Features of urine S100B and its ability to rule out intracranial hemorrhage in patients with head trauma: a prospective trial.

PURPOSE: Traumatic brain injury causes morbidity and mortality worldwide. S100B is the most documented emergency brain biomarker and its urine-assay might be advantageous because of easier sampling. The primary aim was to evaluate urine S100B's ability to rule out intracranial hemorrhage. Secondary aims included S100B temporal pattern for 48 h post-trauma and chemical properties of urine that affect urine S100B. METHODS: Patients with head trauma were sampled for serum and urine S100B. Patients who were admitted for intracranial hemorrhage were sampled for 48 h to assess S100B-level, renal function, urine-pH, etc. RESULTS: The negative predictive value of serum S100B was 97.0% [95% confidence interval (CI) 89.5-99.2%] and that of urine S100B was 89.1% (95% CI 85.5-91.9%). The specificity of serum S100B was 34.4% (95% CI 27.7-41.6%) and that of urine was 67.1% (95% CI 59.4-74.1%). Urine-pH correlated strongly with urine S100B during the first 6-h post-trauma. Trend-analysis of receiver operator characteristics of S100B in serum, urine the arithmetic difference between serum and urine S100B showed the largest area under the curve for arithmetic difference, which had a negative predictive value of 93.1% (95% CI 89.1-95.8%) and a specificity of 71.8% (95% CI 64.4-78.4%). CONCLUSION: This study cannot support ruling out intracranial hemorrhage with urine S100B. Urine-pH might affect urine S100B and merits further studies. Serum and urine S100B have poor concordance and interchangeability. The arithmetic difference had a slightly better area under the curve and can be worth exploring in certain subgroups.

A proposed amendment to the current guidelines for mild traumatic brain injury: reducing computerized tomographies while maintaining safety.

PURPOSE: Head trauma is a common complaint in emergency departments. Identifying patients with serious injuries can be difficult and generates many computerized tomographies. Reducing the number of computerized tomographies decreases both cost and radiation exposure. The aim of this study was to evaluate whether the current Scandinavian Neurotrauma Committee guidelines could be revised in such a way that would enable hospitals to perform fewer computerized tomographies while maintaining the ability to identify all patients requiring neurological intervention. METHODS: A retrospective study of the medical records of adult patients suffering a traumatic brain injury was performed. A total of 1671 patients over a period of 365 days were included, and 25 parameters were extracted. Multitrauma patients managed with ATLS™ were excluded. The Scandinavian Neurotrauma Committee guidelines were amended with the previously derived "low-risk proposal" and applied retrospectively to the cohort. RESULTS: Incidence of intracranial hemorrhage was 5.6% (93/1671). Application of the current Scandinavian Neurotrauma Committee guidelines would have resulted in 860 computerized tomographies and would have missed 11 intracranial hemorrhages. The proposed amendment with the low-risk proposal would have resulted in 748 CT scans and would have missed 19 intracranial hemorrhages (a relative reduction of 13%). None of the missed intracranial hemorrhages required neurological intervention. CONCLUSION: For patients with mild and moderate traumatic brain injuries, application of the Scandinavian Neurotrauma Committee guidelines amended with the low-risk proposal may result in a significant reduction of computerized tomographies without missing any patients in need of neurological intervention.

Prospective comparison of capillary and venous brain biomarker S100B: capillary samples have large inter-sample variation and poor correlation with venous samples.

BACKGROUND: Guidelines for the emergency management of mild traumatic brain injury have been used for over a decade and are considered safe. However, they recommend computerized tomography for at least half of these patients. The Scandinavian Neurotrauma Committee guideline uses serum S100B protein level to rule out intracranial hemorrhage. Analysis of capillary serum S100B protein level has not yet been employed for this purpose. The primary aim of this study was to investigate the correlation and agreement of capillary and venous serum S100B protein level over a spectrum of concentrations typical for mild traumatic brain injury. METHODS: Eighteen patients with traumatic intracranial hemorrhage and 39 volunteers without trauma to the head within the past 7 days were recruited. Blood was sampled from patients with intracranial hemorrhage daily up to four consecutive days and healthy volunteers were sampled once during the study. One venous and two capillary samples were drawn at each sampling event. Samples were analyzed using the Cobas e411 S100 electrochemiluminescence assay. RESULTS: Median serum S100B protein level of capillary sampling 1 was 0.12 (IQR 0.075-0.21) µg/l and median serum S100B protein level of capillary sampling 2 was 0.13 (IQR 0.08-0.22) µg/l. Median serum S100B protein level of all venous samples was 0.05 (IQR 0.03-0.07) µg/l. Correlation plots of capillary and venous samples showed poor correlation and Bland-Altman plots showed a large dispersion of samples and wide limits of agreement. CONCLUSION: The results of this study indicate that correlation and agreement between capillary and venous samples are low, and because of this, we cannot recommend studies on capillary serum S100B protein level to rule out intracranial hemorrhage in mild traumatic brain injury. Given the limitations of the current sampling and analysis methods of capillary protein S100B protein level, we conclude that evaluating its predictive ability to rule out intracranial hemorrhage should be withheld until more reliable methods can be incorporated into the study design.

