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Original Contribution |

Characteristics and Surgical Outcomes of Patients With Refractory Magnetic Resonance Imaging–Negative Epilepsies FREE

Christian G. Bien, MD; Miriam Szinay, MD; Jan Wagner, MD; Hans Clusmann, MD; Albert J. Becker, MD; Horst Urbach, MD
[+] Author Affiliations

Author Affiliations: Departments of Epileptology (Drs Bien, Szinay, and Wagner), Neurosurgery (Dr Clusmann), Neuropathology (Dr Becker), and Radiology/Neuroradiology, University of Bonn, Bonn, Germany (Dr Urbach).


Arch Neurol. 2009;66(12):1491-1499. doi:10.1001/archneurol.2009.283.
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Published online

Objective  To explore several characteristics of patients with pharmacoresistant epilepsy without distinct lesions on magnetic resonance images (MRI), who account for a relevant proportion of presurgical patient cohorts.

Design  Retrospective case series.

Setting  University epilepsy center.

Patients  A cohort of 1200 patients who had comprehensive presurgical assessment from January 1, 2000, through December 31, 2006.

Main Outcome Measures  Frequency of MRI patients in the total presurgical cohort, seizure-free outcome rates in patients who had surgery and those who did not, outcome predictors, and spatial properties of epileptogenic areas in MRI patients with epilepsy. All MRI patients were retrospectively analyzed. Presurgical MRIs were reevaluated for subtle cortical dysplasias by postprocessing and visual reassessment.

Results  One-hundred ninety MRI patients were identified (16% of all presurgical candidates); 29 (15%) had surgery. Eleven (38%) became seizure free (including those with auras only; 45%). Surgical therapy was more frequently offered to MRI+ patients (76%; P < .001), and their outcome was also superior (66% seizure-free; P = .001). The seizure-free rate of 16% in MRI patients who did not have surgery was, however, inferior to that of the MRI patients who did (P = .008). Nine MRI patients who had surgery had distinct histopathological lesions, 8 of which turned out to be retrospectively detectable on presurgical MRI. Seven of the MRI but histopathologically lesional patients became seizure free compared with only 4 of 20 patients without histopathological lesions (P = .003). Three-fifths of the histopathologically nonlesional patients had multifocal or extensive epileptogenic areas.

Conclusions  Patients with epilepsy who are MRI can be successfully treated with surgery. Improved sensitivity of MRI will improve the outcomes of presurgically studied patients. Surgical failures in patients without histopathological lesions mostly result from extensive epileptogenic areas.

Figures in this Article

The rate of successful resective surgery in patients with intractable focal epilepsy has been increasing during the last decades.1,2 This is particularly owing to improved brain magnetic resonance imaging (MRI) acquisition and interpretation during presurgical assessment.3 Resectable epileptogenic brain abnormalities have not only become detectable (like Ammon's horn sclerosis [AHS]); in addition, their extension can be more precisely estimated when the resection is planned (as with cortical dysplasias).46 There are, however, still a proportion of patients seeking presurgical evaluation whose MRIs are not considered to show a lesion potentially causative of chronic epilepsy (referred to hereafter as MRI). These patients have impaired treatment options. Compared with patients with typically epileptogenic structural abnormalities visible on MRI (MRI+ patients), MRI patients are less often offered epilepsy surgery,7 and if operations are done, they have an inferior seizure-free outcome.716 Despite improving MRI technique, MRI patients account for 18% to 43% of presurgically studied patients with epilepsy.7,14,16,17 They can be subdivided into those with distinct epileptogenic lesions on histopathological investigation (histo+ patients) and those without such lesions (histo patients).811,1317 Little is known as to why epileptogenic lesions are not always detected by preoperative MRI and what the epileptological characteristics of the histo patients are. To elucidate these 2 points, we analyzed our presurgically studied cohort of MRI pharmacoresistant patients with epilepsy. The ultimate goal was to explain surgical successes and failures, identify outcome predictors, and draw conclusions about the spatial properties of epileptogenic areas in MRI patients.

