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

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Fig 1. Image using the easymeasure stereology, point counting software showing the landmarks for temporal lobe measurements.

(1) where the lateral ventricle splits into the temporal and frontal horns as the posterior limit for the right temporal lobe in a HSV encephalitis patient; (2) the mid point of the right temporal lobe measurement (in yellow the previously calculated left temporal lobe calculation); (3) the anterior limit of the temporal lobe and (4) the mid point section in (2) showing the volume of the overall damage including that outwith the temporal lobe, where HSV is seen to affect the right temporal lobe on this slice.

Fig 2. Flow chart of inclusion of patients in this study.

Fig 3. Change in volume of most affected temporal lobe over time.

Patients 1 and 3 received corticosteroids during their care in hospital.

Fig 4. Change in volume of total oedema over time.

Patients 1 and 3 received corticosteroids during their care in hospital.

Fig 5. Coronal T2-weighted FLAIR images of a 45 year old woman with HSV encephalitis (Patient 3).

On day 7 of admission a five-day course of corticosteroids was started. The same image slice is depicted from the day 2 scan (Image 1), from day 6 (Image 2) and from day 21 (Image 3)