title: Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.
abstract: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.
authors.affiliation: Marmara University Hospital, Department of Neurology, Istanbul, Turkey. kayihanu@yahoo.com
authors.forename: Kayihan
authors.initials: K
authors.lastname: Uluc
authors.forename: Ozdil
authors.initials: O
authors.lastname: Baskan
authors.forename: Kadriye Agan
authors.initials: KA
authors.lastname: Yildirim
authors.forename: Selda
authors.initials: S
authors.lastname: Ozsahin
authors.forename: Mesrure
authors.initials: M
authors.lastname: Koseoglu
authors.forename: Baris
authors.initials: B
authors.lastname: Isak
authors.forename: G C
authors.initials: GC
authors.lastname: Scheper
authors.forename: Dilek Ince
authors.initials: DI
authors.lastname: Gunal
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
mesh_terms: D000328:Adult; D001226:Aspartate-tRNA Ligase / Q000235:genetics; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001927:Brain Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001933:Brain Stem / Q000473:pathology*; D003401:Creatine / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009154:Mutation; D009431:Neural Conduction / Q000502:physiology; D011522:Protons; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D011522:Protons; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D001226:Aspartate-tRNA Ligase; D003401:Creatine