Mohammad Samadian1,2, Seyed Farzad Maroufi2,3, Mehrdad Hosseinzadeh Bakhtevari4, Hamid Borghei-Razavi5
  1. Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran,
  2. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,
  3. Faculty of Medicine, Tehran University of Medical Sciences, Valiasr, Tehran, Iran,
  4. Department of Neurosurgery, Day General Hospital, Valiasr, Tehran, Iran,
  5. Department of Neurosurgery, Neurological Institute, Cleveland Clinic-Taussig Cancer Center, Cleveland, Ohio, United States.

Correspondence Address:
Mehrdad Hosseinzadeh Bakhtevari, Department of Neurosurgery, Day General Hospital, Valiasr, Tehran, Iran.


Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Mohammad Samadian1,2, Seyed Farzad Maroufi2,3, Mehrdad Hosseinzadeh Bakhtevari4, Hamid Borghei-Razavi5. An isolated cavernous malformation of the sixth cranial nerve: A case report and review of literature. 16-Nov-2021;12:563

How to cite this URL: Mohammad Samadian1,2, Seyed Farzad Maroufi2,3, Mehrdad Hosseinzadeh Bakhtevari4, Hamid Borghei-Razavi5. An isolated cavernous malformation of the sixth cranial nerve: A case report and review of literature. 16-Nov-2021;12:563. Available from:

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Background: Isolated cavernous malformation (CM) of the abducens nerve has not been reported in the literature. Herein, the authors address the clinical importance of these lesions and review the reported cases of CM from 2014 to 2020.

Case Description: A 21-year-old man presented with binocular diplopia and headache from 2 months before his admission. The neurological examination revealed right-sided abducens nerve palsy. The brain MRI revealed an extra-axial pontomedullary lesion suggestive of a CM. The lesion was surgically removed. During the operation, the abducens nerve was resected considering the lesion could not be separated from the nerve and an anastomosis was performed using an interposition nerve graft and fibrin glue. Pathological examination of the resected lesion revealed that it was originated from within the nerve. The patient’s condition improved in postoperative follow-ups.

Conclusion: Surgical resection of the cranial nerves CMs is appropriate when progressive neurological deficits are present. If the lesion is originated from within the nerve, we suggest resection of the involved nerve and performing anastomosis. Novel MRI sequences might help surgeons to be prepared for such cases and fibrin glue can serve as an appropriate tool to perform anastomosis when end-to-end sutures are impossible to perform.

Keywords: Abducens nerve, Cavernous hemangioma, Cranial nerves, Surgical resection


Cavernous malformations (CMs) are occult vascular lesions, defined as hyalinized capillary clusters, without an intervening muscle or neural tissue. These lesions account for 5–15% of all central nervous system vascular lesions[ 18 , 21 , 28 , 33 , 38 , 43 ] and may cause recurrent hemorrhage, with an annual incidence of 0.6–11% per patient-year.[ 3 , 24 , 26 , 35 , 38 , 41 , 43 , 57 ] It has been shown that genetic factors play a role in the occurrence of CMs, as nearly half of them are familial.[ 42 ] They are also equally common in males and females, but tend to occur earlier in men.[ 43 , 56 ]

The supratentorial region is the most common location for CMs followed by the posterior fossa in the pons and the cerebellum.[ 16 , 22 , 38 , 43 , 57 ] As a result of the hemorrhage, CMs commonly present with seizures, headaches, and neurological deficits. However, the symptoms may differ depending on the lesion site. Intralesional hemorrhage, although rare, can cause growth of the lesion and produce mass effects on the surrounding structures. In terms of the diagnosis and evaluation of these vascular lesions, magnetic resonance imaging (MRI) is considered the gold standard imaging modality.[ 14 , 15 , 44 ] CMs appear as berry-like lesions with high- and low-intensity reticulated centers, encompassed by hypointense rims in MRI.[ 11 ]

Although uncommon, CMs with the involvement of different cranial nerves have been reported in the literature. In general, lesions on the abducens nerve are extremely rare. There is only one case of CM associated with the abducens nerve that originated from the Dorello’s canal and encircled the nerve. Herein, we describe the first case of a pathologically proven isolated intraneural and intrafascicular CM of the cranial nerve.


A 21-year-old man was admitted to our clinic with a sudden and progressive headache and binocular diplopia. His symptoms had appeared 2 months before his first visit to the clinic. He had also experienced a similar attack 6 months earlier, but he was in a good general condition. The neurological examination revealed right-sided abducens nerve palsy. A brain computed tomography (CT) scan was acquired, which showed a suspected lesion in the cerebellopontine angle. Brain CT angiography was also performed, which did not reveal any prominent findings. The brain MRI showed an extra-axial pontomedullary lesion with the classic appearance of a CM, that is, a reticulated salt-and-pepper core, surrounded by a halo rim [ Figure 1 ]. With the diagnosis of brain stem CM with a history of multiple hemorrhages, progressive neurological deficit, and pial presentation of the CM, the patient was enlisted for the surgical resection of the lesion.

Figure 1:

Preoperative MRI images. (a) Sagittal T1-weighted contrast-enhanced image; (b) coronal T1-weighted contrast-enhanced image; (c) axial T1-weighted contrast-enhanced image; (d) Sagittal FSE T2-weighted image; (e) axial T2-weighted sequence; and (f) axial T2-weighted sequence.


The patient underwent surgery using the suboccipital retrosigmoid approach with intraoperative neuromonitoring. The procedure was performed through general anesthesia as the patient laid in a lateral position, and his head was fixed in a three-pin Mayfield headrest. After opening the dura, a CM was detected, arising from the sixth cranial nerve, with no invasion to the brainstem or the surrounding tissues. Since the lesion could not be separated from the nerve and its integrity was unclear, we resected the CM by cutting the proximal and distal portions (before the Dorello’s canal) of the sixth cranial nerve [ Figure 2 ]. Intraoperative monitoring was used to detect changes in the function of the nervous structure. Motor and somatosensory evoked potentials were normal during the surgery. Direct nerve stimulation of the sixth nerve was also performed during the surgery. The response to stimulation was normal when stimulating distal to the lesion and weak proximal to the lesion.

Figure 2:

Intraoperative images. (a) A reddish pulsating lesion in the cerebellopontine angle; (b) view of the CM (white arrow) and the distal course of the abducens nerve entering the Dorello’s canal (black arrow); (c) severed abducens nerve distal to the lesion (black arrow); (d) the resected CM with part of the abducens nerve (black arrow), passing through the lesion; (e) the prepared nerve graph (3 cm of the greater auricular nerve); (f) resection cavity after removal of the lesion, with the interposition nerve graft placed meticulously between the proximal and distal ends of the abducens nerve.


The greater auricular nerve (>3 cm) was harvested as an interposition nerve graft. An anastomosis was performed using a fibrin glue sealant, as end-to-end suture was impossible. One day after surgery, the patient showed complete sixth nerve palsy. He was discharged on the 4th postoperative day, without any neurological deficit, except for the right abducens nerve palsy. In the 5-month follow-up visit, he showed complete recovery of the cranial deficit and diplopia. The histopathological examination of the lesion demonstrated typical characteristics of a CM [ Figure 3 ]. To determine the origin of the lesion, immunohistochemistry staining for the S100 marker was carried out, and the results showed the intraneural origin of the lesion [ Figure 3 ]. The follow-up imaging was normal after 2 years, and the patient was symptom free during this period.

Figure 3:

Histopathological image of the lesion. (a) Blood-filled medium-sized vessels (H&E staining; ×100); (b) large cavernous space (H&E staining; ×100); and (c) black stained elongated nuclei of nerve fibers (S100 protein staining, ×100).



Tumors associated with the peripheral nerve are rare entities. Depending on their origin, peripheral nerve tumors are classified into nerve sheath tumors and nonneural sheath tumors.[ 23 ] In general, schwannomas and neurofibromas are considered as the most common benign nerve sheath tumors.[ 48 ] Benign nonneural sheath tumors primarily consist of lipomas and vascular tumors. On the other hand, malignant peripheral nerve sheath tumors are much less frequent and may include metastasis. Cases of vascular lesions associated with the peripheral nervous system are rare and can be classified into three types: Intraneural extrafascicular malformations, intrafascicular encompassing type lesions, and lesions with both intraneural and extraneural components.[ 29 ]

