Information has been received from an investigator concerning a 37 year old female with HIV and a history of migraine headaches and methamphetamine abuse for 20 years who entered a study. On 08-MAY-2009 the patient was enrolled in A5240 and vaccinated IM with the first dose of GARDASIL, 0.5ml, in deltoid. On 22-JUN-2009 the patient developed the following adverse events: altered mental status grade 3 (dysarthria, anomia, confusion); headache grade 3 (presented to HD 22-JUN-09 with AMS, HA). CT angle of head showed diffuse cerebral edema); left hand numbness grade 2. On 02-JUL-2009 the patient developed decreased neurological reflexes grade 4 (life threatening), pupils fixed and dilated bilaterally grade 4 (life threatening), and death. The report was as follows: The patient presented to emergency department on 22-JUN-2009 with migraine-like headache, left hand numbness, dysarthria and anomia. CT read as normal, patient discharged, the patient returned on 23-JUN-2009 with persistent headache, anomia. At that time, she was not on treatment for HIV and her CD4 count was 263. She was admitted to the neurology service and empirically treated with antibiotics for bacterial and HSV meningitis. Lumbar puncture showed borderline low glucose, elevated protein and a lymphocytic pleocytosis without red blood cells, CSF tests for EBV, HSV, VZV, Cryptococcus, VDRL, AFB smear were negative as well as CSF culture for bacteria, fungus and mycobacteria. CSF cytology was negative, flow cytometry was not performed. JC virus PCR was ordered, but results not reported. Toxoplasma IgG was negative. Blood cultures, coccidioidomycosis titers, serum cryptococcal antigen, RPR were all negative. Prior quantiferon testing in 2004 was positive without subsequent isoniazid treatment chest X ray during admission was negative as were 2 sputum for AFB smear and culture. MRI showed diffuse cerebral edema with leptomeningeal enhancement. Repeated lumbar puncture showed normalization of glucose. During the hospitalization, her symptoms had improved. Discharged to home 29-JUN-2009 with diagnosis of resolving viral meningitis vs. HIV encephalopathy. Initial consideration had been made of TB meningitis but her symptomatic improvement without TB treatment made this less likely. HIV treatment was not started during the hospitalization but was planned pending reevaluation after discharge and final review of all cultures and pending test. Re-presented emergency department on 01-JUL-2009 complained of worsening headache, symptoms and confusion; discharged as it was thought her symptoms were consistent with previous status. Returned to emergency department that night with confusion and altered mental status. At 5 AM on 02-JUL-2009, she acutely became unresponsive in the emergency room, requiring intubation and was noted to have fixed, dilated pupils bilaterally. Emergent head CT revealed diffuse cerebral edema and herniation. Pronounced brain dead of unknown cause on 02-JUL-2009. Post mortem pending, would take up to 8 weeks at this site before results were available. Relevant diagnostic tests conducted at the time of death occurred were as follows: On 22-JUN-2009, computerized tomography (CT, CT Scan, CAT Scan) of head: diffuse cerebral edema: 3 am left ICA aneurysm; bilat symm, optic nerve sheath distention. On 23-JUN-2009, magnetic resonance imaging (MRI) of brain: with contrast, diffuse supratentorial leptomeningeal enhancement, consistent with leptomeningitis. Diffuse sulcal effacement. Vague non enhancing T2/FLAIR hyperintensity multiple sites suggestive of infectious or toxic/metabolic etiology or PML. 02-JUL-2009, computerized tomography (CT, CT Scan, CAT Scan) of brain, profound diffuse sulcal effacement throughout cerebral hemispheres and posterior fossa. Severe downward tonsillar herniation and severe upward transtentorial herniation with compression of brainstem. The reporting investigator felt the event death was not related to study therapy. Study therapy association for the other events was not reported. Follow up information has been received from medical records. The patient had a past medical history significant for migraine headaches and HIV (new diagnosis, not on antiretrovirals, recent CD4 count 263 to 381), substance abuse, recent Bell's palsy January 2009 and no known drug allergies. She was on no medications upon admission. The patient's CD4 count on 24-JUN-2009 was 308 and a viral load on 12-JUN-2009 was 45310, diagnosed in March of 2009 and currently not on antiretroviral therapy. She was currently living in a drug rehab facility. The patient also had