Can leukodystrophy be reversible? a LTBL case report

Background Leukoencephalopathy with thalamus and brainstem involvement and high lactate(LTBL) is a hereditary disorder caused by homozygote mutations in the EARS2 gene. Patients exhibit developmental delay, hypotonia, and hyperreflexia. Brain MRI reveals symmetrical cerebral white matter abnormalities with a preserved periventricular rim, and symmetrical signal changes in the thalami, midbrain,pons,medulla oblongata and cerebellar white matter with the involvement of the thalamus has been reported in all patients. We report a case of LTBL,showing significant improvement in neuroimaging and clinical findings. Case A non-consanguineous three-year-old boy exhibited developmental delay from birth,with no family history of neurological diseases. Neurological examination showed prominent truncal hypotonia and hyperreflexia. Brain MRI at two year of age revealed extensive T2-hyperintensities on the cerebral white matter, cerebellum, thalamus,basal ganglia,pons and medulla oblongata. Whole-exome sequencing yielded compound heterozygous EARS2 variants. Carnithine,coenzyme Q10,multivitamin were started. Clinical improvement was seen,at the six month of treatment he began to sit unassisted and at the eight month he was able to walk independent, at one year he could speak several words. Therefore,the findings in MR imaging were significantly reduced and just lesions of subcortical white matter, talamus and dorsal mesencephalon were seen at three years of age. Conclusion We present a case with recovery of brain lesions and healing of clinical symptoms in LTBL. However, unique clinical and MRI findings of this disease may be an important clue for diagnosis,reversibility of lesions on MRI is unusual. We aimed to point a case with reversible neuroimaging findings as promising for patients and caregivers.
Keywords: LTBL, Leukoencephalopathy, lactate, EARS2, MRI