Effect of three-hour ankle joint immobilization with an ankle foot orthosis on corticospinal excitability and ankle joint angle excursion during gait.

[Purpose] Ankle foot orthosis (AFO) is widely used to regain gait function after injuries and/or stroke; however, limited information is currently available on their effects. We herein examined the effects of three-hour immobilization with AFO on corticospinal excitability and ankle joint movement during gait in healthy volunteers. [Participants and Methods] The participants comprised of seven healthy volunteers. Corticospinal excitability and ankle joint excursions were evaluated before and after three hours of immobilization with left limb AFO. We measured motor evoked potentials in the tibialis anterior (TA) and gastrocnemius (Ga) muscles induced by transcranial magnetic stimulation. In a kinematic analysis, we focused on transition points, such as the timing from dorsiflexion to plantarflexion of the ankle joint and/or vice versa, during gait. [Results] Corticospinal excitability in TA and Ga both significantly decreased. During the normalized gait cycle (GC), ankle angles showed less dorsiflexion at 0% GC and 100% GC, and during loading response and mid-swing and terminal swing phases. Furthermore, less plantarflexion was observed during the initial swing phase. [Conclusion] This study showed that short-term ankle joint immobilization with AFO induces a significant decrease in corticospinal excitability and has an effect on ankle joint excursion during gait. Further studies are needed on the effects of long-term immobilization by AFO.

Alertness fluctuations when performing a task modulate cortical evoked responses to transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation can vary substantially between participants and even from trial to trial within individuals. Recent work from resting state functional magnetic resonance imaging (fMRI) studies has suggested that spontaneous fluctuations in alertness over a testing session can modulate the neural dynamics of cortical processing, even when participants remain awake and responsive to the task at hand. Here we investigated the extent to which spontaneous fluctuations in alertness during wake-to-sleep transition can account for the variability in neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked responses with decreasing levels of alertness, even while participants remained responsive in the behavioural task. Specifically, we found that the amplitude of motor evoked potentials peaked during periods of EEG flattening, whereas TMS-evoked potentials increased and remained stable during EEG flattening and the subsequent occurrence of theta ripples that indicate the onset of NREM stage 1 sleep. Our findings suggest a rapid and complex reorganization of active neural networks in response to spontaneous fluctuations of alertness over relatively short periods of behavioural testing during wake-to-sleep transition.

Effect of conditioning and test stimulus intensity on cortical excitability using triad-conditioning transcranial magnetic stimulation.

Cortical facilitation assessed with triad conditioning transcranial magnetic stimulation has been termed triad-conditioned facilitation (TCF). TCF has been supposed to reflect increased intracortical facilitation (ICF) at short interstimulus intervals (ISI) around 10 ms and an intrinsic rhythm of the motor cortex at longer ISI around 25 ms. To gain further insight into the pathophysiological mechanism of TCF, we systematically studied the effect of suprathreshold conditioning stimulus (CS) and test stimulus (TS) intensity on TCF. Various CS intensities and TS intensities were used in a triad-conditioning paradigm that was applied to 11 healthy subjects. ISI between pulses were studied between 5 and 200 ms. TCF at 10 ms ISI enhanced with increasing CS intensity but decreased with increasing TS intensity. The duration of facilitation was longer with higher CS intensity. However, TCF at 25 ms ISI could not be elicited with none of the CS and TS intensities addressed here. Our results are consistent with the notion of TCF at short ISI reflecting ICF. The enhanced and prolonged facilitation with increase of CS without additional isolated facilitation at longer ISI suggest a prolongation of ICF.

A Prospective Look at the Prevalence of Setup Electrode-Swap Errors Across Over 450 Intraoperative Neuromonitoring Cases.

