Unilateral Optic Neuritis Research Articles

Functional magnetic resonance imaging in acute unilateral optic neuritis.

Despite good clinical criteria for diagnosing optic neuritis (ON), only a few techniques can precisely assess its impact on visual brain function. The authors studied whether functional magnetic resonance imaging (fMRI) of visual activation reliably reflects the cerebral consequences of acute unilateral ON, and how fMRI correlates with clinical function and visual evoked potentials (VEPs). Twenty ON patients, before and after steroid treatment, were compared to 20 controls. Each eye was stimulated separately with a checkerboard pattern reversing at 1, 2, 4, and 8 Hz. VEPs were recorded the same day. Initially, affected eye responses differed significantly from those of unaffected counterparts and controls in 12 patients. Post hoc classification by fMRI criteria was correct in approximately 85%. fMRI and VEP response parameters (as well as visual acuity) correlated significantly. The higher stimulation frequencies yielded greater fMRI responses from unaffected eyes, but not from affected eyes, in controls. The fMRI responses were quantifiable in every subject, whereas in 11 ON eyes, no VEPs were obtained during the acute stage. The authors conclude that fMRI is sensitive to the cerebral response alteration during ON and might therefore contribute to evaluating the temporal evolution of the visual functional deficit during recovery or therapy.

Two cases of optic neuritis in which relative afferent pupillary defect and decreased critical flicker fusion frequency could be detected before visual acuity worsened

RAPD (relative afferent pupillary defect) for light reflex and decreased CFF (critical flicker fusion frequency) are sensitive indicators of unilateral optic neuritis. Previous studies have shown that light reflex and CFF usually improve more slowly than visual acuity during the recovery period of optic neuritis. However, there are few chances to observe the relationship between visual acuity and light reflex or between visual acuity and CFF during the early onset of optic neuritis. This paper describes two cases of unilateral optic neuritis in which RAPD and decreased CFF could be detected during early onset before visual acuity worsened. The cases show that a dissociation between visual acuity and light reflex or between visual acuity and CFF may also occur during the early onset of optic neuritis, as it can during the recovery or remission period. That is, light reflex and CFF are affected more rapidly and recover more slowly in optic neuritis. Therefore, when patients with normal visual acuity complain of visual symptoms of unknown origin, investigators must keep the possibility of optic neuritis in mind while observing light reflex and measuring both visual acuity and CFF.

Optic neuritis after anthrax vaccination

Objective To report the occurrence of optic neuritis after anthrax vaccination in two patients. Design Observational case reports, review of literature. Methods Description of clinical history, examination, neuroimaging, and further studies in two patients experiencing optic neuritis in temporal association with anthrax vaccination. Main outcome measures Visual acuity, visual fields. Results Two patients, 39 and 23 years of age, were seen with acute optic neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination and successfully treated with intravenous methylprednisolone. The first patient had a typical presentation and course of unilateral retrobulbar optic neuritis with excellent visual recovery. The second patient had a bilateral anterior optic neuritis and has required chronic immunosuppression to maintain his vision. Retinal and optic nerve autoantibodies were present in the second patient. No cross-reactive epitopes between anthrax vaccine and retina/optic nerve were identified. Conclusion Optic neuritis is a potential adverse reaction of anthrax vaccination.

Optic neuritis in an urban black African community.

To describe the clinical profile of idiopathic optic neuritis in South African blacks. South African black patients with acute isolated idiopathic optic neuritis, treated and followed for at least 3 months at a large medical centre, were studied. Exclusion criteria were other causes of optic neuropathy (such as ischaemic optic neuropathy, toxins or Leber's hereditary optic neuropathy); all causes of optic neuritis (such as HIV, neurosyphilis, sarcoid or connective tissue disease); neurological disease outside of the optic nerves; and any race other than South African black. Patients underwent extensive ophthalmic, neurological, radiological, cerebrospinal fluid and blood assessment. Eighteen eyes of 10 patients were studied. The mean age was 35.7 years and 9 patients were female. Only 2 patients had truly unilateral optic neuritis, the other 8 having either bilaterally simultaneous or consecutive disease. Presenting visual acuity (VA) was less than 6/60 in 17 of 18 eyes, with severe dyschromatopsia in all eyes. Fifteen eyes had optic disc swelling. All patients were treated with corticosteroids. After at least 3 months follow-up only 6 eyes recovered VA of 6/12 or better, with only 3 eyes recovering colour vision of 10/13 or better on Ishihara plate testing. No patient had multiple sclerosis (MS) on presentation, nor developed MS on follow-up. Idiopathic optic neuritis in black South Africans differs from that in whites. The higher prevalence of bilateral cases and of optic disc swelling, the weaker association with MS and the extremely poor visual outcome distinguish optic neuritis in black South Africans.

Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence.

We describe an MRI technique for quantifying optic nerve atrophy resulting from a single episode of unilateral optic neuritis. We imaged 17 patients, with a median time since onset of optic neuritis of 21 months (range 3-81 months), using a coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion of the optic nerves was calculated by a blinded observer from five consecutive 3 mm slices from the orbital apex forwards using a semiautomated contouring technique and compared with data from 16 controls. The mean optic nerve area was 11.2 mm2 in the affected eye of the patients, 12.9 mm2 in the contralateral eye (P = 0.006 compared to the affected eye) and 12.8 mm2 in controls (P = 0.03 compared to the affected eyes). There was a significant negative correlation between disease duration and the size of the affected optic nerve (r = -0.59, P = 0.012). The measurement coefficient of variation was 4.8%. The sTE fFLAIR sequence enables measurement of optic nerve area with sufficient reproducibility to show optic nerve atrophy following a single episode of unilateral optic neuritis. The correlation of increasing optic nerve atrophy with disease duration would be consistent with ongoing axonal loss in a persistently demyelinated lesion, or Wallerian degeneration following axonal damage during the acute inflammatory phase.

Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS

The Optic Neuritis Treatment Trial (ONTT) gathered detailed clinical and MRI data from a large population of patients with acute unilateral optic neuritis (ON) who were then followed prospectively for the development of multiple sclerosis (MS). This dataset created an excellent opportunity to assess the relationship of various parameters, including human leukocyte antigen (HLA)-DR2 allele status, to the development of MS and to the presence of brain MRI signal abnormalities. The study was performed on 178 of the 457 patients enrolled in the ONTT. HLA haplotype DR2 was present in 85 (48%) of the 178 patients. Its presence was associated with increased odds of probable or definite MS at 5 years (odds ratio, 1.92; 95% confidence interval, 1.01 to 3.67; p = 0.04). The association was most apparent among patients with signal abnormalities on baseline brain MRI.—Nancy J. Newman

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study

OBJECTIVESRecovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP)....

Baseline Features of Idiopathic Optic Neuritis as Determined by a Multicenter Treatment Trial in Japan

Background: An optic neuritis treatment trial was conducted at 30 clinical centers in Japan using the same protocol. Patient participation was based on: age range of 14–55 years; acute symptoms indicative of unilateral optic neuritis of unknown or demyelinating origin; visual symptoms of 14-day duration or less; relative afferent pupillary defect in affected eye; and normal or swollen optic disc of affected eye. Cases: Initially, 102 patients qualified for participation; baseline data were obtained for analysis from 70 of these patients. Demographic characteristics of Japanese patients with optic neuritis were clarified and compared with those in a US study. Observations: The incidence of ocular or periocular pain and the presence of periventricular plaques were noted to be lower, and the incidence of disc swelling higher, in the Japanese patients, suggesting racial differences in the characteristics of the disease. Such differences may possibly be related to the lower incidence of multiple sclerosis in Japanese patients. The results of visual function tests were virtually the same in both studies. The nonaffected eyes of more than half the patients showed abnormal mean deviation in Humphrey field analysis, as also noted in the US study. Conclusions: The baseline clinical features of optic neuritis in the Japanese patients have been defined. Some racial differences in the characteristics of the disease may exist.

