Elsevier

Neurologic Clinics

Volume 35, Issue 4, November 2017, Pages 695-705
Neurologic Clinics

Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths

https://doi.org/10.1016/j.ncl.2017.06.006Get rights and content

Section snippets

Key points

  • Herpes simplex virus (HSV) is the most common cause of sporadic encephalitis and should be suspected in patients presenting with acute alteration of consciousness that is otherwise unexplained. However, it remains an infrequent diagnosis in clinical practice.

  • Identification of the viral DNA in the cerebrospinal fluid via polymerase chain reaction is sensitive and specific for the diagnosis of HSV encephalitis.

  • HSV-1 encephalitis nearly always shows characteristic signs on the MRI scan

Basic epidemiologic concepts

HSV-1 seropositivity is high among healthy adults and increases with age; it has been estimated to be 50% to 55% in middle-age and 60% to 90% among older adults.1, 2 Yet, HSV encephalitis is an infrequent diagnosis. Despite being more common than other causes of sporadic infectious encephalitis and accounting for up to 20% of all cases of acute encephalitis, the annual incidence of HSV encephalitis worldwide is only 2 to 4 cases per 1,000,000.3, 4 Among adults, most cases occur in patients

Pathophysiology

HSV-1 and HSV-2 are large, double-stranded DNA viruses belonging to the Herpesviridae family. Other members of this family include the varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpes viruses-6, -7, and -8. Although infections from these other viruses can also involve the brain, their characteristics differ and thus deserve a separate discussion.

HSV gains access to humans through mucous membranes or damaged skin. It then infects sensory neurons and travels by fast

Signs and symptoms

The signs and symptoms of HSV encephalitis are not pathognomonic and resemble those of other causes of acute encephalitis. Confusion, headaches, nausea/vomiting, focal deficits (aphasia, hemiparesis, abnormal sensory perception), and seizures (usually focal or with focal onset) are the most common clinical manifestations (Box 1).5, 9 These signs and symptoms develop rapidly, usually within 1 to 5 days of hospital admission. Depression in the level of consciousness can be seen in more severe or

Diagnostic investigations

Blood tests are useful to exclude alternative diagnoses but cannot confirm the presence of herpes simplex encephalitis. Some patients present with leukocytosis or leukopenia and others develop it during the hospitalization; however, normal white blood cell counts are not incompatible with the diagnosis of HSV encephalitis. Acute thrombocytopenia may be observed in nearly half of the cases.5

More useful tests for the evaluation of HSV encephalitis are the cerebrospinal fluid (CSF) examination,

Treatment

Intravenous acyclovir is highly effective for the treatment of HSV encephalitis.3 In 2 trials against vidarabine, acyclovir was associated with a marked reduction in mortality at 6 months (from 54% to 28% in one trial22 and from 50% to 19% in the other23). The dose of acyclovir is 10 mg/kg every 8 hours for 14 to 21 days. Because the drug is renally cleared, the dose needs to be adjusted in patients with renal impairment (Table 1), but not in those with hepatic dysfunction.

Renal clearance of

Acute complications

Seizures are probably the most common complication during the acute course of HSV encephalitis. Although there is no established indication for the use of preventive antiseizure medications (which is a justifiably common practice), once seizures occur, they must be treated aggressively, as they can rapidly become refractory. Also, it is important to have a low threshold to suspect seizures and obtain an EEG in patients with fluctuating mental function or new focal deficits without

Prognosis

Hospital mortality is approximately 15% and two-thirds of patients are disabled on hospital discharge.5, 11, 12 However, survivors continue to improve over the subsequent year and even longer. In our cohort, we observed a good functional outcome (modified Rankin score 0–2) at 6 to 12 months in 71% of patients who had survived the hospitalization.5 Yet, higher rates of long-term disability have been reported in other contemporary series.27 Prognosis also may be more unfavorable in elderly and

Relapses and sequelae: an autoimmune disorder?

