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.

     

Cytokines and soluble IL-4 in patients with acute optic neuritis and multiple sclerosis

We measured the cerebrospinal fluid (CSF) and plasma concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, TNF-β, interferon (IFN)-γ, the IL-1 receptor antagonist, and soluble IL-4 receptor (sIL-4r) by ELISA in 12 patients each with acute, monosymptomatic, idiopathic optic neuritis (ON), ON as part of MS, other attack forms of MS, and in neurological control subjects. CSF concentrations of IL-1β, IL-2 and IFN-γ differed significantly between the different patient groups and were detected most commonly at the highest concentrations in patients with non-ON attacks of MS. TNF-β was detected exclusively in CSF from neurological control patients. The patients with non-ON attacks of MS also had significantly elevated concentrations of sIL-4r in plasma. Increased CSF concentrations of IL-1β, IL-2 and IFN-γ together with increased plasma concentrations of sIL-4r support the concept of MS as an autoimmune disease with preferential activation of proinflammatory or T-helper type 1-like cells. Patients with idiopathic ON or ON as part of MS may, however, differ immunologically from patients with other attack forms of MS.     

视神经炎与多发性硬化的关系研究

目的为了探讨视神经炎与多发性硬化的关系。方法分析２８例视神经炎患者的头颅磁共振（ＭＲＩ）及体感诱发电位（ＳＥＰ）检查情况。结果（１）头颅ＭＲＩ扫描异常率为３２．１％，病灶呈多发性，主要分布在侧脑室旁、半卵圆中心，长Ｔ２信号，少数合并长Ｔ１信号。（２）ＳＥＰ中枢传导异常率为４２．９％，下肢异常多于上肢，单侧异常多于双侧。（３）发病两次及两次以上，脊髓受累机会增加。结论伴有较多的亚临床损害的视神经炎可能是多发性硬化的一个临床类型     

Clinically isolated syndromes and the relationship to multiple sclerosis

The most common presentation of multiple sclerosis (MS) is with a clinically isolated syndrome (CIS) affecting the optic nerves, brainstem or spinal cord. Two thirds of patients with CIS will have further episodes of neurological dysfunction and convert to relapsing-remitting MS, while the remaining patients have a monophasic illness, at least clinically. Abnormalities on a baseline MRI scan predict the subsequent development of MS in patients with CIS. In the long term, about 80% of patients with an abnormal MRI convert to MS compared with 20% with a normal MRI. For patients who develop MS the long term prognosis is varied. After 20 years, almost half will have developed secondary progressive MS, while around one third have a benign disease course with little physical disability. Disease-modifying treatments delay conversion to MS in selected CIS patients with abnormal MRI but an effect on long term disability has not been demonstrated. In this review we discuss recent advances in the diagnosis, management and prognostication of patients with CIS.     

Asymptomatic visual loss in multiple sclerosis

Visual disturbances are common in multiple sclerosis (MS) and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. This type of silent disease activity was investigated by computerised resolution perimetry, which has the potential to reflect the percentage of functional retino-cortical neural channels. The time of onset and the evolution of asymptomatic visual loss was investigated. One approach was to retrospectively select patients who never had suffered acute optic neuritis from a closely monitored MS population and re-examine them again. Sixteen patients were identified and vision was evaluated during a period of 5.5–9 years of follow-up and compared with that in 14 healthy controls. The mean channel percentage of the MS group was 89 ± 19 % (SD) on entry into the study, compared with 110 ± 15 % (SD) of controls (p < 0.003). At termination of the study the mean percentage was essentially unchanged both in MS patients (87 ± 21 %, SD) and controls (110 ± 19 %, SD). The second approach was to test a group of 7 patients with MS or strongly suspected MS, with the same method, in close connection with their first clinical exacerbation. All cases lacked visual symptoms and none had previously had acute visual loss. Again, virtually all performed subnormally in the vision tests, and to the same degree as in the first group of patients. Results were compared with those obtained from 25 MS patients who had experienced one or more attacks of optic neuritis. Compared with controls the loss of functional retino-cortical neural channels was 20 % in patients without a previous history of optic neuritis and 30 % in patients who previously had experienced optic neuritis. We conclude that asymptomatic visual loss seems to be a universal feature of MS and has a substantial impact on the visual pathways, that it is present already at the time of clinical onset of the disease, and that any progression thereafter is slow enough to elude detection during several years of follow-up. Received: 28 June 2000, Received in revised form: 7 March 2001, Accepted: 23 April 2001     

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.     

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.     

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...     

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.     

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     

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.     

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.     

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.     

