One of the most capricious conditions in neurology is also one of the hardest to diagnose due to the slew of imposters. Here’s how to identify the true culprit. By Jeffrey I. Greenstein, MD Philadelphia 52 Practical Neurology February 2005 ultiple sclerosis can present with a multiplicity the majority of patients with optic neuritis. The amplitude of of symptoms and signs, making it a challenge to the wave is usually reduced if there is axonal injury. Magnetic differentiate this disorder from a variety of neu- resonance imaging of the optic nerve can be applied by using rological or systemic diseases involving the fat suppression. Increased T2-weighted signals and gadolini- Mbrain, optic nerve, spinal cord or all of the um-enhancement may also be present in the affected portion of above. Adding to the complexity, one must take into account the nerve. that MS can present with either a relapsing or progressive If the systemic manifestations of other conditions are not onset, making it particularly important to be certain of your present, then the major decision one has to make when consid- diagnosis. Given the severity of the condition, prompt recogni- ering a diagnosis of multiple sclerosis depends primarily on the tion is critically important in forestalling disability by allowing presence of cerebral or spinal cord lesions on MRI. If three or immediate treatment intervention, which further increases the more ovoid, periventricular or gadolinium-enhancing lesions challenge of making the diagnosis in the earliest stages when are present then the likelihood of MS developing increases con- the clinical picture may still be hazy. siderably.4,5 The presence of oligoclonal bands also increases the Many of the diseases considered to be in the differential likelihood of MS developing but does not have the same prog- diagnosis for MS in the past can now be easily detected by nostic strength of the MRI findings.6 using neuroimaging (MRI in particular) as well as biochemical, In the absence of prior episodes consistent with MS, there is genetic or immunologic tests. However, some of these disorders a wide differential diagnosis to consider (see Table 1). The onset are still worth considering in any formal review of the differen- of optic neuropathy in systemic vasculitis is usually painless, sim- tial diagnosis for MS. ilar to acute ischemic optic neuropathy. A positive antinuclear The differential diagnosis of multiple sclerosis may be con- antibody will differentiate optic neuritis occurring in systemic sidered by disease course or by the affected location. For the lupus erythematosis. Isolated optic neuritis is a rare manifesta- scope of this article, we will consider cerebral, optic nerve and spinal cord presentations and comment within these diseases’ different divisions and tempos. To narrow the field of suspects Table 1. yet further, we will focus on the most common conditions that Differential Diagnosis of Optic Neuritis mimic MS in adults. Steroid-responsive optic neuritis Broadly speaking, MS can present initially with optic neuri- • Idiopathic inflammatory optic neuritis tis, cognitive impairment and cerebral or spinal long-tract and • Neuromyelitis optica (Devic’s disease) brain-stem signs. Here are the telltale distinctions between MS • Systemic lupus erythematosis • Sarcoidosis and other disorders with cerebral presentations (this discussion • Chronic relapsing inflammatory optic neuropathy excludes spinal cord presentations). Inflammatory optic neuritis • Acute disseminated encephalomyelitis Seeing Through Optic Neuritis —Post-infectious This can present acutely, sub-acutely or occasionally with a rare —Post-vaccinal form of chronic inflammatory optic neuropathy.1-3 Patients Infectious optic neuropathies with this condition are typically between 15 and 45 years of age • Lyme disease and predominantly female (75 percent). • Syphilis The most common clinical presentation is monocular visu- • Tuberculosis • Viral optic neuritis al loss associated with periocular pain and pain on eye move- ment. Light flashes—phosphenes or photopsias—are also Toxic and metabolic neuropathies noted occasionally. Examination usually reveals that visual acu- • Vitamin B12 deficiency • Tobacco-alcohol amblyopia ity is decreased to absent (a majority of cases range between • Methanol intoxication 20/25 and 20/200), with poor color vision and contrast sensi- tivity. A variety of visual field defects occur and an afferent pap- Inherited optic neuropathy • Leber’s optic neuropathy illary defect is often present. The disc may be normal or swollen. Pallor of the temporal margin may be present, indicat- Ischemic optic neuropathies ing prior demyelination if the patient is seen early. • Anterior ischemic optic neuropathy • Posterior ischemic