Journal of Neuro-Ophthalmology, March 2011, Volume 31, Issue 1

Magnetic Resonance Findings in the Pregeniculate Visual Pathways in Leber Hereditary Optic Neuropathy

Two relatives, a 61-year-old man and the 21-year-old grandson of his sister, suffered from bilateral visual loss and were diagnosed with Leber hereditary optic neuropathy. In both cases, the diagnosis was molecularly confirmed with the 11778 mitochondrial mutation. MRI showed increased T2 signal not only in the optic nerves and chiasm but also in the optic tracts, extending to the lateral geniculate bodies. To our knowledge, the latter finding has not been described previously.

Magnetic Resonance Findings in the Pregeniculate Visual Pathways in Leber Hereditary Optic Neuropathy Danielle van Westen, MD, PhD, Bjo¨rn Hammar, MD, PhD, Gunnel Bynke, MD, PhD Section Editor: Timothy J. McCulley, MD FIG. 1. Case 1. T2 axial (A, D) and coronal (B, E, C, F) MRI of the optic tracts (arrows). On the initial study, an increased signal is seen (B, C) and the tracts are mildly swollen. The signal abnormality remains in the follow-up study (E, F), and the tracts are now atrophic. Department of Neuroradiology (DvW), Center for Medical Imaging and Physiology, Ska°ne University Hospital, Lund, Sweden; Department of Diagnostic Radiology (DvW), Lund University, Lund, Sweden; and Neuro-Ophthalmology Unit, Department of Ophthalmology (BH, GB), Ska°ne University Hospital, Lund, Sweden. Supported by the Ska°ne County Research and Development Council, the Swedish Research Council, Kronprinsessan Margaretas Arbetsna¨mnd fo¨r synskadade (Crown Princess Margareta's Foundation for the Visually Handicapped), Synskadades Va¨l i O¨ stergo¨tland, and Carmen och Bertil Regne´rs fond (Carmen and Bertil Regne´rs Foundation) and Lund University Hospital funds. Conflict of interest: None. Address correspondence to Danielle van Westen, MD, PhD, Department of Radiology, Lund University Hospital, SE-221 85 Lund, Sweden; E-mail: [e-mail] 48 van Westen et al: J Neuro-Ophthalmol 2011; 31: 48-51 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Abstract: Two relatives, a 61-year-old man and the 21- year-old grandson of his sister, suffered from bilateral visual loss and were diagnosed with Leber hereditary optic neuropathy. In both cases, the diagnosis was molecularly confirmed with the 11778 mitochondrial mutation. MRI showed increased T2 signal not only in the optic nerves and chiasm but also in the optic tracts, extending to the lateral geniculate bodies. To our knowledge, the latter finding has not been described previously. Journal of Neuro-Ophthalmology 2011;31:48-51 doi: 10.1097/WNO.0b013e3181f3f203 2011 by North American Neuro-Ophthalmology Society Case 1: A 61-year-old man, complained of painless decline in vision in both eyes. Three months later, visual acuity was counting fingers (CF) at 1 m bilaterally, kinetic perimetry revealed large central scotomas, and funduscopy was normal. Genetic analysis revealed the mitochondrial DNA 11778 mutation consistent with the diagnosis of Leber hereditary optic neuropathy (LHON). MRI of the brain and orbits performed 1 month later demonstrated increased T2 signal centrally in moderately enlarged prechiasmal optic nerves, optic chiasm, and optic tracts (Figs. 1, 2). Similar signal increase was found on the short time inversion recovery sequence (STIR). No contrast enhancement was present. Repeat MRI exami-nation 9 months later revealed persistent high T2 signal in atrophic retrobulbar optic nerves, chiasm, and optic tracts (Figs. 1, 2). His final visual acuity remained at CF in both eyes. Case 2: A 21-year-old man is the maternal grandson of the sister of Case 1. He experienced decreased vision in his right eye with visual acuity of CF at 1.5 m, loss of color vision, and a central scotoma on visual field testing. Three months later, the visual acuity in his left eye decreased to CF. Six months after the initial visual loss, MRI of the brain and orbits demonstrated increased T2 signal centrally in the prechiasmal optic nerves, optic chiasm, and optic tracts FIG. 2. Case 1. Coronal T2 MRI of retrobulbar (A, D) and prechiasmal (B, E) optic nerves and optic chiasm (C, F). The retrobulbar optic nerves are normal. Arrows indicate increased signal in prechiasmal nerves (B) and chiasm (C), which are slightly swollen. The signal abnormality is present (E, F) in the follow-up examination, although the structures are shrunken. van Westen et al: J Neuro-Ophthalmol 2011; 31: 48-51 49 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. (Figs. 3, 4). There was no contrast enhancement. Repeat MRI 6 months later revealed that the signal abnormality was still present (Figs. 3, 4). His final visual acuity was CF 1 m in both eyes. To the best of our knowledge, this is the first report of signal changes detected on MRI