d in this group are some of the age-speci \201 c epilepsy syndromes. About 20 % of persons have continuous epilepsy, with no periods of remission (pathway d), and about 10 % epileps y with an intermittent pattern of relapse and remission (pathway e). Lifestyle measures Although this chapter is focused primarily on drug treatment, it must be emphasized that this is only part of an approach to ther- apy. Many seizures are provoked by factors such as stress, tired- ness, emotional disturbance, circadian rhythms, the menst rual cycle, alcohol, and lack of sleep. Avoiding provoking factors can be extremely importa nt. Such \200\230lifestyle \200\231 manipulation can assist drug therapy and render a prev iously refractory epilepsy completely con- trolled. These factors should not be overlooked. Their importance varies according to the type of epilepsy. In IGE, especially in ado- lesc ence, the avoidance of sleep deprivation or excessive alcohol intake can be very bene \201 cial. Many patients learn to recognize dangerous times, and take individual avoidance meas ures. Photosensitive patients should be counseled to avoid relevant stimuli. Occasionally, patients with established mild epilepsy can avoid drug treatment altogether with these simp le measures. Alternative or complementary medicine can be a useful adjunct to therapy ( 22 ). Of course, it needs to be emphasized that seizure freedom is not the only good outcome, and therapy will often reduce the severity, timing, or frequency of seizures in bene \201 cia l ways which are not represented in this model. Acknowledgements This chapter is partly derived from Shorvon S. Handbook of Epilepsy Treatm ent (3rd edn). Oxford: Wiley Blackwell, 2009. This work Surgical and dietary therapy Resective surgical therapy for epilepsy should be considered i n all patients with chronic epilepsy, both adults and children ( 28 ) although it will be p ossible or appropriate in only a small minority (perhaps 5 % ). In adults, surgery is most effective in lesional and in mesial temporal lobe epilepsy, where surgical therapy can resu lt in seizure freedom in about 50 % of cases and signi \201 cant improve- ment in a furthe r 30 % ( 29 , 30 , 31 ). In other clinical situations, the outcome of surgery is less good. The assessment of a patient for suitability for epilepsy surgery should be carried out in experienced centers, where the necessary experience and resources are available. Surgical t herapy is considered further in Chapters 27 \200\22329. New onset of seizures Pathway a Pathway b Continuous pattern, or relapse within 5 years of onset ( 40%) Long-term remission developing within 5 years of onset ( 60%) Pathway c Pathway d Pathway e Intermittent pattern \200\223 active epilepsy with periods or remission ( 10%) Long-term remission developing >5 years after onset ( 10%) Continuous patern \200\223 no period of remission ( 20%) Vagal nerve stimulation is another option for intractable epi- lepsy, but must be considere d palliative only, and very few patients become seizure-free using this technique and few b ene \201 t in the longer term. Fig. 23.1 Patterns of epilepsy over time. Neligan A, Bell G, Sander S, Shorvon S. How refra ctory is refractory epilepsy? Patterns of relapse and remission in refractory epilepsy. Epi lepsy Res 2011; 96 (3):225 \200\22330. CHAPTER 23 the medical treatment of chronic active epilepsy 259 was undertaken at UCLH/UCL who received a proportion of fund- ing from the Department of He alth \200\231s NIHR Biomedical Research Centers funding scheme. Myoclonic Epilepsy: The Janz Syndrome , pp. 11 \200\223 32 . Stroud : Wrightson Biomedical Publishing Ltd , 2000 . 19. Zaccara G , Franciotta D , Perucca E . Idiosyncratic adverse reactions to antiepileptic drugs . Epilepsia 2007 ; 48 : 1223 \200\223 44 . 20. Patsalos PN , Perucca E . Clinically important drug interactions in References epilepsy: interactions between antiepileptic drugs and other drugs . Lancet Neurol 2003 ; 2 : 473 \200\223 81 . 1. Shorvon S . The treatment of chronic epilepsy: a review of recent 21. Patsalos PN , Perucca E . Clinically important drug interactions in studies of clinical ef \201 cacy and side effects . Curr Opin Neurol 2007 ; 20 : 159 \200 \223 63 . epilepsy: general features and interactions between antiepileptic drugs . Lancet Neurol 200 3 ; 2 : 347 \200\223 56 . 2. Shorvon SD . The temporal aspects of prognosis in epilepsy. J Neurol 22. Ricotti V , Delanty N . Use of complementary and alternative medicine Neurosurg Psychiatry 1984 ; 47 : 1157 \200\223 65 . in epilepsy . Curr Neurol Neurosci Rep 2006 ; 6 : 347 \200\223 53 . 3. Annegers JF , Hauser WA , Elveback LR . Remission of seizures and 23. Kwan P , Arzimanoglou A , Berg AT , Brodie MJ , Allen Hauser W , Mathern G , et al . De \201 nition of drug resistant epilepsy: consensus proposal by the AD hoc Task Force of th e ILAE Commission on Therapeutic Strategies . Epilepsia 2010 ; 51 : 1069 \200\223 77 . relapse in patients with epilepsy . Epilepsia 1979 ; 20 : 729 \200\223 37 . 