Management of mild traumatic brain injury-trauma energy level and medical history as possible predictors for intracranial hemorrhage.

PURPOSE: Head trauma is common in the emergency department. Identifying the few patients with serious injuries is time consuming and leads to many computerized tomographies (CTs). Reducing the number of CTs would reduce cost and radiation. The aim of this study was to evaluate the characteristics of adults with head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage. METHODS: Medical record data have been collected retrospectively in adult patients with traumatic brain injury. A total of 1638 patients over a period of 384 days were reviewed, and 33 parameters were extracted. Patients with high-energy multitrauma managed with ATLS™ were excluded. The analysis was done with emphasis on patient history, clinical findings, and epidemiological traits. Logistic regression and descriptive statistics were applied. RESULTS: Median age was 58 years (18-101, IQR 35-77). High age, minor head injury, new neurological deficits, and low trauma energy level correlated with intracranial hemorrhage. Patients younger than 59 years, without anticoagulation or antiplatelet therapy who suffered low-energy trauma, had no intracranial hemorrhages. The hemorrhage frequency in the entire cohort was 4.3% (70/1638). In subgroup taking anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and in the platelet-inhibitor subgroup, it was 11.8% (20/169). CONCLUSION: This study demonstrates that patients younger than 59 years with low-energy head trauma, who were not on anticoagulants or platelet inhibitors could possibly be discharged based on patient history. Maybe, there is no need for as extensive medical examination as currently recommended. These findings merit further studies.

Plasma levels of S100B during pregnancy in women developing pre-eclampsia.

OBJECTIVE: S100B is suggested to be a peripheral biomarker of central nervous system injury with increased blood-brain barrier permeability. The aim of this study was to investigate if there is a difference in plasma levels of S100B throughout pregnancy between women developing pre-eclampsia and those who did not. STUDY DESIGN: A nested case-control study within a longitudinal study cohort was performed. Healthy pregnant women were enrolled and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Levels of S100B throughout pregnancy were analyzed with an ELISA assay. RESULTS: The levels of S100B did not change between gestational weeks 10 and 37 (0.047 vs. 0.052; p=0.71) in the healthy controls, but the S100B levels increased between corresponding weeks in women who developed pre-eclampsia (0.052 vs. 0.075; p<0.05). In gestational weeks 33 and 37 women who developed pre-eclampsia had higher levels of S100B than the controls (p=0.047 and p=0.010, respectively). CONCLUSION: S100B levels increase during pregnancy in women who develop pre-eclampsia and there is an increased S100B level in women who develop pre-eclampsia compared with healthy pregnancies several weeks before clinical symptoms of the disease. The increased amount of plasma S100B in women developing pre-eclampsia might be secondary to cerebral vascular damage and S100B is a potential peripheral biomarker reflecting cerebral involvement in pre-eclampsia.

S-100B in serum and urine after traumatic head injury in children.

BACKGROUND: Children with head trauma are frequently seen in many emergency units. The clinical evaluation of these patients is difficult for a number of reasons and improved diagnostic tools are needed. S-100B, a protein found in glial cells, has previously been shown to be a sensible marker for brain damage after head injury in adults, but few studies have focused on its use in children. METHODS: In this study, 111 children with head trauma were included and venous blood and urine samples were taken at arrival (S1 and U1) and 6 hours later (S2 and U2). S-100B levels were analyzed. Clinical and radiologic evaluations were performed according to hospital routine. Two groups were identified- group 1: no computed tomography (CT) scan performed ora CT scan without any sign of trauma-related intracranial pathology (n = 105). Group 2: A CT scan with signs of trauma-related intracranial pathology (n = 6). RESULTS: In group 1, the median (inter quartile range) serum S-100B value in S1-samples was 0.111 microg/L (0.086-0.153), and in group 2, it was 0.282 microg/L (0.195-1.44) (p < 0.01). Also, S2 values significantly differed between the two groups. Urine values were, however, not significantly differing between the groups. CONCLUSIONS: Serum S-100B values within 6 hours after head trauma in children were significantly higher in patients with intracranial pathology compared with those without intracranial complications. Identification of these high-risk patients already in the emergency department is of major importance, and we suggest that S-100B could be a valuable diagnostic tool in addition to those used in clinical practice today.

