By Hai H. Hoang, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: Herpes simplex virus is a common cause of encephalitis worldwide. When treated promptly, the mortality rate decreases from 70% to 15%, but many patients remain disabled. This multicenter cohort study analyzed magnetic resonance imaging in patients diagnosed with herpes simplex encephalitis admitted to the intensive care unit to identify factors associated with poor outcome at 90 days.
SOURCE: Sarton B, Jaquet P, Belkacemi D, et al. Assessment of magnetic resonance imaging changes and functional outcomes among adults with severe herpes simplex encephalitis. JAMA Netw Open 2021;4:e2114328.
Herpes simplex virus (HSV) is a common cause of encephalitis worldwide. Although treatment is available, the mortality rate remains at 15%, but many patients are left with disabling symptoms. The diagnosis of HSV encephalitis is confirmed with cerebrospinal fluid (CSF) detection of HSV polymerase chain reaction (PCR). Other supportive tests include brain magnetic resonance imaging (MRI) to rule out mimics. Typical radiological MRI findings include the presence of asymmetric changes in signal intensities in the mesial temporal lobes, inferior frontal lobes, and insula. Despite advancements in diagnostics, there has been less research on prognostic markers for patients with HSV encephalitis. To address this question, a multicenter cohort study of patients diagnosed with HSV encephalitis was conducted in France. The study looked at brain MRI data and patients’ functional outcomes at 90 days after intensive care unit (ICU) admission.
Observational data were retrospectively collected from the electronic medical record between 2007 and 2019 for patients diagnosed with HSV encephalitis at 34 ICUs in France. Patients were included if they were admitted to the ICU, had CSF positivity for HSV PCR, completed brain MRI, and had follow-up data at 90 days. Data extracted from the chart included patient demographics, patient history, and clinical, laboratory, and brain electrophysiologic data. In addition, baseline health status was graded by Knaus score. Disease severity was denoted with Simplified Acute Physiology Score II and the Sequential Organ Failure Assessment score. Glasgow Coma Scale (GCS) score also was calculated at the time of ICU admission. Patients were included if they had a brain MRI within the first month of ICU admission. The extent of brain lesions was scored on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences. Functional outcomes were graded at 90 days after ICU admission using the Modified Rankin Scale (mRS). The cohort was broken down into poor functional outcome (mRS 3 to 6) vs. good functional outcome (mRS 0 to 2).
Between 2007 and 2019, 138 patients met study inclusion criteria, with a median age of 62.6 years. Functional status before ICU admission was good (Knaus class A or B) in 96.4% of cases. Median time to MRI acquisition was one day. Abnormal FLAIR hyperintensities were seen in 97.8% of cases. FLAIR lesions extending into more than three lobes were identified in 38.4% of patients. DWI abnormalities detected in more than three lobes were identified in 26.9% of patients. Thalamic involvement was noted in 46.3% of patients.
At 90 days, 68.8% of patients had a poor outcome, including death in 11.6%. The odds of an unfavorable outcome at 90 days were higher in patients with extensive brain lesions, both on FLAIR and DWI sequences. Multivariate analysis found that FLAIR sequence signal on more than three brain lobes (odds ratio [OR], 25.71; 95% confidence interval [CI], 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), extensive bilateral parenchymal restricted diffusion patterns (OR, 3.17; 95% CI, 0.64-17.65), and focal diffusion signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were associated with increased odds of unfavorable outcome.
With predictive modeling machine learning methods, the detection of bilateral DWI abnormalities was associated with worse functional prognosis (87.2% of patients). Among patients without bilateral diffusion abnormalities (absence of abnormality or unilateral hypersignal), DWI hyperintensities in the left thalamus were associated with poor outcome, particularly in older patients (100% of patients aged > 60 years). Brain hemorrhages and blood-brain barrier disruption (detected by T2*-weighted and contrast-enhanced T1-weighted sequences, respectively), were not associated with poor functional outcomes.
This is the largest study to date that evaluated functional outcomes in patients with HSV encephalitis based on brain MRI data. A strength of this study is the ability for clinicians to provide a general predictive outcome for their patients by identifying the number of involved lobes on brain MRI, with more than three lobes portending to a poor prognosis. However, there are limitations. Specifically, the study’s retrospective design and lengthy study inclusion period, which do not allow for consistency of neuroimaging procedures or clinical care across this long period of time.