L. Ballonzoli

Optical Coherence Tomography in Neuromyelitis Optica

BACKGROUND Neuromyelitis optica (NMO) is an inflammatory disease with combined features of optic neuritis and myelitis. This pathologic entity may induce severe disability, including visual loss and paraplegia. Other than clinical follow-up, there is no marker for severity of the disease. OBJECTIVES To evaluate the use of optical coherence tomography (OCT) in NMO and to determine whether this new technique could be a good marker of axonal loss in NMO. DESIGN Cross-sectional study. PARTICIPANTS Thirty-five patients with NMO or at a high risk for NMO (having optic neuritis or myelitis and who are positive for NMO antibody) were prospectively studied. Fifteen healthy individuals served as control subjects. MAIN OUTCOME MEASURE All patients underwent a complete ophthalmologic evaluation, including OCT, funduscopy, and visual field, visual acuity, and visual evoked potential testing. Expanded Disability Status Scale scores were assessed but without the visual data. Correlations between the visual test results and demographic or clinical characteristics were evaluated. RESULTS Optical coherence tomography and visual field data were available for only 32 patients because 3 patients were blind. The mean retinal nerve fiber layer thickness was significantly reduced in patients with NMO compared with controls (P < .001). We found good correlation between the OCT results and visual field testing. We also found weak correlation between OCT results and both visual acuity and visual evoked potential latencies. We did not find any correlation between OCT results and age, sex, or disease duration. In contrast, retinal nerve fiber layer thickness was closely correlated with the Expanded Disability Status Scale score (P < .001). CONCLUSIONS Optical coherence tomography results are significantly altered in patients with NMO. Optical coherence tomography is easy to perform, and the results are well correlated with visual acuity and visual field findings. It could be considered a marker of axonal loss because we found good correlation between OCT and the Expanded Disability Status Scale score. These preliminary results will need to be confirmed in a longitudinal prospective study.

RELAPSING INFLAMMATORY OPTICNEURITIS: IS IT NEUROMYELITIS OPTICA?

Subacute loss of vision accompanied by pain is most commonly due to some form of inflammatory optic neuropathy (ON), and may be the first symptom of multiple sclerosis (MS). ON may also be due to viral or bacterial infection or systemic diseases. Although ON is frequently limited to a single episode, some patients experience recurrent episodes. The name recently given to these recurrent episodes of inflammatory ON with a negative workup for MS or other causes of ON is relapsing inflammatory ON (RION).1 MRI scans are normal and oligoclonal bands are rarely found in the CSF. Some patients with an initial diagnosis of RION are, after several years of follow-up, diagnosed with neuromyelitis optica (NMO), due to the occurrence of one or more episodes of myelitis.2 Recently, a specific marker of NMO, named NMO antibody, was found.3 There is now evidence to suggest that patients who experience recurrent episodes of myelitis and are positive for NMO antibodies are at a high risk of developing NMO.4 A similar hypothesis could be applied to RION. In the first study on NMO antibodies, a positive result was found in 2 of 8 patients with RION.3 However, the …

Lyme optic neuritis

Lyme optic neuritis (ON) is a rare disease and only a few cases have been reported. We describe two cases of isolated Lyme ON, one with recurrence 9 months after the appearance of initial symptoms. Diagnosis criteria for multiple sclerosis and neuromyelitis optica were not met. The etiological diagnosis was based on European case definition criteria for neuroborreliosis. Both patients had positive serum and cerebrospinal fluid serology, a positive intrathecal anti-Borrelia antibody index, and a good outcome on ceftriaxone. Specific diagnosis of Lyme ON is important since improvement of visual acuity is possible with specific antibiotherapy, even after many months.

