Headache; Progressive visual loss, vision loss was in the right eye; Left hemiparesis, mild weakness on her left side; Visual loss in the right eye accompained by a left side headache; Acute demyelinating encephalomyelitis, inflammation and swelling in the part of the brain where the optic nerves cross; Mass in the right back part of the brain; Upper respiratory infection; Mild hand weakness; Thrush; Increased blood pressure; Elevated blood sugars; Information has been received from a physician concerning a 16-year-old female with no allergies and a history of apppendectomy, 3 forearm fractures requiring a plate (removed 1984). She has fraternal twins in good health. Both parents healthy and no family history of visual changes, demyelinating disease or inherited disease. There is diabetes type 2 in the father, maternal grandfather and maternal uncle. On 24-APR-2007, the patient was vaccinated with the first dose of HPV rL1 6 11 16 18 VLP vaccine (yeast) injection (lot number 654510/0962F) and a first dose of diphtheria toxoid (+) pertussis acellular 3-component vaccine (+) tetanus toxoid (BOOSTRIX) (lot number AC5ZB006BA), intramuscular (IM) in the right arm. On 26-JUN-2007, the patient was vaccinated with the second dose of HPV rL1 6 11 16 18 VLP vaccine (yeast) injection (lot number 654702/0011U) injection.  The patient sought medical attention and was hospitalized on 09-JUL-2007 after experiencing blindness in her left eye. The patient was diagnosed with multiple sclerosis while hospitalized. The physician noted the blindness had been experienced for approximately 6-8 weeks prior to the hospitalization. At the time of reporting, the outcome was unspecified.   Follow-up information was received from a consulting neurologist via medical record. The patient was hospitalized from 09-JUL-2007 to 27-JUL-2007 for progressive visual loss in association with demyelinating lesions consistent with acute demyelinating encephalomyelitis.   The patient had been experiencing some gradual change in her visual ability of her left eye, perhaps for as long as 6 to 8 weeks prior to her arrival at the emergency room. It was somewhat subtle and not evaluated at that time. She did get her HPV rL1 6 11 16 18 VLP vaccine (yeast) during the time that she was experiencing some visual loss and had her second shot on 26-JUN-2007. Two days before admission to the hospital she began to have some headache and increasing visual loss of both eyes. At the time she went to the emergency room, a brain computed tomography (CT) scan was performed demonstrating large hyperdense lesion in the right posterior parietotemporooccipital region with a lesion also in the chiasm as well as a small hemorrhagic lesion in the left inferior cerebellar hemisphere. She was admitted and started on dexamethasone (MSD). Ophthalmologic examination revealed normal retinae, but some afferent pupillary defect in her left retina and diminished visual acuity. She underwent a biopsy of the right parietal lesion which documented demyelination without evidence of tumor. She was started on IV steroid.   Neurological consultation was obtained and a diagnosis of disseminated demyelination identified with a tumefactive lesion of the right parietal region was made. At that time, her examination disclosed light perception only in her right eye and no visual ability in her left one. She had very mild hand weakness, which gradually improved as she continued on steroid. Her oral dose of dexamethasone was increased to 1000 mg of solu-medrol pulsed over daily amount divided q6h for a 7 day time frame. It was gradually tapered thereafter, and she developed some increase in blood pressure as well as elevated blood sugars. While steroids were gradually being tapered, she received 5 days of intravenous immune globulin at 500 mg/kg dosage. Each of these interventions were without significant improvement, however, she gradually was able to see shapes in her right eye and later count fingers in her nasal field. The weakness in her left hand diminished. The IV gamma globulin was then followed by plasmapheresis for 2 days in sequence followed by every other day phoresis for a total of 5 treatments over a 7 day period. No additional clinical improvement was observed at the time she was discharge home; however, her brain magnetic resonance imaging (MRI) did disclose decreased white matter signal abnormality in the parietal and temporal region as well as a resolution of the high signal lesion evident in her chiasm.    While hospitalized tests performed included collagen vascular evaluation and infection evaluation. This included the following negative tests: ANA, anti-DNA, AFB culture on brain material, fungal culture on brain material negative. Biopsy disclosed defined foci myelin loss well demonstrated on blue stain with associated perivascular lymphocytic inflammation and astrocytic gliosis with proliferation of macrophages and positive GFAP staining. Antibody for Sjorgren's syndrome, anti-Rho and anti-La were negative, pregnancy test negative, CEA antigen and AFP tumor markers were negative. Toxoplasma antibody negative, CMV antibody negative, ESR of 16 with normal serum chemistries and CBC on multiple occasions. Antiphospholipid antibody negative. Cardiolipin antibody for IGM, IGA, and IgG were all negative. Double-stranded DNA antibody negative. Angiotensin converting enzyme normal and neuromyelitis optica autoantibody negative.   