Brainstem cavernomas : a surgical challenge Cavernomas de tronco : desafio cirúrgico

Study carried out at Hospital Israelita Albert Einstein – HIAE, São Paulo (SP), Brazil; Hospital da Santa Casa de Londrina – Londrina (PR), Brazil; Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre (RS), Brazil. 1 Hospital Israelita Albert Einstein – HIAE, São Paulo (SP), Brazil; Neurosurgery Department, Santa Casa de Londrina – Londrina (PR), Brazil; Universidade Federal do Rio Grande do Sul – UFRGS, Rio Grande do Sul (RS), Brazil. 2 Hospital Israelita Albert Einstein – HIAE, São Paulo (SP), Brasil; Neurosurgery Department, Santa Casa de Londrina – Londrina (PR), Brazil. 3 Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre (RS), Brazil. 4 Neurosurgery Department, Santa Casa de Londrina – Londrina (PR), Brazil. 5 Hospital Israelita Albert Einstein – HIAE, São Paulo (SP), Brazil.


INTRODUCTION
Cavernous malformations (CM) has long been recognized as one of the major pathologic categories of vascular malformations of the nervous system (1) .Because no abnormal vascularity is seen on angiography, CM have been included in the description of cryptic or occult vascular malformations (2) .The term used is cavernous angioma, but more recently the term "cavernous malformations" has become more widely accepted, explicitly distinguishing these lesions from true vascular neoplasms as suggested by the term angioma.
CM of the central nervous system affects 0.4 to 0.9% of the population, and accounts for 8 to 15% of all vascular malformations (3) .In the brainstem (medulla, pons, and midbrain), its incidence is estimated to range from 9 to 35%, with a predilection for the pons (4,5) .
Before the era of magnetic resonance imaging (MRI), brainstem CM was only diagnosed at autopsy or in surgery (6) .The MRI appearance consists of a reticulated core of high and low signal intensities surrounded by a hypointense rim of hemosiderin (7) .
Digital subtraction angiography (DSA) is considered an unnecessary tool for diagnosis but it is important in deciding the strategy and approach to surgery (subtemporal, combined petrosal, or interhemispheric) (8) .
The differential diagnosis includes a very large number of conditions, such as hemorrhagic neoplasms, inflammatory lesions, and mixed lesions, capillary telangectasias, and developmental venous anomalies (2) .
The clinical symptoms of brainstem CM are related to the site of bleeding.Ocular motility and facial lesions are the most frequent deficits (6) .
Patients with asymptomatic brainstem cavernoma have a low risk of neurological events (ranging from 0.25 to 6.5% -mean of 4%) (5) .The risks of neurological events with surgery are greater than 10%.Some authors state that surgical treatment of asymptomatic cavernomas has little or no benefit to the patient (6) .
The first neurosurgeon to operate a pontine cavernoma was Dandy, in 1928, and the indication for this surgical procedure was a pontine bleeding.Apparently the diagnosis was established only after surgery (7) .Presence or absence of bleeding, acuteness, localization, and mass effect dictate the timing of the surgery.Several technologies can be applied to the procedure, such as neuronavigation, and intraoperative ultrasound, in particular, if the lesion is too small and in a specific area (8) .
Surgery for supratentorial (and cerebellar) cavernomas in young patients with mild or non-disabling symptoms might be questionable.However, in view of the cumulative risk of bleeding or neurological disability over time, an elective surgical resection might be indicated for some of these individuals.More problematic are the lesions located either within cortical or subcortical eloquent areas and within other functionally important areas, such as basal ganglia and thalamus, or those located within the third ventricle, such as corpus callosum and cingulate gyrus, paraventricular and paratrigonal regions, and deep temporal areas.However, recent publications have demonstrated that lesions within all such locations can also be removed with safety and acceptable morbidity.
Brainstem cavernomas constitute a special entity.The hemorrhage rate of these cavernomas is up to 30 times greater than that of other locations.Due to their anatomy, the hemorrhage is more likely to cause severe neurological deficits.Brainstem cavernomas represent a formidable treatment challenge because of their location within a parenchyma that has critical neurological functions, rendering them much more difficult to remove than those in other locations.

OBJECTIVE
To present the authors' experience in brainstem cavernomas surgery, and compare it with literature data.

METHODS
We retrospectively evaluated our clinical experience from 1998 to 2009.Thirteen patients harboring brainstem cavernomas underwent surgical resection.All plain films, medical records and images were reviewed in order to sample the most important data regarding epidemiology, clinical picture, radiological findings, and surgical outcomes, as well as main complications (Chart 1).

Patient characteristics
The average age was 42.4 years (ranging from 19 to 70).No predominant gender: male-to-female ratio, 6:7 (Table 1).In our case series, the location was pontine in ten cases, mesencephalic in two cases, and thalamomesencephalic in one case.MRI was used as the imaging method to diagnose the cavernomas in all cases.The average follow-up was 71.3 months (ranging from 1 to 138 months).The most common clinical presentation was a single cranial nerve deficit.The most frequent main symptoms were VIII paresis -tinnitus and hearing loss (69.2%), followed by VII paresis (30.7%). in one patient.The approach for pontine cavernomas (Figure 1) was the retrosigmoid approach, because most cases were more lateralized, facilitating the preservation of the seventh and eighth cranial nerves.

Interventions
Complete removal was accomplished in 11 patients, and partial removal in 2. The outcomes were directly related to the location (Figures 2 A-D and 3A-D).Morbidity and mortality rates were 15.3 and 7.6% respectively.

Outcome predictors
One patient had a poor prognosis.This patient underwent surgery for a CM in the midbrain and had acute hydrocephalus.Pneumonia evolved to sepsis, required percutaneous gastrostomy, and tracheotomy.The patient died 6 months after surgery from a general infection.

