Ganciclovir-resistant HHV-6 encephalitis that progressed rapidly after bone marrow transplantation

Imataki, Osamu; Uemura, Makiko

doi:10.1016/j.jcv.2015.06.097

Cited by 6 publications

(13 citation statements)

References 22 publications

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“…An acute encephalitis might occur either after a primary infection in an immunocompetent individual or after becoming immunocompromised due to an underlying condition. Over the past 10 years, viral encephalitis has gained recognition as an important complication in cell and organ transplantation settings (de Ory et al 2013 ; Ibrahim et al 2005 ; Imataki and Uemura 2015 ; Ljungman 2002 ; Steiner et al 2010 ; Michael and Solomon, 2012 ; Scheurer et al 2013 ).…”

Section: Clinical Presentation Of Roseolovirus-associated Encephalitimentioning

confidence: 99%

“…Higher levels post-transplant of either HHV-6 or HHV-7 antibodies, antigenemia, and DNA detection are more frequent in the allogeneic than in autologous recipients. Patients who have undergone total body irradiation (TBI) have faced reactivation of both HHV-6 and HHV-7 more often than those not irradiated (Imataki and Uemura 2015 ; Savolainen et al 2005 ). Males are more frequently affected (Sakai et al 2011 ; Hirabayashi et al 2013 ; Endo et al 2014 ; Ongrádi et al 2014 ).…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

“…Patients of any age with malignancies (Martikainen et al 2013 ) and those who receive HSCT undergo combined chemotherapy regimens, biological therapy (e.g., anti-T cell antibodies), and intracranial or total body irradiation (Drobyski et al 1994 ; Imataki and Uemura 2015 ; Kawamura et al 2013 , 2012 ; Ogata et al 2010 ; Raspall-Chaure et al 2013 ; Wittekindt et al 2009 ; Zerr et al 2011 ). These combinations frequently contain drugs, such as anti-cancer agent histone deacetylase (HDAC) inhibitors, that are able to activate HHV-6 and HHV-7 or other viruses in vitro and in vivo , particularly in the CNS (Yao et al 2008 ).…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

“…Characteristic neuroradiographic signs of HHV-6-associated encephalitis or encephalopathy in both immunocompetent and immunocompromised patients have been recognized using CT scanning (Al-Zubeidi et al 2014 ; Kadwabe et al 2010 ; Yao et al 2010a ; Zerr, 2006 ), MRI (Al-Zubeidi et al 2014 ; Chapenko et al 2016 ; Crawford et al 2009 ; Drobyski et al 1994 ; Hirabayashi et al 2013 ; Kawamura et al 2013 ), and FLAIR MRI (Kawamura et al 2013 , 2012 ; Maramattom 2015 ; Venancio et al 2014 ; Yajima et al 2014 ; Yamamoto et al 2015 ). Findings include diffuse high intensity of the limbic system around bilateral, temporal, occipital, and frontal areas (Imataki and Uemura 2015 ). Susceptibility weighted imaging (Iwasaki et al 2014 ) and acute phase 2-deoxy-(F-18)-fluoro-D-glucose positron emission tomography (FDG-PET; Hubele et al 2012 ) are also used.…”

Section: Diagnosismentioning

confidence: 99%

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Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

