Central nervous system demyelination; Information has been received from the authors of the published literature article, titled as stated below.  Since its inception, the polyvalent vaccine against the Quadrivalent human papilloma virus (HPV), HPV rL1 6 11 16 18 VLP vaccine (yeast), has generated some controversies as a temporal relationship between the administrations of the vaccine and the development of a few autoimmune diseases, such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS) and Guillain-Barre syndrome have been reported. There are two cases whose initial presentation of central nervous system (CNS) demyelination followed in close time relationship the administration of Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL).  The patient in this report is the first case- a 19-year-old woman who received two doses of Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL), 3 months apart, and approximately 1 month after the second dose, she developed numbness to the right foot that within 1 day extended to the contralateral foot and was associated with mid-thoracic back  pain. Her neurological examination was only significant for the altered perception to touch to the feet. Deep tendon reflexes were normal and plantar reflexes in flexion. Magnetic resonance imaging (MRI) of cervical and thoracic spine revealed a total of three lesions with characteristic demyelinating appearance, one of those in the thoracic spine was contrast-enhancing. MRI brain demonstrated one additional white matter lesion also consistent with a demyelinating process. Antinuclear antibody titers and serology for Treponema pallidum and Borrelia burgdorferi were negative; angiotensin converting enzyme (ACE) levels, vitamin B12 and folate levels were normal. Cerebrospinal fluid (CSF) was never tested. The patient was treated in the acute setting with high doses of intravenous methylprednisolone and clinical improvement ensued. Demyelinating disease was felt to be the likely diagnosis and approximately 4 months later treatment with natalizumab was initiated. The patient has remained clinically asymptomatic afterwards but the repeated MRI brain at 1 year showed new lesions in the white matter of both hemispheres and a small contrast enhancing area in the right frontal lobe. The patient tested positive for anti-natalizumab antibodies and the medication was discontinued. Alternative therapy for Multiple Sclerosis (MS) has been instituted.   Since agency approval in June 2006, Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL) has been implicated in the development of acute inflammatory polyneuropathy, MS and ADEM. It has been reported that 12 million doses of HPV vaccines have been distributed and 7802 adverse events were recorded. Of the 10 confirmed cases of Guillain-Barre syndrome, five had received concurrent administration of meningococcal ACYW conj vaccine (dip toxoid) (MENACTRA).  The first case reported here was concerning for causality, as no medical problems were present prior to the administration of the vaccine and the criteria for the diagnosis of MS are met on follow-up MRI scan. In the second case, the development of sensory symptoms approximately 3 weeks before exposure to Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL) poses the question of a pre-existing condition, unmasked by the trauma, reaching its full expression in coincidence with the vaccination.  Administration of Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL) exacerbated the clinical course of three patients who had already manifested neurological symptoms consistent with clinically isolated syndrome and converted to clinically definite MS after the vaccination. A case of ADEM following exposure to HPV vaccine was recently reported and under the assumption that ADEM and MS share some pathophysiological and clinical features, it is conceivable that an immunological stimulus capable of inducing a monophasic deregulated immune response in the CNS could potentially lead to a relapsing-remitting chronic course.  It is plausible that in genetically predisposed individuals, the immunological stimulus of a vaccine or even some immunomodulatory therapies may lead to a deranged immune response that could theoretically trigger an autoimmune disease. In this view, the particularly aggressive course of disease demonstrated by the patient in case No 2 could be the result of such a stimulation that could not be controlled with a first line immunomodulatory therapy.  Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL) has raised no concerns about the risks of transmission of the HPV and the benefits of vaccines are undeniable as several diseases can only be treated by active vaccinations. HPV is the causative agent of a potentially highly morbid illness and its prevention will have a large social impact. Considering the overall limited number of adverse events recorded thus far, it is likely that the benefits outweigh the risks of complications. However, we feel that collecting long term data on the effectiveness of the HPV vaccine and documenting the adverse events is imperative.  Upon internal review, the patient's adverse event was determined to be other important medical event since it was treated with intravenous methylprednisolone.  This is one of several reports received from the same source. The second patient was captured in MARRS# 1110USA01072.  Literature report: Demyelinating disease and polyvalent human papilloma virus vaccination. Nov2011  All telephone attempts to obtain follow-up information have been unsuccessful. Additional information has been requested.  Follow up information has been received on 13-OCT-2020 via a social media post. A consumer posted the aforementioned article with a comment "Acute disseminated encephalomyelitis after Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recomb. Vaccine (GARDASIL)". No additional information was reported.