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Loading Dose of Antiepileptic Reduces Seizure Risk During Functional Mapping

Key findings

  • A history of seizures was not a risk factor for triggering interoperative seizures during mapping, but maintenance antiepileptic drug (AED) therapy may have been protective; when mapping patients who have epilepsy, physicians should ensure therapeutic AED levels
  • The risk of intraoperative seizures associated with electrical stimulation during functional mapping was independently reduced 45% by administering a loading dose of an AED at the beginning of surgery
  • The risk of seizure was doubled in cases where mapping was performed via the Penfield method of stimulation—versus multipulse train technique—and in the presence of diffuse pathology

Removing brain tumors requires brain mapping as to identify and protect eloquent regions of the brain such as those involved in language and sensory-motor functions. The gold standard intraoperative mapping technique is performed via direct electrical stimulation, but this can trigger seizures. The latter not only can lead to erroneous mapping results but also pose a direct safety risk to the patient. At the same time, it is extremely difficult to predict the occurrence of seizures, because risk factors vary considerably between individuals and even between different brain regions of the same individual.

Mirela V. Simon, MD, MSc, of the Department of Neurology at Massachusetts General Hospital, and colleagues have observed that administering an AED at the beginning of the surgery seems to decrease the risk of seizures. They recently confirmed this in a retrospective study reported in Clinical Neurophysiology.

Description of the Cohort

The researchers analyzed 544 patients who had standardized functional mapping performed at Mass General during brain tumor and/or epilepsy surgery. 204 patients had been on maintenance AED therapy for at least three days prior to surgery, sometimes requested by the neurologist for protection during the surgery.

At the beginning of surgery, 356 patients (65%) received AED loading with levetiracetam, fosphenytoin, valproic acid and lacosamide (81%, 18%, and 1%, respectively). 27% of patients who received AED loading had been on maintenance AED therapy; loading was performed in that group because of uncertainty about whether the maintenance AED was effective (e.g., drug levels were low or unavailable, the daily dosage was low, treatment duration had been short).

Incidence of Seizures

Electrographic seizures were triggered intraoperatively in 25% of patients. The researchers explain that this percentage is similar to that noted in some studies and markedly higher than in others. They believe the relatively high incidence of seizures was due to:

  • The sensitivity of their procedure: In mapping cases at Mass General, electrocorticographic recordings are made during the entire electrical stimulation period and are interpreted live by a clinical neurophysiologist
  • The type of population mapped: Most patients come to Mass General for a second or even third opinion and are offered surgery for advanced disease, located near eloquent cortical regions

Multivariate Logistic Regression

  • A loading dose of AED decreased the odds of a seizure by 45% (P = .009)
  • Using the Penfield (versus multipulse train) stimulation paradigm independently doubled the risk of a seizure (P = .01)
  • The presence of diffuse (versus well circumscribed) pathology independently increased the risk of seizure by 2.4 times (P = .003)
  • Maintenance AED treatment, history of seizures, administration of opioids at the time of mapping, age more than 50 years old, stimulation in the temporal lobe and glioma as pathology did not significantly affect the risk of seizure

The researchers note that a history of seizures may not have been an independent risk factor because of the protective effect of maintenance AED therapy. They recommend that when mapping patients who have epilepsy, physicians should ensure therapeutic AED levels.

A New Regime

The results of this study have prompted a change in practice at Mass General. All patients who are to undergo intraoperative mapping via cortical electrical stimulation receive about 20 mg/kg levetiracetam intravenously prior to incision. The specific dose is selected on a case-by-case basis (e.g., renal failure, age, consideration of side effects).

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