The retrobulbar form, which is the more common, and the papillitis form are the two types of optic neuritis. The causes of both forms are the same; it is the site of the lesion in the optic nerve that is different. The patient usually reports pain on movement of the affected eye, either immediately preceding or simultaneously with the onset of blurred vision. Then a precipitous drop in vision occurs, with a lessening or cessation of the pain. The vision stays at a low level for several days or weeks and then slowly but steadily improves over several weeks or months. The prognosis for return to normal or near-normal vision is excellent with the first attack. The prognosis in subsequent attacks is not as good.
Even when full recovery of vision occurs, an obvious temporal or even a generalized optic nerve atrophy is not unusual. This disparity between recovery of acuity and atrophy of the disc is particularly common in optic neuritis owing to multiple sclerosis. In years past, it was said that about 50% of cases of optic neuritis were caused by multiple sclerosis; more recent studies put the figure closer to 78%. Bilateral optic neuritis, even if the two episodes are separate in time, and recurrent optic neuritis are associated with a much higher incidence of multiple sclerosis. The usual field defect is a central scotoma; however, other field defects, such as arcuate scotomas and quadrantic defects, are seen. Some cases of optic neuritis even occur with normal visual acuity but an extrafoveal field defect. In such cases, usually an afferent pupillary defect and a color vision defect exist, as demonstrated by the HRR plates. On rare occasions, the lesion of optic neuritis is located in the nerve just as it enters the chiasm; therefore, it also affects the lower nasal fibers crossing over from the other optic nerve. The result is a junction scotoma, which is an ipsilateral central defect in the affected eye and an upper temporal field cut in the other eye. This type of defect more commonly occurs with chiasmal masses and must therefore be differentiated from optic neuritis.
Occasionally, patients complain of a fluctuation in vision when they take a hot bath or indulge in prolonged and strenuous exercise. The increase in body temperature that results from both types of activity causes a change in the conduction ability of nerves already compromised by the demyelinating process. Such a fluctuation in vision is called Uhthoff's sign.
The usual report of the examination in retrobulbar neuritis is that the patient sees nothing and the physician sees nothing. At the onset of the disease, patients say they see nothing or what they see is blurred. In the retrobulbar form, no fundus or disc changes occur; therefore, the physician sees nothing abnormal. The atrophy comes on later; at this stage, the pupillary signs, the field defect, and the rapid visual loss suggest the diagnosis.
The patient who has a slow and steady visual loss should be regarded as possibly having a condition other than optic neuritis. A mass lesion should be seriously considered in any case of chronic progressive visual loss. In cases of papillitis, the disc is swollen, and hemorrhages may be present around the disc. Swelling of the disc in papillitis cannot be differentiated from papilledema owing to increased intracranial pressure solely from the appearance of the disc. The appearance of the disc in papillitis and papilledema is also similar with fluorescein staining, so fluorescein studies are not useful in differentiating the conditions.
Optic neuritis usually begins in young people, but rarely in those under 10 years of age. If a child has visual loss in one eye, be sudden. Sudden recognition of a visual loss (e.g., in a school vision-screening test) does not always indicate a sudden onset. In a child under 10 years of age, the condition may be a slow-growing optic nerve glioma that is followed only weeks or months later by clinically obvious optic atrophy.
Evaluation of optic neuritis includes a carefully taken history—the signs and symp-toms must fit the diagnosis. The history taking should also include questions about poor eating habits as possible causes of a nutritional amblyopia, particularly if the patient is a fad dieter.
Ask the patient particularly about possible exposure to toxins at work or at home (e.g., lead or mercury). Today, it is especially important to ask about the use of drugs, even the legitimate ones (e.g., ethchlorvynol [Placidyl], birth control pills, ethambutol, and isoniazid). Ask too about the use of tobacco and alcohol; they are more commonly associated with nutritional amblyopia than with true optic neuritis, but still they may contribute to optic neuritis.
Magnetic resonance imaging (MRI) and computed tomography (CT) should be done of the optic canal and sphenoid ridge, and bone changes suggesting tumor should be looked for. Ultrasonography and CT of the retro-orbital space are important in excluding an orbital mass lesion that may be affecting only the optic nerve and not causing ophthalmoplegia or exophthalmos. The two techniques can show the optic nerve to be swollen in optic neuritis, which helps somewhat to confirm the diagnosis. The enlarged optic nerve may also represent an intrinsic tumor such as glioma or meningioma.
The usual treatment of optic neuritis is either no treatment or removal of the offending agent (such as a drug or toxin). Steroid treatment is discussed below.
