Status Epilepticus in Cancer Patients: Does It Make a Difference If the Tumor is a Primary Brain Tumor or Systemic Metastasis?

Abstract & Commentary

By Adilia M. Hormigo, MD, and Cynthia L. Harden, MD, Drs. Hormigo and Harden report no financial relationships relevant to this field of study. Dr. Hormigo works at the Memorial Sloan-Kettering Cancer Center. Dr. Harden works at the Comprehensive Epilepsy Center.

Synopsis: Status epilepticus, in the setting of cancer, is treatable and does not appear to increase mortality above the risk of the underlying disease.

Source: Cavaliere R, et al. Clinical Implications of Status Epilepticus in Patients with Neoplasms. Arch Neurol. 2006;63:1746-1749

Status epilepticus (SE) is defined as a series of recurrent grand mal seizures without return of consciousness between them, or persistent seizure activity for at least 30 minutes. Although the standard definition for SE requires 30 minutes of seizure activity, the need for rapid intervention and early treatment has led to a consideration of impending status with a shorter duration of continuous seizure activity.1 SE is a neurological emergency and stepwise treatment is implemented to control this potentially fatal condition. Patients with brain tumors or intracranial metastases, either in the brain parenchyma or leptomeninges, are at increased risk for developing seizures, and subsequently SE.

This study by Cavaliere, et al analyzed factors that may lead to SE and affect prognosis in the cancer population. Over a period of 8 years, the authors found 35 patients (25 with primary brain tumors) at the University of Virginia who developed SE secondary to the tumor or its treatment. Twenty of those patients (57%) were taking anti-convulsant drugs when they developed SE, and 11 (55%) had subtherapeutic levels. Approximately one quarter of this small cohort developed SE in one of the following 3 settings, determined by brain imaging: 1) at the time of tumor diagnosis, 2) with tumor progression, 3) with stable tumor. The remaining fraction had either tumor regression or insufficient imaging to determine the status of the tumor.

Eight patients (23%) died within 30 days of SE; 5 had systemic cancer and other contributing factors for a seizure disorder, including infections, strokes, intraparenchymal hemorrhage or metabolic imbalance. Half of the subjects with systemic tumors died within 30 days of status epilepticus, in contrast to only 12% of subjects with primary brain tumors. Half of the SE occurrences consisted of generalized tonic-clonic (GTC) seizures, and was the seizure type in most of the subjects who died within 30 days.

Although details are not provided about specific treatment regimens, SE was successfully treated in most patients with benzodiazepines and phenytoin. Three patients required additional phenobarbital, one received propofol, and one required a medically induced coma.

Commentary

This is a retrospective study that looked at the incidence, contributing and prognostic factors for SE among patients with primary or metastatic tumors to the brain and meninges and their treatment. The mortality rate was similar to what has been reported for other causes of SE, and overall survival correlated with the expected survival for the underlying tumor. Patients with systemic cancer had a higher risk of death in the 30-day period after SE; these patients were also older and had other concurrent illnesses. No statistically significance correlation was seen between 30-day mortality after SE and age, seizure type, tumor status, prior seizure disorder, or need for endotracheal intubation.

An important lesson emerges from this study. If a patient has had a seizure and is on AEDs, it is important to keep the dose in a therapeutic range since low AED levels (55% of patients on AEDs) appear to be one modifiable risk factor for developing SE in this population. Secondly, partial SE and any type of SE in patients with primary brain tumors is associated with less risk of death in the short term and therefore, good response to adequate treatment can be expected in this group. Unfortunately, there is no information about the duration of SE or management algorithms. The use of fewer than 3 drugs to control SE suggests that SE in the cancer population is amenable to treatment and efforts should be made to determine the optimal pharmacologic regimen.

Reference:

1. Chen JW, Wasterlain CG. Status Epilepticus: Pathophysiology and Management in Adults. Lancet Neurol. 2006;2:246-256.