Planning extent of resection in epilepsy: Limited versus large resections

Epilepsy & Behavior 20 (2011) 233–240

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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Planning extent of resection in epilepsy: Limited versus large resections Saint V. Okonma a, Jeffrey P. Blount b, Robert E. Gross a,c,d,⁎ a

Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA c Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA d Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA b

a r t i c l e

i n f o

Article history: Received 28 September 2010 Accepted 29 September 2010 Available online 12 November 2010 Keywords: Epilepsy Surgery Prognosis Extent Resection Seizure outcome

a b s t r a c t Aggressive versus limited resection is an often-debated topic in epilepsy surgery. There are two inherent questions within this debate: (1) Can a more limited resection yield seizure freedom rates similar to those afforded by wider/more aggressive resection, with lower rates of neurological complications? (2) Does wider/ more aggressive resection increase seizure freedom rates, with tolerable neurological complications rates? Further, if more limited resection has a lower seizure freedom rate, but fewer complications, is quality of life better or worse than that following a wider/more aggressive resection that increases seizure freedom rate but yields a higher complication rate? Here, we review the literature to address these questions. Because most studies are retrospective observational studies, with limited statistical power to draw strong conclusions, there is a need for more randomized prospective multicenter clinical trials incorporating advances in technique for identifying the seizure onset zone (e.g., subtractive ictal SPECT) and tissue at risk (e.g., diffusion tensor imaging) to inform this discussion. © 2010 Elsevier Inc. All rights reserved.

1. Introduction Mies van der Rohe (1886–1969) is famously quoted as saying, “less is more.” Unquestionably, there has been a trend in recent years, within surgery and neurosurgery, toward more “minimally invasive” surgical techniques, ostensibly minimizing in the process complications and surgical time. This is reflected in the emergence of functional hemispherotomy over anatomic hemispherectomy, and endoscopic resection of hypothalamic hamartomas, for example. This trend is also driven by advances in techniques for more refined visualization of lesions associated with the seizure onset zone, such as subtractive ictal SPECT co-registered to MRI, and for better identification of tissue at risk, such as diffusion tensor imaging. Conversely, there is increasing awareness that some neurological deficit is acceptable if it is in the context of seizure freedom, leading to a push for larger resections. Thus, in this review we address the question: Which leads to better outcome overall: less resection or more resection? Obviously, this one-dimensional scale oversimplifies the main issue: with less resection, there is increased chance of recurrent seizures from epileptogenic tissue left behind, but less chance of incurring a neurological deficit, the converse being true of larger resections (Table 1). A recent Monte Carlo simulation showed that the lowest quality-of-life (QoL) was associated with persistent seizures and side

⁎ Corresponding author. 1365-B Clifton Road NE, Suite 6200, Atlanta, GA 30322, USA. Fax: + 404 712 8576. E-mail address: [email protected] (R.E. Gross). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.09.036

effects from medications in patients undergoing anterior temporal lobectomy [1]. Similarly, a Standard Gamble measure of QoL in epilepsy showed that seizure freedom with a deficit was preferred to not being seizure free (R. Knowlton, Univ. of Alabama, personal communication). Thus, patients may tolerate a deficit related to maximizing resection if it renders them seizure free. The question, then, is where is the scale balanced between maximizing seizure free outcome in the context of preserving neurological function. The key to reducing extent of resection while maximizing outcome is an accurate understanding of the minimal volume or extent of tissue to be resected or disconnected to isolate or remove the epileptogenic zone. This minimal volume can be defined in different (overlapping) ways: (1) by the seizure onset zone defined by electrocorticography; (2) by the lesion, if present, defined on neuroimaging; (3) by the histologically defined lesion; (4) in the absence of a lesion, by a metabolic surrogate, such as PET or SPECT. On the other hand, minimizing risk involves better ways to characterize tissue at risk, including: (1) electrical stimulation testing; (2) functional imaging; and (3) anatomical imaging (e.g., diffusion tensor imaging). There are inherent limitations to the clinical studies that provide the data to address this issue: 1. With rare exception, the relevant studies are retrospective [2], uncontrolled observational studies. 2. Most studies are beset by small sample size and are thus predisposed to type II errors (e.g., “absence of evidence is not evidence of absence” [2,3]) as well as short follow-up duration [2]. 3. Studies often include heterogeneous populations of patients, such as mixing tumors and mesial temporal sclerosis.

