Table 2

MS differential diagnosis11 14 15 18 31 105–107

MS presentationClinical courseMRI findings
Optic neuritis
  • Neurosarcoidosis, SLE, CRION, Behcet’s disease, NMOSD, MOG-associated disease, ADEM, neuroretinitis, infectious*, compressive pathology, vascular†, Toxic-metabolic†† , Genetic- LHON

Brainstem syndrome
  • Malignancy, neurosarcoidosis, NMOSD, Behcet’s disease, histiocytosis, CLIPPERS, SLE, infectious‡, vascular, CPM

Spinal cord syndrome
  • Compression, NMOSD, neurosarcoidosis, SLE, Sjogrens Syndrome, infectious§, vascular¶

Relapsing-remitting
  • Neurosarcoidosis, NMOSD, Behcet’s disease, SLE, Antiphospholipid Syndrome, Sjogren’s Syndrome, Lyme Disease, Vasculitis, CADASIL, LHON

Progressive
  • B12 deficiency, Copper deficiency, Paraneoplastic Syndromes, HTLV, Whipple Disease, SCA, Friedrich Ataxia, ALS or PLS, Celiac Sprue, Leukodystrophies, HSP, dural AV fistula

Small vessel disease
Migraine
CADASIL
Susac Syndrome
ADEM
NMOSD
Vasculitis and Inflammatory
  • Primary CNS, vasculitis, SLE, Sjogren’s Syndrome, Neurosarcoidosis, Neuro-Behcet’s, CLIPPERS, Wegener’s, Crohn’s disease, Celiac disease

Infectious**
CPM
PRES
Wernicke
B12 deficiency
Mitochondrial disorders
Adult-onset leukodystrophies
Neoplasm
  • *Syphilis, Lyme, HIV, Bartonella henselae, neurocysticercosis, TB.

  • †AION, PION, GCA diabetic retinopathy, Susac syndrome, vascular malformations.

  • ‡Infections—syphilis, listeria, Lyme, Whipple’s, TB, viral.

  • §Syphilis, Lyme, TB, HIV, HTLV.

  • ¶Ischemia, AVM.

  • **PML, HIV, Lyme, Whipple’s, neurosyphilis, cysticercosis, toxoplasmosis.

  • ††B12 deficiency, methanol, ethambutol, ethylene glycol.

  • ADEM, acute disseminated encephalomyelitis; AION, anterior ischemic optic neuropathy; ALS, amyotrophic lateral sclerosis; AV, arteriovenous; AVM, arteriovenous malformation; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CPM, central pontine myelinolysis; CLIPPERS, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids; CRION, chronic relapsing inflammatory optic neuropathy; GBS, Guillain-Barre syndrome; GCA, giant cell arteritis; HTLV, human T-lymphotropic virus; LHON, Leber’s hereditary optic neuropathy; NMOSD, neuromyelitis optica spectrum disorder; NO, nitrous oxide; PION, posterior ischemic optic neuropathy; PLS, primary lateral sclerosis; PRES, posterior reversible encephalopathy syndrome; SCA, spinocerebellar ataxia; SLE, systemic lupus erythematosus; TB, tuberculosis.