Optic neuritis is frequently the presenting sign of multiple sclerosis (MS), particularly in young patients. In a large series of patients in England, McDonald found optic neuritis as a presenting sign in 25% of MS patients. Lessell predicted that 74% of females and 34% of males with optic neuritis would eventually become affected with MS. Some investigators believe that a patient who presents with optic neuritis is likely to have a mild form of MS. This impression is difficult to substantiate statistically from the longer longitudinal studies that are now in the literature. Bilateral optic neuritis in the adult has a worst prognosis for the development of MS than does either the unilateral or recurrent form. This is not true in children, in whom the incidence of MS following optic neuritis is not related to the optic neuritis. Children also have a better prognosis for recovery from optic neuritis than do adults.
A central scotoma is the commonest presenting defect in optic neuritis. It is not unusual with minimal decreases in vision to be unable to plot a central scotoma. Gunn, in 1897, first noted that the densest part of the central scotoma is surrounded by an area of a color deficit. I have observed over years of experience that using a red test object rather than a very small white test object or subtle computerized test object allows identification of the scotoma more easily. Kollmer was the first to suggest that red was the preferential color deficit. Mullen's studies seemed to indicate that blue-yellow colors are equally effective. I have performed central scotoma measurements with blue and with red test objects, and the latter are much easier. The defect to blue is frequently difficult to distinguish. The patients frequently can't tell blue from lack of blue or call it "dark," which is impossible to distinguish from a color defect. If red is not a more definitive test, at least it is easier and more accurate for the patient to perform.
Many MS patients who present with another symptom eventually develop optic neuritis. In some studies, between 27 and 37% of such patients have developed optic neuritis. Obviously, the length of follow-up influences this percentage. Hutchinson in Ireland, in a 15-year study, found that 78% of his MS patients exhibited optic nerve involvement at some time in the course of the disease. McDonald also found that optic neuritis occurred in a large proportion (73%) of all MS patients. Similar long-term studies in the United States, however, have reported much lower percentages. Physicians dealing with patients presenting with optic neuritis would like to be able to predict their chances not only of contracting clinically symptomatic MS but also of contracting any significant disability. Many patients with optic neuritis are asymptomatic for the clinical disease of MS but do have other abnormalities, such as abnormal evoked potentials or silent plaques in the brain on MRI, particularly in the periventricular area (Fig. 13.3). Periphlebitis has been previously described as an associated clinical sign of MS. It is extremely rare in my experience. Graham found ocular inflammation in the form of venous sheathing in 18% of 50 cases. Autopsy of 93 eyes with known MS found periphlebitis in only 8.5%. What would be most helpful to optic neuritis patients for projecting their future, particularly if they are young and planning families, is some assessment of the potential degree of their functional disability 10, 20, or 30 years in the future. Available studies of the degree of future disability in patients presenting with optic neuritis and developing MS do not extend far enough to compare their disability with that of MS patients who present with other signs.
Figure 13.3. A. CT image of the brain of a patient with multiple sclerosis shows no lesions. B. MR image of the same patient reveals multiple lesions, especially in periventricular area.
The optic neuritis treatment trial group has tried to determine whether steroids are beneficial in this disease. Their initial conclusion and recommendation was that intravenous methylprednisolone was better than oral steroids or a placebo. They did comment that the final visual result was minimally different at 6 months, and no difference was noted at 1 year. After 1 year in the trial, 20/40 vision or better was obtained in 95% of the placebo group, 94% of the intravenous group, and 91% of the oral steroid group. They felt, however, that intravenous steroids did shorten the course of the disease. The choice of using or not using steroids was governed by the depth of the visual loss and the degree of worsening vision. They also commented on the number of cases developing MS at 2 years. MS occurred in 16.7% of the placebo group and 14.7% of the oral group, but in only 7.5% of the intravenous group. The inference is that oral steroids alone are not as efficacious as intravenous steroids. It is hard to understand why such a short course of immunosuppressive therapy should give that difference as far out as 2 years. Although the statistics are interesting, they don't go out far enough for a valid conclusion. Rizo and Lessell's study at 15 years revealed an incidence of MS of 34% in men and 74% in women. However, 5 years later, it rose to 44.8% in men and to 91.3% in women after one mononeuropathy of optic neuritis. The optic neuritis treatment study group reviewed their statistics at 4 years and found that the incidence of MS in the intravenous group was 24.7%; in the placebo group, 26.9%; and in the oral group, 29.8%. The difference is narrowing. Some studies, such as the one by Herishanu, suggest that intravenous steroids increase the chances of MS. The definitive study on this subject is obviously not yet available.