Intraoperative neurophysiological monitoring (IONM) is shown to be useful in surgeries when the nervous system is at risk. Its success in part relies upon proper setup of often dozens of electrodes correctly placed and secured upon patients and inserted in specific stimulating and recording receptacles. Given the complicated setups and the demanding operating room environment, errors in setup are bound to occur. These have led to false negatives associated with new patient morbidities including, at times, paralysis. No studies quantify the prevalence of these types of setup errors. Approximately 800,000 operations annually utilize intraoperative neuromonitoring in the US alone, so even a small percentage of errors suggests clinical significance. In addition, these types of errors hinder the overall effectiveness of IONM and may result in lower reported sensitivities and lower cost-effectiveness of this important service. We sought to discover through a prospective study and verification through chart review the prevalence of "electrode-swap" errors (when recording and/or stimulating electrodes are incorrectly placed on the patient or in the IONM equipment during setup) across all procedures monitored. We found recording and/or stimulating electrode set up errors in 24 of 454 cases (5.3%). These data and examples of how errors were discovered intraoperatively are reported. We also offer techniques to help reduce this error rate. This study demonstrates a significant potential avoidable error in IONM diagnostic utility, patient outcome, and sensitivity/specificity of alert criteria. The value of identifying and correcting these errors is consequential, multifaceted, and far-reaching.

Perspective: Can intraoperative neurophysiological monitoring (IONM) limit errors associated with lumbar pedicle screw fusions/transforaminal lumbar interbody fusions (TLIF)?

Background: We evaluated whether intraoperative neural monitoring (IONM), including somatosensory evoked potential monitoring (SEP), motor evoked potential monitoring (MEP), and electrophysiological monitoring (EMG), could reduce operative errors attributed to lumbar instrumented fusions, including minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF)/open TLIF. Methods: Operative errors included retraction/stretch or cauda equina neural/cauda equina injuries that typically occurred during misplacement of interbody devices (IBD) and/or malpositioning of pedicle screws (PS). Results: IONM decreased the incidence of intraoperative errors occurring during instrumented lumbar fusions (MI-TLIF/TLIF). In one series, significant loss of intraoperative SEP in 5 (4.3%) of 115 patients occurred after placing IBD; immediate removal of all IBD left just 2 patients with new neural deficits. In other series, firing of trigger EMG's (t-EMG) detected intraoperative PS malpositioning, prompted the immediate redirection of these screws, and reduced the need for reoperations. One t-EMG study required a reoperation in just 1 of 296 patients, while 6 reoperations were warranted out of 222 unmonitored patients. In another series, t-EMG reduced the pedicle screw breech rate to 7.78% (1723 PS) from a higher 11.25% for 1680 PS placed without t-EMG. A further study confirmed that MEP's picked up new motor deficits in 5 of 275 TLIF. Conclusion: SEP/MEP/EMG intraoperative monitoring appears to reduce the risk of surgical errors when placing interbody devices and PS during the performance of lumbar instrumented fusions (MI-TLIF/TLIF).However, IONM is only effective if spine surgeons use it, and immediately address significant intraoperative changes.

Perspective: Triple intraoperative neurophysiological monitoring (IONM) should be considered the standard of care (SOC) for performing cervical surgery for ossification of the posterior longitudinal ligament (OPLL).

Background: Triple Intraoperative Neurophysiological Monitoring (IONM) should be considered the standard of care (SOC) for performing cervical surgery for Ossification of the Posterior Longitudinal Ligament (OPLL). IONM's three modalities and their alerts include; Somatosensory Evoked Potentials (SEP: =/> 50% amplitude loss; =/>10% latency loss), Motor Evoked Potentials (MEP: =/> 70% amplitude loss; =/>10-15% latency loss), and Electromyography (loss of EMG, including active triggered EMG (t-EMG)). Methods: During cervical OPLL operations, the 3 IONM alerts together better detect intraoperative surgical errors, enabling spine surgeons to immediately institute appropriate resuscitative measures and minimize/avoid permanent neurological deficits/injuries. Results: This focused review of the literature regarding cervical OPLL surgery showed that SEP, MEP, and EMG monitoring used together better reduced the incidence of new nerve root (e.g., mostly C5 but including other root palsies), brachial plexus injuries (i.e., usually occurring during operative positioning), and/or spinal cord injuries (i.e., one study of OPLL patients documented a reduced 3.79% incidence of cord deficits utilizing triple IONM vs. a higher 14.06% frequency of neurological injuries occurring without IONM). Conclusions: Triple IONM (i.e., SEP, MEP, and EMG) should be considered the standard of care (SOC) for performing cervical OPLL surgery. However, the positive impact of IONM on OPLL surgical outcomes critically relies on spinal surgeons' immediate response to SEP, MEP, and/or EMG alerts/significant deterioration with appropriate resuscitative measures to limit/avert permanent neurological deficits.

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study.

