Insular Cavernous Malformation

Insular Cavernous Malformation

Surgical management of cavernous malformation (CM) of the insula consists of total resection of the lesion and the surrounding gliosis to avoid or reduce seizures. When located in the dominant hemisphere, an awake craniotomy with intraoperative mapping reduces the risk of functional damage. The insula is covered by the operculum and has a relationship with the middle cerebral artery and its branches that run along its lateral cortical surface. Therefore high expertise is required to manage the exposure of the insula and its complex anatomy.

Insular Cavernous Malformation Classification.

A video of Burkhardt et al. demonstrated the microsurgical resection of a de novo CM adjacent to a previously treated high-grade AVM and clipping of a middle cerebral artery (MCA) aneurysm. A 70-yr-old male with history of radiosurgery for AVM presented with aphasia and confusion. Preoperative angiography showed complete occlusion of the AVM. MRI showed multiple cystic lesions suspicious for radiation-induced necrosis and CM. IRB approval and patient consent was obtained. A pterional craniotomy was performed with transsylvian exposure of the insula. The radiated feeding arteries were followed to the occluded AVM nidus. A CM was noted deep to this candelabra of the MCA vessels, which were mobilized to access and resect the CM. A small incision was made in this insular cortex underneath the malformation circumferentially freeing it of adhesions. The sclerotic AVM nidus was circumferentially dissected and removed en bloc. Thorough exploration of the resection cavity revealed no residual CM or AVM nidus. Attention was then turned to the M2-MCA bifurcation aneurysm, which was occluded with a straight clip. Postoperative imaging confirmed complete CM resection. The patient recovered from his aphasia. This case demonstrates the management of a radiation-induced de novo CM following treatment of a high-grade AVM. Radiographic follow-up for radiosurgically treated AVM is needed to rule out long-term complications. Bleeding from a de novo CM mimics bleeding from residual AVM nidus, requiring careful angiographic evaluation 1).

A video of Norat et al. illustrated the use of a trans-Sylvian, trans-sulcal approach to resect a deep insular/basal ganglia cavernous malformation in a young patient. The use of the neuronavigation is essential for success in these types of operation as this tool limits the surgeon’s footprint in eloquent brain. Unlike superficial lesions where the removal of hemosiderin stained brain is possible and often safe, resection of deep-seated lesions requires the surgeon to distinguish between hemosiderin-stained brain and residual cavernous malformation. This task is not simple, and residual cavernous malformation is the most common reason for re-bleed in patients who have undergone surgery. Resection of symptomatic cavernous malformations in deep locations can be performed safely, but outcomes are heavily influenced by proper patient selection and surgeon experience. In patients with multiple cerebral cavernous malformations, such as the one in this case, genetic testing should be performed 2).

A video of Vigo et al. demonstrated the surgical management of a large left insular CM. A 29-year-old female with multiple CM and 7 years of partial seizures and recent onset of short memory loss. Neuroimaging showed a large left insular and planum polare CM with important mass effect and hemorrhage signs. The patient consented to surgery, and an awake pretemporal craniotomy was carried out with continuous motor evoked potential monitoring. No language function was localized in the superior temporal gyrus; therefore corticectomy of the middle portion was performed to expand the operative corridor. The vessel manipulation during wide opening of the sylvian fissure increased the risk of postoperative vasospasm and blood drain into the surgical field. The CM was exposed and completely removed without functional damage. The patient recovered from surgery without complications, and no seizures occurred at 2 months’ follow-up. Postoperative imaging showed complete removal of the CM 3).

A study included patients affected by iCMs and referred to the Senior Author (FA). All cases were divided in 2 groups, according to a mainly pial growth pattern (exophytic group) or a subcortical one (endophytic group). Endophytic iCM was further subdivided in 3 subgroups, based on the insular gyri involved. According to this classification, each patient underwent a specific additional neuroimaging investigation and surgical evaluation.

Results: A total of 24 patients were included. In the surgical group, trans-sylvian (TS) approach was used in 6 patients with exophytic or Zone I endophytic iCMs. The transcortical (TC) approach with awake monitoring was used in 6 cases of Zone II endophytic vascular lesions. Both TS and trans-intraparietal sulcal (TIS) approach were used for 3 cases of Zone III endophytic iCM. At follow-up, 3 patients were fully recovered from a transient speech impairment while a permanent morbidity was observed in one case.

Conclusions: ICMs represent a single entity with peculiar clinical and surgical aspects. The proposed iCM classification focuses on anatomical and functional concerns, aiming to suggest the best pre-operative work-up and the surgical evaluation 4).

