Multiple sclerosis – white spots and red flags – part 2

Mimics and Variants

Demyelinating disease is a common situation we encounter in neuroradiology, and properly diagnosing and tracking it using MRI is a key skill for neuroradiologists. In this second part of the lecture, Dr. Michael Hoch gives us some tips about other causes of white matter lesion, and information we can use to make our imaging diagnosis of multiple sclerosis more specific.

Clinical history has an important role in determining how specific imaging findings are for multiple sclerosis. Some features may suggest that a patient does not have multiple sclerosis, such as if they are the wrong age (< 20 or > 50 years old), if they have abrupt swift progression, if they have systemic symptoms such as fever or weight loss, and if they have uncommon CNS symptoms such as a movement disorder or meningitis signs. MS lesions also usually occur in some specific locations, such as in the corpus callosum, temporal lobe, periventricular white matter, and juxtacortical white matter.

Mimics of Multiple sclerosis

So, what are some of the common mimics of MS?

Migraine – migraine is the most common cause of non-specific white matter abnormalities in young patients, occurring in more than 50% of patients with migraine

Chronic small vessel ischemia – more common with increasing age, and worsening with risk factors such as diabetes, hypertension, and smoking

CNS vasculitis – an inflammatory syndrome of the intracranial vessels. Be on the lookout if someone has a history of TIAs or thunderclap headache, or systemic symptoms.

Behcet’s disease – a vasculitis most common in young males, characterized by brainstem involvement and oral ulcers

Susac syndrome – an autoimmune microangiopathy overlapping MS in age distribution. However, patients more often have a triad of encephalopathy, hearing loss, and visual changes. Corpus callosum involvement is more likely to be central. 

CADASIL – an autosomal dominant syndrome characterized by frequent infarcts. Look out for the characteristic locations in the temporal poles, external capsules, and paramedian superior frontla lobes. It is also usually quite symmetric.

Other rarer mimics are Neuro-Sweets disease and Lyme disease, which can cause white matter abnormalities.

Key take home points of this lecture include:

  • Multiple sclerosis is a clinical diagnosis, not an MRI diagnosis
  • White spot lesion location matters
  • Juxtacortical lesions must touch the cortex
  • Aggressively window the spine to look for cord lesions
  • Leptomeningeal enhancement is possible in multiple sclerosis

Variants of demyelinating disease

There are several common variants that you should know about across the demyelinating spectrum:

ADEM – acute disseminated encephalomyelitis – an autoimmune mediated and often self limited fulminant demyelinating process. May be related to a viral illness or vaccination.

Marburg disease – a clinically fulminant demyelinating disease usually affecting younger patients with a febrile prodrome.

Balo concentric sclerosis – a rare and monophasic demyelinating disease characterized by large lesions with alternating zones of demyelination/myelination

Tumefactive demyelinating lesions (TDL) – large and often fulminant demyelinating lesions that have mass effect and can mimic tumors. Perfusion imaging with low blood volumes can help differentiate from masses.

Neuromyelitis optica (NMO) – a demyelinating syndrome characterized by post-chiasmatic optic neuritis and long segment spine lesions. This is mediated by an aquaporin-4 antibody.

Progressive multifocal leukoencepalopathy (PML) – a JC virus mediated demyelinating lesion that occurs in immune suppressed patients. Usually has little or no enhancement and favors a subcortical location.


In summary, there are a couple of key things to keep in mind when evaluating potential demyelinating lesions:

  • Read the chart for clinical red flags
  • Look at the MRI for imaging red flags, like strokes, hemorrhages, cysts, findings that are too symmetric, subcortical, or normal
  • Remember that white matter lesions from migraine and microvascular disease are far more common that multiple sclerosis
  • NMO has differentiating features
  • PML is a rare complication of immune suppressing medications in MS patients


The level of this lecture is appropriate for radiology residents, radiology fellows, and trainees in other specialties who have an interest in imaging or treating patients with potential demyelinating diseases.

This video is part of a two part series on multiple sclerosis presented by Dr. Hoch.

If you haven’t seen it already, go back and check out part 1, in which Dr. Hoch discusses the key findings of demyelinating lesions.