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.

Differentials

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

Workup

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Media Gallery

Periventricular increased T2 signal, as shown in this FLAIR image, can be seen in neuromyelitis optica given the dense concentration of aquaporin 4 water channels in this area.
Increased T2 signal at the cervicomedullary junction, as seen in a pediatric patient with MS.
An enhancing lesion in the right superior frontoparietal region. Image 4 shows the same lesion on FLAIR imaging.
FLAIR image of lesion in the right superior frontoparietal region.
This sagittal T2 image of the cervical spine shows small hyperintense lesions typical of MS at C2 C3.
This axial FLAIR image shows bilateral, left predominant confluent signal change. There is also an area of gray matter involvement in the right frontal region. This image would not be sufficient to distinguish an episode of ADEM from pediatric MS in a pre-pubertal child.

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Author

Alice K Rutatangwa, DO, MSc Fellow in Pediatric Multiple Sclerosis/Neuroimmunology, Department of Neurology, University of California, San Francisco, School of Medicine

Alice K Rutatangwa, DO, MSc is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Pediatric Academic Societies, Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Emmanuelle L Waubant, MD, PhD Professor of Clinical Neurology and Pediatrics, Director, Regional Pediatric MS Clinic at UCSF, Director, MS Fellowship Program at UCSF, University of California, San Francisco, School of Medicine; Medical Director, Nancy Davis Center Without Walls

Emmanuelle L Waubant, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Neurological Association

Disclosure: Received grant/research funds from Roche for research project; Received grant/research funds from Biogen Idec for fellowship grant; Received honoraria from Teva for speaking and teaching; Received consulting fee from Novartis for board membership; Received honoraria from Genzyme for speaking and teaching; Received honoraria from Questcor for speaking and teaching.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Tulane University School of Medicine; Pediatric Neurologist and Epileptologist, Ochsner Hospital for Children; Professor of Neurology, Louisiana State University School of Medicine

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, American Neurological Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society

Disclosure: Nothing to disclose.

Additional Contributors

Teri L Schreiner, MD, MPH Instructor, Fellow in Neuroimmunology, Children's Hospital Colorado, University of Colorado School of Medicine

Teri L Schreiner, MD, MPH is a member of the following medical societies: American Academy of Neurology, Child Neurology Society

Disclosure: Received grant/research funds from National MS Society for employment; Received consulting fee from Questcor Pharmaceuticals for consulting; Received grant/research funds from Teva Pharmaceuticals for other.

Pediatric Multiple Sclerosis Differential Diagnoses

Diagnostic Considerations

References

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