A 25-yr-old female presented with an acute-onset right homonymous hemianopsia. Neuroimaging revealed a large left insular CM, adjacent to the posterior limb of IC. After obtaining IRB approval and patient consent, a left pterional craniotomy with a wide distal Sylvian fissure split was completed. Using neuronavigation, an insular entry point was chosen for corticectomy. The CM was opened with subsequent hematoma evacuation and intracapsular resection technique. Inspection of the cavity revealed remnants anteromedially near the IC, which were removed meticulously, mobilizing the CM away from the IC. Postoperative MRI demonstrated gross total resection of the CM. The patient was discharged home on postoperative day 5 with persistent homonymous hemianopia.This case describes the use of a transsylvian-transinsular approach to access deep lesions with the shortest surgical distance and minimal cortical transgression. A wide Sylvian fissure split exposes the M2 MCA and accesses a safe insular zone, keeping the most eloquent structures deep to the lesion in the surgical corridor. This approach can safely expose vascular pathologies in the insular region without the risk of injury to overlying eloquent frontal and temporal lobes, even in the dominant hemisphere 5).


Burkhardt JK, Gandhi S, Tabani H, Benet A, Lawton MT. Left Transsylvian-Transinsular Approach for Radiation-Induced Cavernous Malformation: 3-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2019 Aug 1;17(2):E62-E63. doi: 10.1093/ons/opy357. PubMed PMID: 30418603.

Norat P, Yagmurlu K, Park MS, Kalani MYS. Keyhole, Trans-Sylvian, Trans-Sulcal Resection of an Insular Cerebral Cavernous Malformation: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2019 Jul 1;17(1):E18. doi: 10.1093/ons/opy326. PubMed PMID: 30496497.

Vigo V, Zanabria Ortiz R, Paganelli SL, da Costa MDS, Campos Filho JM, Chaddad-Neto F. Awake Craniotomy for Removal of Left Insular Cavernous Malformation. World Neurosurg. 2019 Feb;122:209. doi: 10.1016/j.wneu.2018.10.220. Epub 2018 Nov 9. PubMed PMID: 30415050.

Fioravanti A, Elia A, Morandini A, Valtulina C, Bertuccio A. Anatomo-functional evaluation for management and surgical treatment of insular cavernous malformation: a case series. Acta Neurochir (Wien). 2022 Jan 23. doi: 10.1007/s00701-021-05089-3. Epub ahead of print. PMID: 35066681.

Mascitelli J, Gandhi S, Wright E, Lawton MT. Transsylvian-Transinsular Approach for an Insular Cavernous Malformation Resection: 3-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2019 Feb 1;16(2):50. doi: 10.1093/ons/opy155. PubMed PMID: 29905877.

Insular glioma surgery

Shawn Hervey-Jumper and Berger from the UCSF Medical Center reviewed the literature for published reports focused on insular region anatomyneurophysiology, surgical approaches, and outcomes for adults with who grade II-IV gliomas.

While originally considered to pose too great a riskinsular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral lenticulostriate artery are critical steps to preventing internal capsulestroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.

The insula’s proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisylvian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area 1).

Advances in microsurgical anatomy and brain mapping techniques have allowed an increase in the extent of resection with acceptable morbidity rates. Transsylvian and transcortical approaches constitute the main surgical corridors, the latter providing considerable advantages and a high degree of reliability. Nevertheless, both surgical corridors yield remarkable difficulties in reaching the most posterior insular region.

see Insular tumor surgery.

Small deep infarcts constitute a well-known risk of motor and speech deficit in insulo-opercular glioma surgery. However, the risk of cognitive deterioration in relation to stroke occurrence in so-called silent areas is poorly known.

In a paper, Loit et al. propose to build a distribution map of small deep infarcts in glioma surgery, and to analyze patients’ cognitive outcome in relation to stroke occurrence.

They retrospectively studied a consecutive series of patients operated on for a diffuse glioma between June 2011and June 2017. Patients with lower-grade glioma were cognitively assessed, both before and 4 months after surgery. Areas of decreased apparent diffusion coefficient (ADC) on the immediate postoperative MRI were segmented. All images were registered in the MNI reference by ANTS algorithm, allowing to build a distribution map of the strokes. Stroke occurrence was correlated with the postoperative changes in semantic fluency score in the lower-grade glioma cohort.

