Discontinuing antiepileptic drugs in children with epilepsy: A prospective study
Corresponding Author
Dr. Shlomo Shinnar MD, PhD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
The Gertrude Sergievsky Center, Columbia College of Physicians and Surgeons, New York, NY
Epilepsy Management Center, Montefiore Medical Center, 111 E. 210th Street, Bronx, NY 10467Search for more papers by this authorAnne T. Berg PhD
Department of Pediatrics, Yale University School of Medicine, New Haven, CT
Search for more papers by this authorSolomon L. Moshé MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Neuroscience, Montefiore, Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorHarriet Kang MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorChristine O'Dell RN, MSN
Department of Nursing, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorMarta Alemany
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorEli S. Goldensohn MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorW. Allen Hauser MD
The Gertrude Sergievsky Center, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorCorresponding Author
Dr. Shlomo Shinnar MD, PhD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
The Gertrude Sergievsky Center, Columbia College of Physicians and Surgeons, New York, NY
Epilepsy Management Center, Montefiore Medical Center, 111 E. 210th Street, Bronx, NY 10467Search for more papers by this authorAnne T. Berg PhD
Department of Pediatrics, Yale University School of Medicine, New Haven, CT
Search for more papers by this authorSolomon L. Moshé MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Neuroscience, Montefiore, Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorHarriet Kang MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Department of Pediatrics, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorChristine O'Dell RN, MSN
Department of Nursing, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorMarta Alemany
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorEli S. Goldensohn MD
Department of Neurology, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Montefiore/Einstein Epilepsy Management center, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx
Search for more papers by this authorW. Allen Hauser MD
The Gertrude Sergievsky Center, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorAbstract
In a prospective study, antiepileptic drugs were discontinued in 264 children with epilepsy after a mean seizure-free interval of 2.9 years. They were then followed for a mean of 58 months to ascertain whether seizures recurred. Seizures recurred in 95 (36%) of the children. Etiology was a significant predictor of outcome (relative risk [RR] = 1.81). On multivariable analysis, significant factors in the idiopathic group included age at onset above 12 years (RR = 5.4), a family history of seizures (RR = 3.1), the presence of slowing on the electroencephalogram prior to medication withdrawal (RR = 2.4), and a history of atypical febrile seizures (RR = 2.8). Specific epileptic syndromes such as juvenile myoclonic epilepsy and benign rolandic epilepsy were also significant predictors of outcome. In the remote symptomatic group, significant predictors of outcome included age at onset older than 12 years (RR = 3.6), moderate to severe mental retardation (IQ < 50) (RR = 2.8), a history of atypical febrile seizures (RR = 2.0), and a history of absence seizures (RR = 0.4). The majority of children with epilepsy in remission while on antiepileptic drug therapy will remain seizure free when medications are withdrawn. A few readily available parameters distinguish those with a good prognosis from those in whom seizures are likely to recur. These data provide the framework for the clinical decision making for withdrawal of medications in these children.
References
- 1 Shinnar S, Vining EPG, Mellits ED, et al. Discontinuing antiepileptic medication in children with epilepsy after two years without seizures: a prospective study. N Engl J Med 1985; 313: 976–980
- 2 Todt H. The late prognosis of epilepsy in childhood: results of a prospective followup study. Epilepsia 1984; 25: 137–144
- 3 Emerson R, D'Souza BJ, Vining EP, et al. Stopping medication in children with epilepsy: predictors of outcome. N Engl J Med 1981; 304: 1125–1129
- 4 Holowach J, Thurston DL, O'Leary J. Prognosis in childhood epilepsy: followup study of 148 cases in which therapy had been suspended after prolonged anticonvulsant control. N Engl J Med 1972; 286: 169–174
- 5 Holowach-Thurston JH, Thurston DL, Hixon BB, et al. Prognosis in childhood epilepsy: additional followup of 148 children 15 to 23 years after withdrawal of anticonvulsant therapy. N Engl J Med 1982; 306: 831–836
- 6 Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients with remission. Lancet 1991; 337: 1175–1180
- 7 Arts WFM, Visser LH, Loonen MCB, et al. Follow-up of 146 children with epilepsy after withdrawal of antiepileptic therapy. Epilepsia 1988; 29: 244–250
- 8 Bouma PAD, Peters ACB, Arts RJHM, et al. Discontinuation of antiepileptic therapy: a prospective trial in children. J Neurol Neurosurg Psychiatry 1987; 50: 1579–1583
- 9 Broeker H, Walter S. Zur frage der rezidive bei ausgeheilten epileprien in erwachsenenalton. Psychiatr Neurol Med Psychol 1981; 33: 536–542
- 10 Forster CH, Schmidberger G. Prognostische Wertigkeit von EEG verlautsuntersuchungen bei Kindern mit anfallsrezidiven nach absetzen der antikonvulsiven therapie. In: H Doose, G Gross Selbeck, eds. Epilepsie. Stuttgart: Thieme, 1978: 252–255
- 11 Juul-Jensen P. Frequency of recurrence after discontinuance of anticonvulsant therapy in patients with epileptic seizures. Epilepsia 1964; 5: 352–363
