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.     

A case of myasthenia gravis associated with optic neuritis

Summary A case of myasthenia gravis is described in association with optic neuritis in which brain-stem auditory and somatosensory evoked potentials were normal. CSF contained alkaline oligoclonal IgG bands. Blood lymphocyte subpopulations showed a decreased number of T-suppressor cells.

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Zusammenfassung Es wird ein Fall von Myasthenia gravis beschrieben bei welchem auch eine Opticusneuritis beobachtet wurde. Die akustischen evozierten Hirnstammpotentiale sowie die somatosensorischen evozierten Potentiale waren normal. Im Liquor fanden sich oligoklonale IgG-Banden. In der Subpopulation der Blutlymphocyten war eine verminderte Zahl von T-Supressorzellen vorhanden.

     

Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis

PURPOSE: To demonstrate whether optical coherence tomography (OCT-3) and scanning laser ophthalmoscopy (HRT-2) can be used to measure changes of the optic disc and peripapillary retinal nerve fiber layer (RNFL) in eyes with acute retrobulbar optic neuritis that have no clinically apparent optic disc swelling. To correlate these findings with presentation magnetic resonance imaging (MRI) of the affected optic nerve. METHODS: Eight consecutive patients with acute retrobulbar optic neuritis, who had no prior optic neuritis in either eye, were prospectively investigated at presentation and at between 1 and 3 months with clinical examination, OCT-3, HRT-2. At presentation, MRI of the optic nerves were performed in 7/8 patients. RESULTS: Compared to unaffected eyes, affected eyes without clinically seen optic disc swelling at baseline, there was a non-significant trend to increased thickness in the total RNFL, superior and nasal measurements. Baseline HRT in affected eyes showed smaller mean cup to disc ratio (p=0.003) and a smaller cup area (p=0.002) compared with the unaffected eye. The MRI-demonstrated optic nerve lesion did not correlate with OCT RNFL thickening or HRT decrease of the physiological cup. Follow-up imaging of the affected eyes showed normalization of HRT cup size parameters and OCT RNFL thickness (p<0.04). At follow-up, the temporal RNFL had thinning in 7/8 affected eyes (46.8 mum, p=0.021) compared with fellow unaffected eyes (57.8 mum), which did not change. CONCLUSION: OCT-3 and HRT demonstrate mild RNFL thickening or optic disc swelling in acute optic neuritis, even when swelling is not seen clinically. OCT-3 appears to reveal measurable RNFL thinning in the temporal quadrant after retrobulbar optic neuritis, even though vision improves. RNFL imaging may be useful in future studies of residual injury after optic neuritis.     

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.     

A clinical and radiological profile of neuromyelitis optica and spectrum disorders in an Indian cohort

Background:

There is insufficient data on the clinical and radiological features of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) from India.

Objective:

The objective of the following study is to examine the clinico-radiological features of NMO and NMOSD in an Indian cohort.

Materials and Methods:

This retrospective study included 44 consecutive patients who (1) satisfied the 2006 Wingerchuk criteria for NMO (16 seropositive and 7 seronegative); or (2) had isolated or recurrent optic neuritis (ON) with seropositivity (n = 4); or (3) had isolated or recurrent myelitis with seropositivity (n = 17).

Results:

The female:male ratio was 7.8:1 with median age of onset 26.5 (range 8-72). Annualized relapse rate (ARR) was comparable across all groups (F [3, 40] = 0.938 and P = 0.431). Various presentations other than ON and myelitis were noted. All 40 patients with myelitis had spinal cord lesions involving ≥3 vertebral segments during the course of the disease. Cervicomedullary involvement was seen in 32.5% (13/40) patients. Brain magnetic resonance imaging was available for 40 patients; eight of these (20%) had brain lesions in locations described in multiple sclerosis (MS), 27.5% (11/40) had lesions at sites unusual for MS and 52.5% (21/40) had normal brain imaging.

Conclusion:

NMO and NMOSD patients in this cohort have comparable ARR regardless of clinical presentation, supporting the emerging trend of treating all patients with immunotherapeutic agents at an early stage. Varied presentations seen in NMO and NMOSD highlight the need for a high index of suspicion for NMO in demyelinating episodes not classical for MS.     

