Atypical Presentation of Optic Neuritis in Multiple Sclerosis : a - - PDF document

Atypical Presentation of Optic Neuritis in Multiple Sclerosis : a Rare Case

Abstract Introduction Optic neuritis is a term used to describe an inflammation of the optic nerve. The pathogenesis of optic neuritis is presumed to be demyelination, as occur in Multiple Sclerosis (MS). Optic neuritis present in about 50% of patients withh MS, customarily with typical demographic and clinical presentation. Purpose To report the occurence of atypical presentation of optic neuritis in a patient with MS. Case report A 19 year-old male first came to Cicendo Eye Hospital on April 2018 with chief complaint

• f blurred vision on the right eye. General examination revealed his Body Mass Index was

36.41, included in obese category. Ophtalmologic examination revealed visual acuity of light perception on the right eye, 1.0 on the left eye, and positive Relative Afferent Pupillary Defect (RAPD). Posterior segment examination of the right eye showed optic disc swelling with segmental pallor, peripapillary hemorrhage, macular star and retinal exudate on the right eye. Laboratory examination showed abnormal lipid profile and no active infection. The patient was diagnosed with right optic disc atrophy as a result of post neuroretinitis with obesity and dyslipidemia. Intravenous methylprednisolone was given as treatment. On June 2018, the patient came with chief complaint blurred vision on the other eye. Ophtalmologic examination revealed visual acuity of hand movement on the right eye, 0.5

• n the left eye. Posterior segment examination on the right eye showed optic disc pallor,

and on the left eye showed optic disc swelling with segmental pallor, and peripapillary

• hemorrhage. The patient was diagnosed with pseudo-foster kennedy syndrome as a result
• f recurrent optic neuritis or ischemic optic neuropathy, with dyslipidemia, and obesity.

The patient was given oral methylprednisolone with gradual tappered dose every week. Visual acuity of the left eye was found to be improved 2 weeks after treatment, as measured 1.0 f2 with snellen chart. On follow up examination, ophtalmologic examination revealed visual acuity of hand movement on the right eye, 1.0 f2 on the left eye. Posterior segment examination on the right eye showed optic disc pallor, and on the left eye showed optic disc swelling and peripapillary hemorrhage. MRI result were consistent with McDonald 2010 criteria for MS. The patient was diagnosed with bilateral optic disc atrophy due to optic neuritis caused by

• MS. The patient was consulted with neurologist and received azathioprine oral as MS

management. Conclusion Clinical presentation of optic neuritis caused by MS usually occur in a typical manner. Although rare, with thorough clinical examination along with careful differentials and aid from neuroimaging modality, atypical presentation of optic neuritis could also be found in patients with MS. Keywords Optic Neuritis, Multiple Sclerosis

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I. Introduction Optic neuritis is a term given to inflammation of the optic nerve. The pathogenesis of optic neuritis presumed to be destruction of myelin sheath, also known as demyelination. Optic neuritis usually occur in primary demyelination process, whether as an isolated process or in patients with Multiple Sclerosis (MS). Optic neuritis usually occur in about 50% of patients with MS, and is the presenting manifestation in about 20%.1,2 This case report will further discuss the occurence

• f atypical presentation of optic neuritis in a patient with multiple sclerosis.
• II. Case Report

A 19 year-old man first came to Cicendo Eye hospital on 17th April 2018 with a chief complaint of blurred vision on the right eye for 2 weeks. The complaint got worse for the last 2 days. He also felt pain around the right eye especially on eye movement, and headache. There were no nausea and vommiting. He did not have any history of previous similar symptoms. He denied any history of head injury, recurrent ocular redness, double vision, fever, flu like symptoms, vaccination, alcohol consumption, hypertension, diabetes mellitus, limb weakness, and problem with balance. Figure 2.1 Cardinal eye position

