Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis: report from the US Pediatric Multiple Sclerosis Network

Charvet, Leigh; O’Donnell, EH; Belman, A. L.; Chitnis, Tanuja; Ness, J.; Parrish, Joy; Patterson, Marc C.; Rodriguez, Moses; Waubant, Emmanuelle; Weinstock‐Guttman, Bianca; Krupp, Lauren

doi:10.1177/1352458514527862

Cited by 71 publications

(56 citation statements)

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“…On the other hand, young patients with MS should be regularly followed up to monitor cognitive maturation and to screen for the possible late emergence of cognitive problems. 15 …”

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confidence: 99%

“…11 Most but not all longitudinal studies to date 6,7,[12][13][14][15] report cognitive worsening, with frequencies varying greatly across studies (table 2).…”

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confidence: 99%

“…In a US study 15 that included 62 patients with MS and 5 patients with CIS, cognitive retesting after 1.6 years showed that most patients remained stable. A total of 13% deteriorated and 20% improved on 2 or more tasks.…”

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Pediatric multiple sclerosis

et al. 2016

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In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of ageexpected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and moodrelated difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research. Neurology ® 2016;87 (Suppl 2):S82-S87 GLOSSARY BNBC 5 Brief Neuropsychological Battery for Children; CIS 5 clinically isolated syndrome; CL 5 cortical lesions; EDSS 5 Expanded Disability Status Scale; FC 5 functional connectivity; fMRI 5 functional MRI; GM 5 gray matter; MS 5 multiple sclerosis; POMS 5 pediatric-onset multiple sclerosis; SDMT 5 Symbol Digit Modalities Test; WM 5 white matter.Patients with pediatric-onset multiple sclerosis (POMS) may be particularly vulnerable to inflammation, demyelination, and axonal damage associated with multiple sclerosis (MS). 1The concurrence of these changes with myelination in the developing CNS that can go on through the third decade of life can damage networks involved in cognition.2 Research suggests loss of myelin in POMS can adversely affect cognition and academic skills.2,3 Whether brain plasticity and compensatory abilities can mitigate against disease-related pathologic changes remains unclear: answers will ultimately emerge through careful long-term studies of cognitive outcomes in POMS.PREVALENCE, NEUROPSYCHOLOGICAL PROFILE, AND CLINICAL CORRELATES Across differing test batteries and definitions of cognitive impairment, cognitive impairment is consistently reported in approximately one-third of patients with POMS (table 1). In interpreting different thresholds used to classify cognitive impairment, it is useful to note that the 5th percentile equates to 1.67 SD.In a US study of 37 POMS cases, 4 35.1% of the patients showed cognitive impairment, defined ...

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“…On the other hand, young patients with MS should be regularly followed up to monitor cognitive maturation and to screen for the possible late emergence of cognitive problems. 15 …”

mentioning

confidence: 99%

“…11 Most but not all longitudinal studies to date 6,7,[12][13][14][15] report cognitive worsening, with frequencies varying greatly across studies (table 2).…”

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confidence: 99%

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Pediatric multiple sclerosis

et al. 2016

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“…22 The tendency for very young patients with MS to manifest with polyfocal neurologic deficits and a high frequency of brainstem symptoms at onset were noted. Over the next 5 years, several key observations emerged: (1) children and adolescents experience relapsing neurologic deficits typical of adult-onset relapsingremitting MS but do not appear to experience primary progressive MS 23 ; (2) CSF analysis reveals the presence of intrathecal oligoclonal bands, a hallmark of MS in adults, in 60%-95% of pediatric patients, but less commonly in younger children 24 ; (3) over 95% of pediatric patients with MS recover well, in terms of physical functioning, from acute episodes early in their disease 25 ; (4) cognitive impairment occurs in approximately 30% of pediatric patients with MS [26][27][28][29][30][31][32] and correlates with MRI measures (reduced brain volume, altered resting state and functional connectivity, and reduced tissue integrity) [33][34][35][36][37][38] ; (5) pediatric patients with MS have higher relapse frequency in the first few years postonset, as compared to patients with adult-onset MS 39,40 ; and (6) time from first attack to secondary progressive MS (a stage of the disease characterized by progressive accrual of neurologic impairment not linked to discrete relapses) appears to take approximately 10 years longer in pediatric-onset patients, although the age at which such deficits appear occurs at a younger age than occurs in adult-onset MS.…”