复发性视神经炎静息态低频振幅功能磁共振成像研究

目的研究复发性视神经炎患者异常神经功能活动脑区的分布差异,探讨基线神经功能及其与临床的关系。方法采用基于低频振幅(ALFF)的静息态f MRI技术对35例复发性视神经炎患者进行研究,并与50例性别、年龄和受教育程度相匹配的正常对照者进行比较,并分析m ALFF值改变脑区与病程、同步听觉系列加法测验(PASAT)评分和视力之间的相关性。结果与正常对照组相比,复发性视神经炎组患者左侧楔叶/楔前叶、左侧颞上回、双侧颞下回、双侧舌回和右侧枕中回m ALFF值降低(P0.01),而双侧额下回和左侧额叶内侧回m ALFF值增加(P0.01)。复发性视神经炎患者仅左侧颞上回(r=0.403,P0.05)和右侧舌回(r=0.472,P0.05)m ALFF值与病程呈正相关。结论静息态f MRI可以检出复发性视神经炎患者参与视觉信息处理的颞枕叶神经功能降低,以及与脑默认网络相关的额叶神经功能增强,为早期评价视神经炎患者神经功能和预测预后提供客观依据。     

Optic perineuritis: A further cause of visual loss and disc edema in children

Background: Optic perineuritis is a rare form of orbital inflammatory pseudotumor in which the specific target tissue is the optic nerve sheath. Patients are mainly represented by adult women. Differential diagnosis with demyelinating optic neuritis is essential in terms of prognosis and treatment. Case presentation: An 8-year-old Caucasian girl presented with bilateral loss of vision, disc edema, eye movement impairment, and diplopia. Brain MRI findings were suggestive of optic perineuritis. The patient received steroid pulse therapy followed by prolonged course of oral steroid therapy. The visual acuity recovered dramatically within 2 days. Two months later, a new MRI investigation was normal. No clinical relapse was observed at the follow-up. Discussion: We first report on a child affected by optic perineuritis. Our observation suggests that optic perineurits should be considered in the differential diagnosis of children presenting with visual loss and disc edema. An early and correct diagnosis may lead to an appropriate therapeutic approach with very good outcome.     

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.

     

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.     

梅毒性视神经炎12例临床分析

目的总结梅毒性视神经炎临床特点和病理生理学机制。方法回顾分析12例梅毒性视神经炎患者的临床症状与体征、实验室检查、电生理学检查、影像学检查、治疗及预后。结果 12例患者(18只眼)均以视力下降为主要表现,呈急性或亚急性起病,呈单眼或双眼先后发病,视力损害程度不尽一致,伴视野缺损、眼底改变;脑脊液白细胞计数增加、蛋白定量升高;血清快速血浆反应素试验(RPR)和梅毒螺旋体血凝试验(TPHA)阳性,脑脊液RPR试验/甲苯胺红不加热血清试验和TPHA试验阳性;视觉诱发电位P100波潜伏期延长、波幅降低;MRI显示视神经萎缩、视神经眶内段或视神经全长异常信号;予水剂青霉素静脉滴注和苄星青霉素肌肉注射后视力好转。结论神经梅毒作为视神经炎的病因临床并不常见,应注意与特发性视神经炎和缺血性视神经病变相鉴别,梅毒血清学和脑脊液检测有助于诊断,早期诊断和规范治疗对视力恢复至关重要。     

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.     

经鼻內镜鼻窦手术治疗视神经炎13例临床分析

目的探讨经鼻内镜鼻窦手术治疗视神经炎的疗效。方法对13例视神经炎合并鼻窦疾病患者采用经鼻内镜鼻窦手术治疗,随访观察手术疗效。结果 11例最佳矫正视力较术前均有不同程度提高,2例视力无改善。视野检查8例中心暗点较术前缩小或消失,5例中心暗点无改变。全部病例术后鼻腔通气良好,各窦口引流通畅、无水肿、囊泡及异常分泌物,鼻窦术腔黏膜光滑。结论经鼻内镜鼻窦手术治疗视神经炎合并鼻窦疾病,具有较好疗效。     

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...     

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     

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.