Intraoperative electrical stimulation of the human dorsal spinal cord reveals a map of arm and hand muscle responses.

Although epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. We hypothesized that lateral stimulation over the dorsal root entry zone would be most effective and responses would be strongest in the muscles innervated by the stimulated segment. Twenty-six people undergoing clinically indicated cervical spine surgery consented to mapping of motor responses. During surgery, stimulation was performed in midline and lateral positions at multiple exposed segments; six arm and three leg muscles were recorded on each side of the body. Across all segments and muscles tested, lateral stimulation produced stronger muscle responses than midline despite similar latency and shape of responses. Muscles innervated at a cervical segment had the largest responses from stimulation at that segment, but responses were also observed in muscles innervated at other cervical segments and in leg muscles. The cervical responses were clustered in rostral (C4-C6) and caudal (C7-T1) cervical segments. Strong responses to lateral stimulation are likely due to the proximity of stimulation to afferent axons. Small changes in response sizes to stimulation of adjacent cervical segments argue for local circuit integration, and distant muscle responses suggest activation of long propriospinal connections. This map can help guide cervical stimulation to improve arm and hand function.NEW & NOTEWORTHY A map of muscle responses to cervical epidural stimulation during clinically indicated surgery revealed strongest activation when stimulating laterally compared to midline and revealed differences to be weaker than expected across different segments. In contrast, waveform shapes and latencies were most similar when stimulating midline and laterally, indicating activation of overlapping circuitry. Thus, a map of the cervical spinal cord reveals organization and may help guide stimulation to activate arm and hand muscles strongly and selectively.

Changing characteristics of epilepsy interventional clinical trials over the last decade: Clinicaltrials.Gov registry.

INTRODUCTION: Epilepsy affects about 1% of the world's population (over 50 million). Of these, one-third have refractory or medication-resistant epilepsy. This group of people drives the development and testing of new interventions for epilepsy. To better address the needs of people with epilepsy, the characteristics of clinical trials, as well as the gaps in the population of interest, need to be evaluated. METHODS: We searched the www.ClinicalTrials.gov database using the keywords "seizure" or "epilepsy" between 9/1/2008-9/1/2018 and filtering for Interventional Clinical trials. The data were categorized by three equal time intervals (tertiles), and evaluated by type of intervention (behavioral, diet, device, drug, other), primary purpose (treatment, diagnosis, prevention, or basic science), gender, age, phase (Phase1 to Phase 4 trials), length and status of the study, enrollment/recruitment/randomization, location, blinding status, assignment group (single/parallel/crossover/factorial/sequential), and funding. We focused on drugs and devices and used a binary logistic regression model to analyze the role of time, length of study, funding, location, randomization, and age. RESULTS: We found 359 epilepsy clinical trials; of these, 245 (68.2%) clinical trials involved drugs, and 55 (15.3%) were device trials. Over the three tertiles, the percentage of device trials increased while medication trials decreased. Device:drug trial odds ratios increased six times by the third tertile. Also, the results showed that clinical trials for drugs and devices occurred more in adults than children. Industry funding decreased 20% over time. The US contribution to clinical research was stable, but device trials were more likely to occur outside of the US. CONCLUSION: Drugs constitute the substantial fields of interventional trials in epilepsy but decreased in proportion over the last decade, while the presence of the device trials steadily increased. Device trials focused on treatment and diagnosis of seizures and have been more invested in non-US countries.

Use of the train-of-five bipolar technique to provide reliable, spatially accurate motor cortex identification in asleep patients.

