Robert N. Holdefer

Dynamic correspondence between Purkinje cell discharge and forelimb muscle activity during reaching

There remain conflicting models of the cerebellar control of limb movement, ranging from the suggestion that the inhibitory output from Purkinje cells (PCs) is meant to suppress unwanted muscle activity, to the hypothesis that the cerebellar cortex embodies complex internal models of limb dynamics. To test these ideas, we undertook a quantitative comparison of PC simple spike dynamics to those of muscle activity. We recorded simultaneously from Purkinje cells in the paravermal anterior lobe and from muscles of the hand and arm in the behaving monkey during a simple, sequential button pressing task. The task-related discharge of each neuron was determined from peri-event histograms aligned to the onset of the behavior. Bursts of discharge were more than twice as common as pauses, but there was no difference in their timing relative to movement. From the same recordings, the similarity between discharge and muscle activity was evaluated by calculating the cross correlation between firing rate and rectified EMG. Surprisingly, given the inhibitory projection of PCs, most of the bursts of PC discharge were positively correlated with muscle activity. Although our results do not support a simple correspondence of pauses and bursts with limb acceleration and deceleration respectively, they are consistent with a more complex PC regulation of cerebellar nuclear activity from task-related, corticopontine drive.

Intraoperative neuromonitoring alerts that reverse with intervention: treatment paradox and what to do about it.

Summary: Intervention-mediated recovery from adversely changed evoked potential recordings may provide evidence for improved outcomes during neurophysiological intraoperative monitoring. However, these reversible signal changes (RSCs) are ambiguous because the patients neurologic status cannot be known either at signal decline or after intervention. This article describes methods to reduce this ambiguity. Randomized control trials are not always possible or ethical. Recent thought on grading evidence has acknowledged that guidelines first described by Sir Austin Bradford Hill may support evidence for causation. Causality guidelines identified RSCs most likely to be truly positive in three reported studies. Diagnostic statistics were revised accordingly. A range of revised positive predictive values and likelihood ratios was calculated in the three studies, using causality guidelines. The revised data were similar to those reported for other diagnostic tests used in medicine. The RSCs may be assessed using causality guidelines for more accurate reporting of diagnostic statistics while preserving information related to surgical intervention and recovery that is lost with end of surgery diagnostics or when RSCs are ignored. A method is described for including RSCs in diagnostic statistics. This approach will more readily permit assessment of the value of neurophysiological intraoperative monitoring in prediction and prevention of neurologic deficits.

Intraoperative local field recording for deep brain stimulation in Parkinson's disease and essential tremor.

Oscillations in the beta frequency range (β‐LFP) are widely distributed throughout the motor system, modulated by dopaminergic medications, and locally generated in the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM). We investigated the feasibility of recording intraoperative β‐LFP signals and their descriptive summary statistics during surgeries for deep brain stimulation (DBS). β‐LFP from the microelectrode and stimulating lead were obtained from the STN in Parkinsons patients, and from the stimulating lead in the VIM of patients with Parkinsons disease or essential tremor. β‐LFP power was obtained over 8 second epochs and displayed online as compressed spectral and density arrays and trend plots. In agreement with other studies, β‐LFP power along microelectrode penetrations was greater in the STN as compared to sites dorsal and ventral to the nucleus. Differences in β‐LFP power were also observed across the contacts of stimulating leads in the STN and VIM. The contact with greatest β‐LFP power was either the most effective contact for clinical stimulation or adjacent to it. These results were obtained from conventional power measurements, spectral displays, and trend plots with equipment commonly used for intraoperative neuromonitoring. We conclude that β‐LFP is an accessible and easily recorded signal intraoperatively with potential usefulness for DBS lead localization and clinical programming of the stimulating lead.

An evaluation of motor evoked potential surrogate endpoints during intracranial vascular procedures.

OBJECTIVE MEPs are used as surrogate endpoints to predict the effectiveness of interventions, made in response to MEP deterioration, in avoiding new postoperative deficits. MEP performance in capturing intervention effects on these outcomes was investigated. METHODS A meta-analysis of studies using MEPs during intracranial vascular surgeries between 2003 and 2014 was performed. MEP diagnostic performance and relative risk of new postoperative deficits for reversible compared with irreversible MEP changes were determined. Intervention efficacy in reversing MEP deterioration and postoperative outcomes was compared across studies. RESULTS MEP diagnostic performance compared favorably with that of other tests used in medicine, with all likelihood ratios >10. The summary relative risk comparing reversible and irreversible changes was 0.40, indicating a 60% decrease in new deficits for reversible MEP changes. The proportion of MEP deteriorations which recovered was negatively correlated with the proportion of new postoperative deficits (r=-0.81, p<.005). CONCLUSIONS The effectiveness of interventions in recovering an MEP decline was predictive of preserved neurologic status. MEPs are provisionally qualified as surrogate endpoints given potentially major harms to the patient if they are not used, compared to the minimal harms and costs associated with their use. SIGNIFICANCE The performance of MEPs as substitute, or surrogate, endpoints during intracranial vascular surgeries for new deficits in motor strength in the immediate postoperative period was directly assessed for ten recent studies.

