Clinical features and visual function of recurrent neuromyelitis optica

Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, Florida, May 5-10, 2002.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Serial cases: visual evoked potentials (VEP) in demyelinating disease

Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis

Background: The visual evoked potential (VEP) is used in the evaluation of multiple sclerosis (MS) patients, showing a delay in P100 wave latency with no changes in amplitude in 60–100% of cases. In the last decade, the recurrent form of neuromyelitis optica (NMO) has been recognized, and clinically characterized by acute events of transverse myelitis (TM) and optic neuritis (ON), differing from MS in clinical and laboratory criteria. Despite these differences, so far, the VEP parameters described in MS have been used in the evaluation of patients with NMO. The objective of this study was to investigate VEP responses in NMO. Methods: Patients with NMO underwent pattern-reversal visual stimulation. Nineteen patients were selected for the study. Results: Among the 38 eyes examined, 18 (47.4%) had no visual evoked responses and 13 (34.2%) had a reduction of P100 wave amplitude with normal latency. Only two (5.3%) had the pattern described in MS and five (13.2%) were normal. Conclusion: Evaluation of VEP in patients with definite NMO revealed a pattern that is different from that of MS in 81.6% of eyes examined, characterized by the absence of responses, or decreased amplitude with normal latency.

To investigate the clinical manifestation, management and prognosis of optic neuritis combined with viral hepatitis. Retrospective study case series. Clinical data from twenty patients with optic neuritis combined with hepatitis who were hospitalized in Beijing Tongren Hospital neural eye ward from September 2003 to June 2010 were collected, the clinical characteristics and visual field changes in the group of patients were summarized, and comparison between the vision before and after treatment was made by the Wingerchuk vision classification. Among the twenty patients, eighteen patients had chronic hepatitis B and two patients had chronic hepatitis C. Thirteen (65%) patient were monocular, sixteen (80%) patients were single-phase course. Twenty-seven eyes were affected. Disc edema was very common which was found in 14 eyes (52%), severe vision impairment (Best corrected visual acuity worse than 20/200) were recorded in 19 eyes (70%). Lower altitudinal visual field impairment was more common which was found in 10 eyes (50%). All patients were followed for 3 months after steroid therapy, complete visual recovery or significant improvement was seen in only 3 eyes (11%) or 4 eyes (15%). Minor improvement was seen in 12 eyes (44%), while 8 eyes (30%) had no improvement. In this study, optic neuritis combined with hepatitis usually showed severe visual impairment. Although the vision of some patients could completely recover after steroid therapy, most of the patients had poor recovery. Combination of steroid and anti-viral therapy should be considered in the management of optic neuritis combined with hepatitis.