PATIENT SELECTION AND MRI PROTOCOL

From the prospective database of patients having comprehensive presurgical evaluation for intractable focal epilepsy at Bonn epilepsy center, we identified 1200 patients studied between January 1, 2000, and December 31, 2006.18 We selected all patients who were diagnosed as MRI. During presurgical evaluation, their MRIs were visually interpreted by experienced neuroradiologists and their findings had been described either as normal or exhibiting abnormalities that are not considered epileptogenic. Patients with the MRI signs of AHS, tumor, malformation of cortical development, vascular malformation, posttraumatic lesions, infarction or bleeding residua, or encephalitis were regarded as MRI+. Magnetic resonance imaging was performed on 1.5-T or, since 2005, 3-T systems (Gyroscan ACS-NT, Gyroscan NT-Intera, Gyroscan Intera, Gyroscan 3 T Intera, or Gyroscan 3T Achieva; Philips Medical Systems, Best, the Netherlands) according to an epilepsy protocol that has been described previously.6 The MRI patients who ultimately had epilepsy surgery formed the core group of this study. The following procedures were performed: standard anteromedial temporal lobe resections, tailored temporal lobe resections (taking into consideration individual results from intracranial electroencephalographic [EEG] recordings), selective amygdalohippocampectomies, and extratemporal focal resections, multilobar resections, or functional hemispherectomies. As outcome comparators, we used all MRI patients who did not have resective surgery and all MRI+ patients (subdivided into surgical and nonsurgical patients). All controls came from the same study period. Nonresective surgery, in terms of callosotomy or pure multiple subpial transections, was done in 5 MRI and 3 MRI+ cases. They were excluded from analysis, leaving a total of 1192 patients as the basic study population.

ASSESSMENT OF PRESURGICAL AND OUTCOME DATA

Patients' history, seizure semiology, and EEG data were obtained from hospital files and from original recordings if there were uncertainties. Fluorodeoxyglucose-positron emission tomographies as well as interictal and ictal single-photon emission computed tomographies (SPECT) were recorded and visually interpreted as part of the regular presurgical evaluation at the Department of Nuclear Medicine of the University of Bonn. In some cases, SPECT and MRI data were postprocessed during preoperative assessment using subtraction ictal SPECT coregistered with MRI (SISCOM).19 Seizure outcome data were obtained from outpatient records of the Department of Epileptology. Patients who were MRI and did not have follow-up studies were contacted by telephone. The follow-up period was defined as 1 week after surgery or presurgical assessment (in the patients who did not have surgery) until the last available follow-up. Seizure freedom was noted if the patient was free of all seizures including auras during the last year. Only patients with follow-ups more than 6 months later were considered. Whereas “not seizure free” was noted for all patients with ongoing seizures and follow-up of at least half a year, follow-up had to be more than 1 year to be considered seizure free; in patients with a seizure-free follow-up of less than 1 year, “no follow-up” was noted. This was done to avoid overestimation of transient postoperative seizure-free periods.

For the purposes of this study, presurgical MRI data obtained using Avanto 1.5 Tesla or Trio 3.0 Tesla systems (Siemens, Erlangen, Germany; if data from these systems were not available, 3-dimensional T1 data sets from one of the aforementioned Philips systems were used) were postprocessed for detection of subtle signs of focal cortical dysplasia (FCD) using a voxel-based, 3-dimensional, morphometric MRI analysis described elsewhere.20,21 In short, this method is based on algorithms of the freely available software for statistical parametric mapping and on additional simple calculations and filters. From a high-resolution T1-weighted 3-dimensional MRI data set, 3 new feature maps were derived that characterize, compared with a normal database, 3 potential features of FCD: the abnormal extension of gray matter into white matter, blurring of the gray matter–white matter junction, and abnormal thickness of the cortical ribbon. Postprocessing was performed by J.W., who at this time was blinded to patients' data. Magnetic resonance images found to be suspicious for presence of FCD were visually reanalyzed by H.U. Postprocessing-negative MRIs were also reread by H.U. for abnormalities potentially overlooked at presurgical assessment. H.U. was not blinded to the patients' clinical and neuropathological data because he participated in the original clinical evaluation and follow-up of most patients.

Presurgical data, MRI postprocessing results and outcome details of the MRI histo patients were reviewed in detail to retrospectively provide a hypothesis regarding the spatial extent of their epileptogenic areas.22

STATISTICS

Two-sided Pearson χ2 tests and t tests were applied as appropriate. P <.05 was considered significant.

