Neurology India, Vol. 58, No. 3, May-June, 2010, pp. 452-456
Inflammatory demyelinating disorders of childhood: Experience with six children
Arathi Srinivasan1, Janani Sankar1, Kumaresan Ganapathi2
1 Department of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
Date of Acceptance: 01-Feb-2010
Code Number: ni10115
Demyelinating disorders of the central nervous system (CNS) in children pose diagnostic and prognostic difficulties in clinical practice. In this report, we describe our experience with inflammatory demyelinating disorders of CNS in six children, classified as per the proposed criteria by the Pediatric Multiple Sclersois Study Group. We emphasize the importance of appropriate diagnosis and follow-up to distinguish transient inflammatory demyelinating diseases from chronic inflammatory demyelinating diseases.
Keywords: Acute disseminated, demyelinations, encephalomyelitis, encephalopathy, multiple sclerosis
Acute disseminated encephalomyelitis (ADEM) is defined as a first clinical event presenting as a polysymptomatic encephalopathy with acute or sub acute onset, showing focal or multifocal hyper intense lesions predominantly affecting central nervous system (CNS) white matter. There should be no previous clinical episode or magnetic resonance imaging (MRI) evidence of demyelinating event.  Though classically ADEM is a monophasic illness, variants such as recurrent and multiphasic ADEM have been described. Recurrent ADEM implies a new demyelinating event occurring within three months after the initial event or at least four weeks after completing steroids with a recapitulation of prior illness, where as multiphasic ADEM differs in involving new areas of the brain.  ADEM per se has a favorable outcome but some of them progress to have a chronic demyelinating disease with relapses and remissions. Thus dilemma does exist regarding prognostication and the probability of developing a chronic demyelinating illness in patients with ADEM. Our experience in this case series reveals the difficulties faced during the evaluation of these cases.
Based on the clinical and neuroimaging findings six children with first CNS demyelinating event were identified to have ADEM as per the criteria defined by the International Pediatric Multiple Sclerosis (MS) Study group. All of them underwent cerebrospinal fluid (CSF) analysis and neuroimaging. CSF analysis showed mild increase in proteins in all the six children and mild lymphocytic pleocytosis in one. MRI was abnormal in all the six children revealing hyper intense white matter lesions. All of them were treated with high dose intravenous methyl prednisolone (MPS) for five days followed by oral steroids which was tapered and stopped. There was a good clinical improvement with intravenous steroid and four children had no residual neurological deficit. Two children had a relapse six months later, one of whom was diagnosed to have recurrent ADEM and the other subsequently diagnosed as a case of MS as per the proposed criteria. The details are given in [Table - 1a and Table - 1b] and [Table - 2].
At the initial presentation all the six children fulfilled the diagnostic criteria of ADEM as per the consensus definition.  Neuroimaging is the investigation of choice in ADEM,  lesions are typically large, multifocal, hyper intense and asymmetric involving the white matter.  Frequently, typical symmetrical grey matter involvement of thalami and basal ganglia are also seen. , Sequential MRI plays an important role in confirming the diagnosis of ADEM which may show either partial or complete resolution of the lesions.  All our patients showed typical lesions of ADEM on MRI [Figure - 1]. Full recovery has been reported in 50% to 80% of patients with the use of high dose intravenous methyl prednisolone for five days followed by oral steroid tapering over four to six weeks. ,, All the six children in our case series showed a rapid recovery with good neurological improvement on steroids. Though good recovery is often the case, subtle neurocongnitive deficits can be seen in these children on longterm follow-up. 
Clinically differentiating the first episode of MS from ADEM is often difficult. Diagnosis of pediatric MS requires multiple episodes of CNS demyelination separated in time and space with "positive MRI".  As per the pediatric MS study group, the second demyelinating event not meeting the criteria for recurrent or multiphasic ADEM would qualify for the initial event for pediatric MS and new T2 MRI lesions developing at least three months from the second event or a new clinical event developing at least three months subsequent to the second event are required for the diagnosis of pediatric MS.  In this series one of the child (Case 5), during the follow-up had met these criteria to be reclassified as a case of pediatric MS.
The McDonald diagnostic criteria for MS proposed in 2001  have been revised and the imaging requirements have been liberalized.  However, the adult-based MRI criteria regarding dissemination in space are not sensitive in children. In view of differences in the distribution of lesions in children, specific modifications are proposed to this adult-based MRI criteria for better diagnostic utility in children. [ni11] To diagnose pediatric MS, at least two of the three criteria have to fulfilled: (1) ≥ 5 T2 lesions (2) ≥ 2 periventricular lesions (3) ≥ 1 brainstem lesion. Recently, MRI criteria have been proposed to differentiate the first attack of MS from ADEM.  When these criteria were applied in these six children, one child (Case 5) satisfied the criteria for the diagnosis of MS [Table - 2]. These criteria require evaluation in a large sample of children for validation.
To summarize, in children it is difficult to differentiate ADEM and MS at the initial presentation. The major inflammatory demyelinating disorders of CNS in childhood are summarized in [Table - 3].  An approach to the childhood demyelinating disorders based on the recommendations by the Pediatric MS Study Group is given in [Figure - 2]. 
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