The incidence of optic neuritis and its prognosis for multiple sclerosis

An incidence study of idiopathic optic neuritis (ON) was carried out in 2 geographic areas of Finland for the 9-year period 1970 to 1978. The southern province of Uusimaa composes a medium-risk and the western province of Vaasa a high-risk area for multiple sclerosis (MS). The risk for subsequent MS was determined. A total of 315 attacks on ON were recorded in 296 patients. The mean annual age-adjusted incidence for ON in Uusimaa was 2.2 and in Vaasa 2.5 per 100,000 population. The incidence figures remained unchanged all the time. The mean age at onset was 30 years. 19% of ON patients developed MS during the mean follow-up period of 5.1 years. When the life-table method of analysis was used, the probability of developing MS was 38% in Uusimaa and 24% in Vaasa 9 years after acute optic neuritis. In Uusimaa the risk of women for MS was significantly higher than in men. In 47%, the MS symptoms and signs developed within 1 year and in 90% within 5 years after the initial bout of ON. It is possible that only one part of idiopathic ON cases do have a relationship with MS.     

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.     

Distribution of HLA-Dw2 in optic neuritis and multiple sclerosis indicates heterogeneity

Introduction – The human leukocyte antigen (HLA) phenotype Dw2 is known to be increased in multiple sclerosis (MS), but only slightly in optic neuritis (ON). Materials and methods — 127 consecutive patients with unilateral monosymptomatic ON were typed genomically for HLA-DR and -DQ genes. Results - The frequency of HLA-Dw2 among ON patients (47%) was found to be significantly higher than among 250 controls (30%) but significantly lower than in a group of 245 MS patients (60%), all of the same ethnic origin. At the group level, these figures can be calculated to indicate that 53% of the ON patients belong to the group of "MS-type ON" (95% confidence limits 25–78%). A compilation of published data on the frequency of the HLA-DR17(3), DQ2 haplotype, prompted by a slight increase in this material, revealed a significant association with this haplotype in ON, after compensation for the increase of Dw2. Conclusion — ON differs from both MS and controls regarding HLA-Dw2. Thus, a substantial number of patients with ON may suffer from conditions not immuno-genetically related to MS, which might be designated as non-MS type ON. This condition may be more common in men and in young patients of both sexes.     

Optic neuritis progressing to multiple sclerosis

We report a partially retrospective and longitudinal study of patients with optic neuritis (ON) that developed multiple sclerosis (MS). We assessed clinical features or factors that might differentiate these patients from those with ON that did not develop MS. Of the cases followed, 110 (67%) were found to have an idiopathic origin of the disease; whereas 55 (33%) were found to develop it secondary to another disease. Of the 110 idiopathic cases, 13 (12%), developed MS over an average of 2 years. The results of these patients in the laboratory analyses of blood and CSF as well as the results of the MRI and evoked potential studies, were significantly different from the ON patients without MS. We conclude that the percentage of patients with ON in our sample that developed MS is similar to that found in Japan and is relatively low in comparison to other reports.     

Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin

Background: Patients with severe visual loss because of optic neuritis refractory to high dose corticosteroids have limited therapeutic options. The use of intravenous immunoglobulin (IVIG) has been advocated in the past, but data are scarce. In this study, we use a protocol different from those used in other studies, with different timing and dosage. Methods: Consecutive patients with corticosteroid‐refractive optic neuropathy were treated with IVIG and compared with control patients who received only corticosteroids in an open‐label, non‐randomized, controlled prospective study. Results: Twenty‐three patients received treatment with IVIG and 24 matched patients who did not receive treatment with IVIG were followed as controls. All patients had visual acuity 20/400 or worse in the affected eye. There was significant improvement in the IVIG group with 18/23 (78%) subjects reaching near normal vision (20/30 or better), compared with the control group with only 3/24 (12.5%) responding similarly. Conclusions: The use of IVIG, following corticosteroids, may be useful using the protocol described herein, with sustained pulsed dosing. A larger controlled trial is indicated to confirm these results.     

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.     

Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.     

