این مقاله بررسی میکند که کودکان مبتلا به بیماری مولتیپل اسکلروزیس (MS) از ابتدا تا شروع علائم بالینی، نسبت به کودکان سالم، استفاده بیشتری از خدمات درمانی داشتهاند و این تفاوتها حتی از سالهای قبلِ تشخیص بیماری قابل مشاهده است. یافتهها نشان داد کودکان مبتلا به MS از شش سال پیش از تشخیص (به ویژه در ویزیتهای پزشک و بستری شدن)، میزان استفاده بیشتری از خدمات درمانی دارند؛ این روند با نزدیک شدن به زمان تشخیص، افزایش می یابد
تفاوتها در نوجوانی و با نزدیک شدن زمان ابتلا بارزتر شد. بحث و اهمیت نتایج بر اساس این مطالعه، احتمال وجود مرحله اولیه (پرودروم) بیماری MS در کودکان طی چند سال پیش از ظهور علائم کلاسیک وجود دارد که میتواند شامل افزایش مراجعات به پزشک، بستری یا مشکلات عصبی و روانی باشد. وجود تفاوت قابل توجه در سالهای ابتدایی زندگی، فرضیه نقش عوامل محیطی و مادری-جنینی در بروز MS را مطرح میکند. بنابراین، دوران کودکی به ویژه سالهای اولیه، دوره مهمی در شکلگیری یا تشدید عوامل خطر بیماری MS محسوب میشود. این تفاوت میتواند نشانه آغاز پنهان بیماری باشد و نقش فعالیتهای پیشگیرانه و تشخیص زودهنگام را برجسته میسازد
Abstract
Background: Investigations of a prodrome in multiple sclerosis (MS) usually have included adults.
Objective: To compare rates and reasons for health care use in youth with and without MS, considering time relative to the MS index date and to birth.
Methods: This retrospective cohort study used population-based administrative data (1991–2020) from Ontario, Canada. We matched youth (<18 years) with MS up to 5:1 to youth without MS by sex, birth year, region, and duration of observation (full cohorts). Subcohorts had data from birth to MS index date (first demyelinating disease claim). We compared health services use, adjusting for age, sex, area-level income, region, and year.
Results: We included 451 individuals with pediatric-onset MS and 1422 without MS. As of 6 years pre-index, the full MS cohort had higher physician services use (year 6: rate ratio (RR) = 1.45; 95% confidence interval (95% CI) = 1.25–1.67) and hospitalizations (RR = 2.79; 95% CI = 1.31–5.94). Findings were similar in subcohorts. The MS subcohort had elevated physician visit rates in early life that rose as the MS index date approached.
Discussion: Youth with pediatric-onset MS exhibit increased health care use from birth. Early life may be a risk period for MS. A prodromal phase may emerge 6 years before the onset of typical MS symptoms.
Keywords: Multiple sclerosis, administrative data, health care use, pediatric
Date received: 23 December 2024; revised: 22 March 2025; accepted: 11 April 2025
Introduction
Multiple reports indicate changes in health care use preceding presentation with multiple sclerosis (MS) by 5–10 years, observed using clinical or administrative databases.¹² These changes in health care use could reflect prodromal disease; rises in serum neurofilament light chain levels 6–10 before clinical presentation biologically support this concept.³⁴ The identification of prodromal disease could lead to earlier intervention and clarify the etiologically relevant period for preventing MS.
Most studies have focused on adult populations¹² in which confounding may occur due to comorbidities, diagnostic delays, and unrelated life experiences. Pediatric populations have a lower comorbidity burden and fewer irrelevant events, offering the opportunity to better characterize the features and onset of prodromal disease. A German study reported that obesity, vision disorders, and skin sensation disturbances were more common 5 years before a first MS diagnostic code among youth with MS than those without MS or with juvenile inflammatory arthritis.⁵ This study was limited to physician billings, suggesting further exploration of health care use preceding presentation with pediatric-onset MS is warranted. However, fluctuations in health care use in childhood related to well-childcare must be considered.
We used population-based data to compare rates of and reasons for hospitalizations and physician services use in youth with and without MS, considering time relative to the MS index date and time relative to birth.
Correspondence to:
RA Marrie
Department of Medicine,
Faculty of Medicine,
Dalhousie University, 487
Bethune Building, 1276
Ruth Park Street, Halifax,
NS B3H 2Y9, Canada
ruthann.marrie@dal.ca
Ruth Ann Marrie
Departments of Medicine
and Community Health
and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS,
Canada Department of Medicine, Nova Scotia
Health, Halifax, NS, Canada
Colleen J Maxwell
School of Pharmacy,
University of Waterloo,
Waterloo, ON, Canada;
ICES, Toronto, ON, Canada
Karl Everett
Ping Li
ICES, Toronto, ON, Canada
Feng Zhu
Yinshan Zhao
Helen Tremlett
Neurology, Faculty of Medicine, The University of British Columbia,
Vancouver, BC, Canada;
Digital Wavelength Centre for Brain Health,
The University of British Columbia, Vancouver, BC, Canada
Kyla A McKay
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm
Sweden Center for Molecular Medicine, Karolinska University Hospital,
Stockholm, Sweden
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