One of the study group's initial conclusions was that there was no testing required as part of the initial event of optic neuritis. It is a :clinical diagnosis. A later review has modified their report. If MRI is performed initially and periventricular lesions are found, their number and size may be of significant predictable value for the onset of clinical MS. If the lesions are less than 3 mm and not periventricular, the incidence for developing MS is only 9.3%. If the lesions are 3 mm or larger and there are more than three, the incidence increases to 43.1%. Their interesting findings bear directly on the workup of optic neuritis and its resultant costs. So far their numbers are too small and the time span too short for a definitive conclusion. However, several of the studies on the significance of MRI findings agree with theirs.
The identification of mononuclear cells in the cerebral spinal fluid has led to the increasing realization that MS has an immunopathologic mechanism. This has led to the suggestion that other immunosuppressive therapies should be used. No definite conclusion has been forthcoming on this form of therapy either.
The correlation between silent MRI lesions and cognitive deficits due to MS has been examined by RAO and Associates. This is additional evidence that confirms the meaning of the silent lesions on MRI. Studies comparing VEPs and MRI seem to prefer the VEP as more sensitive.
In one large study, Weinshenker et al, tried to evaluate disability in all of their MS patients, no matter what clinical signs they presented with. About 17% of all patients presented with optic neuritis. The lower the age at presentation, the higher the percentage of those presenting with optic neuritis. In this study of 1099 patients from Ontario, Canada, the researchers tried to evaluate the overall disability of patients over a prolonged period of time; the median follow-up period was 14 years. This study was conducted at an MS referral center that had all the neurologists in the province either on its staff or associated with it. The researchers were thus able to obtain nearly complete referral of all MS patients in the area. In contrast, many series have been conducted at MS centers to which only the severe cases get referred; this referral pattern may bias the results, shifting the incidence and degree of disability to higher values than they might be with a more representative sample of MS patients.
In their study, Weinshenker et al. used the disability scale status (DSS) to assess their patients. A DSS rating of 6 corresponds to a state in which the patient can still walk but only with an aid; although somewhat impaired, these patients can move around without another person's help. A DSS rating of 8 corresponds to a bedridden status with retention of the use of arms. The median time of onset to progression was 5.8 years in this group of patients. Of those patients who progressed, 33% reached the DSS 6 level within 10 years; one-half of those reaching this level did so within 5 years. At 30 years of age, 83% of the patients who were followed had reached DSS 6, and 34% were rated DSS 8.
Although these studies all differ in one respect or another and are difficult to compare, one fact seems obvious. If patients with optic neuritis are followed long enough, many more of them will develop other signs of MS than we had previously thought. The degree of incapacity that is reached 10 to 20 years after onset of optic neuritis is still an unknown quantity. The hypothesis mentioned above, that patients who present with optic neuritis may manifest a milder form of MS than those who present with some other sign has not been systematically investigated, and more longitudinal studies designed to test this concept are needed.
Most patients with optic neuritis can get used to blurred vision in one eye or even some difficulty with their gait as long as they can remain useful, independent persons. I do not routinely tell such patients (unless they ask me) that they may develop MS. It is difficult to tell young patients, particularly those who recover their vision, that they may have a significant disease later on that may affect their entire lives. I would not like to alter a patient's entire life with statistics that may not apply to him or her or that might alter a very productive life. I believe this approach is particularly appropriate with such patients because at this time, we cannot alter the onset of MS or its final course. The use of different immunosuppressive agents in the treatment of MS is constantly under investigation, but their efficacy is not proven. Their ability to change the ultimate course of the disease is even more in question.
As mentioned above in this chapter, color testing is important in evaluating optic nerve function. Even with visual acuity of 20/40 or better, defects can still be found using the Farnsworth-Munsell 100 HUE test. It is also important, with a history of optic neuritis, to look at these patients in red-free light for the optic nerve dropout that one sees.
In cases of MS, Charcot's triad of nystagmus, intention tremor, and scanning speech is rarely seen at the onset of optic neuritis. The diagnosis of MS is usually made after both white and gray matter have multiple lesions that are separated in time and location and that are characterized by remissions and exacerbations.
The nystagmus in Charcot's triad is usually nonspecific, and it can take any form, including horizontal, vertical, or ocular dysmetria. The nystagmus of internuclear ophthalmoplegia is more specific. The nystagmus occurs in the abducted eye when the eyes are directed into horizontal gaze. When the internuclear ophthalmoplegia is bilateral, the nystagmus occurs in the abducted eye in both directions, and the diagnosis of MS is almost certain. In about 10% of cases of optic neuritis owing to MS, sheathing of the peripheral veins occurs. The sheathing probably represents some degree of periphlebitis, but it is usually so mild that the patient does not have symptoms.
