Objective To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology. Methods Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120 μs using a custom-built cTMS device. Strength–duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data. Results All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength–duration curve time constant is estimated to be 196 μs, 95% CI [181 μs, 210 μs]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies. Conclusions Our strength–duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology. Significance Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.

BackgroundCurrent guidelines recommend that patients with peripheral arterial disease (PAD) cease smoking and be treated with aspirin, statin medications, and angiotensin‐converting enzyme (ACE) inhibitors. The combined effects of multiple guideline‐recommended therapies in patients with symptomatic PAD have not been well characterized.Methods and ResultsWe analyzed a comprehensive database of all patients with claudication or critical limb ischemia (CLI) who underwent diagnostic or interventional lower‐extremity angiography between June 1, 2006 and May 1, 2013 at a multidisciplinary vascular center. Baseline demographics, clinical data, and long‐term outcomes were obtained. Inverse probability of treatment propensity weighting was used to determine the 3‐year risk of major adverse cardiovascular or cerebrovascular events (MACE; myocardial infarction, stroke, or death) and major adverse limb events (MALE; major amputation, thrombolysis, or surgical bypass). Among 739 patients with PAD, 325 (44%) had claudication and 414 (56%) had CLI. Guideline‐recommended therapies at baseline included use of aspirin in 651 (88%), statin medications in 496 (67%), ACE inhibitors in 445 (60%), and smoking abstention in 528 (71%) patients. A total of 237 (32%) patients met all four guideline‐recommended therapies. After adjustment for baseline covariates, patients adhering to all four guideline‐recommended therapies had decreased MACE (hazard ratio [HR], 0.64; 95% CI, 0.45 to 0.89; P=0.009), MALE (HR, 0.55; 95% CI, 0.37 to 0.83; P=0.005), and mortality (HR, 0.56; 95% CI, 0.38 to 0.82; P=0.003), compared to patients receiving less than four of the recommended therapies.ConclusionsIn patients with claudication or CLI, combination treatment with four guideline‐recommended therapies is associated with significant reductions in MACE, MALE, and mortality.

Objectives To determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free survival in critical limb ischemia (CLI) patients. Background CLI is an advanced form of peripheral arterial disease (PAD) associated with nonhealing arterial ulcers and high rates of MACCE and major amputation. While statin medications are recommended for secondary prevention in PAD, their effectiveness in CLI is uncertain. Methods We reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic endovascular intervention from 2006–2012. Propensity scores and inverse probability of treatment weighting were used to adjust for baseline differences between patients taking and not taking statins. Results 246 (65%) patients were prescribed statins. The mean serum low-density lipoprotein (LDL) level was lower in patients prescribed statins (75±28 vs. 96±40 mg/dL, P<0.001). Patients prescribed statins had more baseline comorbidities including diabetes, coronary artery disease, and hypertension, as well as more extensive lower extremity disease (all P <0.05). After propensity weighting, statin therapy was associated with lower one-year rates of MACCE (stroke, myocardial infarction, or death; hazard ratio [HR] 0.53, 95% CI 0.28–0.99), mortality (HR 0.49, 95% CI 0.24–0.97), and major amputation or death (HR 0.53, 95% CI 0.35–0.98). Statin use was also associated with improved lesion patency among patients undergoing infrapopliteal angioplasty. Patients with LDL levels above 130mg/dL had increased hazards of MACCE and mortality compared to patients with lower levels of LDL. Conclusions Statins are associated with lower mortality and MACCE and increased amputation-free survival in CLI patients.

Diabetes mellitus (DM) is a significant risk factor for loss of patency after endovascular intervention, but the contribution of glycemic control to infrapopliteal artery patency among patients with DM is unknown. All percutaneous infrapopliteal interventions among patients with DM from 2006 to 2013 were reviewed and pre-procedure fasting blood glucose (FBG) was recorded. The primary endpoint was primary patency at 1 year as determined by duplex ultrasound. A total of 309 infrapopliteal lesions in 149 patients with DM were treated with balloon angioplasty during the study period. The median FBG was 144 mg/dL. At 1 year, the rate of primary patency was 16% for patients with FBG above the median, compared to 46% for patients with FBG below the median (hazard ratio (HR) 1.82 for FBG ≥144, p=0.005). Amputation rates at 1 year trended higher among patients with high versus low FBG (24% vs 15%, p=0.1). One year major adverse limb event rates were also higher for patients with high versus low FBG (35% vs 23%, p=0.05). Although patients with high FBG were more likely to have insulin-requiring DM (73% vs 50%, p=0.003) the association of high FBG with loss of primary patency remained significant even after adjusting for insulin use as well as other lesion-specific characteristics (adjusted HR 1.8, 95% CI 1.2–2.8). In conclusion, high fasting blood glucose at the time of infrapopliteal balloon angioplasty is associated with significantly decreased primary patency and may also be a risk factor for major adverse limb events among patients with a threatened limb.

Objective While the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT. Methods Left motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT. Results OM-MT was 11.3% higher than EMG-MT (p<0.001), ranging from 0-27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%. Conclusions These findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits. Significance For applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG-MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.