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Table 1 Planning the extent of resection in epilepsy surgery.

Large resection Small resection

+

–

Complete resection of EZ No deficit

Deficit Persistent seizures Multiple interventions

Note. With less resection, there is increased chance of recurrent seizures from epileptogenic tissue left behind, but less chance of incurring a neurological deficit; the converse is true of larger resections.

4. There is great variation across studies with regard to surgical methodology, intraoperative measurement of extent of resection, use of ECoG, non-MRI validation of the extent of resection [4], measurement of outcome, and unmasking of outcome assessment [2], among other factors. For these reasons, clinical studies addressing this issue are often contradictory and inconclusive [3]. Moreover, the vast degree of

complexity and variation within and between brain regions makes it very unlikely that general principles will pertain to the entire cerebrum. It is self-evident that there is a great need for wellconducted prospective studies [2]. Despite the shortcomings, we review the literature for inferences that can be made from epilepsy surgery studies examining whether the extent of surgical resection is predictive of surgical outcome. Given the variations in the predilection of various brain regions for epilepsy, and the extent to which resections predispose to neurological complications across different brain regions, we approach this debate on a lobe-by-lobe basis, after first discussing several studies that address non-lobar-specific results. 2. Discussion 2.1. Non-lobar-specific results Awad et al. examined outcome as a function of extent of resection in 47 consecutive patients with structural lesions in various lobes [5] (Table 2). Eighteen of the patients underwent complete resection of

Table 2 Non-lobar-specific studies. Duration of follow-up, mean (range)

Comments

Yes 1. Extent of lesion resection (P = 0.003 two-level outcome; P = 0.002 three-level outcome) 2. Extent of focus resection correlated significantly with seizure outcome as a dichotomous variable (P = 0.048) Yes (P value not stated)

41.4 (20–114) months

Maximum resection of the lesion offers the best chance at controlling intractable epilepsy.

4.3 (1–15) years (follow-up in 27 patients in cortical dysplasia group)

Yes

Yes (P = 0.0001)

5.0 (1–15) years (follow-up in 24 patients)

149 Yes

Yes

Yes (P b 0.0001)

≥ 2 years in all patients ≥ 5 years in 113 patients

166

Yes

Yes (P b 0.001 by 7.94 years multivariate analysis)

23

Yes

Completeness of excision of cortical tissue displaying ictal or continuous epileptogenic discharges correlated positively with surgical outcome. Complete excision of ≥ 50% of the lesion led to good surgical outcome. Only extent of removal of the structural abnormality correlated with seizure control. Completeness of excision of the epileptogenic area did not correlate significantly with seizure control. Patients with complete resections (defined as complete removal of structural abnormality detected on MRI or ECoG abnormalities) had superior surgical outcomes as compared with those with incomplete resection. Incomplete resection of epileptogenic area was associated with poor surgical outcomes. Poor surgical result correlated with the presence of additional hypometabolic zones outside the surgical area (on PET).

Study

Pathological diagnosis (histology)

Awad et al., 1991 [5]

Structural lesions (neoplasms, hamartomas, vascular malformation, tuberous sclerosis, cytoarchitectural dysmorphism)

47

Yes

Palmini et al., 1995 [6]

1. Cortical dysplasia group 2. Nondysplastic structural lesions (gliomas, oligodendroglioma, etc.) group

34

Yes

Palmini et al., 1991 [7]

Focal cortical dysplasia, tuberous sclerosis

26

Krsek et al., 2009 [8]

Focal cortical dysplasia

Kim et al., 2009 [9]

Focal cortical dysplasia

Chugani et al., Intractable infantile 1993 [12] spasms

N

Extent of resection determined by Seizure outcome correlates with Intracranial Intended MRI ECoG amount resected monitoring resection (postop) (post(P value) resection)

