Differentiating Multiple Sclerosis Mimics on MRI

A proper MS diagnosis can only be made after obtaining imaging from the entire brain and understanding the clinical context.

The accurate diagnosis of multiple sclerosis (MS) typically presents several challenges: There is no definitive test for the disease, and symptoms vary widely between patients. The initial symptoms in particular – such as numbness, tingling, and blurred vision, for example – may be highly nonspecific.

“MRI imaging of the brain provides the objective support needed to endorse the diagnosis,” though it is only one of many tools that help guide the diagnostic process, according to Dale J. Lange, MD, and Darius P. Melisaratos, MD, of Hospital for Special Surgery (HSS) in New York. Dr Lange is the chief neurologist at HSS and a professor of neurology at Weill Medical College of Cornell University, and Dr Melisaratos is a board-certified radiologist at HSS who specializes in neuroradiology.

Though the vast majority of MS patients have abnormalities on brain MRI, an estimated 5% of patients have normal imaging.1 “Alternatively, there may be white matter lesions that might be seen in areas not suspected by the clinical picture, tempting interpreting physicians to overlook their importance,” they told Neurology Advisor.

Further complicating the process are the numerous other disorders that can cause the same imaging findings that are characteristic of MS.2 These encompass a wide range of conditions, including various inflammatory disorders, CNS infections, genetic disorders, nutritional deficiencies, and more. This can make it especially difficult to exclude other potential diagnoses before MS can be diagnosed.

Inaccurate MRI interpretation is the most common cause of incorrect diagnoses in patients with MS, underscoring the critical importance of the physician’s familiarity with MS mimics.2 “Taking a thorough medical history focused on questioning the patient about prior neurological episodes that might have been overlooked or dismissed by the patient remains crucial in any assessment for MS,” said Nicoline Schiess MD, MPH, an assistant professor of neurology at Johns Hopkins University Multiple Sclerosis Center. “The clinical presentation of characteristic focal neurologic attacks as well as ruling out other MS mimics is essential to making an accurate diagnosis,” she told Neurology Advisor.

Some of the most common mimics include migraine and chronic cerebrovascular disease, according to Dr Schiess. Vasculitic autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome can also result in white matter abnormalities on MRI. Neuromyelitis optica spectrum disorders (NMOSD) also share several characteristics with MS and need to be ruled out. Though relatively rare, neurosarcoidosis can share features with MS and is important to consider in differential diagnosis, as well. Genetic diseases such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), mitochondrial diseases, and leukodystrophies should also be considered.

White matter lesions observed on brain MRI are usually characteristic and occur in specific areas including the corpus callosum and pons. “However, in many cases, the white matter lesions as isolated observations are nonspecific” and could be due to MS or another cause, explained Drs Lange and Melisaratos. “The only way to tell is to determine if there are co-existing abnormalities in other parts of the brain and this must be incorporated within the context of the clinical condition,” they said.

Dr Schiess added that ancillary testing, including blood work, CSF findings, optical coherence tomography (OCT), and evoked potentials can also facilitate diagnosis. Additionally, careful assessment of “the so-called MRI red flags, such as the presence of infarcts, microbleeds, meningeal enhancement, and calcifications, among others, are very helpful in suggesting a diagnosis other than MS,” according to research published in the Handbook of Clinical Neurology.3 

“The most important point to take from this series is that many images can be compatible with MS. However, an accurate diagnosis can be made only after thorough review of images obtained from the entire brain and by understanding the clinical context,” Drs Lange and Melisaratos concluded.

In the below slideshow, Drs Lange, Melisaratos, and Schiess shared a collection of MRI findings from their clinical practice to illustrate a selection of MS mimics.

Click here to view the slideshow. 


  1. Magnetic resonance imaging (MRI). National Multiple Sclerosis Society website. http://www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-Tools/MRI. Accessed September 2, 2016.
  2. Chen JJCarletti FYoung VMckean DQuaghebeur G. MRI differential diagnosis of suspected multiple sclerosis. Clin Radiol. 2016;71(9):815-27.
  3. Aliaga ESBarkhof F. MRI mimics of multiple sclerosis. Handb Clin Neurol. 2014;122:291-316.