Transabdominal motor evoked potential neuromonitoring of lumbosacral spine surgery.

BACKGROUND CONTEXT: Transcranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. PURPOSE: To evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. DESIGN: We present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. PATIENT SAMPLE: Two hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Intraoperative neuromonitoring data was correlated to immediate post-operative neurologic examinations and chart review. METHODS: Baseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of pre-operative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. RESULTS: TaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three pre-existing motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. CONCLUSIONS: These findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery.

Responsive neurostimulation for regional neocortical epilepsy.

OBJECTIVE: Surgical resection of seizure-producing brain tissue is a gold standard treatment for drug-resistant focal epilepsy. However, several patient-specific factors can preclude resective surgery, including a spatially extensive ("regional") seizure-onset zone (SOZ). For such patients, responsive neurostimulation (RNS) represents a potential treatment, but its efficacy has not been investigated in this population. METHODS: We performed a multicenter retrospective cohort study of patients (N = 30) with drug-resistant focal epilepsy and a regional neocortical SOZ delineated by intracranial monitoring who were treated with the RNS System for at least 6 months. RNS System leads were placed at least 1-cm apart over the SOZ, and most patients were treated with a lead-to-lead stimulation pathway. Five patients underwent partial resection of the SOZ concurrent with RNS System implantation. We assessed change in seizure frequency relative to preimplant baseline and evaluated correlation between clinical outcome and stimulation parameters. RESULTS: Median follow-up duration was 21.5 months (range 6-52). Median reduction in clinical seizure frequency was 75.5% (interquartile range [IQR] 40%-93.9%). There was no significant difference in outcome between patients treated with and without concurrent partial resection. Most patients were treated with low charge densities (1-2.5 µC/cm2 ), but charge density, interlead distance, and duration of treatment were not significantly correlated with outcome. SIGNIFICANCE: RNS is a feasible and effective treatment in patients with drug-resistant regional neocortical seizures. Prospective studies in larger cohorts are necessary to determine optimal lead configuration and stimulation parameters, although our results suggest that lead-to-lead stimulation and low charge density may be effective in some patients.

Responsive neurostimulation: Candidates and considerations.

Responsive neurostimulation (RNS) has recently emerged as a safe and effective treatment for some patients with medically refractory focal epilepsy who are not candidates for surgical resection. Responsive neurostimulation involves an implanted neurostimulator and intracranial leads that detect incipient seizures and respond with electrical counterstimulation. Over 1800 patients have been treated with RNS since its FDA approval in 2013. Despite its widespread use, however, RNS presents distinct challenges for clinicians. What types of patients are most well-suited for treatment with RNS? Given the availability of two other neurostimulation modalities, vagus nerve stimulation (VNS) and thalamic deep brain stimulation (DBS), what patient characteristics favor or disfavor RNS? Once RNS candidates are identified, lead placement presents another challenge. Unlike VNS and thalamic DBS, which both involve prespecified electrode locations, RNS involves intracranial strip and/or depth electrodes that can be flexibly configured based on knowledge of the seizure onset zone. The efficacy of RNS may depend on optimal lead configuration, but there are few resources to guide clinicians in formulating lead placement strategies. Here, we address these challenges, first by reviewing clinical trial data supporting the safety and efficacy of RNS. Then, through a series of clinical vignettes from our center, we provide a framework for RNS patient selection. For each clinical scenario, we illustrate typical strategies for RNS lead placement. We outline considerations for choosing among available neurostimulation devices based on their intrinsic features. For example, a unique feature of RNS is that the neurostimulator provides chronic electrocorticography (ECoG), which has powerful diagnostic potential. We highlight emerging applications of chronic ECoG, and we discuss how the limitations of RNS will inform development of next-generation devices.

Sensitivity of a Reduced EEG Montage for Seizure Detection in the Neurocritical Care Setting.

INTRODUCTION: Neurocritical care units commonly implement the double-distance reduced EEG montage in postoperative neurosurgic patients who have structural barriers that hinder the placement of a standard 10-20 system array. Despite its widespread use, its sensitivity has not been adequately addressed. We evaluated the sensitivity and specificity of this montage for seizure detection. METHODS: One hundred fifty-five full-montage continuous EEGs (cEEGs) completed in the Johns Hopkins University neurocritical care unit containing unequivocal electrographic seizures, status epilepticus, or other abnormalities were selected, comprising 73 ictal and 82 nonictal EEGs. EEGs were reformatted to the reduced montage, and 2-hour clips were reviewed independently by 2 epileptologists who documented the presence of seizures, status, or background abnormalities. RESULTS: The sensitivity and specificity of the reduced montage for electrographic seizure detection was 81% and 92% with substantial interrater agreement (kappa 0.71). The sensitivity for status epilepticus was lower at 69%, but specificity remained high at 97% (kappa 0.67). Several EEGs miscategorized as nonictal were labeled as rather having rhythmic activity or periodic discharges. Evaluation of background patterns on the ictal-interictal continuum resulted in sensitivities ranging from 68% to 83%. CONCLUSIONS: Although the specificity of the reduced array is good, epileptologists should remain vigilant when monitoring patients using this montage, given its reduced sensitivity for epileptic activity, especially status epilepticus.

