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Lennox-Gastaut Syndrome Treatment & Management

  • Author: Koshi A Cherian, MD; Chief Editor: Amy Kao, MD  more...
 
Updated: Apr 15, 2016
 

Approach Considerations

The goals of treatment for patients with Lennox-Gastaut syndrome (LGS) are the same as for all patients with epilepsy: the best quality of life with the fewest seizures (ideally, none), the fewest adverse treatment effects, and the least number of medications.

A variety of therapeutic approaches are used in LGS, ranging from conventional antiepileptic agents to diet and surgery.[8] Unfortunately, much of the evidence supporting these approaches is not robust, and treatment is often ineffective.[9, 10]

The medical treatment options for patients with LGS can be divided into the following 3 major groups:

  • First-line treatments based on clinical experience or conventional wisdom (eg, valproic acid, benzodiazepines [specifically clonazepam, nitrazepam, clobazam [11, 12, 13] ])
  • Treatments suspected to be effective on the basis of open-label uncontrolled studies (eg, vigabatrin, [14] zonisamide [15] )
  • Treatments proven effective by double-blind placebo-controlled studies (eg, lamotrigine, [16] topiramate, [17, 18, 19] felbamate [20] , rufinamide [21, 22, 23] )

The ketogenic diet may be useful in patients with LGS refractory to medical treatment. Surgical options for LGS include corpus callostomy, vagus nerve stimulation, and focal cortical resection.[24]

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Antiepileptic Therapy

Antiepileptic drugs (AEDs) are the mainstay of therapy for patients with LGS. Unfortunately, no one AED gives satisfactory relief for all or even most patients with LGS. A combination of agents frequently is required. Patients with LGS experience frequent exacerbations of their seizures that may require inpatient adjustment of AEDs.

Patients with LGS have a recognized high risk for status epilepticus. Because of the consequent risk of injury or death, a medication for emergency intervention (eg, rectal diazepam) should be prescribed.

Valproate

Valproate (Depakote, Depakene, Depacon) has been considered the first-line treatment option for children with LGS for the past 2 decades. It is reported to be more effective in patients with cryptogenic LGS than in those with symptomatic LGS.

Lamotrigine

The efficacy of lamotrigine (Lamictal) as adjunctive therapy against seizures associated with LGS was demonstrated in 2 controlled trials and multiple open-label studies. This agent is valuable for patients with LGS, despite its risk of idiosyncratic dermatologic reactions, and its use should be considered as soon as diagnosis of LGS is made. Proper attention to concomitant medications, low starting dose, and very slow titration can minimize the risk of dermatologic reactions.

Topiramate

In a multicenter, double-blind, placebo-controlled trial, topiramate (Topamax) was found to be safe and effective as adjunctive therapy for patients with LGS.[19] The target dose was 6 mg/kg/d. In a long-term open-label extension portion of this trial (mean dosage 10 mg/kg/d), drop attacks were reduced by greater than half in 55% of patients, and 15% of patients were free of drop attacks for over 6 mo at the last visit.[18]

Felbamate

Felbamate (Felbatol) was found to be safe and effective in patients with LGS in a randomized, double-blind, placebo-controlled adjunctive therapy trial, and 12-month follow-up in patients who completed controlled part of study confirmed long-term efficacy.[20] Despite the efficacy of felbamate, the significant risk of idiosyncratic reactions associated with its use make it a third-line or fourth-line drug for LGS.

Zonisamide

The effectiveness of zonisamide (Zonegran) in LGS has been investigated in 3 small open-label studies, with promising results. A multicenter study of zonisamide for long-term adjunctive therapy in 62 children with LGS found that it was safe and effective; 4.8% of children had 100% seizure freedom, and 22.6% had >75% reduction in their seizures, independent of seizure type.[15]

Vigabatrin (Sabril)

Vigabatrin (Sabril) was approved by the US Food and Drug Administration (FDA) in 2009 as monotherapy for infantile spasms in patients 1 month to 2 years old, and as adjunctive therapy for adults with refractory complex partial seizures. In 6 open-label studies involving 78 patients with LGS, 15% became completely seizure free and 44% had a >50% reduction in seizure frequency.[25]

Rufinamide

The FDA approved rufinamide (Banzel) in 2008 for the adjunctive treatment of seizures associated with LGS in children 4 years and older and adults. In a double-blind, randomized, placebo-controlled trial by Glauser et al, rufinamide produced a statistically significant decrease in total seizure frequency and tonic-atonic seizures in individuals aged 4-30 years.[21] A 2009 open-label European study also demonstrated decreased seizure frequency amongst those with LGS.[22]

