A Woman With Progressive Gait Difficulty and White Matter Abnormalities

Abstract

A 45-year-old woman was assessed for slowly progressive gait difficulty. Eight years earlier, she first noticed dragging of her right foot and stumbling on uneven surfaces. She also described difficulty bending the right knee and intermittent spasms of the right leg. She reported bilateral, mild hand weakness when she was doing repetitive tasks such as using scissors. She reported increasing urinary urgency and frequency over the past 3 years. Magnetic resonance imaging of the spinal cord showed continuous, relatively symmetric, T2 hyperintensity of the dorsal columns and, to a lesser extent, the lateral columns, as well as medullary pyramids. Brain magnetic resonance imaging showed T2 hyperintensity in the corticospinal tracts bilaterally extending from the precentral gyrus through the corona radiata and again seen in the pons. Review of the magnetic resonance imaging pattern of white matter abnormalities led to specific clinical suspicion for leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, an autosomal recessive condition due to DARS2 gene sequence variation. Brain magnetic resonance spectroscopy did not show lactate peaks. Genetic testing findings were abnormal and showed compound heterozygous DARS2 sequence variations. The presence of DARS2 sequence variations confirmed the diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. The patient was counseled that gradual progression of her gait difficulties could be expected. The following year she reported increasing urinary urgency and several episodes of urge incontinence. She was referred to the urology clinic. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a leukodystrophy that most commonly presents clinically with spasticity, dorsal column dysfunction, cerebellar ataxia, and sometimes mild cognitive decline. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation classically has a childhood onset and therefore may not be included in the differential diagnosis of chronic progressive white matter disease in adults.