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

Abstract

ObjectivesTo 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.MethodsThe 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.ResultsTemporal 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.ConclusionsThis 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.

Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study

“…For the main analyses, patients in each cohort were categorised into three diagnostic groups: (i) HSV encephalitis (referred to as 'HSV'), (ii) Encephalitis of Other Identified Causes (referred to as 'Other'), and (iii) Encephalitis of Unknown Cause (referred to as 'Unknown'). This was done according to predetermined case definitions for HSV and other infectious causes [25][26][27] and autoimmune encephalitis [28]. Medical notes and discharge letters were additionally reviewed by the study's panel of infectious disease and neurology specialists.…”

“…Long-term outcome cohort. Patients in the long-term outcome cohort were identified by consultants across ENCEPH UK hospital sites, from the Public Health England study database [2] or they self-referred in response to a notice by the Encephalitis Society [27]. There were 81 https://doi.org/10.1371/journal.pone.0230436.g001…”

“…In the short-and medium-term outcome cohort, MRI scans were obtained during the course of clinical care [27]; the scan closest in date to the first neuropsychological assessment was analysed.…”

Protocol for DexEnceph: a randomised controlled trial of dexamethasone therapy in adults with herpes simplex virus encephalitis

“…23 However, because corticosteroids cause immunosuppression, which in theory facilitates increased viral replication, their role is uncertain. 32 In other brain infections, including bacterial meningitis and tuberculous meningitis the benefit of corticosteroids has been demonstrated in large clinical trials. 33 For HSV encephalitis the potential benefit of using corticosteroid as an adjunct to aciclovir therapy has been suggested from small case series and retrospective comparisons, but there has been no prospective randomised study reported.…”

“… 23 However, because corticosteroids cause immunosuppression, which in theory facilitates increased viral replication, their role is uncertain. 32 …”