Understanding the New Diagnostic Criteria for Multiple System Atrophy (MSA)

Speaker: Daniel Di Luca, MD, MSc – Movement Disorders Neurologist, Washington University in St. Louis
Event: Annual All-Community Virtual MSA Conference 2025

Diagnosing Multiple System Atrophy (MSA) accurately and early has long been a challenge for neurologists. In this presentation from the Annual All-Community Virtual MSA Conference 2025, Dr. Daniel Di Luca breaks down the critical transition from the older 2008 consensus criteria to the updated 2022 Movement Disorder Society (MDS) criteria for MSA.

These updated guidelines represent a major step forward, addressing past limitations to improve early clinical recognition, enhance patient quality of life, and facilitate faster enrollment into MSA clinical trials.

Why Were the MSA Diagnostic Criteria Updated?

The previous 2008 diagnostic guidelines were limited by suboptimal accuracy and low sensitivity during the early stages of the disease. This meant that many patients went undiagnosed for years until their symptoms became severe. The 2022 MDS criteria were developed by the MDS MSA Study Group specifically to solve this problem, shifting the focus toward early recognition and intervention.

Key Changes in the 2022 MDS Criteria for MSA

The new guidelines bring several major updates to how neurologists evaluate and diagnose this rare neurodegenerative condition:

• Four New Diagnostic Categories: To capture the disease in its earliest stages, the 2022 criteria use a four-tier system:
  1. Neuropathologically Established MSA (Confirmed post-mortem)
  2. Clinically Established MSA
  3. Clinically Probable MSA
  4. Possible Prodromal MSA (A newly introduced category designed to catch the disease in its earliest, most subtle stages before major motor symptoms appear).
• Simplified Autonomic Testing: Assessing autonomic dysfunction (such as urinary incontinence, voiding difficulties, and orthostatic hypotension) is critical for an MSA diagnosis. The new guidelines simplify these definitions, allowing doctors to use basic clinical measurements (like a 3-day bladder diary or a standard blood pressure drop check) rather than requiring complex autonomic laboratory testing.
• Greater Integration of Brain Imaging (MRI): Under the 2008 rules, MRI findings were merely supportive. Today, specific MRI markers—such as pontine atrophy, putaminal changes, and the “hot cross bun” sign—are far more integral to confirming a clinical diagnosis of MSA.
• Clearer Exclusion Criteria: The updated criteria provide strict “red flags” to help doctors rule out MSA. If a patient shows a substantial and persistent response to Levodopa, early-onset dementia, or unexplained loss of smell (anosmia), clinicians are directed to look for alternative conditions, such as Parkinson’s disease or Dementia with Lewy Bodies.

The Future of MSA Diagnosis: Biomarkers

Currently, there is no universally validated “gold-standard” biomarker for MSA mandated by the new criteria. However, Dr. Di Luca highlights that researchers are making incredible progress. Fluid and tissue biomarkers, such as Neurofilament light chain (NfL) and alpha-synuclein skin biopsies, hold massive potential for the future. While currently limited in clinical availability, their continued validation will eventually allow doctors to predict, diagnose, and track the progression of MSA with unprecedented accuracy.

Validation and Improved Accuracy

Is the new system working? According to early retrospective validation studies—including data from the Mayo Clinic—the 2022 MDS criteria offer a significantly better balance of diagnostic sensitivity and specificity compared to the 2008 guidelines. While the old criteria often misdiagnosed patients, the new Clinically Established and Clinically Probable tiers vastly reduce the chances of misdiagnosis, ensuring patients receive the right care, faster.