Somatosensory Conduction Pathway in Spastic Paraplegia Type 5

We describe herein the case of a 37-year-old woman who presented with slowly progressive lower-limb stiffness and gait ataxia. She complained of running difficulties since the age of 10 years, gait impairment since the age of 30 years, and uri-nary urgency during the past 2 years. Her family history was unremarkable. At the last examination she exhibited spastic gait, pyramidal signs, severe impairment of the vibration sense in the lower limbs, and the Romberg sign. She achieved a Spastic Paraplegia Rating Scale score of 9/52. Blood tests were normal except for elevated serum levels of cholesterol (223 mg/dL, normal range 110–200 mg/dL) and thyroid-stimulating hormone (4.67 μUI/mL, normal range 0.45–3.50 μUI/mL). The patient was treated with levo-thyroxine for previous autoimmune thyroiditis. Infectious and autoimmune diseases, vitamin deficiencies, and genetic mutations associated with the most frequently occurring inherited ataxias and spastic paraplegias (SPGs) were excluded (i.e., Friedreich's ataxia, spinocerebellar ataxia types 1, 2, 3, and 6, and SPG4 and 7). Brain MRI findings were normal, but spinal MRI revealed severe thinning of the dorsal medulla. Visual and brainstem auditory evoked potentials were normal, but motor evoked potentials exhibited prolonged central motor conduction times (CMCTs) from the abductor hallucis (26.5/26.3 ms for left/ right) and normal CMCTs from the thenar eminence muscles. Somatosensory evoked potentials demonstrated elongated central conduction times on stimulation of the median and tibial nerves: N13–N20 interval, 15.5/14.6 ms for left/right; and N22–P37 interval, 25.8/24.6 ms for left/right. The pa-tient's cortical response amplitudes were mildly reduced for stimulation at the upper limbs (1.4/1.0 μV for left/right), and severely reduced for stimulation at the lower limbs (0.9/0.5 μV for left/right). Her peripheral motor-sensory conduction times were preserved. Magnetoencephalography (MEG) was conducted using a 306-channel helmet-shaped magnetoencephalograph (Neu-1 with 1-Hz stimulation of the median, ulnar, and tibial nerves, to obtain somatosensory evoked fields (SEFs). For upper limb stimulation, generators of the first cortical peak of the SEF (corresponding to N20) were identified and localized in the sensorimotor cortical areas, although the latency was increased (Fig. 1). No magnetic components were obtained for lower-limb stimulation. The association between sensory ataxia and spastic para-plegia led us to suspect that this patient had SPG5: mutational screening for the gene encoding oxysterol-7-alpha hydroxy-lase (CYP7B1) 2 was performed, and the serum level of 27-hy-droxycholesterol was measured. SPG5 patients generally present with increased serum levels of 27-hydroxycholesterol due to a deficiency of the P450 family enzyme oxysterol-7-alpha …