eMedicine Specialties > Ophthalmology > Neurologic Disorders

Multiple Sclerosis

Author: Andrew G Lee, MD, Professor, Departments of Ophthalmology, Neurology and Neurosurgery, University of Iowa Hospitals and Clinics
Coauthor(s): Fiona Costello, MD, FRCP, Assistant Professor, Departments of Ophthalmology and Medicine (Neurology), Neuro-ophthalmologist, Clinical Neurologist and Clinical Investigator, University of Ottawa; Cecil L Berlie, MD, Consulting Staff, Department of Ophthalmology, Luther Midelfort Eye Clinic
Contributor Information and Disclosures

Updated: Jan 26, 2007

Introduction

Background

Multiple sclerosis (MS) is a common neurologic disorder with protean manifestations. The disease is characterized by myriad multifocal neurologic signs and symptoms, which tend to relapse and remit in the initial stages of the illness and then culminate in progressive neurologic disability over time.

Clinical subtypes of MS include the following: clinically isolated syndromes, primary progressive MS (PPMS), relapsing remitting MS (RRMS), and secondary progressive MS (SPMS).

It is not uncommon for patients with MS to present initially to the ophthalmologist with symptoms, including acute monocular visual loss (ie, optic neuritis [ON]), diplopia (eg, internuclear ophthalmoplegia, sixth nerve palsy), or oscillopsia (ie, nystagmus). No single test can be done to help establish or exclude a diagnosis of MS. Instead, MS is a clinical diagnosis supported by laboratory studies and neuroimaging findings. Early recognition of the disease is important because several immunomodulatory therapies are currently available that might slow the rate of conversion to clinically definite MS (CDMS) after a clinically isolated syndrome (eg, ON) and potentially reduce the progression of the disorder.

Ophthalmologic manifestations of MS that are discussed in this article include ON, nystagmus, and internuclear ophthalmoplegia (INO).

Pathophysiology

The pathophysiology of MS is not known but is probably multifactorial. Several mechanisms have been proposed, including immune mediated; postinfectious (eg, viral), environmental, and geographical exposures; and hereditary factors. The underlying pathologic insult is demyelinating and inflammatory, but, ultimately, axonal loss may result in permanent neurologic deficit. Demyelinating lesions that may produce clinical symptoms occur in the periventricular white matter, the brainstem, the cerebellum, the spinal cord, and optic nerves.

Frequency

United States

Prevalence rates of 17-90 cases per 100,000 have been reported. One population-based study conducted in Rochester, Minnesota, reported an annual incidence of all cases of ON to be 6.4 per 100,000.

International

An increase in prevalence exists with increasing latitude from the equator. This condition is less frequent in the Mediterranean region and is rare in Africa and Asia.

Studies in Europe and Scandinavia demonstrate an incidence of 0.94-2.5 cases per 100,000. The following prevalence rates have been reported (per 100,000): Canada (100); Italy (30-60); Sardinia (60-100); Spain (4-50); Japan, Taiwan, Korea, Malaysia, and China (1-4); Kuwait, Libya, and Saudi Arabia (6-8); and Australia (18-75, south-to-north decreasing prevalence).

Mortality/Morbidity

Mortality in MS can be attributed to numerous factors late in the disease course. The disease itself is extremely variable in severity. Patients with severe MS may succumb to respiratory failure or infection. In the Danish Multiple Sclerosis Registry (n=9881), the median survival time from onset was approximately 10 years shorter for patients with MS than for the age-matched general population, and MS was associated with an almost 3-fold increase in the risk for death. According to death certificates, more than half (56.4%) of the patients had died from complications of MS.

Race

MS is more frequent in whites of northern European origin, and, in this population, up to 1 in 1000 develop MS. MS is less common in individuals of African, Asian, or Mediterranean extraction.

Sex

A female preponderance of 1.6:1 exists in MS, but, in the primary progressive form, males predominate. In the Optic Neuritis Treatment Trial (ONTT), 77% of patients with ON were female. Miller reported that, on average, women were 3 times more likely to develop ON than men. The reason for this difference between men and women is not known.