40

28.3 (4–67) months

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the structural lesion, 23 underwent incomplete resection, and 6 had no resection. Both extent of resection of the structural lesion and, to a lesser degree, extent of resection of the epileptogenic focus were significantly associated with outcome. When the structural lesion was completely resected, extent of focus resection was not important. When the structural lesion resection was incomplete, however, extent of focus resection became more important. Studies specifically of malformations of cortical development (MCDs) indicate a relationship between extent of resection and outcome. Palmini et al. [6] examined patients with cortical dysplasias in various regions. Nine of 12 patients who had resections that included characteristic ictal or continuous epileptogenic discharge patterns achieved seizure freedom of N90% reduction. On the other hand, none of the six patients who had persistent discharges post-resection experienced seizure freedom, indicating a significant difference between the groups (P b 0.01). A previous smaller study that included patients with tuberous sclerosis found that the predictive variable was percentage of the structural lesion removed, but not the completeness of the resection of epileptogenic tissue [7]. Recently, however, Krsek et al. analyzed a large cohort (149) of pediatric patients with MCDs [8]. The only significant predictor of outcome at 2 years (P b 0.0001) was the “completeness of resection,” where a complete resection was defined by a team at the time of surgery, based on complete resection both of the structural lesion on MRI scan (if present) and of “significant EEG abnormalities” (see references therein). Seventy percent of patients who underwent complete resection were seizure free, compared with 22% of patients who had incomplete resections. The primary reason for incompleteness of resection was proximity of the lesion/EEG abnormalities to eloquent brain regions; patients with multiple subpial resections within the latter also faired more poorly than patients with complete resections. No statistical difference was seen between complete and incomplete resection groups at 5 and 10 years, however, likely a combination of recurrence in some patients and a decrease in the size of the groups (and thus statistical power). Similarly, Kim et al. [9] found that incompleteness of resection of the epileptogenic region was a strong predictor of poor seizure outcome on univariate and multivariate analyses. Complete resection was performed in 111 of 166 patients. The remainder had incomplete resection because of involvement of eloquent brain areas or multifocal or extensive epileptogenic areas. Lerner et al. [10], in their extensive review of cortical dysplasia, reviewed these and two other smaller studies, finding numbers similar to those of Krsek et al. After complete resection of MCDs, 77% (182/237) of patients were seizure free, whereas after incomplete resection, only 20% (41/200) of patients were free from seizures. The authors concluded that “the most consistently reported predictor of seizure freedom is complete resection of the lesion.” More severe and extensive histopathological lesions, lesions involving the central insular region or multilobar lesions, are more predisposed to incomplete resection and poorer outcome, as compared with lesions in the temporal lobe, for example, which can be more completely resected [11]. In these cases, multilobar resections, or even hemispherectomy, can be very beneficial: Chugani and colleagues found significant reduction in seizures in 14 of 18 patients with infantile spasms and extensive MCDs (12 seizure free) [12,13]. 2.2. Temporal lobe The extent of resection within the temporal lobe must be addressed separately for mesial temporal structures (amygdala, hippocampal formation) and the lateral temporal lobe. 2.2.1. Mesial temporal lobe The topic of extent of mesial temporal resection was recently extensively addressed by Schramm [14]. There is suggestive evidence, albeit from the sole prospective randomized blinded trial that bears

