Human herpes 6 virus encephalitis complicating allogeneic hematopoietic stem cell transplantation

Bhanushali, Minal; Kranick, Sarah M.; Freeman, Alexandra F.; Cuéllar-Rodríguez, Jennifer; Battiwalla, Minoo; Gea-Banacloche, Juan; Hickstein, Dennis D.; Pavletić, Steven Z.; Fahle, Gary A.; Nath, Avindra

doi:10.1212/wnl.0b013e31828cf8a2

Cited by 77 publications

(82 citation statements)

References 12 publications

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“…3,7,[36][37][38]41,42 Some investigators have termed this finding 'post-transplant acute limbic encephalitis (PALE) 38,40,[42][43][44] and HHV-6 PALE has been diagnosed when the patient has detectable HHV-6 DNA in cerebrospinal fluid in the context of acute-onset altered mental status, amnesia, seizures or other evidence of medial temporal lobe disease involving the limbic system and no other identifiable etiology. 38,42 A recent retrospective study 45 showed, however, not all cases of HHV-6-associated CNS dysfunction meet the criteria for PALE. HHV-6 may also cause myelitis that presents with systemic pruritus and severe pain in the extremities.…”

Section: Disease Associations: We Do Not Know the Precise Disease Assmentioning

confidence: 99%

“…[50][51][52][53] Criteria frequently used in the literature to define HHV-6 encephalitis include: the presence of neurological symptoms (altered mental status, altered level of consciousness, amnesia, seizures and change in personality and behavior); positive PCR results for HHV-6 in cerebrospinal fluid (ciHHV-6 should be excluded); and the absence of other identified etiologies of CNS dysfunction. 5,15,37,44,45,54 This criterion may enable physicians to diagnose HHV-6 encephalitis effectively and efficiently. False-positive results for HHV-6 DNA in cerebrospinal fluid may occur, 50,52,55 and hence positive results must be interpreted carefully in conjunction with clinical symptoms and negative results for other etiologies.…”

Section: Disease Associations: We Do Not Know the Precise Disease Assmentioning

confidence: 99%

“…5,42 INCIDENCE AND RISK FACTORS: WE KNOW UCBT IS A RISK FACTOR OF HHV-6 ENCEPHALITIS, BUT DO NOT KNOW THE TRUE INCIDENCE AND OTHER RISK FACTORS Reported incidences of HHV-6 encephalitis in allo-HCT recipients have ranged from 0.95 to 11.6% (Table 1). [3][4][5]8,42,44,45,47,54,55,[59][60][61][62] Many factors will affect the reported incidence, including the proportion of stem cell sources in the analyzed population, study design, definitions of HHV-6 encephalitis, selection of immunosuppressants and efforts toward diagnosis. Clearly, UCBT represents a strong risk factor for HHV-6 encephalitis ( Table 1).…”

Section: Hhv-6 Reactivation and Hhv-6 Encephalitis: We Know Hhv-6 Reamentioning

confidence: 99%

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Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Ogata

Fukuda²,

Teshima

2015

Bone Marrow Transplant

102

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Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after umbilical cord blood transplantation, typically around 2-6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication.

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Section: Disease Associations: We Do Not Know the Precise Disease Assmentioning

confidence: 99%

Section: Disease Associations: We Do Not Know the Precise Disease Assmentioning

confidence: 99%

Section: Hhv-6 Reactivation and Hhv-6 Encephalitis: We Know Hhv-6 Reamentioning

confidence: 99%

See 1 more Smart Citation

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Ogata

Fukuda²,

Teshima

2015

Bone Marrow Transplant

102

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“…Although this disease generally manifests as a benign self-limiting febrile illness (2), in rare cases it can cause severe complications, including encephalitis (3,4) and fulminant hepatitis (5). HHV-6B reactivation has clinical manifestations in transplant recipients, such as skin rash and fever (6,7) and bone marrow suppression and posttransplant acute limbic encephalitis (8)(9)(10)(11)(12)(13). Antiviral drugs, such as ganciclovir (GCV) and foscarnet, have been used to treat transplant recipients with HHV-6B-associated encephalitis (8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

