A Comparison of Neuropsychological Outcomes following Responsive Neurostimulation and Anterior Temporal Lobectomy in Drug-Resistant Epilepsy.

Neuropsychological outcomes following temporal lobe resection for drug-resistant epilepsy (DRE) are well established. For instance, left anterior temporal lobectomy (LATL) is associated with a greater risk for cognitive morbidity compared to right (RATL). However, the impact of neuromodulatory devices, specifically responsive neurostimulation (RNS), remains an area of active interest. There are currently no head-to-head comparisons of neuropsychological outcomes after surgical resection and neuromodulation. This study reports on a cohort of 21 DRE patients with the RNS System who received comprehensive pre- and post-implantation neuropsychological testing. We compared both cognitive and seizure outcomes in the RNS group to those of 307 DRE patients who underwent LATL (n = 138) or RATL (n = 169). RNS patients had higher seizure rates pre-intervention. While fewer in the RNS group achieved Class I Engel outcomes compared to the ATL cohorts, RNS patients also showed seizure frequency declines from pre- to post-intervention that were similar to those who underwent resective surgery. Moreover, the RNS and RATL groups were similar in their neuropsychological outcomes, showing no significant cognitive decline post-intervention. In contrast, the LATL group notably declined in object naming and verbal list learning. Direct comparisons like this study may be used to guide clinicians in shared decision making to tailor management plans for patients' overall treatment goals.

Responsive Neurostimulation of the Anterior Thalamic Nuclei in Refractory Genetic Generalized Epilepsy: A Case Series.

Genetic generalized epilepsies (GGEs) are thought to represent disorders of thalamocortical networks. There are currently no well-established non-pharmacologic treatment options for patients with drug-resistant GGE. NeuroPace's Responsive Neurostimulation (RNS) System was approved by the United States Food and Drug Administration to treat focal seizures with up to two ictal foci. We report on three adults with drug-resistant GGE who were treated with thalamic RNS. Given the severity of their epilepsies and the potential ictogenic role of the thalamus in the pathophysiology of GGE, the RNS System was palliatively implanted with leads in the bilateral anterior thalamic nuclei (ANT) of these patients. The ANT was selected because it was demonstrated to be a safe target. We retrospectively evaluated metrics including seizure frequency over 18-32 months. One patient required explantation due to infection. The other two patients were clinical responders. By the end of the observation period reported here, one patient was seizure-free for over 9 months. All three self-reported an improved quality of life. The clinical response observed in these patients provides 'proof-of-principle' that GGE may be treatable with responsive thalamic stimulation. Our results support proceeding to a larger study investigating the efficacy and safety of thalamic RNS in drug-resistant GGE.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

Epilepsy surgery: factors that affect patient decision-making in choosing or deferring a procedure.

Surgical resection for well-selected patients with refractory epilepsy provides seizure freedom approximately two-thirds of the time. Despite this, many good candidates for surgery, after a presurgical workup, ultimately do not consent to a procedure. The reasons why patients decline potentially effective surgery are not completely understood. We explored the socio cultural, medical, personal, and psychological differences between candidates who chose (n = 23) and those who declined surgical intervention (n = 9). We created a novel questionnaire addressing a range of possible factors important in patient decision making. We found that patients who declined surgery were less bothered by their epilepsy (despite comparable severity), more anxious about surgery, and less likely to listen to their doctors (and others) and had more comorbid psychiatric disease. Patients who chose surgery were more embarrassed by their seizures, more interested in being "seizure-free", and less anxious about specific aspects of surgery. Patient attitudes, beliefs, and anxiety serve as barriers to ideal care. These results can provide opportunities for education, treatment, and intervention. Additionally, patients who fit a profile of someone who is likely to defer surgery may not be appropriate for risky and expensive presurgical testing.

The diagnosis and treatment of attention deficit hyperactivity disorder in patients with epilepsy.

Attention deficit/hyperactivity disorder (AD/HD) can cause significant impairment in psychosocial and scholastic achievement. AD/HD should be appropriately managed even if patients have comorbid epilepsy. The diagnosis and treatment of AD/HD in patients with epilepsy presents several challenges. Differentiating independent problems in attention from frequent epileptic seizures is the first step in evaluating these individuals. Once this is accomplished the formal independent diagnosis of AD/HD can be pursued. Data from non-epileptic AD/HD populations should be applied with caution to patients with epilepsy. Once attention deficit disorder has been diagnosed formally, choices in treatment can create other problems as some pharmacological treatments for AD/HD pose a risk of exacerbating seizures. This article serves as a review for the diagnosis and treatment of AD/HD spectrum disorders in patients with epilepsy.

Rescue therapies for seizures.

Most medical therapies for epilepsy consist of daily (or multiple-daily) dose, fixed-schedule, pharmacologic oral agents. Despite adherence, many patients continue to experience seizures. Various products have been discovered, designed, and marketed to serve as seizure-abortant therapies. These agents can be administered rapidly, as a "rescue" therapy, once a clinical seizure or cluster of seizures starts. Rescue medications are given as needed in an attempt to disrupt progression of a given seizure, and forestall what would otherwise be a more prolonged or more severe clinical event. Seizure-abortants also serve to aid in the management of seizure emergencies, such as prolonged, repetitive seizures, or status epilepticus. These compounds are not appropriate for all patients. Nevertheless, they do provide therapeutic benefit to several groups of patients: 1) those who perceive the onset of their seizures and have time to perform a self-intervention, 2) patients' caregivers who administer the therapy when they witness the onset of an ictal event, and 3) patients who are in the midst of an out-of-the-hospital seizure emergency (a seizure cluster or status epilepticus). In this article we will review currently available and future rescue therapies for seizures: US Food and Drug Administration (FDA) approved and FDA nonapproved drugs, nonpharmacologic behavioral treatments, the vagus nerve stimulator and the NeuroPace RNS® System (Mountain View, CA).

An update on brain stimulation for epilepsy.

Brain stimulation for epilepsy has been explored for decades. Nevertheless, this area has traditionally been associated with small poorly controlled trials, inconsistent results, and a resultant lack of widespread use of these technologies. Due to the success of deep brain stimulation for movement disorders and unprecedented advances in computer technology and bioengineering, brain stimulation recently has again generated great interest in epilepsy care. Several large-scale, randomized, blinded, multicenter trials have been conducted; the most up-to-date findings are summarized in this article. These treatment modalities will likely improve over time. The hope that they provide to patients with refractory epilepsy cannot be underestimated.

Sarcoid meningitis with fulminant delirium and markedly abnormal cerebrospinal fluid.

OBJECTIVE: To describe a patient with an acute fulminant delirium and eventual spinal fluid block secondary to sarcoid meningitis. DESIGN: Case report. SETTING: Hospital and Neurology Clinic. PATIENT: A previously healthy, 24-year-old man. INTERVENTIONS: Antimicrobials, corticosteroids, lumbar puncture, myelography, and lymph node biopsy. MAIN OUTCOME MEASURES: Cerebrospinal fluid, clinical status. RESULTS: The patient improved after treatment with corticosteroids. CONCLUSION: Sarcoid meningitis may present with delirium and spinal block.