et al. 2016

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The roseoloviruses, human herpesvirus (HHV)-6A, HHV-6B, and HHV-7, can cause severe encephalitis or encephalopathy. In immunocompetent children, primary HHV-6B infection is occasionally accompanied by diverse clinical forms of encephalitis. Roseolovirus coinfections with heterologous viruses and delayed primary HHV-7 infection in immunocompetent adults result in very severe neurological and generalized symptoms. Recovery from neurological sequelae is slow and sometimes incomplete. In immunocompromised patients with underlying hematological malignancies and transplantation, frequent single or simultaneous reactivation of roseoloviruses elicit severe, lethal organ dysfunctions, including damages in the limbic system, brain stem, and hippocampus. Most cases have been due to HHV-6B with HHV-6A accounting for 2–3%. The most severe manifestation of HHV-6B reactivation is post-transplantation limbic encephalitis. Seizures, cognitive problems, and abnormal EEG are common. Major risk factors for HHV-6B-associated encephalitis include unrelated cord blood cell transplantation and repeated hematopoietic stem cell transplantation. Rare genetic disorders, male gender, certain HLA constellation, and immune tolerance to replicating HHV-6 in persons carrying chromosomally integrated HHV-6 might also predispose an individual to roseolovirus-associated brain damage. At this time, little is known about the risk factors for HHV-7-associated encephalitis. Intrathecal glial cell destruction due to virus replication, overexpression of proinflammatory cytokines, and viral mimicry of chemokines all contribute to brain dysfunction. High virus load in the cerebrospinal fluid, hippocampal astrogliosis, and viral protein expression in HHV-6B-associated cases and multiple microscopic neuronal degeneration in HHV-7-associated cases are typical laboratory findings. Early empirical therapy with ganciclovir or foscarnet might save the life of a patient with roseolovirus-associated encephalitis.

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Section: Clinical Presentation Of Roseolovirus-associated Encephalitimentioning

confidence: 99%

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

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Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

et al. 2016

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“…This report is consistent with our case, where the patient's mental status improved significantly after being switched to GCV from ACV. However, it has been reported that some strains of HHV‐6 are resistant to GCV, but the data describing the prevalence of GCV‐resistant HHV‐6 are limited . Consequently, if GCV is prescribed for HHV‐6 encephalitis, it is important to monitor the signs and symptoms of the patient and consider switching to foscarnet if the patient fails to improve.…”

Section: Discussionmentioning

confidence: 99%

Human herpesvirus‐6 encephalitis following chemotherapy induction for acute myelogenous leukemia

Frey

Cherabie

Assi

2017

Transplant Infectious Dis

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We report a case of human herpesvirus-6 (HHV-6) encephalitis in a neutropenic patient who had undergone chemotherapy induction for acute myelogenous leukemia while on broad-spectrum antimicrobial therapy. The patient displayed symptoms of confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic resonance imaging of the brain were unremarkable. Following diagnosis, the patient was successfully treated with ganciclovir. HHV-6 encephalitis should be considered in immunocompromised patients who become encephalopathic.

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Betaherpesvirus Complications and Management During Hematopoietic Stem Cell Transplantation

Yoshikawa

2018

Advances in Experimental Medicine and Biology

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Two of the four betaherpesviruses, Cytomegalovirus (CMV) and human herpesvirus 6B (HHV-6B), play an important role in opportunistic infections in hematopoietic stem cell transplant (HSCT) recipients. These viruses are ubiquitous in humans and can latently infect mononuclear lymphocytes, complicating the diagnosis of the diseases they cause. Although the detection of viral DNA in a patient's peripheral blood by real-time PCR is widely used for monitoring viral infection, it is insufficient for the diagnosis of virus-associated disease. Theoretically, end-organ disease should be confirmed by detecting either viral antigen or significant amounts of viral DNA in a tissue sample obtained from the involved organ; however, this is often difficult to perform in clinical practice. The frequency of CMV-associated diseases has decreased gradually as a result of the introduction of preemptive or prophylactic treatments; however, CMV and HHV-6B infections remain a major problem in HSCT recipients. Measurement of viral DNA load in peripheral blood or plasma using real-time PCR is commonly used for monitoring these infections. Additionally, recent data suggest that an assessment of host immune response, particularly cytotoxic T-cell response, may be a reliable tool for predicting these viral infections. The antiviral drugs ganciclovir and foscarnet are used as first-line treatments; however, it is well known that these drugs have side effects, such as bone marrow suppression and nephrotoxicity. Further research is required to develop less-toxic antiviral drugs.

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Ganciclovir-resistant HHV-6 encephalitis that progressed rapidly after bone marrow transplantation

Cited by 6 publications

References 22 publications

Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

Human herpesvirus‐6 encephalitis following chemotherapy induction for acute myelogenous leukemia

Betaherpesvirus Complications and Management During Hematopoietic Stem Cell Transplantation

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