Age

Symptoms of MS typically present in persons aged 18-50 years, and the age of onset of ON is typically younger for women than for men. According to a study conducted by Wray, the mean age of onset for women is 30.2 years, with a range of 9-55 years. Men typically have a later average age of onset of ON (31.1 y) than women, with the range being 16-60 years. MS can develop in children and in older adults.

Clinical

History

The classic clinical picture of MS is one of multiple neurologic symptoms "disseminated in space and time." More specifically, patients manifest episodic neurologic dysfunction due to inflammation in different regions of the central nervous system over time. Common neuro-ophthalmologic symptoms include unilateral visual loss due to ON and oscillopsia due to nystagmus and diplopia (eg, INO, ocular motor palsy). Other common neurologic symptoms include sensory disturbances, motor weakness, and trigeminal neuralgia. For this reason, patients with ophthalmic symptoms consistent with a possible MS attack should be questioned about historical features that may be suggestive of MS (eg, prior neurologic deficit, prior diplopia or loss of vision, prior neuroimaging studies).

• Afferent visual pathway manifestations - ON
  • Frequency in MS: Approximately 20% of patients with MS present with ON as a first demyelinating event, while 40% of patients may present with ON during the course of their disease. Pathological studies have demonstrated that subclinical optic nerve involvement is very common among patients with MS, and the percentage of patients with anterior visual axis involvement from the disease is likely much higher. Therefore, diagnosing ON is potentially an important step in providing appropriate therapy for the patient; however, not everyone who develops ON develops MS.
  • Clinical onset: ON typically causes acute-to-subacute unilateral loss of visual acuity (which may progress over days to weeks), color and contrast sensitivity, and visual field changes.
  • Pain: Most patients with ON develop retrobulbar pain that is worse with extraocular movement. In the ONTT, mild to severe pain was present in 92.2% of patients. Pain was constant in 7.3% of patients, was constant and worse upon extraocular motility in 51.3% of patients, and was noted only with eye movement in 35.8% of patients.
  • Visual acuity: The loss of visual acuity in patients with ON may range from minimal to profound. At entry into the ONTT, 35% of patients had visual acuities of 20/40 or better, 30% of patients had visual acuities of between 20/50 and 20/200, and 35% of patients had visual acuities of 20/200 or worse. Only 3% of patients were no light perception (NLP). Therefore, NLP should be considered a red flag for a diagnosis of ON, and other potential etiologies for vision loss (eg, inflammatory, infiltrative, neoplastic) might need to be considered.
  • Color vision: In the ONTT, nearly 100% of patients whose visual acuities were 20/50 or worse had a defect in their color sensitivity, and, in those patients with visual acuities of 20/20 or better, 51-70% had altered color vision.
  • Phosphenes: Patients with ON may describe phosphenes or transient flashes of light or black squares lasting from hours to months. Either movement or sound may induce them. They may occur before or during an ON event or even several months following recovery.
  • Visual field function: Visual field changes are common in patients with ON and are typically nerve fiber layer defects. The classic visual field defect of ON is the central scotoma, but any nerve fiber type defect may occur. In the ONTT, the most common visual field defects were, in decreasing order of frequency: altitudinal (28.8%), 3 quadrant (14.0%), 1 quadrant (11.8%), centrocecal (8.7%), hemianopic (8.3%), peripheral rim (7.0%), arcuate (7.4%), central (7.0%), enlarged blind spot (2.6%), and nasal step (1.3%).
  • Other visual symptoms: Other reported visual changes in patients with ON include decreased visual acuity in bright light (about 50% of patients see better in dim light than in bright light), flickering scotomata, and the Uhthoff phenomenon. The Uhthoff phenomenon is an exacerbation of the patient's symptoms when exercising or when exposed to temperature change. The most notable symptoms affected by the Uhthoff phenomenon are transient visual obscurations, dyschromatopsia, and contrast sensitivity changes. The symptoms tend to resolve with restoration of euthermic conditions. Most symptoms of the Uhthoff phenomenon resolve from within 60 minutes to 24 hours.
  • Clinical course: The ONTT found that 74% of patients with ON recovered visual acuities of 20/60 or better by 8 weeks, and most patients had visual acuities of better than 20/40 by 6 months. Although visual acuity typically recovers after ON, patients may continue to complain of residual deficits in color, contrast sensitivity, brightness, and stereovision.
• Efferent visual pathway manifestations - Diplopia, oscillopsia, and nystagmus
  • Diplopia may be due to an INO or an ocular motor cranial neuropathy (typically a sixth nerve palsy).
  • Brainstem involvement producing gaze palsies, nystagmus, or a skew deviation may occur.
  • The occurrence of bilateral INO is considered to be highly suggestive of MS, especially in young patients.

