The focus of this research project is to determine the feasibility of conducting a natural history study of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) in a group of pediatric and adult patients with LBSL through remotely conducted virtual assessments.

LBSL is a rare neurologic disorder characterized by motor impairment and characteristic white matter changes on MRI caused by biallelic mutations in the DARS2 gene, which encodes mitochondrial aspartyl tRNA synthetase. Ataxia, spasticity and weakness are often reported. There is little information available about the progression of neuromotor impairment and it is unclear if a DARS2 genotype-phenotype relationship exists. We hypothesized that 1) a remotely conducted study would be feasible and result in high participant satisfaction and 2) neuromotor tests performed in participant’s homes would have good sensitivity for detecting disease signs.

The study design tests participants’ ability to perform neuromotor tasks through virtual visits in their homes with the aid of off-site research staff via web connection. Specifically, we used video conferencing to conduct gait, balance and manual dexterity tests using a wearable sensor system (OPAL™) and the Standardized Assessment and Rating of Ataxia (SARA) scale.

Data on stride velocity and stride length obtained using the OPAL™ system is well-validated against electronic walkway data collected in the physical therapy lab (Lin’s concordance correlation coefficient 0.84-0.89 and 0.73-0.82 respectively). Remotely conducted tests of gait and postural sway have good sensitivity to detect signs of cerebellar and corticospinal tract disease. The mean SARA score for the cohort was in the mildly ataxic range (mean 9.5(5.5), range 0 to 40).  

Our findings indicate that neuromotor assessments performed at home are a feasible and efficient method for characterizing the natural history of motor impairment in rare neurogenetic diseases.