Sex: F
Vaccine: FLU4, FLUX
Symptoms: Fungal test negative, HIV test negative, Headache, Herpes simplex test negative, Laboratory test normal
Clinical narrative: This case was reported in a literature article and described the occurrence of bilateral optic neuritis in a 23-year-old female patient who received Influenza  vaccine Quadrivalent (unspecified  season). On an unknown date, the patient received Influenza vaccine Quadrivalent unspecified season at an unknown dose. On an unknown date, 14 days after receiving Influenza vaccine Quadrivalent unspecified season, the patient experienced bilateral optic neuritis (serious criteria hospitalization and GSK medically significant), frontal headache (serious criteria hospitalization), blurred vision (serious criteria hospitalization), painful eye movement (serious criteria hospitalization), visual acuity decreased (serious criteria hospitalization), dyschromatopsia (serious criteria hospitalization), peripheral vision defective (serious criteria hospitalization), relative afferent pupillary defect (serious criteria hospitalization), optic disc engorgement (serious criteria hospitalization and GSK medically significant), leukocytosis, thyroid nodule, lymphocytic infiltration, loss of vision (serious criteria GSK medically significant) and vision decreased. The patient was treated with corticosteroid NOS. On an unknown date, the outcome of the bilateral optic neuritis, frontal headache, painful eye movement, dyschromatopsia, peripheral vision defective, relative afferent pupillary defect, optic disc engorgement, leukocytosis, thyroid nodule, lymphocytic infiltration, loss of vision and vision decreased were unknown and the outcome of the blurred vision and visual acuity decreased were recovering/resolving. The reporter considered the bilateral optic neuritis, frontal headache, blurred vision, painful eye movement, visual acuity decreased, dyschromatopsia, peripheral vision defective, relative afferent pupillary defect, optic disc engorgement, leukocytosis, thyroid nodule, lymphocytic infiltration, loss of vision and vision decreased to be possibly related to Influenza vaccine Quadrivalent unspecified season. Additional information was provided. This case was reported in a literature article and described the occurrence of idiopathic, atypical, sequential, bilateral optic neuritis in 23-year-old female patient who was vaccinated with unspecified inactivated influenza vaccine (manufacturer unknown). The patient had no other constitutional symptoms such as skin rash, fever, and muscle aches and no recent history of febrile illness or tick exposure. No information on patient's family history or concomitant medication or concurrent condition was provided. On an unspecified date, the patient received unspecified inactivated influenza vaccine (administration route and site unspecified; dosages unknown; batch number not provided) as a requirement for college admission. On an unspecified date, 2 weeks after vaccination, the patient developed right frontal headache, blurred vision and pain on eye movement of the right eye. The patient presented to the neuro-ophthalmology clinic because of a 5-day history of right frontal headache and a 3-day history of blurred vision and pain on eye movement of the right eye. Initial ophthalmologic examination of the right eye showed reduced visual acuity (20/40), dyschromatopsia (4/10 on Hardy-Rand-Rittler [HHR] test), a visual field defect (constriction of peripheral visual field) on Humphrey automated perimetry, a relative afferent pupillary defect, and optic disc swelling suggestive of optic neuritis. The left eye was normal on examination, and neurologic examination was otherwise unremarkable. Magnetic resonance imaging (MRI) of the brain and orbits with and without gadolinium showed enhancement of the right retrobulbar optic nerve and right hemispheric leptomeninges. MRI of the brain with and without gadolinium showed: T1 axial with contrast showed enhancement of the right optic nerve; T1 axial with contrast showed enhancement of the leptomeninges on the right frontoparietal lobes; FLAIR axial showed increased intensity of the leptomeninges on the right frontoparietal lobes. Given the atypical presentation of optic neuritis, further evaluation was performed. Serologic studies showed increased erythrocyte sedimentation rate (37 mm/h) and C-reactive protein (1.7 mg/L), mildly elevated immunoglobulin G4 (IgG4) (112.7 mg/dL) and low vitamin D; however, antinuclear antibody, antineutrophil cytoplasmic antibody, anti-Ro/La, C3/4, aquaporin 4 (AQ4) antibody, angiotensin-converting enzyme (ACE), Lyme, syphilis, HIV, Bartonella, Brucella, and quantiferon gold were negative. Vitamins B1, B6, B12 and E levels were normal. Opening pressure on lumbar puncture was 23 cm H2O, and cerebrospinal fluid (CSF) showed leukocytosis (45/uL; mononuclear dominant), normal protein and glucose levels, no oligoclonal IgG, negative tests for cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and varicella-zoster virus, and negative cultures for Mycobacterium and other fungi. Chest computed tomography was normal except for a small thyroid nodule. Positron emission tomography (PET) scan showed no lesion outside the brain and orbit. Her vision of the right eye started improving, and she deferred treatment and did not receive corticosteroid. About 3 weeks after the initial visit, the patient developed mild pain and blurred vision in the fellow (left) eye. Repeat brain MRI with and without gadolinium showed new abnormal enhancement of the left optic nerve. Given the atypical presentation of the inflammatory optic neuritis and the involvement of fellow eye, she underwent meningeal and brain biopsies with craniotomy from the right frontal lobe, which showed reactive astrogliosis with lymphocytic infiltration without evidence of neoplasm, granulomas, or vasculitis. At hospital day 4, the patient's vision started improving and had improved to 20/20 in both eyes by the time of discharge. She deferred intravenous corticosteroid therapy but received oral corticosteroid for 14 days with tapering. A week after completing the course of oral corticosteroids, the patient experienced worsening of the vision in her right eye (counting fingers at 3 ft). Repeat brain and spinal MRI showed enhancement of the right optic nerve. Repeated rheumatologic work-up, infectious disease work-up, CSF analysis, and paraneoplastic antibody assay, including repeated AQ4 antibody, were unremarkable or negative. This case has been considered serious due to hospitalisation. The patient received a 3-day course of intravenous corticosteroid, with minimal improvement of her vision, and then received 5-day plasmapheresis. The patient's vision of the right eye recovered to 20/25 in 2 weeks after the completion of the treatment and in 3 weeks after recurrence of vision loss. The authors commented, "The temporal relationship between vaccine administration and the onset of acute optic neuritis in the absence of known infectious or non-infectious inflammatory aetiologies, coupled with some evidence from biological plausibility studies, suggests that the concept of an immune-mediated attack against optic nerves after vaccination in genetically susceptible individuals does exist, and the possible link should be considered. Here we present a case of optic neuritis that could be linked to alteration of immune systems by influenza vaccination." The authors stated, "Post-influenza vaccination optic neuritis is uncommon. The pathophysiology of development is presumably immune-mediated. Based on a review of most of the reported cases (including outs), optic neuritis usually develops around 2 to 3 weeks after influenza vaccination. Systemic corticosteroid therapy may facilitate recovery and prevent vision loss. To prove the causality between influenza vaccine and optic neuritis, extensive epidemiological studies would be required, but the rare occurrence of influenza vaccine-associated optic neuritis and the underreporting of such cases might be a limitation in collecting data to support such causality. Well-designed animal studies may help reveal the causality and understand the pathophysiologic mechanism of development of post-influenza vaccination optic neuritis."