Closing the loop: Novel quantitative fMRI approach for manipulation of the sensorimotor loop in tremor.

Tremor is thought to be an effect of oscillatory activity within the sensorimotor network. To date, the underlying pathological brain networks are not fully understood. Disentangling tremor activity from voluntary motor output and sensorimotor feedback systems is challenging. To better understand the intrinsic sensorimotor fingerprint underlying tremor, we aimed to disentangle the sensorimotor system into driving (motor) and feedback/compensatory (sensory) neuronal involvement, and aimed to pinpoint tremor activity in essential tremor (ET) and tremor-dominant Parkinson's disease (PD) with a novel closed-loop approach. Eighteen ET patients, 14 tremor-dominant PD patients, and 18 healthy controls were included. An MR-compatible wrist manipulator was employed during functional MRI (fMRI) while muscle activity during (in)voluntary movements was concurrently recorded using electromyography (EMG). Tremor was quantified based on EMG and correlated to brain activity. Participants performed three tasks: an active wrist motor task, a passive wrist movement task, and rest (no wrist movement). The results in healthy controls proved that our experimental paradigm activated the expected motor and sensory networks separately using the active (motor) and passive (sensory) task. ET patients showed similar patterns of activation within the motor and sensory networks. PD patients had less activity during the active motor task in the cerebellum and basal ganglia compared to ET and healthy controls. EMG showed that in ET, tremor fluctuations correlated positively with activity in the inferior olive region, and that in PD tremor fluctuations correlated positively with cerebellar activity. Our novel approach with an MR-compatible wrist manipulator, allowed to investigate the involvement of the motor and sensory networks separately, and as such to better understand tremor pathophysiology. In ET sensorimotor network function did not differ from healthy controls. PD showed less motor-related activity. Focusing on tremor, our results indicate involvement of the inferior olive in ET tremor modulation, and cerebellar involvement in PD tremor modulation.

Directionality of corticomuscular coupling in essential tremor and cortical myoclonic tremor.

OBJECTIVE: A role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study 'familial cortical myoclonic tremor with epilepsy' (FCMTE) and slow repetitive voluntary movements with a known cortical drive. METHODS: Directionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls. RESULTS: Efferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5-6 Hz. CONCLUSIONS: Possible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling. SIGNIFICANCE: A linear cortical drive is lacking in the majority of ET patients.

Estimating ankle torque and dynamics of the stabilizing mechanism: No need for horizontal ground reaction forces.

Changes in human balance control can objectively be assessed using system identification techniques in combination with support surface translations. However, large, expensive and complex motion platforms are required, which are not suitable for the clinic. A treadmill could be a simple alternative to apply support surface translations. In this paper we first validated the estimation of the joint stiffness of an inverted pendulum using system identification methods in combination with support surface translations, by comparison with the joint stiffness calculated using a linear regression method. Second, we used the system identification method to investigate the effect of horizontal ground reaction forces on the estimation of the ankle torque and the dynamics of the stabilizing mechanism of 12 healthy participants. Ankle torque and resulting frequency response functions, which describes the dynamics of the stabilizing mechanism, were calculated by both including and excluding horizontal ground reaction forces. Results showed that the joint stiffness of an inverted pendulum estimated using system identification is comparable to the joint stiffness estimated by a regression method. Secondly, within the induced body sway angles, the ankle torque and frequency response function of the joint dynamics calculated by both including and excluding horizontal ground reaction forces are similar. Therefore, the horizontal ground reaction forces play a minor role in calculating the ankle torque and frequency response function of the dynamics of the stabilizing mechanism and can thus be omitted.

Effect of Amplitude and Number of Repetitions of the Perturbation on System Identification of Human Balance Control During Stance.

