title: Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction.
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.
authors: 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.
authors: Agathe
authors: A
authors: Roubertie
authors: CHU Montpellier, Department of Neuroradiology, Montpellier, France; CHU Montpellier, Institut d'Imagerie Fonctionnelle Humaine, Montpellier, France.
authors: Nicolas
authors: N
authors: Leboucq
authors: CHU Montpellier, Centre d'Investigation Clinique, Montpellier, France INSERM, CIC 1411, Montpellier, France.
authors: Marie Christine
authors: MC
authors: Picot
authors: CHU Montpellier, Centre d'Investigation Clinique, Montpellier, France INSERM, CIC 1411, Montpellier, France.
authors: Erika
authors: E
authors: Nogue
authors: CHU Montpellier, Department of Neuroradiology, Montpellier, France.
authors: Hervé
authors: H
authors: Brunel
authors: CHU Montpellier, Department of Neuroradiology, Montpellier, France; CHU Montpellier, Institut d'Imagerie Fonctionnelle Humaine, Montpellier, France.
authors: Emmanuelle
authors: E
authors: Le Bars
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France.
authors: Gael
authors: G
authors: Manes
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France.
authors: Claire
authors: C
authors: Angebault Prouteau
authors: CHU Montpellier, Department of ENT, Montpellier, France.
authors: Catherine
authors: C
authors: Blanchet
authors: CHU Montpellier, Department of ENT, Montpellier, France.
authors: Michel
authors: M
authors: Mondain
authors: CHU Montpellier, Centre d'Investigation Clinique, Montpellier, France INSERM, CIC 1411, Montpellier, France.
authors: Hugues
authors: H
authors: Chevassus
authors: INSERM, U-1083, Angers, France.
authors: Patrizia
authors: P
authors: Amati-Bonneau
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France.
authors: Emmanuelle
authors: E
authors: Sarzi
authors: CHU Montpellier, Department of Neurology, Montpellier, France.
authors: Michel
authors: M
authors: Pagès
authors: CHU Montpellier, Centre of Reference for Genetic Sensory Diseases, Montpellier, France.
authors: Max
authors: M
authors: Villain
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France; CHU Montpellier, Centre of Reference for Genetic Sensory Diseases, Montpellier, France.
authors: Isabelle
authors: I
authors: Meunier
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France.
authors: Guy
authors: G
authors: Lenaers
authors: INSERM, U-1051, Institut des Neurosciences, Montpellier, France; CHU Montpellier, Centre of Reference for Genetic Sensory Diseases, Montpellier, France.
authors: Christian P
authors: CP
authors: Hamel
mesh_terms: D000293:Adolescent; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics / Q000473:pathology*; D009043:Motor Activity; D009460:Neurologic Examination; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: Brain imaging; Dominant optic atrophy; Magnetic resonance spectroscopy; Mitochondrial disorders; OPA1; Optic nerve