One hundred fifteen patients were included. Areas of reduced ADC were observed in 27 out of 54 (50%) patients with a lower-grade glioma, and 25 out of 61 (41%) patients with a glioblastoma. Median volume was 1.6 cc. The distribution map revealed five clusters of deep strokes, corresponding respectively to callosal, prefrontal, insulo-opercular, parietal, and temporal tumor locations. No motor nor speech long-term deficits were caused by these strokes. Cognitive evaluations at 4 months showed that the presence of small infarcts correlated with a slight decrease of semantic fluency scores.

Deep small infarcts are commonly found after glioma surgery, but their actual impact in terms of patients’ quality of life remains to be demonstrated. Further studies are needed to better evaluate the cognitive consequences-if any-for each of the described hotspots and to identify risk factors other than the surgery-induced damage of microvessels 2).


Awake Brain Mapping in Dominant Side Insular Glioma Surgery: 2-Dimensional Operative Video 3).



Hervey-Jumper SL, Berger MS. Insular glioma surgery: an evolution of thought and practice. J Neurosurg. 2019 Jan 1;130(1):9-16. doi: 10.3171/2018.10.JNS181519. Review. PubMed PMID: 30611160.

Loit MP, Rheault F, Gayat E, Poisson I, Froelich S, Zhi N, Velut S, Mandonnet E. Hotspots of small strokes in glioma surgery: an overlooked risk? Acta Neurochir (Wien). 2018 Nov 10. doi: 10.1007/s00701-018-3717-3. [Epub ahead of print] PubMed PMID: 30415385.

Hameed NUF, Zhu Y, Qiu T, Wu J. Awake Brain Mapping in Dominant Side Insular Glioma Surgery: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2018 Feb 16. doi: 10.1093/ons/opx299. [Epub ahead of print] PubMed PMID: 29471530

Update: Insular glioma

Glioma of the insular lobe has a unique origin and biological behavior.
They are quite frequent, however treatment of patients with this pathology still remains a challenging and controversial issue of neurosurgery.


Berger Sanai classification.
Magnetic resonance imaging (MRI) with T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images best delineates the extent of tumour infiltration, which can be limited to the insular lobe (Yasargil type 3a) or reach the perisylvian opercula (type 3b) and other paralimbic areas, namely the orbitofrontal and temporopolar regions (type 5), with or without involvement of core limbic structures 1).
Although the classification of insular glioma has been established based on the anatomical location in order to facilitate personalized surgical resection, the diagnosis based on anatomical and functional characteristics becomes more complex when insular tumors extend into either the frontobasal brain region and/or the temporal lobe, as part of the limbic system.
The study findings of Wang et al., suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas 2).


Due to its challenging technical access 3) 4) 5) 6) 7) 8) 9) 10) 11) and until the publication of Yaşargil et al. 12) , the insula has been considered surgically inaccessible for a long time. Thanks to a better understanding of the insular functional anatomy, several experiences of insular surgery have been reported in the last decades 13) 14) 15) 16) 17) 18) 19) 20).
The surgical treatment should aim to achieve the total (or more than total) resection while avoiding neurological deficits. To achieve these goals, a combination of functional neuroimaging, intraoperative neurophysiology and awake craniotomies have been introduced into the clinical practice of neurosurgical centers dealing with those lesions. Nevertheless, these instruments are insufficient without a deep understanding of regional functional and microvascular anatomy.
The question of potential vascular injuries during resection of insular gliomas is well known, in particular with reference to the potential damage to the lenticulostriate arteries.
Since the first report by Yasargil, few authors have dealt with the surgical treatment of tumours infiltrating the insula
A number of authors have emphasized the importance of functional mapping because of the eloquent nature of both insular and periinsular structures.
The use of sensory and/or motor evoked potentials or ESM provide additional intraoperative landmarks by which to safely resect insular masses. Dominant hemisphere cortical language localization is advisable although language interference from direct stimulation of the insular cortex has seldom been reported.


Prognosis of insular tumor resection is still controversial. Further analysis of subgroup characteristics of insular grade II gliomas based on clinical and molecular analysis is required to reliably determine patients’ survival rates.


M1 segment of the middle cerebral artery, M2 segment of the middle cerebral artery, lenticulostriate arteries, basal ganglia, and internal capsule involvement, causes a high rate of postoperative complications in these patients.


