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Woman with recurrent optic neuritis presents with left eye pain
The patient had a complicated ocular history involving multiple episodes of optic neuritis affecting the right eye.
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A 41-year-old woman of Chinese descent known to the neuro-ophthalmology service came into the clinic for an urgent visit. She complained of pain in the left eye for a few days that was worse with eye movement. Despite this, there was no change in vision. She reported numbness and tingling in both hands several days earlier, which had been present intermittently for several years.
History
| Shazia Ahmed | My Hanh T. Nguyen |
The patient had a complicated ocular history involving multiple episodes of optic neuritis affecting the right eye. Her initial episode occurred 11 years earlier and was treated with intravenous and oral steroids. At the time her vision recovered to 20/20 in both eyes. In subsequent years, the patient had several recurrences of optic neuritis including one in June 1999 with visual recovery to 20/25, another in July 1999 with visual recovery to 20/200 and yet another in July 2005 with visual recovery to 20/400. She had several MRI scans of the brain and orbits showing enhancement of the right optic nerve and a small signal abnormality in the corpus callosum.
Her medical history was significant for a double-stranded DNA antibody titer that was positive. A subsequent test did not detect any antibodies. In addition, she had a pulmonary mass found on a chest radiograph several years ago with an unremarkable pulmonary workup. The patient had no known drug allergies, denied taking any medications and did not use tobacco or alcohol. Her family history was noncontributory.
Examination
On examination, the patient’s vision was 20/400 in the right eye and 20/20 in the left eye, which represented her baseline visual potential. A right afferent pupillary defect was unchanged from previous examination. Anterior segment examination revealed a white, quiet eye with no abnormalities. The optic nerve head in the right eye was pale, and both nerves were slightly tilted. There was no edema of the optic nerve heads. The retina was unremarkable. Automated perimetry showed no specific abnormalities in the left eye and no changes from the last examination in the right eye (Figure 1). The patient was reassured and told to return if she had problems.
Three weeks later, the patient returned reporting 2 days of blurred vision in the left eye. She had slight pain when squeezing her eye shut, although she had none with eye movement. Her vision was still 20/400 in the right eye and 20/20 in the left eye. The afferent pupillary defect was unchanged. She was able to see all the color plates in the left eye. Automated perimetry showed an inferior defect in the left eye (Figure 2). There were no new optic nerve head findings.
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Images: Yoon MK, Hedges TR |
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The patient was started on intravenous methylprednisolone 1 gram daily for 12 days followed by oral prednisone, which was prescribed by the patient’s neurologist. On day 9 of the steroid regiment, an MRI of the brain showed no evidence of inflammation affecting the optic nerves (Figure 3). There was mild increase in signal intensity along the corpus callosum seen on a sagittal section. At this point, vision was 20/60 in the left eye. Subsequent perimetry examinations over the next 3 weeks revealed a similar defect with mild improvement in the mean deviation.
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What is your diagnosis?
Optic neuropathy
The patient had a complicated disease course that affected both of her optic nerves.
The differential diagnosis for optic neuropathies is quite broad and can be divided into several broad categories. Optic neuritis secondary to multiple sclerosis occurs in young and middle-age women. However, the absence of plaques in the white matter of the brain does not support this diagnosis.
Infectious optic neuropathies can be caused by Lyme disease, syphilis, tuberculosis and various viruses. These may manifest with systemic symptoms including meningitis or encephalitis. Blood testing, imaging or lumbar puncture can help identify these etiologies, but there can also be associated findings that were not present in our patient.
Inflammatory and autoimmune causes such as sarcoidosis, Behçet’s disease and systemic lupus erythematosus were ruled out with negative workups. With an absence of intracranial or intraorbital masses, compressive optic neuropathy was also ruled out. The patient did not have any risk factors for anterior ischemic optic neuropathy (eg, cardiovascular disease, hypertension, diabetes mellitus, age over 50 years or obstructive sleep apnea). The patient had no evidence of toxic or nutritional deficiency. She had never been treated with medications such as ethambutol, isoniazid or amiodarone.
Because the patient’s history and workup were not consistent with any of the listed causes of optic neuropathy, the diagnosis of neuromyelitis optica was investigated further.