To unravel the underlying mechanisms of human balance control, system identification techniques are applied in combination with dedicated perturbations, like support surface translations. However, it remains unclear what the optimal amplitude and number of repetitions of the perturbation signal are. In this study we investigated the effect of the amplitude and number of repetitions on the identification of the neuromuscular controller (NMC). Healthy participants were asked to stand on a treadmill while small continuous support surface translations were applied in the form of a periodic multisine signal. The perturbation amplitude varied over seven conditions between 0.02 and 0.20 m peak-to-peak (ptp), where 6.5 repetitions of the multisine signal were applied for each amplitude, resulting in a trial length of 130 sec. For one of the conditions, 24 repetitions were recorded. The recorded external perturbation torque, body sway and ankle torque were used to calculate both the relative variability of the frequency response function (FRF) of the NMC, i.e., a measure for precision, depending on the noise-to-signal ratio (NSR) and the nonlinear distortions. Results showed that the perturbation amplitude should be minimally 0.05 m ptp, but higher perturbation amplitudes are preferred since they resulted in a higher precision, due to a lower noise-to-signal ratio (NSR). There is, however, no need to further increase the perturbation amplitude than 0.14 m ptp. Increasing the number of repetitions improves the precision, but the number of repetitions minimally required, depends on the perturbation amplitude and the preferred precision. Nonlinear contributions are low and, for the ankle torque, constant over perturbation amplitude.

Venous Thrombosis in Children with Acute Lymphoblastic Leukemia Treated on DCOG ALL-9 and ALL-10 Protocols: The Effect of Fresh Frozen Plasma.

Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9-12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29-11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13-12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.

Assessment of the underlying systems involved in standing balance: the additional value of electromyography in system identification and parameter estimation.

BACKGROUND: Closed loop system identification (CLSIT) is a method to disentangle the contribution of underlying systems in standing balance. We investigated whether taking into account lower leg muscle activation in CLSIT could improve the reliability and accuracy of estimated parameters identifying the underlying systems. METHODS: Standing balance behaviour of 20 healthy young participants was measured using continuous rotations of the support surface (SS). The dynamic balance behaviour obtained with CLSIT was expressed by sensitivity functions of the ankle torque, body sway and muscle activation of the lower legs to the SS rotation. Balance control models, 1) without activation dynamics, 2) with activation dynamics and 3) with activation dynamics and acceleration feedback, were fitted on the data of all possible combinations of the 3 sensitivity functions. The reliability of the estimated model parameters was represented by the mean relative standard errors of the mean (mSEM) of the estimated parameters, expressed for the basic parameters, the activation dynamics parameters and the acceleration feedback parameter. To investigate the accuracy, a model validation study was performed using simulated data obtained with a comprehensive balance control model. The accuracy of the estimated model parameters was described by the mean relative difference (mDIFF) between the estimated parameters and original parameters. RESULTS: The experimental data showed a low mSEM of the basic parameters, activation dynamics parameters and acceleration feedback parameter by adding muscle activation in combination with activation dynamics and acceleration feedback to the fitted model. From the simulated data, the mDIFF of the basic parameters varied from 22.2-22.4% when estimated using the torque and body sway sensitivity functions. Adding the activation dynamics, acceleration feedback and muscle activation improved mDIFF to 13.1-15.1%. CONCLUSIONS: Adding the muscle activation in combination with the activation dynamics and acceleration feedback to CLSIT improves the accuracy and reliability of the estimated parameters and gives the possibility to separate the neural time delay, electromechanical delay and the intrinsic and reflexive dynamics. To diagnose impaired balance more specifically, it is recommended to add electromyography (EMG) to body sway (with or without torque) measurements in the assessment of the underlying systems.

Computer-based estimation of the hip joint reaction force and hip flexion angle in three different sitting configurations.

