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Epilepsy surgery in children: are we doing enough? by Professor J Helen Cross

This article first appeared in our Epilepsy Professional magazine in March 2011.

UK clinicians seem reluctant to refer children with epilepsy for surgical intervention. Prof J Helen Cross outlines surgical options for epilepsy – and wonders why we keep hesitating

Epilepsy surgery is defined as the removal or modification of part of the brain with the specific aim of treating epilepsy. It is not a new concept; it has been used in the management of epilepsy for over 100 years. However, it is only relatively recently that it has gained momentum as a realistic choice in the management of epilepsy in children.

Resective surgery of the epileptogenic focus can be curative in 40-80 per cent of selected candidates. (This is dependent on the procedure as well as the underlying pathology responsible for seizure activity.) Further, with careful evaluation, morbidity – referring to the risk of resulting complications – remains low. However, despite this – and the relatively high chance of seizure freedom – many professionals remain reluctant to refer children with epilepsy.

As a result of this reluctance, surgery is often delayed in the natural history of a child’s epilepsy (Berg et al, 2006). Referral is more likely in catastrophic than focal epilepsies. (Epilepsy may be referred to as catastrophic when seizures are sudden and frequent in onset, difficult to control and when the epilepsy in question is associated with an effect on learning ability.) It remains unclear whether this is a true reluctance resulting from a lack of awareness about suitable candidates or possible benefits. It may simply represent concern about a high chance of complications.

Who should be considered?

Surgery is most likely to be curative where the area of brain responsible for seizure onset can be removed. This may involve the removal of a small, localised area of the brain, or wider unilateral abnormality lobar, multilobar or hemispheric resection. Presurgical evaluation aims to determine whether seizures arise from one area that can be removed or disconnected without further functional compromise to the child.

Further, a degree of drug resistance should be recognised. Traditionally, the unsuccessful use of at least two drugs over at least two years would be considered appropriate criteria for referral. Data suggest that the likelihood of achieving seizure freedom after a second unsuccessful anti-epileptic drug (AED) remains extremely small (Kwan and Brodie, 2000). Many young children, however, will have tried two AEDS relatively quickly after being diagnosed. For them, the likelihood of achieving seizure freedom through drug treatment remains extremely small.

A more recent evaluation of drug resistance was published by the ILAE Commission for Therapeutics. This evaluation suggests a useful definition of treatment failure. Adequate trials of two tolerated and appropriately chosen AED schedules – whether as monotherapies or in combination – should fail to achieve sustained seizure freedom. Here, treatment response is defined as seizure freedom lasting at least three times the longest seizure-free interval prior to a new intervention. This would take into consideration even the very young with catastrophic onset epilepsy. Further, it does not define any measure of severity or frequency of seizures. Individuals with ongoing seizures should be considered for referral, regardless of frequency or severity. Decisions as to whether consideration should be given to surgery should be made jointly between the family and an experienced surgical team.

Following a consensus conference undertaken in 2003, international criteria were agreed for referral and evaluation of children for surgical assessment (Cross et al, 2006). It was agreed that children should be referred to comprehensive epilepsy centres rather than isolated surgical units. It was also recognised that certain subgroups of surgical candidates should be referred to an experienced surgical unit. Such a unit should be equipped with multidisciplinary personnel and have access to advanced technologies such as PET, SPECT and functional MRI. Such candidates may have high surgical risk:benefit ratios, or may present some difficulty in localisation of seizure onset.

Core components to the presurgical assessment were also agreed. All candidates should have at least the following.

  • An interictal EEG recording to include sleep (with video EEG strongly recommended)
  • An MRI with a specified epilepsy protocol
  • An age-appropriate neuropsychological/developmental assessment.

Conference delegates also agreed that access to functional imaging should be readily available, as well as neuropsychiatric assessment. It was further agreed that children should be evaluated in dedicated centres, as opposed to in adult units. It was also asserted that there should be strategies for specific epilepsy syndromes in childhood.

Although many specific improvements and procedures were agreed at the conference, there were concepts that required further evaluation. There was a need for epidemiological data as to what epilepsy surgery in childhood comprises. Further, the role of additional investigative techniques required further evaluation. Minimal criteria for the definition of a surgical unit could not be formulated at that time and methods of outcome assessment required standardisation.

Since this time, a survey of epilepsy surgical procedures – along with presurgical evaluation – has been undertaken. Twenty centres from 10 countries participated, reporting on 548 patients who underwent surgery in 2004 (Harvey et al, 2008). This revealed the scope of procedures being undertaken (figure 1). It also confirmed the specific syndromes dealt with in paediatrics, as well as the age dependence.

Not surprisingly, the survey demonstrated that the majority of procedures undertaken were multilobar (including hemispherectomy). It further demonstrated that the most common underlying pathology was malformations of cortical development. At the time, this was a contrast to most adult series.

