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CC BY-NC-ND 4.0 · International Journal of Epilepsy 2020; 06(01): 15-23
DOI: 10.1055/s-0040-1712777
Review Article

Management of Refractory Epilepsy

Rajveer Singh 
1   Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
,
Kamalesh Chakravarty
1   Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
,
Jitupam Baishya
1   Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
,
Manoj K. Goyal
1   Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
,
Parampreet Kharbanda
1   Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
› Institutsangaben Funding None.
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Abstract

Drug refractory epilepsy, defined as a failure of adequate trials of two (or more) tolerated, appropriately chosen, and appropriately used antiepileptic drug (AED) regimens (whether administered as monotherapies or in combination) to achieve freedom from seizures, affects approximately 30% of patients with new-onset epilepsy. Persistent epileptic seizures in these patients, in addition to having deleterious effects on health, are also associated with psychosocial, behavioral, cognitive, and financial consequences. Despite availability of several new drugs, response to therapy remains poor in most of drug refractory cases. Also despite several ongoing treatment trials, ideal combination of AEDs remains to be identified. Careful attention to ruling out alternative diagnoses, optimal selection of AEDs, rational use of combination therapy, as well as attention to patient-specific factors, such as poor compliance and drug abuse, remain cornerstone of therapy. In view of poor response to polytherapy, if possible, surgical intervention should be contemplated early. In future, development of new drugs with better efficacy and tolerability and minimal drug interactions, as well as better nonpharmacological therapeutic techniques, will help in managing these patients better.

Keywords

refractory epilepsy - rational polytherapy - antiepileptic drug


Publikationsverlauf

Artikel online veröffentlicht:
01. Juni 2020

© .

