356 Arch Dis Child 1999;81:356–359

CURRENT TOPIC Arch Dis Child: first published as 10.1136/adc.81.4.356 on 1 October 1999. Downloaded from

Update on surgery for

J H Cross

Surgery for epilepsy is not new, it has been per- area of the that is functionally silent formed for over 100 years. However, there has (table 2). The size of the area may be relatively been a reluctance to consider young children small or large, partly dependent on underlying for surgery other than in exceptional circum- pathology and partly the area of brain involved. stances, owing in part to the invasive nature of Complete removal or disconnection of one the presurgical evaluation. Recent advances in (hemispherectomy) may investigative techniques have allowed identifi- be considered where there is a pre-existing cation of candidates early in their natural hemiplegia associated with a structural abnor- history avoiding the long term consequences of mality of the contralateral hemisphere, and sei- chronic epilepsy. Based on a prevalence rate of zures have been proved to arise from that 3–6/1000 and current population figures of hemisphere. With either of these techniques, 60 000 children with epilepsy, about 15 000 presurgical evaluation is aimed at determining are unresponsive to anticonvulsant medication, whether such surgery is likely to cure or and of these as many as 3000 might benefit improve seizures without deterioration in func- from surgery. There are currently six centres in tion. Temporal resection is the most common the UK oVering surgery to children. Of these, operation in paediatric and adult practice, but Great Ormond Street in London operates hemispherectomy comprises up to a quarter of exclusively on children (30 cases/year), al- procedures in paediatric practice, whereas few though for each child who comes to surgery it are performed in adults. Extratemporal resec- is likely four have been evaluated. tion is diYcult in the absence of a known structural lesion, but may be more common The case for early surgery where invasive (EEG) Most adults coming to an is available. programme have had a history of seizures since In children there may be some diYculty in childhood,1 the consequences of which are sev- determining when seizures are drug resistant

eralfold. Studies of selected groups of children and at what point surgery should be consid- http://adc.bmj.com/ with ongoing seizures suggest that severe ered. In adults, medical intractability may be epilepsy is associated with cognitive decline2 considered as failure to respond to at least two and that early cessation of seizures is associated anticonvulsant drugs over at least two years; with better developmental outcome.3 The psy- these rules may not be appropriate in paediat- chological consequences of recurrent seizures ric practice. In an infant with catastrophic through school and teenage years are also onset epilepsy, seizure frequency may be such apparent, both to the individual and the that a greater number of drugs are tried over a community.4 In addition, recurrent epileptic lesser time. There may be pressure in such on October 1, 2021 by guest. Protected copyright. seizures are not without risk to the individual, cases to suppress seizures as early as possible to both with regard to self injury during a seizure try and reduce the developmental morbidity and the risk of sudden death.5 With advances in Table 1 Types of surgery for epilepsy neurosurgical and neuroanaesthetic tech- niques, morbidity from planned neurosurgical Focal resection—temporal or extratemporal procedures is now low. In addition, postopera- Hemispherectomy Functional procedures tive outcome of seizure control in studies performed to date in children are similar to Multiple subpial transection those in adults.6 There is consequently no jus- tification in conducting a “wait and see” policy Table 2 Criteria for consideration for surgery for epilepsy rather than referral in children with epilepsy, Consultant in particularly in early onset catastrophic epi- Focal resection Paediatric Neurology lepsy, which may have a focal onset. Seizures arise from a single area of the brain that is functionally silent and Honorary Senior Drug resistant Lecturer, Great Candidate selection Hemispherectomy Ormond Street Structural abnormality demonstrable of one cerebral Hospital for Children Procedures on oVer can be divided broadly hemisphere NHS Trust, Institute of into two categories: resective and functional Seizures lateralised to that cerebral hemisphere Child Health, London surgery (table 1). Traditionally, consideration Pre-existing hemiplegia (in the absence of progressive disease) WC1N 3JH, UK is given to focal resection of the seizure focus, J H Cross Drug resistant either temporal or extratemporal. To be Corpus callosotomy considered for such surgery most seizures have Drop attacks, whether atonic, myoclonic or tonic Correspondence to: Specific vocational goals to surgery Dr Cross. to been proved to arise exclusively from one Update on surgery for epilepsy 357

