Skip to Content


MDS makes every effort to publish accurate information on the website. "Google Translate" is provided as a free tool for visitors to read content in one's native language. Translations are not guaranteed to be 100% accurate. Neither MDS nor its employees assume liability for erroneous translations of website content.

International Parkinson and Movement Disorder Society
Main Content

        VOLUME 28, ISSUE 1 • March, 2024.  Full issue »

A Summary of the MDS ‘Statement of the MDS on Biological Definition, Staging and Classification of Parkinson’s Disease’

The recent discussion on disease staging and/or biological definition of Parkinson’s Disease (PD) has led to controversy, requiring a statement from the International Parkinson Disease and Movement Disorders Society (MDS). To tackle the issue of PD definition, classification and staging, MDS convened a meeting in April 2023. The gathering included a diverse group of international experts, including a patient representative. In the published statement of MDS1, we summarized those foundational principles for the development of a biological definition, classification, and staging system for PD. They were discussed at the meeting and further developed among MDS leaders.  

In this statement we followed the principles coming from the field of cancer, which unfortunately cannot be directly transferred to PD. In the former, the key anchor is the neoplastic cell, whose pathogenic role is undisputable. Moreover, the cancer classification and staging schemata are capable of predicting clinical course, therapeutic response, and prognosis. This is not the case of the recently developed proposals for PD and related conditions. The cancer TNM system may be the aim of a final development in PD, but we are still far away from a treatment-relevant staging or classification system in PD.  

As you can read in the statements from groups such as the development of a biological definition as published from Höglinger et al2 or the staging system of PD as published by Simuni et al3, and probably even more ideas and proposals to come, MDS feels a need for a wide international consensus for the classification of PD, with the involvement of all stakeholders including clinicians, scientists, as well as patients.

In the MDS statement, we provide definitions of terminology and try to clarify the current situation and the status of research available now. 

MDS understands the current need to develop a biologically driven diagnosis underlying the clinically defined disease that has been used for decades. The challenge of any biological and clinical diagnosis system, however, is its reliability and specificity and the global use in a practical way, which is currently possible for the clinical diagnosis.

There is ongoing debate regarding whether a common biological diagnosis exists that includes the large variation of phenotypes in PD. Alpha- synuclein (α-syn) aggregation is currently proposed to be a possible prevailing biological event present in a majority of cases with the final pathologically confirmed diagnosis of PD. There are exceptions, however, that have led to further discussion if α-syn is a crucial element in all phenotypes and genotypes. In the MDS paper1, we review the key information of so-called alpha-synuclein seed amplification assay (SAA) in the CSF and other biological materials. 

Even if one disregards the biological concerns related to the test, there is no reliable way of predicting if, when, and which clinical syndrome an SAA-positive individual will develop. Moreover, as SAA is a qualitative test, it does not correlate with clinical progression. This leads to ethical questions both for people with a positive or negative result. Negative individuals who develop clinically diagnosed PD may face a particularly challenging situation. This may be the case of some genetic forms of PD, particularly associated with LRRK2 mutations. 

Staging systems should only be developed after the consensus of a biological definition. Currently we have the Hoehn and Yahr4 clinical stages of PD, which was developed after observing patients and ranking their parkinsonism (unilateral vs bilateral) and disability level, and presence or absence of balance impairment4. This clinical staging system is not anchored on a biological or pathological basis. There are considerations from MDS to update this system accordingly. 

In our recent statement, we discussed the development of a staging system that should be a combination of both motor and non-motor clinical features and biological systems.  

We discussed the role and the current availability of biomarkers. Future studies need to assess how well biomarkers correlate to clinical features, course of the disease, and the post-mortem pathology of PD. The discussion of neuropathology emphasized the need for a biological definition of PD to distinguish it from other neurodegenerative parkinsonism. 

Genetic findings are one of the most controversially discussed issues in relation to biological definition, classification, and staging systems, as the SAA can turn out negative in some monogenic forms of PD such as LRRK2 and is excluded as pure “PD” in one of the staging systems.  

When considering any staging system for clinical practice, the considerations must focus on the patient's experience and the tools available in the clinic. From geographical locations, only a small amount of centers in Europe and North America and some big university centers in other parts of the world are currently be able to perform all the requested tests for the proposals of biological diagnosis and staging. Even if SAA tests are validated, they should be used for research alone until it is proved that people will benefit from the new criteria as part of regular clinical care to avoid confusion among patients and neurologists. 

We also need to be cautious and to foresee the mechanisms needed to implement new disease diagnosis and systems within the global health systems. Many of them provide care based on the World Health Organization International Classification of Diseases (ICD) codes.  

For clinical trials, a well-defined clinical syndrome is needed. There is also the need for clear outcome measures that correlate with the severity and progression of the disease. SAA does not meet these requirements. 

In summary, MDS recognizes the value and efforts of current proposals for a biological diagnosis, classification, and staging or classification systems in PD. Before application in any clinical practice or trials, there is the need to validate the proposed biological classification systems on long-term observations of populations with and without PD and other Parkinson syndromes, and the expert community should find a consensus of how to apply biological markers for establishing a PD diagnosis and clinical staging.



1. Cardoso F, Goetz CG, Mestre TA, et al. A Statement of the MDS on Biological Definition, Staging, and Classification of Parkinson's Disease. Mov Disord 2023. 

2. Hoglinger GU, Adler CH, Berg D, et al. A biological classification of Parkinson's disease: the SynNeurGe research diagnostic criteria. Lancet Neurol 2024;23(2):191-204. 

3. Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal alpha-synuclein disease: towards an integrated staging system for research. Lancet Neurol 2024;23(2):178-190. 

4. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17(5):427-442. 


Read more Moving Along:

Full issue    Archives

We use cookies to give you the best possible experience with our website. These cookies are also used to ensure we show you content that is relevant to you. If you continue without changing your settings, you are agreeing to our use of cookies to improve your user experience. You can click the cookie settings link on our website to change your cookie settings at any time. Note: The MDS site uses related multiple domains, including and This cookie policy only covers the primary and domain. Please refer to the MDS Privacy Policy for information on how to configure cookies for all other domains on the MDS site.
Cookie PolicyPrivacy Notice