Acute hemorrhagic leukoencephalitis (AHLE);   Information has been received from the authors of a published literature article, regarding a 14 year old male patient.  The patient had no concurrent conditions, medical history as was reported to be a healthy boy. The concomitant therapies were not provided.  On an unspecified date, the patient was vaccinated with the first dose of hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) 0.5 milliliter, intramuscularly for prophylaxis.  Three weeks after vaccination, the patient presented headache. Over the following 2 weeks, the patient's headache worsened, and he became increasingly fatigued. On the day of presentation (40 days post-vaccination), he developed left-sided weakness, urinary incontinence, and confusion, which prompted his family to bring him to a local emergency department. There, head computed tomography (CT) was normal and labs, including Complete blood count (CBC), complete metabolic panel, and urine toxicology screen, were unremarkable. He was then transferred to our tertiary hospital for further evaluation and management. Neurologic exam upon admission was notable for left sided extremity weakness, tremors of left extremities, and mild confusion. Brain magnetic resonance imaging (MRI) revealed diffuse hyperintensities on T2 and FLAIR sequences within the subcortical white matter, thalamus, and basal ganglia; also reported as neuroimaging findings. MRI scan of the brain revealed T1-weighted, T2 FLAIR, gradient echo sequence, and the images at the level of midbrain, basal ganglia and centrum semiovale. Bilateral asymmetric foci of increased T2-signals were demonstrated involving the thickened cortices, thalami, and globus pallidi but sparing the posterior fossa structures (not shown), brainstem or centrum semiovale. Gradient echo sequence images showed no hemorrhagic areas. The areas of T2-prolongation did not show diffusion restriction or contrast enhancement (not shown). Cerebrospinal fluid examination showed a lymphocytic pleocytosis with 56 WBC (reference range 0-5), 77% of which were lymphocytes, along with normal protein and glucose. Extensive serologic and nucleic acid amplification testing of his CSF for bacterial and viral pathogens was negative, as were blood cultures. CRP was normal.   Given the combination of his clinical picture, neuroimaging, and laboratory results, the patient was diagnosed with acute disseminated encephalomyelitis (ADEM) and started on treatment with intravenous methylprednisolone, 1 gram daily. Despite this treatment, the patient's encephalopathy worsened, necessitating transfer to the Pediatric Intensive Care Unit (PICU) on the second day of hospitalization. Upon transfer to the PICU, the patient was non-verbal and only intermittently following commands. Exam at the time was notable for left sided facial weakness, increased tone in the left extremities, bilateral ankle clonus, and left patellar hyperreflexia. After an episode of bilateral shoulder twitching concerning for seizure, continuous video electroencephalogram monitoring was initiated and revealed severe multifocal disturbance of cerebral function, but no epileptiform activity. On the third day of hospitalization, the patient had a rapid deterioration in his neurologic exam and developed agonal breathing, emesis, tachycardia, and fixed and dilated pupils. Emergent non-contrast head CT showed severe cerebral edema with impending cerebral herniation, for which he was treated with hyperventilation, hypertonic saline and intravenous mannitol. An emergent right hemicraniectomy was performed. Post-operatively, 400 mg/kg of intravenous immunoglobulin (IVIG) daily was added as treatment for ADEM, but the patient had no neurologic recovery. Neurologic exam performed 3 days post-operatively was consistent with brain death.   Following the patient's death, the family consented to autopsy. Neuropathologic examination revealed an acute vascular inflammatory process with fibrinoid vascular necrosis, marked macrophage infiltrates, parenchymal necrosis, numerous hemorrhages, and areas of myelin and axonal loss, and postmortem histology revealed perivenular sleeves of tissue damage, myelin loss surrounding small parenchymal vessels, and diffuse hemorrhagic necrosis; all consistent with acute hemorrhagic leukoencephalitis.   The histopathologic findings from a biopsy specimen of the right parietal lobe showed: A section stained with ''H&E'' revealed that parenchymal vessels were surrounded by a marked mixed inflammatory infiltrate with fibrinoid necrosis and perivascular hemorrhage. A section stained with Luxol fast blue and ''H&E' revealed peri-vascular demyelination. A section immunohistochemically stained for CD68 antigen revealed a marked macrophage infiltrate. A section immunohistochemically stained for neurofilament revealed patchy axonal loss.  Action taken was not applicable.  The hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) was a recombinant vaccine that included the major capsid (L1) protein of 9 HPV types in highly purified virus-like particles. Sequence homologies between astrocyte water channel aquaporin 4 and several of the HPV L1 capsid proteins have been identified,15 suggesting that molecular mimicry was a biologically plausible mechanism by which HPV vaccination could trigger demyelinating disease.  Upon internal review the event of acute disseminated encephalomyelitis (ADEM) was considered medically significant.  A copy of the published article is attached as further documentation of the patient's experience.; Reported Cause(s) of Death: ADEM; diffuse hemorrhagic necrosis; Autopsy-determined Cause(s) of Death: myelin loss surrounding small parenchymal vessels; perivenular sleeves of tissue damage