title: MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis.
abstract: Currently, it is unclear whether pediatric multiple sclerosis (PMS) is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS). Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM) and white matter (WM) tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12 years), LOPMS patients (onset ≥12 years), and healthy controls (HC). This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p < 2.2 × 10(-5)). MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p = 1.8 × 10(-4)). Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed.
authors: Bernstein Center for Computational Neuroscience Berlin, Charité - Universitätsmedizin, Berlin, Germany ; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany.
authors: Martin
authors: M
authors: Weygandt
authors: Department of Pediatrics and Pediatric Neurology, and German Center for Multiple Sclerosis in Childhood and Adolescence, University Medicine Göttingen, Germany.
authors: Hannah-Maria
authors: HM
authors: Hummel
authors: Institute of Neuroradiology, University Medicine Göttingen, Germany.
authors: Katharina
authors: K
authors: Schregel
authors: Bernstein Center for Computational Neuroscience Berlin, Charité - Universitätsmedizin, Berlin, Germany ; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany.
authors: Kerstin
authors: K
authors: Ritter
authors: Bernstein Center for Computational Neuroscience Berlin, Charité - Universitätsmedizin, Berlin, Germany.
authors: Carsten
authors: C
authors: Allefeld
authors: Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors: Esther
authors: E
authors: Dommes
authors: Department of Pediatrics and Pediatric Neurology, and German Center for Multiple Sclerosis in Childhood and Adolescence, University Medicine Göttingen, Germany.
authors: Peter
authors: P
authors: Huppke
authors: Bernstein Center for Computational Neuroscience Berlin, Charité - Universitätsmedizin, Berlin, Germany ; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany.
authors: John Dylan
authors: JD
authors: Haynes
authors: NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany ; Institute of Neuroradiology, University Medicine Göttingen, Germany.
authors: Jens
authors: J
authors: Wuerfel
authors: Department of Pediatrics and Pediatric Neurology, and German Center for Multiple Sclerosis in Childhood and Adolescence, University Medicine Göttingen, Germany.
authors: Jutta
authors: J
authors: Gärtner
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000465:Algorithms; D001921:Brain / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis*
keywords: Biomarkers; Diagnostic information; Early onset pediatric multiple sclerosis; Pediatric multiple sclerosis