9/22/2009 Case 2: Herpes simplex encephalitis

Presented by: Dr. Leroy Sharer - New Jersey Medical School

Clinical History:

A 61 year old man developed acute myelogenous leukemia in 2005, which was treated, with remission.  He relapsed in 5/07 and had allogeneic unrelated donor hematopoietic stem cell transplantation.  He relapsed one year later.  He was admitted in 11/08 with new onset left-sided weakness.  MRI with and without contrast showed changed including reduced diffusion in the middle cerebellar peduncles and posterior cerebral white matter, suggesting posterior reversible encephalopathy syndrome (PRES).  The differential also included rhombencephalitis due to Listeria and acute disseminated encephalomyelitis (ADEM) without enhancement of the lesions.  There was also what was interpreted as a stable area of chronic ischemia in the right basal ganglia and internal capsule region.  During the hospitalization the patient had progressive neurological deterioration, eventually becoming unresponsive.  CSF examination 6 days prior to death showed 40 cells (96% lymphocytes), protein 37, glucose 52, with atypical lymphocytes on cytology.  PCR on the CSF yielded negative results for JC virus, HSV1 and HSV2.  Up to 984 copies per ml of Epstein Barr virus DNA were present in CSF.  WBC was 9,100, rising to 21,500 on the day prior to death, with 84% neutrophils and platelets of 130,000.  Hepatic enzymes became elevated, as did BUN and creatinine.  Despite all efforts, the patient expired 18 days after admission.  Autopsy was limited to examination of the brain which weighed 1400 grams and was mildly swollen.  There were small hemorrhages in both middle cerebellar peduncles and in the pons, as well as the right cingulate gyrus and right centrum semiovale, with some softening in the right basal ganglia.  Submitted sections show the right middle cerebellar peduncle or the pos plus middle cerebellar peduncle.

Histology showed many plasma cells, especially in the perivascular spaces, with macrophages and hemorrhage.  Luxol fast blue staining showed some myelin loss and some axonal preservation, with hemorrhage.  Many microglia and macrophages were seen using the antibody Iba-1.  Ground glass nuclei and atypical large nuclei were present and could represent endothelial or glial nuclei.  Pertinent additional history was an admission in 8/08 for multiple palatal ulcers consistent with herpesvirus infection.  The brain lesions were positive for HSV1 and HSV2 but negative for VZV and negative for EBV by in situ hybridization. 

Diagnostic Notes:

The diagnosis was Herpes simplex encephalitis. Dr. Sharer noted that HSV is not usually found in cases of AML/myelocytic disorders.  HSV encephalitis has been described in the brainstem.

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