Understanding NORSE & FIRES
New Onset Refractory Status Epilepticus (NORSE) and its sub-type, febrile infection-related epilepsy syndrome, (FIRES) are rare, severe neurological conditions. Understanding their complexity helps guide treatment and support for patients and families facing these challenges.
What is NORSE?
In layman’s language, NORSE refers to the unstoppable, prolonged seizures that strike suddenly from out of the blue with no clearly identifiable cause in healthy people without epilepsy.
NORSE stands for New Onset Refractory Status Epilepticus where Status Epilepticus refers to the prolonged, life-threatening seizures. Refractory refers to the seizures that remain resistant to drugs that usually are effective in stopping them but not in these cases. And New Onset refers to the unexpected, sudden appearance of these seizures that seem to have no apparent cause in people who do not have epilepsy.
The consensus definition of NORSE, published in 2018, is complicated because the syndrome is so rare and remains poorly understood. NORSE is defined as a clinical presentation, not a specific diagnosis.
It is a presentation of a syndrome that may later be found to have one of a number of specific underlying causes. The term NORSE is often applied to cases after a process of elimination– after it has been concluded that the seizures were NOT the result of a clear acute or active structural, toxic or metabolic cause or relevant other preexisting neurological disorder. In layperson’s language: the seizures were NOT the result of, for example, a traumatic brain injury, a stroke or the effects of alcohol or recreational drugs.
Many tests to identify the cause of these seizures (that don’t have obvious cause) require up to 72 hours to complete. The most commonly identified underlying cause of NORSE is autoimmune encephalitis. In about half of the cases, the cause of the seizures remains unknown despite extensive testing. These cases are referred to as cryptogenic NORSE or c-NORSE.
NORSE is presumed to have several possible underlying causes, referred to as having heterogeneous etiology, but the tests by which to identify those causes have not yet been developed.
What is FIRES?
Febrile Infection-Related Epilepsy Syndrome (FIRES) is a subtype of NORSE in which patients experience a fever between two weeks and twenty-four hours before seizure onset. Once conceptualized as a pediatric syndrome separate from NORSE, FIRES is now defined as a subtype within the overall category of NORSE.
FIRES can affect both adults and children and is no longer considered a separate condition from NORSE.
NORSE is an umbrella term that includes FIRES. The incidence of NORSE has been estimated to be ~3200 cases in the US each year although that number is calculated from the expected cases of status epilepticus that are refractory and new onset. Because the terms NORSE and FIRES are relatively new and refer to a presentation as opposed to a formal diagnosis, cases may not be recognized or documented a such, and therefore NORSE is likely to be underreported.
Currently, inflammation and immune dysfunction are seen to play pivotal roles in the syndrome, but the exact mechanisms are not yet entirely understood.
The Urgency and Impact of NORSE
NORSE is a life-threatening syndrome that demands immediate intervention from critical care and epilepsy specialists experienced in its management. Rapid access to appropriate treatment is essential.
Treatment often includes placing the patient in a medically induced coma, which may last for weeks or even months. The condition carries a high risk of death and long-term complications.
Many survivors develop epilepsy and require intensive cognitive, psychological, and physical rehabilitation after leaving intensive care. While full recovery occurs in only a small number of cases, it is possible.
Other terms for NORSE & FIRES
The term NORSE is a relatively new one, the first reference to NORSE in a medical journal was in 2005. Since then researchers have used various terms to describe this syndrome (a condition characterized by a set of associated symptoms): super-refractory status epilepticus, autoimmune encephalitis, de novo refractory status epilepticus or presumed encephalitis with refractory status epilepticus. The terms devastating epileptic encephalopathy in school-aged children (DESC), acute encephalitis with refractory, repetitive partial seizures (AERRPS) and infantile hemiconvulsion-hemiplegia and epilepsy syndrome (IHHES) have been used to describe pediatric illnesses similar to FIRES. The common element in all these terms is the cascades of seizures that seem to come from out of the blue in healthy people with no history of epilepsy, and the refractory nature of these seizures they do not respond to traditional anti-epileptic drugs.
