Neurophysiologic Intraoperative Monitoring for Spine Surgery: A Practical Guide From Past to Present.

Intraoperative neuromonitoring was introduced in the second half of the 20th century with the goal of preventing patient morbidity for patients undergoing complex operations of the central and peripheral nervous system. Since its early use for scoliosis surgery, the growth and utilization of IOM techniques expanded dramatically over the past 50 years to include spinal tumor resection and evaluation of cerebral ischemia. The importance of IOM has been broadly acknowledged, and in 1989, the American Academy of Neurology (AAN) released a statement that the use of SSEPs should be standard-of-care during spine surgery. In 2012, both the AAN and the American Clinical Neurophysiology Society (ACNS) recommended that: "Intraoperative monitoring (IOM) using SSEPs and transcranial MEPs be established as an effective means of predicting an increased risk of adverse outcomes, such as paraparesis, paraplegia, and quadriplegia, in spinal surgery." With a multimodal approach that combines SSEPs, MEPs, and sEMG with tEMG and D waves, as appropriate, sensitivity and specificity can be maximized for the diagnosis of reversible insults to the spinal cord, nerve roots, and peripheral nerves. As with most patient safety efforts in the operating room, IOM requires contributions from and communication between a number of different teams. This comprehensive review of neuromonitoring techniques for surgery on the central and peripheral nervous system will highlight the technical, surgical and anesthesia factors required to optimize outcomes. In addition, this review will discuss important trouble shooting measures to be considered when managing ION changes concerning for potential injury.

The Effect of Electroencephalography Leads on Image Quality in Cerebral Perfusion SPECT and 18F-FDG PET/CT.

Cerebral perfusion SPECT and 18F-FDG PET/CT are commonly performed diagnostic procedures for patients with epilepsy. Individuals undergoing these tests are often inpatients with electroencephalography leads. We have routinely removed these leads because of concern that they would lead to imaging artifacts. The leads would then be replaced at the conclusion of the scan. The goal of our study was to determine whether the electroencephalography leads actually do cause artifacts that can lead to erroneous scan interpretation or make the scan uninterpretable. Methods: 18F-FDG PET/CT and 99mTc-pertechnetate SPECT were performed on a 2-dimensional brain phantom. The phantom was scanned with standard leads, CT/MR-compatible leads, and no leads. The quality of the images was ranked by 3 experienced nuclear medicine physicians, who then determined whether they could differentiate each of the scans from a scan in which it was known that no leads were present. Results: No differences could be detected between scans obtained without leads and scans obtained with either set of leads. The standard electroencephalography leads did create artifacts in the CT portion of the PET/CT images, whereas the CT/MR-compatible leads did not. Conclusion: This phantom study suggests that electroencephalography leads, whether standard or CT/MR-compatible, do not need to be removed for SPECT or PET procedures. Further study evaluating the effect on actual patient scans would be of value to support this conclusion.

Critical review of the responsive neurostimulator system for epilepsy.

Patients with medically refractory epilepsy have historically had few effective treatment options. Electrical brain stimulation for seizures has been studied for decades and ongoing technological refinements have made possible the development of an implantable electrical brain stimulator. The NeuroPace responsive neurostimulator was recently approved by the FDA for clinical use and the initial reports are encouraging. This device continually monitors brain activity and delivers an electric stimulus when abnormal activity is detected. Early reports of efficacy suggest that the device is well tolerated and offers a reduction in seizure frequency by approximately half at 2 years.

Evidence of altered corticomotor system connectivity in early-stage Alzheimer's disease.

