Abstract Cerebral cavernous malformations (CM) arewell-circumscribed vascular malformations that oftenpresent with epileptic seizures. Although patients mayinitially benefit from antiepileptic drugs, surgical treat-ment may become necessary due to medically intractableseizures. However, it is unclear whether lesionectomyalone or tailored epilepsy surgery with previous invasivemonitoring is the optimal strategy in such cases. We re-port two patients with epileptic seizures due to CM. Onepatient with few seizures prior to surgery became sei-zure-free following resection of the CM and the sur-rounding tissue. In the second patient with long-lastingepilepsy, lesionectomy was performed because of theproximity to a functioning left hippocampus. This limit-ed resection failed and the patient still had seizures. Sub-sequently, invasive monitoring with intracranial depthand strip electrodes was performed in order to localizethe epileptogenic area and determine whether the lefthippocampus could be spared. The invasive studyshowed the seizure origin in the tissue around the formerCM but no epileptic discharges in the hippocampus. In asecond operation, an anterior temporal resection was per-formed with removal of the epileptogenic surroundingtissue and the patient became seizure-free without cogni-tive deficits. The optimal surgical strategy for CM pre-senting with epileptic seizures must take into accountvarious factors such as underlying mechanisms and dura-tion of epilepsy, and location of the lesion.

Key words Cavernous malformations · Epilepsy ·Lesionectomy · Epilepsy surgery · Dual pathology

Introduction

Among vascular malformations of the central nervoussystem, cavernous malformations (CM) are the leastcommon type, having a prevalence of about 0.5% [1–3].Clinically, CM may remain asymptomatic, but they oftenpresent with epileptic seizures, clinically significanthemorrhages, chronic headache, or focal neurologicaldeficits [2, 4–7].

Therapeutic options in cerebral CM consist of conser-vative management and surgical intervention. In CMpresenting with epilepsy, antiepileptic drugs (AED) areoften the initial treatment and satisfactory seizure controlmay be thus achieved [8]. However, surgery may be-come necessary due to medically intractable seizuresand/or clinically significant hemorrhages from the CM[8]. Despite the large number of cases reported in the lit-erature, the optimal surgical strategy is still controversial[9]. Currently, options for surgical treatment include: (1)non-tailored en bloc resection (i.e., removal of the CM-containing lobe), (2) pure lesionectomy, and (3) and le-sion excision with tailored resection of the adjacent epi-leptogenic brain tissue. The first option has largely beenreplaced by the use of microsurgical techniques in per-forming the latter two. However, which of these two op-tions is favorable has not been determined.

In this paper, we discuss the role of the different sur-gical strategies based on the underlying pathophysiolog-ic mechanisms in two patients harboring a CM present-ing with seizures.

Case report

Case 1

In this 30-year-old right-handed woman, a CM in the right infero-lateral frontal lobe was incidentally detected by magnetic reso-

A.M. Siegel (✉)Epilepsy Program, Department of Neurology,University of Zurich, Frauenklinikstrasse 26,8091 Zurich, Switzerlande-mail: Adrian.Siegel@nos.usz.chTel.: +41-1-255-55-39, Fax: +41-1-255-44-29

P.D. WilliamsonNeurology Section, Dartmouth-Hitchcock Medical Center,Lebanon, NH 03756, USA

D.W. Roberts · R.E. HarbaughNeurosurgery Section, Dartmouth-Hitchcock Medical Center,Lebanon, NH 03756, USA

Neurosurg Rev (2000) 23:80–83 © Springer-Verlag 2000

O R I G I N A L A RT I C L E

Adrian M. Siegel · David W. RobertsRobert E. Harbaugh · Peter D. Williamson

Pure lesionectomy versus tailored epilepsy surgery in treatmentof cavernous malformations presenting with epilepsy

Received: 22 September 1999 / Accepted: 13 January 2000

Examination

Her general and neurological examinations were unremarkable.Interictal scalp EEGs were repeatedly normal. Two ictal scalpEEGs did not show a clear seizure onset but revealed a left-sidedpredominant postictal slowing. MRI showed a 1.5 cm CM in theleft medial temporal lobe just lateral to the anterior part of thehippocampal formation (Fig. 2A). Both hippocampi were ofnormal appearance. Neuropsychological testing was normalexcept for slightly impaired visual memory. A Wada test demon-strated left-sided speech dominance and intact memory perfor-mance bilaterally.