4. Geerts A , Arts WF , Stroink H , Peeters E , Brouwer O , Peters B , et al . Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch Study of Epileps y in Childhood . Epilepsia 2010 ; 51 : 1189 \200\223 97 . 24. Shorvon SD . Medical assessment and treatment of chronic epilepsy . 5. Lindsten H , Stenlund H , Forsgren L . Remission of seizures in a Br Med J 1991 ; 302 : 363 \200\2236 . population-based adult cohort with a newly diagnosed unprovoked epileptic seizure . Epileps ia 2001 ; 42 : 1025 \200\223 30 . 25. Schiller Y . Seizure relapse and development of drug resistance following long-term seizure remission . Arch Neurol 2009 ; 66 : 1233 \200\223 9 . 26. Berg AT , Levy SR , Testa FM , D \200\231Souza R . Remission of epilepsy after two 6. MacDonald BK , Johnson AL , Goodridge DM , Cockerell OC , Sander JW , Shorvon SD . Factors predicting prognosis of epilepsy after presentation with seizures . Ann Neurol 2000 ; 48 : 833 \200\223 41 . drug failures in children: a prospective study . Ann Neurol 2009 ; 65 : 510 \200\223 19 . 27. Callaghan BC , Anand K , Hesdorffer D , Hauser WA , French JA . 7. Kwan P , Brodie MJ . Early identi \201 cation of refractory epilepsy . Likelihood of seizure remission in an adult population with refractory epilepsy . Ann Neuro l 2007 ; 62 : 382 \200\223 9 . N Engl J Med 2000 ; 342 : 314 \200\223 19 . 8. Semah F , Picot MC , Adam C , Broglin D , Arzimanoglou A , Bazin B , 28. Choi H , Heiman G , Pandis D , Cantero J , Resor SR , Gilliam FG , et al . Seizure remi ssion and relapse in adults with intractable epilepsy: a cohort study . Epilepsia 2008 ; 49 : 1440 \200\223 5 . et al . Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neuro logy 1998 ; 51 : 1256 \200\223 62 . 9. Moran NF , Poole K , Bell G , Solomon J , Kendall S , McCarthy M , et al . 29. Jeha LE , Najm IM , Bingaman WE , Khandwala F , Widdess-Walsh P , Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utiliza tion and impact on life in 1652 people with epilepsy . Seizure 2004 ; 13 : 425 \200\223 33 . Morris HH , et al . Predictors of outcome after temporal lobectomy for the treatment of int ractable epilepsy . Neurology 2006 ; 66 : 1938 \200\223 40 . 30. de Tisi J , Bell GS , Pea cock JL , McEvoy AW , Harkness WF , Sander JW , et al . The long-term outcome of adult epil epsy surgery, patterns of seizure remission, and relapse: a cohort study . Lancet 2011 ; 37 8 ( 9800 ): 1388 \200\223 95 . 10. Shorvon SD . Historical introduction: The causes of epilepsy in the pre-molecular era ( 1860 \200\2231960) . In: Shorvon SD , Andermann F , Guerrini R (eds) The Causes of Epilepsy Common and Uncommon Causes in Adults and Children , pp. 1 \200\223 20 . Cambridge: Cambri dge University Press , 2011 . 31. Cross JH , Jayakar P , Nordli D , Delalande O , Duchowny M , Wieser HG , et al. International League against Epilepsy, Subcommission for Pediatric Epilepsy Surgery; Commissions of Neurosurgery and Pediatrics . Proposed criteria for referral and evaluation of children for epilepsy surgery: recommendations of the Subcommission for Pediatric Epile psy Surgery . Epilepsia. 2006 ; 47 : 952 \200\223 9 . 11. French JA , Kanner AM , Bautista J , Abou-Khalil B , Browne T , Harden CL , et al . Ef \201 cacy and tolerability of the new antiepileptic drugs II: treat ment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommit tee and Quality Standards Subcommittee of the American Academy of Neurology and the America n Epilepsy Society . Neurology 2004 ; 62 : 1261 \200\223 73 . 32. Cohen-Gadol AA , Wilhelmi BG , Collignon F , White JB , Britton JW , Cambier DM , et al . Long-term outcome of epilepsy surgery among 399 patients with nonlesional seizure foci i ncluding mesial temporal lobe sclerosis . J Neurosurg 2006 ; 104 : 513 \200\223 24 . 12. Levy RH , Mattson RH , Meldrum B , Perucca E . Antiepileptic drugs ( 5th edn ). Philade lphia, PA : Lippincott, Williams & Wilkins , 2002 . 13. Shorvon SD . Management of chronic epilepsy . In: Shorvon SD , 33. Keene DL . A systematic review of the use of the ketogenic diet in Perucca E , Engel J (eds) Treatment of epilepsy ( 3rd edn ), pp. 153 \200\223 62 . Oxford : Blackwell Science , 2009 . childhood epilepsy . Pediatr Neurol 2006 ; 35 : 1 \200\223 5 . 34. Goodridge DM , Shorvon SD . Epileptic seizures in a population of 6000. II: Treatment a nd prognosis . Br Med J 1983 ; 287 : 645 \200\223 7 . 35. Shorvon S , Luciano AL . Prognos is of chronic and newly diagnosed 14. Shorvon SD . Handbook of the treatment of epilepsy ( 3rd edn). Oxford : Wiley-Blackwell , 2010 . 15. Glauser T , Ben-Menachem E , Bourgeois B , Cnaan A , Chadwick D , epilepsy: revisiting temporal aspects . Curr Opin Neurol 2007b ; 20 : 208 \200\223 12 . 