2020 PLS Consensus Diagnostic Criteria — Turner et al., JNNP
For decades after Pringle et al. defined PLS in 1992, no standardized diagnostic criteria existed that the field widely accepted. Different clinicians and research groups used different thresholds, making it hard to compare studies or run multicenter trials. The 2020 consensus criteria paper changed that. Turner and colleagues convened an international expert group, reviewed the accumulated natural history evidence, and produced the criteria that are now the standard in clinical practice and research worldwide.
The problem with earlier criteria
Pringle's 1992 criteria required a 3-year observation period of pure upper motor neuron syndrome before diagnosing "definite PLS." Other groups used different thresholds — some requiring 5 years, others as few as 2. This inconsistency was not merely academic: a patient diagnosed at 2 years under one system might be called "probable ALS" under another. For researchers trying to compare cohorts across institutions or countries, the variation made pooled analysis unreliable.
The field needed criteria that were: anchored in actual natural history data (not arbitrary cutoffs); specific enough to exclude ALS with high probability; sensitive enough to allow clinical diagnosis within a reasonable timeframe; and standardized enough to enable multicenter research.
What they did
Turner and colleagues convened an international expert consensus group, including neurologists with specific PLS expertise from North America, Europe, and Australia. The group reviewed the accumulated natural history evidence — particularly the data on ALS conversion rates and timing from cohorts including the NEALS registry — and used formal consensus methods to agree on criteria and thresholds.
The process was structured as an expert opinion-based consensus exercise, not a systematic review or randomized trial. This reflects the state of the evidence: PLS is rare and the evidence base, while growing, does not yet support purely data-driven threshold selection. Expert consensus is the appropriate methodology when evidence is limited but a standardized approach is urgently needed.
The 2020 criteria
Core requirements (all must be present)
Regardless of duration, a diagnosis of PLS requires:
- Progressive upper motor neuron dysfunction in at least 2 body regions (e.g., both legs, or one leg and speech/swallowing)
- Absence of active lower motor neuron degeneration on EMG (no fibrillations, fasciculations, or denervation consistent with ALS)
- Absence of sensory symptoms or signs
- Absence of alternative diagnoses that could explain the UMN syndrome (hereditary spastic paraplegia gene mutations, structural spinal cord or brainstem lesions, multiple sclerosis, other UMN diseases)
Diagnostic tiers
Probable PLS: Pure UMN syndrome meeting core criteria for 2–4 years from symptom onset. At this stage, ALS has not been excluded with high confidence — approximately 23% of patients presenting with probable PLS eventually convert to ALS within the first 4 years — but the diagnosis warrants the PLS designation for clinical planning and research enrollment purposes.
Definite PLS: Pure UMN syndrome meeting core criteria for 4 or more years from symptom onset. At this point, ALS conversion is substantially less likely — the data suggest that most patients who will convert have done so within the first 4 years.
Supportive features (not required but diagnostically helpful)
MRI findings consistent with PLS (T2 signal along the corticospinal tract, reduced motor cortex thickness, corpus callosum abnormalities), absence of lower motor neuron findings on EMG, and normal nerve conduction studies support the diagnosis but are not required for it. The El Escorial criteria — the diagnostic framework used for ALS — are specifically noted as not applicable to PLS.
What the thresholds are based on
The 2-year threshold for "probable PLS" and the 4-year threshold for "definite PLS" are grounded in conversion rate data. Approximately 23% of patients who initially present with a pure UMN syndrome consistent with PLS will eventually develop lower motor neuron signs and receive an ALS diagnosis. The majority of these conversions happen within the first 4 years of symptom onset.
This means the 4-year threshold is not arbitrary: it is the point at which, based on the available natural history data, the probability of future conversion drops substantially. A patient who has had a pure UMN syndrome for 4 years is much more likely to have PLS than a patient at 1 or 2 years. The threshold does not eliminate the conversion risk — it does not go to zero — but it meaningfully reduces it.
Why it matters
The 2020 criteria are the framework that enables PLS to exist as a research-ready entity. Before standardized criteria, every multicenter PLS trial faced the problem of patient-definition heterogeneity: were the patients enrolled in one center actually comparable to those in another? The 2020 criteria provide a common language.
For clinical practice, the criteria matter enormously. The difference between "you have probable PLS" and "you have early ALS" is not merely semantic — it is the difference between planning for decades of slowly progressive disability and planning for 2–5 years of rapid decline. Getting this right has profound consequences for patients and families, and the 2020 criteria give clinicians a standardized framework for making that determination.
The criteria also have implications for clinical trial enrollment. The PNHS (Mayo Clinic natural history study) uses the 2020 criteria to define its cohort. Any future treatment trial in PLS will use them. Standardized criteria mean standardized cohorts, which means results from one trial can be compared to another.
Current debates and future revisions
The 2020 criteria are not final. Two developments are driving discussion about future revision. First, improving biomarker techniques — particularly fluid biomarkers like NfL and advanced neuroimaging — may allow earlier biological confirmation of PLS before the 4-year threshold. If a blood test could reliably distinguish PLS from ALS at 18 months, maintaining a 4-year observational threshold becomes harder to justify. Second, the Netherlands natural history study (2025) and the PNHS are generating prospective data that will allow more rigorous, data-driven calibration of diagnostic thresholds.
The 2020 criteria should be understood as the current best standard, not the final answer. The field expects them to be updated as the evidence base develops.
How this connects
These criteria were built on the natural history data from Gordon 2006 and subsequent cohorts. They have been validated in an independent European population by the Netherlands natural history study. The PNHS uses them as its enrollment criteria. For what the diagnostic timeline means in practice, see Diagnosis and Prognosis. The natural history evidence base that underlies them is synthesized in the Scirocco 2025 review.
Citation
Turner MR, Barohn RJ, Corcia P, et al. Primary lateral sclerosis: consensus diagnostic criteria. Journal of Neurology, Neurosurgery & Psychiatry. 2020;91(4):373–377. doi:10.1136/jnnp-2019-322541