Internuclear ophthalmoplegia, cerebellar ataxia, intention tremor, urinary sphincter problems, sensory changes, motor disturbances, and emotional aberrations are all part of the symptom complex that suggests MS. Electric shock–like waves moving down the spinal cord, particularly with neck flexion (Lhermitte's sign), suggest MS, but they can also be seen with spinal cord tumors (Fig. 13.4, A–E).
Figure 13.4. Bilateral intranuclear ophthalmoplegia. A. Poor adduction of right eye in left gaze. B. Poor adduction of left eye In right gaze. C. Straight in the primary position. C, D. Discrete lesion in the MLF on MRI. C, D. Discrete lesion in the MLF on MRI. E. Anatomy of intranuclear ophthalmoplegia. (Courtesy of Dr. Caleb Gonzalez.)
The diagnosis of MS is usually made on the basis of the occurrence of remissions and exacerbations and the presence of widely separated lesions in the central nervous system (CNS). Occasionally, laboratory studies can help in making the diagnosis. In 50% of cases, there is a slight increase in the spinal fluid cell count (the count should not exceed 50 cells/mm3).
Oligoclonal bands may not be present during quiescent periods of demyelinating disease, since they represent activity. Because the onset of optic neuritis is evidence of activity, we would expect oligoclonal bands also to be present, but in fact they cannot always be demonstrated. Newer laboratory techniques have decreased the negative responses in clinically evident cases of MS to about 10%. I know of no study that correlates optic neuritis with oligoclonal bands and predicts with longitudinal findings who will and will not get MS.
T-lymphocyte subpopulations have also been studied in acute optic neuritis as a possible diagnostic test to confirm MS as the probable cause. In MS patients, the appearance of new lesions on MRI has been associated with reduced suppressive cell activity. Investigation of this phenomenon in patients with acute optic neuritis has been disappointing so far.
Trying to predict which patients with unilateral optic neuritis will develop MS is impossible at this state of our knowledge. Examining the spinal fluid of these patients for pleocytosis, IgG, or oligoclonal band distribution is a poor prognosticator for the development of MS.
Immersing a patient suspected of having MS in a hot bath is a test that has been used for many decades. Worsening of the patient's symptoms and signs or the development of new symptoms or signs is positive evidence that a conduction defect exists in the affected nerves. Rasminsky demonstrated that increases in temperature of as little as 0.5° could induce symptoms. This worsening of nerve function is probably related to a change in sodium and potassium flux in and around the myelin sheath. This test should not be undertaken lightly because permanent defects have been reported. Since the hot-bath test is clumsy and may be detrimental, an alternative approach may be preferable. By appropriate questioning, you may discover that patients do not take hot baths because they feel very weak or their vision dims if they do. Similarly, patients may report that they do not play tennis or jog for the same reasons. Any activity that heats up the core body temperature can cause a worsening of whatever part of the nervous system is affected. This phenomenon is called Uhthoff's sign. The part of the nervous system that is affected may, under normal circumstances, produce no or subclinical symptoms until challenged. Patients usually do not relate such symptoms to their present problem and may not volunteer the information unless properly asked about it.
In looking for widely separated signs in the CNS, the VEP has been a useful tool. The VEP may demonstrate a conduction defect in one optic nerve, suggesting its involvement when the patient has no present symptoms or past history of that nerve being involved, This would then fix the criteria for separation in time and space in a person who was having unexplained paresthesias. In the interpretation of the VEP, not only the absolute latency but also the intraocular differences in latency and the waveform are all diagnostic. In recent years, a constant, reversing checkerboard pattern has produced a more consistent response than the old flash technique. Demyelinating disease is not the only disease that can produce these abnormal changes in the VEP. Similar abnormalities can be seen in glaucoma or in the sector optic atrophy of ischemic optic neuritis. Both of these latter diseases may spare fixation, suggesting that these VEP changes are not specific for the papillomacular bundle but reflect only axonal damage. It is, therefore, not a specific test for MS. However, as an adjunct test in establishing the diagnosis of MS, Halliday, McDonald, and Mushin found conduction delays in one or both optic nerves in many patients who had no history of optic nerve involvement in the disease process.