She had undergone imaging with both MRI, CT scanning, magnetic resonance angiography (MRA) and repeat MRI prior to discharge home. Full spine MRI was normal. Cerebrospinal fluid (CSF) studies were deferred as she had undergone brain biopsy prior to her discharge.  Since being sent home she has had no decline in function. Her vision remained impaired significantly, but she had identified some improvement in terms of color vision perception in her right eye. She continued to have no vision in her left eye. Flash visual evoked potentials showed visual signal in the right optic pathways and none evident in the left optic pathways.   She had no paresthesia, weakness, headache, vertigo, dysphagia, shortness of breath, neck pain, back pain, weight loss, bowel or bladder dysfunction, gait disturbance, joint swelling, bone pain, rash, fever, altered consciousness, overt convulsion or involuntary movements. She had some thrush during her steroid treatment, treated with nystatin.   Physical examination revealed: No acute distress, alert and cooperative. Speech clear and coherent. Full ocular movement, no nystagmus, pupils round, positive afferent pupillary defect in the left pupil and there was no consensual light response in the right pupil and perceived light in the temporal field of her right eye was questionable. No evident light perception in the left eye at all. Sensation of the face was full. Full facial movement and symmetry appreciated. Hearing intact to whisper. Normal gait to toe, heel and tandem walk. Strength, bulk and tone symmetric, normal throughout. No involuntary movement.   Assessment: Despite aggressive intervention with high dose steroids combined with intravenous immunoglobulin and followed by plasmapheresis, little vision has returned; however, some improvement has been appreciated with now counting fingers with the right medial hemifield and light perception in the right lateral hemifield with some color appreciation in the right eye only.   As her MRI of the brain documents a large tumefactive lesion as well as chiasm, there were no other satellite lesions evident beyond a small hemorrhagic lesion in the right inferior hemisphere of the cerebellum. There was no spinal cord lesion and now subsequent neuromyelitis optica autoantibody was also negative. There is no radiographic evidence to support a firm diagnosis of multiple sclerosis at this time, and acute demyelinating encephalomyelitis is a working diagnosis. Should she have recurrence of symptoms, additional symptoms or new lesions evidenced on neural imaging in the upcoming months, a diagnosis of multiple sclerosis may be considered.   We reviewed the potential etiologies, and while we cannot completely identify the HPV rL1 6 11 16 18 VLP vaccine (yeast) immunization as causative, it is at least a possible provocative.   The initial reporting physician felt that the acute demyelinating encephalomyelitis was serious due to hospitalization, life threatening, disabling, and medically significant event.  A standard lot check investigation was performed. All in-process quality checks for the lot numbers in question were satisfactory. In addition, an expanded lot check investigation was performed. The testing performed on the batch prior to release met all release specifications. The lot met the requirements of the agency and was released.   Follow-up information was received from a licensed practical nurse at the physician's office via telephone call. The outcome of the increased blood sugars, increased BP, thrush, and headache was unknown. She reported that the patient had visited the office in September 2007 for treatment of an upper respiratory infection (URI). At that time, they did not do any testing, she was only treated for the URI. The outcome of the URI was not reported.  It was reported in a published article, title as stated above that a 16-year-oId previously healthy girl presented 10 the emergency room with an acute onset of visual loss over 48 hours. Initially, there was visual loss noted in the right eye accompanied by a left side headache. These symptoms worsened over the next 24 hours to include visual loss involving the left eye with a more diffuse headache. When evaluated in the emergency room at 48 hours after onset, her vital signs were blood pressure 116/65, pulse 68/minute, respirations 14/minute, and temperature 98ºF, with a completely normal general physical examination and no signs of systemic illness. Her examination disclosed a visual acuity of only counting fingers bilaterally with mild left side weakness accompanied by sensory loss to pinprick in the left arm. There was a left afferent pupillary defect and normal fundoscopic examination. Her visual ability deteriorated further to inconsistently identifying light and movement from the left eye only. She complained of no other symptoms and denied antecedent trauma or prodromal illness. She had, however, received her second vaccination against human papilloma virus 10 days prior to her presentation.  