MDS Diagnostic Criteria: PD, MSA & PSP
This article summarizes the current International Parkinson and Movement Disorder Society (MDS) diagnostic criteria for three major parkinsonian syndromes: Parkinson’s disease (Postuma et al., 2015), multiple system atrophy (Gilman et al., 2008; Wenning et al., 2022), and progressive supranuclear palsy (Höglinger et al., 2017). These criteria are used in clinical practice and research to improve diagnostic accuracy and enable earlier identification of these neurodegenerative disorders.
Bottom Line: Key Diagnostic Features
- PD: Bradykinesia + resting tremor or rigidity; supported by levodopa response, olfactory loss, cardiac MIBG denervation; ~84% clinical accuracy by movement disorders specialists
- MSA: Autonomic failure + levodopa-resistant parkinsonism or cerebellar ataxia; the 2022 MDS criteria add MRI markers and a prodromal category; definite diagnosis requires neuropathology (GCIs)
- PSP: Four core domains (ocular motor, postural instability, akinesia, cognitive dysfunction); multiple phenotypic variants beyond classic Richardson syndrome; onset always >40 years
Part 1: Parkinson’s Disease (MDS 2015)
The MDS clinical diagnostic criteria for PD (Postuma et al., 2015) were developed to replace the UK Brain Bank criteria and provide a more objective, evidence-based diagnostic framework. Clinical diagnostic accuracy by movement disorders specialists is approximately 84%; definitive diagnosis requires neuropathologic confirmation (substantia nigra dopaminergic cell loss with Lewy body/neurite accumulation).
Core Diagnostic Criteria
Parkinsonism is the entry criterion, defined as:
- Bradykinesia (slowness of movement with progressive reduction in amplitude) PLUS at least one of:
- Resting tremor (4–6 Hz, typically asymmetric)
- Rigidity (increased resistance to passive movement, independent of velocity)
Diagnostic Categories
| Category |
Requirements |
| Clinically established PD |
Parkinsonism (as defined above) + absence of absolute exclusion criteria + at least 2 supportive criteria + no red flags |
| Clinically probable PD |
Parkinsonism + absence of absolute exclusion criteria + red flags counterbalanced by supportive criteria |
Supportive Criteria
- Clear and dramatic beneficial response to dopaminergic therapy
- Presence of levodopa-induced dyskinesias
- Resting tremor of a limb (documented on clinical examination)
- Olfactory loss (anosmia or hyposmia) OR cardiac sympathetic denervation on MIBG scintigraphy
Levodopa Challenge Test
- No standardized protocol exists
- Consider a total daily levodopa-equivalent dose ≥600 mg/day
- Per-dose strategy may need titration up to 2–3 tablets of carbidopa/levodopa 25/100 mg
- Use a standardized scale to document response; tremor may not respond or respond incompletely
- If no response, consider gastric emptying study to exclude impaired absorption
Red Flags (Suggesting Alternative Diagnosis)
| Red Flag |
Alternative to Consider |
| Rapid progression of gait impairment requiring wheelchair within 5 years |
PSP, MSA |
| No motor progression for 5 years |
Essential tremor, dystonia syndrome |
| Early bulbar dysfunction (dysarthria, dysphagia) |
MSA, PSP |
| Inspiratory respiratory dysfunction |
MSA |
| Severe autonomic failure within 5 years |
MSA |
| Recurrent falls (>1/year) due to impaired balance within 3 years |
PSP |
| Disproportionate anterocollis within 10 years |
MSA |
| Bilateral symmetric disease at onset |
MSA, PSP |
| Absence of nonmotor symptoms |
Essential tremor, dystonic tremor |
| Unexplained pyramidal signs |
MSA, PSP |
Exclusion Criteria
| Exclusion Criterion |
Alternative |
| Unequivocal cerebellar signs |
MSA, ataxia syndromes |
| Downward vertical supranuclear gaze palsy or selective slowing of downward saccades |
PSP |
| Probable bvFTD or PPA within 5 years of onset |
bvFTD, PPA |
| Parkinsonian features restricted to lower limbs >3 years |
Vascular parkinsonism, NPH |
| Treatment with DA receptor blocker in dose/time consistent with DIP |
Drug-induced parkinsonism |
| No response to high-dose levodopa (≥600 mg/d LED) |
Atypical parkinsonism |
| Cortical sensory loss or clear ideomotor apraxia |
CBS |
| Normal presynaptic dopaminergic imaging |
Essential tremor, DIP |
Part 2: Multiple System Atrophy (2008 & 2022)
Two sets of criteria are currently in use: the 2008 second consensus criteria (Gilman et al.) and the 2022 MDS criteria (Wenning et al.). The MDS criteria improve sensitivity at earlier stages while maintaining high specificity, and add a prodromal category and MRI markers.