New or worsening neurologic signs and symptoms suggestive of a relapse after apparent resolution of the acute infection can be seen in a small proportion of adults (this may be more common in children). Antibodies against neuronal surface antigens have been reported in some of these patients and it is becoming increasingly accepted that a secondary cerebral autoimmune disease can take place after appropriate treatment of an episode of HSV encephalitis. Anti-N-methyl-d-aspartate receptor

Summary

HSV encephalitis is a serious condition, but it has a very effective treatment. Prompt recognition of the diagnosis and initiation of intravenous acyclovir can greatly improve the chances of recovery with minor or no sequelae. The classic teaching of this disorder is contaminated by some myths that must be dispelled (Table 2). Additional practical advice is listed in Box 2.

First page preview

First page preview
Click to open first page preview

References (35)

  • T.D. Singh et al.

    Predictors of outcome in HSV encephalitis

    J Neurol

    (2016)
  • G. Smith

    Herpesvirus transport to the nervous system and back again

    Annu Rev Microbiol

    (2012)
  • K.T. Thakur et al.

    Predictors of outcome in acute encephalitis

    Neurology

    (2013)
  • S. Miller et al.

    Herpes simplex virus 2 meningitis: a retrospective cohort study

    J Neurovirol

    (2013)
  • N. McGrath et al.

    Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome

    J Neurol Neurosurg Psychiatry

    (1997)
  • G. Rawal et al.

    HSV encephalitis with normal CSF—a case report with review of literature

    J Clin Diagn Res

    (2015)
  • A.W. Saraya et al.

    Normocellular CSF in herpes simplex encephalitis

    BMC Res Notes

    (2016)
  • Cited by (32)

    • Viral encephalitis

      2023, Molecular Medical Microbiology, Third Edition
    • Acute Encephalitic Syndrome Induced by Scleromyxedema

      2020, American Journal of the Medical Sciences
      Citation Excerpt :

      Interestingly, our patient exhibited high fever and decreased level of consciousness initially misdiagnosed as acute infectious encephalitis. This was supported by the fact that normal cytological and acellular CSF findings could not rule out the herpes encephalitis diagnosis. 9 Also, environmental factors such as warmer than average temperatures in the Mediterranean summer raised the possibility of the West Nile encephalitis. 10

    • Neuroimaging of Patients in the Intensive Care Unit: Pearls and Pitfalls

      2020, Radiologic Clinics of North America
      Citation Excerpt :

      Encephalitis is the presence of intracranial infection with parenchymal involvement, which can include the cerebral hemispheres (cerebritis) or cerebellum manifested by abnormal T2/FLAIR hyperintensity and swelling. Cerebritis of the medial temporal lobes, either unilateral or bilateral, has a special differential diagnosis, which includes herpes encephalitis (Fig. 8).32 Limbic encephalitis is an immune-mediated encephalitis sometimes associated with a systemic malignancy and has an overlapping appearance with herpes encephalitis, although it often does not enhance.33

    • Relapse of herpes simplex encephalitis in a patient with metastatic small cell lung cancer following scalp sparing whole brain radiotherapy

      2019, IDCases
      Citation Excerpt :

      As larger numbers of patients survived HSE, it became apparent that 10%–25% of survivors experience relapse or recurrence of neurologic symptoms despite adequate treatment with intravenous acyclovir [9]. Interestingly, most of these “relapsed” cases had no evidence of replicating virus neither in brain tissue nor viral DNA in CSF, suggesting an immune-mediated mechanism accounting for the recurrences of neurologic symptoms [10]. It is now believed that antibody against the N-methyl-D-aspartate receptor (NMDAR) is key factor in the pathogenesis of neurologic symptoms following recovery from the initial episode of HSE resulting in an autoimmune neurologic relapse [11] suggesting that only a minority (<5%) of adequately treated adult patients with HSE experience a “true” virologic relapse [12] making it a rare clinical entity.

    • Recurrent Herpes Simplex Virus Encephalitis after Epilepsy Surgery

      2019, Canadian Journal of Neurological Sciences
    View all citing articles on Scopus

    Disclosures: No relevant disclosures.

    View full text