Encephalitis in bone marrow transplant patient

Clinical History

50-year-old man presented with acute onset confusion Day 49 post bone marrow transplant for relapsed ALL (Acute lymphocytic leukaemia)
Transplant conditioning regime: Melphalan, Fludarabine, Alemtuzumab
Other background history: Appendectomy, Inguinal hernia repair
CSF virology: positive for HHV 6 (Human Herpesvirus)
EEG: non-specific

Imaging Findings

The patient underwent CT brain initially which showed periventricular deep white matter low attenuation change of uncertain significance.
He subsequently had an MRI brain performed which showed symmetric high T2 signal and oedema in the mesial temporal lobes. High signal was noted in the medial temporal lobes. No abnormal enhancement post contrast. The diagnosis was made of mesolimbic encephalitis secondary to Human Herpes Virus 6 (HHV6) infection.
After diagnosis, he completed 3 weeks of Ganciclovir treatment and by day 82 his confusion was improving. A repeat MRI scan was recommended, and was performed approximately two weeks post initial MRI scan. This showed partial resolution of the findings in the mesial temporal lobes.

Discussion

Approximately 80-90% of adults have serum anti-human HHV 6 antibody/detectable HHV 6 in peripheral blood mononuclear cells or saliva. The reported incidence of HHV 6 reactivation post haematopoietic stem cell transplant is 28%-78%, and is reportedly higher post allogeneic cord blood stem cell transplantation vs allogeneic bone marrow transplant. [1]
Symptoms of reactivation include skin rash, fever, myelosuppresion, pneumonitis, GVHD, encephalitis.
Diagnosis of HHV 6 encephalitis is based on a triad of
(i) neurological manifestations-confusion, agitation, seizures
(ii) evidence of HHV 6 infection in CSF (plasma HHV 6 may be negative)
(iii) absence of other pathogens/pathology (infections, drug toxicity, metabolic abnormalities)
Classically HHV 6 involves the medial temporal lobe and hippocampi, followed by the amygdala and the parahyppocampal gyrus, but can present with non-specific white matter changes on MRI. [2] This manifests clinically as acute hippocampal dysfunction (loss of short term memory, sleep disturbances and confusion).
CT findings are usually unremarkable with HHV 6 encephalitis but in our patient showed periventricular deep white matter low attenuation change. [3]
Of note, our patient was given Alemtuzumab as part of his conditioning regimen which has been linked with an increased incidence of HHV 6 encephalitis but usually in patients who develop GVHD. [2]
After diagnosis, he completed 3 weeks of Ganciclovir treatment and by D+82 his confusion was improving.
It is important to have a high index of suspicion and recognize neurological symptoms early in patients post BMT as prompt diagnosis and treatment can result in an excellent outcome.

Differential Diagnosis List

Final Diagnosis

HHV 6 encephalitis

URL:	https://www.eurorad.org/case/13246
DOI:	10.1594/EURORAD/CASE.13246
ISSN:	1563-4086