A report about NORSE written by Drs Gaspard and Hirsch filed with the National Organization for Rare Disorders (NORD) can be found here.
You can listen to an interview of Dr. Nicolas Gaspard about the nuanced changes in the conceptualization of NORSE reflected in the newly-proposed consensus definitions. We are grateful to Dr. Joseph Sirven, Editor-in-Chief of the Epilepsy Foundation's website, epilepsy.com, for conducting this interview as part of his Hallway Conversations series.
Why did this happen?
No one knows for certain why NORSE strikes some people and not others.
The exact cause of the disorder is similarly unknown and the best medical treatments for it are also not yet established. NORSE is a rare disorder with one estimate being around 3,200 cases per year in the U.S. Underreporting and misdiagnoses are likely since the term itself is new and not well established. There is no evidence as yet for a genetic basis for NORSE; and no reports of NORSE striking more than once in a family.
As of now, there is no established biological marker that distinguishes NORSE as a specific disease. It’s possible that this presentation of symptoms is a syndrome resulting from a number of different causes.
NORSE Glossary of Terms
The following are terms that may come up in your conversations with medical staff that you should know. (The NORSE Institute is grateful to Erica Sieg, PsyD, Northwestern University Feinberg School of Medicine for providing this content.)
Terms often used in medical conferences
Acquired brain injury vs Traumatic Brain Injury: Acquired brain injury is an umbrella term for any type of injury to a person’s brain. Traumatic brain injury is a specific type of acquired brain injury that refers to some force external to the person that causes injury such as a car accident, fall, assault, gun shot etc. that damages the brain. Some examples of acquired non-traumatic brain injury (that occur from within a person) include stroke, brain tumors, encephalitis, and NORSE and FIRES among others.
Breakthrough Seizures: Sudden unexpected seizures in someone who previously had achieved reliable seizure control with medications.
Cognition: Broad term for mental abilities (“thinking”) related to information processing such as attention, processing speed, working memory, language, visual spatial, problem solving, planning, and memory.
Comorbidities: Additional illnesses or all the illnesses present in a person, not just the primary one being discussed. For example, someone may have epilepsy and also have comorbidities of depression, anxiety, or cognitive impairment. Comorbidities can be physical, cognitive, or psychiatric.
Electroencephalography (EEG) Monitoring: the most common way to monitor brain functioning for seizure activity. It does not hurt and is not dangerous as it is only a recording device for brain waves. It does not transmit, shock, or produce any kind of electrical current. Electrodes (small metal recording devices) are placed on the surface of the scalp and secured with a safe glue or tape. Once in place, electrodes measure the electrical activity in the brain through the skull. The electrodes send the information by attached wires to a computer to be recorded and analyzed by doctors.
Epilepsy: Epilepsy is a disease characterized by an enduring predisposition to generate epileptic seizures. A seizure is one event (see below) and epilepsy is the disease involving recurrent, unprovoked seizures.
Function: What someone can do; how well they can perform or complete tasks.
Neurobehavior: Behavioral, emotional, or personality changes associated with changes in brain structure or function. Examples are aggression, irritability, apathy, crying, sadness, hallucinations, eating more/less, sleeping more/less, repeating the same activity multiple times, or not engaging in normal activities.
Neuroimaging: Any procedure that provides visual information about the structure of the brain. This includes brain scans such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) scan or single-photon emission computerized tomography (SPECT) among others.
Neurologic state: The state of a person’s central nervous system which includes the brain and spinal cord. When a change in this system occurs, immediate medical intervention is needed because the central nervous system regulates important aspects of the body’s internal environment like breathing and heart rate, processes all sensory information such as sight and sound, and is responsible for conscious awareness, voluntary body movement, thinking, learning, and feeling.
Seizure: Abnormal excessive or synchronous neuronal activity in the brain. In other words, an episode when the cells of the brain are too active or start acting together in ways that are atypical. This interrupts normal brain functioning and produces the associated symptoms of changes in awareness, thinking, moving, speaking, or feeling (the brain’s normal processes). Most seizures do not last longer than 2 minutes.
Status Epilepticus (“Status”): A medical emergency defined as a continuous seizure lasting more than 5 minutes, or two or more seizures without full recovery of consciousness between any of them. Essentially, this is when seizures last too long or don’t stop. This is dangerous because it can cause significant brain damage or even death.
This site has integrated most of the research in abbreviated form for non-medical readers. You can read what physicians are reading about NORSE by going onto Pubmed which is an archive of the biomedical and life science journal articles at the U.S. National Institute of Health National Library. You can start your search here. A list of relevant publications curated by Dr Gaspard is also available on the Medical Professionals segment of this website.
Things to Consider:
Diagnostic Checklist, Medical Conferences, Palliative Care
NORSE is not a specific diagnosis. The proposed consensus definition defines NORSE as a “clinical presentation.” This assessment of NORSE is arrived at by a process of observations of the patient, extensive medical testing and elimination of other causes. This process takes time for tests to be administered, sent to laboratories (often off premises) and then the wait for results. The frustrating thing is that even if or when doctors conclude that the patient has NORSE, the precise cause of NORSE may not ever be identified, and a specific treatment protocol to follow has not been formally established for NORSE.
Many hospitals have their own protocol for treating refractory status epilepticus. The Medical Advisory Board of the NORSE Institute has generated a preliminary Diagnostic Checklist for NORSE. Both the checklist and a treatment protocol for convulsive status epilepticus developed at Yale-New Haven Hospital are available on the website’s Medical Professional resources which may be shown to your doctors. As a disclaimer, it should be clear that each patient requires treatment unique to that patient. These protocols developed by doctors who have experience treating NORSE are offered only as a starting reference point other centers may wish to consider.
Request Periodic Medical Conferences. A patient with NORSE symptoms will most likely be seen by a number of doctors: neurologists, specialists in critical care, epilepsy, nephrology and cardiology as the seizures, the anti-seizure and anesthetic drugs and the prolonged immobility can cause negative effects on the body. Try to identify the one or two doctors who lead the case to help you integrate and interpret their information. Ask for a medical conference with this lead doctor and other doctors key to the case to assess what is currently known and expected to happen. Understand that early in the case, the doctors are still struggling to identify the cause of the illness to determine the best treatment. That identification process is largely a process of elimination that takes time. Keep a daily record of your own observations and questions to ask at the conference. The condition of your loved one will likely change over time. Request additional medical conferences to be informed of the patient’s current condition and planned course of treatment.
Consider Involving a Palliative Care Team. A palliative care team can help support communication among the medical teams and between the doctors and the family. There are misconceptions on the part of both the public and doctors about palliative care. Many times a palliative care team or a palliative care approach is not called in until death is imminent. As a result, palliative care is often erroneously associated exclusively with end of life care. Palliative care is relevant when illness is life-threatening and life-altering for survivors. The World Health Organization’s definition of palliative care is “an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.” It “intends neither to hasten or postpone death “and is applicable early in the course of illness, in conjunction with other therapies that are intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications.” Read full definition here
Full recovery from NORSE is possible. Requesting palliative care services does not negate that hope. Morbidity and mortality are also possible. Early involvement of a palliative care team can help doctors and families be on the same page regarding the patient’s current condition, and what to hope and plan for given the expected outcomes. It can be upsetting to hear that doctors are uncertain of the cause and the outcomes for a patient. NORSE is full of uncertainty for both families and doctors. You can read about the differing perspectives on communication here. Frequent and frank discussion of what is known and what remains uncertain may help doctors and families plan together for the best course of action for the patient.
Listen to Recordings from our Family & Scientific Conferences
Contribute Your Expertise
We invite clinicians, researchers, and medical professionals to contribute to the growing knowledge base on NORSE and FIRES. If you have published articles, recorded podcasts, or developed insights or resources that could benefit others, please get in touch.
If you have been directly involved in the clinical care of a NORSE patient and wish to be listed in the NORSE Medical Directory, please get in touch with us by completing the form.
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Too many families face this devastating illness with no answers, limited treatments, and little support. The NORSE Institute is a 501(c)(3) charitable organisation through the fiscal sponsorship of CURE Epilepsy.
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