a history of past methamphetamine abuse and had been sober since March of 2009. The patient also had a questionable psychiatric history with a potential diagnosis of anxiety, borderline personality disorder, and depression. The patient also had a history of migraine disorders. She presented with a headache typical of her migraines but with additional features of left hand numbness, dysarthria, and anomia. The patient underwent a CT scan which was negative in the ED, and was initially sent home, and re-presented the next day with similar headache with anomia without hand numbness. A lumbar puncture was performed in the ED, remarkable for lymphocytic pleocytosis and decreased glucose, as well as elevated protein, and an MRI showed evidence for meningoencephalitis. The patient was admitted to the neurology service for further work up. The patient was hospitalized from 23-JUN-2009 to 28-JUN-2009. She was initially placed on vancomycin, cefapime, acyclovir, and ampicillin for bacterial meningitis treatment and HIV encephalitis treatment. When the results of the lumbar puncture were obtained, the antibiotics were discontinued and the patient remained on acyclovir until her PCR came back as negative. Infectious disease was consulted and upon discussion with them, the most likely differential diagnosis of the patient's encephalitis was HIV encephalitis. Initially, a diagnosis of possible TB meningitis/encephalitis was entertained given the slightly low glucose. However, given that the glucose normalized on repeat lumbar puncture, the improvement of the patient's condition throughout the hospitalization, and relatively benign course of the patient's encephalopathy, it was felt that TB was much less likely. Lymphoma was still a possibility for the patient's symptoms, and cytology was pending, although this was felt to be a much less likely diagnosis. The patient was discharged back to her program, with plans for close followup: retroviral therapy was to be initiated and she was to be followed up in neurology within 1 to 2 weeks. The discharge diagnosis on 28-JUN-2009 was human immunodeficiency virus (HIV) encephalopathy. Discharge medications included IMITREX, amlodipine, compazine (10 mg PO Q8H, PRN nausea/vomiting), ibuprofen (PRN headache). The patient was hospitalized again on 02-JUL-2009 with acute mental status changes. She was brought to the ED and around midnight or 12:15 on 02-JUL-2009 and it was noted at that time that the patient seemed to again have worsening headache, worsening confusion, as well as progressive acute mental status changes. Neurology was not contacted regarding the patient as the ED felt that the previous work up was satisfactory from a neurological standpoint. Primary medicine evaluated the patient, and it was determined she would be taken to their service. It was noted at 5:30 a.m. that the patient had a CT requested by the primary medicine serve to the ED prior to her transition up to the floor. Subsequently after that, the patient was noted at approximately 6 a.m. to have fixed pupils bilaterally and a change in blood and change in heart rate from an atypical bradycardia in the 40's to a tachycardia. It was thought that the patient would be unable to protect her airway, and the decision was made to intubate the patient. The patient was subsequently successfully intubated after several tries. She was noted to have an acute decrease in her blood pressure to a hypotension of 50's/40's. It was then thought the patient was acutely decompensating, and the decision to place a central line was made in collaboration between the ED and the ICU staff. The ICU staff became involved at approximately 6:20 a.m. during the tail end of the intubation period. Central line was placed in the jugular vein. At the same time, the patient's systolic blood pressure returned to the 110s. It was then noted that the patient was moving toward hypertension, and her dopamine was weaned from 10 to 5 and subsequently settled to about 8. She was brought to CT scan and subsequently to the floor. The initial read by the on-call radiologist demonstrated what appeared to be some mild edema, but otherwise negative. At approximately 8:30 the patient was being rounded on the ICU by the faculty and staff, and staff had noted dilated pupils bilaterally while in the ED after intubation and presented this to the team. During the examination by the attending physician, the radiology attending came and noted that the original read had missed important information regarding the patient's clinical status. The attending contributed that the patient, in