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General examination revealed body height 169 cm, body weight 104 kg, with Body Mass Index (BMI) 36.41, which belong in obese category. Ophtalmology examination showed visual acuity was light perception on the right eye, and 1.0 on the left eye. Eye position was orthotropia, no ocular movement deficit or pain. Intraocular pressure were 17 mmHg on the right eye and 15 mmHg on the left eye. Anterior segment examination revealed pupillary light reflex were ↓/+ on the right eye with relative afferent pupillary defect (RAPD) grade IV and +/↓ on the left eye. Other anterior segment examination were within normal limit. Posterior segment examination revealed optic disc swelling with segmental pallor, peripapillary hemorrhage, macular star and retinal exudate on the right eye. Left eye were within normal limit. Figure 2.2 Fundus Photograph on April 2018 . Color and contrast sensitivity were difficult to examine for the right eye and revealed normal for for left eye. Visual field were difficult to asses for the right eye, and the left eye were within normal limit, as demonstrated by examination using humphrey visual field perimetry.

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Figure 2.3 Humphrey visual field result of the left eye on April 2018 The patient underwent blood extraction for laboratory examination, that revealed reactive IgG toxoplasma 314.6 IU/mL, reactive IgG Rubella 301.3 IU/mL, reactive IgG CMV 84.42 U/mL, but none of the IgM were reactive. Lipid profile revealed high total colesterol 227 mg/dL, high LDL cholesteerol 165 mg/dL,low HDL cholesterol 38 mg/dL, and high triglyceride 244 mg/dL. Others were within normal

• limit. The patient was advised to underwent brain Magnetic Resonance Imaging

(MRI) examination with contrast. The patient was diagnosed with early right optic disc atrophy as a result of post neuroretinitis or compressive optic neuropathy and ischemic optic neuropathy as a differential diagnosis, with obesity and dyslipidemia. The patient was treated with intravenous methylprednisolone 4 x 250 mg for 3 days, intravenous ranitidine 2 x 50mg, intravenous mecobalamin 1 x 500 mcg, and oral Ca hydrogen phosphate 500 mg, vitamin D3 (cholecalciferol) 133 IU 3 x 1 tablet. The patient was consulted to nutrition specialist for his obesity, and to internal medicine specialist for his dyslipidemia. On the third day, visual acuity on the right eye, anterior segment and posterior segment examination still showed the same result. The treatment then continued with

• ral methylprednisolone 1mg/kg body weight, that was tapppered weekly.

On 26th June 2018, the patient came with chief complaint of blurred vision on the left eye. Ophtalmology examination revealed visual acuity was hand movement

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• n the right eye, and 0.5 on the left eye. Eye position was orthotropia, no ocular

movement deficit or pain. Intraocular pressure were 17 mmHg on the right eye and 19 mmHg on the left eye. Anterior segment examination revealed pupillary light reflex were ↓↓/↓ on the right eye and ↓/↓↓ on the left eye. Other anterior segment examination were within normal limit. Posterior segment examination revealed optic disc pallor on the right eye, and optic disc swelling with peripapillary hemorrhage on the left eye. Humphrey visual field perimetry was performed which revealed severe visual field defect with constriction of visual field. Figure 2.4 Humphrey visual field result of the left eye on June 2018 The patient was diagnosed with pseudo-foster kennedy syndrome as a result of recurrent optic neuritis or ischemic optic neuropathy, dyslipidemia, and obesity. Foster kennedy syndrome from space occupying lesion considered as a differential diagnosis The patient was treated with oral methylprednisolone 1mg/kg body weight, oral ranitidine 2 x 150 mg tablet, oral mecobalamin 1 x 500 mcg tablet, oral citicholine 1 x 1000 mg tablet, Ca hydrogen phosphate 500 mg, vitamin D3 (cholecalciferol) 133 IU 3 x 1 tablet. The methylpredisolone dose was adjusted with tappered dose every week, along with follow up examination. The visual acuity of the lef eye was found to be improved by two weeks follow up, with visual acuity 1.0f2.

