Encephalitis

By Marcello Cherchi, MD PhD

For patients

In simple terms, the word “encephalitis” refers to inflammation of brain tissue. There can be many causes of encephalitis. In some cases encephalitis can cause eye movement abnormalities. Patients with encephalitis are usually very ill and may be cared for in an intensive care unit.

For clinicians

Overview

Encephalitis can be caused by numerous infectious agents and can be associated with a broad variety of antibodies.  Since encephalitis can affect any part of the brain, the symptoms can be variable.  Ocular motor abnormalities occur in encephalitis, but are not sensitive or specific for a particular infectious agent or antibody.

While one might expect there to be a one-to-one correlation between a particular infectious agent and a specific ocular motor abnormality, or between a particular antibody and a specific ocular motor abnormality, unfortunately no firm correlations have been identified.  Consequently, there is no ocular motor finding that can diagnose a specific infectious agent, or particular antibody, in encephalitis.

Introduction

Encephalitis is an immense topic. Here we will not provide a comprehensive review of its diagnosis and management. Rather, our goal is to give a sense of the breadth of the pathogens, antibodies, and ocular motor findings in encephalitis.

Pathophysiological mechanism of disease

In principle any area of the central nervous system can be affected by inflammation; involvement of the brain is termed encephalitis, and involvement of the spinal cord is termed myelitis. Encephalitis can occur separately from meningitis, or concomitantly (in which case it is termed meningoencephalitis). Inflammation itself can result from a variety of etiologies, such as infectious and autoimmune; in many cases the etiology of encephalitis remains undetermined. Neurons, glial cells and myelin can all be damaged by inflammation.

Some nervous system tissues exhibit selective vulnerability to certain inflammatory diseases. In other cases the source of inflammation can damage neural tissue indiscriminately.

Etiologies: infectious

A large number of infectious agents have been detected or suspected as causes of encephalitis. Many infectious encephalidities have been reported in association with ocular motor abnormalities, including:

  • Arbovirus (Suardi, Di Lauria et al. 2020)
  • Coronavirus (Luis, Hipolito-Fernandes et al. 2020)
  • Epstein-Barr virus (Demey, Martin et al. 1988, Hussain and Hussain 2013, Wade, Toupin et al. 2021)
  • Flavivirus (Pradhan, Pandey et al. 1999, Withana, Rodrigo et al. 2014)
  • Herpes simplex virus 1 (Hirst, Clark et al. 1983, Shaikh, Termsarasab et al. 2013)
  • Herpes simplex virus 6 (Carvajal, Verdeguer et al. 2001), Orientia tsutsugamushi (Karanth, Gupta et al. 2013)
  • West Nile virus (Malhotra, Ramanathan et al. 2014).

Etiologies: immune-mediated

In cases of encephalitis associated with ocular motor abnormalities (to be discussed below), many different auto-antibodies have been detected, including:

  • AMPA (Matthews, Schmitt et al. 2022)
  • CASPR2 (Joubert, Gobert et al. 2017)
  • DPPX (Doherty, Gold et al. 2017, Blackburn, Vernino et al. 2020)
  • GAD65 (Mirabelli-Badenier, Morana et al. 2012, Vale, Pedroso et al. 2015, Baizabal-Carvallo 2019, Muniz-Castrillo, Vogrig et al. 2020, Tsiortou, Alexopoulos et al. 2021, Zhou, Xie et al. 2022)
  • GD1b (Jeong, Nam et al. 2011)
  • GM1 (Jeong, Nam et al. 2011)
  • GQ1b (Jeong, Nam et al. 2011)
  • Hu (Saiz, Bruna et al. 2009)
  • KLHL11 (Bohm, Eggenberger et al. 2021)
  • Ma2 (Garcia-Reitboeck, Thompson et al. 2014)
  • mGluR65 (Zhang, Lian et al. 2023)
  • MOG (Olbert, Brunner et al. 2022)
  • NMDA (Tsuyusaki, Sakakibara et al. 2014)
  • Ri (Mitchell, Bakhos et al. 2015)

Clinical presentation

The clinical presentation of encephalitis depends on which areas of the brain are affected. Common presentations include cognitive changes, seizures and coma. Many descriptions of encephalitis do not mention whether any eye movement abnormalities are present, but it is likely that such abnormalities are under-reported because the clinical picture is dominated by more dramatic features.

Ocular motor examination

Many reports of encephalitis comment on the presence of ocular motor abnormalities, but often they are not described (Carvajal, Verdeguer et al. 2001, Mirabelli-Badenier, Morana et al. 2012, Hussain and Hussain 2013, Joubert, Gobert et al. 2017, Suardi, Di Lauria et al. 2020).

Fortunately many examiners have described in some detail the ocular motor abnormalities that can occur in association with encephalitides, such as:

  • Central positional nystagmus (Jeong, Nam et al. 2011)
  • Spontaneous down beat nystagmus (Shimizu, Weinberger et al. 1975, Hirst, Clark et al. 1983, Prasad, Brown et al. 2006, Saiz, Bruna et al. 2009, Shaikh, Termsarasab et al. 2013, Malhotra, Ramanathan et al. 2014, Tsuyusaki, Sakakibara et al. 2014, Vale, Pedroso et al. 2015, Baizabal-Carvallo 2019, Tsiortou, Alexopoulos et al. 2021, Wade, Toupin et al. 2021)
  • Gaze evoked nystagmus (Jeong, Nam et al. 2011, Karanth, Gupta et al. 2013, Alroughani, Thussu et al. 2015, Muniz-Castrillo, Vogrig et al. 2020, Olbert, Brunner et al. 2022)
  • Horizontal nystagmus (not further specified) (Withana, Rodrigo et al. 2014, Luis, Hipolito-Fernandes et al. 2020, Zhou, Xie et al. 2022, Zhang, Lian et al. 2023)
  • Ocular bobbing (Rudick, Satran et al. 1981)
  • Opsoclonus (Pradhan, Pandey et al. 1999, Blackburn, Vernino et al. 2020)
  • Optokinetic abnormalities (Furman, Brownstone et al. 1985)
  • Periodic alternating nystagmus (Davis and Smith 1971, Jeong, Nam et al. 2011, Bohm, Eggenberger et al. 2021)
  • Rebound nystagmus (Yoshimoto and Koyama 1991)
  • Reduced caloric responses (vestibular weakness) (Ito, Sakakibara et al. 2006)
  • Saccadic hypometria (Blackburn, Vernino et al. 2020)
  • Saccadic intrusions (Baizabal-Carvallo 2019)
  • Skew deviation (Mitchell, Bakhos et al. 2015)
  • Smooth pursuit abnormalities (Furman, Brownstone et al. 1985)
  • Torsional nystagmus (Blackburn, Vernino et al. 2020)
  • Spontaneous up beat nystagmus (Blackburn, Vernino et al. 2020)
  • Vertical nystagmus (not further characterized) (Demey, Martin et al. 1988, Saiz, Bruna et al. 2009, Jeong, Nam et al. 2011, Matthews, Schmitt et al. 2022)

This range of ocular motor abnormalities is remarkable, but also unsurprising given that encephalitis can affect nearly any part of the brain.

Down beat nystagmus is probably the most commonly reported ocular motor abnormality in encephalitis, and this finding localizes to the cerebellum. The cerebellum exhibits selective vulnerability to some disease processes, such as paraneoplastic syndromes.

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Page first published on March 17, 2023. Page last updated on December 26, 2023

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