Figure 1 shows the numbers of MRI+ and MRI patients, with the proportions of patients who had surgery and those who were ultimately seizure free. Demographic data, information on presurgical investigations, types of surgery, and follow-up of the groups are given in Table 1. The MRI patients who had surgery had taken at least 4 antiepileptic drugs without achieving seizure control with tolerable adverse effects; those who did not have surgery were resistant to at least 3 antiepileptic drugs. The number of patients who had surgery was smaller in the MRI than in the MRI+ cohorts (15% vs 73%; P < .001). Reasons for not performing surgery on MRI patients were lack of clear-cut focus hypothesis after noninvasive monitoring (n = 65; 40%); multiple foci revealed by noninvasive monitoring (n = 10; 6%); multifocal seizure onset documented by invasive monitoring (n = 19; 12%); expected neurological or neuropsychological risks (n = 2; 1%); patient finally decided against surgical approach, in particular, denial of electrode implantation (n = 28;18%); other reason (n = 29; 18%); and more than 1 reason (n = 8; 5%). The proportion of seizure-free MRI patients who had surgery was lower than in the MRI+ group who had surgery (38% vs 66%; P = .003) but higher than in the MRI patients who did not have surgery (38% vs 16%; P = .008).

Place holder to copy figure label and caption
Figure 1.

Overview of all presurgically evaluated patients and their outcomes (excluding 8 patients who had callosotomy or pure multiple subpial transections). Percentages are related to the respective total patient numbers. MRI+ indicates magnetic resonance imaging positive (ie, MRI shows a typically epileptogenic lesion); MRI, MRI negative. Of the 18 MRI patients who had surgery and were not totally seizure free, 2 had only auras. Thus, 13 of 29 patients (45%) were seizure free or had auras only.

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Table Graphic Jump LocationTable 1. Patient Data at Presurgical Assessment and Follow-up
PREDICTIVE VALUE OF NONINVASIVE PRESURGICAL STUDIES

The predictive value was estimated for all 29 MRI patients. The results are given in Table 2. Localizing information was classified as correct positive, correct negative, false positive, false negative, or inconclusive; positive and negative predictive values were calculated (Table 2).

Table Graphic Jump LocationTable 2. Predictive Value of Noninvasive Diagnostic Tools in Presurgical Assessment of MRI and Histo Patientsa

Postprocessing of MRI and seizure semiology both have a relatively low chance of providing localizing information, but if they do, the positive and negative predictive values are high. Other good outcome predictors are surface EEG and SISCOM.

POTENTIAL ROLE OF TYPE OF SURGERY ON OUTCOME

Different types of operative interventions in the MRI and MRI+ groups may account for their different seizure-free outcome rates. Large, less focused standard interventions may offer a higher chance of seizure freedom than small, selective operations. However, in the temporal lobe surgery group, large operations were more common in the MRI patients than small interventions (eg, selective amygdalohippocampectomy). There was no significant difference between small (focused) and large extratemporal operations (multilobar resections and hemispherectomies) (Table 1). Taken together, there is no indication that the surgical approaches caused the inferior outcome of the MRI group.

HISTOPATHOLOGY OF MRI PATIENTS AND RELATED OUTCOME

Nine MRI patients were histo+; 3 had FCD type IIB, 2 FCD type IIA,23 3 AHS, and 1 cavernoma (Figure 2). The remaining 20 patients had normal or nonspecifically altered histopathological findings. The outcomes of the histo+ patients were better than those of the histo patients (7 of 9 vs 4 of 20 patients seizure free; P = .003). The seizure freedom rate in the MRI histo+ group (78%) is similar to that of MRI+ patients (67%; P = .47). Only the 2 patients with FCD IIA did not achieve seizure freedom. There was no significant correlation between the seizure-freedom rate and site of surgery (7 of 22 patients were seizure free after temporal lobe surgery vs 4 of 7 after extratemporal surgery).

Place holder to copy figure label and caption
Figure 2.

Histopathology-related outcome of all magnetic resonance imaging (MRI)–negative patients. AHS indicates Ammon horn sclerosis; EA, epileptogenic area; FCD, focal cortical dysplasia; histo−/+, histopathologically negative/positive; MRI+, MRI positive (ie, MRI shows a typically epileptogenic lesion); MRI, MRI negative (ie, MRI does not show a typically epilogenetic lesion).

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MRI REASSESSMENT OF MRI HISTO+ PATIENTS

Seven of 16 MRI patients who had 1.5-T scans and 2 of 13 who had 3-T scans were diagnosed with typically epileptogenic lesions on histopathological examination (P = .1). Eight of the 9 histopathological abnormalities could be identified on reassessment of pre–surgically-acquired MRI data. Using voxel-based morphometric MRI postprocessing combined with subsequent visual reinspection of MRIs, all 3 patients with FCD IIB and 1 of the 2 with FCD IIA could be unequivocally detected. Two of the 3 histopathologically diagnosed AHS were still difficult to detect on visual reassessment because of the poor signal to noise ratio of the MRIs; the third AHS was clearly visible and had simply been overlooked during presurgical assessment. Also, the temporolateral cavernoma was readily detectable on reinspection of the presurgical images on which it had been missed. One temporolateral FCD IIA remained undetectable on presurgical MRI data, even with use of MRI postprocessing and visual reassessment, knowing the lesion site and histopathological diagnosis.

