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Neuropediatrics 2012; 43(06): 332-338
DOI: 10.1055/s-0032-1329395
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early-Onset LBSL: How Severe Does It Get?

M. E. Steenweg
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
L. van Berge
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
C. G. M. van Berkel
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
I. F. M. de Coo
2   Department of Child Neurology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
,
I. K. Temple
3   Department of Medical Genetics, School of Medicine, Princess Anne Hospital, University of Southampton, Southampton, United Kingdom
,
K. Brockmann
4   Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany
,
C. I. P. Mendonça
5   Department of Pediatric Neurology, Hospital de Faro, Faro, Portugal
,
S. Vojta
6   Department of Pediatrics, Kinderzentrum München, München, Germany
,
A. Kolk
7   Department of Pediatrics, Children's Clinic of Tartu, University Hospital, Tartu, Estonia
,
D. Peck
8   Department of Genetics, Children's Hospital, University of Missouri Health Care, Columbia, Missouri, United States
,
L. Carr
9   Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom
,
G. Uziel
10   Department of Child Neurology, National Institute for Neurology “Carlo Besta,” Milan, Italy
,
A. Feigenbaum
11   Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
,
S. Blaser
12   Division of Pediatric Neuroradiology, Hospital for Sick Children, Toronto, Canada
,
G. C. Scheper
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
M. S. van der Knaap
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

15 July 2012

13 August 2012

Publication Date:
12 October 2012 (online)

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Abstract

Aim Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities.

Method MRIs of approximately 3,000 patients with an unknown leukoencephalopathy were retrospectively reviewed for extensive signal abnormalities of the cerebral and cerebellar white matter, posterior limb of the internal capsule, cerebellar peduncles, pyramids, and medial lemniscus. Clinical data were retrospectively collected.

Results Eleven patients fulfilled the MRI criteria (six males); six had DARS2 mutations. Clinical and laboratory findings did not distinguish between patients with and without DARS2 mutations, but MRI did. Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles. Also, involvement of the globus pallidus was associated with DARS2 mutations. Earliest disease onset was neonatal; earliest death at 20 months.

Interpretation This study confirms the occurrence of early infantile, severe LBSL, extending the known phenotypic range of LBSL. Abnormality of specific brainstem tracts and cerebellar peduncles are MRI findings that point to the correct diagnosis.

Keywords

childhood white matter disorder - MRI pattern recognition - phenotypic variation
 

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