Neuromielitis óptica de Devic: análisis de siete casos

Devic's optic neuromyelitis is an unusual condition characterized by the association of unilateral or bilateral optic neuritis and myelitis, both of which are relapsing. Prognosis is usually poor, both for the optic nerve and for the spinal medulla which becomes cavitated. This leads to severe handicap and deterioration in quality of life, except in cases presenting as children. We studied seven cases of this condition and describe their clinical and neuroimaging features, cerebrospinal fluid (CSF), evaluation, complications, prognosis and treatment. This data was compared with that in the literature. 1. It is an unusual condition--only 7 cases have been seen at our centre--making up approximately 0.1% of the inflammatory pathology of the spinal cord seen. 2. During the first few hours or days the clinical and radiological findings may not correspond. There may be marked deterioration of CNS function but with normal neuroimaging findings. This may lead to serious problems in diagnosis, which can usually be resolved by repeating the investigation. 3. Differential diagnosis should be made with intramedullary tumors when on neuroimaging there is increased spinal cord diameter with uptake of contrast, and psychiatric disorders when this is normal. 4. The condition usually deteriorates leading to severe disability, since loss of visual acuity is added to the severe spinal cord lesion. 5. Diagnosis should be made by application of the criteria of clinical evolution, imaging and biochemistry defined in the literature, although firm diagnosis can only be made on anatomopathological studies, usually at autopsy.

Visual activation patterns in patients with optic neuritis: an fMRI pilot study.

We studied the use of functional MRI (fMRI) with visual stimulation in nine patients with unilateral optic neuritis. Eight healthy subjects served as controls. Patients showed reduced activation upon stimulation of the affected eye, on average 33% (range 0 to 156%) of the average monocular activation in the control group. Decreased activation was also seen for the unaffected eye (61% of control values, range 3 to 133%). We conclude that fMRI with visual stimulation is feasible in patients with optic neuritis and deserves future study.

Optic neuritis in chronic relapsing experimental allergic encephalomyelitis in Biozzi ABH mice: Demyelination and fast axonal transport changes in disease

The encephalitogenicity of optic nerve tissue was demonstrated in Biozzi ABH (H-2 dq1) mice. Acute experimental allergic encephalomyelitis (EAE) occurred in 11/14 animals and 4/5 exhibited relapse. The involvement of the optic nerve in spinal cord homogenate induced chronic relapsing EAE (CREAE) was demonstrated by mononuclear cell infiltration and myelin degradation in the optic nerve prior to and during clinical disease. During the relapse phase gross pathological assessment revealed swollen and translucent plaques on the optic nerves. Advanced lesions showed widespread demyelination, astrocytic gliosis and fibrotic changes of the blood vessels. Physiologically, the fast axonal transport of proteins from the retina to the optic nerve and superior colliculus was significantly decreased during relapse. The association of inflammation and demyelination with physiological deficit in the optic nerve highlights the usefulness of this model in the study of multiple sclerosis in which acute monosymptomatic unilateral optic neuritis is a common manifestation. Furthermore, the novel induction of CREAE with optic nerve homogenate suggests that optic nerve antigens play a significant role in the pathophysiology and progression of neurological disease in CREAE which may be relevant to studies of optic neuritis in multiple sclerosis.

Optic neuritis and cytokines: no relation to MRI abnormalities and oligoclonal bands.

Acute unilateral monosymptomatic optic neuritis (ON) is a common first manifestation of MS if associated with multiple MS-like lesions on brain MRI and oligoclonal IgG bands (OB) in the CSF, whereas ON patients lacking these laboratory abnormalities are considered to have a good prognosis regarding future MS development. Several cytokines involved in immune regulation are upregulated in blood and even more noticeable in CSF in MS. To study a possible relation between cytokine profiles and presence versus absence of MS-like brain MRI lesions and CSF OB, we used in situ hybridization to examine mRNA expression of the proinflammatory interleukin-12 (IL-12), interferon-gamma, and tumor necrosis factor-alpha and the immune response downregulating IL-10, transforming growth factor-beta, and IL-4 in blood and CSF mononuclear cells (MNC) from 59 patients with untreated ON. There were no differences in numbers of MNC in blood or CSF expressing any of the cytokines under study, upon subgrouping the ON patients regarding presence (n = 31) versus absence (n = 28) of MRI lesions, presence (n = 45) versus absence (n = 14) of OB, or duration after onset of ON (<1 month, n = 30, versus >1 month, n = 29). Similarly, no differences were observed for numbers of myelin basic protein-reactive blood MNC expressing any of these cytokines after subgrouping according to these variables. Our findings suggest that the cytokine profile, as examined in this study, is less useful to determine the risk of future development of clinically definite MS in ON patients or as indicator for therapeutic interventions in ON. An upregulation of both pro- and anti-inflammatory cytokines in ON patients seems to be more related to the CNS disease per se, whether limited to the optic nerve or not, than to the inflammatory process characteristic for MS.