in the optic tracts of patients with LHON. Anatomic changes in LHON in-clude reduction of the optic nerve diameter, central axonal loss, and sometimes minimal inflammatory changes (1-3). In a whole brain specimen from a patient with the classical clinical profile of LHON, severe loss of retinal ganglion cells and axons was present as well as central demyelination in the optic nerves chiasm and optic tracts (4). Thus, LHON seems to affect the retinal ganglion cells along the whole length of the axon. In our patients, signal changes in the optic tract in subacute LHON were accompanied by enlargement of the structures involved, possibly due to edema with or without axonal swelling. In the chronic phase, signal changes persisted, most likely representing gliosis. Considering that histopathologic studies have shown involvement of the retinal ganglion cell axon along its entire length, it is remarkable that MRI demonstration of the optic tract involvement in LHON has not been re-ported previously. Generally, no abnormalities are seen on MRI of the brain and orbits in patients with LHON (5-7). A few reports document T2 and STIR signal abnormalities several months to years after the onset of visual loss (6-10). Signal changes in the optic chiasm have been reported twice (11,12). We reviewed the findings in these reports, but ad-equate imaging of the optic tracts was not performed. Failure to detect optic tract involvement in LHON may be due to lack of awareness and failure to use an exami-nation designed to image the optic tracts. In case 1, such images were accidentally obtained because the patient was evaluated with a combined orbit and pituitary protocol. Case 2 was subsequently examined with the same protocol. The frequency of our finding can be established only when dedicated imaging of the optic tracts is performed routinely in patients with LHON. FIG. 3. Case 2. T2 sagittal (A, D) and coronal (B, E, C, F) MRI of the optic tracts (arrows). Initial study (A, B, C) reveals increased signal within slightly swollen optic tracts. Follow-up images (D, E, F) show that the signal abnormality persists, and the tracts are now smaller in size. 50 van Westen et al: J Neuro-Ophthalmol 2011; 31: 48-51 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. REFERENCES 1. Saadati HG, Hsu HY, Heller KB, Sadun AA. A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy. Arch Ophthalmol. 1998;116:911-916. 2. Sadun AA, Kashima Y, Wurdeman AE, Dao J, Heller K, Sherman J. Morphological findings in the visual system in a case of Leber's hereditary optic neuropathy. Clin Neurosci. 1994;2:165-172. 3. Kerrison JB, Howell N, Miller NR, Hirst L, Green WR. Leber hereditary optic neuropathy: electron microscopy and molecular genetic analysis of a case. Ophthalmology. 1995; 102:1509-1516. 4. Adams JH, Blackwood W, Wilson J. Further clinical and pathological observations on Leber's optic atrophy. Brain. 1966;89:15-26. 5. Newman NJ. Leber's hereditary optic neuropathy: new genetic considerations. Arch Neurol. 1993;50:540-548. 6. Kermode AG, Moseley IF, Kendall BE,Miller DH, MacManus DG, McDonald WI. Magnetic resonance imaging in Leber's optic neuropathy. J Neurol Neurosurg Psychiatry. 1989;52: 671-674. 7. Dotti MT, Caputo N, Signorini E, Federico A. Magnetic resonance imaging findings in Leber´s hereditary optic neuropathy. Eur Neurol. 1992;32:17-19. 8. Mashima Y, Oshitari K, Imamura Y, Momoshima S, Shiga H, Oguchi Y. Orbital high resolution magnetic resonance imaging with fast spin echo in the acute stage of Leber's hereditary optic neuropathy. J Neurol Neurosurg Psychiatry. 1998;64:124-127. 9. Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, Da Costa J, Harding AE. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995; 118:319-337. 10. Inglese M, Rovaris M, Bianchi S, La Mantia L, Mancardi GL, Ghezzi A, Montagna P, Salvi F, Filippi M. Magnetic resonance imaging, magnetization transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber´s hereditary optic neuropathy. J Neurol Neurosurg Psychiatry. 2001;70: 444-449. 11. Phillips PH, Vaphiades M, Glasier CM, Gray LG, Lee AG. Chiasmal enlargement and optic nerve enhancement on magnetic resonance imaging in Leber hereditary optic neuropathy. Arch Ophthalmol. 2003;121:577-579. 12. Batiog˘lu F, Atilla H, Eryilmaz T. Chiasmal high signal on magnetic resonance imaging in the atrophic phase of Leber hereditary optic neuropathy. J Neuroophthalmol. 2003;23: 28-30. FIG. 4. Case 2. T2 sagittal MRI of the prechiasmal optic nerves (A, D) and optic chiasm (B, E) and coronal view of the optic chiasm (C, F). Arrows indicate increased signal in mildly swollen optic nerves (A) and chiasm (B, C) in the initial study, which persists (D, E, F) 6 months later. van Westen et al: J Neuro-Ophthalmol 2011; 31: 48-51 51 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.