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Banerjee PN, Filippi D, Allen Hauser W. The descriptive epidemiology of epilepsy-a review. Epilepsy Res 2009; 85 (01) 31-45
    CrossrefPubMedGoogle Scholar
  • 2 Callaghan N, Garrett A, Goggin T. Withdrawal of anticonvulsant drugs in patients free of seizures for two years. A prospective study. N Engl J Med 1988; 318 (15) 942-946
    CrossrefPubMedGoogle Scholar
  • 3 Chang H-J, Liao C-C, Hu C-J, Shen WW, Chen T-L. Psychiatric disorders after epilepsy diagnosis: a population-based retrospective cohort study. PLoS One 2013; 8 (04) e59999
    CrossrefPubMedGoogle Scholar
  • 4 Picot MC, Baldy-Moulinier M, Daurès JP, Dujols P, Crespel A. The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country. Epilepsia 2008; 49 (07) 1230-1238
    CrossrefPubMedGoogle Scholar
  • 5 Mohanraj R, Norrie J, Stephen LJ, Kelly K, Hitiris N, Brodie MJ. Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study. Lancet Neurol 2006; 5 (06) 481-487
    CrossrefPubMedGoogle Scholar
  • 6 Lawn ND, Bamlet WR, Radhakrishnan K, O’Brien PC, So EL. Injuries due to seizures in persons with epilepsy: a population-based study. Neurology 2004; 63 (09) 1565-1570
    CrossrefPubMedGoogle Scholar
  • 7 McCagh J, Fisk JE, Baker GA. Epilepsy, psychosocial and cognitive functioning. Epilepsy Res 2009; 86 (01) 1-14
    CrossrefPubMedGoogle Scholar
  • 8 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; 51 (06) 1069-1077
    Google Scholar
  • 9 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342 (05) 314-319
    CrossrefPubMedGoogle Scholar
  • 10 Arts WF, Brouwer OF, Peters AC. et al. Course and prognosis of childhood epilepsy: 5-year follow-up of the Dutch study of epilepsy in childhood. Brain 2004; 127 (Pt 8) 1774-1784
    CrossrefPubMedGoogle Scholar
  • 11 Choi H, Heiman G, Pandis D. et al. Seizure remission and relapse in adults with intractable epilepsy: a cohort study. Epilepsia 2008; 49 (08) 1440-1445
    CrossrefPubMedGoogle Scholar
  • 12 Schiller Y. Seizure relapse and development of drug resistance following long-term seizure remission. Arch Neurol 2009; 66 (10) 1233-1239
    CrossrefPubMedGoogle Scholar
  • 13 Berg AT, Rychlik K, Levy SR, Testa FM. Complete remission of childhood-onset epilepsy: stability and prediction over two decades. Brain 2014; 137 (Pt 12) 3213-3222
    CrossrefPubMedGoogle Scholar
  • 14 Sato S, White BG, Penry JK, Dreifuss FE, Sackellares JC, Kupferberg HJ. Valproic acid versus ethosuximide in the treatment of absence seizures. Neurology 1982; 32 (02) 157-163
    CrossrefPubMedGoogle Scholar
  • 15 Genton P. When antiepileptic drugs aggravate epilepsy. Brain Dev 2000; 22 (02) 75-80
    CrossrefPubMedGoogle Scholar
  • 16 Cascino GD. Intractable partial epilepsy: evaluation and treatment. Mayo Clin Proc 1990; 65 (12) 1578-1586
    CrossrefPubMedGoogle Scholar
  • 17 Reutens DC, Berkovic SF. Idiopathic generalized epilepsy of adolescence: are the syndromes clinically distinct. ? Neurology 1995; 45 (08) 1469-1476
    CrossrefPubMedGoogle Scholar
  • 18 Semah F, Picot MC, Adam C. et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence?. Neurology 1998; 51 (05) 1256-1262
    CrossrefPubMedGoogle Scholar
  • 19 Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol 2006; 13 (03) 277-282
    CrossrefPubMedGoogle Scholar
  • 20 Aronica E, Gorter JA, Jansen GH. et al. Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 2003; 118 (02) 417-429
    CrossrefPubMedGoogle Scholar
  • 21 Tishler DM, Weinberg KI, Hinton DR, Barbaro N, Annett GM, Raffel C. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 1995; 36 (01) 1-6
    CrossrefPubMedGoogle Scholar
  • 22 Sisodiya SM, Lin WR, Harding BN, Squier MV, Thom M. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 2002; 125 (Pt 1) 22-31
    CrossrefPubMedGoogle Scholar
  • 23 Siddiqui A, Kerb R, Weale ME. et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2003; 348 (15) 1442-1448
    CrossrefPubMedGoogle Scholar
  • 24 Bournissen FG, Moretti ME, Juurlink DN, Koren G, Walker M, Finkelstein Y. Polymorphism of the MDR1/ABCB1 C3435T drug-transporter and resistance to anticonvulsant drugs: a meta-analysis. Epilepsia 2009; 50 (04) 898-903
    CrossrefPubMedGoogle Scholar