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One month later, the patient came for follow up with subjective feeling of improved vision on the left eye. Ophtalmology examination revealed visual acuity was hand movement on the right eye, and 1.0 f2 on the left eye. Eye position was

• rthotropia, no ocular movement deficit or pain. Intraocular pressure were 19

mmHg on the right eye and 16 mmHg on the left eye. Anterior segment examination revealed pupillary light reflex were ↓↓/↓ on the right eye and ↓/↓↓ on the left eye. Other anterior segment examination were within normal limit. Posterior segment examination revealed optic disc pallor on the right eye, and optic disc swelling with peripapillary hemorrhage and segmental pallor on the left eye. Color and contrast sensitivity were difficult to examine for the right eye and revealed normal for for left eye. Figure 2.5 Fundus Photograph, Humphrey Visual Field and OCT results

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The patient underwent fundus photograph, Optical Coherence Tomography (OCT)

• ptic nerve head and retina nerve fiber layer, also humphrey visual field perimetry.

Humphrey visual field revealed constricted visual field defect on the left eye with some improvement from the last examination, and OCT showed thinning of RNFL in both

• eyes. Brain MRI with contrast showed multiple hyperintens lesion that encompasses

cerebral substantia alba juxta cortical and right cerebelli medulla juxta 4th ventricle, suggestive of multiple sclerosis that met Disseminated in Space of 2010 Revised McDonald Multiple Sclerosis Diagnostic Criteria. No sign of optic neuritis, cerebral infaction, hemorrhage, or space occupying lesion was present. Figure 2.6 MRI result suggestive of Multiple Sclerosis The patient was diagnosed with bilateral optic disc atrophy as a result of recurrent

• ptic neuritis caused by multiple sclerosis with dyslipidemia and obesity. The oral

methylprednisolone were continued with tappered dose, other medication were also

• continued. The patient were consulted to neurology specialist that agreed with

diagnosis of multiple sclerosis, and was given oral azathioprine 1 x 25 mg tablet.

• III. Discussion

Optic neuritis is term given to inflammation of the optic nerve. It is referred as papilitis or anterior optic neuritis when there is asscoiated swollen optic disc.

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Retrobulbar optic neuritis are the used terminology when the optic disc appear to be normal. Optic neuritis can be caused by primary demyelinating disease, infectious or parainfectious, postvaccination, inflammatory, or miscellaneous causes.1,3 The incidence of unilateral optic neuritis around the world ranges from 0.94 to 2.18 per 100 000 per year. In temperate latitudes and white populations optic neuritis is commonly associated with Multiple Sclerosis (MS). In south east asia, MS is still relatively an uncommon disease.4,5 Optic neuritis can be classified on clinical grounds as typical or atypical optic

• neuritis. Typical optic neuritis is defined by its characteristic presenting features

and clinical course. Typical optic neuritis is generally associated with MS or regarded as a demyelinating clinically isolated syndrome at risk of conversion to

• MS. The patients with higher risk for typical optic neuritis include female, aged 15-

45 years old. Recently, obesity has emerged as an important risk factor for MS. Association between body mass index at adolescent age and MS onset later in life was observed, where obese participants demonstrated greater than a twofold increase in risk of MS compared to those at normal weight. The atypical optic neuritis patients have a definable process other than MS, and can be classified into those with or without systemic disease. The clinical course also differ from typical

• ptic neuritis.4,6,7 The patient in this case report was male, with age of 19 year-old,

and south-east asia decendant. This feature is relatively uncommon in patients with

• ptic neuritis caused by multiple sclerosis. BMI of this patient was 36.41 or

included in obese category. Presumably, this increases the risk for this patient to develop MS. Multiple Sclerosis is a chronic demyelinating disease of the central nervous system that can involve the optic nerve. Optic neuritis is one of the most common initial clinical presentations of MS without any prior history of a demyelinating

