Discussion
CMs, by having an incidence of 0.1%–0.8% in the normal population, are the most common intracranial vascular malformation and are seen in the familial form in 40 to 60% of cases (1, 5). They can cause headache, FND and seizure and have a potential risk of hemorrhage. CMs are mostly located in supratentorial regions, but infratentorial CMs, representing 1/5 of lesions, have a higher risk of bleeding (up to 10.6% per year) and, due to their adjacency to sensitive structures, cause more severe FNDs (5).
Although conservative treatment along with annual imaging are the proposed policy in cases with asymptomatic CMs, the standard treatment in symptomatic patients is the surgical resection. The initial reports of surgical removal of this pathology return to more than a hundred years ago, and during the years, the efficacy and safety of surgical approaches have been improved by advancements in technics and instruments (21).
During the last decades, there has been a trend toward the application of minimally invasive methods, which provide satisfactory outcomes and a low rate of complications. SRS has been used for different pathologies, but the procedure’s efficacy is not predictable in all cases (2). For instance, it is observed that control of epilepsy is achieved lately after SRS and its efficacy in complex seizure situations is under debate (4). Risk of secondary cyst and CM formation should also be considered (2, 18).
Since the early 90s, there have been reports of thermal ablation of cerebral lesions. Since the initial days of using this method, the main challenges were avoiding thermal injury to the adjacent structures and possible deviation (22). Tendency of the lesions for bleeding and providing a safe trajectory are other barriers.
MRI-guided LITT provides a real time (or near to real-time) monitoring of thermal changes of the tissue by obtaining different sequences such as T1 weighted, water proton resonance frequency, etc. Outcomes of the LITT for other pathologies such as tumors, metastasis, seizure foci, etc., have been discussed in numerous reports and reviews (13).
In certain pathologies, such as seizure, LITT's results are comparable to those of open microsurgical techniques. According to our review of the limited available data, 83.3% of patients who underwent LITT for their CMs became seizure-free. A larger systematic review of 1226 patients who had supratentorial cerebral CMs who presented with seizure episodes and underwent microsurgical lesion removal resulted in seizure freedom in 75% of patients (23). Long-term follow-up after surgical resection of supratentorial CMs in Kwon et al. study demonstrated 82.1% of patients were free from impairing seizures. Kapadia et al. survey on patients with supratentorial CM after early surgery either by open craniotomy or microsurgical resection demonstrated the rate of seizure freedom at 1 year was 94.7% and 62.5% in patients with ≤2 and >2 seizures, respectively (24). Considering all data together, it seems that LITT should be considered a potent therapeutic modality in patients with CMs but in order to verify the efficacy of this treatment, longer follow-up in patients who received LITT is crucial.
During the last three years, the application of LITT for cerebral CMs has been in the spotlight. CMs are angiographically occult and have low flow blood circulation (5). These characteristics rationalize their low tendency for bleeding during the ablation or insertion of the probe into the CM (1, 19).
The majority of CMs are found in supratentorial regions, and up to 70% of individuals with such lesions have seizures (1). Ring of hemosiderin deposits, irritation, and gliosis of the brain parenchyma are regarded as the cause of the seizure (1, 3). Open microsurgical resection of CMs recognized as the epileptic foci can result in satisfactory outcomes in up to 80% of cases (21). Nevertheless, microsurgery for cerebral CMs necessitates direct access to the lesions by incision and craniotomy, which increases the potential of inadvertent collateral damage (particularly in deep or eloquent areas) (25), and lobectomies result in more severe neurocognitive impairments (26, 27).
SRS is a non-invasive option that results in seizure freedom rates, comparable to surgical resection. The seizure control rate by SRS for cerebral CMs has risen from 53% in studies two decades ago (28) to more than 80% in more recent studies (29). SRS for cerebral CM is linked to a prolonged temporal course and symptomatic radiation necrosis, particularly at doses used to treat seizures (25, 30, 31).
LITT, on the other hand, is minimally invasive and, in most situations, instantly effective. Furthermore, LITT's high rate of seizure control is equivalent to that of open surgery, and earlier ablation showed to be no obstacle to successful open surgery in those patients who were not initially seizure-free. Prior therapies, including as SRS and vagus nerve stimulation, were not contraindication for new ablative process (4).
It is also believed that early intervention after initial epileptic attacks can provide better results (1).
It is an essential factor to have a precise evaluation of seizure foci, especially in cases having multiple CMs and to have an intervention on the specified area, like what Satzer et al. performed for a patient with a familial type of CM (2). Expanded epileptogenic foci, like 2 cases in Willie et al. series who underwent open resection, is regarded as the cause of insufficient response of seizure to LITT (4, 10). An initial minimally invasive approach does not preclude later open resection.
