Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations.

BACKGROUND: Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. OBJECTIVE: To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. METHODS: A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. RESULTS: Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8-18.0). Populations included typical development (n = 118), perinatal stroke/cerebral palsy (n = 101), mild traumatic brain injury (n = 121) neuropsychiatric disorders (n = 37), and other (n = 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. CONCLUSIONS: Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.

Accuracy of Postoperative Risk Scores for Survival Prediction in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 Continuous-Flow Left Ventricular Assist Device Recipients.

In this study, we sought to determine the accuracy of several critical care risk scores for predicting survival of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 patients after continuous-flow left ventricular assist device (CF-LVAD) placement. We retrospectively analyzed the records of 605 patients who underwent CF-LVAD implantation between 2003 and 2016. We calculated the preoperative HeartMate II Risk Score (HMRS) and preoperative Right Ventricular Failure Risk Score (RVFRS) and the following risk scores for postoperative days 1-5: HMRS, RVFRS, Model for End-stage Liver Disease (MELD), MELD-eXcluding International Normalized Ratio, Post Cardiac Surgery (POCAS) risk score, Sequential Organ Failure Assessment (SOFA) risk score, and Acute Physiology and Chronic Health Evaluation III. The preoperative scores and the postoperative day 1, 5-day mean, and 5-day maximum scores were entered into a receiver operating characteristic curve analysis to examine accuracy for predicting 30-day, 90-day, and 1-year survival. The mean POCAS score was the best predictor of 30-day and 90-day survival (area under the curve [AUC] = 0.869 and 0.816). The postoperative mean RVFRS was the best predictor of 1-year survival (AUC = 0.7908). The postoperative maximum and mean RVFRS and HMRS were more accurate than the preoperative scores. Both of these risk score measurements of acuity in the postoperative intensive care unit setting help predict early mortality after LVAD implantation.

Use of percutaneous closure devices in the removal of central venous catheters from inadvertent arterial catheterizations.

Although rare, misplacement of central venous catheters in supra-aortic arteries is potentially fatal. Five patients had safe catheters removal using percutaneous closure devices. Three patients were coagulopathic, 3 under intensive care and 1 in immediate postoperative limb amputation. Patients were treated successfully, with immediate hemostasis and without complications in a mean follow-up of 12.5 months. Although the number of patients is small, the closure devices proved to be safe. This is a minimally invasive alternative technique in the management of large bore catheters removed from non-compressible puncture sites such as subclavian and brachiocephalic arteries.

Is there evidence that cerebral protection is beneficial? Clinical data.

Advances in angioplasty techniques and the development of low-profile, flexible, tapered nitinol stents designed specifically for carotid applications have made carotid artery stenting a viable alternative to carotid endarterectomy for treatment of occlusive disease of the carotid arteries. During the stenting process, however, debris may be released and cause distal embolization that can lead to stroke or death. Thus, several embolic protection devices have been developed for use in carotid stenting, two of which are available in the United States. In the past 5 years, data from several large trials, series, and registries of carotid artery stenting-reflecting the experience in thousands of patients-have become available. These investigations include the CAVATAS study, the Global Carotid Artery Stent Registry, the SAPPHIRE study, the ARCHeR trials, the CABERNET registry, the BEACH registry, the SECuRITY registry, the German Registry, and the EVA-3S trial. The studies have provided considerable evidence that use of an embolic protection device decreases the incidence of cerebral embolic events during carotid stenting in both symptomatic and asymptomatic patients. They have also shown that increased experience with angioplasty in the carotid artery decreases complication rates associated with the procedure, even when a protection device is not employed. Although the benefits of routine use of cerebral protection have not been confirmed by level 1 evidence, a consensus supports such use.

Techniques for carotid artery stenting under cerebral protection.