In a multicenter clinical trial of 59 patients with LGS, rufinamide was found to decrease the frequency of tonic-atonic seizures by 24.2%, versus 3.3% with placebo, and total seizures by 32.9%, versus 3.3% with placebo. Adverse events in the rufinamide group included decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%).[26]

In February 2015, rufinamide was approved in pediatric patients aged 1 to 4 years based on a pharmacokinetic bridging study of a Phase III clinical trial which demonstrated the pharmacokinetic and safety profiles are consistent with those seen in ages ≥ 4 years.[27]

Benzodiazepines

Clonazepam (Klonopin) is considered an effective first-line AED therapy for seizures associated with LGS. However, the adverse effects and development of tolerance limit its usefulness over time. Dosing on an every-other-day schedule or alternating 2 benzodiazepines daily may slow development of tolerance. The benzodiazepine clobazam, which is widely used as an anticonvulsant in other countries, was approved by the FDA in October 2011.[13] The combination of valproic acid and a benzodiazepine may be better than either drug alone.

In the CONTAIN study of patients with LGS given clobazam, more than 50% of patients had a 50% or greater decrease in weekly drop- and total-seizure frequency. The percentage of patients achieving 100% reduction in drop seizures was 33% for clobazam-treated patients (vs. 7% for placebo) in Quartile 1 (least severe LGS), and 5% of clobazam-treated patients in Quartile 4 (most severe LGS) achieved 100% reduction in drop seizures, versus 0% for placebo.[28]

In a second study (OLE study), through 5 years of clobazam therapy, more than 50% of patients in all 4 quartiles (least severe to most severe LGS) demonstrated a decrease of 50% or more in weekly frequency for drop seizures. More than 12% of patients in Quartile 4 achieved 100% reduction in drop seizures from month 3 through year 5.[28]

The FDA has issued a warning that clobazam, used as add-on therapy to treat seizures in patients with LGS, may trigger Stevens-Johnson syndrome and toxic epidermal necrolysis, rare but potentially fatal cutaneous reactions.[29, 30] The risk of developing these disorders is increased during the first 8 weeks of treatment or when treatment is resumed after it is discontinued.

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Corpus Callostomy

Corpus callosotomy is effective in reducing drop attacks but is typically not helpful for other seizure types. It is considered palliative rather than curative. Seizure freedom following corpus callosotomy is rare but can occur.

A 2006 study showed a greater than 90% seizure reduction in 52 of 76 patients with LGS who underwent an extended, one-stage, callosal section (splenium intact); 7 of the 76 patients were seizure free.[31] The mean follow-up time was 4.7 years. The seizure types most responsive to surgery were atonic and atypical absence.

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Vagus Nerve Stimulation

Vagus nerve stimulation by means of a surgically implanted programmable device is approved by the FDA as an adjunctive treatment for refractory partial-onset seizures in adults and adolescents older than 12 years. In 3 published small studies, approximately three fourths of patients with LGS experienced greater than 50% reduction in seizure frequency with a follow-up period as long as 5 years.[32]

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Focal Cortical Resection

In rare cases, resection of a localized lesion (eg, vascular lesion, tumor) can improve seizure control in LGS.

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Ketogenic Diet

The ketogenic diet comprises a high ratio of fats (ketogenic foods) to proteins and carbohydrates (antiketogenic foods). The ratio of ketogenic to antiketogenic foods in the diet ranges from 2:1 to 4:1 or higher. In general, the benefits of the diet for people with epilepsy include fewer seizures, less drowsiness, better behavior, and need for fewer concomitant AEDs.

Based on multiple open-label and, most recently, randomized controlled studies, the ketogenic diet appears to be a useful therapy for patients with LGS. Efficacy appears greatest for atonic, myoclonic, and atypical absence seizures, but other seizure types (tonic-clonic, secondarily generalized tonic-clonic) may also respond.

In a 2008 randomized controlled trial of the ketogenic diet in children with daily seizures who had a poor response to at least 2 AEDs, 38% of the children in the diet arm had a greater than 50% reduction in seizures. Of the 145 children randomized to the ketogenic diet or control, only 14 had LGS.[33]

A blinded, crossover study of the ketogenic diet in 20 children with LGS showed a moderate reduction in parent-reported myoclonic-atonic events. Ketosis was not eliminated in the placebo arm; thus, there was no difference observed between the 2 groups regarding reduction in EEG-identified events. When patients who are seizure free for extended periods of time should be weaned from the diet is not clear.[34]

The ketogenic diet is not always successful. The following 3 factors are associated with successful implementation of the diet:

  • Dedicated, compliant family willing to alter the entire family's lifestyle
  • Family able to follow (without wavering) the strict guidelines of the diet
  • Team of professionals (centered around a dietitian) trained and experienced in the use of the diet

Potential serious adverse effects include dehydration, clinically significant metabolic acidosis when the diet is initiated, renal stones, cardiac abnormalities, and abnormal lipid profile.

