Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course

TY - JOUR

T1 - Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course

AU - Groeschel, Samuel

AU - Kehrer, Christiane

AU - Engel, Corinna

AU - I Dali, Christine

AU - Bley, Annette

AU - Steinfeld, Robert

AU - Grodd, Wolfgang

AU - Krägeloh-Mann, Ingeborg

PY - 2011/10

Y1 - 2011/10

N2 - OBJECTIVE: Metachromatic Leukodystrophy (MLD) is a rare disorder leading to demyelination and neurological impairment. A natural history study within the German leukodystrophy network analyzed MRI changes with respect to the clinical course.METHODS: 113 MR images of 68 patients (33 late-infantile, 35 juvenile) were studied cross-sectionally and longitudinally. MRI and motor deterioration were assessed using standardized scoring systems.RESULTS: The temporal and spatial patterns of MR severity scores differed between the late-infantile and juvenile form. Although early (involving central white matter, corpus callosum) and late signs (involving pons, cerebellum, cerebral atrophy) were similar, high MRI scores (mean 18, SD 1.2, p < 0.001) were evident in the juvenile form already at the onset of first symptoms and even in presymptomatic patients. The progression rate of the MRI score was clearly higher and more uniform in the late-infantile (on average 8 per year, p < 0.0001) than in the juvenile patients (on average 0.4 per year, p < 0.08). In late-infantile patients, MRI changes correlated highly with motor deterioration (rho = 0.73, p < 0.001), this was less remarkable in the juvenile form (rho = 0.50, p < 0.01). Severe motor dysfunction was associated with U-fiber involvement and cerebellar changes (p < 0.05).CONCLUSIONS: MRI showed a typical spatial pattern, which evolved gradually and uniformly during disease progression in late-infantile MLD. In juvenile MLD MRI changes were already observed at disease onset and temporal patterns were more variable. As therapeutic options for MLD are evolving, these findings are not only important for patient counseling but also for the evaluation of therapeutic interventions.

AB - OBJECTIVE: Metachromatic Leukodystrophy (MLD) is a rare disorder leading to demyelination and neurological impairment. A natural history study within the German leukodystrophy network analyzed MRI changes with respect to the clinical course.METHODS: 113 MR images of 68 patients (33 late-infantile, 35 juvenile) were studied cross-sectionally and longitudinally. MRI and motor deterioration were assessed using standardized scoring systems.RESULTS: The temporal and spatial patterns of MR severity scores differed between the late-infantile and juvenile form. Although early (involving central white matter, corpus callosum) and late signs (involving pons, cerebellum, cerebral atrophy) were similar, high MRI scores (mean 18, SD 1.2, p < 0.001) were evident in the juvenile form already at the onset of first symptoms and even in presymptomatic patients. The progression rate of the MRI score was clearly higher and more uniform in the late-infantile (on average 8 per year, p < 0.0001) than in the juvenile patients (on average 0.4 per year, p < 0.08). In late-infantile patients, MRI changes correlated highly with motor deterioration (rho = 0.73, p < 0.001), this was less remarkable in the juvenile form (rho = 0.50, p < 0.01). Severe motor dysfunction was associated with U-fiber involvement and cerebellar changes (p < 0.05).CONCLUSIONS: MRI showed a typical spatial pattern, which evolved gradually and uniformly during disease progression in late-infantile MLD. In juvenile MLD MRI changes were already observed at disease onset and temporal patterns were more variable. As therapeutic options for MLD are evolving, these findings are not only important for patient counseling but also for the evaluation of therapeutic interventions.

KW - Adolescent

KW - Brain/diagnostic imaging

KW - Child

KW - Child, Preschool

KW - Cross-Sectional Studies

KW - Disease Progression

KW - Female

KW - Humans

KW - Infant

KW - Leukodystrophy, Metachromatic/diagnostic imaging

KW - Longitudinal Studies

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Monitoring, Physiologic/methods

KW - Motor Activity/physiology

KW - Radiography

KW - Severity of Illness Index

U2 - 10.1007/s10545-011-9361-1

DO - 10.1007/s10545-011-9361-1

M3 - SCORING: Journal article

C2 - 21698385

VL - 34

SP - 1095

EP - 1102

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

IS - 5

ER -