DETAILED ASSESSMENT OF MRI HISTO PATIENTS

Twenty MRI patients had normal findings or nonspecific alterations on histopathological evaluation. Individual data of these patients and retrospective hypotheses about their epileptogenic areas are given in Table 3 and Table 4. Seventeen had temporal lobe resections. In the remaining 3, extratemporal topectomies were performed (2 in the anterior parts of the medial frontal cortex, 1 in the posterior cortex). One frontal and 3 temporal resections resulted in seizure-free outcomes (Table 3 and Table 4; patients 1-3 and 18). All seizure-free patients were female (P = .02) and had a higher age at onset than the non–seizure-free patients (median age, 29; range 14-31 years vs median, 8; range, 2-19 years; P = .006); epilepsy duration was, however, not different between seizure-free and non–seizure-free patients (median, 20; range, 8-40 years vs median, 18; range, 3-29 years). No seizure-free and 4 non–seizure-free patients had a history that was potentially related to subsequent epilepsy, ie, initial precipitating injuries (3 cases of encephalitides and 1 brain trauma; P = .45).

Table Graphic Jump LocationTable 3. Patients Without Definite Histopathological Diagnosis: Demographical Data and Results of Presurgical Evaluation (Part 1)
Table Graphic Jump LocationTable 4. Patients Without Definite Histopathological Diagnosis: Results of Presurgical Evaluation (Part 2), Surgical Outcome, and Final Hypothesis on Epileptogenic Area

A case-by-case review of the 20 MRI histo patients led to the following hypotheses regarding the spatial extent of their epileptogenic areas according to 5 possible scenarios24:

  • Adequate determination of a circumscribed epileptogenic area and sufficient resection, as evidenced by postsurgical seizure freedom (n = 4). The 3 patients who became seizure free after temporal resections had highly concordant presurgical results (patients 1-3). Surprisingly,this strong concordance was not present in the 1 seizure-free patient who had frontomedial resection (patient 18).

  • Insufficient resection owing to neurosurgical failure (n = 1). The temporolateral seizure-onset zone of patient 4, as determined by invasive EEG monitoring, had been incompletely resected, as evidenced by coregistration of MRI with intracranial electrodes and postoperative MRI. No structural abnormality was suggested by postprocessing of preoperative MRI data. This patient was offered a repeated operation but she did not give consent.

  • Epileptogenic area missed during presurgical assessment (n = 4). In patients who had temporal lobe operations (patients 5-8) without subsequent seizure freedom, postoperative review suggested an epileptogenic area outside of the presurgically designated region and, therefore, not approached by the surgical procedure. In 2 of these 4 patients, MRI postprocessing with subsequent visual reassessment of MRIs suggested dysplastic tissue outside of the resected areas at sites emerging as probably epileptogenic on review of the other presurgically obtained data. In 1 patient with daily seizures (patient 7), this postoperative discovery on the preoperative MRI data led to exploration of the suspected area plus adjacent parts of the same lobe by intracranial depth and subdural electrodes. The depth electrode inserted at the site indicated by MRI postprocessing showed focal low amplitude fast activity at seizure onset. Subsequently, this area was resected. On histopathological examination, no abnormal neurons were found. The fragmented state of the material, however, did not permit assessment of potential architectural abnormalities. At the most recent follow-up, 6 months after this second surgical procedure, the patient was still continuously seizure free.

  • Multifocal epileptogenic areas (n = 4). This was hypothesized retrospectively in patients 9 through 12, who had temporal lobe resections: 1 had an additional frontal and 4 had additional contralateral temporal epileptogenic areas. None of these patients had an additional MRI abnormality on postprocessing and visual MRI reassessment.

  • Extensive epileptogenic area insufficiently determined (epileptological failure, n = 8). In these patients (patients 13-17, 19, and 20), the epileptogenic areas were, in part, removed but obviously extended broadly beyond the designated resection borders, as evident on reanalysis of the presurgical data. None of these patients had an additional MRI abnormality on postprocessing and visual MRI reassessment.