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on the issue of extent of resection, that greater extent of resection increases seizure-free outcome. Wyler et al. conducted a blinded, randomized, prospective, longitudinal clinical study in 70 patients with complex partial seizures of medial temporal lobe origin [15] (Table 3). Patients who underwent mesial resection only to the level of the anterior margin of the cerebral peduncle were less likely to be seizure free at 1 year (38%) as compared with those who underwent resection to the level of the superior colliculus (64%), with no difference in loss of material-specific memory [15]. Further, only the extent of resection was found to be predictive of surgical outcome. This study supports the conclusion that greater extent is more effective, with no difference in neuropsychological adverse effects (on memory). However, it is important to note that the limited resection group actually had more sparing of the hippocampal formation than almost all other series of hippocampectomy, with minimal resection even of the entorhinal cortex (Fig. 1). The question of how much of the hippocampus beyond the anterior margin should be resected thus remains unaddressed. Moreover, the relative lack of material-specific memory effects is not independent of the neuropathological substrate for the epilepsy: in this study the 77% (27/35) of patients in the total resection group, whose resection specimens could be analyzed, had hippocampal sclerosis, which is associated with a lesser degree of postoperative impairment of memory function than observed in those patients without sclerosis. Interestingly, only 70% of patients undergoing partial resection had hippocampal sclerosis (18/26) thus confounding the outcome results from this study, in terms of both seizure freedom and adverse memory effects. Some retrospective studies are also suggestive of a greater benefit of larger resections of mesial temporal lobe, whereas other studies are not. Wyler et al. reviewed 37 patients with temporal lobe epilepsy whose seizures had failed to respond to initial epilepsy surgery, arguing that insufficient hippocampal resection was mostly responsible for high seizure rate after surgery and that re-operation in patients with incomplete resection was beneficial [16]. Similarly, Germano et al. performed a retrospective review of 40 patients at the Montreal Neurological Institute who underwent reoperation of the temporal lobe for recurrent seizures. In all patients, postoperative neuroimaging studies were done and revealed some residual mesiotemporal structures after initial surgery; a second operation removing these structures was performed in 30 patients [17]. Of these 40 patients, 25 (63%) became seizure free or had rare seizures (two or fewer seizures per year), supporting the contention that greater resection is associated with improved seizure outcome. It was observed that patients with recurrent seizures after reoperation had unresected EEG abnormalities in other non-mesiotemporal regions of the brain. The authors concluded that “more complete resection of the mesiotemporal structures during first operation, even in the absence of intraoperative electrographic abnormalities, could prevent the need for reoperation in defined cases” [17]. Additionally, Kanner et al. conducted a retrospective study of 24 patients with temporal lobe epilepsy to evaluate the effect of extent of resection (of the mesial temporal structures) on postoperative seizure freedom [18]. Resections were tailored based on interictal epileptic activity on ECoG, and the extent of resection was validated using MRI. Thirteen of 15 patients were seizure free (and the other 2 had rare seizures) who underwent MRI-confirmed resection sparing the hippocampus, or even sparing the amygdala (5/6 seizure free). The results suggest that “sparing or limited resection of amygdala and/or hippocampus is not necessarily associated with a poor seizure outcome.” However, it is unclear what the pathological substrate was in the patient cohort; only 6 patients, at most, had changes suggestive of hippocampal sclerosis on preoperative MRI. McKhann et al. [19] conducted a very interesting study determining the extent of resection of the mesial structures on the basis of the presence of interictal epileptiform activity on ECoG. The authors concluded that, with this paradigm, seizure outcome was independent of extent of

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Table 3 Temporal lobe epilepsy studies: Mesial temporal lobe epilepsy. Study

Wyler et al., 1995 [15]

Pathological diagnosis (histology)a

MTS±

Wyler et al., 1989 [16]

Patients undergoing reoperation of temporal lobe (and other regions); Primary pathology: OD, CD, cortical infarct, TS Patients undergoing Germano et al., 1994 reoperation; primary pathology: minimal [17] changes, MTS, encephalitis, low-grade astrocytoma, cyst Kanner et al., No comment 1995 [18]

McKhann et al., 2000 [19]

MTS±

Jooma et al., 1995 [20]

Astrocytoma, glial hamartoma, cavernous angioma, gangliogliomas, OD

a

N

Extent of resection determined by MRI (postop)

ECoG (postresection)

Seizure outcome correlates with Intracranial Intended amount resected? monitoring resection (P value)

Total hippocampectomy results in better seizure outcome than partial hippocampectomy. Material-specific memory morbidity is not associated with the extent of hippocampal resection. Insufficient hippocampal resection is associated with poor seizure outcome.

Yes (P value not stated)

4.8 ± 2.7 (2–11) years

More complete resection of the mesiotemporal structures could prevent need for reoperation.

Yes

No (P value not stated)

38.5 months (18 months–5 years) (except for 1 patient who died 6 months postop)

Yes (in all cases)

No (r = –0.08, P = 0.31)

30 (18–64) months

Yes (in some cases)

Yes (P = 0.0001)

Group A: 33 months Group B: 52 months

Sparing or limited resection of amygdala and/or hippocampus is not necessarily associated with poor seizure outcome provided there is absence of epileptiform activity during ECoG. Extent of hippocampal resection is not correlated with seizure outcome. However, the presence of post-resection hippocampal epileptiform activity on ECoG is associated with significantly worse seizure outcome; therefore, intraoperative hippocampal ECoG should be used to maximize seizure-free outcome. Better seizure control was achieved in patients with ECoG and resection of the epileptogenic zone along with the lesion compared with lesionectomy alone.

