EN - Current Management of Brainstem Cavernomas

Abstract
The last 30 years of advanced diagnostic tools and clinical experience, as well as improvements in minimally invasive microsurgical techniques, have made it possible to treat brainstem cavernoma surgery. Currently, brainstem cavernoma can be treated by microsurgery with excellent results and an acceptable morbidity rate. The preferred surgical route has gradually shifted from dorsal to lateral treatment, but this continues to depend on the presence of a brainstem lesion. Comparison and management of all cases of this rare country should be done by the local team.

Introduction
In recent years, the incidence of cerebral cavernous malformations (CM) has increased (prevalence 0.4-0.9%) due to the widespread use of magnetic resonance imaging (MRI) in clinical units and diagnostic improvements. Brainstem cavernomas account for 8-22% of all intracranial cavernomas. This subgroup, namely brain canal cavernous malformations, shows significantly more bleeding (up to 30%), is more likely to cause serious surgical sequelae and also has a higher risk of recurrent bleeding internal bleeding than other bleeding. Here we briefly summarize the literature and our experience in treating this disease.
Clinical Findings
The annual risk of brain canal cavernoma bleeding is 3.8-6%, with an observed value of 30~60% and an abnormally high bleeding recurrence rate. The probability of recurrence is very high (Figure-1). The extent of permanent change sequelae was with recurrent bleeding rates and rebleeding attacks occurred at increasingly shorter time intervals. In cases affected by brain canal cavernoma, 20% of bleeding may be lost. This rate is quite high and is 1% in hands exposed to microsurgery. Neurological sequelae depend largely on the location of the lesions and vary considerably, including varying degrees of internuclear ophthalmoplegia, worsening hemiparesis, facial or abducens paresis, gaze palsy, numbness of the face, trunk, and extremities, dysphagia, dysarthria, and gait ataxia. Clinically, they usually present subacutely over hours or days and are treated temporarily with dexamethasone in most cases to prevent malignant brainstem swelling and secondarycomplications. Acute events with loss of consciousness or respiratory distress are very rare.

Figure 1. The MRI on the right was taken on 18.06.2024 after the first hemorrhage. The patient, who was scheduled for surgery, stated that the complaints of weakness on his right side had increased when he came for surgery. In his examination, it was determined that the right hemiparesis had increased significantly compared to the first examination, and a new MRI was performed (MRI on the left, 18.09.2024) and it was determined that the acute bleeding and cavernoma size had increased.

Imaging
The gold standard for imaging anatomic and pathologic findings, such as the extent of lesion and hemorrhage, is MRI. High-field (1.5 or 3.0 Tesla) images with T1 (with or without contrast enhancement), T2, and gradient echo sequences in all three planes (axial, coronal, sagittal) are critical to guiding all decisions. Additional tools such as T2-based imaging and fiber tracking do not provide the true anatomic detail that was initially thought. To understand the true dimensions of the Brainstem Cavernoma, T1-weighted sequences must be evaluated.

Surgical Treatment

Indications, purpose and timing of surgery

Expert opinions differ on the indication and timing of surgery, but if hemorrhage appears to be associated with worsening neurological deficit, surgical evacuation of the lesion and hematoma is recommended. A surgical case example is shown in Figure-2. Exceptionally, surgery is recommended even for asymptomatic patients. As a general rule, clinical symptoms should be the main indication for surgery and the patient's preference should preferably be included in the decision-making process. The main goal of surgery is to eliminate the risk of recurrent hemorrhage and to avoid complications. Therefore, complete excision of the lesion is essential to prevent rebleeding, which can occur in up to 43% of surgical cases. However, there is a 4.4% postoperative rebleeding rate in brainstem cavernoma series. The risk of leaving residual parts of the lesion behind depends on the surgeon's experience. The larger the series, the lower the incidence of residuals. Over the past two decades, it has been recommended to wait four to six weeks after a hemorrhagic event to stabilize the patient's condition and to allow the hematoma to organize to achieve less active gliosis. However, the incidence of rebleeding is around 21.8% in the month following the wedge Figure-1. Therefore, surgery should be planned immediately unless the patient with bleeding has significant brainstem edema. Before surgery, steroid therapy may be recommended for one or two weeks to resolve the edema and to benefit from hematoma cavity formation.