36 . Del Felice A , Beghi E , Boero G et al . Early versus late remission in a cohort of patie nts with newly diagnosed epilepsy . Epilepsia 2010 ; 51 : 37 \200\223 42 . 37. Shorvon SD , Sander JW . Temporal patterns of remission and relapse in patients with epilepsy . Schmid t D , Morceli P. (eds) Intractable Epilepsy: experimental and clinical aspects , pp. 13 \200\223 23 . New York : Raven Press , 1986 . Guerreiro C , et al . ILAE treatment guidelines: evidence-based analysis of antiepileptic d rug ef \201 cacy and effectiveness as initial monotherapy for epileptic seizures and syndr omes . Epilepsia 2006 ; 47 : 1094 \200\223 120 . 16. Marson AG , Al-Kharusi AM , Alwaidh M , Appleton R , Baker GA , Chadwick DW ; SANAD Stu dy group . The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxca rbazepine, or topiramate for treatment of partial epilepsy: an unblended randomized control led trial . Lancet 2007 ; 369 : 1000 \200\223 15 . 17. Luciano AL , Shorvon SD . Results o f treatment changes in patients 38. Sillanpaa M , Schmidt D . Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study . Brain 2006 ; 129 : 617 \200\223 24 . with apparently drug- resistant chronic epilepsy . Ann Neurol 2007 ; 62 : 375 \200\223 81 . 39. Neligan A , Bell G , Sander S , Shorvon S . How refractory is refractory epilepsy? Patt erns of relapse and remission in refractory epilepsy . Epilepsy Res 2011 ; 96 ( 3 ): 225 \200\223 30 . 18. Genton P , Gelisse P , Thomas P . Juvenile myoclonic epilepsy today: Current de \201 nitions and limits . In: Schmitz B , Sander T (eds) Juvenile This page intentionally left blank CHAPTER 24 Epilepsy in Remission Jerry J. Shih Introduction The question of whether an epileptic condition is likely to go into remission is arguably the single most important question patients have for their treating physicians. When seizures go into remission there is a dramatic increase in quality of life ( 1 , 2 ) and sense of well-being, as well as the opening up of avenues for employment and greater pe rsonal freedoms such as driving ( 3 ). Together with being side effect-free on seizure trea tment, seizure freedom consti- tutes one of the major goals of successful epilepsy manageme nt. who have been refractory to multiple treatment approaches ( 7 ). Elderly patients suffering from post-stroke epilepsy have differing outcomes compared to children with familial epile psies. Thus, in terms of clinical usefulness, any discussion on seizure remission needs to take into account patient demographics and the etiology of the seizure disorder. Population-based studies have fairly consistently shown that 60 \200\22380 % of patients di agnosed with a new-onset seizure disorder will achieve seizure remission in their lifetime ( 4 , 8 , 9 ). We routinely teach neurology trainees the dictum that \200\230you can make about two-thirds of your epilepsy patients seizure free with antiseizure medication treat- ment \200\231 (Table 24.1 ). However, depending on the clinical history and epilepsy syndro me, individual patients can expect varying chances of seizure remission. In general, the id iopathic generalized epilepsies have a higher seizure remission rate than partial-onset epi lepsy or symptomatic epilepsy ( 9 \200\22311 ). Certain epilepsy syndromes have a poor prog nosis for seizure control. This chapter will review seizure remission rates by age group, e pilepsy syndromes, and the speci \201 c clinical circumstance of medically refractory epil epsy. Favorable and unfavorable factors affecting outcome will be discussed. This topic has been the subject of numerous studies over the past 50 years. However, it is important to note that this extensive litera- ture is not homogenous. Methodologies differ, and research design varies greatly based on the speci \201 c questions asked. Many of the earlier studies on seizure remission rates were drawn from select populations seen at tert iary medical centers ( 4 ). Some more recent studies are retrospective population-based, and derived from rural populations ( 5 , 6 ), but may lack the rigorous data collection see n in earlier single center studies. Studies also differ in terms of when their populations were evaluated vis- -vis the disease and then remission process. Some studies speci \201 cally evaluated patients with newly diagnosed or untreated epilepsy; others recruited only patients who were deemed medically intractable and have failed at least several anticonvuls ant medications. Patients with new-onset seizures represent a different epilepsy population than patients New-onset seizures By de \201 nition, epilepsy is diagnosed after a patient has two or mor e unprovoked seizures. A person who presents with a single Table 24.1 Terminal remission data from selected studies ( 7 ) Reference Study setting Special study features No. of patients Median follow-up (years) Years in remission % in remission at median follow-up Elwes et al. ( 10 ) Hospital 