Sitting is part of our daily work and leisure activities and can be performed in different configurations. To date, the impact of different sitting configurations on hip joint loading has not been studied. We therefore evaluated the hip joint reaction force (HJRF) and hip flexion angle in a virtual representative male Caucasian population by means of musculoskeletal modelling of three distinct sitting configurations: a simple chair, a car seat and a kneeling chair configuration. The observed median HJRF in relation to body weight and hip flexion angle, respectively, was 22.3% body weight (%BW) and 63° for the simple chair, 22.5%BW and 79° for the car seat and 8.7%BW and 50° for the kneeling chair. Even though the absolute values of HJRF are low compared to the forces generated during dynamic activities, a relative reduction of over 50% in HJRF was observed in the kneeling chair configuration. Second, the hip flexion angles were both in the kneeling chair (-29°) and simple chair configuration (-16°) lower compared to the car seat and, as such, did not reach the threshold value for femoroacetabular conflict. In conclusion, the kneeling chair appears to hold the greatest potential as an ergonomic sitting configuration for the hip joint.

Compliant support surfaces affect sensory reweighting during balance control.

To maintain upright posture and prevent falling, balance control involves the complex interaction between nervous, muscular and sensory systems, such as sensory reweighting. When balance is impaired, compliant foam mats are used in training methods to improve balance control. However, the effect of the compliance of these foam mats on sensory reweighting remains unclear. In this study, eleven healthy subjects maintained standing balance with their eyes open while continuous support surface (SS) rotations disturbed the proprioception of the ankles. Multisine disturbance torques were applied in 9 trials; three levels of SS compliance, combined with three levels of desired SS rotation amplitude. Two trials were repeated with eyes closed. The corrective ankle torques, in response to the SS rotations, were assessed in frequency response functions (FRF). Lower frequency magnitudes (LFM) were calculated by averaging the FRF magnitudes in a lower frequency window, representative for sensory reweighting. Results showed that increasing the SS rotation amplitude leads to a decrease in LFM. In addition there was an interaction effect; the decrease in LFM by increasing the SS rotation amplitude was less when the SS was more compliant. Trials with eyes closed had a larger LFM compared to trials with eyes open. We can conclude that when balance control is trained using foam mats, two different effects should be kept in mind. An increase in SS compliance has a known effect causing larger SS rotations and therefore greater down weighting of proprioceptive information. However, SS compliance itself influences the sensitivity of sensory reweighting to changes in SS rotation amplitude with relatively less reweighting occurring on more compliant surfaces as SS amplitude changes.

Characterizing human skin blood flow regulation in response to different local skin temperature perturbations.

Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact.

Reproducibility of axon reflex-related vasodilation assessed by dynamic thermal imaging in healthy subjects.

INTRODUCTION: Small nerve fiber dysfunction is an early feature of diabetic neuropathy. There is a strong clinical need for a non-invasive method to assess small nerve fiber function. Small nerve fibers mediate axon reflex-related vasodilation and play an important role in thermoregulation. Assessing the reflex vasodilation after local heating might elucidate some aspects of small fiber functioning. In this study, we determined the reproducibility of the reflex vasodilation after short local heating in healthy subjects, assessed with thermal imaging and laser Doppler imaging. METHODS: Healthy subjects underwent six heating rounds in one session (protocol I, N=10) or spread over two visits (protocol II, N=20). Reflex vasodilation was elicited by heating the skin to 42°C with an infrared lamp. Skin temperature and skin blood flow were recorded during heating and recovery with a thermal imaging camera and a laser Doppler imager. Skin temperature curves were fitted with a mathematical model to describe the heating and recovery phase with time constant tau (tauHeat and tauCool1). RESULTS: The reproducibility of tau within a session was moderate to excellent (intra-class correlation coefficient 0.42-0.86) and good (0.71-0.72) between different sessions. Within one session the differences in tauHeat were small (bias±SD -1.3±18.9s); the bias between two visits was -1.2±12.2s. For tauCool1 the differences were also small, 1.4±6.6s within a session and between visits -1.4±11.6s. CONCLUSIONS: The heat induced axon reflex-related vasodilation, assessed with thermal imaging and laser Doppler imaging, was reproducible both within a session and between different sessions. Tau describes the temporal profile in one parameter and represents the effects of all changes including blood flow and as such, is an indicator of the vasodilator function. TauHeat and tauCool1 can accurately describe the dynamics of the axon reflex-related vasodilator response in the heating and recovery phase respectively.