Objective: The effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging (rs-fMRI). Method: A total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% resting motor threshold (rMT), and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential (MEP) amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation (ALFF) and regional homology (ReHo) at 0.01-0.08 Hz, 0.01-0.027 Hz, and 0.027-0.073 Hz. Results: After cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01-0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01-0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area. Conclusion: Repetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice.

Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke.

Background: Transcranial magnetic stimulation (TMS) is often used to examine neurophysiology. We aimed to investigate the inter-rater reliability and agreement of single pulse TMS in hospitalised acute ischemic stroke patients. Methods: Thirty-one patients with first-time acute ischemic stroke (median age 72 (IQR 64-75), 35% females) underwent TMS motor threshold (MT) assessment in 4 muscles bilaterally, conducted by 1 of 2 physiotherapists. Test-retest reliability was evaluated using a two-way random effects model (2,1) absolute agreement-type Interclass Correlation Coefficient (ICC). Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC) were used to evaluate agreement. Results: Reliability, SEM, and SDC of TMS was found to be moderate in right opponens pollicis (0.78 [CI 95% 0.55-0.89], SEM: 4.51, SDC: 12.51), good in right vastus medialis and tibial anterior (0.88 [CI 95% 0.72-0.96], SEM: 2.89, SDC: 8.01 and 0.88 [CI 95% 0.76-0.94], SEM: 2.88, SDC: 7.98 respectively), and excellent in right and left biceps brachii (0.98 [CI 95% 0.96-0.99], SEM: 1.79 SDC: 4.96, and 0.94 [CI 95% 0.89-0.97], SEM: 2.17 SDC: 6.01), opponens pollicis (0.92 [CI 95% 0.83-0.96], SEM: 2.68 SDC: 8.26, vastus medialis (0.92 [CI 95% 0.84-0.96], SEM: 2.87 SDC: 7.95), and tibial anterior (0.93 [CI 95% 0.86-0.96], SEM: 2.51 SDC: 6.95). Conclusion: The TMS demonstrated moderate to excellent inter-rater reliability confirming the ability of these measures to reliably discriminate between individuals in the current study sample. Improvements of less than 4.96 to 12.51 could be a result of measurement error and may therefore not be considered a true change.

Postoperative Focal Lower Extremity Supplementary Motor Area Syndrome: Case Report and Review of the Literature.

Supplementary motor area (SMA) syndrome refers to varying degrees of transient hemiparesis and mutism following insult to the medial posterior frontal lobe. We describe a rare case of an isolated lower limb SMA deficit with associated pre- and post-operative multimodality neurophysiological monitoring data. We review the literature on SMA somatotopy and the prognostic abilities of intraoperative motor evoked potentials in suspected SMA dysfunction. A 45-year-old male underwent staged resection of a complex parasagittal WHO grade II meningioma involving the posterior superior frontal gyrus bilaterally. Intraoperative neurophysiological monitoring with transcranial motor evoked potentials (TCMEP) and direct cortical motor evoked potentials (DCMEP) were used during both stages of resection. The patient developed an isolated left foot drop despite unchanged DCMEP and TCMEP data obtained during the first stage of the procedure. During the second stage of resection 3 days later, repeat neurophysiological monitoring confirmed intact corticospinal tracts. Deep peroneal somatosensory evoked potentials (SSEPs) revealed good morphology, appropriate latency and amplitudes during the second stage of resection. These results suggested a diagnosis of focal SMA dysfunction. Left foot drop persisted 7 days post-operatively. At one month follow up, the patient was neurologically intact with full strength noted in all muscle groups of the left lower extremity. An improved understanding of the somatotopic organization of the SMA with additional neuromonitoring data can allow neurosurgeons to better predict and understand perioperative SMA dysfunctions.

Validation of Quantitative Scores Derived From Motor Evoked Potentials in the Assessment of Primary Progressive Multiple Sclerosis: A Longitudinal Study.