It is assumed that removal of the hemosiderin ring is a crucial step in the control of the seizure, and in all LITT reports, ablation of the surrounding hemosiderin depositions was noted (1).
CMs have high susceptibility for thermal conduction, and the surrounding rim also enhances this event. Willie et al. observed that thermal spread around the CM can interrupt the precise thermal monitoring during LITT (32).
CMs which are located in either brain stem or basal ganglia are mostly presented with FNDs, and their surgical resection is always considered a challenge which requires experienced surgical teams. Resection of basal ganglia CMs have a 10% risk of morbidity, and neurologic deficits might be expected after the surgery, especially for lesions located in the globus pallidus and posterior limb of the internal capsule (3). Contralateral partial hemiparesis is the most common adverse event in the surgical treatment of basal ganglia CMs (33). Exacerbation of hemiparesis was also reported in a case of Malcolm et al., and it was among the only few adverse events of LITT for CMs which was not resolved over the time (19).
For CMs located in the brain stem, selecting the proper trajectory is an influencing factor on the resulted complications (17). Of the three patients with brain stem CM who underwent LITT, two developed transient post-operative FND which gradually improved, and it was attributed to the damaged structures along the trajectory (11, 17). In a study by Ashraf et al., performed on the posterior fossa neoplasms, a higher rate of complications was observed during and after the procedure for brain stem lesions compared to lesions in the cerebellum (34).
In most reports, postoperative adverse events were transient and were resolved or improved after a while (35). Some authors recommend performing LITT for lesions in sensitive regions in awake situation to monitor any change in neurological status, but some studies disagree due to the possibility movements and disruption of MRI based monitoring (19).
It is supposed that edema around the ablated target is the leading cause of transient subsequent adverse events (35). It is believed that after the ablation, it takes time (up to 90 days) that the size of the lesion would turn to half of the primary CM volume, and the perilesional change in the vasculature is assumed as the reason (12). Malignant edema and progressive FND were the cause of mortality in the Patel et al. study (35). However, LITT does not lead to mortality in reported CMs cases (35). A meta-analysis revealed that the total risk ratio of bleeding after SRS for brain stem CMs was 0.161 and 11.8% of patients experienced transitory or persistent neurological impairments (36).
In cases where surgeons doubt the sufficiency of the volume of the ablated target, using different trajectories is recommended, but it may increase the risk of complications (4, 35, 37).
In a study on 242 patients with brain stem CM, preoperative annual hemorrhage and re-hemorrhage rates were determined at 5.0% and 60.9% preoperatively, respectively, while the postoperative annual hemorrhage rate was 0.4 percent (38). In addition, about 40% of cavernoma remnants after surgery carry a risk of rebleeding (5), while re-hemorrhage was not seen after the LITT for CMs, even in cases with prior history of bleeding.
The findings of Monaco et al. study suggest that SRS may have a role in the treatment of symptomatic CMs of the brainstem, and appears to lower rebleeding rates from 32.38% to 8.22 within the first 2 years of follow-up (39).
In comparison with other therapeutic modalities such as SRS and surgery, LITT seems also a safe and compelling technique in the treatment of supratentorial CMs, with low risk of bleeding and FND, while for the purpose of confirming the safety and efficacy of this treatment, the longer follow-up and larger sample sizes are essential. Similar to brainstem CM’ surgical resection, which have higher risks and complications than other parts of the brain, LITT should be used with caution in these locations, and further experiments on larger cohorts are required to determine the method's safety and efficacy.
Pathological study of the resected tissue in cases who underwent open surgery due to ineffective LITT showed reactive gliosis and sclerosis of the vascular structures, which did not resemble the CMs common pathological characteristics (1, 4, 18).
Cyst formation in the location of ablated CM was the only reported long-term complication. The patient had CM formation after the SRS and 18 months after LITT, developed a growing cyst in previous location. Authors assume that this event could not be originated from the initial SRS (due to the duration between SRS and cyst formation), and vascular damage of LITT might be the probable cause (18).
Small sample sizes in most studies, heterogeneous CMs’ locations, the thinness of MRI slices used to evaluate volume measurements in some studies, patients lost to follow-up and also the absence of long-term follow-up, lack of high-power studies, and insufficient power to adequately prove the efficacy or safety profile of LITT for CMs are all limitations of this systematic review.
Further randomized controlled studies with larger patient sample sizes and adequate follow-up are needed to further validate the efficacy of LITT for CMs.