Withdrawal of antiepileptic drugs after stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy.

OBJECTIVE: This retrospective study investigated the success rate of withdrawal of antiepileptic drugs (AEDs) following stereotactic laser amygdalohippocampotomy (SLAH) for mesial temporal lobe epilepsy (MTLE), and identified predictors of seizure recurrence. MATERIALS AND METHODS: We retrospectively assessed 65 patients who underwent SLAH for MTLE (59 lesional). Patients' demographics, disease characteristics and post-surgical outcomes were evaluated for their potential to predict seizure recurrence associated with withdrawal of AEDs. RESULTS: The mean period of observation post SLAH was 51 months (range 12-96 months) and the mean period to initial reduction of AEDs was 21 months (range 12-60 months). Reduction of AEDs was attempted in 37 patients (57 %) who were seizure free post SLAH and it was successful in approximately 2/3 of them. From the remainder 1/3 who relapsed, nearly all regained seizure control after reinstitution of their AEDs. The likelihood of relapse after reduction of AEDs was predicted only by pre-operative seizure frequency. At the end of the observation period, approximately 14 % of all SLAH patients were seizure free without AEDs and approximately 54 % remained seizure free on AEDs. Compared with preoperative status, the number of AEDs were reduced in 37 % of patients, unchanged in 51 % of them and increased in 12 % of them. CONCLUSIONS: Successful SLAH for MTLE allows for reduction of AEDs in a significant portion of patients and complete withdrawal of AEDs in a subset of them. Patients with higher pre-operative seizure frequency exhibit a greater chance of relapse post reduction of AEDs.

MRI-guided stereotactic laser corpus callosotomy for epilepsy: distinct methods and outcomes.

OBJECTIVE: Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames. METHODS: The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms. RESULTS: Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20-49 years), the median duration of epilepsy was 21 years (range 9-48 years), and median postablation follow-up was 20 months (range 4-44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%-80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2-2.0 mm) versus 2.4 mm (range 0.6-6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique. CONCLUSIONS: This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Case Series: Unilateral Amygdala Ablation Ameliorates Post-Traumatic Stress Disorder Symptoms and Biomarkers.

BACKGROUND: Post-traumatic stress disorder is a severe psychobiological disorder associated with hyperactivity of the amygdala, particularly on the right side. Highly selective laser ablation of the amygdalohippocampal complex is an effective neurosurgical treatment for medically refractory medial temporal lobe epilepsy that minimizes neurocognitive deficits relative to traditional open surgery. OBJECTIVE: To examine the impact of amygdalohippocampotomy upon symptoms and biomarkers of post-traumatic stress disorder. METHODS: Two patients with well-documented chronic post-traumatic stress disorder who subsequently developed late-onset epilepsy underwent unilateral laser amygdalohippocampotomy. Prospective clinical and neuropsychological measurements were collected in patient 1. Additional prospective measurements of symptoms and biomarkers were collected pre- and post-surgery in patient 2. RESULTS: After laser ablation targeting the nondominant (right) amygdala, both patients experienced not only reduced seizures, but also profoundly abated post-traumatic stress symptoms. Prospective evaluation of biomarkers in patient 2 showed robust improvements in hyperarousal symptoms, fear potentiation of the startle reflex, brain functional magnetic resonance imaging responses to fear-inducing stimuli, and emotional declarative memory. CONCLUSION: These observations support the emerging hypothesis that the right amygdala particularly perpetuates the signs and symptoms of post-traumatic stress disorder and suggests that focal unilateral amydalohippocampotomy can provide therapeutic benefit.

Stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy.

OBJECTIVE: To evaluate the outcomes 1 year and longer following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a large series of patients treated over a 5-year period since introduction of this novel technique. METHODS: Surgical outcomes of a consecutive series of 58 patients with mesial temporal lobe epilepsy who underwent the surgery at our institution with at least 12 months of follow-up were retrospectively evaluated. A subgroup analysis was performed comparing patients with and without mesial temporal sclerosis. RESULTS: One year following stereotactic laser amygdalohippocampotomy, 53.4% (95% confidence interval [CI] = 40.8-65.7%) of all patients were free of disabling seizures (Engel I). Three of 9 patients became seizure-free following repeat ablation. Subgroup analysis showed that 60.5% (95% CI = 45.6-73.7%) of patients with mesial temporal sclerosis were free of disabling seizures as compared to 33.3% (95% CI = 15.0-58.5%) of patients without mesial temporal sclerosis. Quality of Life in Epilepsy-31 scores significantly improved at the group level, few procedure-related complications were observed, and verbal memory outcome was better than historical open resection data. INTERPRETATION: In an unselected consecutive series of patients, stereotactic laser amygdalohippocampotomy yielded seizure-free rates for patients with mesial temporal lobe epilepsy lower than, but comparable to, the outcomes typically associated with open temporal lobe surgery. Analogous to results from open surgery, patients without mesial temporal sclerosis fared less well. This novel procedure is an effective minimally invasive alternative to resective surgery. In the minority of patients not free of disabling seizures, laser ablation presents no barrier to additional open surgery. Ann Neurol 2018;83:575-587.

Intractable epilepsy in patients treated for childhood acute lymphocytic leukemia.

PURPOSE: In the 1970s and 80s, standard treatment for childhood acute lymphocytic leukemia (ALL) included both intrathecal methotrexate and whole-brain irradiation. During acute treatment, seizures were not uncommon. The development of intractable epilepsy years after treatment, however, has not been well described in the literature. We describe five patients who were treated for acute lymphocytic leukemia as children, who later developed intractable epilepsy. RESULTS: All of the patients were diagnosed with leukemia before age seven. Treatment included both whole-brain irradiation and intrathecal chemotherapy. All five received intrathecal methotrexate; in addition, two also received intrathecal cytosine arabinoside. The first seizure occurred at a mean of 7.5 years after diagnosis. Four patients have multiple seizure types, and all patients have been on multiple antiepileptic drugs. All five patients are cognitively impaired. CONCLUSIONS: Successful treatment for childhood leukemia may be followed by signs of late cerebral injury including intractable epilepsy. We propose that neurotoxicity resulting from exposure to intrathecal methotrexate and cranial irradiation may have contributed to the intractable epilepsy seen in our five patients.