Aug. 29, 2025
Mayo Clinic's multiple sclerosis (MS) team has extensive experience with distinguishing progressive MS from its many mimics. Timely diagnosis of progressive MS means patients receive care that can help slow disease progression and improve quality of life.
"Progressive MS can be difficult to diagnose. But with new therapies becoming available, early and accurate diagnosis is even more important," says Eoin P. Flanagan, M.B., B.Ch., a neurologist at Mayo Clinic in Rochester, Minnesota, and chair of Multiple Sclerosis and Autoimmune Neurology.
Mayo Clinic sees more than 4,300 adults and children with MS every year. In addition to subspecialized neurologists, the care team includes neuroradiologists, neuro-ophthalmologists, physical medicine and rehabilitation specialists, urologists, and psychiatrists.
"Our physicians take the time to obtain a complete history, perform a physical examination and interpret diagnostic tests, taking into consideration updated criteria for accurate diagnosis," says Vanessa V. Marin Collazo, M.D., a neurologist at Mayo Clinic in Jacksonville, Florida.
Mayo Clinic uses cutting-edge imaging to identify MS plaques and biomarkers. Patients also have access to testing for novel biomarkers and the resources of Mayo Clinic's distinguished autoimmune laboratory.
"Integrating technology with a careful patient history and examination helps achieve an accurate diagnosis without having to allow more time for progression to occur," says Dean M. Wingerchuk, M.D., a neurologist at Mayo Clinic in Phoenix/Scottsdale, Arizona. "Our level of experience is also very helpful, especially for atypical presentations."
State-of-the-art patient evaluations
Mayo Clinic has been at the forefront of efforts to define autoimmune neurology diseases. Differentiating among these diseases is key for accurate diagnosis and optimal care. "We see patients referred for other neurologic diseases and we're able to demonstrate that they actually have MS — and vice versa," Dr. Wingerchuk says.
Technology that captures MS biomarkers
On the left, 3T susceptibility-weighted MRI shows a nonspecific lesion in the white matter (arrow). On the right, at 7T a central vein (arrow) is clearly seen within the lesion, as well as a hypointense border (arrowheads) indicative of a paramagnetic rim.
Mayo Clinic uses 7T MRI to identify novel MS biomarkers, such as paramagnetic rim lesions and the central vein sign. Those biomarkers were added to the McDonald criteria for the diagnosis of MS in 2024.
"Incorporating these two highly specific markers was a paradigm shift that highlights the profound impact of 7T MRI on MS," says Erik H. Middlebrooks, M.D., a neuroradiologist at Mayo Clinic's campus in Florida. "MRI has often been limited in its ability to differentiate MS from common mimics. But 7T MRI is significantly better at identifying these important biomarkers." Mayo Clinic researchers demonstrated 7T MRI's superior ability to detect the central vein sign in MS in a study published in the American Journal of Neuroradiology.
"With new therapies becoming available, early and accurate diagnosis is even more important."
Testing for neurofilament light chain protein provides additional information. When elevated, the protein can be a nonspecific biomarker of MS. Mayo Clinic Laboratories offers a unique neurofilament light chain serum assay.
"It's an adjunct tool — a good biomarker when MS is active or more inflamed," Dr. Flanagan says. "Neurologic examination and MRIs might tell only part of a patient's story. Matching the assay to those other parameters can really help us get an overall picture and see what's happening beneath the surface."
Optical coherence tomography can assess retinal damage related to MS. Gait testing is another diagnostic tool for early neurodegeneration. Mayo Clinic has laboratories equipped with tools to record every aspect of gait and balance. "These measures of function may predict neurological deterioration before it's clearly evident on clinical examination," Dr. Wingerchuk says.
On a research basis, Mayo Clinic uses microglial PET scans to identify activated microglia, an important source of oxidated damage in MS. Serum and cerebrospinal fluid testing can identify cytokines and chemokines, which also are MS biomarkers. Experts in clinical genomics can help determine if a patient's progressive neurologic problems are due to a genetic disorder, such as adult-onset leukodystrophy, rather than MS.
"All of these tools give us a more rounded approach to the diagnosis of progressive MS," Dr. Flanagan says. "We have good experience distinguishing the causes of spinal cord syndromes, which is how most progressive MS presents."
Individualized treatment approach
Mayo Clinic's multispecialty team meets to recommend the optimal treatment approach for each patient. "The complexity of MS — presenting with multifocal neurological deficits and disability — requires that multidisciplinary, individualized approach," Dr. Marin Collazo says. "There are a wide number of disease-modifying therapies and options for managing symptoms. At Mayo Clinic, we strive to design a plan that is effective and safe for each patient."
Biomarker test results have potential to help guide this decision-making. For example, individuals with activated microglia on PET scan might be likelier to benefit from Bruton tyrosine kinase inhibitors, which target microglia. Currently used only on a research basis, these tools offer promise for the future.
Patients with progressive MS are followed closely, with comprehensive testing at every visit and treatment adjustments as needed. MS pharmacists advise on treatment regimens.
"Patients might take multiple medications to reduce symptoms. These medications can interact and cause various complications. But our MS pharmacists are available to comprehensively review the medication regimen, advise on interactions and counsel on potential risks," Dr. Flanagan says.
Physical medicine and rehabilitation specialists help patients maximize function. Subspecialized MS nurses educate patients and families. Mayo Clinic's multispecialty approach also provides overall health guidance for individuals with MS.
"Medical comorbidities interact with MS. People who smoke, for example, have more rapidly progressive MS," Dr. Wingerchuk says. "We emphasize the importance of general health and help our patients to achieve that."
Mayo Clinic's team approach means people with progressive MS generally can see multiple specialists in a single day. "Multidisciplinary care is really what's crucial," Dr. Flanagan says. "At Mayo Clinic, the doctors all talk to one another and work together. We can usually get things done rapidly to make it a seamless experience for patients."
For more information
Multiple Sclerosis and Autoimmune Neurology. Mayo Clinic.
Okromelidze L, et al. Central vein sign in multiple sclerosis: A comparison study of the diagnostic performance of 3T versus 7T MRI. American Journal of Neuroradiology. 2023;45:76.
Refer a patient to Mayo Clinic.