Inducing any virtual two-dimensional movement in humans by applying muscle tendon vibration.

In humans, tendon vibration evokes illusory sensation of movement. We developed a model mimicking the muscle afferent patterns corresponding to any two-dimensional movement and checked its validity by inducing writing illusory movements through specific sets of muscle vibrators. Three kinds of illusory movements were compared. The first was induced by vibration patterns copying the responses of muscle spindle afferents previously recorded by microneurography during imposed ankle movements. The two others were generated by the model. Sixteen different vibratory patterns were applied to 20 motionless volunteers in the absence of vision. After each vibration sequence, the participants were asked to name the corresponding graphic symbol and then to reproduce the illusory movement perceived. Results showed that the afferent patterns generated by the model were very similar to those recorded microneurographically during actual ankle movements (r=0.82). The model was also very efficient for generating afferent response patterns at the wrist level, if the preferred sensory directions of the wrist muscle groups were first specified. Using recorded and modeled proprioceptive patterns to pilot sets of vibrators placed at the ankle or wrist levels evoked similar illusory movements, which were correctly identified by the participants in three quarters of the trials. Our proprioceptive model, based on neurosensory data recorded in behaving humans, should then be a useful tool in fields of research such as sensorimotor learning, rehabilitation, and virtual reality.

A novel method for neck coordination exercise--a pilot study on persons with chronic non-specific neck pain.

BACKGROUND: Chronic neck pain is a common problem and is often associated with changes in sensorimotor functions, such as reduced proprioceptive acuity of the neck, altered coordination of the cervical muscles, and increased postural sway. In line with these findings there are studies supporting the efficacy of exercises targeting different aspects of sensorimotor function, for example training aimed at improving proprioception and muscle coordination. To further develop this type of exercises we have designed a novel device and method for neck coordination training. The aim of the study was to investigate the clinical applicability of the method and to obtain indications of preliminary effects on sensorimotor functions, symptoms and self-rated characteristics in non-specific chronic neck pain METHODS: The study was designed as an uncontrolled clinical trial including fourteen subjects with chronic non-specific neck pain. A new device was designed to allow for an open skills task with adjustable difficulty. With visual feedback, subjects had to control the movement of a metal ball on a flat surface with a rim strapped on the subjects' head. Eight training sessions were performed over a four week period. Skill acquisition was measured throughout the intervention period. After intervention subjects were interviewed about their experience of the exercise and pain and sensorimotor functions, including the fast and slow components of postural sway and jerkiness-, range-, position sense-, movement time- and velocity of cervical rotation, were measured. At six-month follow up, self-rated pain, health and functioning was collected. RESULTS: The subjects improved their skill to perform the exercise and were overall positive to the method. No residual negative side-effects due to the exercise were reported. After intervention the fast component of postural sway (p = 0.019) and jerkiness of cervical rotation (p = 0.032) were reduced. The follow up showed decreased disability (one out of three indices) and fear of movement, and increased general health (three out of eight dimensions). CONCLUSION: The results support the clinical applicability of the method. The improvements in sensorimotor functions may suggest transfer from the exercise to other, non-task specific motor functions and justifies a future randomized controlled trial.

A comparison of two different assays for determining S-100B in serum and urine.

BACKGROUND: Brain injury after head trauma can be detected by S-100B measurements in serum. Recent preliminary studies indicate that urinary levels of S-100B are also increased after head injury, a finding that is of possible clinical value. The aims of the present study are two-fold: to compare serum measurements of two assays, the Liaison Sangtec 100 system and the Elecsys S100 test, and to investigate to what extent they can detect and measure S-100B in urine. METHODS: A total of 191 serum and 174 urine samples from 107 patients (children aged between 1 and 18 years following head trauma) were measured with both assays. The results were compared using correlation analysis and Bland-Altman difference plots. RESULTS: Serum values of the Sangtec system ranged from 0.02 to 2.28 microg/L, and from 0.005 to 2.13 microg/L for the Elecsys test. Comparisons showed a clear correlation (correlation coefficient 0.80) but not an agreement between the methods. The Sangtec system could only detect S-100B in 20 out of 174 urine samples (range 0.02-0.06 microg/L), whereas the Elecsys test could detect S-100B in 171 samples (range 0.005-0.14 microg/L). No clear relation was observed between the two methods in urine analysis (correlation coefficient 0.60). CONCLUSION: The Sangtec and Elecsys assays are not interchangeable methods when analyzing S-100B in serum or urine samples after head injury.