Figure-2
MRI of a 72-year-old patient with ataxia, hemiparesis and left pontomesencephalic cavernoma hemorrhage (Top left image). Arrows represent the approach to the cavernoma. The left retrosigmoid region was prepared with the park bench position (bottom left image). The surgery was performed with a combined supracerebellar and retrosigmoid approach with an extended retrosigmoid craniotomy on the left side (Top right image). Early postoperative image is also available on CT (bottom right). After surgery, there were no additional deficits and subsequent follow-up showed almost complete resolution of preoperative symptoms.

Recently, a grading scale has been developed by Dr Edward Lawton at the Barrow Institute of Neurosurgery for evaluation purposes. According to this, it is possible to decide which patient is a candidate for surgery and which patient should be treated conservatively rather than surgically (Table).
Table. Surgical grading scale for brainstem cavernous malformations.

Peatures	Points
Size ≤2 cm >2 cm	0 1
Crossing Midline No Yes	0 1
Develepmental Venous Abnormality No Yes	0 1
Patient Age ≤40  Age >40 Age	0 1
Hemorrage Akut (0-3 weeks) Subakut (3-8 weeks) Kronik (>8 weeks)	0 1 2

Scoring ranges from 0 to 7. Patients with scores of 5, 6 and 7 are likely to have increased deficits and complications after surgery, so it is thought that it would be appropriate to perform follow-up instead of surgery, especially for patients with scores of 6 and 7. However, we must evaluate each patient on their own terms.

Surgical approaches to the brainstem and intraoperative monitoring
In many cases of brainstem cavernoma, a variety of surgical approaches are available, including suboccipital midline, retrosigmoid, or subtemporal approaches. The selection of the appropriate approach depends on the relationship between the cavernoma and the pial or ependymal surface of the brainstem. Cavernomas close to the surface are a plus sign for surgical decision-making. Because the floor of the fourth ventricle contains structures with important functions, a lateral access is preferred whenever possible. The supracerebellar infratentorial approach is suitable for many lesions and has yielded favorable patient outcomes; it is our preferred access route. Intraoperative electrophysiologic monitoring of the long pathways (MEP and SEP), AEP, and cranial nerves is mandatory during brainstem surgery.

Complications, morbidity and mortality
Postoperative morbidity may result from brainstem parenchymal manipulation or edema, and persistent morbidity in the range of 12%~21% has been previously reported. However, the morbidity rate is clearly related to surgical experience. In recent times, this rate has been considerably lower.

Alternative treatments

Stereotactic radiosurgery
The use of radiosurgery for covernomas remains controversial, as the primary goal of radiosurgery should be to significantly reduce the risk of bleeding. Some authors have insisted on the efficacy of radiosurgery for intracranial cavernomas because of the decreased risk of bleeding after a latency period of 2 years. However, the annual risk of bleeding during the latency period after radiosurgery is greater than 10%. In our opinion, stereotactic radiosurgery should not be considered as a first-line treatment for intracranial or brainstem cavernomas because it does not eliminate the risk of bleeding. If radiosurgery is adopted as the preferred treatment modality, proper evaluation must be performed in a neurosurgical center that performs these operations, since the lesion is not surgically inaccessible, as is often said in the phrase “surgically incurable.” For example, in a published series, Lunsford et al. presented cases of cerebellar cavernoma that were surgically accessible in experienced hands.

Wait and see treatment (conservative treatment)
Long-term outcomes were worse in the non-surgical group (42% worse outcome) than in patients who underwent surgical treatment (9%). However, conservative treatment plays an important role in patients with small lesions, rapid clinical improvement after bleeding episodes, and a non-aggressive appearance of the lesion on MRI. In such cases, it is important to inform the patient about the estimated individual bleeding risk, and all treatment options and possible morbidities should be discussed in detail. However, mortality may occur regardless of the decision. More than 50 patients with initially small or non-bleeding (incidental findings) lesions have been followed conservatively, and none of these patients experienced life-threatening bleeding. Follow-up should also be considered in cavernomas detected incidentally without any symptoms or complaints. However, the risk of rebleeding in bleeding brainstem cavernomas is 30-60% in the first year (Figure-1). Therefore, surgery should be considered in these cases.

Follow-up and further treatment
We perform the first MRI after surgery or a few days after the first hemorrhage and a follow-up MRI after 2-3 months. Annual MRI should be considered for all patients, with or without surgery, and follow-up should be performed at a center experienced in brainstem cavernomas.

Conclusion
Modern treatment options for brainstem cavernomas include a variety of diagnostic and surgical tools, experience and dedication. Together, positive results can be achieved and surgically incurable lesions are extremely rare. The most important factor is that the patient is referred to a surgically experienced clinic at the beginning of the diagnosis.