While the benefits of an extensive initial resection of a insular glioma have been widely demonstrated, the best management of residual tumor still represents an open question.
Only 3 investigations analyzed the role of second surgery in case of tumor recurrence (TR). 21) 22) 23).
For the first time Schmidt et al. provided clinical evidence of the safety of a second surgery in 40 patients.
Martino and coworkers analyzed the clinical outcomes of 19 patients with recurrent LGGs in eloquent areas, strengthening the concept of possible functional reshaping occurrence after the first surgical procedure.
In line with these findings, Ius et al., showed that a second surgery is a safe and effective procedure, even for recurrent insular low grade gliomas..
Another possible reason for the positive outcome after a second surgery may be the smaller tumor volume at relapse.
The investigation of Ius et al., also highlights that seizure recurrence in patients who were seizure-free after the first surgery is associated with tumor progression.

From a strictly surgical point of view, there are some technical key points to take into consideration at second surgery. At recurrence, there is no intracranial hypertension. Tumor recurrence volume is smaller than the volume at first surgery and the cavity left by the previous operation allows a larger surgical field. The recurrent mass of tumor tissue mainly regrows from the walls of the previous resection into the cavity.
Ius et al., have noticed, also, a better definition between the healthy parenchyma and the tumor tissue, which is softer and, consequently, easier to remove. Moreover, at second surgery, the risk of damaging the vascular structures is much lower, because dissection of the middle cerebral artery (MCA) and its branches has already been performed during the first surgical procedure.
The only difficulty of second surgery is represented by the adhesions. They may cause pain during the opening; moreover, adhesions between dura mater and cortex, on the dominant side, may represent a risk of damage to the cortical language areas. In conclusion, the newly infiltrated deep tumoral tissue is not resected if it has been shown to still be functional based on brain mapping results.

The study of Ius et al., has potential limitations. First, it is a retrospective study; thus it is limited in nature. Patients with recurrence insular LGGs that are suitable for second surgery are per se highly selected. Thus, the number of our samples is limited, but, if we consider the papers, mentioning insular second surgery, the overall number of patients is 32; thus the study population (23 patients) is not considerably small and it is statistically sufficient to draw some preliminary considerations, which need to be confirmed by enlarging the case study. Moreover, insular surgery is rare at first diagnosis and even rarer at second surgery, so it is not easy to find large population in literature. In any case, it is unlikely that a prospective, randomized study will be designed to address these issues; thus, they believe retrospective, matched studies or prospective observational trials may be a more practical solution, as previously described.
The findings should be validated in a wider series, using multi-institutional cohort to create a potential model able to stratify the risk of TR after the first surgery. In this way, it would be possible to anticipate adjuvant postoperative treatments, also in patients with a diagnosis of pure LGG.
The timing of second surgery has not been well defined yet. Anyway, as previously remarked by Martino et al, it is better to “overindicate” an early second surgery than performing a late surgery when the tumor has already transformed into high-grade gliomas, especially in consideration of the low morbidity profile associated with reoperation 24).

Case series


A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved theputamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil’s classification, was examined using multivariate analyses.
Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil’s classification.
The study findings of Wang et al., suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas 25).

From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0T iMRI integrated Neurosurgical Suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping (ESM) was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. DTI (diffusion tensor imaging) tractography-based navigation, continuous motor evoked potential (MEP) monitoring and subcortical ESM were applied to localize and monitor the motor pathway in all cases. iMRI was employed to assess the extent of resection (EOR). The results of intraoperative imaging, IONM and the surgical consequences were analyzed.
Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median EOR was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P=0.018) in low-grade gliomas (LGGs). The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P=0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively.
The combination of iMRI, awake craniotomy, multi-modal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma 26)


A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations.
At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that tumor recurrence (TR) is influenced by the following: extent of resection (EOR) (P < 0.002), ΔVT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001).
In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery 27).

In a retrospective study 20 purely insular grade II gliomas patients and 22 paralimbic grade II gliomas that involved frontal and/or temporal lobes were compared with regard to epidemiological and clinical characteristics. The molecular profiles including Isocitrate dehydrogenase 1 (IDH1), telomerase reverse transcriptase (TERT) promoter, and P53 mutations, 1p19q co-deletion were analyzed, and microRNA profiles were assessed by microarray and bioinformatics analysis. Purely insular grade II gliomas displayed a high frequency of IDH1 mutations with favorable outcome. IDH1 mutated paralimbic glioma shared many parameters with the purely insular glioma in respect to growth patterns, survival, and microRNA profile, but differed significantly from the IDH1 wild type paralimbic gliomas. The findings suggest that IDH1 mutations can define subpopulations of insular gliomas with distinct disease entities regardless of tumor extension patterns. These findings could be useful to develop a customized treatment strategy for insular glioma patients 28).

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