Longitudinal follow-up of vision in a neuromyelitis optica cohort

Background: Neuromyelitis optica (NMO) is an inflammatory disease associated with optic neuritis and myelitis. Recently, several studies showed that optical coherence tomography (OCT) could be an interesting method for the evaluation of disease severity; however, to date there are no studies with a longitudinal follow-up of visual function in NMO. The aim of this study was to assess the ability of OCT to evaluate the progression of visual dysfunction in NMO. Patients and methods: A group of 30 NMO patients (thus, 60 eyes), comprised of 20 women and 10 men with a mean age of 43.7 +/− 12.3 years, were prospectively evaluated clinically and by a whole neuro-ophthalmological work-up, including: visual acuity (VA), fundoscopy, visual evoked potential (VEP), visual field (VF) and optical coherence tomography (OCT). All patients were tested at baseline (after a mean disease duration of 6.1 years) and after a mean time of follow-up of 18 months (range: 12–36 months). Results: Mean VA was similar at the two evaluation times (0.77 +/− 0.36 versus 0.77 +/− 0.35). The mean VF defect decreased slightly, but the difference was not significant (−5.9 +/− 1.3 dB versus −5.3 +/− 1.3 dB). In contrast, the mean retinal thickness seen on OCT decreased from 87.4 +/− 23.3 µm to 79.7 +/- 22.4 µm (p = 0.006). These modifications were only observed in eyes with a past or a recent history of optic neuritis (−15.1 µm; p < 0.001) and not in eyes without any history of optic neuritis (−2.4 µm; not significant). Also, they occurred independently of the occurrence of relapses (n = 13) and especially optic neuritis episodes; however, the number of optic neuritis episodes was low (n = 5). Conclusion: OCT seems to be a more sensitive test than VA or VF for monitoring ophthalmological function in NMO and it seems to be helpful for the detection of infra-clinical episodes in patients with a past history of optic neuritis. Our results suggest that this easily performed technique should be used in the follow-up of NMO, but complementary studies are warranted to confirm its interest at an individual level.

Central nervous system abnormalities in patients with PMP22 gene mutations: a prospective study

Background Mutations of the peripheral myelin protein-22 (PMP22) gene are the most common cause of inherited disease of the peripheral nervous system (PNS), with its deletion resulting in hereditary neuropathy with liability to pressure palsies (HNPP), and its duplication inducing Charcot–Marie–Tooth 1A (CMT1A) disease. Although mainly expressed in the PNS, PMP22 mRNA and protein are also present in the central nervous system (CNS). Objective To investigate whether patients with PMP22 mutations present with CNS abnormalities. Methods Fifteen patients with HNPP and 15 patients with CMT1A disease were prospectively included and their brain MRI and neuropsychological assessment were compared with those of healthy subjects. We evaluated, in particular, the volumes of grey and white matter (GM and WM) and looked for metabolic changes using spectroscopy, and abnormal architecture using fractional anisotropy (FA) measurement. A post mortem examination of the CNS of a patient with PMP22 gene duplication was also performed. Results We found a decrease in the volume of WM in 70% of patients, a reduced creatine level in WM in 28% and a cognitive impairment in 70%. FA was significantly altered in several areas of WM, including the columns of the fornix. The results for WM volume, creatine level in WM and cognitive testing showed that 47% of patients (patients with HNPP and those with CMT1A) presented with at least two abnormal results. Pathological examination of the brain of a patient with PMP22 gene duplication showed diffuse hypomyelination sparing the U fibres. Conclusions This study demonstrates that altered PMP22 gene expression induces significant CNS alterations in patients with HNPP and CMT1A, including cerebral WM abnormalities and cognitive impairment.

549 Rupture sclérale spontanée révélée par une maculopathie d’hypotonie

Cases of a spontaneous scleral rupture are very uncommon. Their diagnosis can be challenging because the scleral lesion might be invisible on clinical examination. We describe herein one case revealed by hypotony maculopathy. A 30-year-old woman presented with severe visual loss in one eye caused by sudden hypotony. Funduscopy revealed a chorioretinal coloboma in the periphery of the retina associated with a hypotony maculopathy. Extensive work-up included optical coherence tomography (OCT), fluoroangiography, ultrasonography, and magnetic resonance imaging examinations. A search for infectious and inflammatory diseases was conducted. Inflammatory and infectious work-ups were not contributive. A surgical exploration was performed, which showed a spontaneous scleral perforation within the coloboma. A patch of polytetrafluoroethylene was sutured on the damaged sclera and air was injected into the vitreous cavity. Vision and ocular pressure were rapidly restored. Spontaneous scleral rupture cases associated with hypotony and visual loss are rare, with only a few cases reported in the literature. Hypotony maculopathy with sclerochoroidal lesion may be the cause of such cases. Excellent outcome can be obtained with surgical diagnosis and repair.

