Surgical treatment of symptomatic cerebral cavernous

Acta Neurochir DOI 10.1007/s00701-012-1411-4

CLINICAL ARTICLE

Surgical treatment of symptomatic cerebral cavernous malformations in eloquent brain regions Maria Wostrack & Ehab Shiban & Kathrin Harmening & Thomas Obermueller & Florian Ringel & Yu-Mi Ryang & Bernhard Meyer & Michael Stoffel

Received: 13 March 2012 / Accepted: 29 May 2012 # Springer-Verlag 2012

Abstract Background Despite the increased risk of hemorrhage and deteriorating neurological function of once-bled cerebral cavernous malformations (CM), the management of eloquently located CMs remains controversial. Methods All eloquently located CMs (n045) surgically treated between 03/2006 and 04/2011 in our department were consecutively evaluated. Eloquence was characterized according to Spetzler and Martin's definition. The following locations were approached: brainstem, n016; sensorimotor, n 08; visual pathway, n 07; cerebellum (deep nuclei and peduncles), n07; basal ganglia, n04, and language, n03. Follow-up data was available for 41 patients (91 %) with a median interval of 14 months. Outcomes were evaluated according to the Glasgow outcome and the modified Rankin scale. Results Immediately after surgery, 47 % (n021) had a new deficit. At follow-up, 80 % (n036) recovered to at least preoperative status or were better than before surgery, 9 % (n04) exhibited a slight, and 7 % (n03) had a moderate neurological impairment. Only two cases (4 %) with a new permanent severe deficit were observed, both related to M. Wostrack : E. Shiban : K. Harmening : T. Obermueller : F. Ringel : Y.-M. Ryang : B. Meyer : M. Stoffel Department of Neurosurgery, Technical University of Munich, Munich, Germany M. Stoffel Department of Neurosurgery, Helios hospital, Krefeld, Germany M. Wostrack (*) : M. Stoffel Department of Neurosurgery, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany e-mail: [email protected]

dorsal brainstem surgery. The outcome after the surgery of otherwise located brainstem CMs was as beneficial as that for non-brainstem CMs. Patients with initially poor neurological performance fared worse than oligosymptomatic patients. Conclusions Despite the high postoperative transient morbidity, the majority improved profoundly during follow-ups. Compared with natural history, surgical treatment should be considered for all eloquent symptomatic CMs. Dorsal brainstem location and poor preoperative neurological status are associated with an increased postoperative morbidity. Keywords Cavernous malformation . Brain cavernoma . Eloquent brain surgery . Brainstem surgery

Introduction Cavernous malformations (CM) are histologically benign vascular lesions consisting of irregular, thin-walled sinusoidal vascular channels without interposed brain tissue. CMs comprise 5–13 % of CNS vascular malformations, representing the second most common vascular lesions after venous angiomas [4, 50]. The incidence averages approximately 0.5 % based on larger MRI and autopsy series [31, 39, 42, 50]. CMs seldom produce large hematomas. More common are repetitive episodes of circumscribed micro-bleedings inside or outside the lesion that increase the CM size and hemosiderin fringe. Such repetitive micro-bleedings may lead to progressive neurological symptoms or seizures in up to 16.5 % of patients per year [50]. Although up to 39 % of CMs remain asymptomatic [54], clinical presentation strongly depends on their location within the brain. The risk of a new neurological deficit rises with the proximity to delicate regions, reaching up to 30 % of

