Clinical, imaging and follow-up study of optic neuritis associated with myelin oligodendrocyte glycoprotein antibody: a multicentre study of 62 adult patients.

BACKGROUND AND PURPOSE: There are few clinico-radiological data on optic neuritis (ON) with myelin oligodendrocyte glycoprotein antibody (MOG-IgG). The objective was to characterize the clinico-radiological phenotype and outcome of patients with MOG-IgG-related ON. METHODS: The records of all adult patients admitted in three medical centres with MOG-IgG-associated ON who underwent orbital and brain magnetic resonance imaging (MRI) at the acute phase were reviewed. Spinal cord MRI within 1 month from the ON and all of the follow-up MRI were reviewed. RESULTS: Of 62 patients, 41.9% had bilateral ON and 66.2% optic disc swelling. On initial MRI, lesions were anterior (92%), extensive (63%) and associated with optic perineuritis (46.6%). Silent brain lesions were found in 51.8% of patients but were mainly non-specific (81%). Of 39 individuals with spinal MRI at onset, nine had abnormal findings (four were asymptomatic). Two symptomatic patients had longitudinally extensive myelitis with concurrent H-sign. At last follow-up, 5% of patients had visual acuity ≤0.1. Brain MRI remained unchanged in 41 patients (87%). CONCLUSIONS: Our study supports a mostly benign ophthalmological course of MOG-IgG-associated ON, despite initially longitudinally extensive lesions and development of optic nerve atrophy on orbital MRI. Spinal MRI could be of interest in detecting silent suggestive lesions.

[Raxone in the Leber optical neuropathy: Parisian experience]. / Raxone dans la neuropathie optique de Leber : retour d'expérience parisienne.

INTRODUCTION: Leber's Hereditary Optic Neuropathy (LHON) causes a rapid and severe decrease in visual acuity. Raxone® (Idebenone, Santhera) is the only drug to have a European Marketing Authorization for the treatment of this optic neuropathy. It can be proposed in the first months after the onset of this optic neuropathy, according to an international consensus meeting. PATIENTS AND METHODS: Retrospective study of the efficacy of Raxone® on the visual acuity of patients with genetically confirmed LHON who were followed in four Parisian hospitals. The primary endpoint is the best recovery of LogMar visual acuity between baseline and the end of follow-up. The secondary endpoints are the evolution of LogMar visual acuity of the best eye at baseline and change in LogMar visual acuity for each eye considered separately. RESULTS: Seventeen patients, three women and 14 men, mean age 34.2 years, naive to treatment with Raxone® were included in this study. The mean duration of treatment was 11.0±6.6 months. A mitochondrial DNA mutation was found in all patients. Only 2 had the 14484 mutation. A recovery of better LogMar visual acuity was found at the end of the treatment for 4 eyes (23.5 %), and a deterioration was observed for 8 (47.0 %). Only 2 eyes (11.7 %) with the best visual acuity at baseline improved. On the other hand, 17.6 % of the eyes considered separately had an improvement in their LogMar visual acuity at the end of the treatment. CONCLUSION: The results confirm the trend of Raxone® treatment to improve patients' visual acuity. Given the recommendations of a consensus conference, this treatment should be started early after the onset of LHON. It is therefore important to look for this diagnosis in the presence of any hereditary optic neuropathy, in order to be able to initiate this treatment.

Stress-induced flexibility and individuality in female and male zebra finch distance calls.

Vocal recognition is central to the coordination and organization of behavior in pair-bonding species such as zebra finches. Zebra finches' vocalizations are individualized and support acoustic discrimination processes. Physiological states - such as the ones involved in emotional stress - can modify vocal production and consequently the structure of vocalizations. These modifications might signal the state of the caller but also impair individual recognition processes. This may represent a signaling trade-off, especially in contexts where both pieces of information can be critically important, for example when mates use calls to reunite after social isolation. Here we study the impact of a stress on the individual vocal signature in both female and male zebra finch distance calls. We built a manually curated database of distance calls of several individuals (both females and males) recorded in control and stress conditions. The stress was induced either by social isolation of the bird or using exogenous corticosterone. We developed a machine learning approach to assess the impact of stress on the individual characterization of calls. We show that while calls' spectral structure is significantly modified by stress, it still allows for the correct classification of calls to the caller. Moreover, we also show that the stress-induced modification of calls' structure is not a 'general feature signal' that can be detected as a 'stress' signal regardless of identity. Thus, female and male zebra finch calls' structure show stress-induced flexibility that stays within the range of individual vocal signatures.