BACKGROUND AND PURPOSE: There is increasing evidence for subtle motor dysfunction early in Alzheimer disease (AD), including common motor behaviors that were once considered unaffected early in the disease process. Our objective was to assess whether functional neural networks underlying motor behavior are altered by AD. METHODS: We investigated AD-related differences in regional brain activation during motor performance. Nine older adults with early-stage AD and 10 without dementia underwent functional magnetic resonance imaging while performing a visually directed simple motor task (hand squeeze). RESULTS: Despite some similarity in brain activation during motor performance, we found that individuals without dementia exhibited greater activation in accessory motor regions, supplementary motor area, and cerebellum compared with those with AD. We also assessed disease-related differences in regions where activity was functionally integrated with primary motor cortex. Using a psychophysiological interaction analysis, we found that those with AD displayed increased coactivation with primary motor cortex of bilateral motor and visual regions. DISCUSSION AND CONCLUSIONS: These AD-related differences in regional coactivation during motor execution may represent inefficiency in the motor network as a consequence of the disease process. Alternatively, they may represent compensatory activation. These findings provide further evidence that in early stages of AD, neuromotor function is altered even during simple motor behaviors. The results may have implications for performance of more complex tasks and may be associated with the well-characterized decline in dual-task performance in those with AD.

Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer disease.

Exercise and cardiorespiratory (CR) fitness may moderate age-related regional brain changes in nondemented (ND) older adults. The relationship of fitness to Alzheimer disease (AD)-related brain change is understudied, particularly in the hippocampus, which is disproportionately affected in early AD. The role of apolipoprotein E4 (apoE4) genotype in modulating this relationship is also unknown. ND (n=56) and early-stage AD patients (n=61) over the age of 65 years had magnetic resonance imaging and CR fitness assessments. Voxel-based morphometry techniques were used to identify AD-related atrophy. We analyzed the relationship of CR fitness with white and gray matter within groups, assessed fitness-related brain volume change in areas most affected by AD-related atrophy, and then analyzed differential fitness-brain relationships between apoE4 carriers. Atrophy was present in the medial temporal, temporal, and parietal cortices in patients with mild AD. There was a significant positive correlation of CR fitness with parietal and medial temporal volume in AD patients. ND patients did not have a significant relationship between brain volume and CR fitness in the global or small volume correction analyses. There was not a significant interaction for fitness x apoE4 genotype in either group. In early-stage AD, CR fitness is associated with regional brain volumes in the medial-temporal and parietal cortices suggesting that maintaining CR fitness may modify AD-related brain atrophy.

Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs.

Monodesmethyl cyamemazine and cyamemazine sulfoxide, the two main metabolites of the antipsychotic and anxiolytic phenothiazine cyamemazine, were investigated for their effects on the human ether-à-go-go related gene (hERG) channel expressed in HEK 293 cells and on native I(Na), I(Ca), I(to), I(sus) or I(K1) of human atrial myocytes. Additionally, cyamemazine metabolites were compared with terfenadine for their effects on the QT interval in anaesthetized guinea pigs. Monodesmethyl cyamemazine and cyamemazine sulfoxide reduced hERG current amplitude, with IC50 values of 0.70 and 1.53 microM, respectively. By contrast, at a concentration of 1 microM, cyamemazine metabolites failed to significantly affect I(Na), I(to), I(sus) or I(K1) current amplitudes. Cyamemazine sulfoxide had no effect on I(Ca) at 1 microM, while at this concentration, monodesmethyl cyamemazine only slightly (17%), albeit significantly, inhibited I(Ca) current. Finally, cyamemazine metabolites (5 mg kg(-1) i v.) were unable to significantly prolong QTc values in the guinea pig. Conversely, terfenadine (5 mg kg(-1) i.v.) significantly increased QTc values. In conclusion, cyamemazine metabolite concentrations required to inhibit hERG current substantially exceed those necessary to achieve therapeutic activity of the parent compound in humans. Moreover, cyamemazine metabolites, in contrast to terfenadine, do not delay cardiac repolarization in the anaesthetized guinea pig. These non-clinical findings explain the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.

Anesthetic properties of a propofol microemulsion in dogs.

