January 2023

Chief Complaint

Gradual painless vision loss in the left eye

History of Present Illness

28-year-old female with G6PD deficiency and otherwise unremarkable past medical history presents to the emergency department with 2-week history of painless, decreased vision of the left eye. Additionally, she reported a left sided headache for the first week and endorsed discomfort with left eye movement. She denied head trauma, fever, paresthesia, weakness, changes in hearing, tinnitus, pain when chewing, tearing, redness, or recent flu like symptoms. She recalled a similar episode of vision loss in the left eye that resolved in 3 weeks with no intervention approximately 4 months ago. 

Ocular History

• None

Past Medical History

• G6PD deficiency

Medications

• None

Allergies

• No known drug allergies

Family History

• None

Social History

• Daily E-Cigarette use

Review of Systems

• As noted in HPI, otherwise negative

Ocular Exam

Imaging

MRI Face/neck/orbit with and without contrast

Abnormal appearance of left optic nerve including prominent asymmetric increased T2 signal throughout the left optic nerve which appears most pronounced intracranially where there is also mild enlargement and prominent enhancement of the nerve which extends slightly into the left side of the optic chiasm. There is lesser enhancement of the orbital portion of the left optic nerve without apparent enlargement. These findings are indicative of acute optic neuritis. Normal MRI examination of the right optic nerve performed with and without contrast. 

MRI Brain with and without contrast 

There is a single high T2 signal intensity lesion in the left precentral gyrus suspicious for demyelinating disease given its appearance and location, particularly given the patient's clinical presentation and apparent left optic neuritis on the concurrent MRI examination of the orbits. The remaining brain is within normal limits. 

MRI/MRV Head without contrast

Nromal MR venogram of the brain. Specifically, there is no evidence of dural venous sinus thrombosis

MRI Cervical Spine and Thoracic with and without contrast

Essentially normal MRI of the cervical and thoracic spine

Laboratory Testing

• ESR, CRP, IgG, HIV, ANA negative/unremarkable
• CSF Oligoclonal bands- positive (type 2)
• CSF ACE- negative
• NMO AQP4-IgG- negative
• MOG-IgG- negative
• CSF analysis: cell count 4WBC (89% lymphs), glucose: 89, IgG: 1,232
• CSF with cx: mild pleocytosis, normal protein, no polymorphonuclear lymphocyte
• CSF IgG index 1.6 (high), IgG synthesis rate 4.2 (high)
• Meningoencephalitis panel- negative

Differential Diagnosis

• Clinically isolated syndrome (CIS) of optic neuritis (ON) or prodromal of multiple sclerosis
• Neuromyelitis optica spectrum disorder
• Anti-myelin oligodendrocyte glycoprotein syndrome
• Lupus

Clinical Course

The patient is a 26-year-old female with a past medical history of G6PD deficiency who was

admitted for recurrent subacute left-sided visual loss with APD and contrast-enhancing left optic nerve on imaging, concerning optic neuritis. MRI of the brain showed central vein sign

consistent with demyelinating disease. The patient received a 3-day course of SoluMedrol with

improvement in vision and was discharged with a steroid taper. The patient followed up with the neurology outpatient clinic after discharge. Oligoclonal IgG bands (type 2) were positive and the patient was diagnosed with Multiple Sclerosis (MS).

Discussion

Optic neuritis is an acute, inflammatory condition of the optic nerve associated with asymmetric vision loss and eye pain. The etiology of optic neuritis, while often idiopathic, can be secondary to demyelination, self-directed antibodies, autoimmune inflammation, infections, and post-infectious/post-vaccination. Central to the pathophysiology are T and B cell lymphocytes that initiate a faulty immune response by recognizing neural autoantigens as foreign proteins. The resulting inflammatory response leads to demyelination, axonal loss, and the subsequent ocular symptomatology.

Optic neuritis classically presents in a young female (age 20-40) with symptoms of unilateral vision loss, pain with eye movement, a deficiency in color vision, and a history of a prior episode that had spontaneously improved. Optic Neuritis is a clinical diagnosis ascertained by physical exam findings such as decreased Snellen visual acuity, decreased color vision on Pelli-Robson or Vistech test, RAPD on swinging flashlight test, pain on extraocular motility exam, nerve fiber layer or central loss shown on visual field exam, and optic disc edema on dilated fundus exam (present in up to 35% of patients). The presentation of this patient generally supports the body of literature that describes epidemiology and symptomatology commonly associated with optic neuritis. A patient of female sex in her early 20s presenting with recurrent neurologic deficits and unilateral, red-denatured paints the clinical picture (Toosy et al, 2014).

For diagnostics, MRI of the brain and Orbit can help elucidate the etiology of optic neuritis. In typical Optic Neuritis, MS shows on MRI as a segment of contrast enhancement of the optic nerve and a high intensity T2 weighted lesion white matter lesions located in the periventricular, juxtacortical, infratentorial, and/or spinal cord white matter. In non-typical ON, white matter lesions may appear outside of typical locations and optic nerve enhancement is more posterior in the optic chiasm and tract. This patient underwent an MRI of the brain and orbit to validate suspicion of a CNS process that might have affected white matter structures. Asymmetric increase of T2 signal throughout the left optic nerve supports suspicion of local inflammation. 

Additional testing includes CSF analysis for oligoclonal bands to confidently diagnose MS. In this patient, the oligoclonal bands detected on electrophoresis and the recurrent nature further support MS, a commonly observed etiology of optic neuritis. For non MS etiologies, VDRL and FTA-ABS can test for syphilis, antibody titers can test for lyme disease, chest x-ray and serum angiotensin-converting enzyme levels test for sarcoidosis, and ANA for Systemic lupus erythematosus and vasculitis. 

The clinical evidence in this case indicates an inflammatory process, thus initial treatment of methylprednisolone was prescribed. Treatment is guided by the The Optic Neuritis Treatment Trial which evaluated the efficacy and safety of an oral placebo, oral prednisone, and  IV methylprednisolone followed by oral prednisolone in treating acute ON. The 1000 mg IV methylprednisolone daily for 3 days and 11 day oral prednisone taper was found to accelerate visual recovery fastests in the first 4-6 weeks post onset but did not improve long-term outcomes. Additionally, patients who took oral steroids in conventional doses alone were found to have higher rates of recurrence of ON and are thus contraindicated in acute ON.

Overall, Optic neuritis is a complicated pathology with several etiologies and diagnostic algorithms. While multiple sclerosis is the most common typical etiology for optic neuritis, immediate treatment is the same for most causes followed by further investigation to treat the underlying cause. In this case, the patient’s clinical presentation and MRI and lab results lead towards the diagnosis and treatment of Multiple Sclerosis

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