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.

Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage-/- mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.

Acute idiopathic optic neuritis: not always benign.

BACKGROUND AND PURPOSE: Few recent data are available concerning idiopathic optic neuritis (ON). We aimed to describe a large cohort of patients with idiopathic ON. We compared this cohort with patients with ON related to myelin oligodendrocyte glycoprotein (MOG) or ON related to aquaporin-4 (AQP4) antibodies. METHODS: This was a monocentric retrospective observational study. Inclusion criteria for idiopathic ON were as follows: age ≥ 16 years, follow-up of at least 2 years, negative for antibodies against MOG and AQP4 immunoglobulin G, and no magnetic resonance imaging (MRI) lesions suggestive of demyelination (two brain MRI scans, one at baseline and one during follow-up, and one spinal cord MRI scan). RESULTS: Among 23 patients with idiopathic ON (female, 82.6%; median age, 36 years; median follow-up time, 41.4 months), 56.5% had recurrent ON (median time to a second ON episode, 6 months). The final visual acuity in this group (median, 0; mean, 0.43; range, 0-3) was similar to that in the AQP4 group (n = 18; P-value after Bonferroni correction = 0.936) but worse than that in the MOG group (n = 25; P-value after Bonferroni correction = 0.019). At the last evaluation, visual acuity levels were ≤0.5 and <0.2, respectively, in 36.8% and 21% of the idiopathic ON group, 58.3% and 26.7% of the AQP4 group, and 0% and 0% of the MOG group. CONCLUSION: The recovery of visual acuity among patients with idiopathic ON was poor, similar to that observed in the AQP4 group.

Etiologies of acute demyelinating optic neuritis: an observational study of 110 patients.

BACKGROUND AND PURPOSE: New criteria for the diagnosis of multiple sclerosis (MS) and discovery of myelin oligodendrocyte glycoprotein (MOG) or aquaporin-4 (AQP4) antibodies (Abs) have changed the management of optic neuritis (ON). Our aim was to specify, in view of these recent advances, the etiologies of acute demyelinating ON for consecutive patients. METHODS: Retrospective database analysis was undertaken of consecutive adult patients with acute ON admitted from 1 December 2014 to 31 January 2016. Diagnosis of MS was made according to the 2010 McDonald criteria. Patients with Abs to AQP4 or MOG were classified as ON-AQP4 and ON-MOG, respectively. Patients who did not fulfill the diagnostic criteria and were negative for AQP4 and MOG Ab tests were classified as having idiopathic ON. RESULTS: Of 110 patients assessed, 78 had ON related to MS (70.9%). All patients without MS were tested for AQP4 and MOG Abs: 11 had MOG Ab (10%), 5 had AQP4 Ab (4.5%) and 16 were considered as having idiopathic ON (14.5%). Presence of intrathecal IgG oligoclonal bands was strongly associated with MS (mean, 88.4% vs. 34.4% in patients without MS; after Bonferroni correction, P < 0.0001). CONCLUSIONS: Optic neuritis related to MOG Ab was the second cause identified of demyelinating ON in our center. Idiopathic ON was as frequent as both ON-AQP4 and ON-MOG combined.

Combined brain and anterior visual pathways' MRIs assist in early identification of neuromyelitis optica spectrum disorder at onset of optic neuritis.

