Effects of stimulus waveform on transcranial magnetic stimulation metrics in proximal and distal arm muscles.

OBJECTIVES: The purpose of this study was to determine the effect of common transcranial magnetic stimulation (TMS) waveforms (monophasic and biphasic) on resting motor threshold (RMT), active motor threshold (AMT), and motor evoked potential (MEP) amplitudes in the biceps and first dorsal interosseous (FDI) because waveforms may affect motor targets differently. We also determined test-retest reliability. METHODS: Ten individuals participated in two sessions of TMS delivered to the motor cortex. Monophasic stimulation to induce a posterior-anterior current in the brain (monoPA) and biphasic posterior-anterior then anterior-posterior (biPA-AP) were applied in each session in random order. In each session, there were four blocks of measurements (2 muscles × 2 waveforms) of RMT, AMT and MEPs at the hotspot location. MEPs were normalized to the maximum EMG signal. RESULTS: RMTs and AMTs were lower for monoPA compared to biPA-AP stimulation for the biceps (p<0.01) and FDI (p<0.01). Normalized MEPs were greater for monoPA compared to biPA-AP stimulation in the FDI (p=0.01) and not different in the biceps (p=0.86). Motor thresholds were not different between sessions suggesting high reliability (p<0.01). Normalized MEPs had very low reliability across sessions in the FDI, and moderate reliability in the biceps. DISCUSSION: Preliminary investigation suggests the effect of TMS waveform on motor thresholds is similar in upper limb proximal and distal muscles, but the effect differs per motor target for MEPs. Further, test-retest reliability of waveform effects was sensitive to target muscle. These findings may contribute to improve the efficacy and reliability of TMS for clinical use.

Intermittent theta burst stimulation modulates biceps brachii corticomotor excitability in individuals with tetraplegia.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (TMS) that can increase corticomotor excitability of hand muscles in individuals with spinal cord injury (SCI). The objective of this study was to determine the effect of iTBS on the corticomotor excitability of the biceps brachii in individuals with tetraplegia. METHODS: Ten individuals with low cervical SCI (C5-C8) and ten nonimpaired individuals completed three independent sessions. Motor evoked potentials (MEPs) served as our measure of corticomotor excitability and were collected before and after iTBS. MEPs were normalized by the electromyography corresponding to maximum voluntary contraction and analyzed using linear mixed effects models to determine the effect of iTBS (active or sham) on normalized MEPs (nMEPs). iTBS effects were compared to a ratio of active and resting motor thresholds as a measurement of corticomotor conductance potential. RESULTS: Relative to sham, active iTBS increased nMEPs over time (p < 0.001) in individuals with SCI, but not nonimpaired individuals (p = 0.915). The amplitude of nMEPs were correlated with the biceps corticomotor conductance potential (p < 0.001), with nMEPs decreasing as the ratio increased at different rates after sham or active iTBS. CONCLUSIONS: Preliminary results suggest that iTBS increases biceps corticomotor excitability in individuals with tetraplegia with effects that may be predicted by corticomotor conductance potential. Clinical trial registration NCT03277521 Registered on clinicaltrials.gov on August 24, 2017.

Effect of neuroanatomy on corticomotor excitability during and after transcranial magnetic stimulation and intermittent theta burst stimulation.

Individual neuroanatomy can influence motor responses to transcranial magnetic stimulation (TMS) and corticomotor excitability after intermittent theta burst stimulation (iTBS). The purpose of this study was to examine the relationship between individual neuroanatomy and both TMS response measured using resting motor threshold (RMT) and iTBS measured using motor evoked potentials (MEPs) targeting the biceps brachii and first dorsal interosseus (FDI). Ten nonimpaired individuals completed sham-controlled iTBS sessions and underwent MRI, from which anatomically accurate head models were generated. Neuroanatomical parameters established through fiber tractography were fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD) at the point of stimulation. Cortical magnetic field induced electric field strength (EFS) was obtained using finite element simulations. A linear mixed effects model was used to assess effects of these parameters on RMT and iTBS (post-iTBS MEPs). FDI RMT was dependent on interactions between EFS and both FTSA and TFC. Biceps RMT was dependent on interactions between EFS and and both FTSA and BSD. There was no groupwide effect of iTBS on the FDI but individual changes in corticomotor excitability scaled with RMT, EFS, BSD, and FTSA. iTBS targeting the biceps was facilitatory, and dependent on FTSA and TFC. MRI-based measures of neuroanatomy highlight how individual anatomy affects motor system responses to different TMS paradigms and may be useful for selecting appropriate motor targets when designing TMS based therapies.