“…The antiviral effect of GCV against HHV-6B has been demonstrated using in vitro susceptibility assays (17)(18)(19). The in vivo efficacy of GCV remains inconclusive, despite its general use in patients with HHV-6 encephalitis posttransplantation (8)(9)(10)(11)(12)(13). The U69 gene in HHV-6 is a homologue of the HCMV UL97 gene, and it phosphorylates GCV (20,21).…”

mentioning

confidence: 99%

Analysis of Ganciclovir-Resistant Human Herpesvirus 6B Clinical Isolates Using Quenching Probe PCR Methodology

Hiramatsu

Suzuki

Yamada

et al. 2015

Antimicrob Agents Chemother

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cQuenching probe PCR (QP-PCR) analysis was used to determine the frequency of ganciclovir (GCV) resistance among clinical isolates of human herpesvirus 6B (HHV-6B) obtained from patients with primary viral infection and viral reactivation. Fortytwo HHV-6B clinical isolates were repeatedly recovered from 15 hematopoietic stem cell transplant (HSCT) recipients, and 20 isolates were recovered from 20 exanthem subitum (ES) patients. Of the 15 HSCT recipients, 9 received GCV during the observation period; however, none of the ES patients were treated with GCV. Two established laboratory strains, Z29 and HST, were used as standards in this study. Regions 1 and 2 of the U69 gene of all of the clinical isolates demonstrated the same melting temperature as regions 1 and 2 of the Z29 strain. For region 3, the melting temperatures of all clinical isolates fell between the melting temperature of the plasmid containing the A462D single nucleotide polymorphism (SNP) and the melting temperature of the Z29 strain, and the melting temperatures profiles of all clinical isolates were similar to the melting temperature profile of the Japanese HST strain. As expected, none of the 20 clinical isolates recovered from the ES patients and the 14 isolates recovered from the HSCT recipients who did not receive GCV treatment carried the six known SNPs associated with GCV resistance. Interestingly, these six SNPs were not detected in the 28 clinical isolates recovered from the 9 HSCT recipients who received GCV. Additional sequence analysis of the U69 gene from the 15 representative isolates from the 15 HSCT recipients identified other SNPs. These SNPs were identical to those identified in the HST strain. Therefore, the rate of emergence of GCV-resistant HHV-6B strains appears to be relatively low, even in HSCT recipients treated with GCV.

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Neuroinfectious Diseases

Nath

2015

JAMA Neurol

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Despite significant advancements in the management of infectious diseases, central nervous system (CNS) infections remain a major challenge. They are often difficult to diagnose, and treatments are inadequate or nonexistent. Not surprisingly, encephalitis has been the subject of several recent movies and of fiction and nonfiction books, and outbreaks have received wide attention by the popular media. For example, bovine spongiform encephalopathy (mad cow disease) continues to get wide media coverage despite the absence of human cases in United States. Emergence of New InfectionsWith the globalization of human travel, new infections can spread worldwide in record time. Recent examples include the West Nile, chikungunya, dengue, Hanta, Marburg, and influenza viruses; severe acute respiratory syndrome; and now the Ebola virus and enterovirus D68. There is the reemergence of meningococcal meningitis, poliomyelitis, and measles. Bioterrorism is another threat because CNS pathogens can be weaponized. Human and animal products for treatment also pose a risk.

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Human herpes 6 virus encephalitis complicating allogeneic hematopoietic stem cell transplantation

Abstract: Objective: To describe the presentation and management of encephalitis due to human herpes 6 virus (HHV-6) in patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT), via retrospective chart review.

Cited by 77 publications

References 12 publications

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Analysis of Ganciclovir-Resistant Human Herpesvirus 6B Clinical Isolates Using Quenching Probe PCR Methodology

Neuroinfectious Diseases

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