In this cohort, patients with MRI epilepsies have a lower chance of having surgery than those with lesions demonstrated by presurgical MRI and, if so, less chance of becoming seizure free. This confirms previous data.7,25 The seizure-free outcome rate of MRI patients who had surgery is, on the other hand, better than that of those who did not. This has not been demonstrated before by direct comparison. The MRI patients for whom surgery was successful demonstrate that the process of multimodal presurgical evaluation may lead to good outcomes in patients with refractory focal epilepsies, even if they do not have an MRI correlate. When choosing a particular test modality, MRI postprocessing, interictal EEG, and semiology have the highest likelihood of providing inconclusive results. If a certain brain area is contemplated as the to-be-resected area, any conclusive test result may be weighted according to the data given in Table 2. Concordant data from MRI postprocessing, semiology, and ictal surface EEG, in that order, are the best predictors of a seizure-free outcome if the planned resection is done. Discordant results of MRI postprocessing, interictal surface EEG, semiology, and SISCOM are the strongest predictors of a non–seizure-free outcome if the contemplated operation is performed. These predictive values and suggestions have, however, several limitations. They are the results of decisions of the center's clinicians, and the values of these tests may vary depending on the location of the pathology (positron emission tomography, for example, is probably better in identifying mediotemporal lobe than extratemporal foci). Both potential biases can hardly be controlled for in this type of retrospective analysis and small sample size. Epilepsies that are MRIare not necessarily nonlesional. Thirty percent of MRI patients in this study and a median proportion of 46% in other series811,1317 have epileptogenic lesions. In the present cohort, these MRI histo+ patients had a postoperative seizure-free outcome as favorable as that of the MRI+ control patients, clearly better than that of the histo patients who had surgery. Conversely, the proportions of seizure-free patients in the MRI+ and MRI cohorts who did not have surgery are almost identical, suggesting more similarities than dissimilarities regarding the underlying pathology of the epilepsies. It may be expected that previously MRI histo+ patients will be found to be MRI+ in the near future, which will increase their chances of proceeding to successful resective epilepsy surgery. Improved MRI acquisition at field strengths of more than 1.5 T and appropriate postprocessing techniques, together with growing experience of MRI evaluators, will likely contribute to this advance.20,26 This assumption is supported by the results of this series; about three-fourths of the false-negative MRIs (ie, those of MRI histo+ patients) were acquired using 1.5 T systems. Reevaluation by postprocessing and visual reinspection of existing MRI data permitted the detection of underlying brain lesions in all but 1 of 9 such patients. Only 1 temporal lobe FCD IIA remained undetected. Furthermore, the renewed MRI assessment indicated nonresected dysplastic lesions in 2 histo patients who did not become seizure free after resection of an MRI histo area. In both, renewed assessment of presurgical data confirmed that their epileptogenic areas were congruent with the retrospectively identified lesions and had been missed during the original preoperative evaluation. One subsequently had resection after intracranial studies unequivocally confirmed seizure onset in the area, found to be dysplastic during MRI postprocessing.

Presurgical detection of focal lesions by MRI not only guides presurgical evaluation along more effective pathways26; epilepsies caused by such focal lesions appear different in nature from histopathologically nonlesional ones. Seizures related to FCD or AHS arise mostly from strictly circumscribed, and therefore completely resectable, epileptogenic areas (tightly related to the structural abnormalities). In contrast, the major reasons for frequently unsuccessful focal resections in cases without such lesions were multifocality or large extension of the epileptogenic areas (12 of 20, ie, three-fifths). Initial precipitating injuries that cause extended brain damage such as trauma or encephalitis may contribute to widespread epileptogenic areas in those cases. This study further supports the concept that many MRI patients have poorly localized epileptogenic areas; more than two-thirds of MRI patients were rejected from surgery after comprehensive evaluation owing to multifocality or poor demarcation of the epileptogenic area. These observations may indicate a more elaborate and extensive presurgical diagnostic procedure (including, for example, more extensive electrode implantations) in this patient group.

Only 3 of 20 histo patients (15%) had sufficiently restricted epileptogenic areas to become seizure free after resections of typical extension. In this series, seizure-free histo patients had a relatively high age at epilepsy onset (median, 29 years) and were all female; the meaning and predictive relevance of these features, however, are unclear.

In summary, it is worthwhile to perform presurgical epileptological evaluation of patients with features compatible with monofocal epilepsy, even in the absence of a typically epileptogenic MRI lesion. Patients with concordant noninvasively obtained focus signs should have intracranial EEG and proceed to epilepsy surgery if a monofocal, resectable epileptogenic area is found. At the same time, all efforts should be made to improve the yield of MRI because of the higher effectiveness of presurgical evaluation in MRI+ epilepsy patients.