Second Consensus Criteria (Gilman et al., 2008)
| Category |
Requirements |
| Definite |
Neuropathologic demonstration of synuclein-positive glial cytoplasmic inclusions (GCIs) with neurodegenerative changes in striatonigral or olivopontocerebellar systems |
| Probable |
Sporadic, progressive, adult-onset (>30 years) + autonomic failure (urinary incontinence with ED in males, OR orthostatic BP drop ≥30/15 mmHg within 3 min) + poorly levodopa-responsive parkinsonism OR cerebellar syndrome |
| Possible |
Sporadic, progressive, adult-onset + parkinsonism or cerebellar syndrome + at least one feature suggesting autonomic dysfunction + at least one additional clinical or imaging feature |
MDS Criteria (Wenning et al., 2022)
| Category |
Requirements |
| Neuropathologically established |
Same as 2008 definite (GCIs + neurodegeneration) |
| Clinically established |
Sporadic, progressive, adult-onset + autonomic dysfunction (voiding difficulties with PVR ≥100 mL, urge incontinence, OR neurogenic OH ≥20/10 within 3 min) + poorly levodopa-responsive parkinsonism or cerebellar syndrome + ≥2 supportive features + ≥1 MRI marker + no exclusion criteria |
| Clinically probable |
Sporadic, progressive, adult-onset + ≥2 of: autonomic dysfunction, parkinsonism, cerebellar syndrome + ≥1 supportive feature + no exclusion criteria (MRI not required) |
| Possible prodromal (research) |
Sporadic, progressive, adult-onset + RBD or neurogenic OH or urogenital failure + subtle parkinsonian or cerebellar signs + no exclusion criteria |
Supportive and MRI Features (2022 Criteria)
| Category |
Features |
| Motor supportive |
Rapid progression within 3 years; moderate-severe postural instability within 3 years; craniocervical dystonia (levodopa-induced, without limb dyskinesia); severe speech/dysphagia within 3 years; Babinski sign; jerky myoclonic tremor; postural deformities (anterocollis, camptocormia, Pisa) |
| Non-motor supportive |
Stridor; inspiratory sighs; cold/discolored hands and feet; erectile dysfunction (<60 years, for probable); pathologic laughter or crying |
| MRI markers (MSA-P) |
Putaminal atrophy (with signal decrease on iron-sensitive sequences); middle cerebellar peduncle, pontine, or cerebellar atrophy; hot cross bun sign; increased putaminal or MCP diffusivity |
| MRI markers (MSA-C) |
Putaminal atrophy (with signal decrease on iron-sensitive sequences); infratentorial atrophy (pons, MCP); hot cross bun sign; increased putaminal diffusivity |
Key Exclusion Criteria (2022)
- Substantial and persistent beneficial response to dopaminergic medications
- Unexplained anosmia on olfactory testing
- Fluctuating cognition with visuoperceptual decline
- Recurrent visual hallucinations (not drug-induced) within 3 years
- Dementia within 3 years of onset
- Downgaze supranuclear palsy or slowing of vertical saccades
- MRI suggesting alternative diagnosis
Distinguishing MSA from PD
- Anosmia: Common in PD, uncommon in MSA — useful differentiator
- MIBG scintigraphy: Typically normal in MSA (preganglionic pathology) vs. reduced heart-to-mediastinum ratio in PD (postganglionic)
- Alpha-synuclein SAA: Can differentiate PD/DLB from MSA in CSF; different strain conformations
- Neurofilament light chain: Markedly elevated in plasma/CSF in MSA (and PSP/CBS) compared to PD
- Skin biopsy: Alpha-synuclein in somatosensory fibers at distal sites in MSA vs. autonomic fibers at proximal sites in PD/DLB
- Tremor: MSA typically has postural/action tremor with myoclonus vs. classic pill-rolling rest tremor in PD
Part 3: Progressive Supranuclear Palsy (MDS 2017)
The MDS-PSP diagnostic criteria (Höglinger et al., 2017) replaced the 1996 NINDS-SPSP criteria to capture the broadening phenotypic spectrum beyond classic Richardson syndrome. The criteria use four core functional domains with graded levels of certainty.