Does it do any good?

The primary aim of epilepsy surgery is seizure freedom, or – at the very least – reduction of seizures. Seizure outcome appears to be dependent on several factors. These are the degree of resection and the underlying pathology, as well as the type of procedure performed (Edwards et al, 2000; Lerner et al,  2009; Paolicchi et al, 2000). A wider range of procedures are performed in children – with a greater proportion involving developmental malformations – when compared to adults (Harvey et al, 2008).

Children undergoing temporal lobe resection are more likely to achieve seizure freedom than in cases of extratemporal resection (removing sections of the brain outside the temporal lobes). Those with stroke-like lesions are more likely to achieve seizure freedom than those with developmental malformations. The success rate stands at around 60 per cent in focal resections for cortical malformations. This may increase to 85 per cent in temporal resections for hippocampal sclerosis or developmental tumours.

Aside from varying pathologies, the most important determinant of whether seizure freedom will be achieved remains whether the resection of the seizure focus is complete. This may be electrically or structurally determined. Weaning a child off their medication is often also an aim of parents. Unfortunately, even with a successful resection, this cannot be guaranteed. Although data are limited, they suggest this may be possible in up to 50 per cent of children who remain seizure-free.

Of course, there may be secondary aims of a surgical resection, such as cognitive and behavioural improvements. Although such improvements are possible, they are much less predictive. The rate of cognitive dysfunction in children coming to surgery is high. This is most likely when seizure onset occurred under two years of age (Vasconcellos et al, 2001). A series of children presenting for temporal lobectomy showed 57 per cent with intellectual impairment. This series also showed a high degree of correlation between intellectual impairment and age of onset of epilepsy. Eighty-two per cent of children whose seizure onset occurred under the age of one year demonstrated intellectual dysfunction (Cormack et al, 2007).

One argument for early surgery is the likely (presumed) improved developmental outcome following seizure control. Some individuals – especially those with early onset catastrophic epilepsy – may show quite dramatic improvements. (This is presumed to be the result of having reduced or removed any epileptic activity.) Not all surgical candidates should expect such dramatic improvements. However, studies on a group basis demonstrate that postoperative developmental trajectories will at least be maintained. Any gains are generally demonstrated with longer follow-up (Freitag and Tuxhorn, 2005; Skirrow et al, 2010).

The rate of psychiatric disorder in children coming to surgery also remains high. This is the case both in extratemporal (Colonnelli et al, 2010) and temporal lobe epilepsy (Mclellan et al, 2005). Improvements in a psychiatric disorder cannot be guaranteed following surgery, and in fact diagnoses may evolve after resection. However – although appropriate counselling will need to be undertaken prior to surgery – it is clear that psychiatric disorders do not represent a contraindication to surgery.

What is the need?

There are several pieces of recent data suggesting that we appear reluctant to refer children for surgery. Moreover, such data suggest that this has resulted in many children experiencing an unnecessary wait for a possible curative procedure.

One recent study demonstrated that the mean age of onset of epilepsy was 14.6 years in individuals with focal epilepsy (the majority having temporal lobe epilepsy). Despite this, the average age at presentation for evaluation for surgery was 36.7 years (Berg et al, 2006). Meanwhile, the 2004 survey revealed that 60 per cent of children coming to surgery had developed epilepsy before the age of two. However, only 35 per cent underwent surgery within two years of onset (Harvey et al, 2008) – despite the ability to recognise drug resistance relatively early.

Meanwhile, a 2009 paper outlined epidemiological data on imaging and surgical assessment of children within a prospectively collected cohort of newly diagnosed epilepsy. These children were followed over ten years. This data estimated that 127 children in every 1,000,000 presented with drug resistant epilepsy each year (Berg et al, 2009). Fifty-two in every 1,000,000 children should have undergone a presurgical evaluation (this works out at 780 children a year in the UK). Finally, 27 in every 1,000,000 children should undergo a resective surgical procedure. This works out at 405 children in the UK every year who should be undergoing a resective procedure. And yet, audit data have suggested that only a quarter as many procedures are currently being undertaken in the UK. This is unlikely to be totally down to the available resources. Children continue to be referred quite late in their natural history – when earlier surgery could have led to significant benefits.

Currently the Safe and Sustainable Services neurosurgical review is addressing the likely structure of paediatric neurosurgical provision in the UK, which is likely to include epilepsy surgery. However, the issue of appropriate and early referral of children still needs to be addressed. The NICE guidelines clearly outline recommendations of when children should be referred to tertiary care (see table 1). If these guidelines were followed, many of these issues would probably be addressed – and the rate of referrals increased.

