Provocative test for early diagnosis of multiple sclerosis

A new provocative test for early diagnosis of Multiple Sclerosis (MS) is presented. It is based on the recording of pattern visual evoked responses (VER) before and after exposing patients to a high luminance background. All 13 patients tested showed a biphasic enlargement of the P100 wave after bleaching even in the absence of an increased P100 latency. This biphasic enlargement can be interpreted as a fatigue or a saturation-like phenomenon as can be seen psychophysically. The saturation-like effect involves probably only affected fibers. No change in the VER was observed in 20 Normal observers examined in the same way. This test can be usefully employed in dubious cases of MS where routine VER do not provide reliable results.Reprint requests: Clinica Oculistica dell'Università, Via del Pozzo 71, 41100 Modena, Italy     

112例多发性硬化的眼部改变

为了加深认识多发性硬化（ｍｕｌｔｉｐｌｅｓｃｌｅｒｏｓｉｓ，ＭＳ）与眼科的关系，回顾性分析ＭＳ１１２例，首发症状中有视力障碍者占６５．１％眼科检查要见多各视野改变，并有眼肌麻痹，眼震，瞳孔及眼底改变等，临床定位累及视神经占６７．８％，文中探讨视神经炎（ｏｐｔｉｃｎｅｕｒｉｔｉｓ，ＯＮ）与ＭＳ的联系，并认为Ｄｅｖｉｃ氏病系ＭＳ的一个类型，眼科医师应与神经科医师协作进行必要的检查，以期尽早确诊，强调早     

Symptomatic intraocular inflammation in multiple sclerosis

Purpose : The aim of this study was to determine the type and outcome of uveitis in patients with multiple sclerosis. Methods : A retrospective study of 16 patients attending the uveitis clinic who had a clinically definite diagnosis of multiple sclerosis and symptomatic intraocular inflammation. The type of uveitis and complications present as well as the outcome of therapeutic intervention, either medical or surgical, was determined. Results : Chronic, bilateral anterior uveitis was present in six patients. Secondary cataracts requiring surgery occurred in 10 eyes, and trabeculectomy was done on five eyes for secondary glaucoma. Symptomatic vitritis (visual blurring and/or visually significant floaters) occurred in eight patients and was bilateral in four. Occlusive peripheral retinal vasculitis with subsequent areas of ischaemia and neovascularization requiring panretinal laser photocoagulation developed in eight eyes, five of which also required vitrectomy. Other posterior segment complications included macular oedema (four) and epiretinal membrane involving the macula (two). Five patients required systemic steroids for control of posterior uveitis. The median visual improvement following cataract surgery or vitrectomy was 3 Snellen lines to a median visual acuity of 6/18. Conclusions : A wide range of clinical patterns of uveitis, which may be both symptomatic and sight‐threatening, occur in patients with multiple sclerosis. In addition, the complications of uveitis may cause significant visual morbidity, much of which is amenable to appropriate surgical intervention. It is important that these potentially remediable conditions are recognized and treated to ensure that patients with multiple sclerosis retain optimum visual function.     

Fluctuations of visual evoked potential amplitudes and of contrast sensitivity in Uhthoff's symptom

Visual evoked potentials (VEPs) to pattern reversal and psychophysical contrast sensitivity (CS) were tested in five patients with Uhthoff's symptom before and after exercise. Four of the cases were related to a demyelinating disease and one patient had a severe brain injury. Uhthoff's symptom occurred also in neuropathies without previous clinical neuritis and in eyes with normal latency time of the VEPs. A depression of CS was observed by all five patients after exercise; a transient overshoot of CS following the depression was present in three of the patients. VEP amplitudes were reduced by exercise in three cases. Responses by stimulation with small checks were more affected. Paradoxical increased VEP amplitudes after exercise in the presence of a loss of psychophysical CS were found in one case.     