• event. It is not always possible to predict the conversion or long-term prognosis of

a clinical first event, but some factors might be helpful to predict the risk of conversion to MS. Even though there is no single biomarker to calculate this risk, magnetic resonance imaging (MRI) findings seem to predict strongly the risk of

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developing MS. A patient with a first episode of optic neuritis who has normal brain MRI seems to have 25% risk of developing MS at 15 years, this risk is lower compared to patient with one or more lesions, or around 72% in 15 years.8–10 The clinical presentations of patient with MS are highly variable. The disease itself is classified as either relapsing-remitting or primary progressive based on the initial disease course. Relapsing remitting multiple sclerosis is more common, affecting 85–90% of patients with multiple sclerosis, and is characterised by relapses, or episodes of neurological dysfunction lasting at least 24 hours in the absence of fever or infection, followed by periods of remission. Recovery from relapses is variable and can be incomplete. Primary progressive multiple sclerosis, in 10–15% of patients, is characterised by an insidious, slowly progressive increase in neurological disability over time. People with relapsing-remitting multiple sclerosis may develop a progressive course with time or secondary progressive multiple sclerosis, with a gradual increase in disability with or without relapses. A first episode of neurological dysfunction, presumably due to relapsing-remitting multiple sclerosis, is called a clinically isolated syndrome.8,11 Based on Optic Neuritis Treatment Trial (ONTT), patients with typical optic neuritis are usually aged between 15 and 45 years, and 75% are female. The patients usually complain of acute monocular vision loss which develop during hour to days, and periocular pain exacerbated by eye movement. In affected eyes, visual acuity ranges from 20/20 or better to no light perception, with 55% having between 20/25 and 20/200. Afferent pupil defect is always present unless the fellow eye is, or has been, equivalently damaged. Optic nerve appears completely normal in approximately 65% of patients, with the remaining presenting with optic disc

• edema. Visual field defects are nonfocal or focal with nerve fiber bundle
• configuration. Central defects are more common than peripheral ones. Additional

findings include abnormalities in contrast acuity and color vision. Other described symptoms include the presence of phosphenes, Uhthoff’s phenomenon, and the Pulfrich phenomenon.2,4,6,8,12 The atypical features of optic neuritis include absence of pain prior to vision loss. Severe visual loss with no light perception, progression of vision problems, or

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persistence of pain for more than 2 weeks, and lack of recovery even after a couple

• f weeks after the initial presentation are all unexpected features. Bilateral

simultaneous or sequential optic neuritis is also not expected. Fundus examination may show atypical findings, which include marked swelling of the optic nerve, retinal exudates, and peripapillary hemorrhages.8,12,13 Any abnormalities of the retina, choroid, or vitreous should cast doubt on the diagnosis of typical optic neuritis. Neuroretinitis is characterized by acute unilateral visual loss in the setting of optic disc swelling and hard exudate arranged in star figure around the fovea. In many cases, neuroretinitis is related to an infectious process that may be precipitated by a number of different agents. The most common causes are catscratch disease, syphilis, lyme disease, and leptospirosis. Non- infectious systemic inflammatory disorders may also produce neuroretinitis, such as sarcoidosis. MS is generally not associated with the development of neuroretinitis, yet a study by Williams et al found 3 of 35 patients with neuroretinitis were diagnosed with MS, suggesting that neuroretinitis can be an associated manifestation of multiple sclerosis.1,14 Patients with neuroretinitis is usually feel painless, but some patients may complain of an eye ache that worsen with eye movements. Visual acuity at the time

• f presentation can range from 20/20 to light perception. The degree of color deficit

is usually worse than the degree of visual loss would suggest. The most common field defect is cecocentral scotoma, but the peripheral field may be nonspecifically

• constricted. A relative afferent pupillary defect is present in most patients. The

degree of optic disc swelling is variable, in severe cases, splinter hemorrhage may