- 12 Juul Jensen P. Frequency of recurrence after discontinuance of anticonvulsant therapy in patients withepileptic seizures: a new followup study after 5 years. Epilepsia 1968; 9: 11–16
- 13 Keranen T. Discontinuation of antiepileptic drugs. In: M Sillanpaa, SI Johannessen, G Blennow, M Dam, eds. Pediatric epilepsy. Petersfield, Great Britain: Wrightson Biomedical, 1990: 333–340
- 14 Matricardi M, Brinciott M, Benedetti P. Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy. Epilepsia 1989; 30: 582–589
- 15 Nalin A, Galli V, Ferrari P, Ciccaron V. Sospensione della therapia antiepilettica in soggetti con epilessia insorta nell'eta infantile. Pediatr Med Chir 1982; 4: 601–606
- 16 Pestre M, Loiseau P, Larrieu E, et al. Withdrawal of antiepileptic drug therapy in adolescent epileptic patients. 1987; 16: 395–400
- 17 Tsuchiya S, Maruyama H, Maruyama K, et al. A follow up study of 1007 epileptic children with anticonvulsant therapy for more than 10 years. No To Hattatsu 1985; 17: 23–28
- 18 Visser LH, Arts WFM, Loonen MCB, et al. Follow-up study of 166 children with epilepsy after withdrawal of anticonvulsant therapy. Adv Epileptol 1987; 16: 401–404
- 19 Gross-Tsur V, Shinnar S. Discontinuing antiepileptic drug therapy in patients with epilepsy. In: E Wyllie, ed. The treatment of epilepsy: principles and practice. Philadelphia: Lea & Febiger, 1993: 858–866
- 20 Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994 (in press)
- 21 Pedley TA. Discontinuing antiepileptic drugs. N Engl J Med 1988; 318: 982–984
- 22 Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975; 16: 1–66
- 23 Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981; 22: 489–501
- 24 Nelson KB, Ellenberg JH. Prognosis of children with febrile seizures. Pediatrics 1978; 61: 720–727
- 25 National Institutes of Health. Febrile seizures: consensus development conference summary, vol 2, no 2. Bethesda, MD: National Institutes of Health, 1980
- 26 Gross Tsur V, Shinnar S. Convulsive status epilepticus in children. Epilepsia 1993; 34 (suppl 1): 512–520
- 27 Maytal J, Shinnar S, Moshe SL, Alvarez LA. The low morbidity and mortality of status epilepticus in children. Pediatrics 1989; 83: 323–331
- 28 Commission on classification and terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30: 389–399
- 29 J Roger, C Dravet, M Bureau, et al, eds. Epileptic syndromes in infancy, childhood and adolescence. London: John-Libbey Eurotext, 1985
- 30 Commission on epidemiology and prognosis, International League Against Epilepsy. Guidelines for epidemiologic studies on epilepsy. Epilepsia 1993; 34: 592–596
- 31 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481
- 32 Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163–170
- 33 Tarone RE, Ware J. On distribution-free tests for equality of survival distributions. Biometrika 1977; 64: 156–60
- 34 Elandt-Johnson RC, Johnson NL. Survival models and data analysis. New York: Wiley, 1980: 150–180
- 35
Cox DR.
Regression models and life-tables.
J R Stat Soc (B)
1972;
34:
187–220
10.1111/j.2517-6161.1972.tb00899.x Google Scholar
- 36 Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: Wiley, 1980: 70–142
- 37 WJ Dixon, ed. BMDP statistical software 1981. Berkeley, CA: University of California Press, 1981: 555–575
- 38 Hauser WA, Hesdorffer DC. Epilepsy: frequency, causes and consequences. New York: Epilepsy Foundation of America-Demos, 1990
- 39 Huttenlocher PR, Hapke RJ. A follow up study of intractable seizures in childhood. Ann Neurol 1990; 28: 699–705
- 40
Sillanpaa M.
Social functioning and seizure status of young adults with onset of epilepsy in childhood. An epidemiological 20 year follow up study.
Acta Neurol Scand Suppl
1983;
96:
7–77
10.1111/j.1600-0404.1983.tb01529.x Google Scholar
- 41 Goulden KJ, Shinnar S, Koller H, et al. Epilepsy in children with mental retardation: a cohort study. Epilepsia 1991; 32: 690–697
- 42 Freeman JM, Tibbles J, Camfield C, et al. Benign epilepsy of childhood: a speculation and its ramifications. Pediatrics 1987; 79: 864–868
- 43 Shinnar S. Treatment decisions in childhood seizures. In: WE Dodson, JM Pellock, eds. Pediatric epilepsy: diagnosis and therapy. New York: Demos, 1993: 215–221
- 44 Dodson WE, DeLorenzo RJ, Pedley TA, et al. The treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America's working group on status epilepticus. JAMA 1993; 270: 854–859
- 45 Annegers JF, Hauser WA, Elveback LR. Remission of seizures and replase in patients with epilepsy. Epilepsia 1979; 20: 729–737
- 46 Reynolds EH. Chronic antiepileptic toxicity: a review. Epilepsia 1975; 16: 319–352
- 47 American Academy of Pediatrics, Committee on Drugs. Behavioral and cognitive effects of anticonvulsant therapy. Pediatrics 1985; 76: 644–647
- 48 Masur DM, Shinnar S. The neuropsychology of childhood seizure disorders. In: S Segalowitz, I Rapin, eds. Handbook of neuropsychology, vol 7. Childhood neuropsychology. Amsterdam: Elsevier, 1992: 457–470
- 49 Trimble MR. Anticonvulsant drugs and cognitive function: a review of the literature. Epilepsia 1987; 28 (suppl 3): S36–S45
- 50 Vining EPG, Mellits ED, Dorsen MM, et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 1987; 80: 165–174
- 51 Shinnar S. Seizures in adolescents. In: SB Friedman, M Fisher, SK Schonberg, eds. Comprehensive adolescent health care. St. Louis: Quality Medical, 1992: 458–467
- 52 Chadwick D. Drug withdrawal and epilepsy when and how? Drugs 1988; 35: 579–583
- 53 Scheuer ML, Pedley TA. The evolution and treatment of seizures. N Engl J Med 1990; 323: 1468–1474
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