Adult-Onset Leukodystrophies Mimicking Multiple Sclerosis

Although individually rare, adult-onset leukodystrophies represent a non-negligible diagnostic challenge to clinicians assessing patients for MS. Patients with adult-onset leukodystrophies often present with multifocal white matter involvement that may mimic MS lesions. Their variable clinical presentation, often characterized by progressive spasticity, ataxia, and cognitive decline, can overlap with that of primary progressive MS, further adding to the diagnostic challenge of correctly identifying these rare disorders. The impact on patients is considerable and extends from potential exposure to inappropriate immunomodulatory treatments to missing timely genetic counseling and targeted leukodystrophy-specific therapies. Thus, it is crucial to know clinical and radiologic red flags for adult-onset leukodystrophies that can assist the differential diagnosis.