Evaluation of corneal sensitivity in multiple sclerosis patients

Purpose:To measure the corneal sensitivity in patients with multiple sclerosis (MS), to compare it with normal values and to study its correlation with different disease characteristics.Methods:Corneal sensitivity of 28 MS patients was compared to corneal sensitivity of 28 age- and gender-matched normal controls. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer and was correlated to the duration, type and severity indexes of the disease.Results:Corneal sensitivity was comparable between both groups (P = 0.79). No statistically significant correlation was found between corneal sensitivity and the duration of MS (P = 0.55) nor the severity indexes of MS (expanded disability status scale [EDSS] P = 0.52, global multiple sclerosis severity score [MSSS] P = 0.64). Following subgroup analysis, only the primary progressive (PPMS) form of MS had a reduced corneal sensitivity with P = 0.023, while remittent-recurrent (RRMS), secondary progressive (SPMS), and clinically isolated (CIS) forms of MS did not have any reduction in the corneal sensitivity. “ROC curve analysis” showed an area under the curve of 0.48.Conclusion:In the exception of PPMS subtype, MS patients have similar corneal sensitivity in comparison to controls. Cochet-Bonnet esthesiometer does not seem to be a good diagnostic tool or a disease severity marker for patients with MS.     

多发性硬化眼部表现的临床分析

目的:探讨多发性硬化(multiple sclerosis,MS)患者伴发眼部异常的临床表现和相关检查。方法:收集1993/2007期间的多发性硬化住院患者资料34例。所有纳入病例均按照统一的诊断标准。分析其眼部及全身临床特点和相关检查。结果:本组病例首发年龄最小为16岁,最大为62岁,男女患者性别构成比例为1∶2.8。在所纳入的34例MS患者中,出现视力下降16例,占47%,其中以视力下降为首发者15例。16例患者中,69%(11/16)出现不同程度的肢体麻木、感觉异常、无力,尿便潴留等脊髓受累表现,19%(3/16)出现复视、眼震、步态不稳、言语不清、语言障碍等脑干、小脑及大脑异常表现。对34例患者进行脑脊液检查,68%(23/34)出现寡克隆区带阳性或IgG指数升高,即CSFOB/IgG(+)。将34例患者分为伴有视力下降组和不伴有视力下降组,两组MS患者CSFOB/IgG(+)的比率接近。在28例进行VEP检查的患者中,64%(18例)结果异常。21例进行了MRI检查,76%(16例)结果异常。结论:多发性硬化患者伴随眼部异常发生率较高,脑脊液生化检查、VEP及MRI对MS的诊断和随访有重要意义。     

多发性硬化症眼科误诊的临床分析

目的:分析以单眼视神经受损为首发症状的多发性硬化症的临床特点,探讨误诊原因。方法:对3例诊断为视神经炎及球后视神经炎,给予详细的眼科检查、VEP检查及颅脑MRI检查。结果:通过眼部检查、相关辅助检查及颅脑磁共振检查最后确诊3例单眼视神经受损的患者均为多发性硬化症。结论:多发性硬化症若以视神经受累为首发症状而无全身其他症状时,容易诊断为单纯性视神经炎而漏诊。     

Evolutionary history of neuro-ophthalmology

An acute painful unilateral loss of vision in a young adult with obvious signs and symptoms of optic neuropathy usually suggests a diagnosis of optic neuritis. However, a similar clinical picture can be caused by a compressive lesion in the anterior visual pathways. Although such lesions are rare, they can only be diagnosed through neuroimaging studies.We describe a 37-year-old Chinese female, who presented with mild pain and decreased vision in the left eye two weeks prior to consultation. A diagnosis of retrobulbar optic neuritis was made and she underwent pulsed intravenous therapy of 1 g methyl-prednisolone daily over three days. The magnetic resonance imaging done three days later showed a partially thrombosed paraseller aneurysm, abutting and displacing the optic chiasm laterally. She underwent a right temporal craniotomy and clipping of the aneurysm. This report highlights the importance of neuroimaging in unmasking compressive lesions in patients presenting with presumed optic neuritis.     

