Diagnostic and therapeutic strategies in early onset scoliosis: A current concept review.

Substantial advances in the treatment of early onset scoliosis (EOS) over the past two to three decades have resulted in significant improvements in health-related quality of life of affected children. In addition to classifications that address the marked heterogeneity of this patient population, increasing understanding of the natural history of the disease, and new implants and treatment techniques have resulted in innovations unlike any other area of pediatric orthopedics. The growing understanding of the interaction between spinal and thoracic growth, as well as dependent lung maturation, has had a lasting impact on the treatment strategy of this potentially life-threatening disease. The previous treatment approach with early corrective fusion gave way to a growth-friendly concept. Despite the steady development of new growth-friendly surgical treatment options, whose efficacy still needs to be validated, as well as a revival of conservative growth control with serial casts and/or braces, the psychosocial burden of the long lasting and complication-prone treatments remains high. As a consequence, EOS still represents one of the greatest pediatric orthopedic challenges.

Safety and efficacy of growth-friendly instrumentation for early-onset scoliosis in patients with spinal muscular atrophy type 1 in the disease-modifying treatment era.

Purpose: To evaluate the safety of growth-friendly instrumentation for early-onset scoliosis (EOS) in patients with spinal muscular atrophy (SMA) type 1 who received disease-modifying treatment (DMT) and analyze short-term efficacy. Methods: Retrospective search was conducted between 2017 and 2023. Patients with genetically confirmed SMA type 1 who were surgically treated for spinal deformity and receiving DMTs (nusinersen, risdiplam, or onasemnogene abeparvovec) were included. SMA types 2 and 3 and patients who do not receive DMTs were excluded. Clinical and radiographic data were collected at preoperative, postoperative, and latest follow-up visits. Results: Twenty-eight patients (mean follow-up: 16 months (range 2-41)) were included. The mean age at surgery was 60 months (range 29-96). Fifteen were treated with dual magnetically controlled growing rods (MCGR), four with unilateral MCGR and a contralateral guided growth system, three with Vertical Expandable Prosthetic Titanium Rib (VEPTR®) implants, five with self-distracting systems, and one with traditional dual growing rods. The mean amount of correction was 57% (44°± 17) for scoliosis and 83% (13°± 11) for pelvic obliquity. The mean T1-12 height gain during surgery was 31 mm (±16 mm), while the mean T1 S1 height gain was 51 mm (±24 mm), and instrumented growth was observed during follow-up. Five patients (18%) developed six serious adverse events: three surgical site infections, two anchor failures, and one rod fracture, and all required unplanned reoperations. No neurologic complication, difficulty during nusinersen injections, or respiratory decline was recorded. Conclusion: We report that spinal deformity in this population can be safely treated with growth-friendly instrumentation, with similar complication rates when compared with SMA type 2.

The global impact of the COVID-19 pandemic on pediatric spinal care: A multi-centric study.

Background: The COVID-19 pandemic has affected healthcare worldwide since December 2019. We aimed to identify the effect of the COVID-19 pandemic on outpatient clinic and surgical volumes and peri-operative complications for pediatric spinal deformities patients. Methods: In this multi-center retrospective study, outpatient visits (in-person and virtual care) and pediatric spine surgeries volumes in four high-volume pediatric spine centers were compared between March and December 2019 and the same period in 2020. Peri-operative complications were collected and compared in the same periods. Descriptive statistics were calculated, and comparative analyses were performed. Results: During the 2020 study period, the outpatient visit (in-person and virtual care) volume decreased during local lockdown periods by 71% for new patients (p < 0.001) and 53% for returning patients (p = 0.03). Overall, for 2020, there was a 20% reduction in new patients (p = 0.001) and 21% decrease in returning patients (p < 0.001). During the pandemic, there was also 20% less overall surgical volume of adolescent idiopathic scoliosis (AIS) patients undergoing primary posterior spinal fusion, with a 70% reduction during lockdown times (p < 0.001). Complication rate and profile were similar between periods. Conclusion: There was a significant decrease in outpatient pediatric spine outpatient visits, particularly new patients, which may increase the proportion of pediatric patients with spinal deformities that present late, meeting surgical indication. This, in combination with the reduction in surgical volume of AIS over the first year of the pandemic, could result in an extended waitlist for surgeries during years to come. Complication rate was similar for both periods, suggesting it is safe to continue elective pediatric spine surgery even in a time of a pandemic. Level of evidence: level IV.

