New-onset refractory status epilepticus

What causes new-onset refractory status epilepticus (NORSE)?

The cause of status epilepticus (SE) can be found during initial tests in about 80% of cases. The remaining cases are classified as new-onset refractory status epilepticus (NORSE). Further, more extensive testing finds a cause in about 40% of NORSE cases, including autoimmune encephalitis paraneoplastic encephalitis, other known inflammatory or autoimmune diseases, rare genetic disorders including metabolic disorders, and uncommon viral infections. The cases that continue to have an unknown cause are classified as cryptogenic NORSE, which includes FIRES.

Some researchers believe cryptogenic NORSE, including FIRES, may be an inflammatory disorder. Others suggest that an unidentified brain infection may cause some cases. Currently there is no evidence that NORSE runs in families (hereditary), but researchers suspect changes in certain genes may increase a person's risk for developing NORSE. However no associated genetic changes have yet been found.

Last updated on 05-01-20

How is new-onset refractory status epilepticus (NORSE) diagnosed?

New-onset refractory status epilepticus (NORSE) is not a specific diagnosis but rather a clinical presentation or condition. Therefore a person has NORSE when they do not have a previous history of seizures, but developed seizures that progressed over a few days to status epilepticus (new-onset SE). In NORSE, the SE does not respond to anti-seizure medications (refractory SE) and it does not have a clear or obvious cause found during initial testing. Since there is no specific test to determine if a person has NORSE, other causes of the seizure activity must be ruled out (excluded). Common causes ruled out in the initial testing include changes in the brain structure due to trauma or stroke, metabolic imbalances, alcohol or drug intoxication, central nervous system (CNS) infections, and alcohol withdrawal. Tests may include imaging studies such as CT scan and MRI, various blood tests, and CSF studies.

If initial testing does not find a cause, further, more extensive testing will be performed to rule out rare causes of new-onset refractory SE, such as known inflammatory and autoimmune diseases, rare genetic disorders including metabolic disorders, and less common viral infections. The NORSE Institute provides a suggested Diagnostic Checklist.

When extensive testing does not find a cause, the condition is called cryptogenic NORSE. FIRES is a sub-type of cryptogenic NORSE. People with FIRES have a fever a day to two weeks before the seizures begin. Even though a fever may or may not be present at the time seizure activity begins, FIRES has not been found to be caused by any known infection.

Last updated on 05-01-20

What is the long term outlook for people with new-onset refractory status epilepticus (NORSE)?

New-onset refractory status epilepticus (NORSE) can cause significant brain damage and death. Between 20-30% of people with cryptogenic NORSE, including those with FIRES, do not survive the prolonged, super-refractory status epilepticus (SE), also called the acute phase, most often due to complications of being in an extended medically-induced coma, having prolonged, uncontrollable seizure activity, and/or being on a "breathing machine" (ventilator).

Many survivors of cryptogenic NORSE, including those with FIRES, are left with long-term mental and/or physical disabilities and lifelong epilepsy. This is referred to as the chronic phase of NORSE. Mental disabilities range from mild to severe and may include lower IQ, memory problems, learning disabilities, difficulties with language, difficulties controlling emotions, and behavior problems. Physical disabilities include difficulties controlling movement. In a majority of cases, the epilepsy continues to be difficult to control (refractory). Some people may die in the chronic phase due to having a severe seizure. In some cases, people with NORSE make a full recovery and are able to resume their previous lifestyle.

Last updated on 05-01-20

How might new-onset refractory status epilepticus (NORSE) be treated?

Treatment for NORSE (including FIRES) requires being cared for in an intensive care unit, at least until status epilepticus (SE) subsides and consciousness is regained. If an underlying cause of new-onset refractory status epilepticus (NORSE) is identified, treatment will include addressing the cause. There is no standard treatment for cryptogenic NORSE (when the cause cannot be found).

