Your comprehensive evidence-based neurology knowledge base.
347 topics across 9 neurology specialties
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)
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) 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
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
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
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