Physical

• Patients with ON typically have loss of both visual acuity and visual field in the ipsilateral eye. Contralateral and often asymptomatic visual field loss may also be detected. A relative afferent pupillary defect is present in unilateral cases and bilateral but asymmetric cases, but the relative afferent pupillary defect may be absent in bilateral and symmetric cases. The visual field defect is often a central scotoma but may be of any optic nerve related field loss.
• Anterior ON (ie, papillitis): Although most patients with demyelinating ON have retrobulbar neuritis, the disc may show mild hyperemia. Severe disc edema, marked hemorrhages, or exudate should prompt reconsideration of a diagnosis of demyelinating ON.
• Posterior ON (ie, retrobulbar ON): Most cases of ON are retrobulbar. In these cases, "the patient sees nothing, and the doctor sees nothing" (ie, the fundus is normal).
• Optic disc pallor, sector or diffuse, often follows either anterior ON or posterior ON.
• Other fundus findings, including anterior uveitis, vitreitis, vascular sheathing, and disc and papillary hemorrhages, as well as compromise of the central arterial and venous circulations, are uncommon. The amount of inflammation, the changes in visual field, and the loss of visual acuity do not correlate directly with the appearance of the disc.
• Patients with MS may present with diplopia due to an INO. In an INO, an adduction deficit of the ipsilateral eye is present, with horizontal gaze nystagmus in the contralateral abducting eye. The lesion involves the medial longitudinal fasciculus (MLF). As stated previously, a bilateral INO is strongly suggestive of a diagnosis of MS. Diplopia in MS may also be due to an ocular motor cranial neuropathy, and a sixth nerve palsy is the most common manifestation. Third and fourth cranial neuropathies are uncommon in MS. Combinations of deficits, including horizontal or vertical gaze palsies, wall-eyed bilateral INO (WEBINO) or wall-eyed monocular INO (WEMINO), paralytic pontine exotropia, or the one-and-a-half syndrome, may also occur in MS.
• Oscillopsia secondary to various types of nystagmus may occur in MS. A new onset acquired pendular nystagmus is relatively common, but upbeat, downbeat, convergence-retraction, and other forms of nystagmus may occur in MS depending on the location of the demyelinating lesion.

Causes

The most important association of ON is with MS. Although ON is generally an idiopathic or demyelinating process, other conditions can produce an optic neuropathy, including the following:

• Inflammatory (eg, sarcoidosis, systemic lupus erythematosus, polyarteritis nodosa, Wegener granulomatosis)
• Infectious (eg, spirochetes, Lyme disease, syphilis, hepatitis B, varicella zoster, human immunodeficiency, Epstein-Barr, cytomegalovirus, mycobacteria, fungi)
• Infiltrative processes (eg, leukemia, lymphoma)
• Toxins (eg, antimetabolites, phenothiazines, isoniazid, ethambutol)
• Nutritional deficiencies (eg, vitamin B-12 level, folate)
• Compressive lesions (eg, tumor, aneurysm, thyroid orbitopathy)
• Ischemic optic neuropathy (eg, anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, antiphospholipid antibody syndrome)

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