that may occur in association with frequent STRUCTURAL IMAGING seizures in early life, clinical or subclinical. Postoperative follow up studies have shown Arch Dis Child: first published as 10.1136/adc.81.4.356 on 1 October 1999. Downloaded from A further issue may arise in deciding whether more favourable outcome with regard to seizures or seizure syndromes are focal in seizure control where lesions are detected origin and therefore treatable with surgery. within the surgical specimen.11 MRI has Certain syndromes are catastrophic in early enabled the detection of such pathology preop- childhood and the question is often how hard eratively. This has included an increased detec- should we look for a focal or lateralised onset. tion of developmental abnormalities such as Chugani et al highlighted this with the use of dysembryoplastic neuroepithelial tumours and positron emission tomography (PET) in infan- focal cortical dysplasia previously undetected tile spasms, apparently increasing the number on computed tomography, as well as hippo- amenable to surgery7; 30 of 140 of children campal sclerosis, the lesion most commonly presenting with infantile spasms had focal responsible for temporal lobe epilepsy (TLE) lateralised abnormalities. It appears likely how- in adults (fig 1).12 There continues to be ever that lateralisation may be apparent clini- discussion as to the relevance of the hippocam- cally or on EEG or both in patients where sur- pus in childhood epilepsy, and whether hippo- gery is going to be helpful and, in many, such campal sclerosis is an acquired lesion.13 Surgi- abnormalities may be seen on good quality cal series in childhood have indicated a magnetic resonance imaging (MRI).8 This relatively high incidence of tumours and a low does not preclude the fact that all children pre- incidence of hippocampal sclerosis as the senting with infantile spasms should have underlying responsible lesions, but recent data detailed in the form of optimised indicate that this may be equally common in MRI and, where a lateralised structural abnor- children as in adults with TLE, and that it can mality is found, referred for surgical opinion be detected on MRI (as high as 60%).12 14 even if there is initial control of seizures with Visual inspection of the and anticonvulsants. This is to allow rapid interven- temporal lobe may also be greatly enhanced, tion should seizures return or developmental and detection of abnormalities increased by progress appear compromised with continuing quantitative and semiquantitative tech- epileptiform activity. Other syndromes that niques.15–17 Further detailed analysis of three require rigorous investigation for a localised dimensional datasets may also provide infor- structural abnormality are those that present mation, particularly in extratemporal epilepsy, with an autistic-type language disorder in not only about localised abnormalities (fig 2) association with epilepsy.9 but also about more widespread developmental Functional procedures involve modification structural abnormalities not initially apparent of brain function rather than tissue removal. from visual inspection.18 This may provide Corpus callosotomy—division (either two some prediction of the likely outcome of thirds or complete) of the corpus callosum—is surgery with regard to seizures.19 Such tech- considered in individuals having frequent niques are generally available only in centres “drop” attacks, whether myoclonic, atonic or specialising in epilepsy and epilepsy surgery, tonic. Another technique recently advocated by and therefore a normal routine MRI in the http://adc.bmj.com/ Morrell et al is multiple subpial transection, presence of clinical or EEG suspicion of focal used in the surgical management of Landau epilepsy does not preclude referral. In children KleVner syndrome (LKS).10 This procedure undergoing evaluation for hemispherectomy, involves transection of transverse fibres leaving MRI also plays a major role, not only in longitudinal fibres intact. For epileptic aphasia (LKS) the technique is performed over Wer- nickes area on what is thought to be the leading side as determined by preoperative investiga- on October 1, 2021 by guest. Protected copyright. tion. The technique may also be considered in individuals where the seizure focus lies within a functionally eloquent area of cortex (such as the motor cortex).

Presurgical evaluation The primary aim of presurgical investigation is to determine whether an area of the brain responsible for seizures can be accurately defined. In addition, it has to be determined that removal of that area is not going to cause deterioration of function, whether it be control of movement, or language. It is highly desirable to use a non-invasive approach where possible, more recently made possible by developments in neuroimaging. There is no doubt that an epilepsy surgery programme should have ready access to expertise in neuro- physiology, neuroimaging, and neuropsychol- Figure 1 Coronal section magnetic resonance image, ogy, but access to such expertise should not inversion recovery sequence, perpendicular to the axis of the temporal lobes. The right hippocampus is smaller than the detract from the need for detailed clinical left, with loss of signal from within, suggestive of right evaluation and interictal EEG studies. hippocampal sclerosis. 358 Cross

NEUROPSYCHOLOGY

The role of neuropsychology testing in the Arch Dis Child: first published as 10.1136/adc.81.4.356 on 1 October 1999. Downloaded from determination of verbal and non-verbal func- tion in older children cannot be underplayed. There is also a role in the determination of cerebral dominance, and Wada (sodium amytal) testing may be required in older children to lateralise language function. How- ever, early onset localisation related epilepsy, particularly that associated with a structural abnormality, is likely to lead to some relocalisa- tion of function. Functional imaging tech- niques (MRI or PET) are increasingly being used to localise language function and may preclude the need for Wada testing in the future.22