Objective: To evaluate the sensitivity to change of differently calculated quantitative scores from motor evoked potentials (MEP) in patients with primary progressive multiple sclerosis (PPMS). Methods: Twenty patients with PPMS had MEP to upper and lower limbs at baseline, years 1 and 2 measured in addition to clinical assessment [Expanded Disability Status Scale (EDSS), ambulation score]; a subsample (n = 9) had a nine-hole peg test (NHPT) and a timed 25-foot walk (T25FW). Quantitative MEP scores for upper limbs (qMEP-UL), lower limbs (qMEP-LL), and all limbs (qMEP) were calculated in three different ways, based on z-transformed central motor conduction time (CMCT), shortest corticomuscular latency (CxM-sh), and mean CxM (CxM-mn). Changes in clinical measures and qMEP metrics were analyzed by repeated-measures analysis of variance (rANOVA), and a factor analysis was performed on change in qMEP metrics. Results: Expanded Disability Status Scale and ambulation score progressed in the rANOVA model (p < 0.05; post-hoc comparison baseline-year 2, p < 0.1). Lower limb and combined qMEP scores showed significant deterioration of latency (p < 0.01, MEP-LL_CxM-sh: p < 0.05) and in post-hoc comparisons (baseline-year 2, p < 0.05), qMEP_CxM-mn even over 1 year (p < 0.05). Effect sizes were higher for qMEP scores than for clinical measures, and slightly but consistently higher when based on CxM-mn compared to CxM-sh or CMCT. Subgroup analysis yielded no indication of higher sensitivity of timed clinical measures over qMEP scores. Two independent factors were detected, the first mainly associated with qMEP-LL, the second with qMEP-UL, explaining 65 and 29% of total variability, respectively. Conclusions: Deterioration in qMEP scores occurs earlier than EDSS progression in patients with PPMS. Upper and lower limb qMEP scores contribute independently to measuring change, and qMEP scores based on mean CxM are advantageous. The capability to detect subclinical changes longitudinally is a unique property of EP and complementary to clinical assessment. These features underline the role of EP as candidate biomarkers to measure effects of therapeutic interventions in PPMS.

Increased Finger-Tapping Related Cerebellar Activation in Cervical Dystonia, Enhanced by Transcranial Stimulation: An Indicator of Compensation?

Background: Cervical dystonia is a movement disorder causing abnormal postures and movements of the head. While the exact pathophysiology of cervical dystonia has not yet been fully elucidated, a growing body of evidence points to the cerebellum as an important node. Methods: Here, we examined the impact of cerebellar interference by transcranial magnetic stimulation on finger-tapping related brain activation and neurophysiological measures of cortical excitability and inhibition in cervical dystonia and controls. Bilateral continuous theta-burst stimulation was used to modulate cerebellar cortical excitability in 16 patients and matched healthy controls. In a functional magnetic resonance imaging arm, data were acquired during simple finger tapping before and after cerebellar stimulation. In a neurophysiological arm, assessment comprised motor-evoked potentials amplitude and cortical silent period duration. Theta-burst stimulation over the dorsal premotor cortex and sham stimulation (neurophysiological arm only) served as control conditions. Results: At baseline, finger tapping was associated with increased activation in the ipsilateral cerebellum in patients compared to controls. Following cerebellar theta-burst stimulation, this pattern was even more pronounced, along with an additional movement-related activation in the contralateral somatosensory region and angular gyrus. Baseline motor-evoked potential amplitudes were higher and cortical silent period duration shorter in patients compared to controls. After cerebellar theta-burst stimulation, cortical silent period duration increased significantly in dystonia patients. Conclusion: We conclude that in cervical dystonia, finger movements-though clinically non-dystonic-are associated with increased activation of the lateral cerebellum, possibly pointing to general motor disorganization, which remains subclinical in most body regions. Enhancement of this activation together with an increase of silent period duration by cerebellar continuous theta-burst stimulation may indicate predominant disinhibitory effects on Purkinje cells, eventually resulting in an inhibition of cerebello-thalamocortical circuits.

Intraoperative Triggered Electromyography Recordings from the External Urethral Sphincter Muscles During Spine Surgeries.