  • 25 Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Löscher W. Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 2007; 52 (02) 333-346
    CrossrefPubMedGoogle Scholar
  • 26 Remy S, Beck H. Molecular and cellular mechanisms of pharmacoresistance in epilepsy. Brain 2006; 129 (Pt 1) 18-35
    CrossrefPubMedGoogle Scholar
  • 27 Remy S, Gabriel S, Urban BW. et al. A novel mechanism underlying drug resistance in chronic epilepsy. Ann Neurol 2003; 53 (04) 469-479
    CrossrefPubMedGoogle Scholar
  • 28 Kwan P, Poon WS, Ng HK. et al. Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression. Pharmacogenet Genomics 2008; 18 (11) 989-998
    CrossrefPubMedGoogle Scholar
  • 29 Loup F, Picard F, Yonekawa Y, Wieser HG, Fritschy JM. Selective changes in GABAA receptor subtypes in white matter neurons of patients with focal epilepsy. Brain 2009; 132 (Pt 9) 2449-2463
    CrossrefPubMedGoogle Scholar
  • 30 McKnight K, Jiang Y, Hart Y. et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology 2005; 65 (11) 1730-1736
    CrossrefPubMedGoogle Scholar
  • 31 Dalmau J, Gleichman AJ, Hughes EG. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7 (12) 1091-1098
    CrossrefPubMedGoogle Scholar
  • 32 Lancaster E, Lai M, Peng X. et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010; 9 (01) 67-76
    CrossrefPubMedGoogle Scholar
  • 33 Vincent A, Irani SR, Lang B. The growing recognition of immunotherapy-responsive seizure disorders with autoantibodies to specific neuronal proteins. Curr Opin Neurol 2010; 23 (02) 144-150
    CrossrefPubMedGoogle Scholar
  • 34 Waldbaum S, Patel M. Mitochondria, oxidative stress, and temporal lobe epilepsy. Epilepsy Res 2010; 88 (01) 23-45
    CrossrefPubMedGoogle Scholar
  • 35 Voss LJ, Jacobson G, Sleigh JW, Steyn-Ross A, Steyn-Ross M. Excitatory effects of gap junction blockers on cerebral cortex seizure-like activity in rats and mice. Epilepsia 2009; 50 (08) 1971-1978
    CrossrefPubMedGoogle Scholar
  • 36 Lopez-Garcia MA, Feria-Romero IA, Fernando-Serrano H, Escalante-Santiago D, Grijalva I, Orozco-Suarez S. Genetic polymorphisms associated with antiepileptic metabolism. Front Biosci (Elite Ed) 2014; 6: 377-386
    CrossrefPubMedGoogle Scholar
  • 37 Depondt C. The potential of pharmacogenetics in the treatment of epilepsy. Eur J Paediatr Neurol 2006; 10 (02) 57-65
    CrossrefPubMedGoogle Scholar
  • 38 Franco V, Perucca E. The pharmacogenomics of epilepsy. Expert Rev Neurother 2015; 15 (10) 1161-1170
    CrossrefPubMedGoogle Scholar
  • 39 Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 2011; 365 (10) 919-926
    CrossrefPubMedGoogle Scholar
  • 40 Livingston JH. Management of intractable epilepsy. Arch Dis Child 1991; 66 (12) 1454-1456
    CrossrefPubMedGoogle Scholar
  • 41 French J. Pseudoseizures in the era of video-electroencephalogram monitoring. Curr Opin Neurol 1995; 8 (02) 117-120
    CrossrefPubMedGoogle Scholar
  • 42 Tabarki B, Thabet F. [Vitamin-responsive epilepsies: an update]. Arch Pediatr 2013; 20 (11) 1236-1241
    CrossrefPubMedGoogle Scholar
  • 43 Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30 (04) 389-399
    CrossrefPubMedGoogle Scholar
  • 44 Sazgar M, Bourgeois BF. Aggravation of epilepsy by antiepileptic drugs. Pediatr Neurol 2005; 33 (04) 227-234
    CrossrefPubMedGoogle Scholar
  • 45 Smith D, Chadwick D. The management of epilepsy. J Neurol Neurosurg Psychiatry 2001; 70 (suppl 2) II15-II21
    CrossrefPubMedGoogle Scholar
  • 46 Patsalos PN, Berry DJ, Bourgeois BF. 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 (07) 1239-1276
    CrossrefPubMedGoogle Scholar
  • 47 Cramer JA. Optimizing long-term patient compliance. Neurology 1995; 45 (2, suppl 1) S25-S28
    PubMedGoogle Scholar
  • 48 Toenders W. Patient compliance in medical practice and clinical trials. Int J Risk Saf Med 1992; 3 (05) 338
    CrossrefPubMedGoogle Scholar
  • 49 Perrine K, Congett S. Neurobehavioral problems in epilepsy. Neurol Clin 1994; 12 (01) 129-152
    CrossrefPubMedGoogle Scholar
  • 50 Mattson RH, Cramer JA, Collins JF. et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313 (03) 145-151
    CrossrefPubMedGoogle Scholar
  • 51 St Louis EK. Truly “rational” polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol 2009; 7 (02) 96-105
    CrossrefPubMedGoogle Scholar