Core Diagnostic Domains
| Domain |
Level 1 (Highest Certainty) |
Level 2 (Mid) |
Level 3 (Lowest) |
| Ocular motor (O) |
O1: Vertical supranuclear palsy |
O2: Slowed vertical saccades |
O3: Square-wave jerks or eyelid apraxia |
| Postural instability (P) |
P1: Repeated unprovoked falls within 3 years |
P2: Tendency to fall on pull test within 3 years |
P3: Retropulsion on pull test within 3 years |
| Akinesia (A) |
A1: Gait freezing within 3 years | A2: Axial rigidity, levodopa resistance | A3: Asymmetric tremor/rigidity, levodopa responsive |
| Cognitive (C) |
C1: nfPPA or apraxia of speech | C2: Frontal behavioral (apathy, disinhibition, perseveration) | C3: CBS features (apraxia, cortical sensory loss, alien limb) |
Diagnostic Categories
| Category |
Requirement |
| Definite |
Neuropathologic confirmation |
| Probable |
High specificity; e.g., O1 + P1 = probable PSP-Richardson syndrome |
| Possible |
Increased sensitivity with trade-off in specificity; e.g., O2 + P2/P3 = possible PSP-RS |
| Suggestive of |
Features that alone or in combination suggest early PSP |
PSP Phenotypic Variants
| Variant |
Key Clinical Features |
Predominant Location |
| PSP-Richardson syndrome |
Classic: early falls, vertical gaze palsy, axial rigidity, dysarthria, frontal dementia |
Brainstem |
| PSP with parkinsonism (PSP-P) |
Asymmetric tremor/rigid bradykinesia; moderate levodopa response early; progresses to Richardson phenotype; ~1/3 of PSP cases; survival ≥9 years |
Brainstem |
| PSP with gait freezing (PSP-PGF) |
Early gait difficulty, freezing, motor block, micrographia; disease duration 11–15 years |
Brainstem |
| PSP with frontal presentation (PSP-F) |
Prominent apathy, impulsiveness, disinhibition; may mimic bvFTD |
Cortical |
| PSP with speech-language disorder (PSP-SL) |
Nonfluent aphasia or apraxia of speech; precedes typical PSP motor features |
Cortical |
| PSP-CBS overlap |
Asymmetric dystonia, apraxia, cortical sensory loss, myoclonus, alien limb |
Cortical |
| PSP with ocular motor dysfunction |
Predominant ocular motor features; recognized at possible/suggestive level |
Brainstem |
| PSP with postural instability |
Predominant falls without other classic features early; may mimic vascular parkinsonism or MSA |
Brainstem |
Key Clinical Features of PSP
- Falls: Early (<3 years), backward, often unexplained; “rocket sign” (impulsively standing without assistance)
- Ocular motor: Slowed downward saccades are most sensitive and specific; progresses to full vertical then horizontal gaze palsy; “round-the-house sign” (curved downward saccades); square-wave jerks; photosensitivity (“sunglass sign”)
- Speech: Spastic-hypokinetic dysarthria (“growling”), monotonous, sometimes with stuttering or palilalia
- Gait: Stiff, broad-based, arms at sides, knees extended; ataxic and clumsy; pivot on heels when turning
- Facial: Astonished expression with frontalis activation or procerus contraction (“procerus sign”); wide eyes
- Cognition: Progressive frontal-executive dementia; bradyphrenia; reduced verbal fluency
- Mood: Apathy, depression (screen for suicidality), pseudobulbar affect (most frequent among parkinsonian syndromes)
- No onset <40 years: Such a presentation should prompt consideration of alternative diagnoses
- RBD uncommon: In contrast to PD and other synucleinopathies, RBD and RLS are relatively rare in PSP
Supportive Features and Exclusion Criteria
| Supportive Features |
Exclusion Criteria |
| Levodopa resistance |
Episodic memory deficits (Alzheimer-type) |
| Spastic-hypokinetic dysarthria |
Prominent dysautonomia |
| Early dysphagia |
Appendicular ataxia |
| Photophobia |
Hallucinations or cognitive fluctuations |
| Midbrain atrophy or hypometabolism on imaging |
Motor neuron findings |
| Postsynaptic striatal dopaminergic degeneration (e.g., abnormal IBZM-SPECT or DMFP-PET) |
Encephalitis history; sudden onset or stepwise progression |
|
Severe leukoencephalopathy, hydrocephalus, major stroke, or focal brain lesions on MRI |
Key Imaging Findings
- PD: Generally normal structural MRI; abnormal DAT-SPECT confirms presynaptic dopaminergic deficit (cannot distinguish PD from atypical parkinsonism); reduced MIBG uptake (postganglionic)
- MSA-P: Putaminal atrophy with hyperintense rim (T2), signal decrease on iron-sensitive sequences, increased diffusivity
- MSA-C: Pontine and MCP atrophy, hot cross bun sign (cruciate T2 hyperintensity), cerebellar atrophy
- PSP: Midbrain atrophy (“hummingbird sign” on sagittal), superior cerebellar peduncle atrophy; FDG-PET may show frontal hypometabolism
Emerging Biomarkers
- Alpha-synuclein seed amplification assay (SAA): Can differentiate PD/DLB from MSA and from non-synucleinopathies in CSF, skin, and saliva; different a-synuclein strains (GCIs vs. Lewy bodies)
- Skin biopsy for phosphorylated alpha-synuclein: Somatosensory fibers (distal) in MSA vs. autonomic fibers (proximal) in PD/DLB
- Neurofilament light chain (NfL): Markedly elevated in MSA, PSP, and CBS compared to PD; correlates with disease severity and progression
- Combined SAA + NfL: Higher diagnostic value than either test alone for differentiating MSA/PSP from PD
- Tau PET: Under investigation for PSP and CBS; 4-repeat tau pathology distinct from Alzheimer 3R/4R tau
References
- Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591-1601. doi: 10.1002/mds.26424
- Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670-676. doi: 10.1212/01.wnl.0000324625.00404.15
- Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022;37(6):1131-1148. doi: 10.1002/mds.29005
- Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: The Movement Disorder Society criteria. Mov Disord. 2017;32(6):853-864. doi: 10.1002/mds.26987
