Agathe Roubertie1, Nicolas Leboucq2, Marie Christine Picot3, Erika Nogue3, Hervé Brunel4, Emmanuelle Le Bars2, Gael Manes5, Claire Angebault Prouteau5, Catherine Blanchet6, Michel Mondain6, Hugues Chevassus3, Patrizia Amati-Bonneau7, Emmanuelle Sarzi5, Michel Pagès8, Max Villain9, Isabelle Meunier10, Guy Lenaers5, Christian P Hamel10. 1. CHU Montpellier, Department of Pediatric Neurology, Gui de Chauliac Hospital, Montpellier, France; INSERM, U-1051, Institut des Neurosciences, Montpellier, France. Electronic address: a-roubertie@chu-montpellier.fr. 2. CHU Montpellier, Department of Neuroradiology, Montpellier, France; CHU Montpellier, Institut d'Imagerie Fonctionnelle Humaine, Montpellier, France. 3. CHU Montpellier, Centre d'Investigation Clinique, Montpellier, France INSERM, CIC 1411, Montpellier, France. 4. CHU Montpellier, Department of Neuroradiology, Montpellier, France. 5. INSERM, U-1051, Institut des Neurosciences, Montpellier, France. 6. CHU Montpellier, Department of ENT, Montpellier, France. 7. INSERM, U-1083, Angers, France. 8. CHU Montpellier, Department of Neurology, Montpellier, France. 9. CHU Montpellier, Centre of Reference for Genetic Sensory Diseases, Montpellier, France. 10. INSERM, U-1051, Institut des Neurosciences, Montpellier, France; CHU Montpellier, Centre of Reference for Genetic Sensory Diseases, Montpellier, France.
Abstract
OBJECTIVE: OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. METHODS: Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. RESULTS: Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. CONCLUSIONS: Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration.
OBJECTIVE:OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1patients. METHODS: Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. RESULTS: Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. CONCLUSIONS: Our results demonstrate that brain imaging abnormalities are common in OPA1patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration.