Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI

When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p = 0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p = 0.004) and incomplete visual acuity recovery (⩽6/12) after 1 year (p = 0.002). Lower conversion rates were found in patients with optic disc edema (p = 0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate.     

Optic neuritis in relation to multiple sclerosis

Summary Available estimates of the frequency with which a patient with optic neuritis develops multiple sclerosis range from as low as 13 percent to as high as 87 percent. In an effort to obtain a better estimate, a nation-wide study of optic neuritis was carried out in Israel. Patients who fulfilled strict diagnostic criteria of optic neuritis were identified and examined periodically.Between 1955 and 1964, 105 patients were found and on the basis of these, the average annual age-adjusted incidence of optic neuritis in Israel was 0.56 per 10⁵ population compared to 1.2 per 10⁵ cases of multiple sclerosis per year, i.e. optic neuritis was about half as frequent as multiple sclerosis each year. As with multiple sclerosis, optic neuritis was more common in European immigrants to Israel than in Afro-Asian immigrants.During a follow-up interval which ranged from 3.3 to 15.6 years (mean 9.5 years), at least 27 of the 105 patients developed multiple sclerosis (28 percent). A life-table analysis showed that after 10 years 32.3 ± 5.6 percent of patients with optic neuritis would develop multiple sclerosis and, after 14 years, about half would develop multiple sclerosis.Risk of dissemination was highest in those who were youngest when optic neuritis developed. Neither sex nor ethnic background influenced risk significantly. Results of the present study support earlier work using life-table methods carried out in Hawaii which also showed that between 29 and 39 percent of patients with optic neuritis will develop multiple sclerosis within 10 years of onset. The life-table method is a better predictor of prognosis than newer laboratory techniques such as spinal fluid studies of IgG, kappa-lambda light chain ratios and serum/CSF IgG ratios.

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Zusammenfassung Schätzungen der Häufigkeit, mit der ein Patient mit Retrobulbärneuritis eine Multiple Sklerose bekommt, schwanken zwischen 13 und 87%. Um zu genaueren Werten zu kommen, wurde eine die ganze Bevölkerung umfassende Studie in Israel ausgeführt. Patienten mit den typischen Merkmalen einer Retrobulbärneuritis wurden erfaßt und periodisch untersucht.Zwischen 1955 und 1964 wurden 105 Patienten gefunden. Das ist eine durchschnittliche jährliche altersbereinigte Häufigkeit der Retrobulbärneuritis in Israel von 0,56 bei einer Bevölkerungszahl um 10⁵. Verglichen damit ist die jährliche Häufigkeit der Multiplen Sklerose 1,2 auf 10⁵, d. h. die Retrobulbärneuritis ist halb so häufig wie die MS. Wie die MS ist die Retrobulbärneuritis häufiger in Israel unter europäischen Einwanderern als bei Afro-Asiaten.Während der Kontrollperiode von 3,3 bis 15,6 Jahren (Durchschnitt 9,5 Jahre) zeigte sich bei 27 der 105 Patienten eine MS (28%). Die Sterbetafeln ergaben eine Häufigkeit von 32,3 ± 5,6% nach 10 Jahren, nach 14 Jahren zeigte sich etwa bei der Hälfte der Patienten eine MS. Das Risiko war am höchsten bei den jüngsten Patienten. Weder Geschlecht noch ethnische Abstammung beeinflußten dieses Risiko signifikant.Die Ergebnisse der Studie bestätigten frühere Untersuchungen in Hawaii, die nach den Sterbetafeln eine Häufigkeit von 29 bis 39% ergab, mit welcher innerhalb von 10 Jahren nach Ausbruch der Retrobulbärneuritis eine MS auftrat. Die Sterbetafeln gestatten eine bessere Voraussage der Prognose als neuere Labortechniken wie die Untersuchung der IgG im Liquor, der Kappa-Lambda leichte Kettenrationen und IgG in Serum und Liquor.

