Seizure Clusters and Status Epilepticus in TSC
Epilepsy is a very common manifestation of tuberous sclerosis complex (TSC), occurring in 84% of patients registered in the TS Alliance Natural History Database. Potential complications of epilepsy include seizure clusters and status epilepticus.
What is a seizure cluster?
The definition of a seizure cluster varies from one individual to another, but in general the term refers to a group of seizures occurring over a number of hours or days in a way that differs from an individual’s usual seizure pattern. For one patient, having three seizures over the course of two hours may represent a seizure cluster, while for another a seizure cluster may be represented by the occurrence of three seizures over the course of two days.
Adverse effects of seizure clusters include risk of injury from the seizures themselves, prolonged recovery time after seizures and missed work, school or social activities. Seizure clusters may progress into status epilepticus. Of note, infantile spasms, a very common seizure type in babies with TSC, by nature occur in clusters and do not require rescue medication administration.
What is status epilepticus?
The official definition of status epilepticus has evolved over time, but the term generally refers to a prolonged seizure that may not stop on its own without intervention. The most recent definition presented by the International League Against Epilepsy identifies generalized convulsive (tonic-clonic) status epilepticus as a seizure lasting longer than five minutes, with an increased risk of brain injury if the seizure continues for 30 minutes or longer.
For other seizure types, such as focal or absence seizures, these time points may be more prolonged. The majority of seizures in individuals with TSC are short and terminate on their own in less than two to three minutes. However, if status epilepticus occurs, it is a medical emergency that may result in severe consequences if not treated rapidly.
What causes seizure clusters and status epilepticus?
People with intractable epilepsy (seizures that are not controlled by medication) are at higher risk for having seizure clusters or status epilepticus, but these episodes may also occur in people whose seizures are usually well controlled.
Some common triggers for seizure clusters or status epilepticus include:
- missed antiseizure medication doses,
- sleep deprivation, and
For some women, seizure clusters may occur in relation to their menstrual cycle. However, seizure clusters or status epilepticus may also occur without an apparent trigger. Keeping a seizure diary may be helpful in identifying triggers.
How can seizure clusters and status epilepticus be treated?
Prompt treatment of seizure clusters and status epilepticus is important in limiting the duration of seizures and may prevent the need for more intensive hospital-based treatment.
Medications to treat seizure clusters or status epilepticus are often called rescue medications. Several rescue medications are now available for out-of-hospital treatment. All of these medications are part of the benzodiazepine group of drugs, which are the first choice for treatment of prolonged seizures in the hospital. While benzodiazepines used in the hospital are usually given intravenously (IV), benzodiazepine medications available for out-of-hospital treatment may be given orally, rectally, or nasally.
All benzodiazepines have the same potential side effects, which include drowsiness, dizziness, and impaired coordination. At high doses they may cause respiratory depression. In general, emergency services should be contacted after administration of any of these medications to provide assistance if the seizure continues or if serious adverse effects occur.
- Oral Medications used for seizure clusters include clonazepam (Klonopin ®), lorazepam (Ativan ®), and diazepam (Valium ®). These medications may be swallowed or given by gastrostomy tube, and some come in forms that can dissolve on the tongue. Absorption of medications given by mouth is slower than the other treatment options, and these are therefore not a good option for treating status epilepticus. It is important that a person be alert and responsive before administering an oral medication to reduce the risk of aspiration. A person experiencing a seizure may also inadvertently bite down and injure someone trying to put something in his or her mouth.
- A Rectal Medication used for seizure clusters or status epilepticus is diazepam gel (Diastat ®). Diastat is provided as a needleless syringe containing a weight-based dose of diazepam gel that is administered into the rectum, where it is quickly absorbed into the bloodstream. Diastat is often preferred for use in young children, as the method of administration is undesirable for many adolescents and adults. The medication does not require refrigeration and has a long shelf life. Diastat is FDA-approved for the treatment of children over two years of age and adults, but many pediatric neurologists also recommend the use of this medication in children under two years of age.
- Nasal Medications may be used to treat seizure clusters but are not FDA-approved for the treatment of status epilepticus. These medications are sprays that are administered into the nose. There are currently two FDA-approved nasal medications: intranasal midazolam (Nayzilam ®) for ages 12-plus and intranasal diazepam (Valtoco ®) for ages six-plus. Both of these options are safe to store at room temperature and have a long shelf life. There are currently no FDA-approved intranasal rescue medications for children younger than six years of age. There are several potential benefits to nasal medications, including ease of usage, safety for the person administering the medication, and avoidance of potential embarrassment for adolescents and adults that may otherwise require a rectal medication. However, nasal medications may not be a good option for everyone. There are limits to how frequently these medications should be given, so they may not be a good option for those with frequent seizure clusters.
When should rescue medications be used for seizure clusters or status epilepticus?
Every person with TSC and epilepsy should develop a plan with his or her medical provider that details the indications for use of a seizure rescue medication and which medication should be used. This plan should be implemented as soon as possible once a seizure cluster or status epilepticus is identified. The plan should be written down and be available for anyone who might be with the individual when they experience a seizure. For those known to have frequent seizure clusters or status epilepticus, a plan should also be available for emergency medical personnel. Most schools and daycare providers require a written Seizure Action Plan for all children with epilepsy that details the types of seizures they have, what should be done if they have a seizure, and when rescue medications should be given.
Co-written by Derek Bauer, MD, University of Virginia at Charlottesville and Laura Jansen, MD, PhD, Washington University St. Louis (July 2020).