Herpetic brainstem encephalitis

Roman-Campos, Gustavo; Toro, Gerzaín Rodríguez

doi:10.1212/wnl.30.9.981

Cited by 53 publications

(12 citation statements)

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“…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%

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: 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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“…However, in these reports pathological changes indicating HSE were not limited to the brain stem, but were found also in the temporal lobe, frontal cortex, cingulate gyrus, occipital lobe or cerebellum [8,9]. The circumscribed nature of HSV infection limited to the brain stem has been histologically documented in only two cases [10,11].…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex virus infection limited to the brainstem

Jereb¹,

Lainščak²,

Marin

et al. 2005

Wien Klin Wochenschr

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Focal meningoencephalitis is commonly caused by Herpes simplex virus infection, which typically affects temporal or frontal lobes, and carries a mortality rate of 70% if untreated. On rare occasions, however, the infection is restricted to the brain stem. Polymerase chain reaction analysis of cerebrospinal fluid is the gold standard for the diagnosis of herpes simplex encephalitis. A 46-year-old male was admitted to the hospital with a three-day history of headache and fever up to 39 degrees C. Cerebrospinal fluid findings were in accordance with aseptic meningitis. On the third hospital day, the patient presented with double vision followed by confusion, and gaze paresis developed. The condition rapidly progressed from stupor to coma. A second examination of cerebrospinal fluid revealed a low glucose level (1.2 mmol/l) and cefotaxime with ampicillin were started empirically. All cerebrospinal fluid specimens were negative for bacteria and fungi. Serum IgG antibodies for herpes simplex virus type 1 were found with no intrathecal specific antibody synthesis. A polymerase chain reaction analysis of cerebrospinal fluid sample performed on the seventh day of his illness was negative for herpes simplex virus 1 and 2. A computer tomography scan of the brain did not show any abnormality. Despite antimicrobial and supportive intensive care, the condition of the patient progressively deteriorated and he died on the 11th day after admission. An autopsy revealed hemorrhagic and necrotic brainstem meningoencephalitis, and herpes simplex virus type 1 infection was confirmed by hybridization in situ. Herpes simplex virus encephalitis carries a mortality rate of 70% if untreated. The atypical location of the infection, as well as an atypical clinical manifestation with negative radiological and microbiological tests, could be the reasons for false diagnoses and mistreatment. Many authors advocate the use of empiric acyclovir in any patients with unexplained encephalopathy, since delay in treatment may greatly affect outcome. We describe a patient who died due to a herpes simplex virus 1 encephalitis affecting the brainstem, where nucleic acids were found post mortem by in situ hybridization. On rare occasions, the herpes simplex viral infection, as well as clinical manifestations and pathological changes, is restricted solely to the brainstem.

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“…Their MRI showed that the responsible sites are comparable with those reported in experimental studies 1-3. Herpes simplex virus type 1 (HSV-1) infection also causes brainstem lesions7 8 characterised by acute onset of multiple cranial nerve palsies, ataxia, and pyramidal tract involvement. Disturbances of consciousness and respiration are not uncommon.…”

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confidence: 99%

Micturitional disturbance in herpetic brainstem encephalitis; contribution of the pontine micturition centre

Sakakibara

Hattori

Fukutake

et al. 1998

Journal of Neurology, Neurosurgery & Psychiatry

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Micturitional disturbance is rarely mentioned in human herpetic brainstem encephalitis although the pontine tegmentum, called the pontine micturition centre, seems to regulate the lower urinary tract in experimental animals. The case of a 45 year old man, who developed subacute coma and hiccup-like dysrhythmic breathing, and needed assisted ventilation is reported. Examination of CSF showed mononuclear pleocytosis and antibody against herpes simplex virus type 1, but the opening pressure was 90 cm H 2 O. Brain CT showed brain swelling, predominantly in the posterior fossa, and bilateral subdural eVusion. Herpetic brainstem encephalitis was diagnosed, and he received 900 mg/day vidarabine. On regaining consciousness, he had left trochlear nerve palsy, left corectopia, ageusia, and urinary retention. Brain MRI showed right side dominant, bilateral pontine segmental lesions extending slightly to the midbrain and medulla. After two weeks he was able to urinate but showed nocturnal urinary frequency, urinary incontinence, and voiding diYculty. Urodynamic studies showed a residual urine volume of 350 ml and detrusor hyporeflexia on voiding. Micturitional disturbance gradually disappeared together with the neurological signs. The bilateral pontine tegmental lesions in this patient are similar to those in previous findings on brainstem strokes, evidence of the presence of a pontine micturition centre in humans. (J Neurol Neurosurg Psychiatry 1998;64:269-272)

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Herpetic brainstem encephalitis

Cited by 53 publications

References 0 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

Herpes simplex virus infection limited to the brainstem

Micturitional disturbance in herpetic brainstem encephalitis; contribution of the pontine micturition centre

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