     

Tumor necrosis factor alpha gene polymorphism in multiple sclerosis and optic neuritis

The NcoI tumor necrosis factor (TNF alpha) polymorphism was studied in relapsing/remitting multiple sclerosis and monosymptomatic optic neuritis. The frequency of the NcoI marker phenotypes did not differ between healthy controls and the two disease groups. No extra or missing DNA fragments were observed in the disease groups when compared with controls.     

伴视神经炎的多发性硬化患者外周血CD19+B细胞中基因差异表达及相关通路的研究

目的 利用生物信息学方法分析伴视神经炎的多发性硬化患者外周血CD19+B细胞中基因标记物的特征.方法 从GEO数据库获取伴视神经炎的多发性硬化患者外周血CD19+B细胞中基因芯片表达谱,利用GEO2R软件进行差异表达分析,应用GO和KEGG对差异基因进行功能注释和通路分析,并进一步应用stringdb数据库进行蛋白相互...     

Evaluation of gelatinases and IL-6 in the cerebrospinal fluid of patients with optic neuritis,multiple sclerosis and other inflammatory neurological diseases

The activities of the metalloproteinase gelatinase B, and the presence of IL-6, an inducer of metalloproteinase inhibitors, were investigated in CSF samples of 190 patients with multiple sclerosis (MS; n = 55), optic neuritis (ON; n = 46), other inflammatory neurological diseases (OIND; n = 27) or control patients (CON) with non-inflammatory neurological diseases (n = 62). IL-6, measurable as hybridoma growth factor activity (detection limit 3 pg/ml), was found in only four of these 190 CSF samples (three OIND, one CON). Elevated CSF gelatinase B levels were detected in 40%, 35% and 54% of the patients with MS, ON and OIND, respectively, while all control CSFs were devoid of gelatinase B activity. Clinical and laboratory data were compared with gelatinase B levels. No correlation was found between the CSF cytoses and gelatinase B levels, suggesting that this enzyme in the CSF originates from CNS lesions rather than from CSF cells. However, the occurrence of the gelatinase B significantly correlated with the IgG index in the MS patient group. This study stimulates further investigation into the possible usage of protease inhibition in demyelinating diseases.     

Optical coherence tomography (OCT) in optic neuritis and multiple sclerosis

Optical coherence tomography (OCT) is a non-invasive imaging technique routinely used in ophthalmology to visualize and quantify the layers of the retina. It also provides information on optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume, which correlate with axonal loss. These measurements are of particular interest in optic neuropathies and in multiple sclerosis, and OCT parameters are now used as endpoints in neurologic clinical trials.     

Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: A review

Multifocal visual evoked potential (mf-VEP) represents a new approach to the classical full field (ff-)VEP with separate responses from up to 60 sectors of the visual field. A thorough literature survey of the use of mf-VEP in optic neuritis (ON) and multiple sclerosis (MS) is presented (38 published studies were retrieved). Mf-VEP provides direct topographical information of specific lesions and facilitates investigations on structural-functional correlations thus providing new methods for exploring the interplay between demyelination, atrophy and remyelination in MS. Good correlation was shown between mf-VEP and OCT, ff-VEP, MRI (MTR, DTI), 30-2 standard automated perimetry and low-contrast-visual acuity. All but one study showed superior sensitivity and specificity compared to ff-VEP, especially with regards to small, peripheral lesions or lesions of the upper visual field. Mf-VEP has shown superior sensitivity and specificity than established methods in diagnosing optic nerve lesions and tracking functional recovery following lesions. Abnormal mf-VEP responses in the fellow, non-ON afflicted eye may predict MS risk in ON patients. No standardization currently exists and no direct comparisons in ON and MS between at least 5 different commercially available mf-VEP systems have so far been published. Despite these limitations, mf-VEP is a promising new tool of diagnostic and prognostic value of mf-VEP in ON and MS.     

