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  • Writer's pictureP.K. Peterson

Encephalitis: What Is It and How to Avoid It

“Encephalitis affects people across the lifespan, has high rates of morbidity and mortality, and results in significant neurological sequelae with long-term consequences to quality of life and wider society.”

Julia Granerod, et al, University of Liverpool, Liverpool, United Kingdom


“Avoidance has never been a great tactic in solving any problem. For most situations in life, not addressing what's going on only makes matters worse.”

Luvvie Ajayi, Nigerian–American author, speaker, and digital strategist




Most Germ Gems readers have heard of encephalitis—inflammation of brain tissue— and know it is a serious condition. (The term is derived from Greek enkephalos [brain] and itis [inflammation].) But, I suspect many readers do not know what causes the disease (the etiology) or how it develops (the pathogenesis). My goal this week is to fill you in on both. In today’s post, I provide a brief summary of the etiology and pathogenesis of encephalitis and suggest ways to avoid this serious infectious disease.

Different kinds of brain inflammation.  Encephalitis refers to inflammation within the parenchyma (substance) of the brain. This is in contrast to inflammation of the membranes that cover the brain (“meningitis”) or inflammation of the fluid filled structures deep within the brain (“ventriculitis”). These sites can be inflamed at the same time, however. For example, meningoencephalitis is an inflammation of the brain substance and its membranous covering. (Tissue damage caused by inflammation isn’t unique to the brain; it’s also seen in a multitude of other pathological conditions, e.g. arthritis, pneumonitis, cellulitis, myocarditis, etc.)


Causes of encephalitis.  Viruses that attack the brain cause a large majority of cases of encephalitis. SARS-CoV-2, the virus that causes COVID-19, and the monkey pox virus (mpox) are the most recent additions to the list of viruses that cause encephalitis. Some of the viruses on this list, e.g. measles, mumps and rubella, have a decreased incidence due to vaccination. Now the most common viral etiologies of encephalitis include herpes simplex virus (HSV) types 1 and 2, varicella virus (VZV), enteroviruses, and HIV.  


Several zoonotic infections are responsible for the most serious cases of encephalitis. These include three viruses that are transmitted by infected bats or other animals—rabies virus (close to 100% fatal), Nipah virus (60% mortality), and Ebola virus (55% to 60% mortality).


Arboviruses—a group of viruses transmitted by arthropods (mosquitos and ticks)—are another significant cause of encephalitis. These include West Nile virus and Japanese encephalitis virus (JEV) that are carried by mosquitos, Powassan fever virus—a tick-borne encephalitis, and Zika and chikungunya, emerging viruses transmitted by mosquitoes.


In addition to inflammation provoked by infectious agents, autoimmune encephalitis—a group of  disorders involving the brain— is increasing around the world. In these disorders, cells of the body’s immune system mistakenly attack healthy tissues in the brain. The cause of autoimmune encephalitis is in most cases unknown.


While it is essential to establish the cause of encephalitis, the percentage of cases of encephalitis with no known etiology is surprisingly large, ranging from 32% to 75% depending on the area of the world from which the data are reported. As pointed out in a December 2023 article in Clinical Infectious Diseases, “Global Landscape of Encephalitis: Key Priorities to Reduce Future Disease Burden,” the true incidence of encephalitis is currently unknown due to inaccurate reporting systems. Nonetheless, the importance of encephalitis has grown over recent years due to the impact of climate change, especially because it promotes vector-borne infections.

 

Before describing the clinical features of encephalitis, a brief description of the pathogenesis of the disease is in order. In other words, how the brain itself contributes not only to its self defense but can also play a role in brain injury.


The battlefield. The human brain contains around 86 billion neurons and roughly the same number of supporting cells called glia. The glial cells include astrocytes, microglia, and oligodendrocytes.

Microglia are resident immune cells in the brain. Like macrophages in the body, when microglia become activated, they can produce abundant amounts of inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species. While these inflammatory mediators play a role in defense of the brain against foreign invaders (microbes), they can also contribute to brain damage.


Thus, in addition to immune cells from the body (lymphocytes, neutrophils, and monocytes) that are summoned into the brain for defense against invading microbes, glial cells that are already stationed in the brain parenchyma can contribute substantially to the inflammatory process called encephalitis.


Clinical manifestations of encephalitis. The clinical manifestations of encephalitis are diverse and include fever, headache, altered mental status (confusion, memory impairment), changes in personality, focal neurologic deficits, seizures, and cognitive dysfunction. Symptoms can occur within a few days or up to several weeks after a viral infection.


A medical evaluation is needed to confirm the diagnosis. Diagnostic measures typically include analysis of cerebrospinal fluid (obtained by lumbar puncture), serologic testing, polymerase chain reaction assays, cultures, and radiologic techniques, like magnetic resonance imaging. As a rule, consultations by a neurologist and an infectious diseases specialist are required.


Treatment. Prompt diagnosis and treatment are essential to improving outcomes. Treatment may include antiviral drugs or anti-inflammatory drugs. Hospital care is usually necessary.


In all suspected cases of herpes encephalitis (caused by HSV-1 or HSV-2), the Infectious Diseases Society of America recommends initiating empiric antiviral therapy with acyclovir before the diagnosis is established. These viruses and the related herpes group virus VZV, the cause of chickenpox and herpes zoster, are the only viruses for which a specific antiviral therapy exists. (This is both a surprising and disappointing fact given the large list of viruses that cause encephalitis.)

How to avoid encephalitis. The therapeutic armamentarium against most causes of viral encephalitis is limited. But the good news is that there already are vaccines that are routinely administered that prevent encephalitis caused by some of these infections. These vaccines include the MMR (measles, mumps, rubella), VZV, JEV, dengue, SARS-CoV-2, and mpox. In addition, when clinically indicated, there is a vaccine that works against rabies—the most dreaded viral enemy of all.


There are also certain behavioral measures to take to protect yourself from mosquito or tick bites. You can: stay out of high risk, wooded areas; wear protective clothing; use sprays containing DEET; and keep the area around your home free from stagnant or standing water—a perfect breeding ground for mosquitos.


But for those readers who think that avoidance isn’t a perfect strategy for solving the problem of encephalitis, be patient. In 1796, Edward Jenner first vaccinated against the variola virus—the cause of smallpox (and also a cause of encephalitis). One hundred and eighty-four years later, the World Health Organization declared its campaign to eradicate smallpox a success. It may take time (hopefully not 184 years), but with persistence and vaccines, we should be able to relegate other viral causes of encephalitis to the history books.  

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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