Generalized Tonic-Clonic Seizures Treatment & Management

  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Jun 8, 2011
 

Approach Considerations

A number of antiepileptic drugs (AEDs) are used for the treatment of generalized tonic-clonic seizures. The choice of drug should be tailored to the individual patient and to the epilepsy syndrome, not to the seizure type only.

Go to Epilepsy and Seizures, First Adult Seizure, and First Pediatric Seizure for an overview of these topics.

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Anticonvulsant Therapy

Valproic acid is considered the agent of first choice for patients who have multiple seizure types, including generalized tonic-clonic seizures (except in female patients with reproductive capability), since it treats a broad spectrum of seizure types, including myoclonic seizures. The unblinded, randomized, controlled Standard Antiepileptic and New Antiepileptic Drug (SANAD) study on the effectiveness of valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy supported the primacy of valproate.[4]

Phenytoin and carbamazepine are reasonable second options among the older group of AEDs. However, the newer medications (eg, lamotrigine, topiramate, zonisamide,[5] levetiracetam) tend to work as well if not better and have better side-effect profiles, especially regarding long-term side effects. Phenobarbital is still used by many neurologists, though its adverse cognitive effects have led to a decline in its use.

For refractory generalized epilepsy, felbamate also is used as an agent of last resort and is very effective. The adverse effects of felbamate necessitate very careful monitoring of blood counts and liver function tests.

The agent rufinamide (Banzel) has been approved as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome.[6, 7]

Special considerations

Certain AEDs are enzyme inducers and decrease the levels of oral contraceptive agents. Warn patients of this, and advise them to use additional contraceptive precaution while on enzyme-inducing agents such as phenytoin, carbamazepine, and phenobarbital.

The older first-generation AEDs (eg, phenytoin, carbamazepine, phenobarbital, valproic acid) are all known teratogenic agents.

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Vagus Nerve Stimulation

The US Food and Drug Administration (FDA) has approved vagus nerve stimulation (VNS) only for the treatment of partial seizures. Open-label VNS registry results have also shown that some patients with generalized tonic-clonic seizures respond well. In many years of clinical use of VNS, many patients with primary generalized seizures have had seizure reduction.

No other surgical option exists for pure generalized tonic-clonic seizures. Patients must be carefully evaluated because some partial seizures with quick secondary bilateral synchrony may be labeled as primary generalized tonic-clonic.

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Ketogenic Diet

A ketogenic diet can be tried to improve seizure control in younger patients whose condition is refractory. The ketogenic diet was developed at the Mayo Clinic and Johns Hopkins Institute, and it was based on the observation that seizures improved during periods of starvation. Studies have shown a substantial reduction in seizure frequency in 50% of patients placed on the diet.

The exact mechanism by which this diet works is not known. The diet typically contains a fat-to-carbohydrate ratio of 4:1. This diet produces a ketotic state but provides adequate calories for nutrition from proteins and fat.

The ketogenic diet is used for intractable epilepsy, especially in childhood. It is less commonly prescribed for adults because the diet, being very restrictive, is very difficult to maintain.

Adverse effects are mainly gastrointestinal and include bloating, constipation, renal stones, and bone and weight loss. Urinary ketones are checked daily and need to be greater than 4+ (80-160 mg/dL.

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Activity Restriction

Driving is restricted if patients are still having seizures as per particular state laws. In addition, common-sense restrictions for patients with epilepsy should be followed, such as not operating dangerous equipment, not swimming alone, and not taking baths unsupervised, among others.

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Contributor Information and Disclosures
Author

David Y Ko, MD  Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of Southern California

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Headache Society

Disclosure: GSK Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Lundbeck Consulting fee Consulting; Westward Consulting fee Consulting

Coauthor(s)

Soma Sahai-Srivastava, MD  Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, Keck School of Medicine of the University of Southern California

Soma Sahai-Srivastava, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Ramon Diaz-Arrastia, MD, PhD  Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital

Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jose E Cavazos, MD, PhD, FAAN  Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the eMedicine articles that I wrote or edited.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

References
  1. Walczak TS, Leppik IE, D'Amelio M, Rarick J, So E, Ahman P, et al. Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study. Neurology. Feb 27 2001;56(4):519-25. [Medline].

  2. Elzawahry H, Do CS, Lin K, Benbadis SR. The diagnostic utility of the ictal cry. Epilepsy Behav. Jul 2010;18(3):306-7. [Medline].

  3. Morrell MJ. Differential diagnosis of seizures. Neurol Clin. Nov 1993;11(4):737-54. [Medline].

  4. [Best Evidence] Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. Mar 24 2007;369(9566):1016-26. [Medline]. [Full Text].

  5. Peters DH, Sorkin EM. Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. May 1993;45(5):760-87. [Medline].

  6. Kluger G, Bauer B. Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy). Neuropsychiatr Dis Treat. Feb 2007;3(1):3-11. [Medline]. [Full Text].

  7. [Best Evidence] Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. May 20 2008;70(21):1950-8. [Medline].

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