Symptomatic Generalized Epilepsy 

  • Author: Emily Nakagawa, DO, MPH; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Sep 19, 2011
 

Background

Symptomatic generalized epilepsy (SGE) encompasses a group of challenging epilepsy syndromes. As a group, SGE has 3 main features: (1) multiple seizure types, especially generalized tonic and atonic seizures; (2) brain dysfunction other than the seizures, in the intellectual domain (mental retardation or developmental delay) and in the motor domain (cerebral palsy); and (3) EEG evidence of diffuse brain abnormality.

The following are examples of epilepsy syndromes that are included in the category of SGE:

  • Early myoclonic encephalopathy
  • Early infantine epileptic encephalopathy with suppression bursts or Ohtahara syndrome
  • West syndrome
  • Epilepsy with myoclonic atonic seizures
  • Epilepsy with myoclonic absence
  • Lennox-Gastaut syndrome
  • Progressive myoclonic epilepsies

See the following Medscape Reference epilepsy topics for more information on these conditions:

Next

Pathophysiology

Overall, seizures are a paroxysm of high-frequency or synchronous low-frequency high-voltage electrical discharges that cause a sudden alteration in the CNS. Three conditions are involved: (1) population of pathologically excitable neurons, (2) an increase in excitatory glutaminergic activity, and (3) reduction of inhibitory GABAergic projections.[1] In symptomatic generalized epilepsy, an underlying structural or metabolic derangement is also present. EEG findings reflect age-related changes as the brain matures.[2]

Previous
Next

Epidemiology

Frequency

Assessing the frequency of symptomatic generalized epilepsy (SGE) is difficult because the definition varies and can be more or less inclusive.

In a study by Ohtahara and Yamatogi, 12 of 16 patients with Ohtahara syndrome developed into West syndrome or infantile spasms between ages 3 and 6 months as defined by EEG findings.[3] Infantile spasms affect 1 in 2000 infants.[4] Lennox-Gastaut syndrome has an incidence of 1.9-2.1 cases per 100,000 children and accounts for 6-7% of intractable pediatric epilepsy; however, this depends of the definition used for Lennox-Gastaut syndrome.

Mortality/Morbidity

A study of social outcomes in a Nova Scotia study found that 20 years after diagnosis of childhood-onset symptomatic generalized epilepsy (SGE), 25% die. All survivors have mental retardation and depend on parents and institutions in terms of living and finances.[5] Most patients with SGE grow up to have intractable epilepsy, with a small percentage who are seizure free with no antiepileptic drugs.[5] In a follow-up study of 14 patients with Ohtahara syndrome, 4 died early and the remaining 10 were severely handicapped.[6]

Age

These refer to age at onset. In adulthood, most patients with symptomatic generalized epilepsy (SGE) have a less well-defined syndrome that still has the characteristics of SGE and is closest to a Lennox-Gastaut syndrome (intractable multiple seizure types, mental retardation, and cerebral palsy). Note the following progression:

  • Neonates - Early myoclonic encephalopathy, early infantine epileptic encephalopathy with suppression bursts, or Ohtahara syndrome
  • Infancy - West syndrome
  • Childhood - Epilepsy with myoclonic atonic seizures, epilepsy with myoclonic absence, Lennox-Gastaut syndrome
  • Adolescence-adults - Progressive myoclonic epilepsies
Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Emily Nakagawa, DO, MPH  Resident Physician, Department of Neurology, University of South Florida College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

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

Specialty Editor Board

Raj D Sheth, MD  Professor, Mayo College of Medicine; Chief, Division of Pediatric Neurology, Nemours Children's Clinic

Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, and Child Neurology Society

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

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. Ropper AH, Samuels MA. Adams and Victor's Principles of Neurology. 9th. McGraw Medical; 2009.

  2. Nabbout R, Dulac O. Epileptic encephalopathies: a brief overview. J Clin Neurophysiol. Nov-Dec 2003;20(6):393-7. [Medline].

  3. Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res. Aug 2006;70 Suppl 1:S58-67. [Medline].

  4. Kossoff EH. Infantile spasms. Neurologist. Mar 2010;16(2):69-75. [Medline].

  5. Camfield P, Camfield C. Long-term prognosis for symptomatic (secondarily) generalized epilepsies: a population-based study. Epilepsia. Jun 2007;48(6):1128-32. [Medline].

  6. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E. The early-infantile epileptic encephalopathy with suppression-burst: developmental aspects. Brain Dev. 1987;9(4):371-6. [Medline].

  7. Vigevano F, Bartuli A. Infantile epileptic syndromes and metabolic etiologies. J Child Neurol. Dec 2002;17 Suppl 3:3S9-13; discussion 3S14. [Medline].

  8. Djukic A, Lado FA, Shinnar S, Moshé SL. Are early myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independent of each other?. Epilepsy Res. Aug 2006;70 Suppl 1:S68-76. [Medline].

  9. Zupanc ML. Clinical evaluation and diagnosis of severe epilepsy syndromes of early childhood. J Child Neurol. Aug 2009;24(8 Suppl):6S-14S. [Medline].

  10. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. Jan 2009;8(1):82-93. [Medline].

  11. Wheless, James W. Managing Severe Epilepsy Syndromes of Early Childhood. Journal of Child Neurology. 8s Aug 2009;24:24s-32s.

  12. Conry JA. Progressive myoclonic epilepsies. J Child Neurol. Jan 2002;17 Suppl 1:S80-4. [Medline].

  13. Zupanc ML. Clinical evaluation and diagnosis of severe epilepsy syndromes of early childhood. J Child Neurol. Aug 2009;24(8 Suppl):6S-14S. [Medline].