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patients per year in the brain stem [13, 34, 38]. Complete surgical removal can permanently eliminate the risk of further growth or hemorrhage [49], representing the first-tier therapy for CM [24, 54]. However, surgery is challenging when performed within eloquent brain regions, defined as those that speak to readily identifiable neurological functions and, if injured, result in a disabling neurological deficit [44]. Due to this fragility, even a slight intraoperative injury, e.g., retraction or postoperative edema, can dramatically deteriorate the patient’s clinical presentation. Spetzler et al. [44] defined the following regions as eloquent: the sensorimotor, language, and visual cortex; the hypothalamus and thalamus; the internal capsule; the brain stem; the cerebellar peduncles; and the deep cerebellar nuclei. Surgery near these regions should be carefully weighed against the risk of the natural history. In prior publications of the late 1980s and early 1990s, surgery for eloquent CMs was frequently associated with substantial morbidity and even mortality [46, 52]. Today, the widespread use of MRIs, functional MRIs, and intraoperative neuromonitoring (IONM), including awake craniotomy and neuronavigation, render surgery within eloquent regions safer and therefore more frequent [30, 37, 40, 56]. Still a controversial question remains: Do the results of eloquent CM surgery using modern state-of-the-art techniques provide enough safety to recommend the surgical treatment to every affected patient or should periodic radiological and neurological control examinations be considered as more favorable? The aim of our study was to define the specific disease pattern of eloquent CMs and to evaluate clinical outcomes and prognoses after surgical treatments.

Patients’ characteristics and methods All eloquently located symptomatic cerebral CM treated surgically between March 2006 and April 2011 at our department were consecutively evaluated. The series included 45 patients (22 females and 23 males, with a median age of 50 years in a range of 20–81 years). Clinical performance at admission, immediately after surgery, at discharge, and during follow-ups was evaluated according to the Glasgow outcome scale (GOS) [18] and the modified Rankin scale (mRS) [45] (Tables 1 and 2). The mRS was assigned using a standardized structured interview [51], whereas the GOS was derived from the clinical documentation. Follow-up data was available for 41 patients (91 %) with a median interval of 14 months. As mentioned, eloquence was characterized according to Spetzler and Martin’s classification [44]. The following CM locations were treated: brainstem, n016; sensorimotor region, n08; visual pathway, n07; deep cerebellar nuclei and cerebellar peduncles, n07; basal ganglia/internal capsule,

Table 1 Glasgow outcome scale Grade

Description

5 4

Good recovery: able to return to work or school Moderate disability: able to live independently; unable to return to work or school Severe disability: able to follow commands/ unable to live independently

3 2

Vegetative state: unable to interact with environment; unresponsive

1

Dead

n04; and language cortex, n03. Detailed localization is summarized in Table 3. Figures 1, 2, 3, 4, 5 and 6 demonstrate several representative cases from the series. CM was defined as “symptomatic” if it induced a focal neurological deficit correlative to the CM location or new onset seizures independently of the radiographic changes, since neurological disorders are usually produced by intralesional or perilesional microhemorrhage not necessarily apparent on conventional MRIs [4, 7]. Three Tesla MRIs, including T1 with and without contrast, T2, and T2* sequences, were preformed pre- and postoperatively for all patients. The definite CM size could be determined in 41 patients, with a median diameter of 15 mm (range 3–33 mm). In the other four cases, the size was not possible to measure exactly, due to a concomitant intracerebral hematoma (ICH). The main indication for surgery was CM associated neurological deficits or seizures. In the majority of cases, surgery was performed in the subacute phase, approximately four weeks after the acute onset of symptoms [15]. Neuronavigation (BrainLab AG, Munich, Germany) was used in all cases, except cerebellar lesions. Intraoperative somatosensory (SSEP) and motor (MEP) evoked potential neuromonitoring was performed in the majority of cases (but not for CMs located in a visual Table 2 Modified Rankin scale Grade

Description

0 1

No symptoms at all No significant disability despite symptoms: able to carry out all usual duties and activities Slight disability: unable to carry out all previous activities but able to look after own affairs without assistance Moderate disability: requiring some help, but able to walk without assistance Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance Severe disability: bedridden, incontinent, and requiring constant nursing care and attention

2 3 4

5

Acta Neurochir Table 3 CM Location and presenting symptoms in the first examination/acute phase; CN 0 cranial nerve No.

