at least one of rest tremor or rigidity; postural instability may be evident. Nonmotor symptoms, such as neuropsychiatric symptoms (e.g., depression, anxiety), autonomic dysfunction (e.g., orthostatic hypotension, constipation, incontinence, dysphagia), sleep disorders, and pain are often present, and may precede the development of motor symptoms.[17][68] History should exclude exposure to drugs (such as antipsychotics or antiemetics) that may induce a secondary parkinsonism.
The 2015 Movement Disorder Society (MDS) diagnostic criteria for PD define "parkinsonism" as the presence of bradykinesia with at least one of rest tremor or rigidity.[1][67][69]
Once parkinsonism is diagnosed, supportive criteria for idiopathic PD include a clear response to dopaminergic therapy and/or the presence of levodopa-induced dyskinesias.
A definitive diagnosis of PD is only possible postmortem and requires pathologic examination of the brain.[17]
Examination
A complete neurologic examination should provide objective evidence of parkinsonism in the absence of any other neurologic abnormalities. Often, simple observation reveals generalized slowness and lack of spontaneous movement.
Neurologic examination will support the history:
Slowness executing movements (bradykinesia), and motor arrests or freezing (akinesia) observed during rapid alternating movements and gait portions of examination.
The face is masked, with reduced expressivity, reduced blink rate, and a softened, poorly articulated voice.
Oculomotor examination may reveal abnormalities including impaired saccadic and smooth pursuit, and impaired convergence.
Rigidity is evaluated by passive movement about a joint and can be accentuated or reinforced by asking the patient to move the opposite limb (i.e., in circular motion or open/close fist).
Resting tremor is often passively observed, but distraction can elicit subtle findings. A postural tremor and re-emergent resting tremor may be seen with arms outstretched.
The gait portion of the examination may demonstrate a stooped, shuffling appearance and reduced arm swing. Patients often turn en bloc, requiring numerous steps to complete a 180° turn.
A pull test (briskly pulling the patient backward while standing) is performed to assess postural reflexes. Loss of postural reflexes generally occurs in mid- to late-stage disease.
Patients with idiopathic PD will demonstrate any combination of the above. Generally, findings occur asymmetrically.
A neurologist demonstrates how to identify signs of Parkinson disease on clinical examination.
Atypical parkinsonism
Features that may suggest atypical parkinsonism include:
Acute onset
Rapidly progressive disease
Cognitive impairment
Prominent postural instability
Severe autonomic dysfunction
Significant neuropsychiatric features (e.g., hallucinations, fluctuating levels of arousal).
In addition, early falls, poor response to levodopa, symmetry of motor findings, lack of tremor, and early autonomic dysfunction are features that distinguish other parkinsonian syndromes from PD.[1]
Neurologic examination
Patients should be screened for nonmotor symptoms, such as neuropsychiatric symptoms (e.g., depression, anxiety), dementia, autonomic dysfunction (e.g., constipation, orthostatic hypotension), sleep disorders, and pain. These may precede the development of motor symptoms.[17][68][70][71]
Abnormalities on neurologic examination outside of the extrapyramidal system should alert the physician to a possible alternative diagnosis. Findings such as vertical gaze palsy, aphasia, dementia, weakness, hyperreflexia, cerebellar dysfunction, sensory loss, or marked imbalance are not generally expected in patients with PD.
Screening tools for depression and dementia
The Beck Depression Inventory (BDI), Geriatric Depression Scale (GDS), and Montreal Cognitive Assessment (MoCA) are commonly used.
Validated scales to assess depression in patients with PD are available.[72]
Exclusion criteria
Exclusion criteria for idiopathic PD include: cerebellar abnormalities; gaze palsy; dementia early in the disease course; parkinsonism restricted to the lower limbs for more than 3 years; treatment with a dopamine-receptor blocking agent (drug-induced parkinsonism); absence of response to high-dose levodopa; cortical sensory loss, apraxia, or aphasia; and normal functional neuroimaging of the presynaptic dopaminergic system.[1]
Investigations
If findings on examination are consistent with idiopathic PD, no further testing is required. Objective improvement in signs in response to antiparkinsonian (dopaminergic) medications will confirm a diagnosis.[1]
Although not performed routinely, a smell test can be given to substantiate the presumptive diagnosis.[73][74] Hyposmia or anosmia is a nonspecific finding that can be seen in up to 75% to 90% of patients.[1][75]
Atypical parkinsonism
If atypical features, such as acute onset, rapidly progressive disease, early cognitive impairment, symmetric findings, or upper motor neuron signs, are found, magnetic resonance imaging (MRI) of the brain with and without gadolinium contrast is recommended.
If cognitive impairment is noted on mental status examination, formal neuropsychometric testing should be performed, in addition to MRI, to assist in determining whether the dementia is consistent with PD with dementia or another neurodegenerative disorder.
If features of a psychogenic etiology are noted, or a vascular or drug-induced etiology is suspected, dopamine transporter imaging (e.g., using 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane [FP-CIT] or beta-CIT single-photon emission computed tomography [SPECT], or fluorodopa positron emission tomography [PET]) should be considered when available.[76][77][78][79] Dopamine transporter imaging can also be useful in distinguishing cases of PD with action tremor from cases of essential tremor with parkinsonism.[79]
Cardiac sympathetic innervation using iodine-123 meta-iodobenzylguanidine (MIBG) may be used to distinguish PD from other neurodegenerative parkinsonian syndromes. MIBG uptake by postganglionic cardiac sympathetic neurons is grossly reduced at an early stage of PD in almost all patients with a clinical severity score of Hoehn and Yahr II or higher.[67][80][81][82]
There is insufficient evidence to support the use of levodopa or apomorphine challenge tests in differentiating between PD and other parkinsonian syndromes.[83]
Patients with family history or younger patients
Genetic testing for specific gene mutations known to be associated with PD should be performed if younger-onset disease or a strong family history exists. However, this is often done as part of a research protocol to determine or investigate a particular lineage, and rarely used as a primary means to establish a diagnosis.[84]
In all younger patients (<40 years), a diagnosis of Wilson disease should be excluded. Low serum ceruloplasmin, elevated 24-hour urine copper, and the presence of Kayser-Fleischer rings on slit-lamp exam all support this diagnosis.
Emerging tests
Skin biopsy may be used to detect abnormal dermal alpha-synuclein aggregates, as these have been shown to be similar to midbrain alpha-synuclein in patients with PD, and so may be a suitable surrogate for central nervous system (CNS) pathology. Dermal phosphorylated synuclein is found mainly in autonomic nerve terminals, richly innervating dermal autonomic annexes (blood vessels, pilomotor muscles, and sweat glands).[85][86]
Use of this content is subject to our disclaimer