Optic neuritis as an initial symptom in multiple sclerosis

The present study is based on a multicenter documentation system which includes standardized information on a total of 1271 patients with multiple sclerosis (MS). In 441 (34.7%) cases the optic nerve was involved at the first appearance of the disease, and in 212 (16.6%) subjects optic neuritis (ON) was the sole initial sign. For all MS patients with ON at the onset of the disease the female to male ratio was 1.3, whereas it was 1.5 for the whole series. The mean age at onset was 2 years lower for patients with initial ON as compared with the whole series (29.0 and 31.1 years, respectively). Correlation of the disability of the patients to the duration of the disease revealed the best prognosis for patients with ON as the sole initial sign of MS. The frequency of brainstem/cerebellar and pyramidal signs was lowest among these patients at the time of the present examination. The difference was more pronounced during the first years of the disease and disappeared after longer duration. The correlation curves of disability to the present age of the patients confirmed this pattern. Our findings do not support the idea of initial ON as being a favorable sign of the later course. As an initial bout of MS, it may reflect more precisely the mean age of onset of the disease than other signs.     

T-lymphocyte immunointerferon receptors in patients with multiple sclerosis

Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system (CNS), associated with an altered immunoregulation. Interferon (IFN)-, also known as immune IFN, is a cytokine with several effects on the immune system. Specific IFN- receptors have been found on human lymphocytes, as well as on other cell types (e.g. gliocytes), even in the CNS. The aim of the present study was to evaluate IFN- binding on peripheral blood T-lymphocytes from MS patients, compared with those from healthy subjects. Thirty-two patients were selected according to the classical criteria for definite MS; as controls, 21 healthy subjects were studied. We have found that T-lymphocytes from MS patients bear a significantly smaller amount of IFN- receptors than those from controls [B _max: 568, 18 vs 708, 14 (mean, SE) receptors/cell]. Such IFN- binding sites are of the same type in patients and healthy subjects [K _d: 1.0, 0.05 vs 0.9, 0.02 (mean, SE) nM]. These findings are discussed in terms of immunopathogenesis of MS, since it has been reported that activated T-lymphocytes have decreased amounts of IFN- receptors.     

免疫球蛋白对多发性硬化急性期患者神经功能的改善作用

目的探讨免疫球蛋白对多发性硬化(MS)急性期患者神经功能的改善价值。方法回顾性分析2011-03—2015-09我院90例急性期多发性硬化患者的临床资料。对照组45例行单纯甲泼尼龙治疗方案,观察组45例行甲泼尼龙联合免疫球蛋白治疗方案。比较2组治疗效果、对神经功能的影响及不良反应发生情况。结果观察组总有效率为86.67%,显著高于对照组的68.89%,差异有统计学意义(P0.05)。观察组治疗结束时和治疗后4周神经功能障碍(EDSS)评分分别为(2.78±0.44)分和(1.97±0.23)分,对照组分别为(4.12±0.70)分和(3.16±0.51)分,组间比较差异有统计学意义(P0.05)。2组不良反应发生率比较,差异无统计学意义(P0.05)。结论免疫球蛋白联合激素治疗急性期多发性硬化疗效显著,能显著改善患者神经功能,且不增加不良反应发生率,临床应用价值较高。     

Immunological monitoring of azathioprine treatment in multiple sclerosis patients

Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5–3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-α). The most relevant changes included a decrease in CD3^–CD56⁺ cells, an increase in CD4⁺CD45RA⁺ cells and a decrease in TNF-α levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-α levels and the increase in “suppressor-inducer” lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients. Received: 9 July 1996 Received in revised form: 21 October 1996 Accepted: 22 November 1996     

Hypermetabolism in multiple sclerosis patients

Hypermetabolism, which can lead to wasting syndrome, is well recognized in diseases such as AIDS, cancer, rheumatoid arthritis, sepsis and burns. In these conditions proinflammatory cytokines are thought to be essentially involved. In experimental allergic encephalitis (EAE), which is regarded as an animal model of multiple sclerosis (MS), wasting syndrome and elevated levels of cytokines have also been reported. The aim of this study was to investigate whether hypermetabolism does occur in MS patients. After a 3-day standard diet the basal metabolic rate (BMR) was measured by indirect calorimetry in 20 MS patients and 10 healthy controls. Body composition was assessed using an impedance analyser and lean body mass (LBM) was calculated. Other metabolic disturbances and infectious disease were ruled out by clinical examination and various laboratory tests. Tested by analysis of variance (ANOVA), the BMR corrected for LBM was increased by an average of 6% in the patients group (p < 0.05) as compared to the controls. As far as we know this is the first study demonstrating the presence of hypermetabolism in MS.