106 5.5 2 79 Shafer et al. ( 11 ) Community 432 17 5 66 Collaborative Group ( 12 ) Hospital 280 4 1 70 Cockerell et al. ( 13 ) Community De \201 nite epilepsy 564 7 5 68 Sillanpaa et al. ( 14 ) Hospital Children only 176 28 1 80 Lindsten et al. ( 15 ) Community \211 1 baseline seizure 107 9 5 64 \211 2 baseline seizures 89 9 5 58 Reprinted with permission from Kwan P, Sander JW. J Neurol Neurosurg Psychiatry 2004; 75:13 76 \200\22381. oxford textbook of epilepsy and epileptic seizures 262 unprovoked seizure does not carry the epilepsy diagnosis, but by virtue of having the seizu re, differs from the general population as far as the risk of developing epilepsy. Populati on-based studies place the general risk of a person developing epilepsy in her life- time a t 1 \200\2233 % ( 12 , 13 ). Prospective studies in the pediatric age group and general pop ulation of patients identi \201 ed after a \201 rst unprovoked seizure estimate that abo ut 25 % will go on to have a second unprovoked seizure and be classi \201 ed as epileptic ( 14 , 15 ). In looking at this from a different perspective, 75 % of patients with a singl e unprovoked seizure will achieve \200\230remission \200\231 without any treatment. majority of patients will achieve seizure remission regardless of the speci \201 c form of treatment. An interesting corollary to the question of epilepsy remission with treatment is the issue of spontaneous remission of seizures after a diagnosis of epilepsy is made. Because effecti ve drug treat- ments have been in existence for almost 100 years, there are mini- mal data regarding the natural history of the untreated disease state. There are no prospective long itudinal studies of untreated epilepsy and the prospect of future studies of this kind is u nlikely on ethical grounds. However, data do exist from developing or resource-poor countri es ( 7 ). Nicoletti et al. ( 6 ) conducted an epidemiological survey of an untreated or und ertreated population of chronic epileptics in rural Bolivia. At the 10-year point of follow -up, \200\230adequate \200\231 seizure information was obtained from 71 of the 118 people originally identi \201 ed as having \200\230active epilepsy \200\231. Of these 71 people, 31 (44 % ) were in seizure remission de \201 ned as seizure free for greater than 5 years . A household survey in Ecuador identi \201 ed 1029 people with \200\230probable or de \201 nite \200\231 epilepsy who were untreated or undertreated, and 31 % were in remission for greater than 1 year ( 5 ). A retrospective Finnish study of 33 people with untreated ep ilepsy found a 2-year remission rate of 42 % (20). It is important to point out that these studies suffer from method- ological limitations which reduce the level of scienti \201 c con \201 dence in the results. However, there is no doubt that a small population of perso ns with epilepsy, whether it be 10 % , 20 % , or higher, will achieve long-term spontaneous remission of their seizures. In patients with new-onset epilepsy, several seminal studies over the past 35 years have es tablished the \200\230two-thirds \200\231 dictum. A meta- analysis by Berg and Shinnar ( 1 6 ) of pre-1990 prospective observa- tional studies found that on average, 60 % of patients achieve remission as de \201 ned by seizure freedom for at least 2 years. In a longitudin al study of patients with epilepsy in Rochester, Minnesota, the probability of being in rem ission (at least 5 con- secutive years seizure free, and continuing) at 20 years after diag - nosis was 70 % ( 4 ) (Fig. 24.1 ). A large prospective population-based British study enr olling from 275 general practices found a 5-year seizure remission rate of 68 % in patients with a \200\230de \201 nite \200\231 diagnosis of epilepsy ( 17 ). In a prospective sing le-center study of newly diag- nosed and mostly untreated epilepsy patients, Kwan and Brodi e found 63 % achieved at least a 1-year seizure remission after anti- convulsant treatment ( 18 ). These studies have shown consistently similar results over the last several decades , despite advances in therapy and changes to the classi \201 cation of seizures and epilep sy ( 19 ). This has led to a belief amongst many epileptologists that a Age and remission rates The general perception is that seizures beginning in childhood are more likely to go into remission than seizures that start in adult- hood, although evidence to that effect is sparse. Some of the earli- est data on childhood epilepsy remission rate s were derived from a population-based study in Nova Scotia which followed 504 chil- dren f or an average of 7 years ( 21 ). Even though children with absence epilepsy and minor motor seizures were excluded from the analysis, 55 % of the cohort was in remission at the end o f the follow-up period. A prospective long-term population-based study in Finland followed 144 patients with seizure onset