• present. Posterior inflammatory signs consisting of vitreous cell and venous

sheathing as well as occasional antreior chamber cell and flare may occur. Neuroretinitis is usually a self-limited disorder. Typically in 6 to 8 weeks, the optic disc swelling resolves, and the appearance of disc becomes normal or mildly pale. The macular exudate progress over 7 to 10 days, then remains stable for several weeks before gradual resolution over 6 to 12 months.1,14 The patient in this case report initially presented by blurred vision on the right eye and pain precipitated by ocular movement. On ophtalmologic examination,

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visual acuity on the right eye was light perception, RAPD was present, and optic disc appear to swell with segmental pallor, peripapillary hemorrhage, macular star, and retinal exudate on the right eye. After treatment with intravenous methylpredsinolone, ophtalmologic examination yield the same result. One month later, the patient presented with a chief complaint of blurred vision on the other eye. Posterior segment examination revealed optic disc pallor on the right eye, and optic disc swelling with peripapillary hemorrhage on the left eye. The visual acuity on the left eye was improved after treatment with oral methylprednisolone. This clinical presentation and course were not the typical presentation of optic neuritis caused by MS. The pathophysiology of optic neuritis associated with MS has been studied in human beings and in animal models. The optic nerve lesion is pathologically very similar to MS brain lesions. In the acute phase, inflammatory demyelination occurs, resulting in varying degrees of conduction block and visual loss. Predominant T- cell activation occurs in the acute phase, with release of pro-inflammatory

• cytokines. Resolution of inflammation and visual recovery occur over the next few
• weeks. Remyelination occurs, although it is usually incomplete, and sodium

channels are redistributed over demyelinated segments. This redistribution improves conduction but can make surviving axons vulnerable to damage.3,4 Whilst evaluating patients with a first episode of optic neuritis, in addition to MRI, additional tests including cerebrospinal fluid (CSF) analysis and evoked potential might also be helpful. CSF studies would be recommended for differential diagnosis especially in atypical cases. Visual Evoked Potentials (VEPs) reflect demyelination in the afferent visual pathways. VEPs seem to be sensitive and specific for detecting ON even in silent cases with no apparent clinical presentation and abnormal findings are often observed in silent cases. OCT studies have demonstrated the thickness retinal nerve fiber layer (RNFL). OCT findings seem to be related to visual impairment as well as disease progression.6,8 Diagnostic criteria for MS include clinical and other assessments emphasizing the need to demonstrate dissemination of lesions in space (DIS), dissemination in time (DIT) and to exclude alternative diagnoses. Although the diagnosis can be

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made on clinical grounds alone, MRI of the central nervous system (CNS) can support and supplement clinical criteria. McDonald criteria are the most utilized diagnostic criteria to assess the MS conversion risk in patients with a single demyelinating episode by providing MRI evidence for DIS and DIT.8,15

Table 3.1 The 2010 McDonald Criteria for MS DIS Can be demonstrated by ≥ 1 T2 Lesion at least 2 of 4 area of the CNS :

• Periventricular
• Juxtacortical
• Infratentorial
• Spinal Cord

DIT Can be demonstrated by :

• A new T2 and/ or gadolinum-enhancing lesion(s) on follow-up

MRI, with reference to a baseline scan, irrespective of the timing

• f the baseline MRI
• Simultaneous presence of asymptomatic godanium-enhancing

and non-enhancing lesions at any time

Source : Polman et al15

This patient had done laboratory examination to seek infectious causes and ischemic risk factor. The result revealed reactive IgG toxoplasma, reactive IgG Rubella, and reactive IgG CM, but none of the IgM were reactive, suggested no active infection. Lipid profile revealed high total colesterol, high LDL cholesteerol, low HDL cholesterol, and high triglyceride, suggested possible ischemic risk factor for this patient. Brain MRI examination result showed multiple hyperintens lesion that encompasses cerebral substantia alba juxta cortical and right cerebelli medulla juxta 4th ventricle, suggestive of multiple sclerosis that met Disseminated in Space

• f 2010 Revised McDonald Multiple Sclerosis Diagnostic Criteria.

