Leber’s Hereditary Optic Neuropathy Plus Causing Recurrent Myelopathy due to an MT-DN1 Mutation at G3635A

A 51-year-old man with known Leber’s hereditary optic neuropathy (LHON) presented with worsening lower extremity weakness and numbness. Following an episode of myelopathy two years before, he had been ambulating with a walker but over two weeks became wheelchair bound. He also developed a sensory level below the T4 dermatome to light touch, pinprick, and vibration. MRI of his cervical and thoracic spine showed a nonenhancing T2 hyperintense lesion extending from C2 to T12. At his presentation two years earlier, he was found to have a longitudinally extensive myelopathy attributed to his LHON. Genetic testing revealed a 3635 guanine to adenine mutation. MRI at that presentation demonstrated a C1-T10 lesion involving the central and posterior cord but, unlike the new lesion, did not involve the ventral and lateral horns. Given the similarity to his prior presentation and a negative evaluation for alternative etiologies, he was thought to have recurrent myelopathy secondary to Leber’s Plus. To our knowledge, recurrent myelopathy due specifically to the G3635A mutation in Leber’s Plus has not been reported previously.

Observation of Peripapillary Choroidal Vascularity in Natural Disease Course and After Gene Therapy for Leber's Hereditary Optic Neuropathy

Purpose: To compare peripapillary choroidal vascularity among Leber's Hereditary Optic Neuropathy (LHON) patients at different stages of natural course and healthy controls using optical coherence tomography (OCT), and to evaluate peripapillary choroidal vascularity changes in LHON patients before and after gene therapy.Methods: 57 LHON patients and 15 healthy controls were enrolled in this prospective clinical study. LHON patients were divided into three duration groups based on stage of disease progression. Both patients and healthy controls underwent OCT scans focused on the optic disc at baseline with Heidelberg Spectralis, and patients underwent OCT at 1, 3, and 6 months after gene therapy. OCT images were converted and binarized using ImageJ software. Choroidal thickness (CT), total choroidal area (TCA), and choroidal vascularity index (CVI) in each quadrant of OCT images were measured to evaluate peripapillary choroidal vascularity.Results: At baseline, the average CT was not significantly different between LHON patients at different stages and between healthy controls (P = 0.468). Although average TCA and average CVI were slightly higher in LHON patients at different stages than in healthy controls, the difference was not statistically significant (P = 0.282 and 0.812, respectively). After gene therapy, The average TCA at 1 month after gene therapy was significantly higher than that before gene therapy (P = 0.003), while no significant differences were found in the average CT or average CVI in LHON patients before and 1,3 and 6 months after gene therapy using pairwise comparisons (all P > 0.05).Conclusions: No significant difference was found in choroidal vascularity of LHON patients at different stages and healthy controls. Choroidal vascularity seems to stay stable after gene therapy.

NI-19 A case of Leber’s hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri

BACKGROUND: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The cranial magnetic resonance imaging (MRI) of LHON patients varies from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. CASE REPORT: We report a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2’-deoxyguanosine positivity, suggesting the presence of oxidative stress. CONCLUSION: LHON is extremely difficult to diagnose unless we suspect or know the disease. The present case brings attention not only to LHON but other mtDNA mutated diseases that need to be considered with diffuse white matter changes or GC.