The latency of the human occipital potential induced by a light flash depends on the intensity of the light stimulus. The dimmer the flash of light, the longer the latency. The same difference occurs with equal light flashes to both eyes, but with slower conduction of information to the occipital pole in the damaged nerve. The Pulfrich effect occurs when the CNS cannot correct for the temporal discrepancy in the arrival of information from the two eyes. This lack of CNS correction for temporal discrepancy of sen-sory stimuli has also been shown clinically by Halliday and McDonald. They conducted experiments in which the toe and index finger of a patient were simultaneously stimulated. Because the finger was closer to the brain than was the toe, the patient perceived that the finger was stimulated first. If the brain corrected for any visual time lag, stereoscopy could not occur.
A test for evaluating the conduction velocity of one optic nerve versus the other employs the Pulfrich phenomenon. If an object moves from a normal patient's right field to the left and back again in a straight line. It will be perceived as moving in a straight line. If one eye has a conduction time delay Owing to an optic nerve disease such as optic neuritis, the retinal images of the involved eye will arrive later at the visual cortex than those of the normal eye. The object, therefore, will be perceived as moving in an elliptical fashion rather than in a straight line. This is an example of the temporal discrepancy mentioned before. The background objects may influence the response to this test, and it is best done against a blank background. The experiment should not be performed with a luminous object in a dark room as a technique to decrease visual clues. It should be done in a lighted room so that the retina can be light adapted.
The Pulfrich phenomenon is not meant to replace the VEP, but rather to be another tool for the clinician trying to evaluate subtle decreases in vision. It can help in differentiating subtle macular disease from optic nerve disease, since macular disease does not cause a time delay to the visual cortex. Even patients who apparently have recovered fully from an episode of optic neuritis and who have 20/20 vision, a full visual field, and apparently normal color vision with the pseudo-isochromatic plates, may still complain about their vision. Frequently, they will say that the vision in the affected eye is dull or different. If there is still a conduction defect in that nerve, they may have symptoms as a variation of the Pulfrich phenomenon. Frisen, Hoyt, Bird, and Weale reported patients who had difficulties knowing at what station on the subway to get off because of the induced Pulfrich phenomenon caused by the moving train.
Hoyt, and Van Dalen and Greve believe that the earliest defects in MS are isolated defects in the Bjerrum area, but off center between 15 and 25°. These defects were found in visually asymptomatic patients; however, a central scotoma is the most common field defect in those patients with visual complaints and MS. Hoyt found narrowarcuate defects in the Bjerrum area and correlated them with nerve fiber bundle defects found by the red-free light technique. Patterson and Heron reported a similar experience in patients with MS and no visual symptoms or history of visual system disease.
Vitreous fluorophotometry is one of the new tests for evaluating retrobulbar neuritis. The increased concentration of fluorescein in the posterior vitreous compartment is not specific for retrobulbar neuritis caused by MS. It indicates a disturbance in the vascular-vitreous barrier, which is altered in optic neuritis from any cause. Since most cases of retrobular optic neuritis have normal-appearing nerve heads initially, this test may be of help in cases in which the diagnosis is in doubt.
Neuromyelitis optica is extremely rare today. The sufferer develops bilateral optic neuritis (but both optic nerves are usually not affected simultaneously), which is followed some weeks later by a transverse myelitis at any level of the spinal cord. The transverse myelitis can come first, but it rarely does so. The optic neuritis usually disappears but generally not as fully as in the cases of optic neuritis discussed above. The disc may appear normal, or more typically, a low-grade edema of the nerve head exists. Nystagmus, which is so prominent in MS, is rare in neuromyelitis optica. Usually, some residual paralysis results from the transverse myelitis, but a significant degree of recovery is the rule.
The cause and treatment of neuromyelitis are not known, and its relationship to MS is questionable at best. Despite some of the obvious similarities (noted above), marked differences exist between this disease and MS. Bilateral optic neuritis is rare in MS but the rule in neuromyelitis optica. Significant differences also occur in the pathologic findings.
Schilder's Disease (Encephalitis Periaxialis Diffusa)
Schilder's disease, although rare, should be considered because of its relationship to vision. Its onset is late, in the first decade of life. It is one of the few causes of acquired cortical blindness in children of this age group. Apparent blindness, along with personality changes (unusual crying, irritability, apathy) in a previously healthy child, suggest this disease. Visual problems are not always an early sign, which adds to the difficulty of making the diagnosis. As the disease spreads anteriorly into the internal capsule, spastic paralysis develops. When the frontal lobes become enlarged, intellect and personality further deteriorate.
The fundus may be normal, or it may show papilledema (in about 20% of cases) owing to slightly increased intracranial pressure.
The cause and treatment are unknown, and death usually occurs within a year. Some cases may have a hereditary component, and this possibility should be particularly evaluated in every instance.