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¶

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

  • 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
Susac Syndrome
Vasculitis and Inflammatory
  • Primary CNS, vasculitis, SLE, Sjogren’s Syndrome, Neurosarcoidosis, Neuro-Behcet’s, CLIPPERS, Wegener’s, Crohn’s disease, Celiac disease

B12 deficiency
Mitochondrial disorders
Adult-onset leukodystrophies
  • *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.