A Case of Acute Bilateral Ptosis: SURF-1 Mutation

83 Dear Editor, A 14-month-old girl presented with a one-week history of bilateral ptosis without fluctuations in the intensity and distribution over time. Development stages were normal with no history of seizure, trauma or intoxication. On neurologic examination, bilateral ptosis was present, but eye movements, pupillary light reflexes, fundus and other cranial nerve functions were normal. Toxic, infectious, and metabolic causes that could affect the brainstem were considered in the differential diagnosis. Laboratory investigations revealed elevated serum lactate (31 mg/ dL; reference values: 8-22 mg/dL) with normal pyruvate levels (0.37 mg/dL; reference values: 0.3-0.9 mg/dL). Cerebrospinal fluid (CSF) analysis demonstrated elevated lactate level (32 mg/ dL; reference values: 5-19 mg/dL) with normal protein and glucose levels. Brain magnetic resonance imaging (MRI) showed bilateral and symmetrical non-enhancing lesions with restricted diffusion in the olives, dorsal brainstem tracts, substantia nigra, periaqueductal gray matter and subthalamic nuclei (Figure 1). The MRI pattern was suggestive for cytochrome-c oxidase deficiency with SURF-1 mutation. She was substituted with coenzyme Q10 (100 mg/day), carnitine (1 g/day) and high-dose multivitamin treatment (100 mg/day riboflavin, 100 mg/day thiamine, 10 mg/day biotin). One month after the initial presentation, recovery of ptosis was recognized. Molecular analyses revealed a homozygous c.518_538 (p.V173GfsX) deletion in SURF-1. After 7 months of follow-up, she presented with ataxic gait, confusion, nystagmus, and ptosis. Repeated brain MRI showed additional bilateral and symmetric lesions in the medial cerebellar hemispheres and superior cerebellar peduncles with restricted diffusion (Figure 2). It was learned from the family that they could not access drugs for 2 weeks. Bilateral subthalamic nuclei involvement as T2 and fluidattenuated inversion recovery (FLAIR) hyperintense signal abnormality is a very common neuroimaging finding in Leigh syndrome (LS) with underlying SURF-1 mutations. The additional findings include T1-hypointense and T2 and FLAIR hyperintense signal abnormalities in the inferior olivary nuclei, inferior cerebellar peduncles, central tegmental tracts, reticular formation in the dorsal pons and periaqueductal gray matter in the midbrain (1,2). Our patient had progressive neurologic disease, signs and symptoms of brainstem and/or basal ganglia disease, raised lactate levels in blood and/or CSF and characteristic features of LS on neuroimaging (hyperintense lesions on T2-weighted MRI) (3,4). Though LS is widely known to have a tendency to follow the course of progressive deterioration, we are acknowledge that several pathway-specific compounds such as thiamine and coenzyme Q10 have already been shown to be beneficial in patients. Our patient has already shown remarkable clinical improvement after management with high-dose vitamin and coenzyme Q10 treatment at the first attack, but it was known that spontaneous recovery could be misinterpreted as a positive therapeutic response as a result of the fluctuations of disease severity (5). A high index