Sirs: Neuromyelitis optica (NMO) is characterized by severe attacks of optic neuritis and myelitis. More than half of patients with NMO are positive for NMO-IgG, a serum autoantibody specific to NMO [3]. In NMO, hypothalamic lesions occasionally develop, and cases with endocrinopathy (hyperprolactinemia/galactorrhea or amenorrhea) have been reported [7, 8]. Recently, therapeutic efficacy of plasma exchange (PE) in some corticosteroid-unresponsive cases of idiopathic demyelinating diseases including NMO has been reported [2, 6, 9]. We report a therapeutic efficacy of PE for a hypothalamic lesion in an NMO-IgG-positive NMO patient totally unresponsive to high-dose intravenous methylprednisolone (HIMP). The patient was a 21-year-old woman who had had total blindness in the left eye and upper-half visual field defect in the right eye (Figure 1, A-1) as sequellae of previous attacks of NMO (a total of ten relapses of optic neuritis and myelitis and normal brain MRI). On 5 April 2004 (Day 1), she complained of deterioration of visual field defect in the right eye and was admitted to our hospital. Neurological examination revealed complete blindness in the left eye and blurred vision with visual defect in the right eye except the nasal lower quadrant, abnormal pupillary light reflex (absent on left and sluggish on right), generalized hyperreflexia, left Babinski sign and painful numbness in her left breast. Galactorrhea was not seen. Brain MRI showed T2-hyperintense lesions in the hypothalamus, medulla oblongata, and cervical cord (C2-8). The hypothalamic lesion partly involved the optic chiasma and pituitary stem (Figure 1, B-1). The hypothalamic and cervical cord (C6-7) lesions were enhanced with gadolinium (Gd). Serum NMO-IgG and antinuclear antibody were positive, and serum prolactine (PRL) level was elevated (49.51 ng/mL). Oligoclonal band were not seen. Although she was first treated with two courses of HIMP therapy (1 g/day, for 3 days) on Day 1-3 and Day 9–11, her visual symptom in the right eye became worse (Figure 1, A-2, A-3) and the hypothalamic lesion remained Gdenhanced (Figure 1, C-1). Serum PRL level became even higher (68.35 ng/ml). We then treated her with PE (2 liters of plasma was exchanged with 5% albumin solution each time.) on Days16, 18, 22, and 26. After two sessions of PE, the visual field in the right eye began to improve and later neared the prerelapse level (Figure 1, A-4). In accordance with the clinical improvement, Gd-enhancement of the hypothalamic lesion disappeared (Figure 1, C-2). Serum PRL level also decreased to 41.57 ng/ml. In our patient, the visual impairment and hyperprolactinemia clearly resolved following PE, although a spontaneous resolution or delayed effect of corticosteroid is not ruled out. Keegan et al. reported six out of ten NMO patients showed improvement following PE [2], but a therapeutic effect of PE on hypothalamic lesions in NMO has not been described. The neuropathological finding of hypothalamic lesions in NMO was demyelination with necrotic changes [7] which was similar to the lesions in the optic nerves and spinal cord of NMO. Hypothalamic involvement could be a under-recognized feature of NMO [5]. The hypothalamic lesion could involve the optic tract as seen in our case. Perivascular deposition of immunoglobulins and activated complements is a characteristic finding of NMO as compared with multiple sclerosis [4]. Moreover, rituximab, anti-CD20 monoclonal antibody targeting pre-B cells and mature B cells, may be effective in NMO [1]. PE’s efficacy in our case, the pathological findings and the rituximab trial strongly suggest that humoral immunity plays a role in the pathogenesis of the hypothalamic lesion in NMO. PE should be considered in treating NMO patients with lesions S. Watanabe AE I. Nakashima I. Miyazawa AE T. Misu AE Y. Shiga K. Fujihara (&) AE Y. Itoyama Dept. of Neurology Tohoku University School of Medicine 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan Tel.: +81-22-717-7189 Fax: +81-22-717-7192 E-Mail: fujikazu@em.neurol.med.tohoku. ac.jp

The anterior optic pathway is one of the preferential sites of involvement in CNS inflammatory demyelinating diseases, such as multiple sclerosis and neuromyelitis optica, with optic neuritis being a common presenting symptom. What is more, optic nerve involvement in these diseases is often subclinical, with optical coherence tomography demonstrating progressive neuroretinal thinning in the absence of optic neuritis. The pathological substrate for these findings is poorly understood and requires investigation. We had access to post-mortem tissue samples of optic nerves, chiasms and tracts from 29 multiple sclerosis (mean age 59.5, range 25-84 years; 73 samples), six neuromyelitis optica spectrum disorders (mean age 56, range 18-84 years; 22 samples), six acute disseminated encephalomyelitis (mean age 25, range 10-39 years; 12 samples) cases and five non-neurological controls (mean age 55.2, range 44-64 years; 16 samples). Formalin-fixed paraffin-embedded samples were immunolabelled for myelin, inflammation (microglial/macrophage, T- and B-cells, complement), acute axonal injury and astrocytes. We assessed the extent and distribution of these markers along the anterior optic pathway for each case in all compartments (i.e. parenchymal, perivascular and meningeal), where relevant. Demyelinated plaques were classified as active based on established criteria. In multiple sclerosis, demyelination was present in 82.8% of cases, of which 75% showed activity. Microglia/macrophage and lymphocyte inflammation were frequently found both in the parenchymal and meningeal compartments in non-demyelinated regions. Acute axonal injury affected 41.4% of cases and correlated with extent of inflammatory activity in each compartment, even in cases that died at advanced age with over 20 years of disease duration. An antero-posterior gradient of anterior optic pathway involvement was observed with optic nerves being most severely affected by inflammation and acute axonal injury compared with the optic tract, where a higher proportion of remyelinated plaques were seen. In neuromyelitis optica spectrum disorder, cases with a history of optic neuritis had extensive demyelination and lost aquaporin-4 reactivity. In contrast, those without prior optic neuritis did not have demyelination but rather diffuse microglial/macrophage, T- and B-lymphocyte inflammation in both parenchymal and meningeal compartments, and acute axonal injury was present in 75% of cases. Acute demyelinating encephalomyelitis featured intense inflammation, and perivenular demyelination in 33% of cases. Our findings suggest that chronic inflammation is frequent and leads to neurodegeneration in multiple sclerosis and neuromyelitis optica, regardless of disease stage. The chronic inflammation and subsequent neurodegeneration occurring along the optic pathway broadens the plaque-centred view of these diseases and partly explains the progressive neuroretinal changes observed in optic coherence tomography studies.