  • 52 French JA, Kanner AM, Bautista J. et al. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology; Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62 (08) 1261-1273
    CrossrefPubMedGoogle Scholar
  • 53 Schmidt D. Modern management of epilepsy: rational polytherapy. Baillieres Clin Neurol 1996; 5 (04) 757-763
    PubMedGoogle Scholar
  • 54 Deckers CL, Czuczwar SJ, Hekster YA. et al. Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia 2000; 41 (11) 1364-1374
    CrossrefPubMedGoogle Scholar
  • 55 Patsalos PN, Fröscher W, Pisani F, van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia 2002; 43 (04) 365-385
    CrossrefPubMedGoogle Scholar
  • 56 Deckers CL. Overtreatment in adults with epilepsy. Epilepsy Res 2002; 52 (01) 43-52
    CrossrefPubMedGoogle Scholar
  • 57 Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepilepticdrug effects: a randomized trial. Neurology 2004; 62 (01) 23-27
    CrossrefPubMedGoogle Scholar
  • 58 Naritoku DK, Hulihan JF, Schwarzman LK, Kamin M, Olson WH. Effect of cotherapy reduction on tolerability of epilepsy add-on therapy: a randomized controlled trial. Ann Pharmacother 2005; 39 (03) 418-423
    CrossrefPubMedGoogle Scholar
  • 59 Baulac M. Rational conversion from antiepileptic polytherapy to monotherapy. Epileptic Disord 2003; 5 (03) 125-132
    PubMedGoogle Scholar
  • 60 Stephen LJ, Brodie MJ. Seizure freedom with more than one antiepileptic drug. Seizure 2002; 11 (06) 349-351
    CrossrefPubMedGoogle Scholar
  • 61 Granata T, Marchi N, Carlton E. et al. Management of the patient with medically refractory epilepsy. Expert Rev Neurother 2009; 9 (12) 1791-1802
    CrossrefPubMedGoogle Scholar
  • 62 Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia 2014; 55 (01) 47-56
    CrossrefPubMedGoogle Scholar
  • 63 French JA, Krauss GL, Steinhoff BJ. et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia 2013; 54 (01) 117-125
    CrossrefPubMedGoogle Scholar
  • 64 Spencer S, Huh L. Outcomes of epilepsy surgery in adults and children. Lancet Neurol 2008; 7 (06) 525-537
    CrossrefPubMedGoogle Scholar
  • 65 Téllez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 2005; 128 (Pt 5) 1188-1198
    CrossrefPubMedGoogle Scholar
  • 66 Bien CG, Szinay M, Wagner J, Clusmann H, Becker AJ, Urbach H. Characteristics and surgical outcomes of patients with refractory magnetic resonance imaging-negative epilepsies. Arch Neurol 2009; 66 (12) 1491-1499
    PubMedGoogle Scholar
  • 67 Maehara T, Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia 2001; 42 (01) 67-71
    CrossrefPubMedGoogle Scholar
  • 68 Benifla M, Otsubo H, Ochi A. Snead OC III, Rutka JT. Multiple subpial transections in pediatric epilepsy: indications and outcomes. Childs Nerv Syst 2006; 22 (08) 992-998
    CrossrefPubMedGoogle Scholar
  • 69 Milby AH, Halpern CH, Baltuch GH. Vagus nerve stimulation in the treatment of refractory epilepsy. Neurotherapeutics 2009; 6 (02) 228-237
    CrossrefPubMedGoogle Scholar
  • 70 Neal EG, Chaffe H, Schwartz RH. et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008; 7 (06) 500-506
    CrossrefPubMedGoogle Scholar
  • 71 Kossoff EH, Dorward JL. The modified Atkins diet. Epilepsia 2008; 49 (suppl 8) 37-41
    CrossrefPubMedGoogle Scholar
  • 72 Schachter SC, Guttag J, Schiff SJ, Schomer DL. Summit Contributors. Advances in the application of technology to epilepsy: the CIMIT/NIO Epilepsy Innovation Summit. Epilepsy Behav 2009; 16 (01) 3-46
    CrossrefPubMedGoogle Scholar
  • 73 Fisher R, Salanova V, Witt T. et al. SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010; 51 (05) 899-908
    CrossrefPubMedGoogle Scholar
  • 74 Anderson WS, Kossoff EH, Bergey GK, Jallo GI. Implantation of a responsive neurostimulator device in patients with refractory epilepsy. Neurosurg Focus 2008; 25 (03) E12
    CrossrefPubMedGoogle Scholar
  • 75 Chang EF, Quigg M, Oh MC. et al. Epilepsy Radiosurgery Study Group. Predictors of efficacy after stereotactic radiosurgery for medial temporal lobe epilepsy. Neurology 2010; 74 (02) 165-172
    CrossrefPubMedGoogle Scholar
  • 76 Walker LE, Mirza N, Yip VLM, Marson AG, Pirmohamed M. Personalized medicine approaches in epilepsy. J Intern Med 2015; 277 (02) 218-234
    CrossrefPubMedGoogle Scholar