Sex

Age

Location

Preoperative symptoms

1 2

w w

42 63

brainstem, mesencephalon/dorsal thalamus brainstem, pontomesencephalic

CN V and VII paresis, fine motor skills disorder diplopia, gait ataxia

3

w

47

brainstem, pontomesencephalic

4

w

27

brainstem, pontomesencephalic

diplopia, dysarthria, anisocoria, mild hemiparesis, hypesthesia unilateral ophthalmoplegia, hemiparesis

5

m

55

brainstem, tectum

diplopia

6 7

w w

53 32

brainstem, tectum brainstem, tectum

diplopia diplopia, hemidysesthesia

8

w

31

brainstem, lateral pons

hemiparesis and hemihypesthesia

9

w

36

brainstem, dorsal pons/fossa rhomboidea

hemihypesthesia, CN VI paresis

10 11

m w

38 68

brainstem, dorsal pons/cerebellar peduncle brainstem, dorsal pons/cerebellar peduncle

dysesthesia ataxia, dysarthria, vomiting, nystagmus

12

m

77

brainstem pons/pontomedullar junction

mild hemiparesis, hemihypesthesia, vertigo

13

m

68

brainstem, pontomedullar junction

dysesthesia, diplopia

14

w

47

15 16

m m

47 81

brainstem, 1) pontomedullar junction/fossa rhomboidea 2) medulla oblongata, obex brain stem, medulla oblongata brainstem, medulla oblongata, obex

17 18

w w

31 66

sensorimotor cortex, precentral region sensorimotor cortex, precentral region

diplopia, dysarthria, anisocoria, mild hemiparesis, hypesthesia dysesthesia, dysarthria, diplopia, ataxia hemiataxia, hemiparesis, dysphagia, incomplete caudal CN paresis fine motor skills disorder seizure

19 20 21

m m w

64 50 75

sensorimotor cortex, precentral region sensorimotor cortex, precentral region sensorimotor cortex, central gyrus

seizure high graded hemiparesis mild hemiparesis, hemihypesthesia

22 23

m w

58 63

sensorimotor cortex, central gyrus sensorimotor cortex, postcentral region

high graded hemiparesis hemiparesis

24

w

42

sensorimotor cortex, postcentral gyrus

hemidysesthesia

25 26 27

m m w

30 50 42

visual pathway, chiasma opticum visual pathway, occipital lobe visual pathway, occipital lobe

visual loss unilateral, hemianopsia contralateral quadrantanopia diffuse bilateral visual field defect, cephalgia

28 29 30 31 32 33 34 35 36 37 38 39 40 41

m w w m m m w w m m m m w m

34 20 34 61 77 49 48 45 53 70 74 22 53 56

visual pathway, occipital lobe, lateral ventricular trigone visual pathway, occipital lobe visual pathway, occipital lobe visual pathway, occipital lobe cerebellum, cerebellar peduncle cerebellum, cerebellar peduncle cerebellum, upper vermis near to velum medullar cerebellum, upper vermis cerebellum, middle vermis cerebellum, middle vermis cerebellum, paravermal region basal ganglia, dorsal thalamus basal ganglia, dorsal thalamus basal ganglia, insula

cephalgia, vomiting moderate vision impairment diffuse bilateral visual field defects, cephalgia diffuse bilateral visual field defects ataxia, dysmetria, nystagmus fine motor skills disorder, vertigo, dysarthria vertigo, cephalgia vomiting, vertigo, cephalgia vertigo, ataxia gait and extremity ataxia gait and extremity ataxia, vertigo hemidysesthesia mild hemiparesis and hemihypesthesia seizure

42

m

58

basal ganglia, dominant insula

43 44 45

w m m

37 62 25

language cortex, dominant dorsal operculum/ gyrus angularis language cortex, dominant frontolateral, periopercular region language cortex, dominant frontolateral, periopercular region

hemidysesthesia, incomplete motor aphasia, cephalgia seizure seizure seizure

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Fig. 1 CM in the right central region. a, b and c demonstrate preoperative axial T2*, and axial and sagittal T1 with contrast, respectively. Postoperative T2 in d. The patient presented with a hemiparesis.