DISCUSSION
CM of brainstem is one the most challenging surgical procedures.
The pathological features of cavernomas are sinusoidal spaces lined by a single layer of endothelium, separated by a collagenous stroma devoid of elastin and smooth muscle, the surrounding parenchyma consistently exhibits evidence of worsened micro-hemorrhage, hemosiderin discoloration, and hemosiderin-filled macrophages, within the lesion (9,10) .There may be hyalinization, thrombosis with varying degrees of organization, calcification, cysts, or cholesterol crystals (11) .
Cavernomas had been studied for more than 150 years, but only when MRI was introduced as a diagnostic tool, their natural history and/or indication for surgery were truly studied (12) .In our case series, MRI was the diagnostic procedure of choice for cavernomas, but for diagnosis, head CT, MRI angiography, and CT were performed on all patients (13) .The DSA is unnecessary to establish a diagnosis of CM, but it is very important to show the venous drainage pattern when choosing an approach -subtemporal, interhemispheric or subtemporal (8) .However, MRI angiography could be used for this.The CT scan identified hematoma formation in 48% of cases, calcification in 24%, and edema in 19% (13) .CT localized the cavernomas and their position in relation to the skull.
When the mesencephalon is involved, especially when it is located within the depth of the tegment portion, this continues to be a real challenge (14) .
Brainstem cavernomas are associated with significant focal impairment caused by hemorrhages leading to facial nerves damage (15) .Table 2 shows the clinical manifestation in the majority of series.
Brainstem CM may bleed causing catastrophic neurologic impairment due to their localization, the risk being 0.7% per year per lesion (24) .In our series, only two patients had multiple hemorrhage, and these patients had the worst modified Rankin scale (mRS) rate.The female gender had a greater risk of hemorrhage (5) .Aiba et al. shows that younger females have a greater risk of bleeding events (13) .The recovery from hemorrhage was better described by Fritschi et al. (14) .They analyzed 139 patients, 30 of whom were treated clinically, and full recovery was achieved in 43.3% of cases.Minimal disability 23.3%, moderate and severe disability 6.7%, and 20% mortality.
Using the retrosigmoid approach, as a rule, we observe signs of bleeding on the surface of the brainstem, and through this point we begin the dissection and removal of the cavernoma (8,24) .Ziyal et al. stated that sometimes there is no evidence of bleeding on the surface, and laterally between the V and VII nerve, the cavernoma can be accessed with a transverse incision (24) .Through the lateral mesencephalic sulcus, and the inferior olivary nucleus, the brainstem can be reached without notable neural structure injury (17,25) .The indication to treat patients with CM include lesions that reaches a pial or ependymal surface and that may be approached without the need to reach eloquent brainstem tissues (17) .Complete microsurgical resection can be performed at a rate of 67% to 93% (18) .The overall mortality rate is 10 to 15% (17) .We achieved complete removal in 84.6% of cases.Chart 2 shows indications for surgery according to the literature.Chart 3 shows surgical approaches to brainstem CM.
Our patients had a preoperative mRS of 0 in 84.6% of cases, and a postoperative mRS > 4 in 15.3% of cases.In our case series, we had one death due to pulmonary sepsis, and one patient with a worsened mRS.Fritschi et al. (14) reported 83% of patients with the same or better mRS, and 1% of mortality.6 A cavernous malformation of the brainstem satisfied at least one of the following: (1) it abutted the pial surface or was exophytic, (2) it produced repeated hemorrhage, causing progressive neurological deficits, (3) acute hemorrhage extending outside the lesion capsule, (4) a mass effect was produced by a large intralesional hemorrhage Zimmerman et al. (6) 16 Superficially located, symptomatic cavernomas of the brainstem Fahlbusch et al. (7) 9 Symptomatic brainstem hemorrhage, sudden onset of neurological damage Sindou et al. (15) 12 Patients were referred to surgery because of a sudden or rapidly progressive deterioration of the neurological status.All patients had one or more bleeds Hauck et al. (10) 44 Symptomatic lesions and the natural history of the lesion Fritschi et al. (14) 29 Lesions that become symptomatic either with a sudden onset or are attributable to a hemorrhage or a slow progressive neurological impairment should be considered seriously before surgery Amin-Hanjani et al. (16) 14 Acute severe or progressive neurological deficit and recurrent hemorrhage unless deemed surgically inaccessible Bricolo (25) 6 Patients with a history of progressive neurological deterioration Ferroli et al. (18) 52 Patient presenting neurological deficit and lesion in the surface of the fourth ventricle or the lateral aspect of the brainstem Sakai et al. (26) 5 Symptomatic lesions located near the surface of the brainstem Bouillot et al. (27) 17 All surgically treated patients were symptomatic with one or more bleeding episodes and various neurological damages Steinberg et al. (28) 42 Multiple symptomatic clinical hemorrhage episodes or a single large hemorrhage episode associated with significant neurological deficits Estudo atual 13 Symptomatic lesions and the natural history of the lesion Zimmerman et al. (6) had one death on surgery, and the morbidity rate was 6.3%.Chart 4 shows the surgical outcome in the literature.
There is no consensus on the literature as to which is the best outcome predictor: Rankin, Glasgow outcome scale, Karnofsky, or Drake scale (18) .
Stereotatic radiosurgery has been used as an alternative treatment for brainstem CM, but its use is controversial.Amim-Hanjani et al. (16) reported a 16% incidence of permanent radiological impairment and 3% of mortality associated to radiation.Porter et al. (19) reported 59% of temporary and 4% of permanent complications.

Why do the pontine cavernomas have a poor prognosis?
Probably this is due to the proximity of the oculomotor nuclei.Motor impairment is related to circumferential

What are the best surgical approaches?
The anterior portion of mesencephalus and the interpeduncular fossa tissue may be accessed via subtemporal and retrosigmoidal approach to the posterior portion.However, the posterior portion is better accessed via supracerebellar infratentorial approach, in a semi-sitting portion.We preferred the retrosigmoid approach because it is more used due to the best view to the safety entry zones.Somatosensory evoked potential should be used in all patients in order to avoid nuclear and long tract damage (20) .

CONCLUSION
Cavernomas can be resected safely with optimal surgical approach (feasible entry zone) and microsurgical techniques.Factors that affect the outcome during surgery are preoperative status, size, timing of operation and complete resection.The goal of surgical intervention should be the complete resection of the lesion without any neurological impairment.

Figure 1 .
Figure 1.A 35-year-old female patient, with impairment of VII cranial nerve submitted to a retrosigmoid approach.For 2 months this impairment worsened, but improved and in fact there were no further complaints

Figure 2 .Figure 3 .
Figure 2. (A) Cavernous malformation on midbrain with III cranial nerve impairment; (B) compression on the acqueduct starting a hydrocephalus; (C) postoperative MRI without the compression of acqueduct; (D) postoperative magnetic resonance imaging.Coronal view