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Encephalitis: help from guidelines
  1. Nicholas W S Davies1,
  2. Frances Sanderson2
  1. 1Department of Neurology, Chelsea and Westminster Hospital and Imperial College Healthcare NHS Trust, London, UK
  2. 2Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Dr Nicholas W S Davies, Department of Neurology, Chelsea & Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK; Nicholas.davies{at}

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Physicians frequently bemoan the lack of effective therapeutic interventions in neurology. However, herpes simplex virus (HSV) encephalitis represents a medical success story: mortality in untreated HSV encephalitis is ≈70%—with high-dose intravenous acyclovir it falls to <20%.1

In the UK, acute encephalitis is a rare syndrome. Exact figures are not known despite the requirement by statute for notification of clinical suspicion. It can affect all age groups, with highest incidence in infants and those aged over 65 years. Most cases are sporadic. Recent data from England show that 42% had an infectious aetiology, 21% an immune-mediated cause, whereas 37% had no identifiable cause.2 One-quarter of the cases were caused by acyclovir-sensitive viruses (HSV type 1 and 2; varicella zoster virus). However, the morbidity and mortality was high across aetiologies, including those of unknown cause. Of those with HSV encephalitis, 11% died and at 6 months only 39% had a good outcome (Glasgow outcome score >4). The worst outcome was seen in patients identified retrospectively to have had an antibody-associated encephalitis (voltage-gated potassium channel antibody or N-methyl d-aspartate receptor antibody encephalitis).

How can we improve outcome? For HSV encephalitis, early commencement of antiviral therapy is important3; it seems reasonable that early recognition and treatment might improve the outcome for other infectious and immune-mediated aetiologies as well. Where do problems occur along the diagnostic pathway? Whereas the cardinal symptoms and signs of acute meningitis are well known to the UK general public, are those in the frontline of hospital medicine as much well-versed in recognising acute encephalitis? The two-millennia-old Hippocratic aphorism ‘It is better that a fever should succeed a convulsion than a convulsion follow a fever’ shows that a history now known to indicate brain infection, in antiquity, was recognised to portend a worse outcome.4 In the 21st century, the triad of fever, confusion and seizures should prompt any clinician to consider the diagnosis of acute encephalitis. But encephalitis has many mimics; distinguishing these can be challenging, often necessitating a battery of specialist investigations. In some cases, perhaps having started antimicrobials gives the physician false reassurance, prematurely halting the diagnostic process. Others have highlighted that important confirmatory investigations can be unnecessarily delayed.5

There is often confusion as to the positive and negative predictive values of investigations. Given that the mimics of viral encephalitis are more frequent than the syndrome itself, difficulties arise in trying to exclude it—especially that related to HSV. In the authors’ experience, it is not uncommon for patients with low probability of HSV encephalitis to receive prolonged courses of intravenous acyclovir. Therefore a common problem is when to stop empirical acyclovir treatment. Can a cerebrospinal fluid (CSF) without pleocytosis and negative for HSV DNA by PCR reliably exclude the diagnosis? Can MR brain imaging exclude HSV encephalitis? And in proven cases of HSV encephalitis, how long should treatment with high-dose intravenous acyclovir continue?

The recently published national guidelines by Solomon et al1 seek to provide guidance for these diagnostic and management questions. It includes a useful summary algorithm (figure 1). The authors stress the importance of noting the time point in the disease process when an imaging or CSF test is performed, in order to assess its predictive value. They provide criteria for excluding HSV encephalitis and have adopted the 1996 European consensus guidance for duration of acyclovir treatment.6 The latter requires the absence of HSV DNA in CSF before halting acyclovir therapy. Perhaps the most controversial aspect to the guidelines is the necessity, in many cases, for repeat lumbar puncture—in order to reliably exclude HSV encephalitis and, in those where this is the final diagnosis, to guide treatment duration. This advice is based on expert opinion alone.

Figure 1

Algorithm for the management of patients with suspected encephalitis. Reprinted from Journal of Infection 2012;64:347–73. Solomon T, Michael BD, Smith PE, et al. Management of suspected viral encephalitis in adults. Association of British Neurologists and British Infection Association National Guidelines, with permission from Elsevier.

Are there caveats to these guidelines? For any doctor, especially a junior trainee, to distinguish a predominantly meningitic from a meningoencephalitic illness can be very difficult. Therefore, in practice, these guidelines will need to be used in conjunction with the well-established protocols for the management of acute bacterial meningitis.7 Furthermore, they were written for suspected viral encephalitis; they provide neither management recommendations for the mimics of the syndrome nor detailed information on the treatment of all forms of inflammatory encephalitis. Appropriately, there is information regarding the more recently recognised antibody-associated forms of encephalitis.

These guidelines are published at a time of change in acute service provision and hospital care in the UK: commissioners are insisting on 24/7 acute services with early specialist input and radiology support. This adds weight to recommendations here for early neurologist input and MR scanning within 48 h and greatly increases the likelihood of good practice becoming the norm. The national move to integrated care should also serve to support key recommendations on discharge planning and ongoing rehabilitation.

We hope that this guideline will stand out among the many and, much as with the British Infection Society's meningitis algorithm in 2003, help to transform the management of this important condition. There are plans to update it in 2017; we are only just beginning to recognise the clinical spectrum of antibody-associated encephalitis and at least two important trials—on the roles of corticosteroids and of prolonged oral valacyclovir in managing HSV encephalitis, will have been reported by then.



  • Conflict of interest Both authors assisted in the development and writing of the guidelines.

  • Competing interests None.

  • Provenance and peer review Commissioned. Internally peer reviewed.

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