The effect of intermittent theta burst stimulation on corticomotor excitability of the biceps brachii in nonimpaired individuals.

Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (TMS) that can increase corticomotor excitability in distal upper limb muscles, but the effect on the more proximal biceps is unknown. The study objective was to determine the effect of iTBS on corticomotor excitability of the biceps brachii in non-impaired individuals. Ten individuals completed three sessions, and an additional ten individuals completed one session in a secondary study; each session included sham and active iTBS. Resting and active motor thresholds (RMT, AMT) were determined prior to sham and active iTBS. Motor evoked potentials (MEPs) in response to single pulse TMS served as our measure of corticomotor excitability. In our primary cohort, MEPs were recorded with biphasic stimulation to accurately capture the same neurons affected by biphasic iTBS. MEPs were recorded at an intensity of 120% of RMT, or for instances of high RMTs, 100% of the maximum stimulator output (MSO), at baseline, and 10, 20, and 30 minutes after iTBS. MEPs were normalized by the maximum voluntary isometric muscle activity. In the secondary, MEPs were recorded with monophasic stimulation, which increased our ability to record MEPs at 120% of RMT. Linear mixed effects models were used to determine the effect of iTBS on normalized MEPs (nMEPs), with analyses to evaluate the interaction of the biceps AMT:RMT ratio as a measure of corticomotor conductance. Change in nMEPs from baseline did not differ for the active and sham conditions (p = 0.915 ) when MEPs were assessed with biphasic stimulation. With MEPs assessed by monophasic stimulation, there was an increase in biceps nMEPs after active iTBS, and no change in nMEPs after sham. Our results suggest that when RMTs are expected to be high when measured with biphasic stimulation, monophasic stimulation can better capture changes in MEPs induced by iTBS, and biphasic stimulation appears limited in its ability to capture changes in biceps MEPs in nonimpaired individuals. In both cohorts, increased corticomotor excitability after iTBS occurred when the biceps AMT:RMT ratio was high. Thus, the AMT:RMT ratio may be a predictive measure to evaluate the potential for iTBS to increase biceps corticomotor excitability.

Arterial blood pressure and neurologic outcome after resuscitation from cardiac arrest*.

OBJECTIVES: Guidelines for post-cardiac arrest care recommend blood pressure optimization as one component of neuroprotection. Although some retrospective clinical studies suggest that postresuscitation hypotension may be harmful, and laboratory studies suggest that a postresuscitation hypertensive surge may be protective, empirical data are few. In this study, we prospectively measured blood pressure over time during the postresuscitation period and tested its association with neurologic outcome. DESIGN: Single center, prospective observational study from 2009 to 2012. PATIENTS: Inclusion criteria were age 18 years old or older, prearrest independent functional status, resuscitation from cardiac arrest, and comatose immediately after resuscitation. MEASUREMENTS AND MAIN RESULTS: Our research protocol measured blood pressure noninvasively every 15 minutes for the first 6 hours after resuscitation. We calculated the 0- to 6-hour time-weighted average mean arterial pressure and used multivariable logistic regression to test the association between increasing time-weighted average mean arterial pressures and good neurologic outcome, defined as Cerebral Performance Category 1 or 2 at hospital discharge. Among 151 patients, 44 (29%) experienced good neurologic outcome. The association between blood pressure and outcome appears to have a threshold effect at time-weighted average mean arterial pressure value of 70 mm Hg. This threshold (mean arterial pressure > 70 mm Hg) had the strongest association with good neurologic outcome (odds ratio, 4.11; 95% CI, 1.34-12.66; p = 0.014). A sustained intrinsic hypertensive surge was relatively uncommon and was not associated with neurologic outcome. CONCLUSIONS: We found that time-weighted average mean arterial pressure was associated with good neurologic outcome at a threshold of mean arterial pressure greater than 70 mm Hg.

Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post-cardiac arrest syndrome.

BACKGROUND: Partial pressure of arterial CO2 (Paco(2)) is a regulator of cerebral blood flow after brain injury. Recent guidelines for the management of cardiac arrest recommend maintaining Paco(2) at 40 to 45 mm Hg after successful resuscitation; however, there is a paucity of data on the prevalence of Paco(2) derangements during the post-cardiac arrest period and its association with outcome. METHODS AND RESULTS: We analyzed a prospectively compiled and maintained cardiac arrest registry at a single academic medical center. Inclusion criteria are as follows: age ≥18, nontrauma arrest, and comatose after return of spontaneous circulation. We analyzed arterial blood gas data during 0 to 24 hours after the return of spontaneous circulation and determined whether patients had exposure to hypocapnia and hypercapnia (defined as Paco(2) ≤30 mm Hg and Paco(2) ≥50 mm Hg, respectively, based on previous literature). The primary outcome was poor neurological function at hospital discharge, defined as Cerebral Performance Category ≥3. We used multivariable logistic regression, with multiple sensitivity analyses, adjusted for factors known to predict poor outcome, to determine whether post-return of spontaneous circulation hypocapnia and hypercapnia were independent predictors of poor neurological function. Of 193 patients, 52 (27%) had hypocapnia only, 63 (33%) had hypercapnia only, 18 (9%) had both hypocapnia and hypercapnia exposure, and 60 (31%) had no exposure; 74% of patients had poor neurological outcome. Hypocapnia and hypercapnia were independently associated with poor neurological function, odds ratio 2.43 (95% confidence interval, 1.04-5.65) and 2.20 (95% confidence interval, 1.03-4.71), respectively. CONCLUSIONS: Hypocapnia and hypercapnia were common after cardiac arrest and were independently associated with poor neurological outcome. These data suggest that Paco(2) derangements could be potentially harmful for patients after resuscitation from cardiac arrest.

Multiple organ dysfunction after return of spontaneous circulation in postcardiac arrest syndrome.

OBJECTIVES: Recent guidelines for the treatment of postcardiac arrest syndrome recommend optimization of vital organ perfusion after return of spontaneous circulation to reduce the risk of postresuscitation multiple organ injury. However, the prevalence of extracerebral multiple organ dysfunction in postcardiac arrest patients and its association with in-hospital mortality remain unclear. DESIGN: Single-center, prospective observational study. SETTING: Urban academic medical center. PATIENTS: Postcardiac arrest patients. Inclusion criteria were as follows: age older than 17 years, nontrauma cardiac arrest, and comatose after return of spontaneous circulation. INTERVENTIONS: We prospectively captured all extracerebral components of the Sequential Organ Failure Assessment score over the first 72 hours after return of spontaneous circulation. The primary outcome measure was in-hospital mortality. We used multivariate logistic regression to determine if multiple organ dysfunction (defined as the highest extracerebral Sequential Organ Failure Assessment score) was an independent predictor of death, after adjustment for the presence of cerebral injury (defined as not following commands at any point over 0-72 hr). MEASUREMENTS AND MAIN RESULTS: We enrolled 203 postcardiac arrest patients; 96% had some degree of extracerebral organ dysfunction and 66% had severe dysfunction in two or more extracerebral organ systems. The most common extracerebral organ failures were cardiovascular (i.e., vasopressor dependence) and respiratory (i.e., oxygenation impairment). The highest extracerebral Sequential Organ Failure Assessment score over 72 hours had an independent association with in-hospital mortality (odds ratio 1.95 [95% CI, 1.15-3.29]). Of the individual organ systems, only the cardiovascular and respiratory Sequential Organ Failure Assessment scores had an independent association with in-hospital mortality. CONCLUSIONS: The results of this study support the hypothesis that extracerebral organ dysfunction is common and associated with mortality in postcardiac arrest syndrome. This association appears to be driven by postresuscitation hemodynamic dysfunction and oxygenation impairment. Further research is needed to determine the value of hemodynamic and oxygenation optimization as a part of treatment strategies for patients with postcardiac arrest syndrome.