Clues to the immunopathogenesis of multiple sclerosis by investigating untreated patients during the very early stage of disease

Plethora of abnormalities of the immune system has been described in multiple sclerosis (MS). They include a number of myelin antigens (e. g. MBP, MOG, PLP, MAG), the presence of reactive T cells in blood and, further enriched, in the cerebrospinal fluid (CSF), large numbers of B cells in the CSF secreting antibodies of multiple but unknown specificities, an increase of mononuclear cells (MNC) expressing and secreting both pro- and anti-inflammatory cytokines, including Th1 cytokines interferon-gamma (IFN-γ) and interleukin (IL)-6, the Th2 related IL-4 and IL-10, and the Th3-driven TGF-β, elevated numbers of MNC in both blood and CSF expressing a spectrum of metalloproteinases and their inhibitors, as well as many other aberrations. However, no consistent patterns have emerged that relate any of these findings to clinical variables such as exacerbations, during of disease, disability, or lesions in the central nervous system (CNS) detected at magnetic resonance imaging. In order to elucidate the relevance of these immunological abnormalities in the pathogenesis of MS, my colleagues and I studied patients with acute monosymptomatic optic neuritis (ON) and compared them with patients with clinically definite MS (CDMS). The patients have not been treated and have not received corticosteroids or interferon-β. When comparing these two groups, we were unable to identify any differences in any of the variables mentioned. Thus, very early MS, as represented by ON, shows the same full-blown pattern of immunological abnormalities seen in CDMS. Furthermore, a complete epitope spread affecting MBP, MOG, PLP, MAG and other myelin components is already present in ON. Whether any of these alterations play a pathogenetic role is still unsettled.     

特发性脱髓鞘性视神经炎的临床转归

目的 了解特发性脱髓鞘性视神经炎(IDON)临床转归、转化为多发性硬化(MS)或视神经脊髓炎(NMO)的比例以及相关影响因素.方法 对确诊且临床资料完整的IDON患者进行病例回顾及随访,记录视功能和其他神经功能变化以及MS或NMO转化率,应用卡方检验分析不同临床特征对转化率的影响.结果 共入组资料完整且完成随访的IDON患者107例.多数患者视力恢复较好,12例(11.2%)在随访期间转化为MS或NMO.全部12例患者均符合2005年修订的McDonald诊断标准,其中4例符合1999年NMO诊断标准,其余8例中部分表现为"视神经脊髓型MS".复发性IDON较首次发病患者、伴头颅MRI异常较MRI正常者转化为MS或NMO的比例高,分别为23.1%和4.4%(χ2=6.899,P<0.01)以及18.2%和8.1%.是否伴有视乳头水肿以及不同视力损害程度组之间转化为MS或NMO的比例没有差异.结论 该组IDON患者转化为MS或NMO的比例为11.2%.复发性IDON和伴有头颅MRI异常的患者更易转化为MS或NMO.     

Steriods for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials

We conducted a meta-analysis of randomized controlled clinical trials on steroid treatment for multiple sclerosis and optic neuritis. Of the 25 trials comparing steroids and controls without steroid treatment that we identified 12 were selected for this review. A meta-analysis was conducted to calculate the overall odds ratio across the studies for the numbers of patients without functional improvement and with new relapses. The trials included a total of 1714 patients: 998 with multiple sclerosis and 716 with optic neuritis. Any type of corticosteroids or adrenocorticotropic hormone (ACTH) treatment was considered, as was any dosage, route of administration, and length of treatment. Main outcome measures were: (a) number of multiple sclerosis patients who did not improve by at least one point on the EDSS or equivalent scale, or number of optic neuritis patients without complete recovery of visual acuity at 8 or 30 days and at longer follow-up; (b) number of multiple sclerosis patients with at least one new relapse, or number of optic neuritis patients in whom definite multiple sclerosis was diagnosed at longer follow-up. We found that corticosteroids or ACTH produced a significant improvement in disability or visual acuity at 30 days (odds ratio 0.49; 95 % CI 0.37–0.64). The improvement was not statistically significant at longer follow-up (0.85; 95 % CI 0.67–1.09). The treatment did not significantly reduce the number of patients with relapses (0.74; 95 % CI 0.54–1.01). Both low and high doses were effective for 30-day improvement, but only high-dose and short-term therapy were factors that identified subgroups with some reduction in the risk of new relapse. However, the power of the statistical analysis to detect a reliable difference in the subgroups was low. Steroid treatment is therefore effective in accelerating short-term recovery in patients with multiple sclerosis or optic neuritis. Whether steroids are also effective in reducing the risk of relapse, and the optimal dose and length of treatment must still be determined. Received: 5 August 1999, Received in revised form: 29 December 1999, Accepted: 22 January 2000     

