title: Impaired information-processing speed and working memory in leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) and DARS2 mutations: a report of three adult patients.
abstract: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) is clinically characterized by progressive pyramidal and cerebellar dysfunction, dorsal column dysfunction and sometimes with axonal neuropathy. Magnetic resonance imaging of brain and the spinal cord reveals characteristic findings. LBSL is caused by mutations in the DARS2 gene that encodes the mitochondrial aspartyl-tRNA synthetase. The presentation and clinical course of LBSL is not uniform, and there is lack of longitudinal data on these patients. In addition, the existing data on the prevalence and characteristics of cognitive abnormalities in patients with LBSL are scarce and somewhat conflicting. Here we report long-term data of neurological and cognitive functioning in three non-related adult patients with LBSL. Cognitive impairment seems to be common among patients with LBSL and DARS2 mutations. The cognitive profile in LBSL shares similarities with that reported in multiple sclerosis, as information-processing speed and working memory are especially affected. In addition, our results and the previously reported carrier frequencies of common pathogenic DARS2 mutations suggest that LBSL may be underdiagnosed in the population.
authors: Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland. mikmar@utu.fi
authors: Mika H
authors: MH
authors: Martikainen
authors: Ulla
authors: U
authors: Ellfolk
authors: Kari
authors: K
authors: Majamaa
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001226:Aspartate-tRNA Ligase / Q000235:genetics*; D001933:Brain Stem / Q000473:pathology*; D002648:Child; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood*; D056784:Leukoencephalopathies / Q000473:pathology / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000523:psychology*; D008570:Memory, Short-Term / Q000502:physiology*; D008606:Mental Processes / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D013116:Spinal Cord / Q000473:pathology*; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D001226:Aspartate-tRNA Ligase; C558608:DARS2 protein, human
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