The role of infection and vaccination in the genesis of optic neuritis and multiple sclerosis in children

This article describes the association between previous infection and/or vaccination and the development of optic neuritis (ON) in 18 children. Ten of these children subsequently developed clinically definite multiple sclerosis (MS), while in 8 patients a clinically definite etiology could not be confirmed. Vaccination preceded the first ON attack in 6 patients, all but one of whom subsequently developed MS. It also preceded subsequent demyelinating events in 6 patients. Ten of the patients had a bacterial or viral infection within the 2 weeks prior to the first symptoms of ON. Intrathecal antibody synthesis against 2 or more viruses could be shown in 5 out of 8 patients studied; 5 out of 6 patients had oligoclonal antibodies in CSF and 12 out of 16 patients a high IgG index. Neither intrathecal antibody synthesis against 2 or more viruses nor elevated IgG indexes could be found in the control patients. Measles and mumps occurred at a significantly later age in the children who subsequently developed MS than in the control children, and these patients had significantly more events that might have impaired the blood-brain barrier than the controls. These results indicate that immunological events leading to MS may be triggered during childhood. Vaccination and infection often precede ON in childhood. Intrathecal viral antibody production can occur already in childhood at the time of the first symptoms of MS.     

The clinical and paraclinical profile of optic neuritis: A prospective study

To define the clinical and paraclinical profile of optic neuritis (ON), patients with a suspicion of ON among a population of 1.5 million were examined over 2.5 years. A diagnosis of monosymptomatic ON was established in 74 patients. Cerebrospinal fluid (CSF) studies in 73 patients revealed oligoclonal IgG bands in 67% and 32 of 60 patients examined (53%) had three or more high signal lesions on magnetic resonance imaging (MRI). A strong correlation was found between oligoclonal bands and abnormal MRI. In 52 patients, two or more CSF examinations revealed strong variations in individual patients for mononuclear cell count and IgG index. In contrast, of 39 patients with oligoclonal bands in the first sample, none showed the disappearance of bands, and of 13 patients initially negative for bands, only one developed bands. There was no correlation between exacerbation or remission and CSF findings. During a short-term follow-up of 6–40 months, 19 patients converted to MS.This study was supported by grants from the Swedish Multiple Sclerosis Society (NHR) and Carmen and Bertil Regnér's fund.     

Assessing structure and function of the afferent visual pathway in multiple sclerosis and associated optic neuritis

The afferent visual pathway is commonly affected in MS. Assessment of the afferent visual pathway using clinical, imaging and electrophysiological methods not only provides insights into the pathophysiology of MS, but also provides a method of investigating potential therapeutic measures in MS. This review summarises the various assessment methods, in particular imaging techniques of the visual pathway. Retinal nerve fibre layer (RNFL) thickness is usually reduced following an episode of optic neuritis. Techniques such as optical coherence tomography, scanning laser polarimetry, and confocal scanning laser ophthalmoscopy are used to quantify RNFL thickness. MRI of the optic nerve is not routinely used in the diagnosis of MS or optic neuritis, but is valuable in atypical cases and in research. T2- weighted images of the optic nerve usually show the hyperintense lesion in optic neuritis and gadolinium enhancement is seen in the acute attack. Quantifying atrophy of the optic nerve using MRI gives an indication of the degree of axonal loss. Magnetization transfer ratio (MTR) of the optic nerve provides an indication of myelination. Diffusion tensor imaging (DTI) of the optic nerve and optic radiation provide information about the integrity of the visual white matter tracts. Functional MRI following visual stimulation is used to assess the contribution of cortical reorganisation to functional recovery following optic neuritis. Investigations including logMAR visual acuity, Sloan contrast acuity, Farnsworth- Munsell 100-hue colour vision tests and Humphrey perimetry provide detailed quantitative information on different aspects of visual function. Visual evoked potentials identify conduction block or delay reflecting demyelination. These collective investigative methods have advanced knowledge of pathophysiological mechanisms in MS and optic neuritis. Relevant ongoing studies and future directions are discussed.     

Lymphocyte subclasses and function in patients with optic neuritis in childhood with special reference to multiple sclerosis

Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS.     