optic neuropathy Optic disc swelling with a macular star may be found in • Giant cell arteritis optic neuritis due to Lyme disease or sarcoidosis. Visual evoked potentials demonstrate prolonged latencies of the P100 wave in February 2005 Practical Neurology 53 Differential Diagnosis of MS tion of sarcoidosis. Optic disc swelling may be present. transmitted and males predominate here, unlike the hereditary Optic neuritis may also occur with a basilar meningitis in occurrence of multiple sclerosis which is transmitted more com- sarcoidosis. Mediastinal lymphadenopathy, a positive ACE monly to females. It may approximate multiple sclerosis in level and non-caseating granulomas on tissue biopsy are help- younger individuals with milder fundal abnormalities. The usual ful in the diagnosis of sarcoid optic neuropathy. Neuromyelitis age of onset of this disorder is between 15 and 40, with an acute optica (to be considered later) is suspected with a combination painless monocular loss of vision, an afferent papillary defect and of optic neuritis and transverse myelitis with relatively exten- central or centrocecal visual field abnormality. sive rostral-caudal spinal demyelination (see Table 2).7 Optic atrophy develops months after disease onset. Visual One should be sure there are no brain lesions to confirm the acuity progressively worsens to less than 20/200 and subse- diagnosis. Chronic relapsing inflammatory optic neuropathy is quently the other eye is affected. Improvement may occur in a characterized by a pre- minority of affected individuals. Visual evoked potentials may dominantly bilateral be absent, or painful optic neuropa- demonstrate de- thy with disc swelling layed latency and or pallor. Visual loss is Patients with decreased P100 usually more severe Leber’s hereditary amplitude. A vari- than what is seen in ety of signs may optic neuritis. optic neuropathy suggest multiple Cerebral MRI is nor- can be sclerosis, including mal but the optic differentiated increased reflexes, nerves have high T2- spasticity, ataxia, weighted lesions, from MS patients and a myelopathy. often with gadolini- by the However, this dis- um-enhancement. former’s lack of order can be dif- Chronic steroid ferentiated from administration is MRI or CSF multiple sclerosis required to control abnormalities. because no MRI this condition. or cerebrospinal Bilateral optic neuri- fluid abnormali- tis is often seen in ties occur. A de- acute disseminated finitive diagnosis can made through genetic testing. encephalomyelitis, a feature that serves to support this diagno- sis rather than multiple sclerosis (discussed below). Cerebral Presentations of Mimickers Anterior ischemic optic neuropathy needs to be considered in At times, clues provided by the patient during the history can older individuals with acute visual loss.8 It should not be difficult help you identify some of the most common cases, but a host to distinguish this condition from multiple sclerosis. This condi- of conditions require more specialized observation via neu- tion is the result of ischemia in the post laminar optic nerve and roimaging. Here are some of the mimickers to keep in mind usually occurs in the over-55 age group, but may be seen in any while looking over the scans. individuals over 40. It presents with acute, painless, uniocular Subcortical arteriosclerotic encephalopathy/leukoariosis is visual loss on waking. Visual perception is reduced, but by no due to fibrohyalinosis of the deep penetrating vessels supplying more than 20/60 in as many a half of affected individuals. An the periventricular white matter.10 The strongest correlations afferent papillary defect is present, with altitudinal or inferonasal are with hypertension, diabetes mellitus and episodes of arcuate visual field defects. Optic disc swelling occurs with hypotension. It results in demyelination and astrocytic gliosis flame-shaped hemorrhages and cotton wool spots on the disc or of the deep white matter but spares the subcortical u-fibers. In its margin. The other eye may be affected in 25 percent of cases. its full-blown form it presents with subcortical dementia, gait Unfortunately, there is little visual recovery. Diabetes, hyper- and disturbance and incontinence in elderly patients. hypotension are common accompaniments. Practitioners have described a similar presentation in multi- Leber’s hereditary optic neuropathy is caused by mutations in ple sclerosis, but this can be distinguished from leukoaraiosis mitochondrial DNA coding, mostly for complex I of the oxida- by characteristic antecedent clinical events and cerebrospinal tive phosphorylation pathway.9 The mutations are maternally and evoked potential findings.11 54 Practical Neurology February 2005 From a clinical perspective, the