The Ia afferent feedback of a given movement evokes the illusion of the same movement when returned to the subject via muscle tendon vibration.

The aim of the present study was to further investigate the contribution of primary muscle spindle feedback to proprioception and higher brain functions, such as movement trajectory recognition. For this purpose, complex illusory movements were evoked in subjects by applying patterns of muscle tendon vibration mimicking the natural Ia afferent pattern. Ia afferent messages were previously recorded using microneurographic method from the six main muscle groups acting on the ankle joint during imposed "writing like" movements. The mean Ia afferent pattern was calculated for each muscle group and used as a template to pilot each vibrator. Eleven different vibratory patterns were applied to ten volunteers. Subjects were asked both to copy the perceived illusory movements by hand on a digitizing tablet and to recognize and name the corresponding graphic symbol. The results show that the Ia afferent feedback of a given movement evokes the illusion of the same movement when it is applied to the subject via the appropriate pattern of muscle tendon vibration. The geometry and the kinematic parameters of the imposed and illusory movements are very similar and the so-called "two-thirds power law" is present in the reproduction of the vibration-induced illusory movements. Vibrations within the "natural" frequency range of Ia fibres firing (around 30 Hz) produce clear illusions of movements in all the tested subjects. In addition, increasing the mean frequency of the vibration patterns resulted in a linear increase in the size of the illusory movements. Lastly, the subjects were able to recognize and name the symbols evoked by the vibration-induced primary muscle spindle afferent patterns in 83% of the trials. These findings suggest that the "proprioceptive signature" of a given movement is associated with the corresponding "perceptual signature". The neural mechanisms possibly underlying the sensory to perceptual transformation are discussed in the general framework of "the neuronal population vector model".

Proprioceptive feedback in humans expresses motor invariants during writing.

Proprioceptive feedback from populations of muscle spindle afferents feeds the brain with information relating to the instantaneous velocity and direction of ongoing movements. In this paper, we investigate whether the invariant relationship between the velocity and curvature of a trajectory, i.e. the two-thirds power law, is reflected in this muscle spindle feedback. Sixty unitary muscle spindle afferents from six ankle muscle groups were recorded using intraneural microelectrodes during imposed "writing-like" movements. The movements had kinematic parameters obeying the two-thirds power law and were imposed so that the tip of the foot followed trajectories forming four different letters and six numbers. The responses of the muscle spindle afferent populations were analysed using the population vector model. The results demonstrate that the neuronal trajectories attained from populations of muscle spindles clearly depict the path and kinematic parameters and express the movement invariants, i.e. the trajectory segmentation into units of action and the two-thirds power law. The central vs peripheral origin of such constraints involved in the motor system is discussed.

"Proprioceptive signature" of cursive writing in humans: a multi-population coding.

The goal of the present study was to investigate the firing behavior of populations of muscle spindle afferents in all the muscles acting on the ankle while this joint was being subjected to "writing-like" movements. First it was proposed to determine whether the ensemble of muscle spindles give rise to a unique, specific, and reproducible feedback information characterizing each letter, number or short word. Secondly, we analyzed how the proprioceptive feedback on the whole encodes the spatial and temporal characteristics of writing movements using the "vector population model". The unitary activity of 51 primary and secondary muscle spindle afferents was recorded in the tibial and common peroneal nerves at the level of the popliteal fossea, using the microneurographic method. The units recorded from belonged to the tibialis anterior, the extensor digitorum longus, the extensor hallucis longus, the peroneus lateralis, the gastrocnemius-soleus and the tibialis posterior muscles. The "writing-like" movements were randomly imposed at a "natural" velocity via a computer-controlled machine in a two-dimensional space. In general, muscle spindle afferents from any of the six muscles responded according to the tuning properties of the parent muscle, i.e. increasing their discharge rate during the phases where the direction of movement was within the preferred sensory sector of the parent muscle. The whole trajectory of the writing movements was coded in turn by the activity of Ia afferents arising from all the muscles acting on the joint. Both single afferent responses and population responses were found to be highly specific and reproducible with each graphic sign. The complex multi-muscle afferent pattern involved, with its timing and distribution in the muscle space, seems to constitute a true "proprioceptive signature" for each graphic symbol. The ensemble of muscle spindle afferents were therefore found to encode the instantaneous direction and velocity of writing movements remarkably accurately. It was concluded that the proprioceptive feedback from all the muscles with which the moving joint is equipped provides the CNS with highly specific information that might contribute to a graphic sign identification process.