Immunological effects of oral high-dose methylprednisolone in acute optic neuritis and multiple sclerosis.

The immunological effects of high-dose methylprednisolone in attacks of multiple sclerosis and acute optic neuritis have only been examined in a few randomized, controlled trials. We studied immunological changes in 50 patients with optic neuritis or multiple sclerosis who underwent lumbar puncture before and 1 week after completing a 15-day course of oral high-dose methylprednisolone treatment. Treatment resulted in a decrease in the concentration of myelin basic protein, a decrease in the serum concentration of immunoglobulin G (IgG) and intrathecal IgG synthesis, an increase in the cerebrospinal fluid concentration of transforming growth factor-beta1, and changes in the expression of CD25, CD26, and human leukocyte antigen-DR (HLA-DR) on CD4 T-cells. No effect was seen on the cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix metalloproteinase-9 (MMP-9). The lack of a persistent effect on cerebrospinal fluid leucocyte recruitment and MMP-9 activity, despite changes in IgG synthesis, T-cell activation, and cytokine production, suggests that modulation of the function of inflammatory cells may contribute to the clinical efficacy of oral high-dose methylprednisolone treatment in optic neuritis and multiple sclerosis.     

MRI, VEP, SEP and biothesiometry suggest monosymptomatic acute optic neuritis to be a first manifestation of multiple sclerosis

A cohort of 50 consecutive patients with acute monosymptomatic optic neuritis (ON) from a defined catchment area joined a prospective study. The aim of this study was to compare the sensitivity of magnetic resonance imaging (MRI), electrophysiological methods (VEP and SEP) and biothesiometry to detect abnormalities in other parts of the CNS than the optic nerves during the acute phase of ON. For each method, a scoring system is proposed. This investigation also hoped to achieve a better understanding of the natural history of ON. MRI proved to be the most sensitive tool (63% abnormal) in confirming a second site of involvement, followed by VEP in the clinically unaffected fellow eye (42%), biothesiometry (32%) and SEP (17%). The combination of all these methods, except for MRI (and VEP in eyes with acute ON), revealed abnormalities in 63% of the patients. When the neurophysiological methods were combined with MRI, 79% of the patients had abnormal findings suggesting additional lesions in the CNS. Hence, MRI and neurophysiological examinations supplement each other and together provide evidence that monosymptomatic ON is usually a first manifestation of MS. The development of definite MS at 1-20 months of follow up in 7 patients (all with abnormal MRI initially) supports this view.     

Optic neuritis: oligoclonal bands increase the risk of multiple sclerosis

ABSTRACT- In 1974 we examined 30 patients 0.5–14 (mean 5) years after acute unilateral optic neuritis (ON), when no clinical signs of multiple sclerosis (MS) were discernable. 11 of the patients had oligoclonal bands in the cerebrospinal fluid (CSF). Re-examination after an additional 6 years revealed that 9 of the 11 ON patients with oligoclonal bands (but only 1 of the 19 without this CSF abnormality) had developed MS. The occurrence of oligoclonal bands in CSF in a patient with ON is - within the limits of the present observation time - accompanied by a significantly increased risk of the future development of MS. Recurrent ON also occurred significantly more often in those ON patients who later developed MS.     

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     

Economic consequences of multiple sclerosis for Canadians

Objectives - To estimate the total costs of multiple sclerosis (MS) for all Canadians in 1994.
Methods - Prevalence-based study estimating disease-related societal costs for Canadians with MS in 1994. The human capital approach was used to estimate the value of lost productivity due to illness. Two components were revealed: first, direct costs, in terms of expenditures on hospital care, other institutions, physician services, other health professionals, drugs, and other expenditures; and second, indirect costs, in terms of lost productivity due to premature mortality and disability.
Results - The total costs of MS for Canadians were $502.3 million in 1994, with direct and indirect cost components at $188.6 million and $313.7 million, respectively.
Conclusions - This study highlights the scope and magnitude of the economic consequences of MS for Canadians. The costs calculated may be used to provide guidance in the setting of national priorities for research and prevention activities.