Regulating drivers with epilepsy in Maryland: Results of the application of a United States consensus guideline.

OBJECTIVE: Driving regulations for people with seizures vary widely throughout the United States and the world. Maryland updated their guidelines in 2003 to reflect those of a U.S. consensus guideline requiring a minimum 3-month seizure-free period as well as an individual risk assessment by a Medical Advisory Board (MAB). This retrospective study provides the first analysis of outcomes after the implementation of the consensus guidelines and an assessment of their predictive validity through longitudinal outcome data. METHODS: MAB reviews and licensing records for Maryland driver applicants with seizures between 2004 and 2005 were reviewed, during which 254 first-time applicants were processed. The initial licensing decisions were assessed and the subsequent seizure recurrence and crash rates over the following 7 years were evaluated. RESULTS: The MAB approved driving for 74.8% of initial applicants; most had been seizure-free for over 6 months. Approved drivers had a longer median seizure-free period (563 days) compared to those who were denied (104.5 days, p < 0.01), and 22.7% of approved drivers had seizures recur during monitoring over the next year, although none resulted in crashes or deaths. Of applicants initially denied (n = 50), 89.3% were eventually licensed. Treating physicians recommended driving for 84.4% of applicants rejected by the MAB. SIGNIFICANCE: Maryland's individualized system for assessing driving applicants with seizures resulted in a dynamic process of approvals and denials based on favorable and unfavorable risk factors and lengths of seizure freedom. Seizure recurrences were comparable to internationally accepted rates. Over the course of monitoring, most applicants were eventually licensed. Treating physicians recommended that nearly all their patient applicants be permitted to drive, which raises safety concerns for the 10 states that rely solely on physician recommendations. Further assessment is needed of the risk factors deemed favorable and unfavorable by the U.S. consensus guidelines.

Synthesis and characterization of dual stimuli responsive macromers based on poly(N-isopropylacrylamide) and poly(vinylphosphonic acid).

Stimulus responsive materials hold great promise in biological applications as they can react to changes in physiological stimuli to produce a desired effect. Stimulus responsive macromers designed to respond to temperature changes at or around 37 degrees C and the presence of divalent cations were synthesized from N-isopropylacrylamide, pentaerythritol diacrylate monostearate, 2-hydroxyethyl acrylate, and vinylphosphonic acid by free radical polymerization. Monomers were incorporated into the macromers in ratios approximating the molar feed ratios, and macromers underwent thermogelation around normal body temperature (36.2-40.5 degrees C) as determined by rheology and differential scanning calorimetry. Macromers containing vinylphosphonic acid interacted with calcium ions in solution, displaying decreased sol-gel transition temperatures (27.6-34.4 degrees C in 100 mM CaCl(2)), with decreases of greater magnitude observed for macromers with higher relative vinylphosphonic acid content. Critical micellar concentrations also decreased in a dose-dependent manner with increased vinylphosphonic acid incorporation in solutions with CaCl(2) but not in solutions with NaCl. These dually responsive macromers allow examination of the effect of increasing vinylphosphonic acid content in a macromer, which holds promise in biological applications such as drug and cell delivery or tissue engineering due to the macromer responsiveness at physiological temperatures and concentrations of calcium.

Synthesis and characterization of injectable, thermally and chemically gelable, amphiphilic poly(N-isopropylacrylamide)-based macromers.

In this study, we synthesized and characterized a series of macromers based on poly( N-isopropylacrylamide) that undergo thermally induced physical gelation and, following chemical modification, can be chemically cross-linked. Macromers with number average molecular weights typically ranging from 2000-3500 Da were synthesized via free radical polymerization from, in addition to N-isopropylacrylamide, pentaerythritol diacrylate monostearate, a bifunctional monomer containing a long hydrophobic chain, acrylamide, a hydrophilic monomer, and hydroxyethyl acrylate, a hydrophilic monomer used to provide hydroxyl groups for further chemical modification. Results indicated that the hydrophobic-hydrophilic balance achieved by varying the relative concentrations of comonomers used during synthesis was an important parameter in controlling the transition temperature of the macromers in solution and stability of the resultant gels. Storage moduli of the macromers increased over 4 orders of magnitude once gelation occurred above the transition temperature. Furthermore, chemical cross-linking of these macromers resulted in gels with increased stability compared to uncross-linked controls. These results demonstrate the feasibility of synthesizing poly( N-isopropylacrylamide)-based macromers that undergo tandem gelation and establish key criteria relating to the transition temperature and stability of these materials. The data suggest that these materials may be attractive substrates for tissue engineering and cellular delivery applications as the combination of mechanistically independent gelation techniques used in tandem may offer superior materials with regard to gelation kinetics and stability.