Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid

Tyler, Kenneth L.; Tedder, Davol G.; Yamamoto, Leona; Klapper, J.A.; Ashley, Rhoda; Lichtenstein, Kenneth A.; Levin, M J

doi:10.1212/wnl.45.12.2246

Cited by 43 publications

(16 citation statements)

References 11 publications

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“…Brain stems were chosen for investigation because our previous ex vivo study found this brain region had a high HSV-1 reactivation frequency compared with other CNS regions (frontal cortex, cerebellum, olfactory bulbs, hippocampus, and spinal cord) after cultivating dissociated tissue explants (10). Additionally, recurrent brain stem encephalitis has been reported in patients (20). Mouse neural tissues were harvested 1 to 9 days p.i., frozen, homogenized, frozen, sonicated, and subjected to plaque assay for 3 days to determine viral titers.…”

Section: Resultsmentioning

confidence: 99%

“…In patients, recurrent brain stem encephalitis has been reported, but the case number is much less than for encephalitis localized in the frontal and/or temporal cortex (20,36,37). Our present study employed mice inoculated with virus by the ocular route, which mimics natural infection in some humans and has been the most frequently used model for investigating HSV reactivation.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

Yao

Ling

Tung

et al. 2014

J Virol

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Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. Both primary and recurrent infections can induce diseases, such as encephalitis. In humans, the majority of encephalitis cases occur as a recurrent infection. However, in the past, numerous mouse studies documented that viral reactivation occurs efficiently in the ganglion, but extremely rarely in the brain, when assessed ex vivo by cultivating minced tissue explants. Here, we compare the brains and the trigeminal ganglia of mice latently infected with HSV-1 (strain 294.1 or McKrae) for levels of viral genomes and in vivo reactivation. The numbers of copies of 294.1 and McKrae genomes in the brain stem were significantly greater than those in the trigeminal ganglion. Most importantly, 294.1 and McKrae reactivation was detected in the brain stems earlier than in the trigeminal ganglia of mice treated with hyperthermia to reactivate latent virus in vivo. In addition, the brain stem yielded reactivated virus at a high frequency compared with the trigeminal ganglion, especially in mice latently infected with 294.1 after hyperthermia treatment. These results provide evidence that recurrent brain infection can be induced by the reactivation of latent virus in the brain in situ. IMPORTANCEHerpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. In the past, studies of viral reactivation focused on the ganglion, because efficient viral reactivation was detected in the ganglion but not in the brain when assessed ex vivo by cultivating mouse tissue explants. In this study, we report that the brain contains more viral genomes than the trigeminal ganglion in latently infected mice. Notably, the brain yields reactivated virus early and efficiently compared with the trigeminal ganglion after mice are stimulated to reactivate latent virus. Our findings raise the potential importance of HSV-1 latent infection and reactivation in the brain.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

Yao

Ling

Tung

et al. 2014

J Virol

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“…CSF PCR has been positive in isolated cases of both acute and recurrent brain stem encephalitis (43,156,163). CSF PCR has been used to amplify HSV-1-specific DNA from the CSF of a patient with recurrent episodes of BSE (235). These reports suggest that the diagnosis, as well as the clinical and epidemiological spectra of HSV BSE, may become more clearly delineated with the more widespread use of CSF PCR for antemortem diagnosis.…”

Section: Vol 17 2004 Molecular Methods For Diagnosis Of Viral Encepmentioning

confidence: 99%

Molecular Methods for Diagnosis of Viral Encephalitis

2004

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Hundreds of viruses cause central nervous system (CNS) disease, including meningoencephalitis and postinfectious encephalomyelitis, in humans. The cerebrospinal fluid (CSF) is abnormal in >90% of cases; however, routine CSF studies only rarely lead to identification of a specific etiologic agent. Diagnosis of viral infections of the CNS has been revolutionized by the advent of new molecular diagnostic technologies to amplify viral nucleic acid from CSF, including PCR, nucleic acid sequence-based amplification, and branched-DNA assay. PCR is ideally suited for identifying fastidious organisms that may be difficult or impossible to culture and has been widely applied for detection of both DNA and RNA viruses in CSF. The technique can be performed rapidly and inexpensively and has become an integral component of diagnostic medical practice in the United States and other developed countries. In addition to its use for identification of etiologic agents of CNS disease in the clinical setting, PCR has also been used to quantitate viral load and monitor duration and adequacy of antiviral drug therapy. PCR has also been applied in the research setting to help discriminate active versus postinfectious immune-mediate disease, identify determinants of drug resistance, and investigate the etiology of neurologic disease of uncertain cause. This review discusses general principles of PCR and reverse transcription-PCR, including qualitative, quantitative, and multiplex techniques, with comment on issues of sensitivity, specificity, and positive and negative predictive values. The application of molecular diagnostic methods for diagnosis of specific infectious entities is reviewed in detail, including viruses for which PCR is of proven efficacy and is widely available, viruses for which PCR is less widely available or for which PCR has unproven sensitivity and specificity, and nonviral entities which can mimic viral CNS disease

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“…The trigeminal nerve innervates the meninges, and spread to the orbitofrontal and mesiotemporal lobes could also occur through this route [17]. However, as the sensory nuclei of the trigeminal nerve are located in the brainstem, one would expect the relatively rare occurrence of brainstem encephalitis associated with HSVE to be more common if this were the primary route of entry to the CNS in most cases [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid

Cited by 43 publications

References 11 publications

In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

Molecular Methods for Diagnosis of Viral Encephalitis

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

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