Table 2

MS differential diagnosis11 14 15 18 31 105–107

MS presentation	Clinical course	MRI 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

MS presentation

Clinical course

MRI 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.