Brain MRI follow-up of patients with persistent isolated optic neuritis

In this study a brain MRI long-term follow-up of 19 patients at presentation with Acute Isolated Optic Neuritis (AION), who did not develop further neurological disturbances, was performed to evaluate the frequency of subclinical evolution of the pathological process. At presentation, the brain MRI in nine patients was abnormal and in 10 normal. CSF oligoclonal bands were found in 11 patients, five of whom had normal basal MRI. All patients with abnormal basal MRI had new lesions on follow-up scans, while only one of the patients with a normal basal brain MRI had multiple lesions on the second scan. Our data suggest that about 50% of patients with AION had subclinical activity, even though there were no new clinical relapses.     

Visual evoked potentials after optic neuritis

Visual evoked potentials (VEPs) were compared among six groups of patients tested at various times after an episode of acute unilateral optic neuritis (ON). The incidence of abnormalities ranged from above 90% in patients tested during the first 6 months to about 70% when more than 2 years had elapsed. Compared with the acute stage (1–8 weeks), latency prolongation was almost 50% less in patients tested after 2–19 years. In the latter group, latencies were significantly correlated with the patients' age at the time of the attack. The findings confirm and extend the evidence of serial studies which shows that the shortening of VEP latency is a general phenomenon which proceeds for up to 2 years and possibly for longer in younger patients. When the patients with clinically isolated ON were compared with those who had a history of additional neurological episodes suggestive of multiple sclerosis (MS), up to 4 weeks after ON latencies were more prolonged in the MS group but between 4 and 8 weeks amplitudes were larger and between 8 weeks and 2 years latencies were significantly shorter. No significant differences were found in patients tested after more than 2 years. It is suggested that the electrophysiological deficit may initially be more severe in patients with disseminated disease, but that recovery may occur faster.     

Bilateral and recurrent optic neuritis in multiple sclerosis

Burman J, Raininko R, Fagius J. Bilateral and recurrent optic neuritis in multiple sclerosis.
Acta Neurol Scand: 2011: 123: 207–210.
© 2010 John Wiley & Sons A/S. Objective – To assess the frequency of bilateral and recurrent optic neuritis (ON) in multiple sclerosis (MS) and to compare these results with epidemiological data of ON in neuromyelitis optica (NMO) and recurrent ON without other signs of disease. Methods – We identified 472 patients with diagnosis of MS from the Swedish Multiple Sclerosis Register. These patients were evaluated for the presence of ON and whether the ON was the presenting symptom of MS; unilateral or bilateral; monophasic or recurrent. Results – Twenty‐one percent presented with ON as their first manifestation of MS. The proportion of patients developing a second attack of ON before demonstration of other manifestations of MS was 5.5% and the frequency of recurrent bilateral ON as the presenting symptom was 3.8%. Only two patients presented with simultaneously appearing bilateral ON corresponding to 0.42%. Conclusion – Recurrent ON, whether unilateral or bilateral, is a common presentation of MS. As MS is a much more common disease than NMO, care must be taken when evaluating the work‐up of patients with recurrent ON. In some cases repeated MRI and lumbar punctures are warranted to improve diagnostic accuracy, even in the presence of the serological marker NMO‐IgG.     

