Research Article: A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Sylviane Defres, Simon S. Keller, Kumar Das, Rishma Vidyasagar, Laura M. Parkes, Girvan Burnside, Michael Griffiths, Michael Kopelman, Neil Roberts, Tom Solomon, Nancy M. Sawtell.


To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy.

The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting.

Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids.

This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

Partial Text

Herpes simplex virus (HSV) encephalitis is the most common infectious cause of sporadic encephalitis [1–4]. It leads to haemorrhage, necrosis and extensive oedema, characteristically of the medial temporal lobes, and also additionally extends to affect other limbic areas including insular, cingulate and inferolateral frontal cortices [5]. These changes are best visualized by use of Magnetic Resonance Imaging (MRI) [6]. Although a rare disease with incidence rates of 1 per 250–500,000 [7], the impact of HSV is disproportionately large with huge socioeconomic demands on patients, their carers and the health services [8–9].

There were ten patients who had at least one repeat MRI within 4 weeks of the admission scan. Of these, four could not be analysed: three patients did not have coronal T2-weighted FLAIR scans performed on both sets of scans and one patient had poor quality images on the follow up T2-weighted FLAIR scan (Fig 2).

In this small study of HSV encephalitis most patients on standard therapy had an increase in temporal lobe volume (three out of five) and of overall FLAIR-identified oedema (four out of five) during their acute hospital admission. However, a decrease in temporal lobe and oedema volume was observed in both patients who received corticosteroid therapy. Although the numbers are small in this study, the difference in the total oedema volumes between the patients not treated with corticosteroids and those that were, appears interesting and warrants further study




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