Postoperatively, no new deficit occurred, the hemiparesis remained unchanged without any decrease of muscle strength grade

pathway or in the cerebellum). Facial nerve electromyography (EMG) was used in two cases of brainstem CMs located in the pontomedullary junction. In one patient with a left paraopercular CM, awake surgery with language mapping was performed. The operative approach for brainstem CM was chosen according to the site, where the CM reached the surface (IVth ventricle or CSF cistern) [1, 9, 41]. Cerebellar CMs were removed via a median suboccipital approach. For pericentral or occipital CMs, tailored craniotomies according

to navigation data were performed. CMs in direct proximity to the basal ganglia were resected via a temporal or subtemporal craniotomy with a subsequent transsylvian or transventricular approach, depending on their exact location. Chiasma CM was reached by a pterional craniotomy (Fig. 7). An adjacent developmental venous angioma (DVA) was revealed in 12 patients (33 %) and was preserved in all cases [32, 36] (Fig. 8).

Fig. 2 Diencephalic posterior thalamic CM. a, b, c preoperative axial T2, sagittal and coronar T1 with gadolinium, respectively; d, e, f postoperative axial and sagittal T2. The lesion was removed via a left

frontal paramedian trepanation with a transcortical approach to the left lateral ventricle and subsequent transchoroidal approach to the third ventricle

Acta Neurochir Fig. 3 Cerebellar CM in the superior vermis proximal to velum medullar superius and the roof of the IV ventricle. a sagittal and b axial T2 projection. The preoperative vertigo was significantly worsened immediately after the surgery accompanied by vomiting and ataxia. In the follow-up, the patient was equal to the preoperative status

Multiple CMs (>1 cerebral CM) were present in seven patients. One patient was operated on twice for different CMs with a time delay of >5 months, representing two respective cases in this study. In the second surgery for this patient, two brainstem CMs were resected during the same intervention, which was evaluated as one case (Fig. 9). The choice of the approached CM was guided by the correlation between the lesion site and the clinical symptoms.

pattern or already had had similar prior clinical events in their medical history. The vast majority (84 %) presented with a focal neurological deficit dependent on CM localization. Six patients (13 %) presented with a new onset of epilepsy. Only one patient with a CM located near the visual cortex presented with unspecific symptoms (vomiting, headache) without focal neurological deficits or seizures. The symptoms are presented in detail in Table 3. After the acute phase of symptoms, only six patients could recover nearly to the pre-ictus status before surgery.

Results Surgical results Clinical presentation Seven patients (16 %) presented with intracerebral hematoma. The other 38 (84 %) exhibited a classical radiological pattern of inhomogeneous popcorn-like lesions on T2- or T2*-sequences, suggesting micro-bleeding. Thirty patients (67 %) with unremarkable neurological status before, presented an acute onset of symptoms. Fourteen patients (31 %) had a chronically progressive disease

Fig. 4 CM within visual pathway. Preoperative sagittal T1 with gadolinium and axial T2* in a and b, respectively. Postoperative sagittal T1 with contrast in c. The initial preoperative incomplete hemianopsia

All CMs were resected completely. There was no perioperative mortality. Postoperative complications were meningitis in three cases, deep wound infections in two cases, and severe pneumonia with pleural emphysema in one case. Immediately after surgery, 24 patients (53 %) exhibited no new neurological impairment. To categorize the significance of the new neurological deficit, we differentiated the postoperative change of the deficit-caused disability according to the

was transiently accentuated after the surgery; in follow-up, the patient showed no visual field cut

Acta Neurochir Fig. 5 Basal ganglia CM adjacent to the dorsal thalamus. Axial T2* and T1 in a and b, respectively. Preoperatively, the patient exhibited an acute onset hemidysesthesia, partly improved until surgery. Immediately after the surgery the hemidysesthesia was accentuated; in the follow-up examination the patient had no neurological symptoms

GOS and the mRS compared with the preoperative status. Thereby, we created the following classifications: & & &

Slight impairment: New deficit with no impairment of GOS and/or mRS, or impairment of mRS from 0 to 1 since this does not cause any relevant disability. Moderate impairment: Impairment of mRS and/or GOS of 1 point (except the mRS impairment within the range level 0-1). Severe impairment: Any impairment of GOS and/or mRS for ≥2 points.