Yes

37 MRI done after first surgery

40 MRI done after first surgery

140

30 Yes

Comments

Yes (P = 0.02, odds Minimum = 1 year ratio = 4.16) [for 61 patients with confirmed HS] (P = 0.008, odds ratio = 4.12) [for all 70 patients without HS variable] Yes (P value not None given stated)

70

24 Yes (in all cases)

Duration of follow-up mean (range)

MTS, mesial temporal sclerosis; CD, cortical dysplasia; OD, oligodendroglioma; TS, tuberous sclerosis.

resection when all hippocampal levels from which interictal spikes were recorded were removed. The study argues that greater extent is no more effective when the surrounding hippocampus does not generate epileptiform activity on ECoG. Conversely, it can be concluded that greater extent is necessary, at least sufficient to resect epileptogenic brain, and in those patients in whom such tissue was not resected because of memory concerns, the seizure outcome was worse. Similar results were found previously by Jooma et al. [20]. Unfortunately, McKhann et al. [19] did not examine postoperative memory loss as a function of resection extent, and extensive resections (greater than the anterior hippocampus) were performed only in patients with substantial preoperative memory loss. A number of studies examined difference in outcome as a function of approach to mesial temporal resection; for example, standard anterior temporal lobectomy versus selective amygdalohippocampectomy (e.g., Paglioli et al. [21]), or extent of temporal lobectomy (e.g., Kanner et al. [18]). Most studies found no difference with respect to seizure freedom, because the variable is not extent of resection of the focus per se,

although differences in neurological adverse effects have been found in some studies. As this is more a question of approach than extent of resection of the epileptic focus, we do not further discuss these studies here. 2.2.2. Lateral temporal lobe Several studies conducted on lateral temporal lobe epilepsy support aggressive resection. Minkin et al. [22] examined resection of dysembryoplastic neuroepithelial tumors in a pediatric group (Table 4). In extratemporal cases, simple lesionectomy was sufficient for seizure freedom (9/9). However, in the temporal lobe, 7 of 11 were seizure free with lesionectomy, whereas 4 of 4 who underwent amygdalohippocampectomy in addition were free of seizures. The authors ascribed this finding to a wider epileptogenic zone. Similarly, Van Gompel et al. showed that, in 102 patients with lateral temporal lobe cavernomas, extensive resections resulted in greater seizure freedom than lesionectomies, although the results did not reach statistical significance [23]. In a large retrospective study, using uni-

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patients with limited resections had better neuropsychological outcome compared with those who underwent ATL [24]. 2.2.3. Temporal lobe: Concluding remarks The weight of evidence supports extension of mesial temporal resections to the choroid point or beyond, to the level of the lateral mesencephalic sulcus, perhaps because of incorporation of entorhinal cortex, which reaches to the choroid point. The benefit of resection beyond this point is more debatable; the benefits to memory of limiting extent of resection within the mesial structures remain unanswered. In the lateral temporal region, maximizing extent of resection to include radiological lesions and the epileptogenic regions is likely to increase chances for seizure freedom, while sparing receptive speech regions. 2.3. Frontal lobe epilepsy

Fig. 1. Increasing extent of resection of the hippocampal formation, from 1 to 4 cm measured from the anterior extent of the pes, involves the pes, body, and tail. A resection extending between 2 and 3 cm, to the lateralmost extent of the cerebral peduncle and slightly beyond that the lateral mesencephalic sulcus, is necessary to completely remove the entorhinal cortex (ECtx), which may be critical to maximize seizure-free outcome.

and multifactorial logistic regression analyses, Clusmann et al. evaluated 321 patients who underwent surgery for temporal lobe epilepsy [24]. In regard to patients with temporal lobe lesions (tumors, dysplasias), the study did not find any statistically significant difference in seizure freedom between limited lesionectomy and aggressive resections (standard anterior temporal lobectomy [ATL]) [24]. Although this was a large study overall, the numbers of patients were relatively small in each comparison group (except for those with mesial temporal lobe epilepsy, not considered here as far as extent of the lateral approach is concerned, as discussed above). Nevertheless,