INVASIVE MONITORING Traditionally, invasive EEG techniques were the only definitive way to determine accurately the area of seizure onset. These involved depth electrodes and were associated with relatively Figure 2 Coronal section magnetic resonance image, high morbidity. The current use of subdural reconstructed from a three dimensional magnetisation prepared rapid acquisition gradient echo (MP-RAGE) electrode grids by experienced centres has dataset, showing an area of thickened cortex suggestive of been shown to be well tolerated, even in young cortical dysplasia in the right frontal region. children, and allows not only accurate localisa- tion of seizure onset, but also localisation of detailing the extent and nature of the hemi- function,23 which may be particularly impor- spheric abnormality, but also excluding the tant in children with extratemporal epilepsy, presence of any abnormality on the contralat- either with normal structural imaging (with eral side, which may also have an influence on highly concordant functional data) or with a outcome. structural abnormality close to functionally useful cortex. FUNCTIONAL IMAGING Although there is a high detection rate of focal brain abnormality in children with partial epi- lepsy, such abnormalities may only be assumed Outcome to be related to seizure onset. Video-EEG The clinical spectrum of children coming to monitoring is imperative for documentation of epilepsy surgery is wide. Although freedom clinical symptomology and where possible from seizures is important in determining suc- http://adc.bmj.com/ electrical seizure onset. However, both may be cess, it may not be the primary goal in all chil- misleading in the young child, particularly dren undergoing evaluation. For example, infants. Where such is helpful and correlates compare the teenager in a normal school aim- with a focal structural abnormality, the deci- ing for freedom from seizures from a temporal sion about whether to oVer surgery may be lobectomy with the infant with hemimegalan- relatively easy to make. In children with less cephaly striving to avoid and helpful investigative data, non-invasive func- optimise developmental outcome. In addition, tional imaging in the form of ictal and interic- outcome may depend on a wide range of on October 1, 2021 by guest. Protected copyright. tal single photon emission computed tomogra- factors including the type and extent of the phy (SPECT) or interictal PET may enhance responsible lesions, and extent and type of sur- this information. gery, which can be determined preoperatively Functional imaging in the form of ictal to a certain degree. Consequently it is impor- SPECT can provide information about seizure tant to obtain as much information as possible onset; an area of hyperperfusion seen after about the nature of the epilepsy and the proce- injection of a radioisotope during a seizure is dure planned, with distinct outcome aims highly suggestive of the seizure focus.20 21 Such clarified with the family. A system has been scans however give optimal yield only if proposed that attempts to correlate all such injection of the isotope is truly during a seizure information, and clarify the likely outcome with concomitant EEG monitoring, particu- with the family.24 Information to date suggests larly in extratemporal epilepsy, and if examined that seizure outcome is similar in children and in the context of an interictal scan (to adults; 60–70% seizure free from temporal and determine a change in perfusion), and other extratemporal resection.25 However, the results investigations. Interictal SPECT (showing hy- may not be as good in children with develop- poperfusion) and fluorodeoxyglucose (FDG) mental lesions compared with acquired lesions, PET (showing hypometabolism), are more probably due to the presence of more wide- likely to demonstrate abnormalities relating to spread lesions that cannot be seen with current structural defects. PET may be particularly imaging techniques.26 This does not preclude useful in infants where incomplete myelination considering surgery for these patients, provid- may restrict the structural information pro- ing the aims of surgery are realistic and clearly vided by MRI.8 identified. Update on surgery for epilepsy 359