Acute optic neuritis (ON) is the initial presentation in half of neuromyelitis optica spectrum disorder (NMO-SD) cases. Our objective was to evaluate accuracy of combined MRIs of the anterior visual pathways and of the brain to correctly identify NMO-SD among patients with acute ON. We performed a retrospective study on patients with acute ON in NMO-SD (16 episodes) and first-event non-NMO-SD (32 episodes). All MRIs included exams of the brain and anterior visual pathways using T2-weighted and post-gadolinium T1-weighted coronal thin slices. Images were reviewed by a neuroradiologist who was blinded to the final diagnosis. There were no multiple sclerosis (MS)-like lesions with dissemination in space (DIS) with NMO-SD (0 vs. 53%, p < 0.01). Non-NMO-SD ON usually spared the chiasma (3 vs. 44%, p < 0.01) and the optic tracts (0 vs. 19%, p < 0.01). Optic nerve lesions were longer [median (range) 26 mm (14-64) vs. 13 mm [8-36], p < 0.01] and the number of segments involved higher (3 [1-8] vs. 1 [1-4], p < 0.01) in NMO-SD. Bilateral optic nerve involvement, or involvement of ≥3 segments, or involvement of the chiasma, or optic tracts in the absence of MS-like lesions with DIS were suggestive of NMO-SD with a sensitivity of 69% (CI 95% 41-89) and a specificity of 97% (CI 95% 84-99) (p < 0.01). Combining brain and anterior visual pathways' MRIs seems efficient for detecting acute ON patients who are at high risk for NMO-SD.

Gut: An underestimated target organ for Aluminum.

Since World War II, several factors such as an impressive industrial growth, an enhanced environmental bioavailability and intensified food consumption have contributed to a significant amplification of human exposure to aluminum. Aluminum is particularly present in food, beverages, some drugs and airbone dust. In our food, aluminum is superimposed via additives and cooking utensils. Therefore, the tolerable intake of aluminum is exceeded for a significant part of the world population, especially in children who are more vulnerable to toxic effects of pollutants than adults. Faced with this oral aluminum influx, intestinal tract is an essential barrier, especially as 38% of ingested aluminum accumulates at the intestinal mucosa. Although still poorly documented to date, the impact of oral exposure to aluminum in conditions relevant to real human exposure appears to be deleterious for gut homeostasis. Aluminum ingestion affects the regulation of the permeability, the microflora and the immune function of intestine. Nowadays, several arguments are consistent with an involvement of aluminum as an environmental risk factor for inflammatory bowel diseases.

Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells.

Aluminum (Al), a non-essential element, is ubiquitous in industrialized societies. Whereas adult intake is estimated between 3 and 12 mg/day according to dietary aluminum studies conducted in many countries, it is not known if aluminum may have a toxic effect on intestinal epithelium. The aim of this work was to evaluate the cytotoxicity and RNA expression patterns induced in HT-29 cells by aluminum. Both classical toxicological methods and a global transcriptomic approach were used. Cytotoxicity determined by MTT assay showed a time and dose dependent decrease of cell viability in aluminum treated cells compared to control cells. Cell cycle analysis by flow cytometry revealed that aluminum induced accumulation of cells in phase G0/G1, associated with a decrease in the proportion of cells in S and G2/M phases. Aluminum led to apoptosis as evidenced by nuclear morphology changes and mitochondrial membrane perturbations, and induced reactive oxygen species generation. Transcriptomic pattern argued in favor of pro-tumorigenic and pro-inflammatory effects of aluminum in intestinal epithelial cells. These results highlight several pathways by which aluminum has a disturbing impact on intestinal epithelial cells, supporting that the effects of aluminum on intestine warrants further investigation.

Endovascular treatment of carotid-cavernous fistulae: Long-term efficacy and prognostic factors.