Wennberg et al. [25] assessed 25 patients who underwent ECoG and resection for well-circumscribed frontal lobe lesions of various types (Table 5). A high correlation (P b 0.001) was found between complete surgical resection combined with post-resection absence of epileptic abnormalities beyond the surgical resection border and seizure free outcome. In fact, all 12 patients with this combination were seizure free. Tassi et al. [26] studied a subgroup of 52 patients with focal cortical dysplasia (FCD); in the Taylor-type FCD subgroup (n = 15), of the 12 patients with N1 year follow-up, the authors noted that only those 3 patients whose resection did not include all the epileptogenic abnormality because of involvement of motor and/or language areas were not seizure free. They did not comment on this relationship in the non-Taylor-type FCD (architectural FCD, cytoarchitectural FCD) subgroups. Elsharkawy et al. conducted a retrospective study evaluating surgical outcome in 97 patients who had frontal lobe resections [27]. Their study revealed that, among other factors, incomplete resection was associated with higher rates of poor seizure freedom. Furthermore, Jeha et al. conducted a review of 70 patients who had undergone frontal lobectomy for frontal lobe epilepsy. Univariate and multivariate analyses revealed that again, among other factors, incomplete surgical resection correlated with seizure recurrence and complete resection was predictive of good surgical outcome (RR = 2.56, 95% CI= 1.66– 4.05) [28]. At 1 year, 81% of completely resected and 13% of incompletely resected patients were seizure free; at 3 years, the rates were 66 and 11%, respectively. Although Schwartz et al. [29] found no significant effects of resection size on surgical outcome, 8 of the 10 patients with less than 90% seizure reduction had what they considered to be

Table 4 Temporal lobe epilepsy studies: Lateral temporal lobe epilepsy. Study

Pathological diagnosis (histology)a

Minkin et al., DNET (non-lobar 2008 [22] specific)

N

MRI (postop) 24

Van Gompel et al., 2009 [23]

Cavernous hemangiomas

Clusmann et al., 2002 [24]

MTS, ganglioglioma, 321 Yes (in cases with DNET, CD, tumors) nonspecific gliosis

a

Comments Duration of Seizure outcome follow-up correlates with ECoG Intracranial Intended amount resected? mean (range) (post-resection) monitoring resection (P value)

Extent of resection determined by

61

6.7 (1–16 years)

Yes (in 23 cases)

Yes (in 2 cases)

Yes ( in 161 cases)

Yes 6 months: P = 0.22 1 year: P = 0.26 2 years: P = 0.28) N (P value not stated)

CD, cortical dysplasia; DNET, dysembryoplastic neuroectodermal tumor; MTS, mesial temporal sclerosis.

37 months

38 (12–108 months)

Only 1 of 5 with lateral temporal DNETs was seizure free at 4 years after lesionectomy, perhaps because of wider epilpetogenic zone. Seizure outcome better in lobectomy than lesionectomy. There was a trend toward increased seizure-free status with the use of ECoG, which resulted in larger resections. Seizure outcome similar after anterior temporal lobectomy and selective amygdalohippocampectomy; better neuropsychological outcome in limited resections.

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Table 5 Frontal lobe epilepsy studies. Study

Pathologic diagnosis (histology)a

Wennberg et al., 1999 [25] Tassi et al., 2002 [26]

Neoplasms, hamartomas, 22 and arteriovenous malformations FCD, MCD 52 (non-lobar specific)

Elsharkawy et al., 2008 [27]

Various (FCD, tumors, gliosis, VM, Rasmussen syndrome, MCD, dual pathology) MCD, tumor, VM, cryptogenic, encephalomalacia, dual pathology

Jeha et al., 2007 [28]

Janszky et al., CD, tumor, others 2000 [30] Ferrier et al., 2001 [31]

FCD, neoplasm, VM, Sturge–Weber, scar

N

97 Yes (in all cases)

Yes (in majority of cases)

Yes (P = 0.048)

Mean = 6.9 years +/- 3.8; Range = 2 to 14 years

70 Yes (all cases)

Yes (in some cases)

Yes (RR = 2.56, 95% CI = 1.66– 4.05) (log likelihood-ratio test: P b 0.0001)] Yes (P = 0.002)

Mean = 4.1 years +/- 3.0 years; Range = 1 to 11 years

Incomplete resection of MRI lesion or interictal abnormalities is predictive of poor seizure outcome.

Mean = 1.78; Range = 0.5 to 5 years Mean = 6.0 years +/- 3.8; Range = 2 to 19.5 years

Postoperative epileptiform discharges were associated with poor outcome. Neither incomplete resection of histological abnormalities nor abolition/presence of sporadic spikes in postresection ECoG is associated with poor seizure outcome. Abolition of seizure patterns is associated with favorable surgical outcome (P = 0.031). 1. Better seizure outcomes (P b 0.05) were seen in patients whose ECoG showed infrequent post-resectional spikes and no spikes distant to the resection margin. 2. Best seizure outcome was seen in patients with lesionectomy and corticectomy and in those with complete lesionectomy. 3. The worst outcomes involved patients undergoing multiple subpial transection. Outcome differences between patients who had multiple subpial transection versus other groups (lesionectomy and corticectomy) were statistically significant (P b 0.05). Twenty-two patients underwent resections involving rolandic cortex; 64% class 1, 18% class 2; 20 of 22 patients had postoperative hemiparesis that improved by 6 months.