视觉诱发电位对多发性硬化的诊断价值

目的 探讨视觉诱发电位(VEP)对多发性硬化(MS)的诊断价值。方法 将148例MS患者分为临床确诊型(80例)、临床拟诊型(42例)和临床可能型(26例)三组,用模式翻转视觉诱发电位(PRVEP)进行检查。结果 各临床类型MS的P_(100)潜伏期均较对照组显著延长(P<0.01)。各临床类型的VEP异常率分别为80.0％、52.4％和42.3％。有视神经炎病史和视神经萎缩的患者,其VEP异常率显著高于无视神经受累者(P<0.01)。随着病程的延长,VEP异常率有升高的趋势,但未见二者间有显著相关性。VEP异常以P_(100)潜伏期延长和两眼间P_(100)潜伏期不对称性异常多见,分别占44.3％和45.6％。结论 VEP作为一种电生理检查可客观地反映MS患者视觉通路病变所致的电生理变化,为早期发现临床下病灶提供依据,对MS的早期诊断具有重要意义。     

多发性硬化患者发生视神经炎34例的回顾性分析

目的:探讨视神经炎与多发性硬化(multiple sclerosis,MS)的相互关系,评价甲基强的松龙对多发性硬化的治疗效果。方法:回顾性分析解放军总医院2000/2005年多发性硬化住院患者85例,所有患者均符合Poser诊断标准,用SPSS软件统计并分析这些患者的临床资料。结果:在85例患者中,出现视神经炎36例(42%),其中20例(24%)以视神经炎为首发症状。对所有辅助检查结果分析后发现,有视神经炎患者头部MRI的异常数(64%)高于无眼部症状患者组(30%)(P<0.05,χ2=6.28);有视神经炎患者颈部MRI的异常数(64%)高于无眼部症状患者组(31%)(P<0.05,χ2=4.87)。经过大剂量甲强龙冲击并丙种球蛋白辅助治疗有59例(69%)症状缓解,18例(21%)病情减轻,有视神经炎36例患者31例视力有所提高。结论:对于首发视力障碍就诊于眼科、诊断为视神经炎的患者,应常规行MRI检查以除外MS,大剂量甲强龙冲击并干扰素或丙种球蛋白辅助治疗是MS首选方式。     

Intravenous pulse methylprednisolone in the treatment of uveitis associated with multiple sclerosis

Purpose : To demonstrate the safety and effectiveness of intravenous methylprednisolone (IVMP) in the treatment of uveitis in association with multiple sclerosis (MS). Methods : Uveitis is an unusual manifestation of MS that may be severe, chronic and require systemic immunosuppression therapy. High‐dose IVMP has previously been shown to be effective in the treatment of inflammatory eye disease and MS. Eight episodes of uveitis in five patients with MS were treated over a 10‐year period in an open, uncontrolled trial. Two patients had chronic anterior uveitis, one patient had bilateral panuveitis and two patients had intermediate uveitis. Results : All patients responded to IVMP with evidence of a decrease in intraocular inflammatory activity and improved visual acuity (VA) within 2 weeks of commencing treatment. There were no severe ocular or systemic steroid side effects. Conclusions : Intravenous methylprednisolone is an effective, well‐tolerated form of therapy for uveitis in patients with MS.     

