Consensus definitions for pediatric MS and other demyelinating disorders in childhood

Abstract

In light of the published 2012 International Pediatric Multiple Sclerosis Group definitions for pediatric multiple sclerosis (MS) and related disorders and given that pediatric-onset MS is now formally included in the 2010 McDonald criteria for MS, we sought to review these criteria and summarize their application in children with acquired CNS demyelination. In addition, proposals are made for definitions of no evidence of disease activity and inadequate treatment response that are important because of new therapeutic options and trials. Neurology ® 2016;87 (Suppl 2):S8-S11 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ARR 5 annualized relapse rate; CIS 5 clinically isolated syndrome; DIS 5 dissemination of inflammatory lesions in space; DIT 5 dissemination of inflammatory lesions in time; EDSS 5 Expanded Disability Status Scale; IPMSSG 5 International Pediatric Multiple Sclerosis Study Group; MOG 5 myelin oligodendroglial glycoprotein; MS 5 multiple sclerosis; NEDA 5 no evidence of disease activity; NMO 5 neuromyelitis optica; RIS 5 radiologically isolated syndrome.The International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed definitions for pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and clinically isolated syndromes (CIS) to facilitate research providing consistency in terminology.1 In 2012, these definitions were revised to incorporate advances in research and to include components of the 2010 revision of the McDonald criteria.1,2 The cornerstone of a diagnosis of MS, both in adults and children, is the demonstration of dissemination of inflammatory lesions in space (DIS) and in time (DIT) in association with clinical symptoms consistent with acquired CNS demyelination and after the careful exclusion of numerous differential diagnoses. Incorporation of the 2010 McDonald criteria (that in addition to confirming relapsing-remitting MS diagnosis on the basis of new clinical or MRI disease activity over time, also permit MS diagnosis at the time of a first clinical MS attack if the MRI fulfils specific DIS and DIT criteria) to the revised IPMSSG definitions facilitated earlier diagnosis of pediatric MS and provided inclusion criteria for new therapeutic trials (table).Our aim is to review application of the 2012 IPMSSG definitions in pediatric cohorts with acute demyelinating syndromes, discuss clinical scenarios that do not conform to the current definitions, suggest concepts regarding definition of adequate and inadequate treatment responses, and consider future research directions. 3-7 At time of first CIS, after application of the 2010 McDonald criteria to the initial brain MRI, the diagnosis of MS was met in 53%-63% of the children who subsequently developed a clinical relapse. DIT was less frequently present at initial brain MRI than DIS, which was observed in more than 80% of children. Interestingly, the inclusion of spinal cord imaging did not increase accuracy of MS diagnosis. 4,6 A follow-up MRI performed at ...

Implications of the International Paediatric Multiple Sclerosis Study Group consensus criteria for paediatric acute disseminated encephalomyelitis: a nationwide validation study

“…However, encephalopathy or multifocal neurological deficits were not a prerequisite for the diagnosis of Clinical ADEM. We then compared this ADEM cohort with the IPMSSG criteria of ADEM …”

“…Evidence‐based knowledge of the prognosis after an episode of ADEM is crucial to tailor follow‐up and counsel parents satisfactorily. Therefore, because of the need for new and more accurate ADEM criteria, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) proposed criteria for ADEM and subsequent multiple sclerosis for clinical and research purposes …”

The Secret Lives of Human Herpes Virus 6 (HHV-6)

“…But the biggest difference between childhood MS and adult MS is that, in children, the disease is due to new infection by specific adventitious environmental agents that "rile up" HHV-6, while in adults, with age and prolonged breakdown of myelin sheaths and lamellae during the disease course, the immune system becomes more and more sensitized to these breakdown products, and the disease becomes more and more an autoimmune process. In children and mid-range adults, MS tends to be relapsing-remitting [35], suggesting that repair processes are occurring [36,37], while in MS patients over 50 the progress of the disease typically becomes more progressive [35], suggesting that the immune system is losing control. The connection between the immune system and MS is reflected in the fact that immune-related drugs such as the interferons and Copaxone® were the first reasonably successful MS treatments.…”

“…Then came more specific, antibody-mediated stains such as glial fibrillary protein (GFAP) for astrocytes and myelin oligodendrocyte protein (MOG) for oligodendrocytes. The hallmark of MS is the classic plaque [33,[35][36][37], one of numerous, often extensive whitish regions in autopsy MS brain sections that stain strongly for GFAP, a marker for astrocytes, and poorly for myelin proteins, suggesting that this is a demyelinated area full of dead astrocytes, the so-called "glial scar". MS plaques also often contain evidence of inflammatory processes, such as of perivascular arrays of lymphocytes, and macrophages/microglia that stain for phagocytized myelin proteins.…”

Clinical Reasoning: A patient with a history of encephalomyelitis and recurrent optic neuritis

“…SECTION 2 The International Pediatric Multiple Sclerosis Study Group defined ADEM as a first polyfocal clinical CNS event with encephalopathy that cannot be explained by fever, presumably of inflammatory demyelinating etiology. 1 Brain MRI is abnormal during the acute phase with diffuse, poorly demarcated, large T2-hyperintense lesions involving predominantly cerebral white matter. ADEM requires that there be no new clinical or MRI findings 3 months or more after onset.…”