Article originalMéningiome et neuropathie optique : un piège diagnostiqueOptic neuropathy and meningioma: A diagnostic trap☆

INTRODUCTION Meningiomas are benign primary meningeal tumors. Their diagnosis may be incidental or in response to a work-up for neurological or ophthalmological symptoms. PATIENTS AND METHODS The clinical course of five patients with ophthalmological symptoms leading to the diagnosis of meningioma is described. RESULTS The case reports consist of five women (48 to 54 years old - mean 52 years at the onset of symptoms), all suffering from a progressive unilateral decrease in visual acuity with a normal initial fundus examination and ipsilateral visual field changes. Ancillary testing, in particular MRI and CT-scans, had to be repeated to make the diagnosis of meningioma, which was delayed from 18 months to 4 years. DISCUSSION The clinical presentation of these five cases was that of a retrobulbar optic neuropathy, which biased the work-up towards an inflammatory disease of the central nervous system such as multiple sclerosis. However, the atypical character of the neuropathy, which did not respond to intravenous steroids, caused the diagnosis to be questioned and radiological examinations repeated. The iso-intense appearance of meningiomas on T1 MR imaging and only slightly hyperintense appearance on T2 may result in a diagnostic delay if the exam is not performed and interpreted by an experienced professional. Gadolinium contrast, fat suppression and centration on the anterior visual pathways are essential to a proper MRI examination. CONCLUSION When confronted with a progressive, painless optic neuropathy unresponsive to steroid treatment, the diagnosis of meningioma of the anterior visual pathways must be considered. This diagnosis is enabled by a targeted MRI of the anterior visual pathways.

Méningiome et neuropathie optique : un piège diagnostique

INTRODUCTION Meningiomas are benign primary meningeal tumors. Their diagnosis may be incidental or in response to a work-up for neurological or ophthalmological symptoms. PATIENTS AND METHODS The clinical course of five patients with ophthalmological symptoms leading to the diagnosis of meningioma is described. RESULTS The case reports consist of five women (48 to 54 years old - mean 52 years at the onset of symptoms), all suffering from a progressive unilateral decrease in visual acuity with a normal initial fundus examination and ipsilateral visual field changes. Ancillary testing, in particular MRI and CT-scans, had to be repeated to make the diagnosis of meningioma, which was delayed from 18 months to 4 years. DISCUSSION The clinical presentation of these five cases was that of a retrobulbar optic neuropathy, which biased the work-up towards an inflammatory disease of the central nervous system such as multiple sclerosis. However, the atypical character of the neuropathy, which did not respond to intravenous steroids, caused the diagnosis to be questioned and radiological examinations repeated. The iso-intense appearance of meningiomas on T1 MR imaging and only slightly hyperintense appearance on T2 may result in a diagnostic delay if the exam is not performed and interpreted by an experienced professional. Gadolinium contrast, fat suppression and centration on the anterior visual pathways are essential to a proper MRI examination. CONCLUSION When confronted with a progressive, painless optic neuropathy unresponsive to steroid treatment, the diagnosis of meningioma of the anterior visual pathways must be considered. This diagnosis is enabled by a targeted MRI of the anterior visual pathways.