Correspondence: Christian G. Bien, MD, University of Bonn, Department of Epileptology, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany (christian.bien@ukb.uni-bonn.de).

Accepted for Publication: August 11, 2009.

Author Contributions: The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Bien, Szinay, and Urbach. Acquisition of data: Bien, Szinay, Clusmann, Becker, and Urbach. Analysis and interpretation of data: Bien, Szinay, Wagner, Clusmann, Becker, and Urbach. Drafting of the manuscript: Bien. Critical revision of the manuscript for important intellectual content: Szinay, Wagner, Clusmann, Becker, and Urbach. Administrative, technical, and material support: Clusmann and Becker. Study supervision: Bien, Clusmann, and Urbach.

Financial Disclosure: None reported.

Additional Contributions: The authors would like to thank C. E. Elger, MD, FRCP, University of Bonn, Department of Epileptology and Life and Brain Center, for his kind support and for providing Siemens magnetic resonance imaging data; J. Schramm, MD, for continuous support; and Ms Claudia Ullmann for excellent technical assistance.

Engel  J  JrWiebe  SFrench  J  et al. Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society; American Association of Neurological Surgeons, Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 2003;60 (4) 538- 547
PubMed Link to Article
Téllez-Zenteno  JFDhar  RWiebe  S Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 2005;128 (pt 5) 1188- 1198
PubMed Link to Article
Engel  J  JrWieser  HGSpencer  DD Overview: surgical therapy. Engel  J  JrPedley  TAEpilepsy: a Comprehensive Textbook 2nd ed. Philadelphia, PA Lippincott Williams & Wilkins2007;1747- 1749
Duncan  JS Imaging and epilepsy. Brain 1997;120 (pt 2) 339- 377
PubMed Link to Article
Von Oertzen  JUrbach  HJungbluth  S  et al.  Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy. J Neurol Neurosurg Psychiatry 2002;73 (6) 643- 647
PubMed Link to Article
Urbach  H Imaging of the epilepsies. Eur Radiol 2005;15 (3) 494- 500
PubMed Link to Article
Berg  ATVickrey  BGLangfitt  JT  et al. Multicenter Study of Epilepsy Surgery, The multicenter study of epilepsy surgery: recruitment and selection for surgery. Epilepsia 2003;44 (11) 1425- 1433
PubMed Link to Article
Alarcón  GValentin  AWatt  C  et al.  Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging? J Neurol Neurosurg Psychiatry 2006;77 (4) 474- 480
PubMed Link to Article
Chapman  KWyllie  ENajm  I  et al.  Seizure outcome after epilepsy surgery in patients with normal preoperative MRI. J Neurol Neurosurg Psychiatry 2005;76 (5) 710- 713
PubMed Link to Article
Lee  SKLee  SYKim  KKHong  KSLee  DSChung  CK Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy. Ann Neurol 2005;58 (4) 525- 532
PubMed Link to Article
Sylaja  PNRadhakrishnan  KKesavadas  CSarma  PS Seizure outcome after anterior temporal lobectomy and its predictors in patients with apparent temporal lobe epilepsy and normal MRI. Epilepsia 2004;45 (7) 803- 808
PubMed Link to Article
Spencer  SSBerg  ATVickrey  BG  et al. Multicenter Study of Epilepsy Surgery, Predicting long-term seizure outcome after resective epilepsy surgery: the multicenter study. Neurology 2005;65 (6) 912- 918
PubMed Link to Article
Cukiert  ABuratini  JAMachado  E  et al.  Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids. Epilepsia 2001;42 (7) 889- 894
PubMed Link to Article
Siegel  AMJobst  BCThadani  VM  et al.  Medically intractable, localization-related epilepsy with normal MRI: presurgical evaluation and surgical outcome in 43 patients. Epilepsia 2001;42 (7) 883- 888
PubMed Link to Article
Holmes  MDBorn  DEKutsy  RLWilensky  AJOjemann  GAOjemann  LM Outcome after surgery in patients with refractory temporal lobe epilepsy and normal MRI. Seizure 2000;9 (6) 407- 411
PubMed Link to Article
Scott  CAFish  DRSmith  SJ  et al.  Presurgical evaluation of patients with epilepsy and normal MRI: role of scalp video-EEG telemetry. J Neurol Neurosurg Psychiatry 1999;66 (1) 69- 71
PubMed Link to Article
McGonigal  ABartolomei  FRegis  J  et al.  Stereoelectroencephalography in presurgical assessment of MRI-negative epilepsy. Brain 2007;130 (pt 12) 3169- 3183
PubMed Link to Article
Kral  TClusmann  HUrbach  J  et al.  Preoperative evaluation for epilepsy surgery (Bonn Algorithm). Zentralbl Neurochir 2002;63 (3) 106- 110
PubMed Link to Article
O'Brien  TJSo  ELMullan  BP  et al.  Subtraction ictal SPECT co-registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus. Neurology 1998;50 (2) 445- 454
PubMed Link to Article
Huppertz  HJGrimm  CFauser  S  et al.  Enhanced visualization of blurred gray-white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis. Epilepsy Res 2005;67 (1-2) 35- 50
PubMed Link to Article
Huppertz  HJWellmer  JStaack  AMAltenmüller  DMUrbach  HKröll  J Voxel-based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia. Epilepsia 2008;49 (5) 772- 785
PubMed Link to Article
Lüders  HONajm  INair  DWiddess-Walsh  PBingman  W The epileptogenic zone: general principles. Epileptic Disord 2006;8 ((suppl 2)) 1- 9
Palmini  ANajm  IAvanzini  G  et al.  Terminology and classification of the cortical dysplasias. Neurology 2004;62 (6) ((suppl 3)) S2- S8
PubMed Link to Article
Vives  KLee  GDoyle  WSpencer  DD Anterior temporal lobe resection. Engel  J  JrPedley  TAEpilepsy: a Comprehensive Textbook 2nd ed. Philadelphia, PA Lippincott Williams & Wilkins2008;1859- 1867
Berkovic  SFMcIntosh  AMKalnins  RM  et al.  Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis. Neurology 1995;45 (7) 1358- 1363
PubMed Link to Article
Huppertz  HJKurthen  MKassubek  J Voxel-based 3D MRI analysis for the detection of epileptogenic lesions at single subject level [letter]. Epilepsia 2009;50 (1) 155- 156
PubMed Link to Article