Cell-mediated immunity in acute idiopathic optic neuritis and multiple sclerosis

Lymphocyte transformation responses to phytohaemagglutinin, measles antigen and tuberculin and the absolute numbers of circulating T and SIg+ cells were determined in 16 patients with acute idiopathic optic neuritis (ON), 42 patients with multiple sclerosis (MS) and 78 healthy controls.
Patients with acute ON showed impaired lymphocyte transformation responses in both autologous plasma and AB serum similar in extent to those seen in MS patients in relapse. They were not associated with a reduced total number of circulating T cells.     

Visual evoked blink reflex in optic neuritis

Summary The optically evoked blink reflex (BR) was recorded in 30 patients (20 females, 10 males) with primary acute optic neuritis (ON) unassociated with other CNS disorders. The reflex was studied in the acute stage between the 1st and 6th day after onset, during the 1st month following the acute stage once a week, and then 2 and 6 months later. In patients in whom a relapse occurred, the programme was restarted from the beginning. Control values were taken from prior investigations in 50 healthy subjects. In the acute stage differences in the amplitudes were present in 26 patients, but the latencies remained within normal limits. Six patients (20%) developed multiple sclerosis during the 5-year follow-up until December 1985. In these cases the optic BR showed increased latencies and decreased amplitudes. In patients without manifestation of multiple sclerosis the BR remained normal. In 7 patients cranial magnetic resonance imaging (MRI) was done. All patients with some abnormalities in the visual BR also had an abnormal MRI. The pattern-shift visual evoked potentials were abnormal in the acute stage of ON in 90%, and CSF abnormalities were found in 56.6%. In 4 patients (13%) the visual BR could not be evoked at all.     

Interferon-alpha and interferon-gamma production capacity of idiopathic isolated optic neuritis patients

Interferon-alpha and interferon-gamma production by idiopathic isolated optic neuritis (ON) patients was studied. The production capacity was compared with that in two control groups: patients with iritis and healthy control subjects. A sensitive and reliable interferon bioassay was applied for interferon level measurements. Statistically significant differences were not found between patients and control groups in either interferon-alpha production or interferon-gamma production.     

Long time echo STIR sequence magnetic resonance imaging of optic nerves in optic neuritis

Magnetic resonance images of optic nerves were obtained in 20 patients with acute optic neuritis (ON), and assessed by means of clinical, visual field and visual evoked potential evaluations; the imaging was repeated 1 year later. The results of the conventional Short Tau Inversion Recovery (STIR) sequence obtained using short time echo (STE-STIR: 22 msec) were compared with those of the long time echo sequence (LTE-STIR: 80 msec). The conventional STE-STIR sequence revealed lesions in 57.2% cases of acute ON and in 42.9% of the optic nerves affected by previous ON: the LTE-STIR sequence was diagnostic in 95.2% of acute ON cases and in 85% of patients with previous ON. The calculated length of the optic nerve lesions was significantly longer in the images obtained using the LTE-STIR sequence than in those obtained using conventional STE-STIR sequences.

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Sommario Si descrivono i risultati ottenuti con indagini di Risonanza Magnetica (RM) dei nervi ottici (eseguite all'esordio e 12 mesi dopo) in 20 pazienti affetti da Neurite Ottica (NO) acuta, valutata in funzione della sintomatologia clinica e delle alterazioni campimetriche e del potenziale evocato visivo.Sono state analizzate le immagini RM in Short Tau Inversion Recovery (STIR) mettendo a confronto i rilievi ottenuti con sequenza Short Time Echo (STE-STIR: 22 msec) rispetto a quelli ottenuti con Long Time Echo (LTE-STIR: 20 msec). Mentre con la convenzionale STE-STIR è stato possibile rilevare lesioni a carico dei nervi ottici nel 57.2% delle Neuriti Acute e nel 42.9% delle Neuriti Pregresse, la metodica LTE-STIR è risultata diagnostica nel 95.2% delle Neuriti Acute e nel 85% delle Neuriti Pregresse.Sia nelle NO acute che nelle pregresse, la lunghezza delle lesioni a carico dei nervi ottici sono risultate significativamente maggiori rispetto a quelle ottenute con la convenzionale metodica STE-STIR.

