Human herpesvirus-6 (HHV-6)-associated necrotizing encephalitis in griscelli's syndrome

Abstract

We report a male caucasian German pediatric patient of no Arab or Mediterranean ancestry with virus associated CNS lesions in Griscelli's syndrome (GS; McKusick No. 214450). The boy presented with recurrent infections, and meningitis with subsequent progressive signs of increased intracranial pressure leading to death at 32 weeks of age. At autopsy, various sites of the CNS revealed necroses in gray and white matter. CNS histology revealed numerous and massive predominantly perivascular CD8 positive lymphohistiocytic infiltrates. These findings were associated strictly with the presence of human herpesvirus-6 (HHV-6) genome or the HHV-6 specific late antigen H-AR 3, found in neurons, oligodendrocytes, and astrocytes. The search for HHV-6 replication dependent antigen, HHV-7 DNA, CMV, adenovirus, Coxsackie B1, B2, and B4-antigens, and mycobacteria was not successful. Detection of viruses was attempted using immunohistochemistry, in situ hybridization or nested polymerase chain reaction, respectively. Lymphocyte typing was carried out immunohistochemically. In GS, virus induced CNS damage does not seem to require necessarily active virus replication. It may also appear as a consequence of an immune reaction triggered by antigen expression.

Role of viruses in etiology and pathogenesis of multiple sclerosis

“…HHV-6 has been demonstrated to cause fatal encephalitis in AIDS patients and in individuals immunosuppressed as a consequence of bone marrow transplantation Carrigan, 1994, 1995;Drobyski et al, 1994). Furthermore, a neuropathogenic role for HHV-6 has been suggested, based on the development of a variety of disorders associated with active HHV-6 infection, including fulminant demyelinating encephalomyelitis, subacute leukoencephalitis, necrotizing encephalitis, progressive multifocal leukoencephalopathy, and chronic myelopathy (Kamei et al, 1997;Novoa et al, 1997;Carrigan et al, 1996;Wagner et al, 1997;Mackenzie et al, 1995). Third, one of the fundamental properties of herpesviruses is their VIRUSES IN ETIOLOGY AND PATHOGENESIS OF MS 539 tendency to reactivate.…”

Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes

“…Reactivation of HHV-6 in adults is believed to be responsible for encephalitis in immunocompromized hosts such as bone marrow transplant, organ transplant, and stem cell recipients (Drobyski et al, 1994;Wainwright et al, 2001;Zerr et al, 2001). Furthermore, a neuropathogenic role for HHV-6 has been suggested based on the development of a variety of disorders associated with active HHV-6 infection, including fulminant demyelinating encephalomyelitis, subacute leukoencephalitis, necrotizing encephalitis, progressive multifocal leukoencephalopathy, and chronic myelopathy (Carrigan et al, 1996;Mackenzie et al, 1995;Mock et al, 1999;Novoa et al, 1997;Wagner et al, 1997). More recently, HHV-6B viral proteins have been detected in astrocytes from the hippocampus of patients with mesial temporal lobe epilepsy (MTLE) (Donati et al, 2003).…”

Human herpes virus 6 encephalomyelitis after bone marrow transplantation: Report of an autopsy case

“… 3 Several reports that confirmed the occurrence of HHV6 encephalitis after BMT or HSCT appeared subsequently 4,5 . HHV6 is also known as one of the opportunistic pathogens affecting other immunocompromised patients including those afflicted by AIDS 12–14 . In 2007, Seeley et al.…”

“…4,5 HHV6 is also known as one of the opportunistic pathogens affecting other immunocompromised patients including those afflicted by AIDS. [12][13][14] In 2007, Seeley et al proposed that acute limbic encephalitis after HSCT be considered a distinct clinicopathological entity and reported the clinical findings of nine cases under the term 'post-transplant acute limbic encephalitis'. 6 The neuropathological alterations found in the limbic system of the present patient are essentially similar to those described in previously reported cases of HHV6induced limbic encephalitis after BMT or HSCT.…”