To determine the prognostic value of neuromyelitis optica (NMO)-immunoglobulin G (IgG) in patients with recurrent optic neuritis (ON). The aquaporin-4-specific serum autoantibody, NMO-IgG, is a biomarker for NMO and relapsing transverse myelitis. Recurrent ON may herald multiple sclerosis (MS) or NMO, or it may occur as an isolated syndrome. The prognosis and response to therapy differs in each of these contexts. We evaluated 34 patients who were tested for NMO-IgG between 2000 and 2007 and who had two or more episodes of ON without satisfying a diagnosis of MS or NMO prior to serologic testing. Clinical data were available for 25 Mayo Clinic patients (5 NMO-IgG positive and 20 NMO-IgG negative) and for an additional 9 seropositive patients whose serum was referred to the Mayo Clinic Neuroimmunology laboratory for testing. Twenty percent of the patients with recurrent ON seen at Mayo Clinic were seropositive. All NMO-IgG-positive patients (vs 65% NMO-IgG-negative patients) had at least one attack with visual acuity in the affected eye worse than 20/200 (p = 0.05). In seropositive patients for whom long-term follow-up was possible (median 8.9 years after the initial ON), 6 of 12 (50%) experienced an episode of myelitis and fulfilled criteria for NMO. In contrast, 1 of 15 seronegative patients (6.7%) fulfilled McDonald criteria for MS (p = 0.03). Seropositive patients had a final visual score which was worse than that of seronegative patients (p = 0.02). Neuromyelitis optica (NMO)-immunoglobulin G seropositivity predicts poor visual outcome and development of NMO. Seropositive recurrent optic neuritis is a limited form of NMO.

Objective To investigate the visual field characteristics of patients with anterior ischemic optic neuropathy (AION) and idiopathic optic neuritis (ION) , and explore the occurrence mechanism. Methods The visual field data of patients with AION and idiopathic demyelinating optic neuritis (ION) diagnosed and treated in the Ophthalmology Department of Zhengzhou People’s Hospital from January 2015 to June 2018 were compared. The patient’s gender, age composition, best corrected visual acuity (BCVA), visual field date, pupil size at the time of examination, visual field defect type, location, visual field mean defect (MD), and mode defect (PSD) were recorded. Results There were 36 cases (40 eyes) with AION and 29 cases (33 eyes) with ION. There were significant differences in the mean age, the gender composition, BCVA, the visual field testing duration, the pupil sizes, MD and PSD between these two groups (P<0.05). Conclusions AION and ION are similar in clinical symptoms, but the visual field of the two is more diverse. It is closely related to the pathogenesis of the disease, so it differential diagnosis of the two diseases can be achieved by visual field examination. Key words: Anterior ischemic optic neuropathy; Idiopathic optic neuritis; Visual field

To compare the retinal layer thickness of eyes with optic neuritis (ON) and that of control eyes and ON eyes with and without neuromyelitis optica (NMO) or multiple sclerosis (MS). Horizontal and vertical SD-OCT scans of the fovea were undertaken for 56 patients with ON with and without NMO or MS and for 24 healthy controls. Patients with ON were divided into three groups: NMO, MS and isolated ON without NMO or MS. The thickness of each retinal layer was compared between ON and healthy control eyes, and between ON eyes with and without NMO or MS. Compared with healthy control eyes, ON eyes showed significant thinning of the ganglion cell layer plus the inner plexiform layer (GCL + IPL) at all eight inner and outer macular locations. Significant differences in thickness were observed for the retinal layers of NMO, MS and isolated ON without NMO or MS at several retinal locations. Our SD-OCT data revealed a notable difference in the GCL + IPL thickness between ON and healthy control eyes. It also showed differences in the thickness of several retinal layers for ON subgroups including NMO, MS and isolated ON. This may be helpful for distinguishing the aetiology of ON.