Adaptation of multijoint coordination during standing balance in healthy young and healthy old individuals.

Standing balance requires multijoint coordination between the ankles and hips. We investigated how humans adapt their multijoint coordination to adjust to various conditions and whether the adaptation differed between healthy young participants and healthy elderly. Balance was disturbed by push/pull rods, applying two continuous and independent force disturbances at the level of the hip and between the shoulder blades. In addition, external force fields were applied, represented by an external stiffness at the hip, either stabilizing or destabilizing the participants' balance. Multivariate closed-loop system-identification techniques were used to describe the neuromuscular control mechanisms by quantifying the corrective joint torques as a response to body sway, represented by frequency response functions (FRFs). Model fits on the FRFs resulted in an estimation of time delays, intrinsic stiffness, reflexive stiffness, and reflexive damping of both the ankle and hip joint. The elderly generated similar corrective joint torques but had reduced body sway compared with the young participants, corresponding to the increased FRF magnitude with age. When a stabilizing or destabilizing external force field was applied at the hip, both young and elderly participants adapted their multijoint coordination by lowering or respectively increasing their neuromuscular control actions around the ankles, expressed in a change of FRF magnitude. However, the elderly adapted less compared with the young participants. Model fits on the FRFs showed that elderly had higher intrinsic and reflexive stiffness of the ankle, together with higher time delays of the hip. Furthermore, the elderly adapted their reflexive stiffness around the ankle joint less compared with young participants. These results imply that elderly were stiffer and were less able to adapt to external force fields.

Changes in sensory reweighting of proprioceptive information during standing balance with age and disease.

With sensory reweighting, reliable sensory information is selected over unreliable information during balance by dynamically combining this information. We used system identification techniques to show the weight and the adaptive process of weight change of proprioceptive information during standing balance with age and specific diseases. Ten healthy young subjects (aged between 20 and 30 yr) and 44 elderly subjects (aged above 65 yr) encompassing 10 healthy elderly, 10 with cataract, 10 with polyneuropathy, and 14 with impaired balance, participated in the study. During stance, proprioceptive information of the ankles was disturbed by rotation of the support surface with specific frequency content where disturbance amplitude increased over trials. Body sway and reactive ankle torque were measured to determine sensitivity functions of these responses to the disturbance amplitude. Model fits resulted in a proprioceptive weight (changing over trials), time delay, force feedback, reflexive stiffness, and damping. The proprioceptive weight was higher in healthy elderly compared with young subjects and higher in elderly subjects with cataract and with impaired balance compared with healthy elderly subjects. Proprioceptive weight decreased with increasing disturbance amplitude; decrease was similar in all groups. In all groups, the time delay was higher and the reflexive stiffness was lower compared with young or healthy elderly subjects. In conclusion, proprioceptive information is weighted more with age and in patients with cataract and impaired balance. With age and specific diseases the time delay was higher and reflexive stiffness was lower. These results illustrate the opportunity to detect the underlying cause of impaired balance in the elderly with system identification.

Direct measurement of the intrinsic ankle stiffness during standing.

Ankle stiffness contributes to standing balance, counteracting the destabilizing effect of gravity. The ankle stiffness together with the compliance between the foot and the support surface make up the ankle-foot stiffness, which is relevant to quiet standing. The contribution of the intrinsic ankle-foot stiffness to balance, and the ankle-foot stiffness amplitude dependency remain a topic of debate in the literature. We therefore developed an experimental protocol to directly measure the bilateral intrinsic ankle-foot stiffness during standing balance, and determine its amplitude dependency. By applying fast (40 ms) ramp-and-hold support surface rotations (0.005-0.08 rad) during standing, reflexive contributions could be excluded, and the amplitude dependency of the intrinsic ankle-foot stiffness was investigated. Results showed that reflexive activity could not have biased the torque used for estimating the intrinsic stiffness. Furthermore, subjects required less recovery action to restore balance after bilateral rotations in opposite directions compared to rotations in the same direction. The intrinsic ankle-foot stiffness appears insufficient to ensure balance, ranging from 0.93±0.09 to 0.44±0.06 (normalized to critical stiffness 'mgh'). This implies that changes in muscle activation are required to maintain balance. The non-linear stiffness decrease with increasing rotation amplitude supports the previous published research. With the proposed method reflexive effects can be ruled out from the measured torque without any model assumptions, allowing direct estimation of intrinsic stiffness during standing.

