Prof. Maria Pia Amato

Cognition in pediatric-onset multiple sclerosis

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Patients with onset of multiple sclerosis (MS) before the age of 18 years represent 3-10% of the whole MS population. Research in the field has progressively increased over the past decade and different research groups in the world are performing more  systematic research in order to assess the prevalence of cognitive problems in this population, the neuropsychological profile and the functional impact.  Pediatric patients may be particularly vulnerable to inflammation, demyelination and axonal damage associated with MS.  The concurrence of these changes with myelination in the developing central nervous system (CNS) can damage networks involved in cognitionand research suggests loss of myelin in these patients can adversely affect cognition.  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. 

Based on available evidence, across differing test batteries and definitions of cognitive impairment, cognitive impairment is consistently reported in approximately one-third of pediatric patients (1). The neuropsychological profile is similar to that of adult-onset MS-- showing prominent involvement of complex attention, processing speed and memory-- except that pediatric  patients are more likely to show problems with linguistic skills and general intelligence, possibly associated with younger age at MS onset.

In an Italian, longitudinal  study (2), the follow-up over five years of a cohort of  children and adolescents with MS demonstrated declines in cognitive abilities for a sizeable proportion participants. A US study has also shown that cognitive problems in this population are often associated with psychiatric problems, especially depression and anxiety (3). 

The behavioral, cognitive, and physical changes of pediatric MS clearly take a toll. Grade retention can occur (4), while other aspects of academic functioning, social functioning and engaging in hobbies can all be adversely affected.  Early detection can hopefully lead to counseling,  provision of support services, and efforts at cognitive remediation through rehabilitation strategies specifically targeted to the needs of this young population.  

Future research  in field is warranted (5) and should include further characterization of the neuropsychological  profile in relation to age, risk factors and the potential protective role of cognitive reserve and intellectual enrichment; cognitive and functional outcomes in the adult life; potential role of treatment with disease modifying drugs in preventing/delaying cognitive problems; better understanding of brain changes underlying cognitive impairment and compensatory mechanisms; development  of test batteries that can facilitate international comparisons and collaborative research, finally interventions that can preserve cognitive function and improve behavioral outcomes and quality of life.

References

1. Amato MP, Krupp LB, Charvet LE, Penner I, Till C. Pediatric multiple sclerosis: Cognition and mood. Neurology. 2016 Aug 30;87(9 Suppl 2):S82-7

2. Amato MP, Goretti B, Ghezzi A, Hakiki B, Niccolai C, Lori S, et al.  Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up. Neurology 2014;83(16):1432-1438

3. Weisbrot D, Charvet L, Serafin D, Milazzo M, Preston T, Cleary R, Moadel T, Seibert M, Belman A, Krupp L. Psychiatric diagnoses and cognitive impairment in pediatric multiple sclerosis. Mult Scler. 2014 Apr;20(5):588-9

4. Mikaeloff Y, Caridade G, Billard C, Bouyer J, Tardieu M. School performance in a cohort of children with CNS inflammatory demyelination. Eur J Paediatr Neurol 2010;14(5):418-424

5. Benedict RHB, DeLuca J, Enzinger C, Geurts JJG, Krupp LB, Rao SM. Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward. J Int Neuropsychol Soc. 2017 Oct;23(9-10):832-842