NORSE does not respond to standard treatment of status epilepticus (SE). Standard treatment would normally involve benzodiazepines followed by a standard anti-seizure medicine such as valproic acid, phenytoin, levetiracetam, phenobarbital, or lacosamide (preferably given intravenously). NORSE requires additional treatment with other anti-seizure medicines, medically inducing a coma with an anesthetic drug, and/or trying alternative therapies to control seizures.

Since some researchers suggest cryptogenic NORSE may be caused by an inflammatory process, immune therapies are sometimes tried to shorten the length of SE and minimize brain damage. Although there are reports of positive outcomes with immune therapies, not everyone responds and there have been no controlled studies to determine the effectiveness. First-line immune therapies that may be used include steroids, intravenous immunoglobulins (IVIG), plasmapheresis. Second line therapies include tacrolimus, rituximab, cyclophosphamide, and anakinra. Other alternative treatments that are considered to also be anti-inflammatory include the ketogenic diet (an established treatment for drug‐resistant epilepsy), cannabidiol (FDA approved for two refractory seizure syndromes, Dravet syndrome and Lennox-Gastaut syndrome), and lowering a person's body temperature (therapeutic hypothermia). These treatments have been used with some success in individual cases and small groups of cases, but again without controlled studies to determine their overall effectiveness.

Last updated on 05-01-20

Clinical Research Resources

The NORSE Institute

The NORSE Institute provides information about ongoing and future research on NORSE and FIRES.

Last updated on 04-27-20

Healthcare Resources

Critical Care EEG Monitoring Research Consortium

The Critical Care EEG Monitoring Research Consortium provides a list of members that treat NORSE. The list does not represent a complete list of doctors and facilities that can effectively treat NORSE, but is one place to start a search.

Last updated on 04-27-20

Selected Full-Text Journal Articles

Wilder-Smith EP et al., 2005

Wilder-Smith EP, Lim EC, Teoh HL, Sharma VK, Tan JJ, Chan BP, Ong BK. The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity. Ann Acad Med Singapore. 2005 Aug;34(7):417-20.

Last updated on 04-27-20

Article - New-Onset Refractory Status Epilepticus Mimicking Herpes Virus Encephalitis

Puoti G, Elefante A, Saracino D, Capasso A, Cotrufo R, Anello CB. New-Onset Refractory Status Epilepticus Mimicking Herpes Virus Encephalitis Case Rep Neurol. 2013 Sep-Dec; 5(3): 162-167.

Last updated on 04-27-20

li J et al., 2013

Li J, Saldivar C, Maganti RK. Plasma exchange in cryptogenic new onset refractory status epilepticus. Seizure. 2013 Jan;22(1):70-3.

Last updated on 04-27-20

Gall CR et al., 2013

Last updated on 04-27-20

Name: Epilepsy Foundation 8301 Professional Place East Suite 230
Landover, MD, 20785, United States
Phone: +1-301-459-3700 Toll Free: 800-332-1000 (24/7 Helpline) Fax : +1-301-577-2684 Email: contactus@efa.org Url: https://www.epilepsy.com/ en Español 1-866-748-8008
Name: Association Paratonnerre 16 Rue Masaryk 69009 Lyon
France
Phone: +33 (0)6 60 65 00 91 Email: associationparatonnerre@yahoo.fr Url: http://associationparatonnerre.org/
Name: Epilepsy Action New Anstey House Gate Way Drive
United Kingdom
Phone: 0113 210 8800 (UK) or +44 (0)113 210 8800 (international) Fax : 0113 391 0300 (UK) or +44 (0)113 391 0300 (international) Email: epilepsy@epilepsy.org.uk Url: https://www.epilepsy.org.uk/
Name: The NORSE Institute Email: nora.norse@gmail.com Url: http://www.norseinstitute.org/

Note, these links are external searches against the National Laboratory of Medicine's drug database. You may need to adjust the search if there are no results found.

Drug Name Generic Name
Seizalam midazolam

Connect with other users with New-onset refractory status epilepticus on the RareGuru app

Do you have information about a disease, disorder, or syndrome? Want to suggest a symptom?
Please send suggestions to RareGuru!

The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

People Using the App

Join the RareGuru Community

To connect, share, empower and heal today.

People Using the App