before age 16, an average of 37 years. At the end of follow -up, 67 % of 144 patients were in terminal remission, on or off antiepileptic drugs ( 22 ). About one-third (31 % ) had remission from \201 rst treatment, while 50 % of those in te rminal remission did so with a mean delay of 9 years. In a 15-year Dutch follow-up study of patients diagnosed with childhood new-onset epilepsy, 5-year seizure remission was reached by 71 % of the cohort ( 23 ). Berg and colleagues ( 11 ) pro- spectively followed 613 chil dren with newly diagnosed epilepsy in the US and found a 2-year remission rate of 74 % . Ag e of onset between 5 \200\2239 years old was associated with a substantially increased remi ssion rate. 80 60 n o i s s i m e r n 40 i t n e c r e P Remission ever In remission Without seizures or medication 20 There are far fewer studies evaluating the natural history of adult-onset epilepsy. Elwes e t al. ( 24 ) prospectively assessed the prognosis for seizure control in 106 patients refer red to an adult neurology clinic with previously untreated tonic \200\223clonic, partial, o r mixed seizures. After treatment, 73 % had at least a 2-year remis- sion period at the end of 4 years. However, only 51 of the 106 patients remained seizure free at the termination of the study. Lindsten et al. ( 25 ) followed an adult population-based cohort of 107 patie nts with newly diagnosed epilepsy for approximately 0 5 6 10 15 20 Years after diagnosis Fig. 24.1 Remission of seizures in epilepsy patients followed in Rochester, MN from 1935 \200\2231974. From Annegers et al. Epilepsia 1979; 20:729 \200\22337, with permission. CHAPTER 24 epilepsy in remission 263 their histories showed inclusion/exclusion characteristics of \200\230typi- cal \200\231 a bsence as initially proposed by Panayiotopoulos ( 32 ). Children ful \201 lling the criter ia for \200\230typical absence \200\231 had seizure remission rate of 95 % versus 77 % for the non-Panayiotopoulos group, and termi- nal remission rates of 82 % versus 51 % . While this study suffers from the limitations of a retrospective study, it does highlight the fac t that there may be subgroups within the broad CAE syndrome with slightly different remissi on outcomes. Nevertheless, the likeli- hood of seizure remission for children with CAE is c learly higher than patients in a general population-based study. 10 years. One-year, 3-year, and 5-year seizure remission rates were 68 % , 64 % , and 58 % , respectively. Thus, when one compares population-based studies of purely childhood epilep sy versus adult-onset epilepsy, there is no clear difference in seizure remis- sion rate. T he perception that childhood onset seizures have a higher remission rate likely stems from some studies with high numbers of patients diagnosed with childhood syndromes associ- ated with excellent long-term prognosis. Remission rate and epilepsy syndrome Although the recent International League Against Epile psy (ILAE) Commission on Classi \201 cations recommended changes to termi- nology and conc epts, no changes or revisions were made to the epilepsy syndromes recognized in previous IL AE classi \201 cations ( 19 ). An epilepsy syndrome is de \201 ned as \200\230a complex of signs and symptoms that de \201 ne a unique epilepsy condition \200\231 ( 26 ). The gro ups of syndromes are: idiopathic focal epilepsies of infancy and childhood, familial (autos omal dominant) focal epilepsies, symp- tomatic (or probably symptomatic) focal epilepsies, idiopathic generalized epilepsies, re \202 ex epilepsies, epileptic encephalopathies, prog ressive myoclonus epilepsies, and seizures not necessarily requiring a diagnosis of epileps y. There are over 25 speci \201 c syn- dromes in the 1989 ILAE report. Many syndromes have been extensively studied, and outcome and prognosis data are available. Juvenile absence epilepsy Juvenile absence epilepsy (JAE) is classi \201 ed as an idiopath ic gener- alized epilepsy. The age of onset is typically at or after puberty between the ag es of 10 \200\22317. Unlike in CAE where absence seizures can occur many times per day, abs ence seizures in JAE may only occur sporadically. There is less impairment of consciousness with absence seizures in JAE compared to absences in CAE. Patients with JAE can have gener alized tonic \200\223clonic seizures (usually upon awakening), myoclonic seizures, and even absence status epilepti- cus. There is a strong genetic component with linkage to chromo- somes 5, 8, 18, and 21. The response to antiepileptic medication is usually excellent ( 33 ). Some of the same longitudinal studies which recruited children with CAE also recruited s ubjects diagnosed with JAE. The Dutch Study of Epilepsy in Childhood documented a remission rate of 75 % in their eight subjects around the 15-year follow-up mark ( 23 ). The North A merican study showed 82 % of their 17 JAE patients achieved