     

Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients

Objective

Optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis (MS) research and has been suggested as outcome measure for neuroprotective therapies. However, to date it is not clear whether patterns of retinal nerve fiber layer thickness (RNFLT) loss are different in MS compared to other diseases such as glaucoma and data on RNFLT loss in MS patients with or without optic neuritis (ON/NON) have remained inconsistent or even contradictory.

Methods

In this large cross-sectional study we analyzed the patterns of axonal loss of retinal ganglion cells in MS eyes (n = 262) with and without history of ON (MS/ON: 73 eyes; MS/NON: 189 eyes) and patients eyes with glaucomatous optic disc atrophy (GA: n = 22; 39 eyes) in comparison to healthy control eyes (HC: n = 406 eyes).

Results

We found that significant average and quadrant RNFLT loss is detectable by OCT in both MS and GA patients compared to healthy controls (p < 0.01). The age- and gender adjusted average and quadrant RNFLT did not differ significantly between MS and GA patients (p > 0.05). Average (p < 0.0001) and quadrant (p < 0.05) RNFL thinning is significantly more severe in MS/ON versus MS/NON eyes, and the extent of RNFL thinning varies across quadrants in MS/ON eyes with the highest degree of RNFLT loss in the temporal quadrant (p < 0.001).

Conclusion

RNFLT reduction across all four quadrants in MS patients as a whole as well as in MS/NON eyes argues for a diffuse neurodegenerative process. Superimposed inflammatory attacks to the optic nerve may cause additional axonal damage with a temporal preponderance. Future studies are necessary to further evaluate the capacity of OCT to depict disease specific damage patterns.     

Optical coherence tomography angiography findings of multiple sclerosis with or without optic neuritis

ABSTRACT

Objective: Nowadays, retinal microvascular structures can be investigated using optical coherence tomography angiography (OCTA). We aimed to evaluate the probable vascular changes in the foveal and peripapillary regions of patients with multiple sclerosis (MS).

Methods: A total of 20 patients with relapsing remitting multiple sclerosis (RRMS) and 24 healthy controls were recruited in this study. All participants’ superficial and deeper retinal and peripapillary layers were evaluated using OCTA after a total ophthalmologic examination.

Results: In the superficial plexus, the whole image (49.53 ± 3.9% and 51.83 ± 2.1%, p = 0.009), superior hemisphere (49.44 ± 4.11% and 51.63 ± 2.3%, p = 0.018), inferior hemisphere (49.75 ± 3.9% and 52.03 ± 2.2%, p = 0.012), parafoveal (51.87 ± 3.9% and 53.08 ± 3.46%, p = 0.048) and perifoveal (50.41 ± 3.86% and 52.76 ± 2.1%, p = 0.007) vascular densities were statistically significant lesser in patients with RRMS than in controls. In the optic disc OCTA parameters, the vessel density of the inferior (50.15 ± 6.99% and 53.04 ± 3.63% p = 0.043) and temporal sector (48.09 ± 5.47% and 50.85 ± 5.24%, p = 0.045) were statistically significantly lesser in patients with RRMS than in controls.

Conclusion: The reductions in vessel density of the retinal or peripapillary area of patients with RRMS shown in this study should be investigated further to determine whether it is a secondary lesion to optic neuritis (ON) or a primary vasculopathic condition of MS.