Preoperative Facial Nerve Mapping to Plan and Guide Pediatric Facial Vascular Anomaly Resection

Importance Facial vascular anomalies are surgical challenges due to their vascularity and facial nerve distortion. To assist facial vascular anomaly surgical treatment, presurgical percutaneous facial nerve stimulation and recording of compound motor action potentials can be used to map the facial nerve branches. During surgery, the nerve map and continuous intraoperative motor end plate potential monitoring can be used to reduce nerve injury. Objective To investigate if preoperative facial nerve mapping (FNM) is associated with intraoperative facial nerve injury risk and safe surgical approach options compared with standard nerve integrity monitoring (NIM). Design, Setting, and Participants This investigation was a historically controlled study at a tertiary vascular anomaly center in Seattle, Washington. Participants were 92 pediatric patients with facial vascular anomalies undergoing definitive anomaly surgery (from January 1, 1999, through January 1, 2015), with 2 years’ follow-up. In retrospective review, a consecutive FNM patient cohort after 2005 (FNM group) was compared with a consecutive historical cohort (1999-2005) (NIM group). Main Outcomes and Measures Postoperative facial nerve function and selected surgical approach. For NIM and FNM comparisons, statistical analysis calculated odds ratios of nerve injury and operative approach, and time-to-event methods analyzed operative time. Results The NIM group had 31 patients (median age, 3.3 years [interquartile range, 2.2-11.4 years]; 20 [65%] male), and the FNM group had 61 patients (median age, 4.4 years [interquartile range, 1.5-11.0 years]; 26 [43%] male). In both groups, lymphatic malformation resection was most common (19 of 31 [61%] in the NIM group and 32 of 61 [52%] in the FNM group), and the median anomaly volumes were similar (52.4 mL; interquartile range, 12.8-183.3 mL in the NIM group and 65.4 mL; interquartile range, 18.8-180.2 mL in the FNM group). Weakness in the facial nerve branches at 2 years after surgery was more common in the NIM group (6 of 31 [19%]) compared with the FNM group (1 of 61 [2%]) (percentage difference, 17%; 95% CI, 3%-32%). Anterograde facial nerve dissection was used more in the NIM group (27 of 31 [87%]) compared with the FNM group (28 of 61 [46%]) (percentage difference, 41%; 95% CI, 24%-58%). Treatment with retrograde dissection without identification of the main trunk of the facial nerve was performed in 21 of 61 (34%) in the FNM group compared with 0 of 31 (0%) in the NIM group. Operative time was significantly shorter in the FNM group, and patients in the FNM group were more likely to complete surgery sooner (adjusted hazard ratio, 5.36; 95% CI, 2.00-14.36). Conclusions and Relevance Facial nerve mapping before facial vascular anomaly surgery was associated with less intraoperative facial nerve injury and shorter operative time. Mapping enabled direct identification of individual intralesional and perilesional nerve branches, reducing the need for traditional anterograde facial nerve dissection, and allowed for safe removal of some lesions after partial nerve dissection through transoral or direct excision.

Utility of evoked EMG monitoring to improve bone screw placements in the cervical spine

Study Design: EMG threshold testing as a guide to accurate screw placement was examined during posterior cervical spine instrumentation. The accuracy of screw placements was compared with the surgeon blinded and unblinded to EMG thresholds. Objective: To determine the utility of EMG threshold testing in improving screw placements in the lateral mass and pedicles of the cervical/upper thoracic spine. Summary of Background Data: EMG threshold testing in the lumbar spine is generally thought to improve the accuracy of pedicle screw placements. These results may not generalize to the cervical spine, where smaller pedicles, bicortical pilot holes, and the orientation of lateral mass screws away from midline may result in different alert thresholds. Methods: Triggered EMG thresholds were obtained from pilot holes in 244 lateral mass and 113 pedicles from 32 patients. Thresholds were compared with the accuracy of screw placements as determined from postoperative computed tomography scans. The percentage of inaccurate and potentially dangerous (IAPD) screws with the surgeon blinded and unblinded to EMG thresholds was determined. Results: EMG threshold testing was more accurate in predicting IAPD screw trajectories in the pedicles (likelihood ratio 5.1) as compared with the lateral mass (likelihood ratio 2.9). In the pedicles, the number of IAPD screws decreased from 4.5% in the blinded controls to 0% in the unblinded group. In the lateral mass, there were no IAPD screw placements in the blinded control group, whereas 2% of the screws in the unblinded group were IAPD. Conclusions: EMG threshold testing in the cervical spine (C3, T1) is a moderately accurate diagnostic test and more predictive of potentially dangerous screw trajectories in the pedicles (C7, T1) as compared with the lateral mass (C3–C6). EMG threshold testing may decrease potentially dangerous screw placements in the pedicles, but may have less utility in the case of the lateral mass because of less reproducible placement of the stimulating probe.

Alternative sites for intraoperative monitoring of cranial nerves X and XII during intracranial surgeries.

Summary: During intracranial surgeries, cranial nerve (CN) X is most commonly monitored with electromyographic endotracheal tubes. Electrodes on these endotracheal tubes may be displaced from the vocal folds during positioning, and there is a learning curve for their correct placement. Cranial nerve XII is most commonly monitored with electrodes in the dorsum of the tongue, which are also prone to displacement because of their proximity to the endotracheal tube. A retrospective review was conducted of a consecutive series of 83 skull base surgeries using alternative sites for monitoring CN X and XII. On-going (spontaneous) and evoked electromyography (EMG) were obtained from the cricothyroid muscle for CN X and submental genioglossus for CN XII. Stimulation of CN X or XII evoked specific compound motor action potentials from these muscles, and well-defined on-going EMG was observed during tumor resection in the vicinity of CN X and XII. Volume-conducted responses from the adjacent platysma muscle during CN VII stimulation were identified by concomitant responses from the orbicularis oris and oculi. In conclusion, during skull base surgeries, CN X may be monitored with electrodes in the cricothyroid muscle and CN XII with electrodes in the submental genioglossus. These alternative sites are less prone to displacement of electrodes compared with the more commonly used EMG endotracheal tube and electrodes in the dorsum of the tongue. The cricothyroid muscle should not be used when the recurrent laryngeal nerve is at risk.