First operation

Because of the relatively critical location of the CM just lateral tothe normal functioning left hippocampus and possibly near thetemporal speech area, the decision was made to proceed withlesionectomy without resection of the adjacent hippocampus. On25 June 25, a temporal craniotomy was performed. The CM wastotally removed but the surrounding tissue was not resected(Fig. 2B). The patient awoke after surgery with no discernibleneurological or cognitive deficits. Pathology confirmed thediagnosis of CM.

Intermediate course

The patient had no seizures for the first 6 postoperative weeks, buther typical seizures then returned with increased frequency. Sincethese remained drug-resistant, she was readmitted 5 1/2 monthsafter her surgery for an invasive evaluation. Intracranial EEG re-cording consisted of a 4×8 contact grid electrode over the tempo-ral convexity that included the area of the former lesionectomy, aleft hippocampal 12-contact depth electrode to determine whetherthere was independent epileptic activity in the left hippocampus,and three 1×6 contact and one 1×4 contact subdural strip elec-trodes positioned subtemporally. Five seizures consisting only ofconfusion were recorded. Electroencephalographically, the sei-zures began in the anterior inferior part of the grid and spread tothe hippocampus 10 s later. Functional mapping showed nospeech-associated cortex beneath the grid covering the temporalconvexity.

Second operation

Based on the functional mapping results and the fact that the sei-zures did not begin in the left hippocampus, a left-sided anteriortemporal resection sparing the hippocampus was performed on 14December 1992 (Fig. 2C). The brain tissue adjacent to the formerlesionectomy showed gliotic changes.

Postoperative course

The patient has remained seizure-free during the 7 years followingsurgery. Postoperatively, there was no change in cognitive func-tions.

Discussion

While the optimal surgical strategy for tumors is general-ly given by their pathological differentiation, the mostfavorable technique for surgery of vascular malforma-tions is still controversial. Since CM are commonly well-circumscribed lesions, lesionectomy may appear to bethe approach of choice [9]. However, such a limited re-section may not address the problem of related seizures.Therefore, the type of symptom with its underlying

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nance imaging (MRI) performed for evaluation of new-onset anxi-ety and depression. Because of the lack of CM-related symptomsand specifically any history of clinically significant hemorrhages,conservative therapy was recommended first. One year later, how-ever, the patient experienced two generalized seizures. In order tocontrol seizures and eliminate the potential for gross hemorrhage,resection of the CM was offered.

Examination

The patient’s neurological examination was normal. A repeat MRIshowed the frontal lesion with typical features of a CM consistingof a hemosiderin rim in the T2 weighted images and, in addition, acoexistent developmental venous anomaly next to the CM thatdrained into the superficial venous system (Fig. 1A).

Operation

On 1 September 1995, the patient underwent right frontal craniot-omy. Inspection of the cortical surface revealed the cavernousmalformation in the right inferolateral frontal lobe and the devel-opmental venous anomaly that drained into the superficial venoussystem. The CM was then dissected in a circumferential mannerand removed. The surrounding hemosiderin-stained brain tissuewas also removed, leaving a margin of normal brain tissue (Fig.1B). The patient had no postoperative neurological deficits. His-tology showed typical features of a CM.

Postoperative course

The patient had no further seizures in the postoperative 3-year fol-low-up period.

Case 2

The intrauterine history, birth, and childhood of this 41-year-oldright-handed female teacher were unremarkable, as was the familyhistory. In 1976, at the age of 19 years, she began to experiencesimple partial seizures characterized by hearing lyrics of a song orsomeone’s name that she could not identify. This was followed bylightheadedness, the entire episode lasting up to 30 seconds. Al-though various AED were tried, seizures continued to occur inclusters. At age 34, the character of her seizures changed: they con-sisted of an arrest reaction, staring, lip smacking, manual automat-isms, and loss of consciousness. Because of increased seizure fre-quency and intensity, she was admitted to our institution for furtherevaluation and therapy.

Fig. 1A, B MRI of case 1. A prior to the removal of a superficialleft frontal cavernous malformation. B Following surgery

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pathophysiologic mechanism has to be considered in de-ciding on an optimal surgical strategy.

One cause of chronic focal neurological deficits is themass effect of CM. In addition, intralesional hemorrhagewith acute expansion of the lesion may occur, sometimesthe result of partial thrombosis and increased turgor andsize within a compartment [3]. Since the adjacent brainis not infiltrated by these lesions, it is understandablethat selective lesion excision is often sufficient in pa-tients with focal neurological deficits. In CM presentingwith gross hemorrhages and significant compression ofbrain tissue, the intervention of choice is removal of thelesion and blood clot [3].

