New-onset Refractory Status Epilepticus and Febrile Infection-related Epilepsy Syndrome

New-onset refractory status epilepticus (NORSE) is a very rare and life-threatening condition in which a child develops status epilepticus, or prolonged seizures. It typically affects otherwise healthy elementary school-aged children and can lead to frequent, often continuous seizures that can be difficult to treat. Febrile infection-related epilepsy syndrome (FIRES) is a type of NORSE that occurs after a fever. Together, they are referred to as NORSE/FIRES.

In NORSE, a fever is not required prior to seizure onset. In FIRES, seizures tend to develop within 24 hours to two weeks of a febrile (fever) illness. A child with FIRES may or may not still have a fever at the time seizures start. In NORSE/FIRES, the seizures typically begin as focal seizures, which can cause abnormal muscle movements on one side of the body; vision changes; behavioral changes; and/or altered consciousness. The seizures soon become more frequent and prolonged — lasting longer than five minutes — a situation called status epilepticus. This acute phase of NORSE/FIRES can last up to two weeks or more.

Note: Status epilepticus is considered an emergency and requires immediate medical attention.

Even with treatment, children with NORSE/FIRES can experience long-term cognitive and functional disability and may go on to develop epilepsy.

“NORSE/FIRES” describes clinical symptoms that can be due to multiple different causes. It occurs in children without known neurologic disease or other immediate causes, such as a tumor or low blood sugar. In some children, NORSE/FIRES can be due to autoimmune encephalitis or infectious encephalitis. However, at least half of the time, no specific cause is identified despite extensive testing. This is called cryptogenic NORSE/FIRES. The exact cause of cryptogenic NORSE/FIRES is unknown, but it appears to be a form of severe brain inflammation that occurs in response to a minor febrile infection. Some research suggests that certain children with NORSE/FIRES may have a genetic predisposition to developing it, but this is not yet well-understood.

Your child’s doctor will perform a physical and neurological exam and ask about their medical history and symptoms. They will also recommend other tests to help diagnose NORSE/FIRES, such as:

• Blood tests
• Electroencephalogram (EEG)
• Lumbar puncture (spinal tap)
• MRI scan
• Genetic tests to rule out other causes

The first goal of treatment for NORSE/FIRES is to address status epilepticus. Your child’s doctor may prescribe intravenous (IV) anti-seizure medication. However, many cases of status epilepticus are refractory, which means that they don’t respond to standard treatments. For children with refractory status epilepticus, doctors may medically induce a reversible coma to help stop seizures. Other treatments, such as immunotherapy and ketogenic diet, are often used with anti-seizure medications.

Children who have been diagnosed with and treated for NORSE/FIRES are at risk for further health concerns: Most develop some degree of cognitive and/or physical impairment. Most children with NORSE/FIRES also go on to develop epilepsy, particularly refractory epilepsy that doesn’t respond well to treatment.

At Boston Children’s Hospital, we care for children with NORSE/FIRES in our Neuroimmunology Center and Epilepsy Center. Our team takes a multidisciplinary approach, working with other specialists throughout Boston Children’s who have expertise in caring for children with NORSE/FIRES, including neurologists, epileptologists, rheumatologists, intensive care physicians, neurosurgeons, neuropsychologists, neuroradiologists, occupational therapists, speech therapists, physical therapists, dietitians, education specialists, and others. Together, we will create a treatment plan that puts your family in the center, both while your child is hospitalized in the acute phase and in our outpatient clinic for follow-up.