Subclinical saccadic adduction slowing in patients with monosymptomatic unilateral optic neuritis predicts the development of multiple sclerosis

Parameters of visually guided saccades were studied in 22 patients with monosymptomatic optic neuritis and 21 age-matched control subjects with a precise infrared reflection technique. Follow-up of the patients over 2.2 years, on average, allowed correlations of subclinical saccadic abnormalities, measured at study entry, with the development of clinically definite multiple sclerosis (CDMS). Subclinical adduction slowing defined on statistical grounds was observed in nine patients. Seven of these and four out of five patients with prolonged saccadic latency developed CDMS during the follow-up period. We conclude that subclinical adduction slowing in patients with optic neuritis represents an oculographic finding with pathological significance.

Optic neuritis: imaging with magnetization transfer.

Our objective was to prospectively examine the optic nerves in patients with clinically severe unilateral optic neuritis, using routine spin-echo and magnetization transfer MR imaging. For 39 patients with such lesions, we calculated the magnetization transfer ratio along the involved intraorbital optic nerve and along the asymptomatic contralateral optic nerve in a mirror-image location. Magnetization transfer ratios were correlated with the imaging findings on routine spin-echo MR imaging. Magnetization transfer ratios were decreased in 33 of the 39 clinically symptomatic optic nerves, including 12 of the 18 clinically symptomatic optic nerves in which no abnormality was seen on routine spin-echo MR images obtained before and after administration of gadopentetate dimeglumine. Magnetization transfer imaging reveals intraorbital optic nerve abnormalities in patients with optic neuritis even when such lesions are otherwise occult on routine magnetization transfer imaging.

Unilateral Optic Neuritis Caused by Histoplasma capsulatum in a Patient With the Acquired Immunodeficiency Syndrome

Unilateral Optic Neuritis Caused by Histoplasma capsulatum in a Patient With the Acquired Immunodeficiency Syndrome

The temporal frequency response function of pattern ERG and VEP: changes in optic neuritis

Steady-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) in response to sinusoidal gratings (2 c/deg), sinusoidally counterphased at closely spaced temporal frequencies (TFs) between 4 and 28 Hz, were recorded from 11 patients with unilateral optic neuritis (ON; 11 affected eyes and 10 healthy fellow eyes) and 7 age-matched normal subjects (7 eyes). Amplitude and phase of responses' second harmonics were measured. Responses' apparent latencies were estimated from the rate at which phase lagged with TF. When compared to control values, mean PERG and VEP amplitudes of ON eyes were reduced (by about 0.4 log units) at both low (5–10 Hz) and high (16–20 Hz) TFs. Mean PERG amplitudes of fellow eyes were selectively reduced at low TFs (by about 0.3 log units). Mean PERG apparent latencies of both ON and fellow eyes were delayed (by 15 and 9 ms, respectively). Mean VEP apparent latency of ON eyes was delayed at both low and high TFs (by 24 and 30 ms, respectively), while that of fellow eyes was selectively delayed at high TFs (by 28 ms). The results in ON eyes indicate non-selective abnormalities of PERG and VEP generators responding at both low and high TFs. VEP TF losses may be in part accounted for by corresponding PERG losses. In the fellow eyes of patients, more selective PERG and VEP TF abnormalities may suggest differential impairment of retinal and postretinal subsystems responding better to low and high TFs (i.e. parvo-and magnocellular streams).

The temporal frequency response function of pattern ERG and VEP: changes in optic neuritis

Steady-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) in response to sinusoidal gratings (2 c/deg), sinusoidally counterphased at closely spaced temporal frequencies (TFs) between 4 and 28 Hz, were recorded from 11 patients with unilateral optic neuritis (ON; 11 affected eyes and 10 healthy fellow eyes) and 7 age-matched normal subjects (7 eyes). Amplitude and phase of responses' second harmonics were measured. Responses' apparent latencies were estimated from the rate at which phase lagged with TF. When compared to control values, mean PERG and VEP amplitudes of ON eyes were reduced (by about 0.4 log units) at both low (5–10 Hz) and high (16–20 Hz) TFs. Mean PERG amplitudes of fellow eyes were selectively reduced at low TFs (by about 0.3 log units). Mean PERG apparent latencies of both ON and fellow eyes were delayed (by 15 and 9 ms, respectively). Mean VEP apparent latency of ON eyes was delayed at both low and high TFs (by 24 and 30 ms, respectively), while that of fellow eyes was selectively delayed at high TFs (by 28 ms). The results in ON eyes indicate non-selective abnormalities of PERG and VEP generators responding at both low and high TFs. VEP TF losses may be in part accounted for by corresponding PERG losses. In the fellow eyes of patients, more selective PERG and VEP TF abnormalities may suggest differential impairment of retinal and postretinal subsystems responding better to low and high TFs (i.e. parvo-and magnocellular streams).