a 2-year remission; however, th ree of the 14 (21 % ) adolescents relapsed when followed for longer periods ( 11 ). Therefo re, like CAE, JAE is associated with a high likelihood of seizure remission. However, the n umber of JAE patients in these longitudinal studies is usually smaller, and caution must be used when interpreting these data. Childhood absence epilepsy Childhood absence epilepsy (CAE) is a distinct syndrome in the I LAE Classi \201 cation System ( 19 , 27 ). CAE typically begins between 6 \200\2238 years of age. Patients often have multiple absence seizures daily, but are developmentally and co gnitively normal. Absence seizures are associated with a generalized 3 \200\2234 Hz spike a nd wave pattern on the electroencephalogram (EEG), and may be provoked by hyper- ventilatio n or photic stimulation. An early meta-analysis of the outcome of CAE found widely varying remission rates ranging between 21 \200\22389 % ( 28 ). These differing remission rates ste m mainly from methodological differences in classifying CAE, length of fol- low-up, and the de \201 nition of remission. Some studies de \201 ned remission as seizure freedom off a nticonvulsant treatment for more than 1 year ( 29 , 30 ). Others used terminal remission de \201 ned as sei- zure freedom for more than 1 year at the end of follow-up ( 31 ). The hi ghest remission rate was found in the Dutch Study of Epilepsy in Childhood at 93 % being se izure free for greater than 1 year at the end of at least 12 years of follow-up ( 31 ). The authors also noted that 67 % of the children were free of seizures for over 10 years at st udy termination. In a further subanalysis, the remis- sion rate was 77 % if the criterion o f 1-year seizure remission off medication was applied. A North American study of 75 childre n with CAE found a 2-year remission rate of 88 % ( 11 ). A study in Nova Scotia followed 82 children with typical CAE a mean of 14 years with the goal of determining the proportion a nd character- istics of children who were seizure-free for longer than 1 year at the last y ear of long-term follow-up and who were off of anticonvul- sant medications ( 29 ). Their r emission rate was 65 % , and the devel- opment of generalized tonic \200\223clonic seizures and myoclonic seizures were poor prognostic signs for remission. Grosso and colleagues ret rospectively analyzed 119 children who ful \201 lled the criteria for CAE according to the ILAE classi \201 cation system ( 30 ). The children were further subdivided into two grou ps depending on whether Juvenile myoclonic epilepsy Juvenile myoclonic epilepsy (JME) is also classi \201 ed as an idiopathic generalized epilepsy. The age of onset is usually mid teens. Patients may prese nt with myoclonic jerks upon awakening in the morning. The myoclonus usually involves the n eck, shoulders, arms, or legs with the upper extremities being more frequently affected. Co nsciousness is usually not impaired during the myoclonic sei- zures. Generalized tonic \200 \223clonic and absence seizures are also seen. The interictal EEG consists of generalized p olyspike and wave dis- charges greater than 3 Hz ( 34 ). There is a strong genetic compo- n ent with linkage to chromosomes 2, 3, 5, 6, and 15. The North American cohort included 15 p atients with JME, eight (53 % ) of whom achieved a 2-year remission. However, \201 ve of the eight patients experienced a relapse during extended follow-up ( 11 ). The Dutch cohort had only seven JME patients, and 57 % achieved sei- zure remission ( 23 ). Penry et al. re trospectively analyzed the data of 50 patients with JME to determine long-term seizure cont rol and relapse rates in response to treatment with valproate ( 35 ). Follow-up ranged from 2 months to 9 years. Forty-three patients (86 % ) were seizure-free for over 1 year, but o ver half of this group experienced at least one relapse. Most of the relapses consisted of myoclonic seizures. Thus, the response to AED treatment is often good, but there is a high rate of relapse, especially if drug therapy is subtherapeutic or discontinued ( 33 ). oxford textbook of epilepsy and epileptic seizures 264 Benign childhood epilepsy with centrotemporal spikes Benign childhood epilepsy with centrot emporal spikes (BECTS) is a common focal onset epilepsy syndrome with an age of onset peaki ng between 7 \200\22310 years of age ( 36 ). BECTS is characterized by sensorimotor seizure s affecting the facial and oropharyngeal mus- cles, with clinical manifestations of droolin g, dysarthria or anar- thria, facial paraesthesias, and twitching of the lower face. Seizur es may occasionally evolve to upper extremity clonic shaking or sec- ondarily generalized t onic \200\223clonic seizures. The classic interictal EEG shows high amplitude diphasic spik es in the centrotemporal region(s) with a transverse dipole ( 37 ). As the name implies, BE CTS is