Status Epilepticus-what we all need to know: Feature Article
For this issue of the Northeast Regional Epilepsy Group newsletter Julie Tsao, M.D., epileptologist explained the important topic of status epilepticus (SE) which is defined as a prolonged seizure or repeated seizures without full recovery in between seizures and represents an emergency. We thank her for providing us with a clear explanation of what SE is, what to do about it and what research is coming down the pipeline.
1) What is status epilepticus? What are the types of status epilepticus?
Status epilepticus (SE) is defined as a prolonged seizure or repeated seizures without full recovery in between seizures. SE can occur due to failure of the body's usual mechanisms to stop a seizure or due to triggering of a mechanism that leads to a prolonged seizure. The International League Against Epilepsy (ILAE) recently defined SE as a seizure lasting beyond five minutes and as a condition that can lead to long term consequences if it continues beyond thirty minutes.
There are two main types of SE: convulsive and nonconvulsive. In convulsive status epilepticus (CSE), there is excessive motor activity or shaking of the body/limbs during the SE. CSE can include generalized tonic-clonic convulsions (GCSE), focal motor shaking, myoclonus, or tonic spasms. Nonconvulsive status epilepticus (NCSE) is where no discernible motor activity is present. NCSE includes persistent absence or "petit mal" seizures, simple partial seizures where repeated sensory changes or auras can occur, and complex partial seizures where there is continued confusion but no obvious excessive motor activity.
2) Are some patients with epilepsy more at risk than others? What causes status epilepticus?
In adults, SE is most often caused by an acute structural injury such as a stroke, trauma, hemorrhage (bleed), infection, inflammation, or tumor. A history of such an injury and prior history of epilepsy also increases the risk of SE. People with a history of epilepsy who suddenly discontinue or miss anti-seizure medications are also at risk. Medications and toxic substances that lower the seizure threshold such as certain antibiotics or chemotherapy agents or cause withdrawal seizures such as alcohol can lead to SE. Acute metabolic abnormalities such as sudden drop in sodium or hyper- or hypoglycemia or sepsis also increase the risk of SE.
3) How is status epilepticus treated?
For GCSE, the first-line of therapy is benzodiazepine class of medications such as Ativan, Valium, or Versed. These medications can be administered intravenously or, if there is no IV access, intramuscularly or rectally. While the initial therapy is being administered, second-line antiseizure medications such as phenytoin, valproate, or levetiracetam need to be prepared and administered as soon as possible. If these two measures do not stop the seizure, or if the patient becomes too sedated, the patient will need to be intubated, where a breathing tube and machine are used to support breathing. By this stage, EEG is typically required to evaluate for ongoing seizure activity that may no longer be clinically apparent (visible).
If ongoing seizure activity is present even with the first and second line therapies, the SE is called refractory status epilepticus (RSE). At this point, the treatment typically requires undergoing a "burst suppression protocol," which includes induction of coma in an attempt to suppress the seizure activity with sedative medications. If seizure activity returns after 24 hours of continued sedative medication use, the RSE is now termed super-refractory status epilepticus (SRSE). At this point, therapies including additional sedative medications, immunotherapy, or dietary therapies may be considered.
For NCSE and focal or myoclonic CSE, the treatment is similar to treatment of GCSE. The main difference is that the clinical exam is taken into account. The risks and benefits of inducing coma with sedative medications need to be weighed in each case, as prolonged sedation and intubation increase the risk of infections and overall morbidity and mortality.
4) What can patients and families do to be prepared?
Most convulsions typically end before five minutes. If a seizure lasts greater than five minutes or, if after a convulsion, the patient does not start to wake up as usual, EMS should be activated so that the patient can be treated effectively in a timely manner.
For patients with a prior history of epilepsy, measures to decrease the risk of breakthrough seizures need to be taken: maintain anti-seizure medication compliance, avoid medications that can lower the seizure threshold, avoid sleep deprivation, and avoid excessive alcohol intake or withdrawal.
5) Is there any novel research in the works that will improve this situation in the future?
Many questions remain unanswered in the treatment of SE. Although the second-line medications such as phenytoin, valproate, and levetiracetam are commonly used as a second-line agent, the relative efficacy of these medications is unknown. This question is currently being investigated in the multicenter Established Status Epilepticus Treatment Trial (ESETT).
Ketogenic diet, which is a high fat, low protein and carbohydrate diet, has been used to treat refractory epilepsy. Investigation of its efficacy in the treatment of RSE is underway.
The STATUS trial (SAGE-547 Treatment as Adjunctive Therapy Utilized in Status epilepticus), investigating the efficacy of the SAGE-547 agent specifically in the treatment of SRSE, is also underway.
Thank you so much for this very informative explanation about this important topic of status epilepticus, Dr. Tsao. Although it can be a scary issue initially, the more we know about it, the better prepared we can all be to deal with it effectively.
