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Keywords:

  • Convulsive status epilepticus;
  • Refractory convulsive status epilepticus;
  • Lacosamide

Summary

  1. Top of page
  2. Summary
  3. Methods and Results
  4. Discussion
  5. Acknowledgments
  6. References

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.

Status epilepticus (SE), consisting of convulsive type (CSE) and nonconvulsive type (NCSE), is a clinical emergency and a potentially life-threatening condition. The incidence of SE in Germany, Switzerland, Italy, and in the white U.S. population has been reported to be 10–20/100,000, which is even higher in the developing countries, especially in the children and older age group (Jallon et al., 1999; Coeytaux et al., 2000; Knake et al., 2001; Wu et al., 2002; Vignatelli et al., 2005; DeLorenzo, 2006). The reported mortality varies from 1.9–40% (Rosenow et al., 2007). CSE is the most often encountered type in clinical practice and needs to be interrupted rapidly to avoid death and neurologic sequelae. Refractory CSE (RCSE) is defined as SE not responding to the first and second treatment effort. It is associated with prolonged intensive care and a poor outcome.

Therefore, more effective substances and treatment strategies for SE are needed. Lacosamide (Vimpat) is a novel antiepileptic substance recently licensed for adjunctive therapy for partial-onset seizures. Herein we report the first clinical case of successful treatment of RSCE with lacosamide.

Methods and Results

  1. Top of page
  2. Summary
  3. Methods and Results
  4. Discussion
  5. Acknowledgments
  6. References

A 38-year-old male patient had epileptic seizures due to perinatal hypoxia with resulting infantile cerebral palsy. The seizure semiology was as follows: sudden simple partial seizures with versive movement of the head to the left, myoclonic jerks of the left extremities, followed by complex partial seizures with disturbance of consciousness, and, most often, secondarily generalized tonic–clonic seizures. The mean seizure frequency was around 5–7 per month with duration of 2–3 min. The antiepileptic regimen prior to admission was levetiracetam 2 × 1,500 mg (serum concentration 68 μmol/L), clonazepam 2 mg, and topiramate 200 mg (serum concentration 10 mg/ml). The patient was severely physically disabled with spastic tetrapareses, and a percutaneous gastric fistula was implanted because of reflux esophagitis due to a massive hiatal hernia.

The patient was admitted for a series of complex partial seizures with secondarily generalized tonic–clonic seizures, which had evolved into generalized tonic–clonic SE. The reason for the present SE was unknown. Before arriving at the hospital the patient was intravenously given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam within 45 min without success. After admission 4 mg lorazepam and 1,500 mg levetiracetam were administered via percutaneous gastric fistula within 30 min, without clinical effect. Due to the patient’s low body weight (39 kg), the dose of the antiepileptic drugs was not further increased. Because phenytoin and valproate had previously failed to control the SE in this patient and also because of the restricted infusion rate of phenytoin, we did not use these substances at this time, but treatment with lacosamide via percutaneous gastric fistula was started. After a first dose of 150 mg (minced tablet powder), a temporary interruption of the seizures was achieved. Because of relapse of the seizures, 150 mg syrup was administered, and this led to the complete clinical remission of the epileptic activity within 30 min.

Discussion

  1. Top of page
  2. Summary
  3. Methods and Results
  4. Discussion
  5. Acknowledgments
  6. References

Because convulsive SE is a life-threatening emergency, immediate and effective treatment is of utmost importance in order to save the patient’s life and to prevent adverse neurologic sequelae. The currently valid treatment guidelines for SE, as issued by the International League Against Epilepsy (ILAE) (Kälviäinen, 2007), recommend benzodiazepines as first-line therapy, followed by phenytoin in the event of inefficacy. However, these recommendations are based on open-label studies rather than randomized clinical trials. Furthermore, the doses of phenytoin required to treat SE effectively often exceed the dosage licensed (up to 1,500 mg/day) by the authorities such as the U.S. Food and Drug Administration (FDA). Second, because of the risk of cardiac arrhythmia the infusion rate of phenytoin is limited to 50 mg/min at maximum. Although valproate and levetiracetam have recently been used in some countries as alternative therapy in SE, and their advantages over phenytoin have been recognized by the medical community, these substances are still not licensed for this indication. On the other hand, the possible hepatic toxicity of valproate also limits its clinical application (Siemes et al., 1993).

Lacosamide is a new antiepileptic drug approved as adjunctive therapy for partial-onset seizures. Electrophysiologic studies suggest a dual effect of lacosamide in epilepsy (Beydoun et al., 2009). First, unlike other antiepileptic drugs, including carbamazepine, phenytoin, and lamotrigine, lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, while it does not impact the fast inactivation. Second, it interacts with collapsing response mediator protein-2 (CRMP-2), which is a phosphoprotein and has been found to be aberrantly regulated in epileptic brain. These novel and distinct mechanisms might be of great significance in the treatment of refractory epilepsy, including SE, as evidenced by our observation and that from Kellinghaus and others who reported lacosamide to be effective in NCSE (Kellinghaus et al., 2009). The availability of both an intravenous formulation and of syrup, as successfully used in our case, suggests that lacosamide is a feasible and convenient treatment option for patients unable to swallow. The rapid clinical response to lacosamide in our case might be explained by the potency of lacosamide to restore the membrane potential and, from a pharmacokinetic view, by our patients low body weight. Because diazepam had been administered shortly prior to lacosamide in our patient, a synergistic effect of lacosamide and diazepam, as observed in animal studies, might be considered (Stöhr et al., 2007).

To our knowledge this is the first report of successful use of lacosamide without evidence of side effects in otherwise RCSE. Further clinical studies are needed to evaluate the efficacy and safety of lacosamide in the treatment of SE.

Acknowledgments

  1. Top of page
  2. Summary
  3. Methods and Results
  4. Discussion
  5. Acknowledgments
  6. References

We thank all colleges that participated in the treatment of the patient. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Disclosure: None of the authors has any conflict of interest to disclose.

References

  1. Top of page
  2. Summary
  3. Methods and Results
  4. Discussion
  5. Acknowledgments
  6. References