Pediatric Multiple Sclerosis Differential Diagnoses

Updated: Jan 03, 2022
  • Author: Alice K Rutatangwa, DO, MSc; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Diagnostic Considerations

In general, atypical features of pediatric multiple sclerosis (MS) include fever, encephalopathy, progressive symptoms or disease course, other organ system involvement (including the peripheral nervous system), absence of CSF OCBs, elevated IgG index, and markedly elevated CSF leukocytes. [37] The more atypical features present and the younger the child, the more consideration necessary prior to diagnosing MS.

A thorough history and physical examination, serum and CSF testing, and neuroimaging will likely provide the diagnostic specificity desired to differentiate between acquired demyelinating disorders of the CNS in children and the other disorders.


Other disorders that can mimic MS include the following:

  • Endocrine: Thyroid disorder, diabetes mellitus

  • Inflammatory: Systemic lupus erythematosus (SLE), neurosarcoidosis, Sjögren syndrome, antiphospholipid antibody syndrome (APLAS), Behçet disease, isolated angiitis

  • Mitochondrial: Myoclonic epilepsy with ragged red fibers (MERRF), mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS), Leber hereditary optic neuropathy (LHON), Leigh syndrome, Kearns-Sayre syndrome

  • Leukodystrophy: Metachromatic leukodystrophy, adrenoleukodystrophy, Krabbe disease, Pelizaeus-Merzbacher disease, Refsum disease, vanishing white matter, leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate levels, Wilson disease, Fabry disease, Alexander disease

  • Genetic/metabolic: Inborn errors of metabolism, aminoacidurias

  • Infectious: Neuroborreliosis (lyme disease), HSV encephalitis, HIV infection, neurocysticercosis, poststreptococcal infection, abscess, neurosyphilis, progressive multifocal leukoencephalopathy (PML), Whipple disease

  • Vascular: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), Moyamoya disease, carotid dissection

  • Demyelinating: Clinically isolated syndrome, ADEM, optic neuritis, transverse myelitis, NMO, postvaccination, acute necrotizing encephalopathy

  • Nutritional: Vitamin B12, vitamin E, or folate deficiency; celiac disease

  • Neoplastic: Lymphoma, astrocytoma, medulloblastoma, metastases

  • Toxic: Radiation, chemotherapy (methotrexate, cyclosporine, cytosine-arabinoside), extrapontine myelinosis

  • Other: Langerhans cell histiocytosis, hemophagocytic lymphohistiocytosis