460 Analyse maculaire en spectral domain OCT d’une dystrophie rétinienne de Bietti

Objectif Etudier la retine d’une patiente atteinte de dystrophie microcristalline de Bietti (DMB) grâce a un SD-OCT (tomographie en coherence optique « spectral domain »). La DMB est une dystrophie hereditaire rare, caracterisee par des microcristaux jaunes brillants limbiques et retiniens. L’aspect histologique et OCT de la maladie restent largement meconnus. Materiels et methodes Il s’agit du cas d’une patiente de 29 ans, d’origine turque presentant une baisse d’acuite visuelle chronique bilaterale. L’acuite visuelle etait de 6/10 P2 aux deux yeux. L’examen montrait de nombreux microcristaux au limbe. Au fond d’œil, ces microcristaux etaient presents dans la region maculaire et en moyenne peripherie retinienne. Un examen electrophysiologique de la retine, une angiographie a la fluoresceine, un champ visuel et un examen SD-OCT ont ete realises. Resultats L’angiographie a la fluoresceine revelait de grandes plages d’atrophie de l’epithelium pigmentaire et de sclerose choroidienne peripheriques. Le champ visuel montrait un retrecissement concentrique bilateral, l’electrophysiologie etait tres alteree. Un dosage de l’ornithine serique a elimine le diagnostic d’atrophie gyree et le diagnostic de DMB a ete retenu. Le SD-OCT a permis d’analyser finement la cornee et la region maculaire. Des lesions rondes hyper-reflectives associees a un cone d’ombre posterieur ont pu etre mises en evidence, correspondant aux microcristaux deceles cliniquement. La localisation des microcristaux etait superficielle, dans le stroma anterieur corneen. Dans la retine, les cristaux etaient presents dans toutes les couches et mesuraient de 40 a 50 microns. Il existait une atteinte des photorecepteurs mais l’epaisseur retinienne etait normale. Discussion La DMB serait due a une mutation du gene CYP4V2, jouant sur le metabolisme des acides gras. Les microcristaux sont retrouves dans les keratocytes et dans les lymphocytes circulants et seraient constitues de complexes lipidiques. Aucune etude histologique n’a ete realisee sur la retine. La presence des microcristaux dans toutes les couches de la retine pourrait indiquer une localisation extra cellulaire ou dans les cellules de Muller, les leucocytes ou les cellules de la microglie. Conclusion L’analyse en SD-OCT a permis d’etudier le siege des lesions retiniennes et corneennes dans ce cas. L’etude in vivo de l’evolution de ces lesions pourrait apporter de nouvelles donnees sur la physiopathologie de la DMB.

221 Intérêt de L’OCT dans la maladie de Parkinson

Introduction La maladie de parkinson et les syndromes parkinsoniens sont la premiere cause de maladies neuro-degeneratives a partir de 40 ans. Au bout de quelques annees d’evolution, pres de 50 % des patients presentent des troubles cognitifs accompagnes d’hallucinations visuelles. L’origine exacte de ces hallucinations reste encore indeterminee. Materiels et Methodes Nous avons etudie une cohorte de 30 patients atteints de maladie de Parkinson et souffrant d’hallucinations visuelles, en realisant une analyse de la couche des fibres nerveuses retiniennes en OCT Stratus (protocole Fast RNFL Thickness). Resultats Sur les 30 patients etudies, 3 ont ete exclus pour manque de fiabilite de l’examen et 4 pour autres pathologies papillaires (2 glaucomes connus et traites ; 2 dysversions papillaires). Dans plus de 75 % des cas l’epaisseur des fibres nerveuses retiniennes peripapillaires etait dans les valeurs physiologiques comparee a la base normative. Discussion Devant ces resultats, nous discutons les differentes causes responsables d’hallucinations chez ces patients presentant des troubles du systeme dopaminergique ; quelle est la part de la maladie, du traitement ou d’une alteration de la retine interne (suspectee sur l’amincissement global de la retine maculaire au mapping). Conclusion Les hallucinations observees dans les syndromes et maladies de Parkinson ne semblent pas liees a une anomalie de l’epaisseur de la couche des fibres nerveuses retiniennes. Nous avons en revanche observe un amincissement diffus de la retine maculaire sur le mapping qui apparait aux depends de la retine interne. Ces observations necessitent confirmation par une etude a plus grande echelle, utilisant desormais des OCT de derniere generation.