Skip to main content
AAN.com
Articles
May 9, 2012

Patterns of treatment response in newly diagnosed epilepsy

May 15, 2012 issue
78 (20) 1548-1554

Abstract

Objective:

To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.

Methods:

Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year.

Results:

A total of 1,098 patients were included (median age 32 years, range 9–93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen.

Conclusions:

Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (brodie.pdf)
File (znl02012001542.pdf)

REFERENCES

1.
Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of epilepsy: a systematic review and meta-analysis. Neurology 2011; 77: 1005– 1012 .
2.
Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol 2007; 62: 382– 389 .
3.
Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol 2007; 62: 375– 381 .
4.
Choi H, Heiman G, Pandis D, et al. Seizure remission and relapse in adults with intractable epilepsy: a cohort study. Epilepsia 2008; 49: 1440– 1445 .
5.
Schiller Y. Seizure relapse and development of drug resistance following long-term remission. Arch Neurol 2009; 66: 1233– 1239 .
6.
Sillanpäa M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective long-term population-based study. Brain 2006; 129: 617– 624 .
7.
Berg AT, Levy SR, Testa FM, D'Souza R. Remission of epilepsy after failures in children: a prospective study. Ann Neurol 2009; 65: 510– 519 .
8.
Cockerell OC, Johnson AL, Sander JW, Hart YM, Shorvon SD. Remission of epilepsy: results from the National General Practice Study of Epilepsy. Lancet 1995; 346: 140– 144 .
9.
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314– 319 .
10.
Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol 2006; 13: 277– 282 .
11.
Stephen LJ, Brodie MJ. Selection of antiepileptic drugs in adults. Neurol Clin 2009; 27: 967– 992 .
12.
Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J. Epilepsy seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470– 472 .
13.
Brodie MJ, Kwan P. Staged approach to epilepsy management. Neurology 2002; 58 (suppl 5): S2– S8 .
14.
Patsalos PN, Berry DJ, Bourgeois BFD, et al. Antiepileptic drugs: best practice guidelines for therapeutic drug monitoring: a position paper by the Subcommission on Therapeutic Drug Monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008; 49: 1239– 1276 .
15.
French JA, Pedley TA. Initial management of epilepsy. N Engl J Med 2008; 359: 166– 176 .
16.
Kwan P, Brodie MJ. Combination therapy in epilepsy: when and what to use. Drugs 2006; 66: 1817– 1829 .
17.
Commission on classification and terminology of the ILAE: proposal for revised clinical classification of epileptic seizures. Epilepsia 1981; 22: 489– 501 .
18.
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsy and epileptic syndromes. Epilepsia 1989; 30: 389– 399 .
19.
Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data, 2nd ed. New York: Springer-Verlag; 2003.
20.
Gray RJ. A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141– 1154 .
21.
Callaghan B, Schlesinger M, Rodemer W, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia 2011; 52: 619– 626 .
22.
Choi H, Heiman GA, Clary HM, Etienne M, Resor SR, Hauser WA. Seizure remission in adults with long-standing intractable epilepsy: an extended follow-up. Epilepsy Res 2011; 93: 115– 119 .
23.
Dichter MA. Emerging concepts in the pathogenesis of epilepsy and epileptogenesis. Arch Neurol 2009; 66: 443– 447 .
24.
Engel J, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia 2003; 44: 741– 751 .
25.
Schiller Y, Najjar Y. Quantifying response to antiepileptic drugs: effect of past treatment history. Neurology 2008; 70: 54– 65 .
26.
Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 50: 1069– 1077 .
27.
Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 2011; 52: 657– 678 .
28.
Kwan P, Brodie MJ. Definition of refractory epilepsy: defining the indefinable? Lancet Neurol 2010; 9: 27– 29 .

Information & Authors

Information

Published In

Neurology®
Volume 78Number 20May 15, 2012
Pages: 1548-1554
PubMed: 22573629

Publication History

Received: June 8, 2011
Accepted: October 26, 2011
Published online: May 9, 2012
Published in print: May 15, 2012

Permissions

Request permissions for this article.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

