Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.

Management of Adult Onset Seizures.

Epilepsy is a common yet heterogeneous disease. As a result, management often requires complex decision making. The ultimate goal of seizure management is for the patient to have no seizures and no considerable adverse effects from the treatment. Antiepileptic drugs are the mainstay of therapy, with more than 20 medications currently approved in the United States. Antiepileptic drug selection requires an understanding of the patient's epilepsy, along with consideration of comorbidities and potential for adverse events. After a patient has failed at least 2 appropriate antiepileptic drugs, they are determined to be medically refractory. At this time, additional therapy, including dietary, device, or surgical treatments, need to be considered, typically at a certified epilepsy center. All these treatments require consideration of the potential for seizure freedom, balanced against potential adverse effects, and can have a positive effect on seizure control and quality of life. This review article discussed the treatment options available for adults with epilepsy, including medical, surgical, dietary, and device therapies.

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.

Anterior temporal lobectomy compared with laser thermal hippocampectomy for mesial temporal epilepsy: A threshold analysis study.

PURPOSE: Anterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. METHODS: MEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6-12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS: 350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. CONCLUSIONS: This decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

Temporal lobectomy: resection volume, neuropsychological effects, and seizure outcome.

OBJECTIVE: The goal of the work described here was to evaluate relationships among resection volume, seizure outcome, and cognitive morbidity after temporal lobectomy for intractable epilepsy. METHODS: Thirty patients with mesial temporal sclerosis were evaluated pre- and postoperatively with the Wechsler Adult Intelligence Scale III, Wechsler Memory Scale III, and three-dimensional coronal spoiled gradient recall acquisition MRI. Preoperative whole-brain volumes were calculated with Statistical Parametric Mapping. Resection volume was calculated by manual tracing. Systat was used for statistical analysis. RESULTS: All resections included the temporal tip, at least 1cm of the superior temporal gyrus, and 3 to 5cm of the middle and inferior temporal gyri. Left were significantly smaller than right temporal resections. Seizure-free patients had significantly larger resections. Immediate verbal memory was significantly worse after left temporal lobectomy. Surgical outcome and resection volume did not affect postoperative neuropsychological results. CONCLUSIONS: Dominant temporal lobe resections are associated with immediate verbal memory deficits. Larger resection volume was associated with improved seizure control but not worse cognitive outcome.

Perception of stationary and moving sound following unilateral cortectomy.

The perception of motion is an essential prerequisite to responding adequately to the dynamic aspects of sensory information in the environment. The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we report data on auditory perception of stationary and motion stimuli from a subject with right-sided resection of the anterior temporal-lobe region including medial aspects of Heschl's gyrus, and from three subjects with unilateral (right-sided or left-sided) hemispherectomy. All these subjects had undergone cortectomy decades earlier. The subjects with hemispherectomy were completely unable to perceive auditory motion, but showed slight to moderate deficits in judging stationary location. The subject with temporal lobectomy exhibited quite similar stationary auditory deficits as found in the subjects with hemispherectomy, but was completely normal in judging auditory motion. Thus, there was a clear dissociation of the effects of unilateral temporal lobectomy and hemispherectomy on auditory motion perception. Collectively, these findings suggest that the unilateral anterior temporal-lobe region plays a significant role in the analysis of stationary, but not moving, sound. One may assume that the cortical "motion network" is distinct from the "stationary network", and is located either in the most posterior aspects of temporal lobe, or in non-temporal, most likely parietal, areas.

Beyond pharmacotherapy: surgical management.

PURPOSE: To review the recent advances in the field of temporal lobe epilepsy (TLE) surgery. RESULTS: TLE surgery has recently demonstrated a highly significant superiority over optimal medical therapy in a randomized trial. Accordingly, a median rate of 70% of class I outcome (patients free of disabling seizures postoperatively) has emerged from the pooling of all data published since the early 1990s. In addition, successful TLE surgery appears likely to reduce the risk of seizure-related death. However, it remains largely underused and overly delayed, partly because of the legitimate fears of possible surgical complications, such as verbal memory deficits or failure to control seizures. Reasons for surgical failures are not completely understood, and include bitemporal, pseudotemporal, and temporal-plus epilepsies, as well as insufficient resection of the mesial temporal structures. Developing techniques such as intraoperative MRI, gamma-knife radiosurgery, and various types of cranial nerves or intracerebral chronic stimulation have the potential to alleviate part of the limitations of TLE surgery. CONCLUSIONS: The overall benefit of surgical treatment in patients with drug-resistant TLE should encourage a more frequent and earlier referral of such patients to epilepsy surgery centers. Important progress toward higher rates of seizure-free outcome and lower morbidity remains to be made and may be obtained by taking advantage of the new available technologies.

Temporal lobe stimulation reveals anatomic distinction between auditory naming processes.

BACKGROUND: Language errors induced by cortical stimulation can provide insight into function(s) supported by the area stimulated. The authors observed that some stimulation-induced errors during auditory description naming were characterized by tip-of-the-tongue responses or paraphasic errors, suggesting expressive difficulty, whereas others were qualitatively different, suggesting receptive difficulty. They hypothesized that these two response types reflected disruption at different stages of auditory verbal processing and that these "subprocesses" might be supported by anatomically distinct cortical areas. OBJECTIVE: To explore the topographic distribution of error types in auditory verbal processing. METHODS: Twenty-one patients requiring left temporal lobe surgery underwent preresection language mapping using direct cortical stimulation. Auditory naming was tested at temporal sites extending from 1 cm from the anterior tip to the parietal operculum. Errors were dichotomized as either "expressive" or "receptive." The topographic distribution of error types was explored. RESULTS: Sites associated with the two error types were topographically distinct from one another. Most receptive sites were located in the middle portion of the superior temporal gyrus (STG), whereas most expressive sites fell outside this region, scattered along lateral temporal and temporoparietal cortex. CONCLUSIONS: Results raise clinical questions regarding the inclusion of the STG in temporal lobe epilepsy surgery and suggest that more detailed cortical mapping might enable better prediction of postoperative language decline. From a theoretical perspective, results carry implications regarding the understanding of structure-function relations underlying temporal lobe mediation of auditory language processing.