Early microsurgical resection is an effective and safe therapy for patients with pharmacoresistent CRE, as well as for CCMs with inherent risk of bleeding. The lesion should be completely resected, including surrounding epileptogenic brain tissue, because subtotal removal of a CCM is associated with a high risk of recurrences (Kim et al., 1997). When removing cavernous angiomas, however, the associated venous angioma has to be preserved, which provides anatomically disordered but physiologically essential drainage, because of the possibility of inducing venous infarction (Rabinov, 1999; Buhl et al., 2002).
Microsurgical technique is standard, although variations in surgical approaches exist. Some groups, for instance, describe the routine (Ferroli et al., 2006) or occasional (Kivelev et al., 2011) use of a stereotactic device or frameless neuronavigation system.
Regarding the surgical approach, Ferroli et al. (2006) describe a minimally invasive transsulcal approach. Kivelev et al. (2011) recommend a transsylvian approach for cavernomas located in the anteromedial part of the mesial temporal lobe, and transcortical excision using intersulcal dissection for other locations. Neurophysiologic monitoring techniques such as direct cortical mapping and monitoring of neurologic functions are used for CCMs in eloquent locations (Ferroli et al., 2006).
The amount of tissue resected is also a matter of discussion. Yeon et al. (2009) proposed lesionectomy for patients exhibiting sporadic seizures, except for those harboring mesial temporal lesions; they use extended lesionectomy for pharmacoresistant patients without mesial involvement and standard temporal lobectomy or tailored resection when mesial structures are affected. Ferroli et al. (2006) endorse a two-step surgical policy for patients with CRE, attempting a pure lesionectomy first, followed by invasive localization and tailored removal of the epileptogenic zone in patients with persistent drug-resistant seizures at 1–2 years follow-up.
Radiosurgery can lead to the progressive obliteration of CCMs by endothelial cell proliferation, with consequent luminal closure, a process that takes 1–3 years to complete (Schneider et al., 1997), during which the risk of hemorrhage remains. Serious complications are well recognized, with up to 41% of patients developing neurologic deterioration and 27% requiring surgical treatment (Karlsson et al., 1998). According to newer studies, radiosurgery carries a morbidity risk of 8–20% (Lunsford et al., 2010; Monaco et al., 2010). The indications and appropriate doses for radiosurgery have not been established (Kim et al., 1997). Hsu et al. (2007) found no significant difference in seizure outcome between 15 CRE patients treated surgically and 14 treated with linear accelerator (LINAC) radiosurgery. Therefore, (LINAC) radiosurgery may be an alternative treatment for selected cases of CRE only, for example, when lesions are located in eloquent cortex. However, the limited experience suggests that excision remains the therapeutic strategy of first choice for patients with CRE.
Up to 12–17% of patients may develop neurologic symptoms (sensorimotor deficits and homonymous hemianopia or quadrantanopia) immediately after the operation (Ferroli et al., 2006; Stavrou et al., 2008), but the rate of long-term neurologic deficits is 2.6–8%. These include severe headache, slight dysphasia, sensory disturbances, ataxia, severe hemiparesis, and pontocerebellar degeneration (Zevgaridis et al., 1996; Baumann et al., 2006; Ferroli et al., 2006; Stavrou et al., 2008; Kivelev et al., 2011). No mortality related to the surgical intervention has been reported.
In the series reported by Kivelev et al., 15% of patients complained of postoperative short-term memory deficits, but memory decline was temporary in half of these patients. Neuropsychological evaluation revealed new memory deficit in 4% and worsening of previous symptoms in another 4%. Postoperative new-onset depression and fatigue was reported in 9.4% (Kivelev et al., 2011).
Seizure outcome and predictors
It is not easy to evaluate postoperative seizure outcome in the literature due to the following limitations: inclusion of patients whose main complaint was not epilepsy; unclear definitions of intractability; and diverse subdivision of patient cohorts regarding evolution, frequency, and severity of seizures.
Overall seizure outcome over time
The largest series has been reported by Baumann et al. (2007) and includes 168 patients. After 1 year, 70% of patients had an Engel class I outcome (48% IA), but as previously described (Kim et al., 1997), the success rate declined over time to 68% and 65% for the second and third years, respectively. These results contrast with smaller series that report 82–84% seizure freedom rates (Casazza et al., 1996; Cappabianca et al., 1997); some of these report stable seizure outcome after a 2 year follow-up (Yeon et al., 2009).
There seems to be no correlation between outcome and lobar location or side of CCMs (Cappabianca et al., 1997; Baumann et al., 2007). There are also reports that the location (mesial vs. lateral) of CCMs within the temporal lobe does not predict seizure outcome (Yeon et al., 2009; Kivelev et al., 2011).
Size of lesion
A diameter of <1.5 cm is associated with better seizure control during the first 2 years, but no differences arise at longer follow-up (Baumann et al., 2007; Yeon et al., 2009).
As with other etiologies, patients who have only focal seizures without secondary generalization may be more likely to become asymptomatic than those with secondarily generalized seizures (Baumann et al., 2007).
