Diagnostic algorithm for relapsing acquired demyelinating syndromes in children

Hacohen, Yael; Mankad, Kshitij; Chong, W.K.; Barkhof, Frederik; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Ciccarelli, Olga; Hemingway, Cheryl

doi:10.1212/wnl.0000000000004117

Cited by 158 publications

(173 citation statements)

References 40 publications

(38 reference statements)

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“…Brain imaging was not particularly differentiating for the MOG‐TM group. In a recent study by Hacohen et al . brain stem and cerebellar lesions were seen with high prevalence in patients who were MOG positive, but this was not a common finding in our cohort.…”

Section: Discussioncontrasting

confidence: 68%

Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children

Tantsis

Prelog

Alper

et al. 2018

Develop Med Child Neuro

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Aim We used magnetic resonance imaging (MRI) to compare the neuroimaging of children with their first episode of clinical enterovirus 71‐associated transverse myelitis (EV71‐TM), myelin oligodendrocyte glycoprotein antibody positive transverse myelitis (MOG‐TM), aquaporin‐4 antibody positive transverse myelitis (AQP4‐TM), transverse myelitis in multiple sclerosis (MS‐TM), and unclassified transverse myelitis (UNC‐TM). Method We performed a retrospective blinded radiological assessment and compared the neuroimaging of 52 children (32 females, 20 males; mean age 9y 8mo, SD 5y 5mo, range 5mo–17y) presenting with their first episode of myelitis caused by EV71‐TM (n=11), MOG‐TM (n=10), AQP4‐TM (n=9), MS‐TM (n=13), and UNC‐TM (n=9). Results In the EV71‐TM group, lesions were distributed throughout the cord and enhancement of nerve roots (ventral and dorsal) was common. The MOG‐TM group had lesions distributed throughout the cord and most commonly longitudinally extensive transverse myelitis and lesions involving the grey matter alone on axial scans. The AQP4‐TM group had lesions distributed in the cervicothoracic spine, cavitation, and contrast enhancing lesions. All patients with AQP4‐TM had an abnormal brain MRI scan. The MS‐TM group characteristically had multiple short segment lesions of the cord involving the cervicothoracic spine. The UNC‐TM group did not have distinctive spinal MRI findings but had a relative paucity of lesions on their brain MRI scans. Interpretation There are neuroimaging findings that are helpful in differentiating between myelitis associated with EV71, MOG, AQP4, and multiple sclerosis in children. These features may be useful early in the presentation of transverse myelitis while awaiting infectious/immunological testing, and/or further demyelinating events. What this paper adds Magnetic resonance imaging can help identify aetiologies for children presenting with a first episode of myelitis. Entervirus‐71‐associated myelitis lesions are distributed throughout the cord and enhancement of nerve roots is common. Lesions distributed throughout the cord are commonly seen in myelin oligodendrocyte‐associated myelitis. Aquaporin‐4‐associated myelitis lesions are distributed in the cervicothoracic spine, cavitation and contrast enhancing lesions are common. Short segment lesions in the cervicothoracic spine are commonly seen in multiple sclerosis‐associated myelitis.

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Section: Discussioncontrasting

confidence: 68%

Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children

Tantsis

Prelog

Alper

et al. 2018

Develop Med Child Neuro

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“…In a recent paper, we proposed four main relapsing ADS: multiple sclerosis, AQP4‐Ab‐associated disease, MOG‐Ab‐associated disease, and antibody‐negative relapsing ADS . In this retrospective study, 98.4% of patients with multiple sclerosis had typical MRI with T2‐hyperintense lesions at onset; a neuroradiologist blinded to the clinical features and antibody status of each case correctly classified 93.6% of multiple sclerosis cases and 100% of non‐multiple sclerosis cases.…”

Section: Paediatric Relapsing Demyelinating Syndromes: Multiple Sclermentioning

confidence: 95%

“…Commonly acquired childhood infections have been implicated in the pathogenesis of paediatric multiple sclerosis; however, the interpretation of association is complex and genetic factors are likely to affect this. A history of remote EBV infection was reported in all (62 out of 62) paediatric patients with multiple sclerosis compared with 42% in patients with non‐multiple‐sclerosis relapsing demyelination in one study . In a case–control study of 189 paediatric patients with multiple sclerosis and 66 comparison individuals, EBV nuclear antigen‐1 seropositivity was significantly associated with multiple sclerosis independently of age, sex, ethnicity, and HLA‐DRB1*1501 / 1503 status .…”

Section: Environmental and Genetic Risk Factors: The Complex Interplaymentioning

confidence: 97%

“…Younger children more typically present with many supratentorial brain lesions, whereas older children and adults commonly present with optic neuritis. Patients who are MOG‐Ab‐positive are less likely than those with multiple sclerosis to have intrathecal OCBs and may have cerebrospinal fluid pleocytosis . Of note, many patients originally diagnosed with paediatric multiple sclerosis have been reclassified as having MOG‐Ab‐associated demyelination in recent years.…”

Section: Paediatric Relapsing Demyelinating Syndromes: Multiple Sclermentioning

confidence: 99%

“…Additionally, greater emphasis has been placed on the earlier exclusion of multiple sclerosis mimics to avoid misdiagnosis. Recently, the improved understanding of antibody‐mediated demyelination has led to a marked change in the classification of relapsing demyelinating syndromes, the importance of which has been emphasized by recent studies demonstrating the need for different first‐line treatments in myelin oligodendrocyte glycoprotein antibody (MOG‐Ab)‐associated disease compared with multiple sclerosis …”

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confidence: 99%

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Paediatric multiple sclerosis: a new era in diagnosis and treatment

Duignan

Brownlee

Wassmer

et al. 2019

Develop Med Child Neuro

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Multiple sclerosis is a chronic immune‐mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) and aquaporin‐A antibodies (AQP4‐Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long‐term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow‐up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long‐term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short‐ and long‐term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon‐β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. What this paper adds Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody‐mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

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Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease

et al. 2018

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Diagnostic algorithm for relapsing acquired demyelinating syndromes in children

Abstract: Children with MS and AQP4-Ab NMOSD showed features typical of adult cases. Because MOG-Ab-positive children showed notable and distinctive clinical and MRI features, they were grouped into a unified phenotype (MOG-Ab-associated disease), included in a new diagnostic algorithm.

Cited by 158 publications

References 40 publications

Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children

Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children

Paediatric multiple sclerosis: a new era in diagnosis and treatment

Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease

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