Section: Pediatric Multiple Sclerosismentioning

confidence: 99%

Pediatric multiple sclerosis

Banwell

2016

Neurology

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In 1952, Sydney Carter, MD (1912MD ( -2005; Professor Emeritus, Columbia University), was asked to establish the first independent child neurology program at Columbia Presbyterian Hospital. Prior to this, children with neurologic disorders were largely cared for by general pediatricians, or on occasion, and often with trepidation, by adult neurologists. Dr. Carter recognized the unique care needs of the pediatric neurology patient. He prioritized the requirement to harmonize neuroscience and neurodevelopment, and advocated the need to identify the hallmarks of neurologic illness in the context of the developing central and peripheral nervous systems, and to foster training programs specifically in Child Neurology.It is my sincere honor to be the 2015 Sydney Carter Award recipient, and to pay service to the many colleagues whose dedication, brilliance, and compassion have contributed immeasurably to the content of this lecture. In my lecture, and herein, I summarize the learning curve and milestones achieved in pediatric multiple sclerosis (MS) care and research to date. I have endeavored to mention the work of international colleagues and to emphasize the Canadian Pediatric Demyelinating Disease program. The Canadian program began with a 3-year survey of over 2,400 pediatric health care providers 1-3 to estimate the annual incidence of acute demyelination in Canadian children. 4 Through the creation of the Canadian Pediatric Demyelinating Disease Network with funding by the Multiple Sclerosis Scientific Research Foundation, a prospective cohort (2004-present), a centralized database, biorepository, and high-quality research MRI dataset have contributed to our understanding of the clinical, genetic, epidemiologic, and imaging characteristics of MS in children.Just as Dr. Carter identified a fundamental need for pediatric neurology, formal programs for pediatriconset MS were also born from recognition of a clinical care need. Before 1980, search of the English literature yielded fewer than 30 publications on the topic of pediatric MS, and many believed that MS was a disease solely of adults (reviewed in Ref. 5). The available MS diagnostic criteria proposed by Poser et al.6 specifically excluded the diagnosis of MS in persons younger than 10 years, and did not formally comment on MS in youth. Further complicating the diagnosis and care of pediatric patients with MS is the fact that approximately 70% of pediatric patients with acute demyelination will have a transient illness without clinical or MRI evidence of new lesions over time. Acute disseminated encephalomyelitis (ADEM) typifies monophasic demyelination, particularly in young children. Distinguishing such patients from the 30% ultimately confirmed to have MS has been the focus of much of the research performed in the last 15 years. 7-9The diagnosis of MS rests on clinical features. There are no diagnostically specific genetic mutations or biomarkers for MS. Given this, an initial priority was to define the clinical features of pediatric-onset MS. Since 1980...

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“…The course of cognitive decline in MS has varied across different reports. [22][23][24][25] Uniform sensitive assessment measures and longer periods of follow-up in large patient samples could clarify issues pertinent to rate of decline, relative risk factors, and effects on academic function. Psychosocial difficulties are frequent and contribute to cognitive dysfunction: fatigue is reported in 20%-50%, depression varies from 6% to 30%, [26][27][28][29][30] and other psychiatric disorders such as anxiety can also occur.…”

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International Pediatric MS Study Group Global Members Symposium report

et al. 2016

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The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, "The World of Pediatric MS: A Global Update," in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders. While these criteria currently identify clinical and MRI features for a particular diagnosis, advances in biomarkers may prove to be useful in the future. An update was also provided on environmental factors associated with pediatric MS risk and possibly outcomes, notably vitamin D deficiency. However, optimal vitamin D intake and its role in altering MS course in children have yet to be established. Regarding MS outcomes, our understanding of the cognitive consequences of early-onset MS has grown. However, further work is needed to define the course of cognitive function and its long-term outcome in diverse patient samples and to develop strategies for effective cognitive rehabilitation specifically tailored to children and adolescents. Finally, treatment strategies were discussed, including a need to consider additional drug treatment options and paradigms (escalation vs induction), although treatment should be tailored to the individual child. Of critical importance, clinical trials of newer MS agents in children are required. Although our understanding of childhood MS has improved, further research is needed to have a positive impact for children and their families. Neurology ® 2016;87 (Suppl 2):S110-S116 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ADS 5 acute demyelinating syndrome; AQP4 5 aquaporin-4; CI 5 confidence interval; CIS 5 clinically isolated syndrome; DMT 5 disease-modifying treatment; EDSS 5 Expanded Disability Status Scale; EMA 5 European Medicines Agency; FDA 5 Food and Drug Administration; IPMSSG 5 International Pediatric MS Study Group; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; RDA 5 Recommended Dietary Allowance.Advances in our understanding of epidemiology, pathogenesis, and treatment in multiple sclerosis (MS) have been rapid in the last few years and will have a positive effect for children with the disease. Such progress in the diagnosis and management of pediatric MS and neuroinflammatory disorders includes the following:1. Revised diagnostic criteria for MS, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) across the age spectrum. 2. Improved understanding of the cognitive consequences of MS onset during childhood. 3. Additional drug treatment options, including immunosuppressant, immunomodulatory, and oral medications, and awareness of the need for clinical trials of these agents in children.

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Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis: report from the US Pediatric Multiple Sclerosis Network

Cited by 71 publications

References 25 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

Pediatric multiple sclerosis

International Pediatric MS Study Group Global Members Symposium report

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