Figures

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Figure 1.

Overview of all presurgically evaluated patients and their outcomes (excluding 8 patients who had callosotomy or pure multiple subpial transections). Percentages are related to the respective total patient numbers. MRI+ indicates magnetic resonance imaging positive (ie, MRI shows a typically epileptogenic lesion); MRI, MRI negative. Of the 18 MRI patients who had surgery and were not totally seizure free, 2 had only auras. Thus, 13 of 29 patients (45%) were seizure free or had auras only.

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Figure 2.

Histopathology-related outcome of all magnetic resonance imaging (MRI)–negative patients. AHS indicates Ammon horn sclerosis; EA, epileptogenic area; FCD, focal cortical dysplasia; histo−/+, histopathologically negative/positive; MRI+, MRI positive (ie, MRI shows a typically epileptogenic lesion); MRI, MRI negative (ie, MRI does not show a typically epilogenetic lesion).

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Tables

Table Graphic Jump LocationTable 1. Patient Data at Presurgical Assessment and Follow-up
Table Graphic Jump LocationTable 2. Predictive Value of Noninvasive Diagnostic Tools in Presurgical Assessment of MRI and Histo Patientsa
Table Graphic Jump LocationTable 3. Patients Without Definite Histopathological Diagnosis: Demographical Data and Results of Presurgical Evaluation (Part 1)
Table Graphic Jump LocationTable 4. Patients Without Definite Histopathological Diagnosis: Results of Presurgical Evaluation (Part 2), Surgical Outcome, and Final Hypothesis on Epileptogenic Area