Review: cytokines and the pathogenesis of multiple sclerosis.

Perivascular accumulation of mononuclear cells (MNCs) in the central nervous system (CNS) and high levels of myelin autoantigen-reactive T cells in blood and further enriched in cerebrospinal fluid (CSF) are characteristic for multiple sclerosis (MS) and suggest a role for immunoregulatory cytokines in MS pathogenesis. The difficulties inherent to measurements of cytokine concentrations in body fluids have been partly overcome by adopting techniques allowing cytokine determinations on cellular level. MS is associated with the parallel up-regulation of proinflammatory [interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha, and interleukin (IL)-12] and immune response-down-regulating [transforming growth factor-beta (TGF-beta), IL-10] cytokines systemically. A preferential up-modulation of TNF-alpha and lymphotoxin-alpha is observed in clinical exacerbations and of TGF-beta and IL-10 in remissions. The B cell-stimulating IL-4 and IL-6 are also up-regulated in MS, as is the cytolysis-promoting perforin. Cytokine production is elevated to an even higher degree in the CSF than systemically, underlining the autonomy of the immune responses in the CSF. All cytokine abnormalities are demonstrable already in very early MS, manifested by acute unilateral optic neuritis associated with more than two MS-like lesions on brain magnetic resonance imaging and oligoclonal IgG bands in CSF. The cytokine abnormalities hitherto observed are not MS specific, because they can be found in other inflammatory CNS diseases, e.g., aseptic meningitis and even noninflammatory neurological diseases like stroke. The influence on cytokine profiles, e.g., suppressing proinflammatory cytokines and promoting TGF-beta and IL-10, could be an important way to identify new and promising treatments of MS.

Unilateral Optic Neuritis Caused by Histoplasma capsulatum in a Patient With the Acquired Immunodeficiency Syndrome

To evaluate the potential of Histoplasma capsulatum to cause optic neuritis in the setting of the acquired immunodeficiency syndrome (AIDS). We examined a 35-year-old man with a history of AIDS and disseminated histoplasmosis who developed a unilateral progressive optic neuritis of enigmatic origin. An optic nerve sheath biopsy was performed to provide a tissue diagnosis. Histoplasma capsulatum was identified in both the optic nerve sheath and fungal culture. Histoplasma capsulatum should be considered in the differential diagnosis of optic neuritis in patients with AIDS, even in the absence of chorioretinal findings.

Acute Unilateral Papillitis versus Retrobulbar Neuritis: Relation to Multiple Sclerosis

Prospectively referred patients with unilateral acute optic neuritis (ON) (n = 223; aged 12-57; 158 women), either idiopathic or part of clinically definite multiple sclerosis (CDMS), were systematically examined by the same physician. We analysed whether the 161 patients with retrobulbar neuritis and the 62 patients with papillitis differed from each other clinically or according to paraclinical tests. The following characteristics were observed in retrobulbar ON respectively papillitis: median age 33 and 33 years, women 70% and 73%, clinically definite MS 30% and 27%. Abnormal results in retrobulbar ON and in papillitis (indicated in brackets) did not differ significantly and were found as follows: cerebral MRI in 56% (63%), VEP from the eye with acute ON in 82% (88%), VEP from the eye without acute ON in 38% (33%), SEP from median nerves in 9% (10%), SEP from tibial nerves in 22% (22%) and biotesiometry in 32% (27%). In the CSF, oligoclonal bands were present in 42% (53%), increased IgG-index in 40% (44%) and increased leucocyte count in 39% (29%). The HLA-DRI5 tissue type was present in 47% (43%). There were no significant differences between retrobulbar ON and papillitis when the idiopathic cases and cases with clinically definite MS were analysed separately. Our data document that unilateral retrobulbar ON and papillitis are both part of the MS spectrum and not different from each other with regard to clinical and paraclinical parameters, indicating that the two groups can be pooled in future treatment trials.