You are in: eMedicine Specialties > Radiology > HEAD AND NECK Optic NeuritisArticle Last Updated: Feb 8, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 7
  Author: Pil (Peter) S Kang, MD, Resident Physician, Chief Resident, Diagnostic Radiology, Department of Diagnostic Radiology, Walter Reed Army Medical Center, National Naval Medical Center Pil (Peter) S Kang is a member of the following medical societies: Alpha Omega Alpha Coauthor(s): Fletcher M Munter, MD, Program Director, National Capital Consortium Radiology Residency; Consulting Staff, Department of Radiology, Walter Reed Army Medical Center; Charles Swallow, MD, Department of Radiology, St Marks Hospital Editors: Barton F Branstetter IV, MD, Assistant Professor of Radiology and Otolaryngology, University of Pittsburgh; Director of Head and Neck Imaging, Associate Director of Informatics, Department of Radiology, Division of Neuroradiology, University of Pittsburgh Medical Center; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences Author and Editor Disclosure Synonyms and related keywords: inflammation of the optic nerve, acute vision loss, multiple sclerosis, human leukocyte antigen Dw2, HLA-Dw2, human leukocyte antigen DR2, HLA-DR2, acute optic neuritis INTRODUCTIONSection 2 of 7
  BackgroundOptic neuritis is defined as inflammation of the optic nerve. It is one of the causes of acute loss of vision associated with pain. Optic neuritis can be the initial episode for a patient who will subsequently develop multiple sclerosis. The diagnosis of optic neuritis is usually made clinically. Although direct imaging of the optic nerves by MRI is reserved for atypical cases, MRI of the brain yields information that can change management and yield prognostic information in terms of the patient's future risk for development of multiple sclerosis. PathophysiologyThe inflammation of the optic nerve is mainly due to demyelination and can be idiopathic and isolated. However, this disease has a very strong association with multiple sclerosis. Fifteen to 20% of cases of multiple sclerosis manifest as optic neuritis, and 38-50% of patients with multiple sclerosis develop optic neuritis at some point during the course of their disease. According to one of the more well-known long-term follow-up series of optic neuritis, the risk of development of multiple sclerosis after an episode of isolated optic neuritis was 30% at 5-year follow-up and 38% at 10-year follow-up. Neuromyelitis optica, also known as Devic disease, is a rare demyelinating process that affects the optic nerve. This disease is frequently misdiagnosed as multiple sclerosis, but it is a separate entity that is distinguished from multiple sclerosis by its severity, by disease location (affects the optic nerves and the spinal cord, sparing the brain), and by cerebrospinal fluid analysis (polymorphonuclear pleocytosis and absence of oligoclonal banding). Although demyelination is the most common identifiable cause of optic neuritis, other causes of optic nerve inflammation include Lyme disease, tuberculosis, syphilis, and viral agents such as HIV, hepatitis B virus, herpes virus, and cytomegalovirus. Secondary involvement from paranasal sinus infection and orbital cysticercosis has been described. Optic neuritis also may occur as a complication of radiation therapy. Much rarer causes, such as drugs (concurrent etanercept and isoniazid therapy, ethambutol in the setting of end-stage renal disease, interferon alfa), gluten sensitivity, hypereosinophilic syndrome, and vasculitis (giant cell arteritis), have been reported in the literature as case reports. Lesions of the optic nerve in idiopathic and multiple sclerosis–related optic neuritis are similar to the plaques seen in multiple sclerosis of the brain. In acute optic neuritis, lesions are sharply defined areas of myelin sheath loss with relative preservation of the axons. Large numbers of foamy macrophages are present, along with cholesterol ester droplets and abundant lymphocyte and plasma cell accumulations. In later stages of the disease, the numbers of lymphocytes, plasma cells, and macrophages diminish and astrocytic scar formation occurs. Little remyelination of the damaged axons in lesions is associated with chronic multiple sclerosis, but evidence of oligodendrocyte precursor cells and remyelination attempts in early multiple sclerosis and acute lesions has been documented. This suggests that potential therapeutic interventions that promote myelin formation may play a role in improved recovery. The lack of remyelination in chronic lesions often is manifested clinically by abnormal visual-evoked potentials, even when Snellen chart visual acuity has returned to normal or near normal in most patients. Functional MRI studies have demonstrated extra-occipital sites of activation during visual stimuli, particularly involving the insula, claustrum, lateral temporal lobe, thalamus, and posterior parietal and orbitofrontal regions. This suggests that a functional reorganization of cerebral responses to abnormal or delayed stimuli from the damaged nerves may occur as an adaptive mechanism. Recent long-term visual-evoked potential studies suggest that some degree of partial remyelination or ion channel reorganization in the optic nerves may occur up to 2 years after the initial demyelination event. However, this may be counterbalanced by