associated with an excellent outcome and high remission rates. The Dutch Study of Ep ilepsy in Childhood ( 38 ) followed 29 children diagnosed with BECTS according to the ILAE classi \201 ca- tion. After a follow-up period of 12 \200\22317 years, 96 % had a terminal remission greater than 5 years and 89 % greater than 10 years. In a meta-analysis encompas sing 13 cohort groups and 794 patients, Bouma et al. ( 39 ) found a remission rate of 81 \200\223100 % , with 99.8 % of patients over age 18 being seizure free. These data support the fact that the seizures associated with BECTS are easy to control and will almost always remit by adulthood. epilepsy diagnoses, only 11 % with hippocampal sclerosis were seizure-free with medical tre atment ( 10 ). Because surgery is consid- ered superior to medications for the treatment of mesial temporal lobe epilepsy ( 43 ), most of the seizure remission data for MTLE-HS come from the surgical literature. The majority of patients who undergo surgical resection for M TLE-HS become seizure free ( 44 , 45 ), with the accepted rate of remission around 70 \200 \22380 % . Remission rate in medically refractory epilepsy Epileptologists have long recognized that a subpopulation of per- sons with epilepsy continues to have recurrent seizures despite mult iple medication trials. Terms that have been used to describe these patients include chroni c epilepsy, pharmacoresistant, medi- cation resistant, medically intractable, and medically refractory. For our purposes, the term medically refractory will be used. The current de \201 nition of medically refractory epilepsy that is accepted by most epileptologists encom passes: ( 1 ) failure to achieve seizure freedom after at least two appropriate medication trials, ( 2 ) at least one seizure per month for at least the past 3 months. The Glasgow st udy gave us an indication that seizure remission rates diminished signi \201 cantly after two medication trials ( 18 ). While 47 % of the ini- tial Glasgow cohort became seizure fre e with the \201 rst medication tried and an additional 13 % went into seizure remission w ith the second drug, only 4 % became seizure free with further medication trials. Callaghan and colleagues identi \201 ed 246 patients in a single medical center with medically refr actory epilepsy in 2003 and pro- spectively followed them for up to 7 years ( 46 , 47 ). Th e 12-month seizure remission rate was 5 % per year, but 71 % of these patients experienced a breakthrough seizure within 5 years. A retrospective single center cohort of 187 medicall y refractory epilepsy patients was followed for a mean of almost 6 years ( 48 , 49 ). Using Kaplan \200\223 Meier analysis, the investigators found the probability of attaining 1-yea r seizure remission to be 3 \200\2234 % per year. However, of those achieving remission, th e cumulative probability of seizure relapse was 81 % . A population-based cohort of 128 chi ldren who failed two drugs was prospectively followed for at least 1 year ( 50 ). Seventy-t hree children (57 % ) had a remission period of greater than 1 year. However, of the 124 ch ildren followed for 3 years, only 28 (23 % ) achieved a greater than 3-year remission rate at last con- tact, leading the authors to conclude that remission after two-drug failure in children was common but often temporary. The overall data for seizure control in medically refractory epilepsy demon- strate the chances for seizure remission to be low, with the ad ded unfortunate factor of a fairly high relapse rate. Children have a better prognosis than adults. Lennox \200\223Gastaut syndrome Lennox \200\223Gastaut syndrome (LGS) is classified as an e pileptic encephalopathy. The age of onset is usually before age 8 with a peak age of onset between 3 \200\2235 years of age. The syndrome is char- acterized by a triad of multiple se izure types (tonic and atypical absence are the most common), slow spike and wave on EEG (1 \200\2232.5 Hz), and some degree of mental retardation. The etiology can be symptomatic or cryptogenic, and is often a sequelae of infants diagnosed with infantile spasms or West sy ndrome. Tonic seizures are considered a prerequisite for the diagnosis. The interictal EEG is characterized by slow spike and wave complexes (<2.5 Hz) and activation of generalized p aroxysmal fast activity during sleep. The seizures in LGS are typically refractory to medic al treatment ( 40 ). The North American study ( 11 ) found only one of 19 children (5 % ) d iagnosed with LGS achieved a 2-year remission (Table 24.2 ). That subject went on to relaps e on later follow-up. None of the \201 ve children with LGS in the Dutch study ( 23 ) ach ieved remission. Mesial temporal lobe epilepsy with hippocampal sclerosis Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a symptomatic focal epilepsy and subcategorized as a li mbic epilepsy. The age of onset is typically