M.J. Brodie, MD
From the Epilepsy Unit (M.J.B., G.A.B.), Western Infirmary, Glasgow; Robertson Centre for Biostatistics (S.J.E.B.), University of Glasgow, Glasgow; Centre for Healthcare Randomised Trials (J.D.N.), Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Departments of Medicine and Neurology (P.K.), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia; and Department of Medicine and Therapeutics (P.K.), The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Disclosure
Scientific Advisory Boards:
1.
Pfizer Inc; UCB; Eisai Inc; GlaxoSmithKline; Novartis; Sanofi Aventis; Upsher-Smith; Lundbeck Inc
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
UCB, speaker honoraria and travel to and from meetings; GlaxoSmithKline, speaker honoraria; Eisai Inc, speaker honoraria
Editorial Boards:
1.
Seizure, Editorial Board, 2000 to date; Epilepsy & Behavior, Editoral Board, 2005 to date; CNS Drugs, Editorial Board, 2009 to date; Acta Neurologica Scandinavia, Editorial Board, 2010 to date
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Eisai Inc Speakers’ Bureaus:; UCB; GlaxoSmithKline; Eisai Inc
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Eisai Inc; GlaxoSmithKline
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
S.J.E. Barry, PhD
From the Epilepsy Unit (M.J.B., G.A.B.), Western Infirmary, Glasgow; Robertson Centre for Biostatistics (S.J.E.B.), University of Glasgow, Glasgow; Centre for Healthcare Randomised Trials (J.D.N.), Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Departments of Medicine and Neurology (P.K.), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia; and Department of Medicine and Therapeutics (P.K.), The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
G.A. Bamagous, PhD
From the Epilepsy Unit (M.J.B., G.A.B.), Western Infirmary, Glasgow; Robertson Centre for Biostatistics (S.J.E.B.), University of Glasgow, Glasgow; Centre for Healthcare Randomised Trials (J.D.N.), Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Departments of Medicine and Neurology (P.K.), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia; and Department of Medicine and Therapeutics (P.K.), The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
J.D. Norrie, MSc
From the Epilepsy Unit (M.J.B., G.A.B.), Western Infirmary, Glasgow; Robertson Centre for Biostatistics (S.J.E.B.), University of Glasgow, Glasgow; Centre for Healthcare Randomised Trials (J.D.N.), Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Departments of Medicine and Neurology (P.K.), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia; and Department of Medicine and Therapeutics (P.K.), The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Disclosure
Scientific Advisory Boards:
1.
I have served as independent statistician and/or chair on 7 publicly funded iDMC during the last 2 years.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
I am co grant holder on a number of UK NIHR/HTA and UK NIHR/MRC grants, likewise Scottish Government CSO grants.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
P. Kwan, MD, PhD
From the Epilepsy Unit (M.J.B., G.A.B.), Western Infirmary, Glasgow; Robertson Centre for Biostatistics (S.J.E.B.), University of Glasgow, Glasgow; Centre for Healthcare Randomised Trials (J.D.N.), Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Departments of Medicine and Neurology (P.K.), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia; and Department of Medicine and Therapeutics (P.K.), The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Disclosure
Scientific Advisory Boards:
1.
Pfizer Inc, scientific advisory board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Sanofi, speaker honorarium
Editorial Boards:
1.
Editorial Boards:; Epilepsy and Behavior; Seizure; Epileptic Disorders; CNS Drugs
Patents:
1.
Application filed to patent on a rapid HLA typing method (PCT/CN2009/074891)
Publishing Royalties:
1.
Fast Facts: Epilepsy. By Health Press, Oxford, UK
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
UCB
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Eisai; Johnson & Johnson; Pfizer; UCB
Research Support, Government Entities:
1.
NINDS/Forgarty International Center (1R21NS069223), contact PI, 2000-2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence & reprint requests to Dr. Kwan: [email protected]

Author Contributions

M.J.B. is Director of the Epilepsy Unit where the data were collected and conceived the project. S.J.E.B. and G.A.B. analyzed and managed the data under the supervision of J.D.N. and M.J.B. M.J.B. and P.K. coordinated the data analysis plan and interpretation and drafted the paper. All authors contributed to the revision for important intellectual content and approved the final version.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet, Frontiers in Nutrition, 10, (2024).https://doi.org/10.3389/fnut.2023.1304209
    Crossref
  2. Drug resistance predictive utility of age of onset and cortical imaging abnormalities in epilepsy: a systematic review and meta-analysis, The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 60, 1, (2024).https://doi.org/10.1186/s41983-023-00786-5
    Crossref
  3. Intranasal administration of antiseizure medications in chronic and emergency treatment: Hopes and challenges, Seizure: European Journal of Epilepsy, 115, (62-67), (2024).https://doi.org/10.1016/j.seizure.2024.01.003
    Crossref
  4. Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study, Pediatric Neurology, 150, (91-96), (2024).https://doi.org/10.1016/j.pediatrneurol.2023.10.012
    Crossref
  5. Quality indicators for epilepsy management in China: the development of a tool to assess care and first three-year report, Epilepsy Research, (107295), (2024).https://doi.org/10.1016/j.eplepsyres.2024.107295
    Crossref
  6. The Utility of Responsive Neurostimulation for the Treatment of Pediatric Drug-Resistant Epilepsy, Brain Sciences, 13, 10, (1455), (2023).https://doi.org/10.3390/brainsci13101455
    Crossref
  7. Lippia origanoides essential oil possesses anticonvulsant effect in pentylenetetrazol-induced seizures in rats: a behavioral, electroencephalographic, and electromyographic study, Frontiers in Pharmacology, 14, (2023).https://doi.org/10.3389/fphar.2023.1289336
    Crossref
  8. Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study, Frontiers in Neuroscience, 17, (2023).https://doi.org/10.3389/fnins.2023.1210221
    Crossref
  9. Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study, Frontiers in Neurology, 14, (2023).https://doi.org/10.3389/fneur.2023.1236046
    Crossref
  10. Corticosteroids in childhood epilepsies: A systematic review, Frontiers in Neurology, 14, (2023).https://doi.org/10.3389/fneur.2023.1142253
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share