recurrent subclinical episodes of demyelination. Various genetic and environmental factors are presumed to predispose patients to demyelination as an autoimmune response. The presence of alleles for HLA-Dw2 or HLA-DR2 is a known risk factor in the development of multiple sclerosis and optic neuritis. However, in a Swedish cohort, the allele for HLA-Dw2 was present in only 47% of affected patients. Viral or bacterial infection, stress, and systemic antigens and metabolites have been proposed as possible initiating events that result in autoreactive antibodies and T cells crossing the blood brain barrier and injuring myelin. AnatomyMRI studies have been performed to identify the most common sites of optic nerve involvement in optic neuritis. The nerve can be divided into 5 segments (each with frequency of involvement), including (1) anterior (45%), abutting the optic disc; (2) mid intraorbital (61%); (3) intracanalicular (34%); (4) intracranial prechiasmatic (5%); and (5) chiasmatic segments (2%). Lesions occasionally involve more than one site. Clinical DetailsThe classic triad of optic neuritis consists of (1) loss of vision, (2) eye pain, and (3) dyschromatopsia, which refers to the impairment of accurate color vision. Seventy percent of cases in adults are unilateral. The typical clinical course is that of eye pain and worsening visual function, which progresses over days to weeks. The eye pain usually resolves over days, often as the visual loss begins. The patients usually recover spontaneously, with recovery of visual loss beginning within 2-3 weeks and stabilizing over months. Additional associated clinical findings may include movement- or sound-induced phosphenes, described as brief flashes of light lasting 1-2 seconds. Reduction in vision may worsen in bright light, a symptom that seems paradoxical. The Uhthoff symptom, described as exercise- or heat-induced vision loss, may occur and has been described in 50% of patients with isolated optic neuritis. Physical examination findings may include an afferent pupillary defect and a swollen optic disc. Whites of northern European descent are affected 8 times more frequently than blacks and Asians. Whites of Mediterranean ancestry are at intermediate risk. African blacks and Asians are rarely affected. In the United States, the male-to-female ratio for optic neuritis is 1:1.8. The mean age of onset is approximately 30 years, with most patients presenting from age 20-40 years. The condition is rare in children and is usually related to a postinfectious or parainfectious demyelination. Optic neuritis in children is less likely to progress to multiple sclerosis, but, in some reports, it has a worse prognosis for full vision recovery. In patients older than age 50 years, optic neuritis is less common and may be mistaken for ischemic optic neuropathy, which is more common in persons in this age group. Irreversible optic nerve damage occurs in up to 85% of patients; however, this damage often is subclinical. As many as 80% of patients regain at least 20/30 vision, 45% within the first 4 months and 35% within 1 year. Of patients, 20% have long-term severe vision loss. This morbidity is separate from that associated with multiple sclerosis. Occasionally, subclinical optic neuritis is discovered in patients during an evaluation for demyelination suspected for other reasons. These subclinical cases may be detected electrophysiologically by visual-evoked potentials or by careful physical examination if dyschromatopsia, optic disc pallor, and characteristic nerve fiber layer slits are discovered. The demographics of incidence and prevalence rates of optic neuritis in the United States closely follow those of multiple sclerosis; therefore, the prevalence of optic neuritis is highest among white populations of northern European ancestry, is moderately high in white populations of Mediterranean ancestry, and is low in African black or Asian populations. In the United States, the annual incidence in a predominately white community is 6.4 cases per 100,000 persons. Optic neuritis not uncommonly recurs, either in the same or the contralateral eye. One of the long-term follow up studies of optic neuritis, Optic Neuritis Treatment Trial, has shown that 28% and 35% of patients developed recurrence within 5 and 10 years, respectively. Not surprisingly, recurrence was more common in patients who were subsequently diagnosed with multiple sclerosis. Most persons with optic neuritis recover spontaneously. Intravenous methylprednisolone therapy has shown to increase rates of visual recovery, but without significant long-term benefit for visual function. Corticosteroids, therefore, are considered for patients who require faster recovery, such as monocular patients, patients with severe bilateral visual loss, or those with occupations requiring high level of visual acuity. Treatment with corticosteroids and/or immunomodulation agents (eg, interferon beta-1a, interferon beta-1b, glatiramer acetate) can be considered in patients who are at higher risk of developing multiple sclerosis. This is determined predominantly by MRI of the brain, which is discussed in Preferred Examination. Preferred ExaminationThe diagnosis of optic neuritis is usually made on clinical grounds, supplemented by ophthalmological examination findings. However, in atypical cases (eg, prolonged or severe