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Optic neuritis: guidelines.

A major breakthrough in the therapy of demyelinating disease has recently been disclosed by the Optic Neuritis Treatment Trial. Over the past 6 years the trial has accumulated evidence that a high dose of corticosteroids taken to treat patients with an isolated acute attack of optic neuritis reduces the rate at which multiple sclerosis develops over a 2-year period of follow-up. The findings of the trial have had an immediate impact on the neuro-ophthalmic and neurologic community in the USA; therefore, I have focused my review on this important topic.

Clinical Protocols↗

Postpartum optic neuritis: etiologic and pathophysiologic considerations.

The clinical course of four patients with visual loss in the postpartum period due to acute optic neuritis is described. Factors that disclosed the underlying etiology and expression of disease are discussed. The clinical records of four women examined and managed for visual loss after uncomplicated pregnancies and term deliveries were reviewed. Neurodiagnostic examination, treatment modalities, and outcomes were assessed. These four women with varied and confounding medical histories, all with optic neuropathy, eventually were demonstrated to harbor demyelinating disease. Although visual loss in the postpartum period evokes differential diagnostic considerations, the authors' experience suggests that puerperal immune-mediated changes are responsible for activation of optic neuritis associated with relapsing multiple sclerosis.

Adult↗

Management of optic neuritis and multiple sclerosis.

Optic neuritis and multiple sclerosis (MS) are common causes of visual and neurologic dysfunction in young adults. Advances in magnetic resonance imaging, molecular genetics, and neuroimmunology have increased our understanding of the pathophysiology underlying both disorders. Corticosteroids remain the mainstay of treatment of optic neuritis, but alternate dosages and routes of administration are undergoing investigation. The available therapies for MS have expanded, and there is evidence that early intervention is beneficial. Treatments for MS show sustained efficacy, but are not curative, and adjunctive treatments may prove valuable in patients with progressive visual and neurologic disability.

Humans↗

Optical coherence tomography: measuring in-vivo axonal survival and neuroprotection in multiple sclerosis and optic neuritis.

PURPOSE OF REVIEW: This review considers the latest developments in the use of optical coherence tomography in neuro-ophthalmology. RECENT FINDINGS: Optical coherence tomography can accurately and reproducibly quantitate the micron thickness of the peripapillary retinal nerve fiber layer, as well as the thickness and volume of the macula. It is able to perform both cross-sectional and longitudinal studies in patients with multiple sclerosis and optic neuritis. It is able to measure and assess axonal preservation and protection when used in clinical trials. SUMMARY: Specific guidelines when undertaking optical coherence tomography analyses for patients with multiple sclerosis and optic neuritis are needed to ensure uniformity among clinical trials; this development would be similar to the parameters devised when magnetic resonance imaging emerged as an important technology.

Axons↗

Immunohistochemical evidence of inducible nitric oxide synthase and nitrotyrosine in a case of clinically isolated optic neuritis.

BACKGROUND: Optic neuritis (ON) is a demyelinating inflammation of the optic nerve that may occur as an isolated disease or related to multiple sclerosis (MS). There is little evidence of whether the immunohistochemistry of ON resembles that of typical cerebral MS lesions. METHODS: Pathologic optic nerves were obtained from a patient who died of causes unrelated to ON after clinical recovery from clinically isolated ON. Normal control optic nerves were obtained from an eye bank. Normal and pathologic tissues were probed with antibodies to pathologic proteins including myelin basic protein (MBP) fragment, the inducible form of nitric oxide synthase (iNOS), macrophage markers CD14 and CD64, nitrotyrosine, and cyclooxygenase (COX-2). We also examined MBP, the oligodendrocyte marker cyclic nucleotide phosphodiesterase (CNPase), and glial fibrillary acidic protein. RESULTS: In the affected pathologic nerve, iNOS-positive macrophages/microglia, iNOS-positive astrocytes, COX-2, and nitrotyrosine were observed. iNOS and COX-2 were occasionally observed in the unaffected nerve. Decreased expression of MBP and CNPase was seen in the pathologic optic nerves, along with evidence of gliosis and ongoing myelin degradation indicated by the presence of MBP fragment. CONCLUSIONS: The immunohistochemistry of clinically isolated optic neuritis, as judged by this single case, resembles that of cerebral lesions of MS in showing abnormally high levels of iNOS and nitrotyrosine as well as other mediators of immune damage.

Astrocytes↗

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.

Adolescent↗

Autonomic dysfunction in experimental allergic neuritis.

