Initial unsolicited report received from literature on 02 December 2015. Abstract: Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HPV) and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD) following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patient's visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50 percentage of NMOSD cases, despite testing with the most sensitive assays available), he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD. This case involves a (28-year-old) male patient who was vaccinated with a dose [route and dose series not reported] of Hepatitis B vaccine (HBV) (batch number, expiry date and site of administration were not reported) and also Diphtheria, Tetanus and Acellular Pertussis Vaccine (TDAP) (batch number, expiry date and site of administration were not reported) on an unspecified date. Patient had no medical history. Concomitant medication were not reported. On an unspecified date, 11 days following the vaccination patient experienced pain with eye movements bilaterally and within 24 hours of eye pain onset, he experienced decreased vision in both eyes, progressing to complete loss of vision within one day and this was accompanied by ascending numbness and tingling from his feet to his mid-thoracic region and associated with fatigue, incoordination, optic neuritis, seronegative neuromyelitis optica spectrum disorder (NMOSD), ascending numbness and loss of balance. On an unspecified date patient was hospitalized where MRI of the thoracic spine showed a large no enhancing lesion involving the right side of the spinal cord extending from T6 through T9, as well as a second smaller lesion involving the posterior central thoracic spinal cord at the level of T5. MRI of the brain showed contrast enhancement of bilateral optic nerves on T1-weighted imaging consistent with optic neuritis and a no enhancing T2 lesion with restricted diffusion at the junction of the right thalamus and posterior limb of the internal capsule. Cerebrospinal fluid analysis revealed a cell count with differential, 1/ul, that was within normal limits, absence of oligoclonal bands, and normal glucose, protein, and IgG index. Aquaporin-4 (AQP4) IgG autoantibodies in the serum were negative by enzyme-linked immunosorbent assay (ELISA). MRI of the entire neuraxis 9 months after initial presentation that demonstrated no new lesions and stability of prior lesions. Corrective treatment was intravenous steroids and 5 sessions of plasma exchange. Outcome of events was recovering. Patient was discharged from the hospital after 1 week. Documents held by sender: none.