MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

Till, Christine; Ghassemi, Rezwan; Aubert-Broche, Bérengère; Kerbrat, Anne; Collins, D. Louis; Narayanan, Sridar; Arnold, Douglas L.; Desrocher, Mary; Sled, John G.; Banwell, Brenda

doi:10.1037/a0022051

Cited by 148 publications

(198 citation statements)

References 65 publications

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“…In one study, global brain volume loss in GM was correlated with lower estimated IQ and reduced information processing speed. 8 In another study, 16 more severe damage to GM, especially in the right precuneus and left middle temporal gyrus, was found in cognitively impaired as compared with cognitively preserved patients. In contrast with adult MS studies, using double inversion recovery sequences, the number and volume of cortical lesions (CL) did not differ between cognitively preserved (CL 12%) and impaired (CL 15%) pediatric patients.…”

Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 92%

“…8 Using lesion probability mapping, Rocca et al 16 showed that cognitively impaired relative to cognitively preserved patients were more likely to harbor lesions in the right thalamus, middle and posterior corpus callosum, and bilateral parieto-occipital WM, implicating a posterior pattern of pathology that contributes to cognitive impairment in POMS.…”

Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 99%

“…In contrast with adult MS studies, using double inversion recovery sequences, the number and volume of cortical lesions (CL) did not differ between cognitively preserved (CL 12%) and impaired (CL 15%) pediatric patients. 22 In a study of 35 patients with POMS, 8 the volume of thalamus, which has a key integrative role in diverse cognitive abilities and is vulnerable to pathologic involvement in pediatric MS, emerged as the most robust MRI predictor of global functional outcomes, as well as measures of mental processing speed, visuomotor integration, and vocabulary. Only regional structures (thalamic volume and corpus callosum area), and not global atrophy measures, differentiated patients with POMS identified as having cognitive impairment from those without.…”

Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 99%

“…Longitudinal data of this cohort over 5 years demonstrated declines for most participants, associated with adverse consequences on school achievements and social life. 6,7 A study of 35 Canadian patients with POMS and a similar number of controls 8 showed reduction in functioning predominantly on measures of attention and processing speed (38%), visuomotor integration (23.5%), and expressive vocabulary (9.7%). Full-scale IQ and verbal IQ were significantly reduced in the MS vs control group, though only 5 of the 35 patients (14.3%) were reported to have a full-scale IQ that was below average (i.e., IQ ,85).…”

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confidence: 99%

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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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Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 92%

Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 99%

Section: Mri Correlates Of Cognitive Impairmentmentioning

confidence: 99%

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confidence: 99%

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Pediatric multiple sclerosis

et al. 2016

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“…16 Time to further relapses is not established. EDSS, frequently used for secondary endpoints in adult studies, is typically low in children with MS, 8 18,19 Since accrual of physical disability is rarely observed in the pediatric age group, correlations between EDSS and MRI features may not be robust. Ongoing studies will clarify whether accrual of lesions in pediatric MS is an acceptable surrogate for clinical relapses in clinical trials.…”

Section: Resultsmentioning

confidence: 99%

International Pediatric MS Study Group Clinical Trials Summit

et al. 2013

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Objective: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research.Methods: The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions. Results:The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge. Conclusion:Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders. There are limited studies informing the use of disease-modifying treatments in children with multiple sclerosis (MS). 1 No therapies are approved for pediatric MS by the US Food and Drug Administration (FDA), and only limited interferon use in adolescents with MS has been approved by the European Medicines Agency (EMA).1 As in adults, close to 40% of pediatric patients with MS discontinue treatment due to intolerance, toxicity, persisting relapses, or nonadherence, supporting the need for new therapeutic options in children.2 Several new molecules have shown efficacy in phase III trials and could be available in the near future for adults with MS.

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Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis

Mistri,

Margoni,

Pagani

et al. 2024

Ann Clin Transl Neurol

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ObjectiveThe present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS).MethodsPedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K‐means clustering on cognitive scores. MRI metrics included brain T2‐hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting‐state (RS) functional connectivity (FC) were estimated.ResultsThree cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005).InterpretationWe identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

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MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

Cited by 148 publications

References 65 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

International Pediatric MS Study Group Clinical Trials Summit

Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis

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