Case of the Week

A 6-year-old girl with normal development until new onset of slowly progressive gait difficulty for 6 months. Neurologic examination showed spasticity, hyperreflexia, bilateral Babinsky sign, mild cerebellar ataxia, and abnormal vibration and proprioception. CSF examination (including lactate) normal.

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Maria A. Montenegro, MD, PhD; Diogo Valli Anderle, MD
Department of Neurology
University of Campinas
Brazil

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Axial T2WI (A–D) shows increased supra and infratentorial white matter T2 signal sparing the U-fibers. The posterior limb of the internal capsules, corticospinal tracts of the brainstem, medullary pyramids, and the middle cerebellar peduncles are also involved. Axial and sagittal T2WI of the cervical spinal cord (E–F) shows high T2 signal in the dorsal columns and lateral corticospinal tracts.

Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL)

• Background: LBSL is an autosomal recessive disorder caused by mutation in the DARS2 gene (mitochondrial aspartyl tRNA synthase).
• Clinical Presentation: During childhood or adolescence, patients present with slowly progressive spasticity, cerebellar ataxia, and abnormal vibration/proprioception. Cognition is only mildly affected. Reduced consciousness, neurologic deterioration, and fever may be trigged by minor head trauma.
• Key Diagnostic Features: Diagnosis is made by characteristic clinical presentation and MRI abnormalities,* and confirmed by genetic testing. MRS and CSF may show increased lactate, but this is not mandatory for diagnosis. [* See Appendix slide for more information]
• DDx: Fulfillment of the MRI diagnostic criteria is essentially pathognomonic for LBSL
• Treatment: There is currently no treatment. Management is based on symptom control and physical rehabilitation.

Suggested Reading

van Berge L, Hamilton EM, Linnankivi T, et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain 2014;137:1019–29, 10.1093/brain/awu026

Scheper GC, van der Klok T, van Andel RJ, et al. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nature Genet 2007;39:534–39, 10.1038/ng2013

van der Knaap MS, Salomons GS. Bilateral aberrant internal carotid arteries with bilateral persistent stapedial arteries and bilateral duplicated internal carotid arteries. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington; 2010. [Last Updated February 2015]

A preview from the next case . . .

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