INTRODUCTION: Bowel and bladder function are at risk during tumor resection and other surgeries of the conus, cauda equina, and nerve roots. This study demonstrates the ability to acquire triggered electromyography (t-EMG) from the external urethral sphincter (EUS) muscles by utilizing a urethral catheter with an electrode attached. METHODS: A retrospective analysis of neurophysiological monitoring data from two medical centers was performed. Seven intradural tumors and three tethered cord release surgeries that used urethral sphincter electrodes to record t-EMG were included in the analysis. The patients consisted of five females and five males with ages ranging from eight months to 67 years (median: 49 years). Our neuromonitoring paradigm included upper and lower extremity somatosensory evoked potentials (SSEPs) and transcranial electrical motor evoked potentials (TCeMEPs), as well as spontaneous and triggered electromyography (EMG) from the external anal sphincter (EAS), EUS muscles and lower extremity muscles bilaterally. A catheter with urethral electrodes attached was used for recording spontaneous electromyography (s-EMG), t-EMG, and TCeMEPs from the skeletal muscle of the EUS. Train of four (TOF) was also recorded from the abductor hallucis muscle as well for monitoring the level of muscle relaxant. RESULTS: We were able to successfully record t-EMG responses from the EUS muscles in all patients (100%). It is worthy to note that only one patient presented preoperatively with bladder incontinence, urgency, and frequency. Almost immediately in the postoperative phase, the patient's frequency and urgency improved, and the bladder function normalized within two weeks of having the tumor removed. CONCLUSIONS: In this small series, we were able to acquire t-EMG in 100% of patients when recorded from the EUS using a urethral catheter with electrodes built into it. T-EMGs can be attempted in surgeries that put the function of the pelvic floor at risk. More study is needed to establish better statistical methods, better modality efficacy, and a better understanding of intraoperative countermeasures that may be employed when an alert is encountered to prevent impending neurological sequelae.

Effects of low-gamma tACS on primary motor cortex in implicit motor learning.

In the primary motor cortex (M1), rhythmic activity in the gamma frequency band has been found during movement planning, onset and execution. Although the role of high-gamma oscillatory activity in M1 is well established, the contribution of low-gamma activity is still unexplored. In this study, transcranial alternating current stimulation (tACS) was used with the aim to specifically modulate low-gamma frequency band in M1, during an implicit motor learning task. A 40 Hz-tACS was applied over the left M1 while participants performed a serial reaction time task (SRTT) using their right hand. The task required the repetitive execution of sequential movements in response to sequences of visual stimuli. Sequential blocks were interleaved by a random block, which served as interference to sequence learning. Sham and 1 Hz tACS were used as control. Task performance was examined before, during and after tACS (pre-, online- and post-phase, respectively). Furthermore, cortical reactivity of M1 was assessed in the pre- and post-tACS phases, by measuring motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). Compared to sham and pre-tACS, the 40 Hz stimulation applied during SRTT slowed down response times in blocks that required retrieving previously learned sequences, after performing the random block. In addition, M1 cortical reactivity was selectively inhibited following 40 Hz-tACS, as quantified by reduced MEP amplitude. These results show that low-gamma tACS delivered over M1 during motor learning enhanced susceptibility to interference generated by the random sequence (i.e., proactive interference effect). Importantly, only low-gamma stimulation produced long-lasting effects on M1 cortical reactivity.

Prediction of Motor Recovery Using Quantitative Parameters of Motor Evoked Potential in Patients With Stroke.

OBJECTIVE: To investigate the clinical significance of quantitative parameters in transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP) which can be adopted to predict functional recovery of the upper limb in stroke patients in the early subacute phase. METHODS: One hundred thirteen patients (61 men, 52 women; mean age 57.8±12.2 years) who suffered faiarst-ever stroke were included in this study. All participants underwent TMS-induced MEP session to assess the corticospinal excitability of both hand motor cortices within 3 weeks after stroke onset. After the resting motor threshold (rMT) was assessed, five sweeps of MEP were performed, and the mean amplitude of the MEP was measured. Latency of MEP, volume of the MEP output curve, recruitment ratios, and intracortical inhibition and facilitation were also measured. Motor function was assessed using the Fugl-Meyer Assessment scale (FMA) within 3 weeks and at 3 months after stroke onset. Correlation analysis was performed between TMS-induced MEP derived measures and FMA scores. RESULTS: In the MEP response group, rMT and rMT ratio measures within 3 weeks after stroke onset showed a significant negative correlation with the total and upper limb FMA scores at 3 months after stroke (p<0.001). Multiple regression analysis revealed that FMA score and rMT ratio, but not rMT within 3 weeks were independent prognostic factors for FMA scores at 3 months after stroke. CONCLUSION: These results indicated that the quantitative parameter of TMS-induced MEP, especially rMT ratio in the early subacute phase, could be used as a parameter to predict motor function in patients with stroke.

Ongoing cumulative effects of single TMS pulses on corticospinal excitability: An intra- and inter-block investigation.

