Publications in English were identified by MEDLINE searches (1975 to March, 2007), and the respective bibliographies. Search terms included “multiple sclerosis”, “acute disseminated encephalomyelitis”, “encephalomyelitis”, “transverse myelitis”, “optic neuritis”, “neuromyelitis optica”, “Devic's disease”, and the more general term “demyelination”, combined with either “child(ren)(hood)”, “pediatric(s)”, “adolescen(t)ce”, “early onset”, or “very early onset”. Single case reports or case
ReviewMultiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions
Introduction
Multiple sclerosis (MS) in children and adolescents is increasingly recognised worldwide. The disorder presents almost exclusively as a relapsing-remitting disease in children, and most recover from the initial attacks. The accumulation of disabilities and the development of secondary-progressive MS most commonly occur more than 15 years after the first attack. MRI has contributed substantially to the increasing recognition of and certainty in the diagnosis of MS in children. The potential for advanced MRI techniques to visualise fundamental features of myelin integrity and repair provides exciting opportunities for future research. Treatment is currently based on strategies optimised for adult-onset MS and seems to be safe and well tolerated, although prospective therapeutic trials in paediatric MS have not been done.
We describe the clinical, radiographic, and biological characteristics of MS and the other disorders considered in the differential diagnosis in children. We also describe current therapeutic practice and discuss avenues of future research.
Section snippets
Acute demyelination of the CNS
The first acute demyelinating event, termed a clinically isolated syndrome, can manifest with signs and symptoms caused by a single lesion (monofocal clinically isolated syndrome) or with polyfocal features, implicating multiple lesions. There are published clinical definitions for these various clinical demyelinating presentations (figure 1).1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23
In a prospective study of 296 children with acute demyelination, 81
Differential diagnosis
A cornerstone of the diagnosis of MS in adults and children rests on showing lesion dissemination in space and time and the exclusion of other disorders.7 One approach to discount disorders in the differential diagnosis of acute CNS demyelination was set out in a recent consensus article (figure 2 and webfigure).50 CNS infection and intracerebral malignancy must always be considered. Although CNS lymphoma is rare in children, intracallosal involvement can be similar to the white-matter lesions
Characteristics of child-onset MS
An estimated 3–10% of all patients with MS have onset before the age of 18 years.71, 94, 95, 96, 97 The true frequency of paediatric MS will be determined only from prospective studies from both paediatric and adult clinical centres.
Disability and outcome
Kurtzke's expanded disability status scale (EDSS) is the most common measure of physical neurological sequelae in adults and children with MS (table 3),68, 73, 94, 96, 105 although the measure has several key limitations (non-linear ordinals, wide intraobserver and interobserver variability, and, essentially, exclusive weighting of motor dysfunction at the higher range of the scale).
In a prospective study of 54 children or adolescents with MS disease duration of 8 years or longer, 36 had an
Management
The care of children with MS needs a multidisciplinary team comprising paediatric and adult neurologists, nurses, physiotherapists, occupational therapists, social workers, psychologists, and psychiatrists.130 The diagnosis of chronic illness has substantial emotional effects on children with MS and their families. Compliance with medication, particularly in adolescents, rests on a strong relationship between medical teams, patients, and parents.
Genetic studies
HLA-DR2 was more common in 47 children154 and adults155 with MS from Russia than in the general population. Unlike in adults from the same region with MS, a high prevalence of the TNFα 7 allele was also found, and this was proposed as a potential biomarker for paediatric MS.156 By contrast, a study of 24 children with MS in Turkey did not detect MS-specific TNFα mutations.157 Genetic studies of MOG, the gene encoding myelin oligodendrocyte glycoprotein, located in close proximity to the HLA
Conclusions
The diagnosis and care of children with MS will be helped by the recognition of the presenting features of the disease, the use of MRI, and the laboratory exclusion of the other disorders considered in the differential. Consensus criteria for the diagnosis of paediatric MS now exist, and the development of evidence-based radiographic criteria will promote even greater diagnostic certainty. Immunomodulatory therapies are well tolerated and efficacious, although prospective studies are required
Search strategy and selection criteria
References (180)
Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions
Semin Pediatr Neurol
(2000)- et al.
A case of relapsing acute disseminated encephalomyelitis with high dose corticosteroid treatment
Brain Dev
(1999) - et al.
First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability
J Pediatr
(2004) - et al.
Optic neuritis in children: recurrence and subsequent development of multiple sclerosis
Pediatr Neurol
(1995) - et al.
Rapid recovery from transverse myelopathy in children treated with methylprednisolone
Pediatr Neurol
(1998) - et al.
Transverse myelitis in children: long-term urological outcomes
J Urol
(2006) - et al.
Neuromyelitis optica (Devic syndrome) in a 12-year-old male in a blinded fashionwith complete recovery following steroids
Pediatr Neurol
(1987) - et al.
Neurocognitive outcome after acute disseminated encephalomyelitis
Pediatr Neurol
(2003) - et al.
Optical coherence tomography in multiple sclerosis
Lancet Neurol
(2006) - et al.
Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse
Eur J Paediatr Neurol
(2007)