between late child- hood to mid adolescence. M ost patients report an aura, which con- sists of an epigastric sensation (a rising sensatio n, butter \202 ies, nausea), fear, olfactory hallucinations, lightheadedness, or d j vu ( 41 ). Seizure semiology often involve impairment of cognition and awareness as well as i psilateral upper extremity automatisms, con- tralateral dystonic posturing, Todd \200\231s paralysis, and late forced head turning prior to secondary generalization. Prognostic factors for seizure remission Different studies have used different methodologie s, and prognos- tic factors which were analyzed varied between studies, making strong concl usions untenable. In addition, there are only a few papers with multivariate analysis, and the potential interaction between prognostic factors is not well studied. Nevertheless, a f ew consistent factors emerge for both positive and negative prognosis for seizure remission . Positive predictors for seizure remission include the diagnosis of one of the benign idio pathic epilepsies such as BECTS, CAE, and JAE. Young age of seizure onset, a normal MTLE-HS is often refractory to anticonvulsant drug treatment and one of the most common typ es of epilepsy referred for epilepsy surgery. Kim et al. ( 42 ) followed 104 patients with MRI evidence of mesial temporal sclerosis for more than 2 years. Only 25 % of this cohort e ntered into a 1-year seizure remission period. In a large hospital-based survey of over 220 0 adult patients with varying CHAPTER 24 epilepsy in remission 265 Table 24.2 Remission rates by syndromes ( 11 ) Syndrome grouping a No. total after 2-year reassessment of syndromes and etiology No. ( % ) achieving 2-year remission No. ( % ) relapse Total 594 441 (74) 107 ( 24 ) Partial epilepsies 354 274 (77) 65 ( 24 ) Idiopathic partial: 62 55 (93) 4 ( 7 ) Benign rolandic 59 52 (88) 3 ( 6 ) Benign occipital 3 3 (100) 1 ( 33 ) Symptomatic partial: 205 147 (72) 44 ( 30 ) Cryptogenic partial 87 72 (83) 7 ( 24 ) Generalized epilepsies 191 132 (69) 32 ( 24 ) Idiopathic generalized (IGE): 133 111 (83) 28 ( 25 ) Benign myoclonic epilepsy in infancy 2 2 (100) 0 (0) Childhood absence 75 66 (88) 15 ( 23 ) Juvenile absence 17 14 (82) 3 ( 21 ) Juvenile myoclonic 15 8 ( 53 ) 5 (63) With generalized tonic \200\223clonic seizure on awakening 2 1 ( 50 ) 1 (100) Other IGE/unclassi \201 ed IGE 18 17 (94) 3 ( 19 ) With speci \201 c modes of precipitation 4 3 (75) 1 ( 33 ) Symptomatic/cryptogenic generalized: 49 20 ( 41 ) 4 ( 20 ) Not further classi \201 ed 3 1 ( 33 ) \200\224 West 17 9 ( 53 ) 1 ( 11 ) Lennox \200\223Gastaut 19 1 ( 5 ) 1 (100) Doose 8 7 (88) 1 ( 14 ) With myoclonic absence 2 2 (100) 1 ( 50 ) Symptomatic generalized: 9 1 ( 11 ) 0 (0) With non-speci \201 c etiology 3 0 (0) \200\224 With speci \201 c etiology 6 1 ( 17 ) 0 (0) Epilepsies of undetermined onset 49 36 (73) 10 ( 28 ) Undetermined with both focal and generalized features 2 1 ( 50 ) 1 (100) Undetermined without unequivocal focal or generalized features 47 35 (74) 9 ( 26 ) a A few syndromes with only a single individual were not shown but included in the more gen eral category under which they fell. From Berg AT et al. Epilepsia 2001; 42:1553 \200\22362 , with permission. neurological examination, and generalized onset seizures all por- tend a higher likelihood for seizure remission ( 8 , 51 , 52 ). As shown earlier in this chapter, continued seizure activity after adequate trials of two to three \201 rst-line anticonvulsant drugs portend s a lower possibility of sustained seizure remission. In addition, the duration of active s eizure activity is inversely correlated to the chances of becoming seizure free. Annegers e t al. ( 4 ) demonstrated that only around 10 % of their initial cohort entered remission if the period of active epilepsy was greater than 4 years, with less than 5 % achieving seizu re freedom if their seizures were uncontrolled for greater than 10 years. Frequent generali zed tonic \200\223clonic sei- zures, the presence of multiple seizure types, epileptiform a bnor- malities on the EEG, structural abnormalities on brain imaging, and the presence of m ental retardation also are poor prognostic factors for seizure remission ( 51 , 53 \200\22357 ). Frequent seizures ( \200\230high dens ity \200\231) after initial diagnosis was also found to be a negative predictor ( 58 ). Conclusion The prognosis for persons with epilepsy to enter remission is gen- erally favora ble. Data from resource-poor countries indicate that even some untreated or undertreated pa tients will spontaneously become seizure free. With appropriate treatment, about two-thirds of people will achieve seizure remission. Certain syndromes such as BECTS, CAE, and JAE ar e associated with a high likelihood of seizure control. Other syndromes such as LGS and MTL E-HS are associated with a poor overall prognosis (LGS) or poor prognosis