61 Yes (in 49 cases) 35

52

Benifla et al., 2009 [33]

22

a

Yes (p b 0.001)

Comments

Complete lesion excision was highly correlated with class I outcome. Three of 12 patients had subtotal resections because of functional tissue, and only these had continued seizures. Incomplete resection is predictive of poor seizure outcome.

Pondal-Sordo Neoplasm, MCD, et al., 2006 Rasmussen's encephalitis, OD, [32] others

CD

Duration of Seizure outcome follow-up correlates with MRI ECoG Intracranial Intended amount resected? mean (range) (postop) (post-resection) monitoring resection [P value]

Extent of resection determined by

Yes (in 23 of 25 surgeries done in 22 patients)

No (P value not stated)

Yes (in 48 cases)

Mean = 5.8 years; Range = 1 to 17 years ≥1 year

Yes (ECoG in 30 cases)

See Comments

Yes

See Comments

4.2 ± 3.6 (1–18) years

See Comments

4.1 years (minimum = 2 years)

Yes (in 21 cases)

CD, cortical dysplasia; FCD, focal cortical dysplasia; OD, oligodendroglioma; VM, vascular malformation; MCD, malformation of cortical development.

incomplete resections, and they concluded that this was the most common reason for surgical failure. Janszky et al. [30] did find a statistically significant (P b 0.002) correlation between poor seizure outcome and (1) incomplete resection as determined by postoperative MRI (6 of 8 with focal cortical dysplasia), and (2) persistent interictal epileptiform discharges. Two of five who underwent repeat resection became seizure free. Ferrier et al. performed a retrospective analysis in 35 patients who had frontal lobe resections for epilepsy [31]. Although they found that neither incomplete histological resection nor abolition of sporadic ECoG spikes or their persistence following resection was associated with outcome, abolition of electrographic “seizure patterns” was

associated with a favorable surgical outcome (P = 0.031) [31]. PondalSordo et al. [32], examining 52 patients with perirolandic epilepsy, did see a significant effect (P b 0.05) of better seizure outcomes in patients whose ECoG showed infrequent post-resectional spikes. The best seizure outcome occurred in patients with lesionectomy and corticectomy, and complete lesionectomy, as compared with those who had nonresectable epileptogenic tissue because of the risk of neurological deficits, who instead underwent multiple subpial transections in those regions (P b 0.05). Perirolandic resections did lead to new, severe postoperative neurological deficits in 23% of these patients, with resections in the upper rolandic region and large middle rolandic resections producing the most severe deficits

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postoperatively. There was no association between neurological deficit and seizure outcome. Finally, resections within perirolandic regions were performed knowing there would be a postoperative deficit, in 22 pediatric patients [33]. As expected, 20 of 22 patients experienced new mild to severe hemiparesis, greater in patients with larger resections, which improved in all by 3 to 6 months. Sixty-four percent were free of seizures and 18% had only simple partial seizures at a mean follow-up of 4.1 years (N24 months in all).

80 months. The authors performed logistic regression analysis of predictive factors for outcome, but did not include extent of resection. Finally, Dalmagro et al. conducted a retrospective study in 81 patients with posterior quadrant epilepsy, 44 of whom underwent surgical resection [38]. The authors found that complete resection of the lesion detected on MRI before surgery and aggressive versus limited resections, among other variables, were not associated with surgical outcome [38].

2.3.1. Frontal lobe: Concluding remarks In the frontal lobe, wide resections are generally better tolerated, except when motor or expressive language areas are involved. There is a paucity of class I evidence to guide extent of surgical resection. However, the weight of the uncontrolled evidence supports that resections should seek to encompass the radiological and electrographic abnormalities to maximize prospects for seizure freedom. When these regions encroach on motor/language regions, the patients are more prone to failure when neurological deficits are to be avoided. Although fixed neurological deficits (especially if not unexpected) may be more tolerable to patients than continued seizures, more data need to be acquired regarding the benefit to overall QoL when seizure freedom is sought at the expense of a fixed neurological deficit involving motor and speech. Until then, such decisions should be approached on a case-by-case basis.

