This is the first study reporting long-term longitudinal outcomes in patients with multilobar epilepsy surgery. Following multilobar resections in a group of adult and pediatric patients with medically intractable epilepsy due to various types of pathologies, seizure freedom was achieved in 41% at a follow-up of 10 years. In prior studies, seizure free outcomes at last follow-up ranged between 22% and 55% (Patil et al., 1997; Eriksson et al., 1999; Paolicchi et al., 2000; Elsharkawy et al., 2008; Hemb et al., 2010). The seizure-free rate of 41% at 10 years noted in this study is comparable to reports of 44.4% in series of extratemporal multilobar resections with a similar follow-up period (Elsharkawy et al., 2008). The discrepancy with the other studies may be due to surgical technique; Patil et al. (1997) focused on multiple subpial transections plus topectomy, whereas others reported on the outcome in different patient populations; age <12 in Paolicchi et al. (2000) and strictly pediatric patients in Hemb et al. (2010).
The lack of longitudinal follow-up in many of the prior studies may lead to more optimistic conclusions about surgical outcome when in fact the results may not necessarily be sustained over time. As our data showed, approximately half of the surgical failures after multilobar resections occurred during the first 6 months after surgery and the other half of the failures happened between 6 months and 10 years after resections.
Other studies have reported higher seizure-free rates with unilobar resections in different patient populations (Paolicchi et al., 2000; Fauser et al., 2008; Hemb et al., 2010).
Compared to unilobar surgeries at our center, seizure freedom in 52% of the patients at 5 years was worse than that observed in patients following either temporal lobe (63%) or posterior quadrant (63%) resections (Jeha et al., 2006; Jehi et al., 2009). However, it was better than that following frontal lobe resection (30% at 5 years) in patients in whom medically intractable frontal lobe epilepsy was suspected (Jeha et al., 2007). Clearer trends, however, emerge when the types of resections are analyzed. Extended occipital resections achieved 71% seizure freedom at 5 years, which is even better than in their unilobar counterparts. On the other hand, frontotemporal resections achieved a seizure freedom identical to that observed after unilobar frontal resections.
Although 52% of our patients eventually achieved a favorable outcome, it was interesting to note that 67% of the patients had at least one seizure postoperatively. Seizure recurrence occurred in 48% of the patients during the initial 6 month postoperative period. Patients with late recurrence had a higher chance of achieving seizure freedom as compared to those with early postoperative seizure recurrence. This is similar to our finding in unilobar patients, where the occurrence of two seizures within the 6-month postoperative period was associated with refractoriness (Jehi et al., 2010). Although the reasons behind these differences between the early and late seizure recurrence on the likelihood of seizure outcome at last follow-up are not clear, we suspect that the early recurrence of seizures would probably be due to incomplete resection of the epileptic focus. The late seizure recurrence in this patient population raises the question of epilepsy progression (Sperling et al., 2008). With the limitations of current technology, the seizure-onset zone can be well defined and resected (Rosenow & Luders, 2001). However, no methods currently exist to delineate the “potential seizure onset zone,” which may be the source of this delayed recurrence.
Predictors of recurrence
Patients with an extended occipital resection (occipital plus) had the best seizure-free rates at last follow-up. Our results of an Engel class I of almost 70% at 5 years and 60% at 10 years are similar to those reported Binder et al. (2008), where 70% of patients with extended occipital resections had seizure freedom with a mean follow-up of 6.7 years.
These favorable results contrasted with the extended temporal resections where frontotemporal resections achieved 22% seizure freedom and with temporoparietal resections with 27% seizure freedom at 5-year follow up.
A more aggressive TPO resection will have a higher likelihood of removing the epileptogenic zone. The patients in our cohort had earlier seizure onset and earlier resections as compared to the other groups. The presurgical hypothesis was also clearer, and as a result less invasive monitoring was needed.
Furthermore, epilepsies arising from the more posterior areas likely have better localization due to the absence (or limited presence) of spread patterns to those areas from other regions of the brain.
Occipitotemporal pathways are either direct through the inferior longitudinal fasciculus or indirect through polysynaptic U fibers (Catani et al., 2003). A number of studies have described ictal spread patterns from the occipital lobe with only rare reports of spread patterns to the occipital lobe (Jacobs et al., 2008).
In their cohort of 25 patients with occipital lobe epilepsy, Williamson et al. (1992) were able to document occipitofrontal spread and occipitotemporal spread in 3 and 12 patients, respectively.
In their analysis of 112 seizures of different areas of origin, only one seizure, which was of parietal onset, spread to the occipital lobe (Jenssen et al., 2011).
On the other hand, the more anterior regions have richer connections, and spread patterns to temporal areas have been described from cingulate (Koubeissi et al., 2009), insular (Isnard et al., 2004), and orbitofrontal cortices (Shihabuddin et al., 2001). Insular epilepsy can also falsely localize to the frontal or temporal lobes (Levitt et al., 2010). The possibility remains that with patients who are receiving the indication for resections extending outside the temporal lobe, a more widespread network that includes deeper structures such as the insula is missed (Ryvlin & Kahane, 2005).
Extended frontotemporal resections (after failed frontal lobe surgery) have also been shown previously to be ineffective in achieving seizure freedom (0 of 13) (Salanova et al., 1994).
A complete surgical resection of the epileptogenic tissue, whether based on imaging or intraoperative ECoG, was also associated with better rates of seizure freedom. This has previously been shown in a large series of patients with focal cortical dysplasia (Krsek et al., 2010), and is consistent with the findings in our cohort of frontal lobe epilepsy surgeries (Jeha et al., 2007). In contrast, surgical approaches attempting to spare lesional eloquent cortex run the risk of worse outcomes (Sarkis et al., 2010).
The presence of preoperative auras was a predictor of recurrence in our series. This may have been due to their false-localizing influences. It is possible that the temporal symptomatogenic zone may have been the result of spread from a silent ictal-onset zone and subsequently may have led to the generation of an inaccurate epileptogenic zone hypothesis and surgical exploration. Elsharkawy et al. (2008) noted that the presence of preoperative auditory auras was a predictor of recurrence in their extratemporal surgery series. Almost half of the auras reported in our patient cohort were suggestive of possible temporal lobe onset. Because these auras may be at times mislocalizing of the seizure onset, this may explain the higher rates of seizure recurrences in patients who underwent frontotemporal and temporoparietal resections.
Interictal spikes on postoperative EEG have been established as a useful predictor of seizure recurrence in both temporal and extratemporal epilepsy surgery (Jehi et al., 2010; Rathore & Radhakrishnan, 2010). Our results extend its usefulness to patients with multilobar surgeries as a marker of residual epileptogenic tissue.