Oligoclonal bands predict multiple sclerosis in children with optic neuritis

Heußinger, Nicole; Kontopantelis, Evangelos; Gburek‐Augustat, Janina; Jenke, Andreas; Vollrath, G.; Korinthenberg, Rudolf; Hofstetter, Peter; Meyer, Sascha; Brecht, Isabel; Kornek, Barbara; Herkenrath, Peter; Schimmel, Mareike; Wenner, Kirsten; Häusler, Martin; Lutz, S.; Karenfort, Michael; Blaschek, Astrid; Smitka, Martin; Karch, Stephanie; Piepkorn, Martin; Rostásy, Kevin; Lücke, Thomas; Weber, Peter; Trollmann, Regina; Klepper, Jörg; Häussler, Martin; Hofmann, R. R.; Weissert, Robert; Merkenschlager, Andreas; Buttmann, Mathias; Grace-Ms, for

doi:10.1002/ana.24409

Cited by 65 publications

(48 citation statements)

References 20 publications

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“…[17][18][19][20] IgG OCBs are more common in children with MS than in those with ADEM or other diseases mimicking MS. [17][18][19]21 Presence of IgG OCBs combined with an abnormal MRI was associated with a .26-fold hazard ratio for developing MS in children presenting with incident ON. 22 CSF IgM OCBs can also be found in a subset of patients with pediatric-and adult-onset MS. In adults their presence has been associated with more active/ aggressive disease, 23 but such an association has not been established in pediatric MS. 24 Of note, CSF exhibits age-related changes independent of MS disease mechanisms, particularly around puberty.…”

Section: General Aspects Of Cns Inflammatory Demyelinating Diseases Mmentioning

confidence: 98%

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

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Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric-and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatriconset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. Neurology ® 2016;87 (Suppl 2):S12-S19 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; AQP4 5 aquaporin-4; BBB 5 blood-brain barrier; CBA 5 cell-based assay; EDSS 5 Expanded Disability Status Scale; MBP 5 myelin basic protein; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 NMO spectrum disorder; OCB 5 oligoclonal band; ON 5 optic neuritis; OPC 5 oligodendrocyte precursor cell; TM 5 transverse myelitis.There is presently limited insight into the pathophysiologic mechanisms underlying childhoodonset inflammatory demyelinating diseases. Because these disorders occur in the context of the developing immune and nervous systems, understanding the implications to both disease mechanisms and efficacy and safety profiles of potential therapeutics will help guide optimal management approaches for these children and adolescents. Elucidating the biology of pediatric-onset multiple sclerosis (MS) may provide key insights into earliest targets and processes involved in disease pathogenesis as well as into the broader spectrum of CNS...

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Section: General Aspects Of Cns Inflammatory Demyelinating Diseases Mmentioning

confidence: 98%

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

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“…CSF examination, to detect intrathecal IgG synthesis, is not formally included among diagnostic criteria, nevertheless it can give an additional considerable contribution for diagnosis in patients at their first clinical episode, in addition to MRI [29,72,73].…”

Section: Clinical Aspects: How Similar To Adult Ms?mentioning

confidence: 99%

“…Two recent studies, one including patients with ON at presentation, the other one including patients with ADS, have shown that OBs are linked to a higher risk of subsequent MS, in addition and independently from the presence of lesions at brain MRI [72,73].…”

Section: Differential Diagnosis: Can Clinical Manifestations and Ancimentioning

confidence: 99%

Pediatric versus adult MS: similar or different?

Ghezzi

Baroncini

Zaffaroni

et al. 2017

Mult Scler Demyelinating Disord

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In this review the most important aspects of pediatric multiple sclerosis are presented and compared with the adult form. Some findings appear peculiar of pediatric MS: a. Clinical manifestations are similar in adolescents and adults with MS, however in very young subjects MS frequency at onset is similar in males and females, with a higher frequency of brainstem/cerebellar involvement and acute polysymptomatic/ADEM like onset; b. The course is relapsing-remitting in the large majority of patients, with a high relapse rate; c. Mild or severe disability is reached after a longer interval, but at a lower age compared to adult MS; d. The frequency of cognitive dysfunction is relatively high, with a quick deterioration but also the capability to partially recover with time; e. MRI is fundamental for diagnosis and prognosis: the pattern of MRI has some peculiar aspects in pediatric MS patients: i) the classic diagnostic criteria cannot be fulfilled, ii) lesion load is more relevant, iii) lesions are less destructive, have a more pronounced inflammatory pattern and have enhanced capability to recover with time; f. Diagnostic criteria of adults can be applied to patients with less than 18 years, but with limitations for subjects with less than 12 years and ADEM-like onset; g. The approach in differential diagnosis is particular complex and many disorders with clinical manifestations in the pediatric age must be considered: in this context it is important to pay attention to clinical, MRI and CSF red flags. Anti-MOG abs syndrome has been recently identified and should be carefully considered in patients with Acquired Demyelinating Syndrome; h. CSF oligoclonal bands are less frequent in pediatric MS patients, their presence in patients with Acquired Demyelinating Syndrome is strongly correlated to the risk of MS; i. The interplay between genetic and environmental factors determine the risk of developing MS; j. MS has a more pronounced inflammatory pattern (as suggested by the high relapse rate and the most relevant inflammatory pattern at brain MRI); k. The treatment is based on the approach used for adults: as MS has a strong impact on patients and their family the model of care should involve a team with specialized neurologists, pediatricians and neuro-pediatricians, nurses, psychologists, social workers and specialists of rehabilitative medicine.

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“…CSF oligoclonal bands were found in 80% of pediatric patients with MS and in only 15% of children with monophasic ON. 30 Twenty-six percent of patients with adult MS and 42%-58% of patients with NMO may initially present with ON alone or in combination with other neurologic deficits. 31,32 Although young children may have bilateral severe ON without experiencing recurrence, given the importance of treatment to prevent irreversible visual disability in NMOSD and the high association of serologic markers such as ANA and anti-Ro/SSA with NMOSD, severe bilateral ON, poor response to steroids, or the presence of brain or spinal cord MRI findings typical of NMOSD should lead to evaluation of serum for AQP4 antibodies and concomitant autoantibodies.…”

Section: Neurology 87 (Suppl 2) August 30 2016 S55mentioning

confidence: 99%

Pediatric optic neuritis

et al. 2016

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Optic neuritis (ON) is a common presenting symptom in pediatric CNS demyelinating disorders and may be associated with dramatic visual loss. Knowledge regarding clinical presentation, associated diseases, therapy, and outcomes in ON in children has grown over the past decade. These studies have shown that younger children (,10 years of age) are more likely to present with bilateral ON and older children with unilateral ON. Furthermore, studies focusing on visual recovery have shown excellent recovery of high-contrast visual acuity in the majority of children, but functional and structural studies have shown evidence of irreversible injury and functional decline after ON in children. Although randomized controlled treatment trials have not been performed in children and adolescents with ON, standard of care suggests that the use of highdose pulse steroids is safe and likely effective. This article reviews current knowledge about the clinical presentation and management of pediatric ON, with attention to associated syndromes and evaluative tools that may inform diagnosis and interventions. Neurology ® 2016;87 (Suppl 2): S53-S58 GLOSSARY ADEM 5 acute disseminating encephalomyelitis; AQP4 5 aquaporin-4; HCVA 5 high-contrast VA; CRION 5 chronic relapsing inflammatory optic neuropathy; IVIg 5 IV immunoglobulin; LCLA 5 low-contrast letter acuity; LCVA 5 low-contrast VA; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 NMO spectrum disorder; OCT 5 optical coherence tomography; ON 5 optic neuritis; ONTT 5 Optic Neuritis Treatment Trial; RNFL 5 retinal nerve fiber layer; TPE 5 therapeutic plasma exchange; VA 5 visual acuity; VEP 5 visual evoked potential; VF 5 visual field.

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Oligoclonal bands predict multiple sclerosis in children with optic neuritis

Cited by 65 publications

References 20 publications

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Pediatric versus adult MS: similar or different?

Pediatric optic neuritis

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