In patients diagnosed with optic neuritis, management strategies incorporating acute and long-term therapies need to be made. Several studies have assessed acute corticosteroid treatment for optic neuritis. Optic Nerve Treatment Trial (ONTT) is a multicentered randomized clinical trial with primary objective to assess the efficacy of corticoteroids in the treatment of optic neuritis as an acute management

• strategies. In ONTT patients were assigned to three group, first, patients on oral

prednisone 1 mg/kg/day for 14 days, second, patients who received intravenous

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methylprednisolone 250 mg every 6 hours for 3 days followed by an oral prednisone taper 1 mg/kg/day for 11 days, or third, patients on oral placebo for 14 days. Results

• f the ONTT showed no improvement in visual acuity at 6 months for intravenous

methylprednisolone group versus placebo group, although visual recovery was

• faster. Mild benefits were noted for some secondary outcomes, visual fields,

contrast sensitivity, and colour vision. Patients taking oral prednisone did not differ from those taking placebo in visual outcomes but there was an unexpected increased risk of optic neuritis recurrence for reasons that are unclear. Intravenous methylprednisolone also delayed the onset of clinically definite MS at 2 years, but this difference abated over time. Corticosteroids itself also have been a mainstay of treatment in MS, including in acute relapse episodes.4,8,16 After patients are treated for acute optic neuritis, they should be followed up by a neurologist closely for MS conversion and therefore long-term treatment

• decisions. Dissease-Modifying Therapies (DMTs) have been recommended for

patients with a first demyelinating episode who have high MS conversion risk. A study by Atkins et al has suggested improved clinical outcomes and neuroimaging findings for patient with high MS conversion risk treated with DMTs. DMTs also the standard of care in MS for chronic treatment to prevent relapses. For almost three decades azathioprine (AZA) has been used in many countries to treat relapsing-remitting multiple MS. Following approval of β interferons (IFNs), AZA was no longer recommended as first-line therapy. Nonetheless, a study result by Massacesi and associates showed that azathioprine was at least as effective as β interferons, supporting AZA as a rational and effective alternative to IFNs, particularly considering the convenience of oral administration and the cost, lower than the other available treatments.8,16,17 Patient in this case report received intravenous and oral corticosteroids as an acute optic neuritis management. The patient also had been reffered to neurologist for confirmation of MS diagosis and management. The neurologist diagnosed this patient with MS and treated this patient with azathioprine as an immunomodulating therapy.

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Recovery from typical optic neuritis usually begins within the first few weeks of symptom onset. An initial rapid recovery is followed by a slow improvement that can continue for up to a year after onset. In the ONTT, 64% of patients with perception of light or worse recovered to acuity of 20/40 or better. Poor visual acuity of 20/200 or worse, poor contrast sensitivity or visual mean deviation at 1 month, but not baseline, can predict poor vision at 6 months. Although recovery is usually good, persistent residual deficits can include disturbances of visual acuity, contrast sensitivity, colour vision, visual field, and pupillary reaction. In MS patients, males and subjects with more severe attacks of optic neuritis demonstrated poorer recovery.3,4,9 The prognosis of quo ad vitam in this patient is dubia due to the natural clinical course of MS. Quo ad functionam is dubia, because the right eye of the patient in this case report showed only hand movement visual acuity, or only slight improvent

• f vision form baseline at 1 month. This may predict the poor vision afterward. Yet

visual acuity on the left eye were improved on follow up examination after corticosteroid treatment.

• IV. Conclusion

Optic neuritis is a term used to refer to inflammation of the optic nerve. The pathogenesis of optic neuritis presumed to be demyelination, such as MS. Optic neuritis usually occur in about 50% of patients with MS. Clinical presentation of

• ptic neuritis caused by MS usually occur in typical manner. Although rare, with

thorough clinical examination along with careful differentials and aid from neuroimaging modality, atypical presentation of optic neuritis could also be found in patients with MS.

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