Emergency department inter-hospital transfer for post-cardiac arrest care: initial experience with implementation of a regional cardiac resuscitation center in the United States.

OBJECTIVE: The American Heart Association recently recommended regional cardiac resuscitation centers (CRCs) for post-resuscitation care following out-of-hospital cardiac arrest (OHCA). Our objective was to describe initial experience with CRC implementation. METHODS: Prospective observational study of consecutive post-resuscitation patients transferred from community Emergency Departments (EDs) to a CRC over 9 months. Transfer criteria were: OHCA, return of spontaneous circulation (ROSC), and comatose after ROSC. Incoming patients were received and stabilized in the ED of the CRC where advanced therapeutic hypothermia (TH) modalities were applied. Standardized post-resuscitation care included: ED evaluation for cardiac catheterization, TH (33-34 °C) for 24h, 24h/day critical care physician support, and evidence-based neurological prognostication. Prospective data collection utilized the Utstein template. The primary outcome was survival to hospital discharge with good neurological function [Cerebral Performance Category 1 or 2]. RESULTS: Twenty-seven patients transferred from 11 different hospitals were included. The majority (21/27 [78%]) had arrest characteristics suggesting poor prognosis for survival (i.e. asystole/pulseless electrical activity initial rhythm, absence of bystander cardiopulmonary resuscitation, or an unwitnessed cardiac arrest). The median (IQR) time from transfer initiation to reaching TH target temperature was 7(5-13)h. Ten (37%) patients survived to hospital discharge, and of these 9/10 (90% of survivors, 33% of all patients) had good neurological function. CONCLUSIONS: Despite a high proportion of patients with cardiac arrest characteristics suggesting poor prognosis for survival, we found that one-third of CRC transfers survived with good neurological function. Further research to determine if regional CRCs improve outcomes after cardiac arrest is warranted.

Therapeutic hypothermia and vasopressor dependency after cardiac arrest.

OBJECTIVE: Clinical trials of therapeutic hypothermia (TH) after cardiac arrest excluded patients with persistent hemodynamic instability after return of spontaneous circulation (ROSC), and thus equipoise may exist regarding use of TH in these patients. Our objective was to determine if TH is associated with worsening hemodynamic instability among patients who are vasopressor-dependent after ROSC. METHODS: We performed a prospective observational study in vasopressor-dependent post-cardiac arrest patients. Inclusion criteria were age >17, non-trauma cardiac arrest, comatose after ROSC, and persistent vasopressor dependence. The decision to initiate TH (33-34 ° C) was made by the treating physician. We measured cumulative vasopressor index (CVI) and mean arterial pressure (MAP) every 15 min during the first 6h after ROSC. The outcome measures were change in CVI (primary outcome) and MAP (secondary outcome) over time. We graphed median CVI and MAP over time for the treated and not treated cohorts, and used propensity adjusted repeated measures mixed models to test for an association between TH induction and change in CVI or MAP over time. RESULTS: Seventy-five post-cardiac arrest patients were included (35 treated; 40 not treated). We observed no major differences in CVI or MAP over time between the treated and not treated cohorts. In the mixed models we found no statistically significant association between TH induction and changes in CVI or MAP. CONCLUSION: In patients with vasopressor-dependency after cardiac arrest, the induction of hypothermia was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement.