Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

Abstract

Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

Keywords: HSV; NMDA receptor; aciclovir; encephalitis; meningitis; steroids.

Fig. 1

Management of patients with suspected herpes simplex virus-1 encephalitis (HSVE). Adapted from Venkatesan and Geocadin [101]. cEEG = continuous electroencephalography; CSF = cerebrospinal fluid; ICP = intracranial pressure; ICU = intensive care unit; PCR = polymerase chain reaction; SE = status epilepticus

Fig. 2

Magnetic resonance imaging in acute herpes simplex virus-1 encephalitis. (A) Diffusion restriction on diffusion-weighted imaging (DWI) in the left mesial temporal lobe that corresponded to (B, C) fluid-attenuated inversion recovery (FLAIR) hyperintensity. (D) On day 8, with clinical deterioration, there was increased fluid restriction on DWI in the left mesial temporal lobe with tracking along the cortical ribbon that corresponded with (E, F) increased FLAIR hyperintensity and swelling

Fig. 3

Central nervous system autoimmunity following herpes simplex virus-1 encephalitis. (A–C) Extensive patchy postgadolinium enhancement involving the gray and white matter of the temporal and frontal lobes, and corpus callosum. (D–F) Corresponding fluid-attenuated inversion recovery (FLAIR) sequences demonstrate left > right temporal lobe cystic encephalomalacia and FLAIR hyperintense lesions