Diagnosis
On review of the patient’s medical history, diagnosis of mild transverse myelitis was suspected 4 years earlier by her neurologist, although MRI of the cervical and thoracic spinal cord showed no abnormalities. Given this history as well as the severe bilateral optic neuropathy, the diagnosis of neuromyelitis optica (NMO) was explored. Blood work was positive for IgG antibodies specific for neuromyelitis optica.
Discussion
Neuromyelitis optica, or Devic’s disease, is a severe demyelinating disease that preferentially affects the optic nerves and spinal cord. It is considered by some to be related to multiple sclerosis. NMO typically has a relapsing-remitting course. It may be associated with collagen vascular diseases, systemic lupus erythematosus, Sjögren’s disease, thymoma, Behçet’s syndrome and several viral infections. Typically, nonwhite Americans are affected in a higher percentage than classic multiple sclerosis; 15% to 20% of Asian patients with multiple sclerosis have this optic-spinal form. The mortality can be as high as 35% to 50% in 5 years and up to 20% in the acute stages of disease. Other risk factors for NMO include female sex, older age at onset, longer interval between events and systemic autoimmune disease.
Symptoms include episodic myelitis and paroxysmal tonic spasms of upper extremities. Acute and severe paraparesis or tetraparesis can occur in many patients. Severe unilateral or bilateral optic neuritis occurs either before or after the myelitis occurs.
The diagnosis of NMO requires the presence of optic neuritis, acute myelitis and no clinical disease outside of the optic nerves or spinal cord. Major supportive criteria include a negative brain MRI, spinal cord MRI with abnormalities traversing three spinal segments and cerebrospinal fluid with pleocytosis. Minor supportive criteria include bilateral optic neuritis, vision worse than 20/200 in one eye and severe attack-related weakness in at least one limb. The NMO-IgG antibody was recently discovered to be a relatively sensitive and quite specific serum biomarker for neuromyelitis optica and has been proposed as supportive criteria for diagnosis. Our patient had one major and two minor criteria, which were necessary for diagnosis.
The NMO-IgG antibody localizes to pia and subpia (more specifically to astrocytic end plates), Virchow-Robin space, microvessels and subependymal white matter of the central nervous system. The disease is believed to be an antibody-dependent, complement-mediated attack against myelin.
The treatment for neuromyelitis includes immunosuppressants. Corticosteroids are typically used as a first-line treatment for this disease. Azathioprine can be used as a steroid-sparing agent after acute therapy is initiated. Plasmapheresis has been reported to improve symptoms and outcomes. Intravenous immunoglobulin administration can also be used for treatment.
There are several differences between typical multiple sclerosis and neuromyelitis optica. NMO has a more severe course. Although NMO is limited to the optic nerves and spinal cord, multiple sclerosis can affect any portion of white matter. Cerebral MRI may be normal with NMO, although multiple sclerosis typically shows periventricular plaques. Examination of the cerebrospinal fluid with NMO may show pleocytosis without oligoclonal bands, unlike multiple sclerosis. Coexisting autoimmunity is a risk factor only for NMO. Finally, serum neuromyelitis optica antibody is absent in typical multiple sclerosis.
Patient course
The patient underwent plasmapheresis several weeks later and had improvement in visual acuity to 20/40. In addition, the visual field continued to improve slightly. She has agreed to take mycophenolate in an attempt to prevent recurrences.
For more information:
- Michael K. Yoon, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.
- Edited by Shazia Ahmed, MD, and My Hanh T. Nguyen, MD. Drs. Ahmed and Nguyen can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Ahmed and Nguyen have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
- Cox A, Coles A, et al. Recurrent myelitis and optic neuritis in a 29-year-old woman. Lancet Neurol. 2005;4(8):510-516.
- Cree BA, Lamb S, et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005;64(7):1270-1272.
- Lennon VA, Wingerchuk DM, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112.
- Pirko I, Blauwet LK, Lesnick TG, Weinshenker BG. The natural history of recurrent optic neuritis. Arch Neurol. 2004;61(9):1401-1405.
- Pittock SJ, Lennon VA, et al. Brain abnormalities in neuromyelitis optica. Arch Neurol. 2006;63(7):390-396.
- Weinstock-Guttman B, Ramanathan M, et al. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006;63(7):957-963.
- Wingerchuk DM, Lennon VA, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006;66(10):1485-1489.
- Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology. 2003;60(5):848-853.