The underlying mechanisms for epilepsy in CM aremore complex and still not completely understood. Giv-en the lack of intralesional brain tissue, CM per se areclearly not epileptogenic [3]. Furthermore, the mass ef-fect does not explain the high epileptogenicity of thisvascular malformation. Other lesions of larger size suchas diffuse growing malignant tumors are less commonlyassociated with medically refractory epilepsy [10, 11].The underlying cause of the epileptogenicity of CM ap-pears to be the chronic, clinically silent microhemor-rhages [3, 12]. This results in the deposition of iron-con-taining blood breakdown products such as hemosiderin,a probable degradation product of ferritin, as well ashemin, a globin breakdown product, in the adjacent braintissue. Iron may generate epilepsy by different mecha-nisms. As an electron donor, iron is implicated in theproduction of free radicals and lipid peroxides which in-teract with receptor activity, calcium channels, cellulartransport proteins, intracellular second messengers, andneurotransmitter (glutamate and aspartate)-mediated exc-itotoxicity [12–15]. A further sequel of iron exposure inadjacent tissue is the reactive glial proliferation that isknown to be epileptogenic [12].

The various iron-triggered cellular alterations are likelyto be more significant, the longer the duration of epilepsyand the tissue adjacent to CM becomes increasingly epi-leptogenic [6]. However, whether or not a long duration ofepilepsy results in poor surgical outcome with respect toseizure frequency is still a matter of discussion [6, 9].

Furthermore, iron-laden epileptogenic tissue maycause independent secondary epileptogenic foci in exper-imental animals by kindling. However, it is controversialwhether or not such secondary foci can be found in hu-mans. One indicator of secondary epileptogenesis in hu-mans is the finding of dual pathology, i.e., hippocampalneuronal cell loss in some patients harboring extrahippo-campal lesions such as brain tumor, cortical dysgenesis,or vascular malformation [16–19]. In patients with CM,dual pathology has been rarely found but sometimes re-ported [19, 20]. In these patients, lesionectomy did notresult in seizure control, and subsequent resection of themesial temporal structures became necessary in order toachieve satisfactory seizure outcome [9, 19, 20].

Under this premise, it is obvious that lesionectomyalone in CM presenting with seizures is usually not suffi-cient, and resection of both the CM and the surroundingepileptogenic tissue is probably necessary [21]. The cru-cial role of additional resection of adjacent brain tissue isdemonstrated by the seizure outcome in our two cases:the first patient became seizure-free following resectionof the CM and the hemosiderin-containing surroundingtissue. In contrast, the second patient experienced no im-provement in seizure control following lesionectomy thatwas performed to spare the adjacent speech area and hip-pocampus. Such failures with respect to seizure outcomefollowing incomplete resection of the epileptogenic sur-rounding tissue have been previously reported [6, 21].Following the second operation with resection of the epi-leptogenic tissue surrounding the original CM, this pa-tient became seizure-free. The second case is also of in-terest with respect to the necessity of presurgical inva-sive EEG monitoring.

Resection of CM and surrounding tissue can often beperformed without preoperative invasive studies, particu-

Fig. 2A–C MRI of case 2. A prior to the first operation. B Followingthe lesionectomy sparing the adjacent hippocampus. C After thetailored epilepsy surgery with removal of the adjacent epileptogenictissue

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larly if the lesion is not located in critical brain tissue.However, a few patients require intracranial EEG moni-toring for various reasons: (1) if clinical and electroen-cephalographic findings are noncongruent with the loca-tion of the lesion, the goal of an invasive study is to de-fine the seizure origin; (2) if the lesion is located in acritical brain region (e.g., speech area), intracranial EEGis used to localize the extent of epileptogenic tissue inorder to minimize the resection; and (3) if there is aquestion of dual pathology in extrahippocampal lesions,invasive monitoring can help decide whether resectivesurgery must include the mesial temporal structures. Inour second case, invasive monitoring was performed inorder to rule out dual pathology, and the hippocampuscould be spared.

Seizure elimination is a reasonable goal in surgery forCM-related epilepsy, with the extent of surrounding tis-sue resection dependent upon such factors as duration ofthe epilepsy and location of the lesion.

Acknowledgements Adrian M. Siegel was supported by theSchweizerischer Nationalfonds (Swiss National ResearchFoundation) and the Kommission zur Förderung des akademischenNachwuchses des Kantons Zürich.

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