According to this determination, immediately after surgery, six patients (13 %) were slightly impaired, seven (16 %) had a new moderate deficit, and eight patients (18 %) exhibited a severe impairment. In follow-ups or already at discharge, most of them recovered. The majority (80 %; n036) showed that at least their preoperative status was better. Permanently impaired patients mostly exhibited a mild new deficit (9 %, n04) according to the differentiation Fig. 6 CM rostral to the left frontal operculum. Axial T2 in a and speech fMRT in b. Patient presented with grand-mal seizures. Surgery was performed as awake craniotomy. No new deficit occurred postoperatively. The patient is now seizurefree after 4 months of follow-up

above. A new severe deficit was observed in two patients (4 %). Final examinations showed with 44 % (n020) an amazingly large group of postoperatively improved patients, and 38 % of the patients (n017) had functional improvement with an increase of their disability score. Postoperative outcomes are summarized in Table 4 and visualized as a bar graph in Fig. 10. Six patients in our group initially presented with epilepsy. Immediately after surgery, three further patients, who were operated on for CMs within their brainstems, sensorimotor region, and basal ganglia, respectively, developed new repeated seizures. In one patient, with preoperatively known epilepsy, seizures were observed more frequently than before surgery. Consequently, nine patients required antiepileptic medication at discharge. In follow-ups, eight of nine patients were seizure-free without anticonvulsant medication, including all patients with new postoperative epilepsy. Figure 11 visualizes epilepsyrelated outcomes.

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Fig. 7 a Preoperative coronar T2 revealing a CM within the optic chiasma. b postoperative coronar T2 revealing an additional asymptomatic CM in the left temporal lobe. This patient with familial CM form revealed overall 10 cerebral CMs and one intramedullary CM in

the cervical spinal cord. The patient presented with bilaterally severely impaired vision and visual field cuts, which remained unchanged after surgery

Discussion

probability of symptomatic re-bleeding and incomplete recovery, once-bled eloquent CMs will most probably lead to a progressive neurological deficit in the long run if treated conservatively, rendering the “wait and see” strategy as not maintainable. Hence, particularly eloquently located CMs should be treated, once symptomatic. Considerable risk for a new postoperative neurological impairment frequently confuses the decision for surgery. The postoperative transient neurological morbidity independent of its extent was, in fact, high with 47 % in our patients being similar to those in previous publications [1, 8, 41]. The benefit of the surgery becomes clear during follow-ups with the vast majority of patients (80 %) showing at least the preoperative baseline status, whereas 44 % of all patients had improved and 38 % improved with an increase of the functional grade. The new permanent neurological impairment observed in 20 % was mild in the majority of cases (9 %) without or with insignificant disability amplification. The most favorable results were achieved after CM surgery in non-brainstem eloquent location: 90 % of this group (n026) exhibited no new deficit, and half of them (n013) improved compared with their preoperative neurological status. A new slight deficit was observed in two cases (7 %), and only one patient (3 %) was moderately impaired. No severe impairment was observed in this group. Surgery for brainstem CM was associated with a significantly higher rate of postoperative impairment compared with non-brainstem surgery in our series: Overall, in six of 16 brainstem cases (37.5 %) versus three of 29 nonbrainstem cases (10.3 %), moderate and severe impairment in four of 16 brainstem cases (25 %) versus one of 29 nonbrainstem cases (3.4 %). Two cases in the whole series (4 %), who exhibited a severe impairment in their last postoperative examination, were both associated with brainstem CM surgery. Regarding this difference in outcome, brainstem CM seems not to be comparable with CMs in other eloquent regions at first glance.