Conclusions 11 Fish DR, Smith SJ, Quesney LF, Andermann F, Rasmussen T. Surgical treatment of children with medically intractable Advances in neuroimaging, , and frontal or temporal lobe epilepsy: results and highlights of Arch Dis Child: first published as 10.1136/adc.81.4.356 on 1 October 1999. Downloaded from neuroanaesthesia mean that surgery for chil- 40 years’ experience. Epilepsia 1993;34:244–7. 12 Cross JH, Jackson GD, Neville BGR, et al. Early detection of dren with epilepsy is a real consideration. abnormalities in partial epilepsy using magnetic resonance. There is no reason to delay surgery; whether an Arch Dis Child 1993;69:104–9. 13 Harvey AS, Grattan-Smith JD, Desmond PM, Chow CW, infant presents with catastrophic epilepsy, or an Berkovic SF. Febrile seizures and hippocampal sclerosis: older child is reviewed with ongoing intermit- frequent and related findings in intractable temporal lobe epilepsy of childhood. Pediatr Neurol 1995;12:201–6. tent seizures with little response to medication. 14 Grattan-Smith JD, Harvey AS, Desmond PM, Chow CW. In view of the high morbidity associated with Hippocampal sclerosis in children with intractable tempo- ral lobe epilepsy: detection with MR imaging. AJRAmJ chronic epilepsy, children should be referred Roentgenol 1993;161:1045–8. early for surgical consideration. Nothing is lost 15 Cendes F, Andermann F, Gloor P, et al. MRI volumetric measurement of amygdala and hippocampus in temporal from evaluation without surgery; there is much lobe epilepsy. Neurology 1993;43:719–25. to be lost by the patient experiencing 20 years 16 Jackson GD, Connelly A, Duncan JS, Grunewald RA, Gadian DG. Detection of hippocampal pathology in of seizures that could have been resolved in intractable partial epilepsy: increased sensitivity with quan- childhood. titative magnetic resonance T2 relaxometry. Neurology 1993;43:1793–9. 17 Cross JH, Connelly A, Jackson GD, Johnson CL, Neville 1 Wyllie E, Luders H, Morris HH, et al. Subdural electrodes in BGR, Gadian DG. Proton magnetic resonance spectros- the evaluation for epilepsy surgery in children and adults. copy in children with temporal lobe epilepsy. Ann Neurol Neuropediatrics 1988;19:80–6. 1996;39:107–13. 2 Besag FMC. Cognitive deterioration in children with 18 Sisodiya SM, Stevens JM, Fiah DR, Free SL, Shorvon SD. epilepsy. In: Trimble MR, Reynolds EH, eds. Epilepsy, The demonstration of gyal abnormalities in patients with behaviour and cognitive function. Chichester: John Wiley & cryptogenic partial epilepsy using three-dimensional MRI. Sons Ltd, 1988:113–27. Arch Neurol 1996;53:28–34. 3 Czochanska J, Langner Tyszka B, Losiowski Z, Schmidt 19 Sisodiya SM, Moran N, Free SL, et al. Correlation of wide- Sidor B, Children who develop epilepsy in the first year of spread preoperative magnetic resonance imaging changes life: a prospective study. Dev Med Child Neurol 1994;36: with unsuccessful surgery for hippocampal sclerosis. Ann 345–50. Neurol 1997;41:490–6. 4 Ounsted C, Lindsay J, Richards P. Temporal lobe epilepsy 20 Harvey AS, Bowe JM, Hopkins IJ, Shield LK, Cook DJ, 1948–1986: a biographical study. Oxford: MacKeith Press, Berkovic SF. Ictal 99mTc-HMPAO single photon emission 1987:1–129. computed tomography in children with temporal lobe epi- 5 Nashef L, Fish DR, Garner S, Sander JWAS, Shorvon SD. lepsy. Epilepsia 1993;34:869–77. Sudden death in epilepsy: a study of incidence in a young 21 Harvey AS, Hopkins IJ, Bowe JM, Cook DJ, Shield LK, cohort with epilepsy and learning diYculty. Epilepsia 1995; Berkovic SF. Frontal lobe epilepsy: clinical seizure charac- 36:1187–94. teristics and localization with ictal 99mTc-HMPAO 6 Adams CB, Beardsworth ED, Oxbury SM, Oxbury JM, SPECT. Neurology 1993;43:1966–80. Fenwick PB. Temporal lobectomy in 44 children: outcome 22 Hertz Pannier L, Gaillard WD, Mott SH, et al. Noninvasive and neuropsychological follow-up. Journal of Epilepsy assessment of language dominance in children and adoles- 1990;3(suppl):157–68. cents with functional MRI: a preliminary study. Neurology 7 Chugani HT, Shewmon DA, Shields WD, et al. Surgery for 1997;48:797–800. intractable infantile spasms: neuroimaging perspectives. 23 Duchowny M. Epilepsy surgery in children. Curr Opin Neu- Epilepsia 1993;34:764–71. rol 1995;8:112–16. 8 Chugani HT, Shewmon DA, Khanna S, Phelps ME. 24 Taylor DC, Neville BGR, Cross JH. New measures of Etiologic classification of infantile spasms in 140 cases: role outcome of the surgical treatment of epilepsy. Epilepsia of positron emission tomography. J Child Neurol 1996;11: 1997;38:625–30. 4–48. 25 Gilliam F, Wyllie E, Kashden J, et al. Epilepsy surgery 9 Neville BGR, Harkness W, Cross JH, et al. Surgical outcome: comprehensive assessment in children. Neurology treatment of severe autistic regression in childhood 1997;48:1368–74. epilepsy. Paediatr Neurol 1997;16:137–40. 26 Doring S, Cross H, Boyd S, Harkness W, Neville B. The sig- 10 Morrell F, Whisler WW, Smith MC, et al. Landau KleVner nificance of bilateral EEG abnormalities before and after syndrome; treatment with subpial intracortical resection. hemispherectomy in children with unilateral major hemi-

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