Evidence for sustained cortical involvement in peripheral stretch reflex during the full long latency reflex period.

Adaptation of reflexes to environment and task at hand is a key mechanism in optimal motor control, possibly regulated by the cortex. In order to locate the corticospinal integration, i.e. spinal or supraspinal, and to study the critical temporal window of reflex adaptation, we combined transcranial magnetic stimulation (TMS) and upper extremity muscle stretch reflexes at high temporal precision. In twelve participants (age 49 ± 13 years, eight male), afferent signals were evoked by 40 ms ramp and subsequent hold stretches of the m. flexor carpi radialis (FCR). Motor conduction delays (TMS time of arrival at the muscle) and TMS-motor threshold were individually assessed. Subsequently TMS pulses at 96% of active motor threshold were applied with a resolution of 5-10 ms between 10 ms before and 120 ms after onset of series of FCR stretches. Controlled for the individually assessed motor conduction delay, subthreshold TMS was found to significantly augment EMG responses between 60 and 90 ms after stretch onset. This sensitive temporal window suggests a cortical integration consistent with a long latency reflex period rather than a spinal integration consistent with a short latency reflex period. The potential cortical role in reflex adaptation extends over the full long latency reflex period, suggesting adaptive mechanisms beyond reflex onset.

Parkinson's disease patients compensate for balance control asymmetry.

In Parkinson's disease (PD) subtle balance abnormalities can already be detected in early-stage patients. One feature of impaired balance control in PD is asymmetry: one leg produces more corrective joint torque than the other. We hypothesize that in mild to moderately affected PD patients, the least impaired leg compensates for the more impaired leg. Twenty PD patients and eleven healthy matched control subjects participated. Clinical asymmetry was determined by the difference between the left and right body side scores on the Unified Parkinson's Disease Rating Scale. Balance was perturbed with two independent continuous multisine perturbations in the forward-backward direction. Subsequently, we applied closed-loop system identification, which determined the spectral estimate of the stabilizing mechanisms, for each leg. Balance control behavior was similar in PD patients and control subjects at the ankle, but at the hip stiffness was increased. Control subjects exhibited symmetric balance control, but in PD patients the balance contribution of the leg of the clinically least affected body side was higher whereas the leg of the clinically most affected body side contributed less. The ratio between the legs helped to preserve a normal motor output at the ankle. Our results suggest that PD patients compensate for balance control asymmetries by increasing the relative contribution of the leg of their least affected body side. This compensation appears to be successful at the ankle but is accompanied by an increased stiffness at the hip. We discuss the possible implications of these findings for postural stability and fall risk in PD patients.

Successful use of endoscopy for transcervical cannulation procedures in the goat.

Two methods for transcervical cannulation of the goat were evaluated during a contraception study in 15 adult female Nigerian dwarf and African pygmy goats. Twenty-four transcervical cannulation procedures were conducted in which seven females underwent the procedure 2-3 times. Initially, a rigid 4-mm stainless steel cannula and external light source were used in 19 procedures to introduce the contraceptive compound into the uterus. Placement of the cannula was directed by feel or depth assessment. Of seven females that were euthanized following this procedure, four evidenced complications including penetration of the cervix with the cannula and cervical damage. A 2-mm custom-made endoscope with a specially designed cannula was then used for the remaining five procedures. No complications were found. A single animal, that underwent the endoscopic procedure twice, was euthanized for study purposes and no abnormal findings of the reproductive tract were reported. The use of an endoscope resulted in better outcomes because the uterus could be visualized after traversing the cervix.

Impaired standing balance: the clinical need for closing the loop.

Impaired balance may limit mobility and daily activities, and plays a key role in the elderly falling. Maintaining balance requires a concerted action of the sensory, nervous and motor systems, whereby cause and effect mutually affect each other within a closed loop. Aforementioned systems and their connecting pathways are prone to chronological age and disease-related deterioration. System redundancy allows for compensation strategies, e.g. sensory reweighting, to maintain standing balance in spite of the deterioration of underlying systems. Once those strategies fail, impaired balance and possible falls may occur. Targeted interventions to prevent falling require knowledge of the quality of the underlying systems and the compensation strategies used. As current clinical balance tests only measure the ability to maintain standing balance and cannot distinguish between cause and effect in a closed loop, there is a clear clinical need for new techniques to assess standing balance. A way to disentangle cause-and-effect relations to identify primary defects and compensation strategies is based on the application of external disturbances and system identification techniques, applicable in clinical practice. This paper outlines the multiple deteriorations of the underlying systems that may be involved in standing balance, which have to be detected early to prevent impaired standing balance. An overview of clinically used balance tests shows that early detection of impaired standing balance and identification of causal mechanisms is difficult with current tests, thereby hindering the development of well-timed and target-oriented interventions as described next. Finally, a new approach to assess standing balance and to detect the underlying deteriorations is proposed.

Infantile postoperative encephalopathy: perioperative factors as a cause for concern.

We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were <48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were <60 mm Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were <1 SD of the mean definition of hypotension (<45 mm Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (<35 mm Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants.

Sensory reweighting of proprioceptive information of the left and right leg during human balance control.

To keep balance, information from different sensory systems is integrated to generate corrective torques. Current literature suggests that this information is combined according to the sensory reweighting hypothesis, i.e., more reliable information is weighted more strongly than less reliable information. In this approach, no distinction has been made between the contributions of both legs. In this study, we investigated how proprioceptive information from both legs is combined to maintain upright stance. Healthy subjects maintained balance with eyes closed while proprioceptive information of each leg was perturbed independently by continuous rotations of the support surfaces (SS) and the human body by platform translation. Two conditions were tested: perturbation amplitude of one SS was increased over trials while the other SS 1) did not move or 2) was perturbed with constant amplitude. With the use of system identification techniques, the response of the ankle torques to the perturbation amplitudes (i.e., the torque sensitivity functions) was determined and how much each leg contributed to stabilize stance (i.e., stabilizing mechanisms) was estimated. Increased amplitude of one SS resulted in a decreased torque sensitivity. The torque sensitivity to the constant perturbed SS showed no significant differences. The properties of the stabilizing mechanisms remained constant during perturbations of each SS. This study demonstrates that proprioceptive information from each leg is weighted independently and that the weight decreases with perturbation amplitude. Weighting of proprioceptive information of one leg has no influence on the weight of the proprioceptive information of the other leg. According to the sensory reweighting hypothesis, vestibular information must be up-weighted, because closing the eyes eliminates visual information.

Motor control in complex regional pain syndrome: a kinematic analysis.

This study evaluated movement velocity, frequency, and amplitude, as well as the number of arrests in three different subject groups, by kinematic analysis of repetitive movements during a finger tapping (FT) task. The most affected hands of 80 patients with complex regional pain syndrome (CRPS) were compared with the most affected hands of 60 patients with Parkinson disease (PD) as well as the nondominant hands of 75 healthy control (HC) subjects. Fifteen seconds of FT with thumb and index finger were recorded by a 60-Hz camera, which allowed the whole movement cycle to be evaluated and the above mentioned movement parameters to be calculated. We found that CRPS patients were slower and tapped with more arrests than the two other groups. Moreover, in comparison with the hands of the HC subjects, the unaffected hands of the CRPS patients were also impaired in these domains. Impairment was not related to pain. Dystonic CRPS patients performed less well than CRPS patients without dystonia. In conclusion, this study shows that voluntary motor control in CRPS patients is impaired at both the affected as well as the unaffected side, pointing at involvement of central motor processing circuits.