Diagnostic Approach to Scattered T2/FLAIR Hyperintensities

Primary Diagnostic Considerations

The American Academy of Neurology recommends that MS diagnosis requires at least one typical MS lesion in at least two characteristic regions: periventricular, juxtacortical, infratentorial, and spinal cord 1, 2
Periventricular lesions in MS must directly contact the lateral ventricles without intervening white matter and typically orient perpendicular to the ventricles ("Dawson's fingers") 1, 2
MS characteristically affects U-fibers, which distinguishes it from vascular disease and migraine that spare these well-vascularized structures 3

The Infectious Diseases Society of America suggests that ADEM typically presents with abrupt neurologic symptoms several days after viral illness or vaccination, more common in children, with multifocal, usually bilateral but asymmetric lesions on MRI 5
The American Academy of Neurology recommends that PML should be strongly suspected in immunocompromised patients presenting with subacute progressive symptoms over weeks, with diffuse and large (>3 cm) lesions on MRI 4

The American College of Radiology recommends assessing lesion characteristics, including location, morphology, size, and distribution, to differentiate between MS, ADEM, and other diagnoses 1, 2, 3
Clinical context, including immunosuppression status, recent infection or vaccination, age, and vascular risk factors, is crucial in determining the underlying diagnosis 4, 5

The National Multiple Sclerosis Society recommends that disease-modifying therapy selection for MS is based on disease activity and patient factors 2
The American Academy of Neurology recommends that immediate cessation of immunosuppressive therapy and immune reconstitution is the primary management strategy for PML 4
The Infectious Diseases Society of America suggests that corticosteroids are first-line treatment for ADEM, with plasma exchange reserved for non-responders 5