pain, lack of visual recovery, atypical visual-field loss, evidence of orbital inflammation and/or inflammation), MRI is used to further characterize and to exclude other disease processes. Thin (2-3 mm) fat-suppressed T2-weighted images, such as short tau inversion recovery sequences, through the optic nerves may show characteristic high-signal intensity foci in the minimally or nonexpanded nerve. These lesions frequently enhance following intravenous contrast administration, which is not seen in a healthy optic nerve. Some studies have shown that certain findings, such as optic nerve lesions of greater length and in certain locations (within optic canal), might be associated with a worse visual prognosis and might benefit from certain treatments, but other studies have not supportedthis conclusion. In the future, diffusion-weighted and diffusion-tensor imaging may contribute more data that might prove to have some bearing on treatment and/or on prognosis. The thought is that the loss of anisotropy (manifested by an increase in the apparent diffusion coefficient or decrease in fractional anisotropy) associated with demyelination and/or axonal damage may be more sensitive and/or yield more prognostic information than anatomic imaging findings (size, T2 signal intensity, and enhancement, which suggests loss of the blood-brain barrier due to the underlying pathologic process), which could manifest themselves much later than the findings associated with loss of anisotropy. However, with the current technology, diffusion-weighted and diffusion-tensor imaging of the optic nerves is too time- and labor-intensive for broad clinical application. The real contribution of imaging in the setting of optic neuritis is made by imaging the brain, not the optic nerves themselves. This is due to the fact that the most valuable predictor for the development of subsequent multiple sclerosis is the presence of white matter abnormalities. Twenty-seven to 70% (in various studies) of patients with isolated optic neuritis show abnormal MRI findings of the brain, as defined by 2 or more white matter lesions on T2-weighted images. In the Optic Nerve Treatment Trial, the 5-year risk of developing multiple sclerosis was 16% in patients with normal brain MRI findings, 37% with 1-2 lesions, and 51% with 3 or more lesions. At 10 years, the only statistically significant difference was between no lesions (22% risk) and one or more lesions (56% risk). In addition, information from brain MRI has a potential influence on treatment. It has been shown that in 2-year follow-up of patients with optic neuritis and 2 or more brain lesions on MRIs, the intravenous methylprednisolone therapy group (vs placebo and oral prednisone groups) showed a significantly decreased risk of developing multiple sclerosis. Note that this benefit was not maintained at 3 years. In a study using interferon beta-1a (Avonex) in patients with optic neuritis with 2 or more white matter lesions on MRIs of the brain, a decreased risk of developing multiple sclerosis at 3 years was demonstrated. In those patients who did ultimately developed multiple sclerosis, interferon beta-1a has shown to reduce the disease burden and number of active lesions. DIFFERENTIALSSection 3 of 7
Brain, Multiple Sclerosis Orbit, Infection Sinusitis Tuberculosis, CNS
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| Media file 1: A 43-year-old woman with acute vision loss and eye pain. No prior neurologic symptoms were noted. Axial short tau inversion recovery image demonstrates faint increased signal in the distal left optic nerve. | |
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| Media file 2: A 43-year-old woman with acute vision loss and eye pain. No prior neurologic symptoms were noted. Axial fat-suppressed postgadolinium T1-weighted image through the orbit reveals an intensely enhancing segment of the distal left optic nerve (corresponding to the site of subtle increased signal on the image in Image 1). | |
 | View Full Size Image | Media type: MRI |
| Media file 3: A 43-year-old woman with acute vision loss and eye pain. No prior neurologic symptoms were noted. Coronal fat-suppressed postgadolinium T1-weighted image demonstrates intense enhancement within the optic nerve (same patient as Images 1-2). No significant nerve expansion or enhancement of the adjacent tissues is seen. Note the normal right optic nerve for comparison. | |
 | View Full Size Image | Media type: MRI |
| Media file 4: A 35-year-old woman with acute onset of left eye pain and vision decline. Axial fat-suppressed postcontrast T1-weighted image demonstrates enhancement in the intracanalicular portion of the left optic nerve. | |
 | View Full Size Image | Media type: MRI |
| Media file 5: A 35-year-old woman with acute onset of left eye pain and vision decline. Axial fluid-attenuation inversion recovery image demonstrates bilateral periventricular white matter lesions. Several additional and similar lesions were seen in other locations (not shown). No history of prior neurologic illness was noted in the patient, but in the setting of acute optic neuritis, the multiple white matter lesions in a number and pattern atypical for patient age were considered supportive of the diagnosis of multiple sclerosis (same patient as Image 4). | |
 | View Full Size Image | Media type: MRI |
Article Last Updated: Feb 8, 2006