Proprioceptive population coding of limb position in humans.

The present study investigates the coding of positions reached in a two-dimensional space by populations of muscle spindle afferents. The unitary activity of 35 primary muscle spindle afferents originating from the tibialis anterior, extensor digitorum longus, extensor hallucis longus, and peroneus lateralis muscles were recorded from the common peroneal nerve by the microneurographic technique. The steady mean frequency of discharge was analyzed during 16 passively maintained positions of the tip of the foot. These positions were equally distant from and circularly arranged around the "neutral" position of the ankle. The results showed that a same position of the foot was differently coded depending on whether it was maintained for several seconds or whether it was attained after a movement. Muscle spindle activity was increased or decreased, respectively, when the previous movement lengthened or shortened the parent muscle; the magnitude of change in activity depended on the amount of lengthening or shortening in relation to movement direction. Each muscle surrounding the ankle joint was shown to encode the different spatial positions following a directional tuning curve. Data were analyzed by using the "neuronal population vector model". This model consists of calculating population vectors representing the mean contribution of each muscle population of afferents to the coding of a particular position, and by finally calculating a sum vector. The direction of the sum vector was shown to accurately describe the direction of a given maintained position compared to the initial position. We conclude that muscle spindle position coding is based on afferent information coming from the whole set of muscles crossing a given joint. A given spatial position is associated with a stable muscle afferent inflow where each muscle makes an oriented and weighted contribution to its coding.

The preferred sensory direction of muscle spindle primary endings influences the velocity coding of two-dimensional limb movements in humans.

The present study compares how accurately two different but close velocities of movement are discriminated by populations of muscle spindle primary afferents whether or not one takes into account the direction of the movement and the preferred sensory directions of the units (i.e., the direction of movement to which the afferents are the most sensitive). The activities of 26 muscle spindle primary endings originating from the tibialis anterior, the extensor digitorum longus, the extensor hallucis longus, and the peroneus lateralis muscles were recorded in the lateral peroneal nerve. Their responses to movements imposed at two velocities (12.5 and 18 mm/s) were analyzed. These movements were straight-line movements imposed in eight directions and circular movements in both clockwise and anticlockwise directions. The encoding of the movement velocity was analyzed in two ways. First, the mean frequencies of discharge of the muscle spindle afferents were compared for the two velocities. Second, the data were analyzed using a "neuronal population vector model." This model is based on the idea that such neuronal coding can be analyzed in terms of a series of population vectors (i.e., mean contribution of all the muscle spindle afferents within one directionally tuned muscle) and by finally calculating a sum vector. The results showed no clear and consistent difference in the response frequency of the muscle spindle afferents for the two velocities of movement compared. Rather, the most consistently significant differences between the two velocities were in the lengths of the sum vectors. It is concluded that the encoding of two-dimensional movement velocity relies on populations of muscle spindle afferents coming from the whole set of muscles surrounding a particular joint, each muscle making an instantaneous, oriented, and weighted contribution to the sensory coding of the kinematics parameters.

Increased intra-articular concentration of bradykinin in the temporomandibular joint changes the sensitivity of muscle spindles in dorsal neck muscles in the cat.

The aim of the present study was to investigate to what extent activation of bradykinin-sensitive nerve endings of the temporomandibular joint (TMJ) might induce changes in the muscle spindles output from neck muscles through reflex effects on cervical fusimotor neurones. To this end, 26 muscle spindle afferents (MSAs) emanating from the trapezius and splenius muscles of the anaesthetised cat (alpha-chloralose, initial dosage 60 mg/kg) were recorded during injection of Bradykinin (BK) (12.5-50 microg/ml) in the ipsilateral TMJ. Fifteen (58%) MSAs exhibited statistically significant fusimotor effects to injection of BK into the TMJ. Of the 15, ten MSAs showed a response related to activation of static fusimotor neurones, three MSAs showed a response related to an activation of both static and dynamic fusimotor neurones and two MSAs showed a inhibition of both static and dynamic fusimotor neurones. The control experiments suggests that the effects observed were due to activation of BK sensitive nerve endings in the TMJ. It seems possible that the reflex connections between TMJ nociceptors and the fusimotor-muscle spindle system of dorsal neck muscles might be involved in the pathophysiological mechanisms responsible for the sensory-motor disturbances in the neck region often found on patients with temporomandibular disorders.