2.4.1. Posterior epilepsies: Concluding remarks Few data are available to guide surgical decision making regarding extent of resection. On the one hand, the negative data suggest absence of a relationship, but the caveat that “absence of evidence is not evidence of absence” is important to bear in mind. Likely, the principles that guide posterior epilepsies are the same as those guiding other brain regions, leading us to recommend resection attempt to include the radiological and electrographic lesion. However, there are no data at all regarding the risk/benefit of incorporating posterior brain regions that result in neurological deficits: visual cortex, sensory cortex, and parietal regions that result in Gerstmann's syndrome (dominant) or neglect (nondominant). Visual deficits may be more tolerable than motor (especially dominant) or speech deficits, but may preclude driving. Once again, additional QoL studies are needed, and at this time these cases must be approached on a case-by-case basis.

2.4. Posterior lobe epilepsy

3. Summary

The number of series dedicated to posterior quadrant (parietal, occipital) epilepsy resections is more limited. Salanova et al. [34] analyzed 42 patients (23 “purely” occipital). Predictors of seizure outcome were an extensive lesion, absence of a visible lesion, and presence of post-resection interictal epileptiform discharges (Table 6). In the same era, Williamson et al. [35] examined 25 patients with occipital epilepsy: 16 underwent lesion surgery, “and a limited area of surrounding brain [was] resected.” Fourteen (88%) were seizure free at a mean of 6.4 years. The authors did not relate outcome to extent of resection. Similarly, but more recently, Tandon et al. [36] found that 17 of 21 patients were seizure free (81%), but they did not analyze the relationship of extent of resection to outcome. Binder et al. [37] examined 52 patients with occipital epilepsy, 50 of whom were lesional based on MRI. All patients underwent lesionectomy or topectomy, some with additional multiple subpial transections. Close to 77% of patients were seizure free or had auras only at a mean of

The key to reducing extent of resection and exposure is an accurate understanding of the minimal volume or extent of tissue that must be resected or disconnected to isolate or remove the epileptogenic zone. There is a need for a paradigm shift to better targeting of epileptogenic lesions and foci. Limited resections should come to be seen as better delineation and targeting of lesions. As imaging studies advance, limited resection will become the more attractive option. However, there will always be epileptic foci that involve regions that, when resected, will lead to a fixed neurological deficit. Randomized prospective multicenter clinical trials are needed to evaluate the risk/benefit in terms of QoL from such resections. Further, emphasis should be placed on the importance of MRI validation of the extent of resection, as it has been shown that the achieved resection is not necessarily equivalent to the intended resection [4]. Moreover, studies comparing the volume of resection with the extent of resection (i.e., percentage of lesion removed) are needed. Lastly and importantly,

Table 6 Posterior quadrant epilepsy studies. Study

Pathological diagnosis (histology)a

N

Extent of resection determined by MRI (postop)

ECoG Intracranial (post-resection) monitoring

Comments

Yes (P value not stated)

17 (1–46) years (for 37 patients)

Absence of post-resection epileptiform discharge/ spiking on ECoG or surface EEG was associated with better outcome. After complete resections, 81% of patients were seizure free. Sixty-nine percent of patients were seizure free. No surgical factors correlated with outcome. Aggressive resections were not found to be associated with seizure outcome.

Salanova et al, 1992 [34]

42

Tandon et al., MCD, tumors, gliosis 2009 [36]

21 Yes (in 19 cases)

See Comments

54 (13–157 months)

Binder et al., 2008 [37]

CD, gangliogliomas, VM, etc.

52

See Comments

6.7 years (4 months– 14.4 years)

Dalmagro et al., 2005 [38]

44 Yes Gliosis, VM, MCD, Sturge–Weber disease, brain tumors (DNETs or low-grade gliomas)

No (P = 0.34)

39.7 months (in patients who had surgery)

a

Yes (in 24 cases)

Intended resection

Duration of Seizure outcome follow-up, correlates with amount resected? mean (range) (P value)

Yes (in 34 cases)

CD, cortical dysplasia; FCD, focal cortical dysplasia; DNET, dysembryoplastic neuroectodermal tumor; VM, vascular malformation; MCD, malformation of cortical development.

240

S.V. Okonma et al. / Epilepsy & Behavior 20 (2011) 233–240

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