INTRODUCTION: Carotid-cavernous fistulae are rare and affect visual prognosis. Their clinical presentation is varied and delayed diagnosis is common. They require rapid neuro-radio-ophthalmologic management. PURPOSE: The goal of this study was to evaluate the long-term efficacy and prognostic factors for treatment of carotid-cavernous fistulas by embolization. MATERIALS AND METHODS: A total of 60 patients with direct (10/60, 17%) or indirect (50/60, 83%) carotid-cavernous fistulae suspected during ophthalmological examination underwent cerebral angiography from December 2003 to October 2013. Of these, 59 (59/60, 98%) patients were treated with embolization. Treatment response was assessed with a follow-up angiogram confirming the exclusion of the fistula, and clinically by resolution of the initial symptoms. RESULTS: The diagnosis was suspected on the basis of proptosis in 45 patients (45/60, 75%), corkscrew episcleral vessels in 38 patients (38/60, 63%), chemosis in 37 patients (37/60, 61%), and diplopia in 30 patients (30/60, 50%). The median delay in diagnosis was 5 ± 5 months [0.5 to 24 months], and mean follow-up was 31 ± 31.5 months [0.5-118 months]. Eighteen patients (18/60, 30%) were lost to follow-up. Clinical response was complete in 24 patients (24/42, 57%) and partial in 14 patients (14/42, 33.5%). Symptoms were stable in one patient (1/42, 2.5%) and worsened in 3 patients (3/42, 7%). Morbidity per procedure was 3.3% and there was no postoperative mortality. Forty patients (40/60, 67%) had radiological follow-up and 39 patients (39/40, 97.5%) had a complete exclusion of the fistula. The presence of diplopia on initial examination was more frequently associated with an incomplete cure (P=0.04). CONCLUSION: The combination of proptosis, corkscrew episcleral vessels and diplopia should rapidly lead to head imaging to search for a carotid-cavernous fistula. Fistula embolization is a safe and effective treatment. The presence of diplopia on initial examination may be associated with a poorer outcome (P=0.044).

Open-angle glaucoma and paraoptic cyst: first description of a series of 11 patients.

We report 11 patients who were referred to our institution for severe open-angle glaucoma who had a paraoptic cyst on MR imaging. All cysts were extraoptic and retrolaminar; most were deforming the adjacent optic nerve. Cysts had a high signal on T2 and FLAIR sequences, and a variable signal on T1 and variable echogenicity, suggesting different proteinaceous content. Arterial vascularization of the optic nerve was normal. Cyst volumes were inversely correlated with the severity of glaucoma on the same eye (P < .01-.05, Spearman correlation coefficient). We hypothesized that such cysts may reflect a valve mechanism, which would allow preservation of the translamina cribrosa pressure and thus could preserve visual function. The rarity of this association, together with the frequent mass effect of the cyst on the optic nerve, stresses the necessity of long-term follow-up in these patients.

Optic neuritis revealing Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease is a rare systemic disease with uncommon neurological involvement. We report the case of a 30-year-old Asian woman who presented a rapidly progressive loss of vision. Magnetic resonance imaging (MRI) of the optic nerve revealed an inflammation of the left optic nerve with chiasmatic involvement, without any encephalic or medullar lesion. Thoracic computed tomography scan showed bilateral axillary lymphadenopathy. Analysis of a biopsy of the axillary lymph node showed typical histological findings of Kikuchi-Fujimoto disease. There was no clinical or biological sign of associated systemic lupus erythematosus. The patient spontaneously recovered normal visual acuity in 4 weeks, with resolution of MRI abnormalities. No optic neuritis relapse or neurological event occurred in a 3-year follow-up. To our knowledge this is the first case of optic neuritis associated with Kikuchi-Fujimoto disease.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice.

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

Social experience affects neuronal responses to male calls in adult female zebra finches.

Plasticity studies have consistently shown that behavioural relevance can change the neural representation of sounds in the auditory system, but what occurs in the context of natural acoustic communication where significance could be acquired through social interaction remains to be explored. The zebra finch, a highly social songbird species that forms lifelong pair bonds and uses a vocalization, the distance call, to identify its mate, offers an opportunity to address this issue. Here, we recorded spiking activity in females while presenting distance calls that differed in their degree of familiarity: calls produced by the mate, by a familiar male, or by an unfamiliar male. We focused on the caudomedial nidopallium (NCM), a secondary auditory forebrain region. Both the mate's call and the familiar call evoked responses that differed in magnitude from responses to the unfamiliar call. This distinction between responses was seen both in single unit recordings from anesthetized females and in multiunit recordings from awake freely moving females. In contrast, control females that had not heard them previously displayed responses of similar magnitudes to all three calls. In addition, more cells showed highly selective responses in mated than in control females, suggesting that experience-dependent plasticity in call-evoked responses resulted in enhanced discrimination of auditory stimuli. Our results as a whole demonstrate major changes in the representation of natural vocalizations in the NCM within the context of individual recognition. The functional properties of NCM neurons may thus change continuously to adapt to the social environment.