Figure 1: Proportion of procedures (1a) and underlying pathologies (1b) in children coming to epilepsy surgery

Figure 1: Proportion of procedures (1a) and underlying pathologies (1b) in children coming to epilepsy surgery

Table 1: Indications for referral to tertiary care in children with epilepsy

Refer immediately

  • Behavioural or developmental regression
  • Epilepsy syndrome cannot be identified

Refer soon (a)

Consider when one or more of the following are present:

  • the child is less than two years old
  • AEDs do not control seizures within two years
  • two AEDs have been tried and are unsuccessful
  • there are, or there is a risk of, unacceptable side effects of medication
  • there is a unilateral structural lesion
  • there is psychological and/or psychiatric co-morbidity
  • there is diagnostic doubt about seizure type and/or syndrome

Refer

Specific syndromes such as:

  • Sturge–Weber syndrome
  • the hemispheric syndromes
  • Rasmussen’s encephalitis
  • hypothalamic hamartoma

(a) The GDG considered that ‘soon’ meant being seen within four weeks

Note: psychiatric co-morbidity and/or negative baseline investigations should not be a contraindication for referral to a tertiary centre

Taken from www.nice.org.uk/CGD20  

Summary

Resective surgery for focal epilepsy in children can lead to significant benefits for selected candidates in the long term. Possible candidates can be recognised early in their natural history – however, there is evidence of continued delays in referral and, consequently, in surgical resection. All children with evidence of a focal structural brain abnormality should be considered as possible candidates. This is particularly the case in all children under the age of two years – whether or not a period of control with medication has been achieved – in view of the likelihood of relapse.

Further, all children with evidence of focal onset epilepsy with a history of two failed AEDs should be considered. Even where a structural brain abnormality has not been demonstrated, further evaluation with advanced techniques may reveal that surgery is a possibility. Much can be gained from early referral when surgery is deemed an appropriate option. By the same token, much can be lost in the long term by delaying.

Prof J Helen Cross
The Prince of Wales’s Chair of Childhood Epilepsy
UCL-Institute of Child Health
Great Ormond Street Hospital for Children
London
National Centre for Young People with Epilepsy
Lingfield

Further reading:

  • Berg AT, Mathern GM, Bronen R et al (2009). ‘Frequency, prognosis and surgical treatment of structural abnormalities seen with magnetic resonance imaging in childhood epilepsy’. Brain 132 pp. 2785-2797
  • Berg AT, Vickrey BG, Testa FM et al (2006). ‘How long does it take for epilepsy to become intractable? A prospective investigation’. Annals of Neurology 60, pp. 73-9
  • Colonnelli MC, D’Argenzio L, Davies S et al (2010). ‘Psychopathology in children before and after surgery for extratemporal epilepsy’. Epilepsia (submitted).
  • Cormack F, Cross JH, Vargha-Khadem F et al (2007). ‘The development of intellectual abilities in pediatric temporal lobe epilepsy’. Epilepsia 48 pp. 201-204
  • Cross JH, Jayakar P, Nordli D et al (2006). ‘Proposed criteria for referral and evaluation of children for epilepsy surgery:recommendations of the Subcommission for Paediatric Epilepsy Surgery’. Epilepsia 47 pp. 952-959
  • Edwards JC, Wyllie E, Ruggieri PM et al (2000). ‘Seizure outcome after surgery for epilepsy due to malformation of cortical development’. Neurology 55 pp. 1110-1114
  • Freitag H, Tuxhorn I (2005). ‘Cognitive function in preschool children after epilepsy surgery: rationale for early intervention’. Epilepsia 46 pp. 561-567
  • Harvey AS, Cross JH, Shinnar S et al (2008). ‘Defining the spectrum of international practice in pediatric epilepsy surgery patients’. Epilepsia 49 pp. 146-155
  • Kwan P, Brodie MJ (2000). ‘Early identification of refractory epilepsy’. New England Journal of Medicine 342 pp. 314-319
  • Lerner JT, Salamon N, Hauptman JS, et al (2009). ‘Assessment and surgical outcomes for mild type I and severe type II cortical dysplasia: A critical review and the UCLA experience’. Epilepsia 50 pp. 1310-1335
  • Mclellan A, Davies S, Heyman I et al (2005). ‘Psychopathology in children undergoing temporal lobe resection – a pre and postoperative assessment’. Developmental Medicine and Child Neurology 47 pp. 666-672
  • Paolicchi JM, Jayakar P, Dean P et al (2000). ‘Predictors of outcome in pediatric epilepsy surgery’. Neurology 54 pp. 642-647
  • Skirrow C, Cross JH, Cormack F et al (2010). ‘Long-term outcome after temporal lobe surgery in childhood; Intellectual gains are correlated with brain volume changes’. Neurology (In press)
  • Vasconcellos E, Wyllie E, Sullivan S et al (2001). ‘Mental retardation in pediatric candidates for epilepsy surgery: the role of early seizure onset’. Epilepsia 42 pp. 268-274.

No conflict of interests to declare, although travel expenses were received from companies when speaking at events and in support of the epilepsy training fellowship.

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