Once bled, CMs can present with a wide range of symptoms, varying from mild, non-specific symptoms, such as headaches, to severe neurological deficit or even death, whereas the risk for manifest neurological deterioration rises with the proximity to functionally important structures [14, 16, 19, 41]. Our data supports this evidence, showing the majority of cases (84 %) presented with a new focal neurological deficit and 67 % with acute onset of symptoms. Furthermore, the risk for a re-bleeding from a symptomatic CM rises considerably to 22.9 % per patient per year [2], reaching the maximal risk with 60 % per patient per year in brainstem CMs [48] (compared to a relatively low annual hemorrhage risk for non-symptomatic CMs ranging in most publications between 0.39 % and 4.2 % [2, 7, 28, 38, 47]). Moreover, a chance for complete spontaneous recovery after the acute phase seems to be low, observed in only six patients in our series. Given the high

Fig. 8 Coronar T1 with gadolinium revealing a precentral subcortical CM with an adjacent DVA

Acta Neurochir Fig. 9 Patient presented with 11 cerebral cavernomas a sagittal T1 with contrast revealing multiple brainstem CMs. b and c axial and coronar T2 demonstrating multiple supra- and infratentorial CMs

The following explanation of this limitation within the common classification of eloquence can be assumed: In 1986, when Martin and Spetzler proposed their grading system, a probability for a new postoperative deficit was similar across all of the described eloquent regions, since numerous surgical device technologies were not available or established yet. Today, the widespread use of MRIs, functional MRIs, IONM, neuronavigation, brain mapping, and awake craniotomy could minimize the postoperative morbidity for the most eloquent locations. However, monitoring of brainstem surgery remains deficient, since extended modalities of IONM, such as corticobulbar tract mapping or muscle MEP of motor cranial nerves, are not standardized Fig. 10 Postoperative functional outcome

yet, and monitoring of the swallowing and coughing reflexes remains impossible [40]. However, when specifying the CM location according to the axial arrangement of the lesions within the brainstem, a significant difference can be observed between the outcome of patients with strictly dorsally located brainstem CMs (Table 4, cases Nr. 2, 5, 6, 9, 12, 14, 16) and other brainstem CMs (Fig. 12): Six of seven patients with dorsal brainstem CM showed permanent postoperative worsening compared with only one patient with a slight neurological impairment in the non-dorsal brainstem CM group. The crucial difference can be explained by a higher concentration of critical structures located proximal to the dorsal brainstem surface,

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such as the corpora quadrigemina, the reticular formation, cranial nerves nuclei at the floor of the IV ventricle, the gracile, and the cuneate fasciculi. The risk for retraction associated damage of these structures is high even if the lesion is located superficially. In contrast, during the lateral approaches to the brainstem, eloquent nuclei and tracts are located deeper and it is easier to keep them intact during the removal. Moreover, median suboccipital supra- or infratentorial approaches usually used for surgery of dorsally located brainstem lesions are associated with a higher intraoperative manipulation of adjacent tissue compared with retrosigmoid, pterional, or subtemporal approaches. Given these facts, non-dorsal brainstem CM surgery appears to be as safe as non-brainstem surgery. The decision for surgery of dorsally located brainstem CM should be made very carefully.

Important to note is the final absolute number of severely disabled patients (GOS ≤3 or/and mRS ≥4) with 16 % (n07) independent of the difference between pre- and postoperative status. In most cases (71 %, n05), these patients were already disabled due to the preoperative CM bleeding to a significant extent. A new slight or moderate surgery-related impairment led to a poor outcome in these cases due to a consequent decrease of an already low disability score, whereas unchanged or even slightly improved status reflected no manifest benefit (Table 4). This observation supports the previously reported correlation of postoperative substantial morbidity with poor preoperative performance [8, 10]. Clearly favorable postoperative results are mostly reached in oligosymptomatic patients. Given this, surgical treatment for eloquent CMs should be considered as early as possible, i.e., immediately after the first symptomatic event. Due to a very low risk for a new significant postoperative impairment, surgery for asymptomatic non-brainstem CMs is arguable to prevent bleeding associated neurological deficit. In several non-controlled studies, radiosurgery is reported to be a sufficient alternative to surgery [21]. In our opinion, radiosurgery does not provide enough benefit to be indicated. First, radiosurgery does not implicate a curative effect due to a persistent postinterventional risk for recurrent bleeding [20, 23, 27, 33, 48, 55]. The rebleeding rate after radiotherapy for previously symptomatic patients is reported in a large series with 113 patients to be up to 15 % for the first two years and still present with 2.4 % thereafter with a median follow-up time of four years [55]. Furthermore, this partial risk reduction achieved by radiosurgery is associated with significant radiation induced morbidity [20, 22, 23, 27], particularly in such delicate areas like brainstem or