OBJECTIVE: To evaluate the effects of several single TMS pulses, delivered at two different inter-trial intervals (ITIs), on corticospinal excitability. METHODS: Twelve healthy volunteers participated in two experimental sessions, during which TMS pulses were delivered at random or at fixed ITIs. The TMS single pulse-induced modulation of corticospinal output (motor evoked potential amplitude - MEP) was evaluated on-line. Each session began with a baseline block, followed by 10 blocks, with 20 TMS pulses each. Intra- and inter-block effects were valuated using an ANOVA model, through nested random effect on subjects considering the subject-specific variability. RESULTS: The delivery of successive TMS pulses significantly changed both intra-block and inter-block cortical excitability, as demonstrated by an increase in the amplitude of MEPs (p<0.001) and supported through trend analyses, showing a perfect linear trend for inter-block levels (R(2)=1) and nearly linear trend for intra-block levels (R(2)=0.97). The MEPs significantly increased when the TMS pulses were delivered at both random and fixed ITIs. CONCLUSIONS: Single TMS pulses induce cumulative changes in neural activity during the same stimulation, resulting in a motor cortical excitability increase. SIGNIFICANCE: Particular attention should be taken when several single TMS pulses are delivered in research and clinical settings for diagnostic and therapeutic purposes.

Elevated serum creatine kinase after neurosurgeries in lateral position with intraoperative neurophysiological monitoring is associated with OP duration, BMI and age.

OBJECTIVES: Elevated serum levels of creatine kinase (CK) reflect skeletal muscle injury, which may lead to renal dysfunction following surgery. High CK levels are known to occur after neurosurgical interventions, especially following lateral positioning, but a consensus on possible risk factors is still lacking. Here we investigate risk factors for postoperative CK excess in a patient population at high risk (lateral position) with a special focus on the influence of intraoperative neurophysiological monitoring (IONM), particularly Motor Evoked Potentials (MEPs). METHODS: We analyzed patient charts from elective surgeries in lateral position between 2010 and 2012 and where IONM was performed and where postoperative CK-levels were available. In these patients, the anesthesia regimen excluded muscle relaxants. Patient charts were reviewed retrospectively for patient characteristics, CK levels and indicators of renal dysfunction. The MEP response intensity was measured. These patients were compared to a matched (age, BMI, surgery duration) control group of patients operated with IONM, but operated in prone or supine position. RESULTS: We included 96 patients (55 female, mean age 50years). The maximal CK level (CKmax) occurred on postoperative days 2 or 3 (mean 1763U/L). In a multivariate linear regression model, log(CKmax) correlated positively with duration of surgery (p<0.001) and BMI (p=0.007), and negatively with age (p=0.007), but not with MEP response intensity (p=0.481). We did not observe impaired renal function. CONCLUSIONS: CK excess following neurosurgical procedures in lateral position correlated positively with duration of surgery and BMI and negatively with age. MEP stimulations of the muscles at risk did not cause further CK elevation. SIGNIFICANCE: In patients undergoing long neurosurgeries without muscle relaxants, we recommend special care regarding positioning and perioperative management.

A novel model incorporating two variability sources for describing motor evoked potentials.

OBJECTIVE: Motor evoked potentials (MEPs) play a pivotal role in transcranial magnetic stimulation (TMS), e.g., for determining the motor threshold and probing cortical excitability. Sampled across the range of stimulation strengths, MEPs outline an input-output (IO) curve, which is often used to characterize the corticospinal tract. More detailed understanding of the signal generation and variability of MEPs would provide insight into the underlying physiology and aid correct statistical treatment of MEP data. METHODS: A novel regression model is tested using measured IO data of twelve subjects. The model splits MEP variability into two independent contributions, acting on both sides of a strong sigmoidal nonlinearity that represents neural recruitment. Traditional sigmoidal regression with a single variability source after the nonlinearity is used for comparison. RESULTS: The distribution of MEP amplitudes varied across different stimulation strengths, violating statistical assumptions in traditional regression models. In contrast to the conventional regression model, the dual variability source model better described the IO characteristics including phenomena such as changing distribution spread and skewness along the IO curve. CONCLUSIONS: MEP variability is best described by two sources that most likely separate variability in the initial excitation process from effects occurring later on. The new model enables more accurate and sensitive estimation of the IO curve characteristics, enhancing its power as a detection tool, and may apply to other brain stimulation modalities. Furthermore, it extracts new information from the IO data concerning the neural variability-information that has previously been treated as noise.