A note from the editor:
This section departs from most disease sites in that it is written as if I were speaking directly to you. I assume you have a family member or friend who is currently experiencing symptoms that suggest NORSE, and you are frightened and confused by this life-threatening illness that seems to have come from nowhere. It may seem you and your loved one are alone in a surreal universe. Or you are looking for resources for your NORSE survivor where few people have heard of NORSE.
My son, Daniel, was 22 years old when he died of what was suspected to have have been NORSE in 2013. Frustrated by the lack of knowledge and communication of his illness, I co-founded the NORSE Institute with Lawrence J Hirsch, MD (Yale) and Nicolas Gaspard, MD, Ph.D (Erasme Hospital, Brussels - Yale) in 2015 and created this website.
What follows is a list of basic terms, links to relevant articles and strategies to consider while your loved one is hospitalized—information I wished I had when my son was ill. Information regarding NORSE survivors is generously provided by other NORSE families, patients and professionals. There is still so much that remains unknown about NORSE.
Contributions of your NORSE experience to improve this evolving site are welcome on the Comments page. One hundred percent of the money donated on this site is directed to a fund for NORSE research at the National Organization for Rare Disorders (NORD.)
Nora Wong, Executive Director, Editor-in-Chief
What is NORSE?
NORSE is the abbreviated term or acronym for new onset refractory status epilepticus. In everyday language, it is a life-threatening condition requiring emergency treatment that comes seemingly from out of the blue (new onset), characterized by a prolonged seizure or a cluster of seizures without recovery in between (status epilepticus) without clear cause despite extensive medical testing. The seizures do not respond to the first and second lines of established medical treatments (refractory). Although the cause for the illness is eventually found in about half the cases (usually autoimmune or paraneoplastic encephalitis), in the balance of the cases, the cause is never found and is often termed “cryptogenic” NORSE or NORSE of unknown etiology.
After at least two anti-seizure drugs fail to stop the seizures, patients are typically placed in a coma with anesthetic drugs to protect their brains from the effects of the seizures (often referred to as a medically-induced coma). The hope is that after this period of quiet, the brain has calmed. At some point, doctors carefully reduce the anesthetic drugs, checking for the return of seizures, a process sometimes referred to as "weaning" the patient away from the anesthetics.
The consequences of NORSE vary from rare, full recovery, to mild to significant neurological deficits (morbidity) and death (mortality). Most survivors require extensive rehabilitation therapy and develop epilepsy despite no previous history of epilepsy.
NORSE vs FIRES
According to the newly-proposed consensus definitions of NORSE and FIRES, FIRES, Febrile Infection-Related Epilepsy Syndrome, is a subtype of NORSE that is preceded by a fever. Important: FIRES is not the same as simple febrile seizures common in childhood which are considered benign and self-limiting. Previously, the term NORSE was used to refer to new onset refractory status epilepticus in adults, and the term FIRES was referred to the same condition in children. Now there are no age limits to either condition. Children can have NORSE and adults can have FIRES. Everyone with FIRES, by definition, also has NORSE. The distinguishing characteristic of FIRES is a fever starting between 2 weeks and 24 hours prior to the onset of refractory status epilepticus. NORSE has been observed in all ages but is seen predominantly in young adults and children.
FIRES had been considered a separate entity from NORSE until recently. Even though the proposed consensus definitions linking the two and placing FIRES as a subtype of NORSE have been published and reviewed and endorsed by the Critical Care EEG Monitoring Research Consortium, the diffusion of information is slow. There are still physicians who have never heard of NORSE or FIRES; there are physicians who still think FIRES occurs only in children.
Other terms for NORSE and 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.
These details are from a report on NORSE written by Drs Gaspard and Hirsch filed with the National Organization for Rare Disorders (NORD) that can be found here. An abstract of the article proposing consensus definitions for NORSE and FIRES 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.
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: NORSE Diagnostic Checklist, Medical Conference, 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 many 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.
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.
Despite the fact that the patient never had epilepsy previously, if a diagnosis of NORSE has been given, the patient currently has a disorder that falls under the disease category of epilepsy. A description of epilepsy is here:
Epilepsy is characterized by seizures, but seizures are not all the same. Status epilepticus is considered the most extreme form of seizure, marked by abnormally prolonged seizures that can have severe long-term neurological consequences including death. The knowledge about status epilepticus (sometimes shortened to "status" or "being in status") is evolving such that a revised definition of the term was issued in the fall of 2015 by the International League Against Epilepsy.
Patient outcome refers to the condition of the patient at the end of the disease process or medical treatment. Sometimes doctors will talk about short-term outcomes and long-term outcomes. Functional outcome refers to the specific activities the patient will be able to do at the end of the disease process or medical treatment. Since NORSE patients can experience a range of outcomes from full recovery, to mild to severe brain deficits, to death, ongoing evaluation and discussion of the patient's estimated functional outcomes are vital. It should be noted, however, that doctors can seldom predict the arc of any disease with accuracy. This is even more so in the cases of NORSE. There simply is not enough information about the disorder to form a broad basis of prediction for the way NORSE will proceed and how the patient will end up. So, if the doctors say they simply don't know what the patient outcomes are presently, understand they are probably being candid rather than evasive. Ask again at a later point in time.