References

Engel  J  JrWiebe  SFrench  J  et al. Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society; American Association of Neurological Surgeons, Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 2003;60 (4) 538- 547
PubMed Link to Article
Téllez-Zenteno  JFDhar  RWiebe  S Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 2005;128 (pt 5) 1188- 1198
PubMed Link to Article
Engel  J  JrWieser  HGSpencer  DD Overview: surgical therapy. Engel  J  JrPedley  TAEpilepsy: a Comprehensive Textbook 2nd ed. Philadelphia, PA Lippincott Williams & Wilkins2007;1747- 1749
Duncan  JS Imaging and epilepsy. Brain 1997;120 (pt 2) 339- 377
PubMed Link to Article
Von Oertzen  JUrbach  HJungbluth  S  et al.  Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy. J Neurol Neurosurg Psychiatry 2002;73 (6) 643- 647
PubMed Link to Article
Urbach  H Imaging of the epilepsies. Eur Radiol 2005;15 (3) 494- 500
PubMed Link to Article
Berg  ATVickrey  BGLangfitt  JT  et al. Multicenter Study of Epilepsy Surgery, The multicenter study of epilepsy surgery: recruitment and selection for surgery. Epilepsia 2003;44 (11) 1425- 1433
PubMed Link to Article
Alarcón  GValentin  AWatt  C  et al.  Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging? J Neurol Neurosurg Psychiatry 2006;77 (4) 474- 480
PubMed Link to Article
Chapman  KWyllie  ENajm  I  et al.  Seizure outcome after epilepsy surgery in patients with normal preoperative MRI. J Neurol Neurosurg Psychiatry 2005;76 (5) 710- 713
PubMed Link to Article
Lee  SKLee  SYKim  KKHong  KSLee  DSChung  CK Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy. Ann Neurol 2005;58 (4) 525- 532
PubMed Link to Article
Sylaja  PNRadhakrishnan  KKesavadas  CSarma  PS Seizure outcome after anterior temporal lobectomy and its predictors in patients with apparent temporal lobe epilepsy and normal MRI. Epilepsia 2004;45 (7) 803- 808
PubMed Link to Article
Spencer  SSBerg  ATVickrey  BG  et al. Multicenter Study of Epilepsy Surgery, Predicting long-term seizure outcome after resective epilepsy surgery: the multicenter study. Neurology 2005;65 (6) 912- 918
PubMed Link to Article
Cukiert  ABuratini  JAMachado  E  et al.  Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids. Epilepsia 2001;42 (7) 889- 894
PubMed Link to Article
Siegel  AMJobst  BCThadani  VM  et al.  Medically intractable, localization-related epilepsy with normal MRI: presurgical evaluation and surgical outcome in 43 patients. Epilepsia 2001;42 (7) 883- 888
PubMed Link to Article
Holmes  MDBorn  DEKutsy  RLWilensky  AJOjemann  GAOjemann  LM Outcome after surgery in patients with refractory temporal lobe epilepsy and normal MRI. Seizure 2000;9 (6) 407- 411
PubMed Link to Article
Scott  CAFish  DRSmith  SJ  et al.  Presurgical evaluation of patients with epilepsy and normal MRI: role of scalp video-EEG telemetry. J Neurol Neurosurg Psychiatry 1999;66 (1) 69- 71
PubMed Link to Article
McGonigal  ABartolomei  FRegis  J  et al.  Stereoelectroencephalography in presurgical assessment of MRI-negative epilepsy. Brain 2007;130 (pt 12) 3169- 3183
PubMed Link to Article
Kral  TClusmann  HUrbach  J  et al.  Preoperative evaluation for epilepsy surgery (Bonn Algorithm). Zentralbl Neurochir 2002;63 (3) 106- 110
PubMed Link to Article
O'Brien  TJSo  ELMullan  BP  et al.  Subtraction ictal SPECT co-registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus. Neurology 1998;50 (2) 445- 454
PubMed Link to Article
Huppertz  HJGrimm  CFauser  S  et al.  Enhanced visualization of blurred gray-white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis. Epilepsy Res 2005;67 (1-2) 35- 50
PubMed Link to Article
Huppertz  HJWellmer  JStaack  AMAltenmüller  DMUrbach  HKröll  J Voxel-based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia. Epilepsia 2008;49 (5) 772- 785
PubMed Link to Article
Lüders  HONajm  INair  DWiddess-Walsh  PBingman  W The epileptogenic zone: general principles. Epileptic Disord 2006;8 ((suppl 2)) 1- 9
Palmini  ANajm  IAvanzini  G  et al.  Terminology and classification of the cortical dysplasias. Neurology 2004;62 (6) ((suppl 3)) S2- S8
PubMed Link to Article
Vives  KLee  GDoyle  WSpencer  DD Anterior temporal lobe resection. Engel  J  JrPedley  TAEpilepsy: a Comprehensive Textbook 2nd ed. Philadelphia, PA Lippincott Williams & Wilkins2008;1859- 1867
Berkovic  SFMcIntosh  AMKalnins  RM  et al.  Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis. Neurology 1995;45 (7) 1358- 1363
PubMed Link to Article
Huppertz  HJKurthen  MKassubek  J Voxel-based 3D MRI analysis for the detection of epileptogenic lesions at single subject level [letter]. Epilepsia 2009;50 (1) 155- 156
PubMed Link to Article

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