The cranial nerves, as a part of the peripheral nervous system, may be affected by CMs. In 2014, Rotondo et al.[ 45 ] reviewed the literature on the reported cases of cranial nerves’ CMs. To the best of our knowledge, we have gathered all the reported cases of CMs with cranial nerve involvement from 2014 to 2020 in [ Table 1 ]. The demographic characteristics, clinical characteristics, treatments, and treatment outcomes are also summarized in [ Table 1 ]. Based on our review, the optochiasmatic pathway is the most involved cranial nerve, with at least 75 reported cases, which commonly presented with visual loss and headache.[ 1 , 4 - 6 , 17 , 25 , 31 , 32 , 36 , 46 , 49 , 51 , 53 , 54 , 59 ] There are at least 10 reported cases of CMs in the VII/VIII nerve complex (excluding the internal auditory canal CMs), with the main complaint of hearing loss.[ 10 , 30 , 34 , 46 ] In nine confirmed cases, the oculomotor nerve was involved, mainly with diplopia and ptosis as the prominent manifestations. [ 9 , 39 , 46 ] The CMs of the trigeminal nerve were also described in six cases, typically presenting with facial dysesthesia or hyperesthesia.[ 2 , 20 , 40 , 46 , 47 ] The trochlear nerve CMs have been only reported in five patients, with varying presentations.[ 27 , 46 , 55 ] Furthermore, only one case has been reported for the involvement of each hypoglossal, accessory, and abducens nerve.[ 13 , 37 , 50 ] Lesions originating from the cerebellopontine angle or the internal auditory canal are more common and may have clinical presentations of cranial nerve CMs, caused by the mass effect of the tumor.

Table 1:

Reported case of cranial nerve CMs from 2014 to 2019.


To the best of our knowledge, this is the first case of a pathologically proven isolated intraneural and intrafascicular CM of the cranial nerve. Only one case of the abducens nerve involvement has been described in the literature.[ 37 ] The case was a 54-year-old woman with complaints of diplopia and headache and radiological findings, suggesting the hemorrhagic enlargement of the mass on the right cerebellopontine angle. It was reported that during the operation, a duplicated abducens nerve was observed, with a larger branch encircled with a lesion, originating from the Dorello’s canal.

Our patient presented with recurrent attacks of progressive diplopia, which showed a similar pattern to other cases of cranial nerve CMs, with acute or progressive neurological deficits, associated with the involved nerve. The recurrence of attacks is probably due to hemorrhage, as reported in the latter case. Although some reported cases of cranial nerve CMs associated with nerve deficits resolved without any intervention,[ 8 , 9 ] since patients usually undergo surgery due to its symptomatic nature and neurological deficit, it is unclear whether the patient’s condition improves without any intervention or not.

MRI imaging is crucial for the evaluation of CMs, especially if hemorrhage has occurred previously. In T2-weighted gradient-echo images, lesions with mixed intensity and reticulated cores, surrounded by hypointense rims (corresponding to hemosiderin deposition), suggest CMs. If intact CMs occur, there may not be any prominent feature characteristic of CMs, except for a vague enhancement on gadolinium-based contrast-enhanced MRI. In our case, MRI showed a CM with a previous hemorrhage located at the pontomedullary angle, but we could not determine the origin of the lesion. An important issue that has not been resolved yet is whether CMs develop within the nerve or originate from outside, encompassing the nerve. Although T1- and T2-weighted images are frequently used for the diagnosis of CMs, they cannot provide adequate information about these lesions. The constructive interference in steady-state (CISS) and fast imaging employing steady-state acquisition (FIESTA) sequences is proven to be useful in revealing the lesion boundaries and their relations to the surrounding tissues.[ 58 ] Furthermore, reliable assessment of cranial nerves is feasible by this method.[ 7 , 12 ] It can be safely stated that the CISS/FIESTA sequence should be considered as a tool for evaluating the CM origin and nerve continuity and planning a surgical approach.

Full functional recovery after the surgical repair of the transected abducens nerve has been previously reported.[ 46 ] In our patient, considering the location of the lesion, we could not repair the abducens nerve using sutures. We used fibrin glue, which has been proven as a safe and effective nerve glue, to repair the transected abducens nerve. Its superiority over sutures has been demonstrated in patients for whom nerve repair using sutures is not possible.[ 19 , 52 ] In our case, no postoperative adverse effect was reported, and repair was successful, as his condition improved in the later follow-ups.


CMs of the cranial nerve, although rare, pose a significant threat to the nerve functions. Except for our patient, only one other case of CM affecting the abducens nerve was reported earlier. Due to the limited number of cases and scarce evidence, no definite recommendation is available on the indications of surgery and treatment. However, it seems essential to treat patients with progressive neurological deficits, and physicians should consider novel MRI sequences (e.g., CISS/FIESTA), as the traditional sequences do not provide enough information regarding the nature and location of the lesions.

Declaration of patient consent

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Conflicts of interest

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    James Ausman

    Posted November 20, 2021, 7:17 am

    This is an outstanding Case report and review of the literature of a rare problem . Beautifully written; Scholarly.


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