Acute hemorrhagic leukoencephalitis; dizziness; headache; slurred speech; ataxia; myalgia; fatigue; mental fog; fall; acutely encephalopathic; right side weakness; expressive aphasia; Initial information was received on 27-Oct-2021 regarding an unsolicited valid serious case issued from a literature article.  This case involves a 74-year-old female patient who experienced acute hemorrhagic leukoencephalitis (acute haemorrhagic leukoencephalitis), dizziness, headache, slurred speech (dysarthria), ataxia, myalgia, fatigue, mental fog (mental fatigue), fall, acutely encephalopathic (encephalopathy), right side weakness (hemiparesis) and expressive aphasia (aphasia) after receiving INFLUENZA QUADRIVAL A-B HIGH DOSE HV VACCINE [FLUZONE HIGH-DOSE QUADRIVALENT].  The patient's medical history, medical treatment(s), vaccination(s), concomitant medications and family history were not provided.  On an unknown date, the patient received a dose of suspect INFLUENZA QUADRIVAL A-B HIGH DOSE HV VACCINE lot number not reported via unknown route in unknown administration site for prophylactic vaccination.  On an unknown date the patient developed a serious acute hemorrhagic leukoencephalitis (acute haemorrhagic leukoencephalitis) (unknown latency) following the administration of INFLUENZA QUADRIVAL A-B HIGH DOSE HV VACCINE. The  event was diagnosed with magnetic resonance imaging (MRI) brain which showed significant areas of hemorrhage with vasogenic edema including involvement of the pons. The patient was aggressively treated with plasma exchange and corticosteroids and had a favorable outcome  On an unknown date the patient presented to the emergency department with acute symptoms of dizziness, headache, slurred speech (dysarthria) and ataxia,10 days following the administration of INFLUENZA QUADRIVAL A-B HIGH DOSE HV VACCINE.   On an unknown date, she was complaining of myalgia, fatigue and mental fog (mental fatigue) (unknown latency) since receiving the vaccine  The nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS COV-2 PCR) was negative  Third day of hospitalization, she experienced a fall and became acutely encephalopathic (encephalopathy) with right side weakness (hemiparesis) and had to be intubated and transferred to the intensive care unit (ICU). MRI brain with and without contrast demonstrated bilateral significantly elevated Cerebrospinal fluid (CSF) protein (108 mg/dL) and positive oligoclonal bands. Aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) antibody were negative. She underwent 5 cycles of plasma exchange (PLEX) which started five days from initial presentation and received 5 days of intravenous (IV) solumedrol followed by steroid taper for 5 weeks. Repeat MRI brain without contrast fourteen days from initial presentation showed increased abnormal T2 hyperintensity and small amount of superimposed parenchymal hemorrhage involving the left parietal lobe, right parietal lobe and hemorrhage in pons. She was discharged eventually to a rehabilitation unit after significant improvement and was seen in an outpatient neurology clinic three months from initial presentation. She was ambulatory using a walker and only had mild right sided weakness and mild expressive aphasia (aphasia).   All events were assessed as medically significant, and the patient was hospitalized for the events  At time of reporting, the events hemiparesis and aphasia were not recovered while other events were recovering.  The reporter did not report causality of events with suspect  There will be no information available on the batch number for this case.; Sender's Comments: This case concerns a 74-year-old female patient who was diagnosed with acute haemorrhagic leukoencephalitis having symptoms of dizziness, headache, dysarthria, ataxia, myalgia, fatigue, mental fatigue, fall, encephalopathy, hemiparesis and aphasia after vaccination with FLUZONE HIGH-DOSE QUADRIVALENT. The time to onset is compatible. The magnetic resonance imaging (MRI) brain showed acute haemorrhagic leukoencephalitis and significant areas of hemorrhage with vasogenic edema including involvement of the pons. Additional information regarding patient's medical history and condition at the time of vaccination would be needed for complete assessment of the case. Based upon the reported information, the role of the vaccine cannot be assessed.