Diagnosis and Differential Diagnosis

There are a number of conditions that can mimic pediatric MS. These include certain infections, other disorders of increased inflammation such as lupus, nutritional deficiencies, and inherited disorders. Some children develop new neurological symptoms with confusion or lethargy shortly following a viral illness or fever. This is called acute disseminated encephalomyelitis (ADEM). ADEM is different from MS because most often symptoms only occur once and there are no further “attacks”. Further information can be found  on “ other demyelinating disorders.”

The diagnosis of pediatric MS is usually made by a combination of clinical features, typically repeated “attacks” of new neurological symptoms, and a characteristic appearance of brain lesions on MRI scans. Checking the blood and spinal fluid using a test called a lumbar puncture (also known as a spinal tap) helps rule out the other conditions that may present just like childhood MS. Up to 90% of children with MS have antibodies detectable in spinal fluid that are not detectable in blood (oligoclonal bands or OCBs).1, 2 OCBs may be more likely to be present in older children and if absent at baseline may be detected on repeat CSF testing later on in the disease course.3, 4 Evoked potentials, electrical tests that help that measure how fast the nerves respond to stimulation, may also be used to help with the diagnosis.

Defining MS and other demyelinating disorders

In 2007 and in 2012, the International Pediatric Multiple Sclerosis Group (IPMSSG) published definitions for pediatric multiple sclerosis (MS) and related disorders. (hyperlink to both papers) Since 2012, the definitions have been used and evaluated in several large cohorts of children (groups that can be studied over time) around the world. For further information, read a recent IPMSSG review, “Consensus definitions for pediatric MS and other demyelinating disorders in childhood.

Disease that mimic MS

A recent paper (hyperlink to MISF paper and neurology supplement paper) reviews the definitions in light of this experience and proposes two amendments – one related to the use of the 2010 McDonald criteria for diagnosing MS in children, and the other related to the diagnosis of neuromyelitis (NMO) spectrum disorders. In addition, the new concepts of radiologically isolated syndrome (RIS), “no evidence of disease activity” (NEDA), and definition of treatment response – which are prominent in the literature dealing with adult MS – are discussed for their meaning in children with MS.

Defining MS and other demyelinating disorders and diseases that mimic MS

Despite these advances, the existence of a number of diseases that can mimic an acute inflammatory demyelinating event – including other inflammatory disorders of the white matter, primary tumors in the CNS and neurometabolic diseases (disorders resulting from a lack or dysfunction of an enzyme which affects the development or functioning of the nervous system) – can make the diagnosis of pediatric inflammatory demyelinating disorders very challenging. Physicians need to be aware of these mimics in order to arrive at the correct diagnosis and treatment recommendations. For further information, read “Differential diagnosis and evaulation in pediatics inflammatory demeylinating disorders.”

Another summary to read is Am I missing something? Is it MS? Is it NMO? It discusses MS criteria, prognostic markers in pediatric MS, differential diagnosis of children with an acute demyelinating event and brain biopsy, the role of MOG antibodies in the differential diagnosis, and NMO criteria and how it differs from MS in diagnosis and management of unclear cases.

1. Ghezzi A, Pozzilli C, Liguori M, et al. Prospective study of multiple sclerosis with early onset. Mult Scler 2002;8:115-118.
2. Pohl D, Rostasy K, Reiber H, Hanefeld F. CSF characteristics in early-onset multiple sclerosis. Neurology 2004;63:1966-1967.
3. Mikaeloff Y, Caridade G, Assi S, Suissa S, Tardieu M. Prognostic factors for early severity in a childhood multiple sclerosis cohort. Pediatrics 2006;118:1133-1139.
4. Chabas D, Ness J, Belman A, et al. Younger children with MS have a distinct CSF inflammatory profile at disease onset. Neurology 2010;74:399-405.