OBJECTIVE: Intraoperative cortical and subcortical mapping techniques have become integral for achieving a maximal safe resection of tumors that are in or near regions of eloquent brain. The recent literature has demonstrated successful motor/language mapping with lower rates of stimulation-induced seizures when using monopolar high-frequency stimulation compared to traditional low-frequency bipolar stimulation mapping. However, monopolar stimulation carries with it disadvantages that include more radiant spread of electrical stimulation and a theoretically higher potential for tissue damage. The authors report on the successful use of bipolar stimulation with a high-frequency train-of-five (TOF) pulse physiology for motor mapping. METHODS: Between 2018 and 2019, 13 patients underwent motor mapping with phase-reversal and both low-frequency and high-frequency bipolar stimulation. A retrospective chart review was conducted to determine the success rate of motor mapping and to acquire intraoperative details. RESULTS: Thirteen patients underwent both high- and low-frequency bipolar motor mapping to aid in tumor resection. Of the lesions treated, 69% were gliomas, and the remainder were metastases. The motor cortex was identified at a significantly greater rate when using high-frequency TOF bipolar stimulation (n = 13) compared to the low-frequency bipolar stimulation (n = 4) (100% vs 31%, respectively; p = 0.0005). Intraoperative seizures and afterdischarges occurred only in the group of patients who underwent low-frequency bipolar stimulation, and none occurred in the TOF group (31% vs 0%, respectively; p = 0.09). CONCLUSIONS: Using a bipolar wand with high-frequency TOF stimulation, the authors achieved a significantly higher rate of successful motor mapping and a low rate of intraoperative seizure compared to traditional low-frequency bipolar stimulation. This preliminary study suggests that high-frequency TOF stimulation provides a reliable additional tool for motor cortex identification in asleep patients.

Epilepsy treatment in adults and adolescents: Expert opinion, 2016.

INTRODUCTION: There are over twenty anti-seizure medications and anti-seizure devices available commercially in the United States. The multitude of treatment options for seizures can present a challenge to clinicians, especially those who are not subspecialists in the epilepsy field. Many clinical questions are not adequately answered in double-blind randomized controlled studies. In the presence of a knowledge gap, many clinicians consult a respected colleague with acknowledged expertise in the field. Our survey was designed to provide expert opinions on the treatment of epilepsy in adults and adolescents. METHOD: We surveyed a group of 42 physicians across the United States who are considered experts based on publication record in the field of epilepsy, or a leadership role in a National Association of Epilepsy Centers comprehensive epilepsy program. The survey consisted of 43 multiple-part patient scenario questions and was administered online using Redcap software. The experts provided their opinion on 1126 treatment options based on a modified Rand 9-point scale. The patient scenarios focused on genetically-mediated generalized epilepsy and focal epilepsy. The scenarios first focused on overall treatment strategy and then on specific pharmacotherapies. Other questions focused on treatment of specific patient populations (pregnancy, the elderly, patients with brain tumors, and post organ transplant patients), epilepsy patients with comorbidities (renal and hepatic disease, depression), and how to combine medications after failure of monotherapy. Statistical analysis of data used the expert consensus method. RESULTS: Valproate was considered a drug of choice in all genetically-mediated generalized epilepsies, except in the population of women of child-bearing age. Ethosuximide was a drug of choice in patient with absence seizures, and levetiracetam was a drug of choice in patients with genetic generalized tonic-clonic seizures and myoclonic seizures. Lamotrigine, levetiracetam and oxcarbazepine were considered drugs of choice for initial treatment of focal seizures. Lamotrigine and levetiracetam were the drugs of choice for women of child-bearing age with either genetic generalized epilepsy or focal epilepsy. Lamotrigine and levetiracetam were the drugs of choice in the elderly population. Lamotrigine was preferred in patients with co-morbid depression. Levetiracetam was the drug of choice in treating patients with hepatic failure, or who have undergone organ transplantation. Compared to the 2005 and 2001 surveys, there was increased preference for the use of levetiracetam and lamotrigine, and decreased preference for the use of phenytoin, gabapentin, phenobarbital and carbamazepine. DISCUSSION: The study presented here provides a "snapshot" of the clinical practices of experts in the treatment of epilepsy. The experts were very often in agreement, and reached consensus in 81% of the possible responses. However, expert opinion does not replace the medical literature; instead, it acts to supplement existing information. Using the study results is similar to requesting an expert consultation. Our findings suggest options that the clinician should consider to achieve best practice.

Sociodemographic disparities in epilepsy care: Results from the Houston/New York City health care use and outcomes study.

PURPOSE: The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care. METHODS: Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One-half of the patients were from a Houston site and two NYC sites that serve predominantly low-income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care. RESULTS: Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model. DISCUSSION: There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.