Visual function in multiple sclerosis

126 patients with multiple sclerosis and normal visual acuity were submitted to a battery of tests of visual function. The investigation included visual evoked potential, contrast sensitivity by three methods, and a segment of the Farnsworth-Munsell 100 Hue test.22 of the patients gave a history of unilateral acute optic neuritis and in these the abnormalities were greater in degree.Contrast sensitivity emerged as the most useful test and was abnormal in 92.2% of eyes. Visual evoked potential was delayed in 35.6% and colour vision was abnormal in less than a third.In general, contrast sensitivity was depressed at all frequencies and most of the abnormalities could be identified by testing at a single frequency of 4 cycles/degree.Abbreviations CD clinically definite - CS contrast sensitivity - CP clinically probable - MS multiple sclerosis - VEP visual evoked potential     

Diagnostic techniques in multiple sclerosis

Although multiple sclerosis (MS) has been an area of great interest and effort in numerous scientific disciplines, its etiology, pathogenesis and therapy remain mysterious. Perhaps the most significant advances have resulted from the ability to be more precise in establishing the diagnosis of MS. Among the most important of the new diagnostic tools are electrophysiological techniques for examination of the visual and oculomotor systems. Tests such as the visually evoked potential (VEP) can confirm the existence of clinically suspected lesions and document the presence of asymptomatic ones. Various electrophysiological techniques for detection and evaluation of MS, as well as CSF analysis, psychological and neuroradiological procedures, and immunological observations are described. The relationship between optic neuritis and MS is reviewed, as are therapeutic regimens in use and under study.     

Spatio-temporal processing in multiple sclerosis

The processing of spatial and temporal detail was investigated in patients with multiple sclerosis. Normal observers and 13 patients with optic neuritis secondary to multiple sclerosis performed a battery of visual tests that included contrast sensitivity, temporal integration, evoked potentials, and visual masking. The multiple sclerosis patients exhibited losses of pattern processing, and these deficits became more noticeable when the patterns were presented briefly. Moreover, these patients exhibited diverse response patterns for the different visual tests. For some, temporal integration functions appeared severely attenuated, while evoked potential latency was within normal limits. Others displayed poor performance in the visual masking test, yet contrast sensitivity functions were comparable to those of the control group. We suggest that a battery of tests that incorporates spatial as well as temporal stimuli is necessary for the detection of visual dysfunction in multiple sclerosis.     

视神经炎为首诊的多发性硬化21例

目的:分析以视神经炎(optic neuritis,ON)为首诊的多发性硬化(multiple sclerosis,MS)21例,提高对ON与MS的认识,评价大剂量甲强龙冲击治疗效果。方法:回顾性分析我院2004-04/2008-04收治的以ON为首诊的MS21例的临床表现、诊断及治疗。结果:患者4例符合Poser诊断标准,17例行MRI后确诊;通过给以大剂量甲强龙冲击治疗,15例(71%)患者视力改善。结论:对于首发视力障碍就诊于眼科、诊断为视神经炎的患者,应常规行MRI检查以除外MS,大剂量甲强龙冲击治疗是MS首选方式。     

Monitoring demyelination in multiple sclerosis with multi-flash campimetry

Multi-flash campimetry is a computer-implemented psychophysical technique that allows a rapid and extensive assessment of visual flicker sensitivity. Multi-flash field maps generated from the data typically reveal the presence of islands of degraded temporal resolution in multiple sclerosis (MS) patients, but not in normal control observers. These distinct islands presumably reflect the influence of demyelination as well as a variety of other possible transient factors, such as edema and inflammation of the optic nerve. The question addressed in the present study concerned a means of distinguishing among such influences.The strategy employed was to test MS patients more than once over a period of several months. Under the assumption that there is little or no significant remyelination in the central nervous system, it was argued that islands that remain present over time should be those that principally reflect demyelination. Transient changes that appear in the fields of MS patients probably reflect the influence of other mediating factors. Examples of multi-flash field maps are presented to illustrate this point and to serve as an initial assessment of the reliability of the technique. It is concluded that multi-flash campimetry may prove to be an effective aid in documenting the degree of progressive visual involvement in MS, and provide a means of monitoring the clinical course of demyelination in the visual system.     

