Age: 28.0
Sex: M
Vaccine: HEP, TDAP
Symptoms: CSF immunoglobulin G index, CSF oligoclonal band absent, CSF protein normal, Central nervous system lesion, Coordination abnormal
Clinical narrative: Information has been received from the authors in a published literature. Introduction: Since the mid-1990s, controversy had surrounded the question of potential link between exposure to recombinant hepatitis B vaccine (HBV) and demyelinating diseases of the central nervous system (CNS), in particular multiple sclerosis (MS). While most epidemiological studies had failed to demonstrate a link between HBV (manufacturer unknown) and CNS demyelinating disease, a recent systematic review concluded that, in light of the methodological limitations of these studies, it was not possible at present to determine whether exposure to the vaccine was associated with an increased risk of MS onset or relapse, or of other CNS demyelinating diseases. Numerous case reports exist that describe a temporal relationship between HBV (manufacturer unknown) administration and the onset of CNS demyelinating diseases, including MS, acute disseminated encephalomyelitis, optic neuritis both unilateral and bilateral, and transverse myelitis. Here, the authors presented the case of a patient who developed seronegative neuromyelitis optica spectrum disorder (NMOSD) following exposure to HBV (manufacturer unknown). Case presentation: The patient, a 28-year-old male graduate student with no relevant past medical history, developed pain with eye movements bilaterally 11 days after receiving HBV (manufacturer unknown) and TDAP vaccines before the start of the academic semester. Within 24 h of eye pain onset, he experienced decreased vision in both eyes, progressing to complete loss of vision within 1 day. This was accompanied by ascending numbness and tingling from his feet to his mid-thoracic region and associated with fatigue, incoordination, and loss of balance; however, his strength remained intact. He was admitted to the hospital where Magnetic Resonance Imaging (MRI) of the thoracic spine showed a large nonenhancing 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 nonenhancing 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). The patient received both intravenous steroids and 5 sessions of plasma exchange. He remained in the hospital for 1 week, and prior to discharge, his visual symptoms began to improve. Following discharge, the patient received plasma exchange weekly for 4 additional treatments. At the time he presented to our clinic, which was approximately 3 weeks after discharge from the hospital, his vision had continued to improve, with restoration of color vision and shapes/details, although the vision in his left eye remained subjectively 'darker' compared to the right eye. At that time, his numbness and tingling had also significantly decreased, with improved balance and coordination. The diagnosis of optic neuritis was based on clinical examination findings of bilateral relative afferent pupillary defects, bilateral optic disc pallor, and the MRI finding of enhancement of the optic nerves. The patient was started on mycophenolate mofetil. The patient has relocated for further college education. He now followed with a colleague who informed the authors that as of 9 months after clinical presentation, the patient remains free of new neurological symptoms, with continued improvement of visual acuity and near-complete resolution of numbness, tingling and balance difficulties. He continued on mycophenolate mofetil, which he had tolerated well. The patient had a follow-up MRI of the entire neuraxis 9 months after initial presentation that demonstrated no new lesions and stability of prior lesions. Discussion: While previous case reports have described temporal associations between several CNS demyelinating diseases and preceding exposure to HBV (manufacturer unknown), to the best of our knowledge this case represents the first published report of NMOSD onset following administration of HBV (manufacturer unknown). A recent review of the literature from 1979 to 2013 found 7 cases of NMOSD onset or relapse (both seropositive and seronegative for AQP4-IgG) associated with exposure to various vaccines, with the vaccine against human papilloma virus being the most commonly implicated. One potential limitation of this case was that the authors' patient also received the TDAP vaccine prior to NMOSD onset; however, the authors thought this was unlikely to be of pathogenic significance given that the authors were unable to find any published reports linking TDAP exposure to CNS demyelinating disease. Although it was difficult, if not impossible, to establish a causal relationship between vaccination and CNS demyelinating disease through the temporal association of rare events described in case reports such as this, the authors nevertheless believed it was important to make such cases known, both to contribute to the continued development of safe and efficacious methods of vaccination, as well as to provoke further investigation into the pathogenesis of NMOSD, which might lead to a more refined nosology of this evolving spectrum of disease. The outcome of the event was recovering. The reporter considered the event be related to HBV (manufacturer unknown). Additional information has been requested.