  14. Lombroso CT. Early myoclonic encephalopathy, early infantile epileptic encephalopathy, and benign and severe infantile myoclonic epilepsies: a critical review and personal contributions. J Clin Neurophysiol. Jul 1990;7(3):380-408. [Medline].

  15. Dulac O, N'Guyen T. The Lennox-Gastaut syndrome. Epilepsia. 1993;34 Suppl 7:S7-17. [Medline].

  16. Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev. Oct 8 2008;CD001770. [Medline].

  17. Conry JA. Progressive myoclonic epilepsies. J Child Neurol. Jan 2002;17 Suppl 1:S80-4. [Medline].

  18. Kyllerman M, Ben-Menachem E. Zonisamide for progressive myoclonus epilepsy: long-term observations in seven patients. Epilepsy Res. Jan 1998;29(2):109-14. [Medline].

  19. Lefevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: A systematic review of efficacy. Pediatrics. Apr 2000;105(4):E46. [Medline].

  20. Kilaru S, Bergqvist AG. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia. Epilepsia. Sep 2007;48(9):1703-7. [Medline].

  21. Frost M, Gates J, Helmers SL, Wheless JW, Levisohn P, Tardo C, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia. Sep 2001;42(9):1148-52. [Medline].

  22. Wheless JW. Nonpharmacologic treatment of the catastrophic epilepsies of childhood. Epilepsia. 2004;45 Suppl 5:17-22. [Medline].

  23. Bureau M, Tassinari CA. Epilepsy with myoclonic absences. Brain Dev. Apr 2005;27(3):178-84. [Medline].

  24. Camfield C, Camfield P. Twenty years after childhood-onset symptomatic generalized epilepsy the social outcome is usually dependency or death: a population-based study. Dev Med Child Neurol. Nov 2008;50(11):859-63. [Medline].

  25. Camfield C, Camfield P. Twenty years after childhood-onset symptomatic generalized epilepsy the social outcome is usually dependency or death: a population-based study. Dev Med Child Neurol. Nov 2008;50(11):859-63. [Medline].

  26. Dulac O. Epileptic encephalopathy. Epilepsia. 2001;42 Suppl 3:23-6. [Medline].

  27. Fusco L, Pachatz C, Di Capua M, Vigevano F. Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome). Brain Dev. Nov 2001;23(7):708-14. [Medline].

  28. Genton P, Bureau M. Epilepsy with myoclonic absences. CNS Drugs. 2006;20(11):911-6. [Medline].

  29. Kaminska A, Ickowicz A, Plouin P, Bru MF, Dellatolas G, Dulac O. Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis. Epilepsy Res. Aug 1999;36(1):15-29. [Medline].

  30. Oguni H, Fukuyama Y, Tanaka T, et al. Myoclonic-astatic epilepsy of early childhood--clinical and EEG analysis of myoclonic-astatic seizures, and discussions on the nosology of the syndrome. Brain Dev. Nov 2001;23(7):757-64. [Medline].

  31. Ohtahara S. Zonisamide in the management of epilepsy--Japanese experience. Epilepsy Res. Feb 2006;68 Suppl 2:S25-33. [Medline].

  32. Ohtsuka Y, Yoshinaga H, Kobayashi K, Ogino T, Oka M, Ito M. Diagnostic issues and treatment of cryptogenic or symptomatic generalized epilepsies. Epilepsy Res. Aug 2006;70 Suppl 1:S132-40. [Medline].

  33. Tekgul H, Serdaroglu G, Karapinar B, et al. Vigabatrin caused rapidly progressive deterioration in two cases with early myoclonic encephalopathy associated with nonketotic hyperglycinemia. J Child Neurol. Jan 2006;21(1):82-4. [Medline].

 
Previous
Next
 
Atonic seizure. Abrupt loss of muscle tone is followed by clonic rhythmic movements. This type of seizure is typical for the symptomatic generalized epilepsies of the Lennox-Gastaut type.
Electroencephalogram demonstrating hypsarrhythmia in infantile spasms. Note the chaotic high-amplitude background.
Electroencephalogram demonstrating hypsarrhythmia. Note the electrodecremental response that is associated with a spasm in infantile spasms (ie, West syndrome).
Slow (< 2.5 Hz) electroencephalographic spike and wave discharges associated with atypical absence seizures (ie, Lennox-Gastaut syndrome).
Slow (< 2.5 Hz) electroencephalographic spike and wave discharges in atypical absence epilepsy (ie, Lennox-Gastaut syndrome).
Spike, generalized. Significant spikes usually are followed by a slow wave, as shown here. This example also illustrates that generalized spikes are typically maximal frontally. This is typical of primary (ie, idiopathic, genetic) epilepsies. If burst lasted 3 seconds or more, it could be classified as spike-wave complexes.
Slow spike-wave complexes. In addition to being slower, they are also less monomorphic than 3-Hz spike-wave complexes. With other findings, this often is seen in symptomatic/cryptogenic epilepsies of Lennox-Gastaut type.
Slow spike-wave complexes. In addition to being slower, they are also less monomorphic than 3-Hz spike-wave complexes. With other findings, this often is seen in symptomatic/cryptogenic epilepsies of Lennox-Gastaut type.
Hypsarrhythmia. High-amplitude slowing with no organized background and multifocal spikes (left and right frontal in this sample). This is phenotype of first year of life and is associated with West syndrome (ie, infantile spasms).
Hypsarrhythmia. High-amplitude slowing (note scale) with no organized background and multifocal spikes (right frontal and left occipital in this sample). This is phenotype of first year of life and is associated with West syndrome (ie, infantile spasms).
Generalized paroxysmal fast activity and electrodecrement. This pattern is characteristic of symptomatic/cryptogenic epilepsies of Lennox-Gastaut type and may be subclinical or associated with tonic or atonic seizures.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.