Case Presentation: A 62 year old woman with a history of hypertension suddenly developed a headache starting 3 days after receiving the influenza vaccine. The headache worsened and was associated with nausea, photosensitivity and vomiting. The next day she was lethargic, and that night, her husband states she sat up in bed and started “speaking in tongues” as if she was “possessed”. He brought her to the emergency room where she was extremely disoriented, could not follow commands or respond appropriately. Temperature was 101.2F on presentation, and remained afebrile afterward. She had diffuse hyperreflexia with ankle clonus bilaterally; otherwise exam was unremarkable. Serum white blood count was 12.2, ESR 51, CRP 3.40; anti-cardiolipin IgM and beta-2-glycoprotein were elevated. The remainder of serological studies were unremarkable, including anti-NMDA antibodies, tick borne infections, autoimmune and viral studies. CT head and CTA of the head and neck were unremarkable. Lumbar puncture showed protein of 57, 87 white blood cells and 36 red blood cells; glucose was normal. Other cerebrospinal fluid tests including herpes virus and oligoclonal bands were negative. MRI brain demonstrated multifocal ovoid and serpiginous areas of diffusion restriction and T2/FLAIR hyperintensities in the bilateral mesial temporal lobes, frontoparietal white matter, thalamus, putamen, and globus pallidus; this was thought most consistent with acute disseminated encephalomyelitis (ADEM). She was briefly treated with IV acyclovir (until HSV PCR was found to be negative), and IV steroids for 5 days followed by prednisone taper over about 1 month. Her mental status improved dramatically each day; score on montreal cognitive assessment (MOCA) test was 19/30 on discharge.
At follow up 1 month after presentation, she complained of some problems with short-term memory and balance, but was otherwise back to normal. Examination demonstrated MOCA of 26/30, difficulty with tandem gait, and mild hyperreflexia without clonus; neurologic exam was otherwise normal. Cardiolipin IgM was borderline-positive, ESR 13, CRP 2.2, and beta-2-glycoprotein was negative. Repeat MRI demonstrated resolution of diffusion restriction and improvement in the size and number of T2/FLAIR hyperintensities without any new lesions.

Discussion: ADEM is an inflammatory demyelinating disease of the central nervous system. The assumed mechanism is immune-mediated demyelination triggered by infection, or, rarely, vaccination. For most vaccines, incidence rates of ADEM are as low as 0.1 to 0.2 per 100,000 vaccinated individuals. A pubmed search from 1979 to 2013 showed only 3 cases of seasonal influenza vaccine associated with ADEM. As such, there have been no large population studies with estimated incidence rates yet. Lesion patterns often seen in ADEM include widespread, multifocal lesions in the white and deep grey matter, as seen in our patient.

Conclusions: Significant spontaneous recovery is the expected outcome in most cases of vaccine-induced ADEM, usually occurring within 1-6 months. Based on the current literature, it is difficult to predict who may be at risk. The risk must be balanced by the fact that influenza infection itself is a risk factor for ADEM, which is likely more common than that triggered by the vaccine. We do not advocate avoiding any vaccinations, but wish to promote awareness of this potential complication, as early identification and treatment may improve outcomes, and avoid unnecessary testing and treatment.