Microemulsions of propofol with nanometer droplet diameter are alternatives to soybean macroemulsions for inducing anesthesia, and may have important advantages. We used a propofol (10 mg/mL) microemulsion (particle diameter 24.5 +/- 0.5 nm) and a commercial macroemulsion to induce anesthesia in dogs (n = 10) using a randomized, crossover design separated by a 7-day rest interval. The end points were loss of leg withdrawal after a toe pinch and changes in vital signs. Venous blood samples were acquired at multiple times to measure plasma propofol concentrations and indices of erythrocytes, leukocytes, and coagulation. All dogs were rendered insensitive to pain followed by successful recovery without noticeable complications. Comparing indices between microemulsion and macroemulsion formulations, no differences were noted with respect to dose (10.3 +/- 1.2 and 9.7 +/- 1.6 mg/kg, respectively, P = 0.39), time to induction (1.0 +/- 0.1 and 1.0 +/- 0.2 min, P = 0.39), time to recovery (17.4 +/- 4.6 and 18.2 +/- 3.8 min, P = 0.70), heart rate (P = 0.62), arterial blood pressure (P = 0.81), respiratory rate (P = 0.60), hemogram variables, prothrombin time (P = 0.89), activated partial thromboplastin time (P = 0.76), fibrinogen concentration (P = 0.52), platelet concentration (P = 0.55), or plasma propofol concentrations (P = 0.20). Induction with a propofol microemulsion or macroemulsion did not significantly vary with respect to vital signs, the hemogram, clotting variables, and plasma propofol concentrations.

Effects of cyamemazine on hERG, INa, ICa, Ito, Isus and IK1 channel currents, and on the QTc interval in guinea pigs.

The antipsychotic and anxiolytic phenothiazine, cyamemazine, was investigated for its effects on the hERG (human ether-à-go-go related gene) channel expressed in HEK 293 cells and on native INa, ICa, Ito, Isus, or IK1 of human atrial myocytes. Moreover, cyamemazine and terfenadine were compared for their effects on the QT interval in anesthetized guinea pigs. Cyamemazine reduced hERG current amplitude with an IC50 value of 470 nM. Cyamemazine 1 microM failed to significantly affect INa, Ito, Isus, or IK1 amplitudes and slightly decreased ICa (18%). For comparison, haloperidol (30 nM) and olanzapine (300 nM) reduced hERG current amplitude by 44.2+/-3.9% and 49.7+/-4.2%, respectively. The cardiac safety ratio of cyamemazine, calculated from the IC50/receptor affinity ratios, is 81 and 313 against dopamine D2 receptors and 5-HT2A receptors, respectively. In guinea pigs, QT and QTcBazett were not significantly modified by intravenous cyamemazine when compared to the effects produced by the vehicle. Conversely, terfenadine (5 mg/kg iv) increased significantly QTcBazett (+58 ms), QTcFrediricia (+83 ms) and QTcVan de Water (+78 ms). In conclusion, cyamemazine concentrations required to inhibit hERG current exceed substantially those necessary to achieve therapeutic activity in humans. Moreover, cyamemazine, in contrast to terfenadine, does not delay cardiac repolarization in the anesthetized guinea pig. These non-clinical findings confirm the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome.

OBJECTIVES: The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.

HMR 1556, a potent and selective blocker of slowly activating delayed rectifier potassium current.

The slowly activating delayed rectifier potassium current (IKs) contributes prominently to ventricular repolarization of the cardiac action potential. Development of a selective IKs blocker is important for the elucidation of the physiologic and pathophysiologic relevance of IKs and the development of antiarrhythmic strategies. HMR 1556 [(3R,4S)-(+)-N-[3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy) chroman-4-yl]-N-methylmethanesulfonamide] is a new chromanol derivative developed as a selective IKs blocker. Chromanol 293B, the most specific IKs blocker currently available, also inhibits the transient outward current (Ito). HMR 1556 was examined for its effects on IKs compared with rapidly activating delayed rectifier (IKr), inward rectifier (IK1), Ito, and L-type calcium (ICa.L) currents in canine left ventricular myocytes. HMR 1556 (0.5-500 nM ) inhibited IKs in a concentration-dependent manner (IC50 of 10.5 nM, compared with chromanol 293B's IC50 of 1.8microM). Inhibition of Ito was observed only at relatively high concentrations (IC50 of 33.9 microM comparable to chromanol 293B's IC of 38 microM). High concentrations of HMR 1556 also inhibited ICa.L (IC of 27.5 microM) and IKr (IC50 of 12.6 microM) while IK1 was unaffected. Our results indicate that HMR 1556 is superior to chromanol 293B in its potency and specificity for inhibition of IKs, making it a valuable experimental tool and a potential therapeutic agent.