Using retinal architecture to help characterize multiple sclerosis patients

Objective: We compared retinal nerve fibre layer (RNFL) thickness and visual function in a heterogeneous multiple sclerosis (MS) cohort to determine whether optical coherence tomography (OCT) may complement the existing methods used to characterize MS patients.Design: Cross-sectional cohort study.Participants: One hundred and ninety-three patients with optic neuritis (ON) as a clinically isolated syndrome (CIS) (n = 63), relapsing-remitting MS (RRMS) (n = 108), secondary progressive MS (SPMS) (n = 13), and primary progressive MS (PPMS) (n = 9).Methods: All patients underwent standardized ophthalmic, neurological, and OCT testing at a single academic institution.Results: RNFL values were reduced in PPMS (94.3 μm), RRMS (99.6 μm), and SPMS eyes (84.7 μm) relative to CIS eyes (105.7 μm) (p < 0.0001). RNFL values were lower in eyes with recurrent ON (64.2 μm) relative to eyes affected by a single ON event (86.3 μm) (p < 0.0001). The strongest correlation between RNFL thickness and neurological disability occurred in RRMS patients (r = −0.51, p < 0.0001). RNFL thickness correlated with visual field sensitivity for CIS (r = 0.23, p < 0.01) and RRMS (r = 0.22, p < 0.01) patients. Simple linear regression showed that every 10 μm decrease in RNFL correlated with a 5.8 decibel decrease in visual field sensitivity (adjusted R² = 0.35, p < 0.0001) for RNFL values less than 75 μm.Conclusions: There were robust correlations between RNFL thickness and visual function, particularly in ON eyes. OCT may complement the existing tools used to characterize MS patients, but further studies are needed.     

Tuberous sclerosis

Tuberous sclerosis is a multisystem disorder of autosomal dominant inheritance that has important eye signs which contribute substantially to the diagnosis. The disease has been recognized for over 100 years, classically by the occurrence of the triad of mental retardation, epilepsy and adenoma sebaceum of the face. Children with tuberous sclerosis often present with infantile spasms. Eye manifestations include retinal phakomata which may be granular, white and calcified, or flat, translucent and noncalcified. Additional findings include angiofibromas of the lids, poliosis, retinal and iris depigmentation, and atypical colobomata. Various systemic and ocular signs of tuberous sclerosis may develop over the years. For purposes of both patient management and genetic counselling, diagnosis based on early signs is important. The ophthalmologist may play an important role in this regard, as the characteristic phakomata can often be detected within the first two years of life.     

Uveitis associated with multiple sclerosis:complications and visual prognosis

AIM:To determine the frequency, subtype, complications, treatment and visual prognosis of uveitis in patients with multiple sclerosis (MS).METHODS:A total of 1702 MS patients’ medical records were reviewed for a history of uveitis both with a neurologist and an ophthalmologist.RESULTS:Nine patients (0.52%) with uveitis were detected. Eight of them were female, one was male. The mean age was 42.0±14.1y (range 22-66). Seven patients were relapsing remitting MS, two were secondary progressive MS. The mean duration of MS was 10.8±10.3y, and the mean duration of uveitis 10.3±9.9y. The onset of uveitis preceded that of MS (four patients) by a mean of 5.0±4.3y (range 1-11). MS diagnosed prior to the onset of uveitis (five patients) by an interval of 0.75-16y (mean 4.95±6.24y). There were 16 affected eyes of nine patients. The most common types of uveitis were panuveitis and intermediate uveitis. Uveitis was bilateral in most patients. The most common complications were cataract and glaucoma, and patients with such complications were surgically treated. The range of visual acuity of affected eyes was 20/800 to 20/22, with only six of 16 affected eyes better than 20/40. After treatment, the visual acuity of the affected eyes was better than 20/40 in 11 of 16 eyes.CONCLUSION:Uveitis should be considered when assessing an MS patient with visual loss, as surgical interventions other than medical treatments may be needed to improve visual function. Complications could be seen more often when posterior segment is involved.