Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis

Background: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON. Objective: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity. Methods: Eleven youth living with pediatric-onset MS (ylPOMS) and no previous history of optic neuritis and 18 controls underwent standardized brain MRI, optical coherence tomography (OCT), Magnetoencephalography (MEG)-Visual Evoked Potentials (VEPs), and visual battery. Data were analyzed with mixed effect models. Results: While ON volume, OCT parameters, occipital MEG-VEPs outcomes, and visual function did not differ significantly between ylPOMS and controls, ylPOMS had lower MTsat in the supratentorial normal appearing white matter (−0.26 nU, p = 0.0023), and in both in the ON (−0.62 nU, p < 0.001) and in the normal appearing white matter of the optic radiation (−0.56 nU, p = 0.00071), with these being positively correlated (+0.57 nU, p = 0.00037). Conclusions: Subclinical microstructural injury affects the ON of ylPOMS. This may appear as MTsat changes before being detectable by other currently available testing.

[1]  M. Paley,et al.  Recent advances on optic nerve magnetic resonance imaging and post-processing. , 2021, Magnetic resonance imaging.

[2]  E. Waubant,et al.  Interocular Difference in Retinal Nerve Fiber Layer Thickness Predicts Optic Neuritis in Pediatric-Onset Multiple Sclerosis , 2020, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[3]  T. Witzel,et al.  Axonal damage in the optic radiation assessed by white matter tract integrity metrics is associated with retinal thinning in multiple sclerosis , 2020, NeuroImage: Clinical.

[4]  David H. Miller,et al.  Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria , 2017, The Lancet Neurology.

[5]  Bailey A. Box,et al.  Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis , 2017, Multiple sclerosis journal - experimental, translational and clinical.

[6]  M. Sormani,et al.  Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis , 2017, PloS one.

[7]  T. Aleman,et al.  Optical coherence tomography and visual evoked potentials in pediatric MS , 2017, Neurology: Neuroimmunology & Neuroinflammation.

[8]  Massimo Filippi,et al.  White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders , 2017, Brain : a journal of neurology.

[9]  E. Waubant,et al.  Sex differences and subclinical retinal injury in pediatric-onset MS , 2017, Multiple sclerosis.

[10]  Lynn D. Hudson,et al.  Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis , 2017, Multiple sclerosis.

[11]  Snehashis Roy,et al.  Optical coherence tomography reflects brain atrophy in multiple sclerosis: A four‐year study , 2015, Annals of neurology.

[12]  Avnish Kumar,et al.  Visual Evoked Potentials: Normative Values and Gender Differences. , 2015, Journal of clinical and diagnostic research : JCDR.

[13]  Vladimir S Fonov,et al.  Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth , 2014, Neurology.

[14]  Jacqueline A Palace,et al.  Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. , 2014, JAMA neurology.

[15]  Shinichi Nakagawa,et al.  A general and simple method for obtaining R2 from generalized linear mixed‐effects models , 2013 .

[16]  G. Egan,et al.  Correction: Optic Nerve Magnetisation Transfer Ratio after Acute Optic Neuritis Predicts Axonal and Visual Outcomes , 2012, PLoS ONE.

[17]  G. Egan,et al.  Optic Nerve Magnetisation Transfer Ratio after Acute Optic Neuritis Predicts Axonal and Visual Outcomes , 2012, PloS one.

[18]  Axel Petzold,et al.  The OSCAR-IB Consensus Criteria for Retinal OCT Quality Assessment , 2012, PloS one.

[19]  Massimo Filippi,et al.  Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis. , 2010, Radiology.

[20]  Amy Conger,et al.  Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: A pilot study , 2009, Journal of the Neurological Sciences.

[21]  M. Ramanathan,et al.  Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset , 2009, Multiple sclerosis.

[22]  P. Dechent,et al.  High‐resolution maps of magnetization transfer with inherent correction for RF inhomogeneity and T1 relaxation obtained from 3D FLASH MRI , 2008, Magnetic resonance in medicine.

[23]  David H. Miller,et al.  Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation , 2008, Magnetic resonance in medicine.

[24]  Brian B. Avants,et al.  Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain , 2008, Medical Image Anal..

[25]  David H. Miller,et al.  An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. , 2007, Brain : a journal of neurology.

[26]  Eliza M. Gordon-Lipkin,et al.  Optical coherence tomography and disease subtype in multiple sclerosis , 2007, Neurology.

[27]  D. Miller,et al.  Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis , 2007, Multiple sclerosis.

[28]  F. Hanefeld,et al.  Pediatric multiple sclerosis: detection of clinically silent lesions by multimodal evoked potentials. , 2006, The Journal of pediatrics.

[29]  Stephen J. Jones,et al.  A serial MRI study following optic nerve mean area in acute optic neuritis. , 2004, Brain : a journal of neurology.

[30]  Stephen J. Jones,et al.  Optic nerve diffusion measurement from diffusion-weighted imaging in optic neuritis. , 2004, AJNR. American journal of neuroradiology.

[31]  Stephen J. Jones,et al.  Serial magnetization transfer imaging in acute optic neuritis. , 2003, Brain : a journal of neurology.

[32]  Massimo Filippi,et al.  Irreversible disability and tissue loss in multiple sclerosis: a conventional and magnetization transfer magnetic resonance imaging study of the optic nerves. , 2002, Archives of neurology.

[33]  B K Rutt,et al.  Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS , 2000, Journal of magnetic resonance imaging : JMRI.

[34]  G. Barker,et al.  Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI , 1996, Neuroradiology.

[35]  G J Barker,et al.  Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[36]  W. Mcdonald,et al.  Visual Evoked Response in Diagnosis of Multiple Sclerosis , 1973, British medical journal.

[37]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[38]  D. MacManus,et al.  STIR sequences in NMR imaging of the optic nerve , 2004, Neuroradiology.