Brain inflammation — known medically as encephalitis — remains one of medicine's most dangerous neurological emergencies. In a new invited Seminar published May 16 in The Lancet, Sarosh Irani, B.M., B.Ch., D.Phil., a Mayo Clinic neurologist and neuroimmunologist, outlines the latest advances in recognizing and treating both infectious and autoimmune forms of this serious condition. Here he explains what's driving this growing global threat, how new approaches are transforming diagnosis and treatment, and what it will take to improve outcomes for patients worldwide.

Encephalitis has been called an urgent global health threat. Why is this condition so important right now?

Encephalitis affects more than a million people worldwide each year and causes an estimated 100,000 deaths annually. The World Health Organization has described it as an "increasing global threat" and an urgent public health priority.

Some cases are infectious — triggered by viruses spread by mosquitoes or by re-emerging illnesses such as measles. Others are autoimmune, meaning the immune system mistakenly attacks the brain.

Over the past two decades we've learned that autoimmune forms are at least as common as infectious ones in developed countries. That represents a major shift in how we understand this disease.

What has changed in the way doctors diagnose encephalitis over the past decade?

Historically, encephalitis was thought to be almost entirely infectious. But we now recognize many autoimmune forms defined by specific antibodies targeting the brain. That has transformed diagnosis.

In our Lancet Seminar, we provide a practical clinical approach to help physicians quickly distinguish infectious from autoimmune causes. The goal is simple: help clinicians make the right call within the first 24 hours using the patient's history, brain imaging and spinal fluid testing.

Timing matters enormously. In herpes encephalitis, early antiviral treatment reduces mortality from roughly 70% to about 20%. In autoimmune encephalitis, our work has shown that even short delays in immunotherapy can worsen long-term outcomes.

By giving physicians a structured, bedside decision-making tool, we aim to reduce missed diagnoses and avoid unnecessary or inappropriate treatments. That's a direct example of Mayo Clinic's commitment to transform the practice — translating cutting-edge science into everyday clinical care.

Why is early spinal fluid testing so important?

Spinal fluid testing gives doctors a direct window into what is happening in the brain and is essential when serious inflammation is suspected. However, it is sometimes delayed because of concerns about complications.

We emphasize that, in most patients, early testing is safe and should not be postponed unnecessarily. Delays can mean lost time in starting antivirals or immune treatments — and in this condition, hours truly matter.

You describe emerging therapies, including targeted immune treatments and CAR-T approaches. Are we entering a new era of treatment?

Yes, that's exactly how I would describe it. Traditionally, we've used broad immune-suppressing medications for autoimmune encephalitis. These can work, but they affect many parts of the immune system and elsewhere, carrying multiple side effects.

Now we're seeing the development of more targeted therapies — including treatments that selectively remove harmful B cells or block specific immune pathways. Some experimental approaches are even designed to "reboot" the immune system in a precise way.

This aligns with Mayo Clinic's Precure vision. If we can understand what triggers the immune system to attack the brain in the first place, we move closer not just to treatment, but to prevention — and ultimately cure.

Your paper highlights patient-reported outcomes. Why is measuring recovery beyond survival so important?

Most patients now survive encephalitis. But survival is not the full story.

Many of our patients often experience long-term cognitive, emotional and physical challenges — including memory problems, fatigue, mood changes and difficulty returning to work or school. Traditional outcome scales, often borrowed from stroke care, do not fully capture these lasting effects.

Our team developed the first patient-reported outcome measure specifically for autoimmune cases. Listening directly to patients helps ensure we measure what truly matters and design treatments that improve quality of life — not just survival rates.

What are the biggest unanswered questions in this field today?

We still don't fully understand why autoimmune encephalitis begins. Identifying those triggers — genetic, environmental or infectious — is central to prevention.

Encephalitis costs an estimated $2 billion annually in U.S. hospitalizations alone, not counting long-term rehabilitation and caregiver burden.

The opportunity is enormous. Encephalitis is often called a "knife-edge" disease — devastating if missed, often reversible if caught early. We're bringing research, practical diagnostic tools and patient insights together to help doctors recognize it sooner, treat it more precisely and, ultimately, prevent it.

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