Beat-to-beat variation (R-R variation) in the electrocardiogram was studied in experimental allergic neuritis in the Sprague-Dawley rat. Reduced R-R variations were found in 2 of 10 animals, probably as a sign of autonomic dysfunction. The vagal nerves from these two animals, studied in vitro, showed disturbed conduction. In one animal prolonged conduction latencies to supramaximal electrical stimuli were found. Vagal nerves from controls and from animals without clinical symptoms showed normal conduction. Histologically, the vagal nerves from affected animals showed a slight inflammatory cell infiltration and signs of demyelination but there was no evidence of involvement of the brainstem vasomotor nuclei. Thus, we suggest that the autonomic dysfunction in experimental allergic neuritis, measured as reduced R-R variations, is caused by a peripheral vagal neuropathy.

Animals↗

Magnetic resonance imaging, evoked responses and cerebrospinal fluid findings in a follow-up study of children with optic neuritis.

Fourteen patients with previous optic neuritis (ON) in childhood were examined by magnetic resonance (MR) imaging from two months to 14 years after the onset of symptoms. Five patients had a single monosymptomatic course of ON but 7 developed multiple sclerosis (MS); 2 had another demyelinating disease. Eight patients had high signal intensity areas in the T2 weighted images compatible with MS plaques in MR scan; 2 with monosymptomatic ON, 5 with MS and one with another demyelinating disease. The plaques were periventricular or in the optic radiation. The plaques could already be seen during the first symptoms of ON. All 7 MS patients had abnormal visual evoked response, 3/4 abnormal somatosensory evoked response and 5/6 intrathecal immunoglobulin production, when examined at onset of optic neuritis or at follow-up. All patients except one, with lesions in MR, had either oligoclonal CSF antibodies or Dr2 HLA antigen. We suggest that MR is a very sensitive test showing MR abnormalities in children with ON. It is an important tool in the early assessment of MS.

Adolescent↗

Cerebrospinal fluid myelin basic protein-like material in acute monosymptomatic optic neuritis.

INTRODUCTION: Cerebrospinal fluid (CSF) may provide markers of severity and outcome of optic neuritis. MATERIAL AND METHODS: We examined the CSF from 29 patients with acute monosymptomatic optic neuritis (AMON) for content of myelin basic protein-like material (MBPLM) and correlated the levels with results of cranial magnetic resonance imaging. The length of the time from onset of AMON to the time of CSF collection did not exceed four weeks. RESULTS: Only two patients (7%), one of whom developed an acute myelopathy one month after AMON, showed an elevated value of CSF MBPLM. No MBPLM was detected in 6 patients (21%), and other 21 (72%) had detectable levels of MBPLM but below the upper limit of normal of 0.1 ng/ml. The value of MBPLM was not significantly correlated with the interval to CSF sampling from onset of AMON or with severity of decreased visual acuity. The highest values of CSF MBLPM were observed among patients with severely decreased visual acuity and among patients with an abnormal MRI (13 of 27 i.e. 48%). CONCLUSIONS: CSF MBPLM was rarely abnormal in AMON. However, CSF MBPLM may have potential value in reflecting disease activity, as the highest values were obtained among patients with CSF sampled soon after the maximum visual dysfunction was reached, with severe visual impairment, and with an abnormal MRI.

Acute Disease↗

Recovering optic neuritis during systemic cisplatin and carboplatin chemotherapy.

INTRODUCTION: We describe bilateral optic neuropathy in a patient affected by ovarian carcinoma treated with cis-platin 160 mg/m2 and carboplatin, 640 mg/m2. The patient was followed for 1 year, when recovery appeared. The few previous descriptions of CDDP optic nerve toxicity did not report recovery. METHODS: Computerized visual field, visual evoked potentials, pattern electroretinograms, full field flash electroretinograms were recorded during follow-up. RESULTS: Optic neuritis appeared 13 weeks after cis-platin discontinuation, with right eye central scotoma; 2 days later the patient became bilaterally blind. Visual evoked potentials were initially absent, reappeared, with delayed latencies to left eye stimuli at 6 months, in both eyes at 9 months. At 1 year delayed VEPs were recorded with right eye stimuli, normal VEPs were recorded for left eye. CONCLUSION: Cis-platin can induce delayed optic neuritis, that can recover in 1 year.

Antineoplastic Agents↗

Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis.

UNLABELLED: Acute monosymptomatic optic neuritis (AMON) may be an initial symptom of multiple sclerosis (MS). Coronaviruses have been implicated in the etiology of MS. The objective of the present study was to look for coronaviral RNA in AMON, which could be present in the initial stages of the development of MS. MATERIAL AND METHODS: Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. RESULTS: Four patients and 1 control were positive for HCV-229E. No evidence of HCV-OC43 was found. The frequency of positive samples was low and there was no statistical difference between AMON and controls. CONCLUSION: This study does not provide evidence for an etiological role of human coronaviruses in acute monosymptomatic optic neuritis.

Acute Disease↗

Residual symptoms and signs after untreated acute optic neuritis. A one-year follow-up.