Optical coherence tomography (OCT) analyzes the neurodegeneration in neuromyelitis optica (NMO) and multiple sclerosis (MS) and quantifies optical atrophy. The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness are decreased, and this structural change is correlated with visual function of patients, including contrast vision and visual field deviation. The main objective of this study was to evaluate the Bruch membrane opening minimum rim width (BMO) of the patients with NMO. We studied the thickness of the BMO by OCT, in patients with NMO (n = 25; 34 eyes), MS (n = 50; 70 eyes), and a control group (n = 51; 100 eyes). The study evaluated the structure-function relationship with the correlation between OCT and visual function: Visual acuity, Pelli-Robson score, Sloan 2.5 and 1.25, color vision, standard automated perimetry (SAP), and frequency-doubling technology perimetry (FDT). The average thickness of BMO was significantly reduced in NMO and MS with or without a history of optic neuritis (ON). Significant thinning of the average, nasal, and inferonasal BMO in the absence of ON in NMO was found compared with controls (P = 0.022, 0.006, and 0.026, respectively). BMO was strongly correlated with Pelli-Robson score (P < 0.001), Sloan 2.5 (P < 0.001), and mean deviation of SAP and FDT (P = 0.004). The sectorial study found a high correlation between the BMO and the corresponding sector of the visual field. The BMO thickness is decreased after ON in NMO and MS. This study showed an improved ability of BMO over RNFL and GCL to detect infraclinical impairment in patients with NMO without a history of optic neuropathy. Like the RNFL and GCL, BMO is well correlated with visual function, including contrast vision and visual field deviation.

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI (p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture.

Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage independent of ON (optic radiation lesions), make the visual system a prime candidate for such endeavors. However, while the visual system makes for a convenient model in early stages of MS, processes which may be true in those stages may drastically change as the disease progresses, due to accumulated disease load. Here, we examine whether vision-related tools reflect demyelinative and axonal damage of the visual pathways and may be used for assessment in the clinical setup in progressive multiple sclerosis (MS) patients, in whom disease load may alter the early stage picture.Methods: Forty-eight progressive MS patients, with and without prior optic neuritis (ON), underwent a battery of behavioral tests, visual evoked potential (VEP) tests, optical coherence tomography (OCT), and structural MRI scans, at two time-points. Data were analyzed for stability between visits and for correlation between behavioral and electrophysiological data.Results: All measures were stable between visits. Significant differences were found in all measures between the affected and fellow eyes of ON patients and in VEP latencies between the affected and non-ON eyes. Motion perception differentially correlated with latencies of both ON eyes and with the non-ON eyes. Retinal nerve fiber layer thickness correlated with the latencies of non-ON eyes but not of either ON eye. No difference in lesion load was found between the ON and non-ON patients.Conclusions: ON still leaves its mark in the patient's visual system over time, with all visual measures of the affected eyes notably reduced compared to fellow eyes. Motion perception, reflecting myelination level along the visual pathway, shows its usefulness also in progressive MS. In the non-ON eyes, axonal loss appears to explain prolonged latencies, unlike in ON eyes, where demyelination appears to be the main mechanism. Lastly, the visual measures assessed herein are applicable as valid assessment tools in therapeutic studies.

To investigate the safety and outcomes of off-label immunomodulator Mycobacterium w. (Mw), a TLR 9 antagonist in steroid-resistant idiopathic unilateral optic neuritis. Case series. Eight patients with documented idiopathic unilateral optic neuritis who did not improve with methyl prednisolone followed by oral steroids as per the Optic Neuritis Treatment Trial (ONTT) were administered Mw 5 ml in 500 ml normal saline, 30 days after the last of dose of steroids had been administered. The dose was repeated at 3 months. Outcome measures monitoring the change in the best-corrected visual acuity (BCVA), pupillary reaction, colour vision, visual field (VF) examination (when possible), fundus examination and photography, visually evoked potential (VEP) testing. BCVA, pupillary reaction, and color vision were monitored immediately prior to steroid therapy, on days 1 and 7 post steroid therapy, pre Mw administration (i.e., 30 days after the last dose of steroids had been completed) and post Mw administration on days 1, 7, 30, 90, 120 and 180. VF, VEP and fundus photography was performed immediately prior to steroid administration, 30 days after the last dose of steroids (i.e., immediately prior to Mw), and days 30, 90,120 and 180 post Mw administration. There were five females and three males in an age range of 30-54 years. Six patients were available for follow-up at 6 months. All patients showed improvement in visual acuity, colour vision & pupillary reaction. Visual field monitoring was possible in four patients; all four had a centrocecal scotoma that persisted post steroid therapy but resolved 1 month post Mw therapy. Three out of five patients who had disc edema were available for all follow-ups, and showed resolution of disc edema post Mw therapy. The disc edema had persisted post steroid therapy. No adverse events were seen. The 2nd dose did not improve any of the said parameters. There was no recurrence of the disease up to the end of the follow-up period. Mw appears to improve steroid resistant optic neuritis; future randomized clinical trials would help affirm this observation.