Carotid angioplasty and stenting is an alternative to carotid endarterectomy in the treatment of carotid artery stenosis. During the stenting process, however, distal embolization usually occurs, and the particles released may cause neurologic problems or death. Thus, the safety of carotid stenting depends partly on use of a cerebral protection device during the procedure. Three principal types of protection mechanisms have been developed: distal balloon occlusion, distal filtration, and proximal occlusion with or without reversal of flow. Products using these mechanisms have been manufactured by a variety of companies, and many are used routinely outside the United States (US). One distal filter, the RX Accunet, has been approved by the US Food and Drug Administration for clinical use. Large clinical trials of most of the newest carotid stents and cerebral protection devices are under way, and some initial results have been reported. Several clinical series in which cerebral protection was employed have also been described. Each type of protection device has advantages and disadvantages, which are discussed in this review.

Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs.

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.

Ultrasonography of the knee.

Sonography is a useful modality in the diagnosis of a wide variety of knee disorders, including lesions of the articular cartilage, tendons and ligaments, menisci, synovial space, and adjacent vessels and muscles. Sonography is noninvasive, rapidly performed, widely available, readily accepted by patients, uses no ionizing radiation, and is relatively inexpensive compared to other conventional imaging studies of the menisci, making it a potentially attractive screening examination for knee injuries. Although it is difficult to state the exact place of sonography in the diagnostic workup of knee disorders, we feel that sonography is vastly underutilized. With additional refinements in ultrasound technology and scanning techniques, we expect further expansion of its role in the evaluation of the knee.

Sonography in the detection of meniscal injuries of the knee: evaluation in cadavers.

We evaluated the ability of high-resolution, real-time sonography to identify and characterize artificially produced lesions in the menisci in human cadaveric knee specimens. In total, 20 lesions created in 10 specimens from five knees were prepared and examined sonographically. Four different types of lesions were created: eight vertical concentric tears, four horizontal tears, four vertical radial tears, and four complex lesions including displaced or amputated meniscal edges. All 20 (100%) of the lesions were visualized sonographically. The vertical concentric tears were the easiest to locate and identify, and appeared as highly echogenic lines in the menisci. Tears of this type as small as 2 mm could be visualized. The vertical radial tears were the most difficult to visualize, and no lesions of this type smaller than 5 mm could be seen. Our study shows that under optimal experimental conditions, sonography is capable of reliably demonstrating even small meniscal tears. On this basis, we believe that further clinical studies of the efficacy of meniscal sonography are both reasonable and necessary.

Effects of carotid denervation on interactions between lung inflation and PaCO2 in modulating phrenic activity.

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration. We examined the role of carotid chemoreceptors in this response using an experimental preparation that allowed independent control of lung inflation and CO2 reflexes. Experiments were conducted in intact (n = 6) and carotid denervated (CBX; n = 12) chloralose/urethane anesthetized dogs. Integrated phrenic amplitude (Phr), f, and the inspiratory (TI) and expiratory durations (TE) were measured as a function of Paw (2-12 cm H2O) at levels of PaCO2 between 30 and 80 mm Hg. In intact dogs: (1) f decreased as Paw increased, and elevated PaCO2 decreased the slope of this relationship; (2) neither PaCO2 nor Paw affected TI; and (3) TE increased hyperbolically with Paw, and elevated PaCO2 attenuated this relationship. In CBX dogs: (1) f decreased as Paw increased, but this relationship was not affected by PaCO2; (2) TI increased as PaCO2 increased but was unaffected by Paw; and (3) TE increased as Paw increased but was unaffected by PaCO2. The results indicate that carotid chemoreceptors are necessary in the mechanism whereby hypercapnia attenuates the effects of Paw on f and TE. Furthermore, carotid denervation reveals an effect of hypercapnia on TI, an effect that is not evident in dogs with functional carotid chemoreceptors.

High resolution sonography of the menisci of the knee.

High-resolution real-time ultrasonography (5, 7.5, and 10 MHz) was used to examine the menisci of the knee in ten normal volunteers and in ten patients with knee injuries. The posterior horns of the medial and lateral menisci were easily demonstrated. Normal anatomy and pathologic changes could be imaged in the menisci, capsular ligaments, and articular cartilage. While the menisci were seen in all subjects, the weight-bearing portion of the femoral articular cartilage could not be seen in several of the symptomatic patients who could not flex their knees. Ultrasound promises to be a useful, noninvasive adjunct to conventional techniques in evaluating the injured knee--especially in assessing the posterior horns of the menisci, an area difficult to assess with arthroscopy.