There was no family history of demyelinating disease, collagen-vascular disease, or rheumatological disorders. Magnetic resonance imaging (MRI) of the brain showed swollen enhancement within the chiasm extending into both retrobulbar optic nerves and a right occipitoparietal lobe mass (later disclosed as tumefactive demyelination) with a large zone of surrounding vasogenic edema. Complete spine MRI was normal. Biopsy of the hemispheric mass was performed and histology revealed demyelination. Subsequent cultures for aerobic and anaerobic bacteria, fungus, acid fast bacilli, and examination for parasites were negative as were serum immunoglobulin G and immunoglobulin M titers for Toxoplasma gondii. The erythrocyte sedimentation rate was 16 and the white blood cell count was 6900 with 89% granulocytes and 9% lymphocytes. The patient received a 5-day course of high-dose intravenous steroids (1g  methylprednisolone/divided each 6 hours), followed by 5 double-volume plasma exchanges with no visual improvement. Other diagnostic testing included neuromyelitis optics (neuromyelitis optica-immunoglobulin G), antinuclear antigen, Sjögren syndrome (SS-A, 88-8), rheumatoid factor, angiotensin-converting enzyme, which were all normal or negative. Three months after the onset, the patient still had not regained any visual function, her weakness and sensory deficit recovered completely however. A repeat MRI of the brain revealed resolution of the hemispheric and chlasmallesions. At 6 months her funduscopic examination disclosed bilateral optic disc paIlor. A repeat MRI at this time demonstrated no new lesions and continued resolution of the previously identified chiasmal enhancement and tumefactive lesion. Again complete spine MRI was normal. Cerebrospinal fluid was obtained 6 months after initial symptom onset. Cerebrospinal fluid cytology was negative for malignancy; additional studies  revealed B clear and colorless fluid with 3 white blood cells and 0 red blood cells per microliter, glucose 61 mg/dL and simultaneous serum glucose of 91 mg/dL, protein 30 mg/dL, lactate 1.5 mmol/L, and negative oligoclonal immunoglobulin G hands. At 18 months after the onset of her symptoms, her examination remained stable with no further neurological complaints, persistent profound visual impairment) inconsistently identifying light and movement from the left eye only. An MRI of the brain was performed and was unchanged compared with the previous one done at 6 months. There were no further demyelinating events within the next 18 months. In the context of prior vaccination in a 16-year old girl, acute demyelinating encephalomyelitis is likely to explain the multifocal deficits. This demyelinating event could also represent the index attack of neuromyelitis optics kown to cause severe bilateral visual loss due to optic neuritis with poor recovery. The monophasic course of our  patient's demyelinating event and the lack of "dissemination in time," make a diagnosis of clinically definite multiple sclerosis unlikely. At this time, a divergence of opinion is notable from authors of various case series attempting to identify predictive factors of clinically definite multiple sclerosis in children who present with a first central nervous system demyelinating event or initial bilateral optic neuritis. The brain biopsy in this case showed a primary inflammatory demyelinating process without axonal loss. Lymphocytes and macrophages were present within the plaque and in the perivenular spaces. These findings do not distinguish between multiple sclerosis, acute demyelinating encephalomyelitis, and their variants; a more subtle distinction may lie in the fact that in multiple sclerosis, Inflammatory cells are generally present throughout the plaque rather than restricted only to the perivenular cuff, a feature that is more characteristic of acute demyelinating  encephalo-myelitis. It is possible that human papilloma virus was the precipitant for the demyelinating event in the patient presented here. It is tempting to speculate whether there may be a specific immune mechanism initiated with human papilloma virus not yet identified, which resulted in not only acute demyelinating encephalomyelitis but also in an unusual clinical course that resulted in persistent visual loss.  Upon internal review visual loss in the right eye accompained by a left side headache was determined to be an other important medical event.  Follow-up information has been received from the physician concerning a patient with no known drug allergies and history of arm fractures (1994) and appendectomy (1997), who on 26-JUN-2007 received the second dose of HPV rL1 6 11 16 18 VLP vaccine (yeast) (route an site of injection not reported, lot number reported was valid to Hib conj vaccine (OMPC): 653523/0063U (also reported by the physician as lot number 654510/0962F)).  Approximately, in May 2007 the patient was admitted to the hospital from 09-JUL-2007 through 27-JUL-2007 and a brain biopsy was done, the result revealed inflammation and demyelination process. The patient is totally blind. It was reported that on an unspecified date, the patient experienced left hemiparesis and was resolved (date unspecified).  Demyelination process and left hemipareis were considered to be disabling. Demyelination process and left hemipareis were considered to be immediately life-threatening.  Follow-up information was received on 21-SEP-2023 via social media. The patient experienced vision loss in the right eye accompanied by a left-side headache, significant vision loss with a rapid progression in left eye with a more diffuse headache, mild weakness on her left side, inflammation and swelling in the part of the brain where the optic nerves cross, mass in the right back part of the brain (unspecified date), brain inflammation, demyelinated disease of the optic nerve junction and some parts of the brain, chiasmal neuritis, profound visual impairment, inconsistently identifying light and movement from the left eye only.  This is one of several reports received from the same reporter.; Sender's Comments:  US-009507513-2309USA009623: US-009507513-2309USA009629:, MERCK0708USA02045:Mfr number