Differences and similarities in the evolution of morphologic brain abnormalities between paediatric and adult-onset multiple sclerosis

Abstract

Background:

Paediatric-onset multiple sclerosis (pMS) is multiple sclerosis (MS) occurring before the age of 18 years and may present and develop differently from adult-onset MS (aMS). Whether there are also differences regarding the accrual of brain changes is largely unknown.

Methods:

We compared the evolution of the T2- and T1-lesion load (LL), the black hole ratio (BHR), and annualised brain volume change (aBVC) between 21 pMS patients (age at onset: 14.4±2.3 years) and 21 aMS patients (age at onset: 29.4±6.5 years) matched for disease duration (pMS: 1.0±1.8 years; aMS: 1.6±1.7 years, p=0.27). Follow-up was for 4.2±3.7 years in pMS and 3.1±0.6 years in aMS. Clinical comparisons included the course of disability assessed with the Expanded Disability Status Scale (EDSS) score and annualised relapse rate (ARR).

Results:

At baseline, pMS and aMS had similar EDSS, T1-LL, BHR, whereas T2-LL was higher in aMS (aMS: 9.2±11.6 ccm; pMS: 4.1±6.2 ccm, p=0.02). The change of T2-LL and T1-LL during the observation period was similar in both groups. At follow-up, disability was lower in pMS (EDSS score in pMS: 0.9±0.9; aMS: 1.7±1.3, p=0.04), despite a significantly higher accrual of destructive brain lesions (BHR in pMS: 23.7±23.7%; aMS: 5.9±4.0%, p=0.02) and a similar rate of brain volume loss.

Conclusion:

Our observation of a morphologically more aggressive disease evolution paralleled by less disability in pMS than in aMS (defined using EDSS) suggests a higher compensatory capacity in pMS. This fact may obscure the need for treatment of pMS patients with disease modifying treatments (DMTs) based solely on clinical observation.

Keywords

multiple sclerosis MRI black holes paediatric MS

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References

Boiko

Vorobeychik

Paty

. Early onset multiple sclerosis: a longitudinal study. Neurology 2002; 59: 1006–1010.

Simone

Carrara

Tortorella

. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology 2002; 59: 1922–1928.

Renoux

Vukusic

Mikaeloff

. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007; 356: 2603–2613.

Yeh

Weinstock-Guttman

Ramanathan

. Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis. Brain 2009; 132: 3392–3400.

Waubant

Chabas

Okuda

. Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol 2009; 66: 967–971.

Balássy

Bernert

Wöber-Bingöl

. Long-term MRI observations of childhood-onset relapsing-remitting multiple sclerosis. Neuropediatrics 2001; 32: 28–37.

McAdam

Blaser

Banwell

. Pediatric tumefactive demyelination: case series and review of the literature. Pediatr Neurol 2002; 26: 18–25.

Polman

Reingold

Edan

. Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria’. Ann Neurol 2005; 58: 840–846.

Mikaeloff

Adamsbaum

Husson

. MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 2004; 127: 1942–1947.

10.

Kurtzke

. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–1452.

11.

Enzinger

Ropele

Smith

. Accelerated evolution of brain atrophy and ‘black holes’ in MS patients with APOE-epsilon 4. Ann Neurol 2004; 55: 563–569.

12.

Enzinger

Fuchs

Pichler

. Predicting the severity of relapsing-remitting MS: the contribution of cross-sectional and short-term follow-up MRI data. Mult Scler 2011; 17: 695–701.

13.

Minneboo

Uitdehaag

BMJ

Jongen

. Association between MRI parameters and the MS severity scale: a 12 year follow-up study. Mult Scler 2009; 15: 632–637.

14.

Fazekas

Soelberg-Sorensen

Comi

. MRI to monitor treatment efficacy in multiple sclerosis. J Neuroimaging 2007; 17 (Suppl 1): 50S-55S.

15.

Barkhof

Calabresi

Miller

. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 2009; 5: 256–266.

16.

Van Waesberghe

Kamphorst

De Groot

. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 1999; 46: 747–754.

17.

Fuentes

Collins

Garcia-Lorenzo

. Memory performance and normalized regional brain volumes in patients with pediatric-onset multiple sclerosis. J Int Neuropsychol Soc 2012; 10: 1–10.

18.

Rocca

Absinta

Ghezzi

. Is a preserved functional reserve a mechanism limiting clinical impairment in pediatric MS patients? Hum Brain Mapp 2009; 30: 2844–2851.

19.

Rocca

Absinta

Moiola

. Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing–remitting multiple sclerosis. Radiology 2010; 254: 541–550.

20.

Paus

Collins

Evans

. Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull 2001; 54: 255–266.

21.

Stadelmann

Brück

. Interplay between mechanisms of damage and repair in multiple sclerosis. J Neurol 2008; 255 (Suppl 1): 12–18.

22.

Fisniku

Brex

Altmann

. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131: 808–817.

23.

Truyen

van Waesberghe

van Walderveen

. Accumulation of hypointense lesions (‘black holes’) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 1996; 47: 1469–1476.

24.

Kalkers

Bergers

Castelijns

. Optimizing the association between disability and biological markers in MS. Neurology 2001; 57: 1253–1258.

25.

Fisher

Rudick

Simon

. Eight-year follow-up study of brain atrophy in patients with MS. Neurology 2002; 59: 1412–1420.

26.

Ropele

Fazekas

. Magnetization transfer MR imaging in multiple sclerosis. Neuroimaging Clin N Am 2009; 19: 27–36.

27.

Fazekas

Thompson

. New MRI techniques and ‘aggressive’ multiple sclerosis. Mult Scler 2009; 15: 283–284.

28.

Till

Ghassemi

Aubert-Broche

. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology 2011; 25: 319–332.

29.

Ghezzi

Banwell

Boyko

. The management of multiple sclerosis in children: a European view. Mult Scler 2010; 16: 1258–1267.

30.

Zivadinov

Locatelli

Cookfair

. Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy. Mult Scler 2007; 13: 490–501.