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Injury Prevention

Some patients with LGS wear protective helmets with face guards to maximize protection of the forehead, nose, and teeth (see the image below). Unfortunately, some patients with LGS do not tolerate the helmet with face guards, and even if tolerated, helmets often are uncomfortable and rarely are cosmetically acceptable.

Patient with Lennox-Gastaut syndrome wearing a hel Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures
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Consultations

Pediatric neuropsychologists can assess intellectual function and educational needs and advise on nonpharmacologic management of behavioral problems. Pediatric psychiatrists can advise on pharmacologic management of behavioral problems. Neurosurgeons can assist in the placement of a vagus nerve stimulator and assess the patient as a candidate for corpus callosotomy or focal resection. Dietitians can assist in the institution and maintenance of the ketogenic diet.

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Contributor Information and Disclosures
Author

Koshi A Cherian, MD Assistant Professor, Department of Neurology and Pediatrics, Albert Einstein College of Medicine; Attending Physician, Department of Neurology, Division of Child Neurology and Epilepsy, Montefiore Medical Center; Attending Physician, Department of Pediatrics, Division of Child Neurology, Jacobi Medical Center; Staff Physician (Courtesy), Department of Pediatrics, Division of Child Neurology, St Barnabas Hospital

Koshi A Cherian, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, Child Neurology Society, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Coauthor(s)

Tracy A Glauser, MD Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Comprehensive Epilepsy Center, Co-Director, Genetic Pharmacology Service, Cincinnati Children's Hospital Medical Center

Tracy A Glauser, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society

Disclosure: Received consulting fee from Eisai for consulting; Received consulting fee from Lundbeck for consulting; Received consulting fee from Questcor for consulting; Received consulting fee from ucb Pharma for consulting; Received consulting fee from Supernus for consulting; Received honoraria from Supernus for speaking and teaching; Received consulting fee from Sunovion for consulting; Received royalty from AssureRx for license; Received consulting fee from Upsher-Smith for consulting; Received consul.

Diego A Morita, MD Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Diego A Morita, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association

Disclosure: Nothing to disclose.

Karen Mary Stannard, MD FRCPC

Karen Mary Stannard, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Acknowledgements

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience

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

References
  1. Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia. 1997 Dec. 38(12):1283-8. [Medline].

  2. Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009 Jan. 8(1):82-93. [Medline]. [Full Text].

  3. Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001 Jun. 42(6):796-803. [Medline].

  4. Heiskala H. Community-based study of Lennox-Gastaut syndrome. Epilepsia. 1997 May. 38(5):526-31. [Medline].

  5. Oguni H, Hayashi K, Osawa M. Long-term prognosis of Lennox-Gastaut syndrome. Epilepsia. 1996. 37 Suppl 3:44-7. [Medline].

  6. Ohtsuka Y, Amano R, Mizukawa M, Ohtahara S. Long-term prognosis of the Lennox-Gastaut syndrome. Jpn J Psychiatry Neurol. 1990 Jun. 44(2):257-64. [Medline].

  7. Bare MA, Glauser TA, Strawsburg RH. Need for electroencephalogram video confirmation of atypical absence seizures in children with Lennox-Gastaut syndrome. J Child Neurol. 1998 Oct. 13(10):498-500. [Medline].

  8. Al-Banji MH, Zahr DK, Jan MM. Lennox-Gastaut syndrome. Management update. Neurosciences (Riyadh). 2015 Jul. 20 (3):207-12. [Medline].

  9. van Rijckevorsel K. Treatment of Lennox-Gastaut syndrome: overview and recent findings. Neuropsychiatr Dis Treat. 2008 Dec. 4(6):1001-19. [Medline]. [Full Text].

  10. Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007 Dec. 9(4):353-412. [Medline].

  11. Conry JA, Ng YT, Paolicchi JM, Kernitsky L, Mitchell WG, Ritter FJ, et al. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009 May. 50(5):1158-66. [Medline].

  12. Ng YT, Collins SD. Clobazam. Neurotherapeutics. 2007 Jan. 4(1):138-44. [Medline].

  13. Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11. 77(15):1473-1481. [Medline].