A longer preoperative history of epilepsy has been associated with worse seizure outcome (Morrell, 1985; Cohen et al., 1995; Cappabianca et al., 1997). Most authors reported a significantly poorer outcome for patients with seizure duration over 1–2 years, with the notable exception of patients with sporadic seizures over a long period of time (Cohen et al., 1995; Casazza et al., 1996; Cappabianca et al., 1997; Schroeder et al., 1997; Moran et al., 1999; Zevgaridis et al., 1999; Hammen et al., 2007; Yeon et al., 2009). However, other authors found similar results for patients with 0.5 to >10 years of seizure history (Baumann et al., 2007; Kivelev et al., 2011).
Men reportedly have a higher chance of becoming seizure-free (Cohen et al., 1995; Cappabianca et al., 1997; Stavrou et al., 2008), but this is not a constant finding (Baumann et al., 2007; Yeon et al., 2009).
Some studies show a better outcome in patients whose first seizure occurred after age 30 years (Cohen et al., 1995; Baumann et al., 2007) or 40 years (Cappabianca et al., 1997), but others found no such effect (Moran et al., 1999; Stavrou et al., 2008; Yeon et al., 2009). Baumann et al. (2007) reported better seizure control in patients >30 years at the time of surgery.
A correlation between the presence of epileptiform EEG abnormalities and seizure recurrence was reported in CRE (Vandonselaar et al., 1992). Subjects with normal preoperative EEG were more likely to become seizure-free (Kivelev et al., 2011), compared to patients with multifocal epileptiform activity (Baumann et al., 2007).
Although Kivelev et al. (2011) found no correlation between EEG results and seizure outcome, Di Gennaro et al. (2004) concluded that recording of postoperative epileptiform activity was associated with seizure persistence.
Acute hemorrhage at time of surgery
Perilesional bleeding seen on MRI or direct observation during surgery, whether old or recent, is not associated with outcome according to Baumann et al. (2007), but is considered as an indicator for poorer outcome in a smaller study by Stefan and Hammen (2004).
Frequency and number of seizures
A higher preoperative seizure frequency reportedly predicted worse postoperative outcome in some series (Cohen et al., 1995; Cappabianca et al., 1997; Moran et al., 1999; Stefan & Hammen, 2004; Ferroli et al., 2006; Kivelev et al., 2011), but had no effect in others (Casazza et al., 1996; Baumann et al., 2007; Stavrou et al., 2008). Yeon et al. (2009) found that patients with >1 seizure/month over a 1-year period were Engel class I in 72% (54.5% IA), as opposed to 89.5% (84.2% IA) of subjects with sporadic seizures only.
The role of “pure” lesionectomy
Because CCMs do not contain neuronal tissue they cannot themselves be the ictal-onset zone or epileptogenic zone. Therefore the surgical management of CCMs is inevitably linked to their effects on the surrounding cerebral tissue.
The role of the extension of excision remains subject to controversy due to small sample size and the retrospective nature of the studies. Although most studies report significantly better outcome when the surrounding gliosis and hemosiderin fringe are removed (Piepgras et al., 1993; Yeh et al., 1993; Cohen et al., 1995; Casazza et al., 1997; Kim et al., 1997; Stefan & Hammen, 2004; Baumann et al., 2006; Hammen et al., 2007; Stavrou et al., 2008), others fail to find statistically significant differences (Casazza et al., 1996; Zevgaridis et al., 1996; Cappabianca et al., 1997).
It appears that lesionectomy alone can provide a relatively good outcome for patients with sporadic seizures or a CRE duration <1 year, with reported seizure-free rates of 70–90% (Acciarri et al., 1995; Cohen et al., 1995; Casazza et al., 1996; Zevgaridis et al., 1996; Cappabianca et al., 1997; Ferroli et al., 2006). In a recent systematic review, Englot et al. (2011) observed no difference in seizure-free rates after pure lesionectomy compared with resections that included the hemosiderin fringe. They suggest that prospective data are needed to clarify the issue, given the conflicting findings in previous reports and the retrospective uncontrolled nature of all case series reported so far.
We suggest that future prospective multicenter studies should include the type, number, and medication response of seizures, epilepsy duration, history of bleeding, neurologic examination, paraclinical findings (MRI, EEG, video-EEG, and so on), size, location, surgical approach, resection type, transient and permanent neurologic deficits, ILAE outcome classification, and the length of follow-up. It would also be relevant to determine the volume of cortical and subcortical hemosiderin and gliosis preoperatively and postoperatively.
Although published data do not permit the proposal of an evidence-based treatment guideline with regards to the resection or not of the hemosiderin rim, it appears clear from the above pathophysiologic considerations that seizures do not arise in the CCM itself (which contains no neurons) but rather in the surrounding cortical gliotic tissue usually stained by hemosiderin. At the time being we therefore recommend resection of at least the cortical parts of the surrounding gliotic hemosiderin stained tissue whenever possible without causing deficits.