Fig. 12 Clinical outcome depending on different location within the brainstem: a preoperative axial T2 revealing a dorsally located CM. Patient presented with a mild diplopia, after the surgery of the dorsal brainstem CM he is permanently significantly disabled exhibiting severe gait ataxia and dysarthria. b preoperative axial T2 revealing a

ventrolaterally located CM. Patient presented with incomplete ophthalmoplegia and incomplete hemiparesis, 6 months after the resection of the ventrolateral pontomesencephalic CM the patient was improved exhibiting only a residual latent arm paresis without any significant functional disability

Fig. 11 Perioperative course of CM associated epilepsy

Acta Neurochir Table 4 Final postoperative outcome. Preoperative status was evaluated immediately before surgery (usually after the acute interval). Location of brainstem CM was additionally specified according to the axial arrangement within the brainstem. The cases highlighted in grey have less than 3 months of follow-up data. F/u follow-up

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eloquent cortex. In addition, postoperative radiosurgery for incompletely removed CMs is contraindicated, since radiation associated morbidity seems to be higher for patients who had surgery [23]. Remarkably, the radiosurgery induced hemorrhage risk reduction is not significant until two years after treatment [27, 29]. Regarding the natural history of cerebral CMs, a spontaneous decline in the hazard risk of CM re-hemorrhage approximately two years after a previous hemorrhage, also known as “temporal clustering”, should be noted [3, 48]. Accordingly, the reported results after radiosurgery of CMs may—at least partly—reflect this phenomenon, rendering the treatment effect less significant. Lastly, in several cases radiosurgery was described to induce de-novo formation of cerebral CMs [17, 35, 43, 53]. Epilepsy is described as the most common first presenting symptom of CM, exhibited by up to 80 % patients with cerebral CMs [5, 39, 50, 54]. In our series, only six patients presented with a new onset of seizure, comprising 13 % of the whole group. All of these CMs were located supratentorially: five neocortical and one mesiotemporal archicortical. This low expression of epileptogenicity in our patient group demonstrates the common dependency of CM-associated seizure onset on its supratentorial cortical location [26]. However, focusing only on supratentorial CMs in our treated patients (n022), the rate with 27 % still remains lower than usually reported. Accordingly, CM associated epilepsy seems to be common first of all for non-eloquently localized supratentorial CMs. Similar to former studies [5, 11], our data verifies a favorable prognosis for epilepsy recurrence after CM surgery, since five of initially six affected patients (83 %) in our group were cured. Unfortunately, the effect of antiepileptic drugs could not be assessed in these cases, because they were operated upon after the first few seizures. According to recent literature, CM induced seizures remain medically refractory in up to 58 % of cases [5]. A risk for surgery associated new onset seizure seems to be low, transiently observed only in three patients (7 %) in our group, falling even below the general risk for new onset seizure after craniotomy ranging in the literature between 12 % and 17 % [6, 12, 25].

Conclusions Surgery for eloquent CMs provides a clear benefit compared to natural history. According to the increased re-hemorrhage risk, surgery should be performed in all symptomatic eloquent CMs, as it appears safe under modern monitoring conditions. For incidental eloquent CM, surgery is not advisable due to a still significant risk of postoperative deterioration. In any case, patients with eloquent CMs are obliged to be informed about a high probability of up to 47 % for transient

neurological deterioration. An unfavorable neurological postoperative outcome is conceivable for already preoperatively significantly disabled patients and for patients with dorsally located brainstem CM, thus the decision for surgery in such cases should be made very carefully. Patients with eloquent cerebral CMs presenting with seizures can be cured with surgical treatment.

Conflicts of interest None.

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