fact, did demonstrate a herniation of the posterior brain tissue into the spinal cord region. The patient was initially said to have decreased neurological reflexes in the ED, and this was corroborated and simultaneously neurosurgery and neurology were contacted and activated regarding the patient. Stat orders for mannitol and decadron were sent and administered to the patient. After evaluation by neurology and neurosurgery, it was determined that the patient in fact had suffered brain death. Intervention was discontinued around 10 a.m. and subsequently neurological evaluation for brain death commenced and terminated with determination of brain death at 1 p.m. on the afternoon of July 2, 2009. Support was withdrawn at approximately 1 p.m. The patient's family was present and requested autopsy to be performed. The following laboratory tests were performed during the patient's hospitalizations: sodium of 136, potassium 4.3, chloride of 95, BUN of 12, creatinase of 0.61 and glucose of 111. The patient had an IMR of 1.1, PT of 29.6, white count 7.9, hemoglobin and hematocrit 12.8 and 37.7 respectively with a platelet count in the upper 200s. The patient had blood cultures drawn that were pending, and urinalysis demonstrated 1+ protein, glucose, and bacteria with 0 to 2 white blood cells and 0 to 2 red blood cells. The patient also had a lumbar puncture from 29-JUN-2009 this showed 30 white blood cells and 3 red blood cells in tube 1 and 25 white blood cells and 2 red blood cells in tube 4 that were both lymphocyte predominant. The patient had several studies done in addition, ALF was 23, ABT 20, alkaline phosphatase 57, and total bilirubin 0.4 with a direct bilirubin of 0.1. The patient's urine pregnancy was negative, urine was positive for opiates, and the patient had a serology from a previous admission that showed cocci and crypto negative. The patient also had a lactate of 4.6, protein 0.7, albumin 9.4, calcium 9.4, lipase 24. The patient was also noted to have a viral load of hepatitis C less than 3200, but also had positive hepatitis C antibodies. Hepatitis B and hepatitis A were found to be negative. A chest x-ray on the patient failed to demonstrate focal lesions, although there was mild left-sided hilar congestion. A CT scan of the head that was noncontract demonstrated herniation and edema. ECG demonstrated sinus bradycardia. CT neuro angiogram performed 22-JUN-2009, Impression: 1. Diffuse bilateral sulcal effacement of the cerebral hemispheres without herniation. This is suggestive of diffuse cerebral swelling with causes including toxic, metabolic, or infectious etiologies. 2. Bilateral symmetric optic nerve sheath distention without clear elevation of the optic discs suggestive of elevated intracranial pressure (ICP) correlate with fundoscopic exam findings and/or clinical symptoms referable to elevated ICP. 3. Incidentally noted 3 mm left supraclinoid ICA aneurysm, medially directed, may be a carotid cave aneurysm. 4. No acute large vessel territory ischemia or infarct, intracranial hemorrhage or extra-axial collection. There is no abnormal parenchymal or leptomeningeal enhancement. MRI brain scan with contrast performed 23-JUN-2009. Impression: diffuse sulcal effacement suggesting diffuse swelling. There is FLAIR hyperintensity and prominent enhancement within sulci. This may be due to vessel crowding within the narrowed sulci. However, a leptomeningeal process such as meningitis can also look like this. Correlation with CSF analysis is recommended. 2. Vague enhancing T2/FLAIR hyperintensity in the bilateral frontal white matter, left greater than right subinsular white matter, the left brachium pontis, the bilateral medial thalami, bilateral anteromedial temporal lobes. Diagnostic considerations include infectious etiologies such as HIV encephalopathy, herpes encephalitis, progressive multifocal leukoencephalopathy, or toxic/metabolic etiology. All medical records are available upon request.  9/8/09 Autopsy report received. DOD 7/2/09 Acute cerebrovascular event with uncal and tonsillar herniation due to severe and extensive CNS vasculitis. Additional clinical information abstracted: Migraines, history of substance / methamphetamine use, Bell's palsy, altered mental status, HIV infection. Extensive vasculitis affecting blood vessels in leptomeniniges and throughout the brain and spinal cord. Severe hypoxic ischemic encephalopathy. Chronic meningitis. Heavy and congested lungs. Renal cortical scars, right and left kidneys, suggestive of prior infectious process. Reactive lymphadenopathy of axillary and paraaortic lymph nodes.