  14. Feucht M, Brantner-Inthaler S. Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study. Epilepsia. 1994 Sep-Oct. 35(5):993-8. [Medline].

  15. You SJ, Kang HC, Kim HD, Lee HS, Ko TS. Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience. Brain Dev. 2008 Apr. 30(4):287-90. [Medline].

  16. Motte J, Trevathan E, Arvidsson JF, Barrera MN, Mullens EL, Manasco P. Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group. N Engl J Med. 1997 Dec 18. 337(25):1807-12. [Medline].

  17. Glauser TA. Topiramate. Epilepsia. 1999. 40 Suppl 5:S71-80. [Medline].

  18. Glauser TA, Levisohn PM, Ritter F, Sachdeo RC. Topiramate in Lennox-Gastaut syndrome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia. 2000. 41 Suppl 1:S86-90. [Medline].

  19. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology. 1999 Jun 10. 52(9):1882-7. [Medline].

  20. Pellock JM. Felbamate. Epilepsia. 1999. 40 Suppl 5:S57-62. [Medline].

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

  22. Kluger G, Kurlemann G, Haberlandt E, Ernst JP, Runge U, Schneider F, et al. Effectiveness and tolerability of rufinamide in children and adults with refractory epilepsy: first European experience. Epilepsy Behav. 2009 Mar. 14(3):491-5. [Medline].

  23. Perucca E, Cloyd J, Critchley D, Fuseau E. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia. 2008 Jul. 49(7):1123-41. [Medline].

  24. Ferrie CD, Patel A. Treatment of Lennox-Gastaut Syndrome (LGS). Eur J Paediatr Neurol. 2009 Nov. 13(6):493-504. [Medline].

  25. Lerner JT, Salamon N, Sankar R. Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms. Neuropsychiatr Dis Treat. 2010 Nov 8. 6:731-40. [Medline]. [Full Text].

  26. Ohtsuka Y, Yoshinaga H, Shirasaka Y, Takayama R, Takano H, Iyoda K. Rufinamide as an adjunctive therapy for Lennox-Gastaut syndrome: A randomized double-blind placebo-controlled trial in Japan. Epilepsy Res. 2014 Nov. 108(9):1627-36. [Medline].

  27. Banzel (rufinamide) [package insert]. Woodcliff Lake, NJ: Eisai Inc. 2/2015. Available at [Full Text].

  28. Wheless JW, Isojarvi J, Lee D, Drummond R, Benbadis SR. Clobazam is efficacious for patients across the spectrum of disease severity of Lennox-Gastaut syndrome: Post hoc analyses of clinical trial results by baseline seizure-frequency quartiles and VNS experience. Epilepsy Behav. 2014 Oct 2. 41C:47-52. [Medline].

  29. Lowes R. Clobazam (Onfi) can cause serious skin reactions, FDA warns. Medscape Medical News. December 3, 2013. Available at http://www.medscape.com/viewarticle/815303. Accessed: December 8, 2013.

  30. FDA Drug Safety Communication. FDA warns of serious skin reactions with the anti-seizure drug Onfi (clobazam) and has approved label changes. December 3, 2013. Available at http://www.fda.gov/Drugs/DrugSafety/ucm377204.htm. Accessed: December 8, 2013.

  31. Cukiert A, Burattini JA, Mariani PP, Câmara RB, Seda L, Baldauf CM, et al. Extended, one-stage callosal section for treatment of refractory secondarily generalized epilepsy in patients with Lennox-Gastaut and Lennox-like syndromes. Epilepsia. 2006 Feb. 47(2):371-4. [Medline].

  32. Ben-Menachem E, Hellström K, Waldton C, Augustinsson LE. Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology. 1999 Apr 12. 52(6):1265-7. [Medline].

  33. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun. 7(6):500-6. [Medline].

  34. Freeman JM, Vining EP, Kossoff EH, Pyzik PL, Ye X, Goodman SN. A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia. 2009 Feb. 50(2):322-5. [Medline].

  35. De Los Reyes EC, Sharp GB, Williams JP, Hale SE. Levetiracetam in the treatment of Lennox-Gastaut syndrome. Pediatr Neurol. 2004 Apr. 30(4):254-6. [Medline].

 
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Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures
Slow spike wave pattern in a 24-year-old awake male with Lennox-Gastaut syndrome. The slow posterior background rhythm has frequent periods of 2- to 2.5-Hz discharges, maximal in the bifrontocentral areas, occurring in trains as long as 8 seconds without any clinical accompaniment.
 
 
 
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