PURPOSE: To study the symptoms and signs one year after optic neuritis. METHODS: Seventy population-based untreated patients, (44F, 26M; median age 35 years, range 14-48 years) were eligible for study, but the 11 bilateral cases were excluded. Among 59 patients participating in a one-year follow-up of the visual function, 58 answered a questionnaire. RESULTS: At follow-up 59% of the patients complained of visual impairment, though 49% of these patients had a Snellen visual acuity of 6/9 or better. The affected eyes showed decreased visual acuity in 34%, decreased contrast sensitivity in 63%, an abnormal score in 40% with the Lanthony D-15 desaturated panel, and in 13% with the Ishihara test, prolonged latencies of VEP in 58%, and decreased amplitudes of VEP in 41%. CONCLUSIONS: All tests except for VEP correlated significantly to the degree of perceived visual impairment. Subjective visual complaints and more sensitive tests than visual acuity should be used to evaluate the visual function following optic neuritis.

Acute Disease↗

Cutaneous larva migrans, sacroileitis, and optic neuritis caused by an unidentified organism acquired in Thailand.

We report the case of a 32-year-old pregnant woman with an unidentified intraocular parasite. The parasite, which had been acquired in Thailand, caused cutaneous larva migrans, sacroileitis, and 2 years later optic neuritis and panuveitis. The patient was successfully treated with ivermectin and albendazole. The diagnostic possibilities of this peculiar presentation are discussed. Parasitic infections are a leading cause of medical problems in travelers to tropical countries.1 While most parasites cause gastrointestinal problems, some may migrate throughout the body and lodge in critical organs. Ocular parasitic infections may occur by direct inoculation onto the eye,2 or incidentally during systemic migration. Subconjunctival parasites are easily diagnosed by removal and careful microscopic examination.3 Parasites, which lodge within the eye, are more difficult to diagnose, especially if not removed. In this report we describe a patient who presented with an intraocular parasite causing optic neuritis and panuveitis, 2 years after travel to Thailand.

Adult↗

Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS which leads to demyelination, axonal destruction and neuronal loss in the early stages. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of ciliary neurotrophic factor (CNTF) on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. This study demonstrates that CNTF has a neuroprotective effect on affected RGCs during acute optic neuritis. Furthermore, we demonstrate that CNTF exerts its neuroprotective effect through activation of the Janus kinase/signal transducer and activator of transcription pathway, mitogen activated protein kinases and a shift in the Bcl-2 family of proteins towards the anti-apoptotic side. In summary, our results demonstrate that CNTF can serve as an effective neuroprotective treatment in a rat model of MS that especially reflects the neurodegenerative aspects of this disease.

Analysis of Variance↗

Symptoms, signs and early course of optic neuritis.

The study was an anlysis of the early course of optic neuritis based on the case histories of 185 patients, 57% of whom were females and 43% males. More than half of the patients suffered from multiple sclerosis. In 28% of the patients the etiology remained unknown. The most common initial symptom was acute decrease in visual acuity, but in 25% the onset was subacute or slow. Pain occured in 62% and preceded decrease in visual acuity in 16% of the cases. The initial attack was unilateral in 70% and bilateral in 30% of the patients. On admission, in 64% of the involved eyes, visual acuity was poor and in 73% the defect in the visual field involved the central field. The optic disc was normal in 46%, blurred and /or hyperaemic in 20%, oedematous in 23% and in 11% there was temporal or total pallor already on admission. The last finding was common in patients with bilateral optic neuritis with a slow onset. Six months after admission visual acuity was good or excellent in 56% and the visual field was normal in 45% of the involved eyes.

Adolescent↗

Uncomplicated retrobulbar neuritis and the development of multiple sclerosis.

A retrospective study of 30 patients hospitalized with a diagnosis of uncomplicated retrobulbar neuritis was carried out. The follow-up period was 2-11 years; 57% developed multiple sclerosis. When the initial examination revealed oligoclonal bands in the cerebrospinal fluid, the risk of developing multiple sclerosis increased to 79%. With normal cerebrospinal fluid the risk decreased to only 10%. In the majority of cases, the diagnosis of MS was made during the first 3 years after retrobulbar neuritis.

Adult↗

Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis.

Post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. Such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. These viruses include measles, Epstein-Barr, influenza A and B, and others that cause upper respiratory infections. Several regions identified in myelin basic protein and P2 protein can be related to experimental allergic encephalomyelitis or neuritis in laboratory animals.

Animals↗

Optic neuritis in the Landry-Guillain-Barré-Strohl syndrome.

A patient with typical Landry-Guillain-Barré-Strohl syndrome (LG-BS) developed bilateral optic neuritis. Laboratory studies showed hypersensitivity to both central and peripheral nervous tissue myelin. The occurrence of optic neuritis is presumably due to autohypersensitivity to central nervous tissue myelin. The initial lesions of the LG-BS syndrome in the peripheral nerves might have liberated sequestered antigens that cross-reacted with central nervous system myelin.

Adolescent↗