Traditional T1-S1 Measurement of the Spinal Length on X-ray Images Does Not Correlate With the True Length of the Spine.

BACKGROUND: The T1-S1 distance to evaluate spinal length is traditionally measured as a straight line on an anteroposterior radiograph. However, this method may not reflect the true 3-dimensional (3D) spinal length. The objective of the study was to evaluate the difference between the traditional T1-S1 measurement and a 3D reconstruction from standard x-ray imaging. METHODS: Radiological assessment and 3D reconstruction of spinal length in pediatric patients with various spine deformities. The 3D reconstruction derived from standard biplanar spine x-ray images using a specialized but free available software and calibration device. Direct comparison of length, intraobserver variance for repeated measurements, as well as interobserver correlation for both measurement methods and between different levels of training were evaluated. Furthermore, the influence on spinal length by the degree of spinal deformity as well as other factors was analyzed. RESULTS: A total of 39 x-ray images from 35 patients at a mean age of 15.4 years (8.9-26.8 years) were evaluated. There was excellent agreement for intra- and interobserver correlation for both measurement techniques. Spinal length assessed using 3D reconstruction was significantly longer compared with the traditional T1-S1 distance, on average 2.7 cm (0.5-6.1 cm). There was also a significant positive correlation between the maximum extent of the deformity and the difference in spinal length. CONCLUSIONS: Traditional T1-S1 distance significantly underestimates the true length of the spine. A 3D measurement reflects the real length of the spine more adequately. CLINICAL RELEVANCE: Such information is relevant to the treating spine surgeon when planning or assessing therapeutic measures, especially in advanced deformities.

Conservative treatment and outcome of upper cervical spine fractures in young children: A STROBE-compliant case series.

ABSTRACT: Cervical spine (C-spine) fractures in young children are very rare, and little information on treatment modalities and functional, radiographic, and patient-reported outcome exists. In this 2-center, retrospective case series, we assessed subjective and functional mid-term outcomes in children aged ≤5 years whose C-spine fractures were treated nonoperatively.Between 2000 and 2018, 6 children (median age at injury: 23.5 months; range: 16-31 months) with C1 or C2 injuries were treated with Minerva cast/brace or soft collar brace at 1 of the 2 study centers. Two patients suffered C1 fractures, and 4 patients had lysis of the odontoid synchondrosis. Overall, 3 children had sustained polytrauma. One child died due to the consequences of massive head injury.For the primary outcome parameter, we recorded subjective symptoms such as pain and functional restrictions due to the sequelae of C-spine injuries at follow-up.Based on medical records, we also assessed the causes of injury, diagnostic procedures, treatments and complications, and time to fracture consolidation.Median follow-up of the 5 surviving children was 51 months (range: 36-160 months). At the latest follow-up, 4 of 5 children did not complain of any pain. One child who sustained an open head injury in combination with a subluxation of the odontoid and undisplaced fracture of the massa lateralis reported occasional headache. All patients experienced complete fracture healing and normal range of motion of the cervical spine.Median duration of cast/brace treatment was 8.5 weeks. Fracture healing was confirmed by computed tomography in all patients.All C-spine injuries were managed with either Minerva cast/Halo brace or soft collar brace without complications.In our retrospective case series, nonoperative treatment of atlas fractures and dislocations or subluxations of the odontoid in young children using Minerva casts or prefabricated Halo braces resulted in good subjective and functional outcomes at mid-term. We observed no complications of conservative treatment of C1 and C2 injuries in young children.

Long term outcome of vertical expandable prosthetic titanium rib treatment in children with early onset scoliosis.

The vertical expandable prosthetic titanium rib (VEPTR) device was originally developed for the treatment of thoracic insufficiency syndrome with the aim of improving respiratory function of affected patients. Although clinically obvious, the changes in pulmonary function of VEPTR-treated patients are difficult to assess when using common lung function tests, and newer techniques based on functional magnetic resonance imaging (MRI) are currently being evaluated. The potential of improving lung function and simultaneously controlling the spinal deformity has continuously broadened the spectrum of indications for VEPTR, not least due to the frequent reports of complications with spine-based traditional growing rods (tGR). However, the initial enthusiasm of spine-sparing deformity correction has progressively subsided with the increasing number of reports on complications, including the detection of extraspinal ossifications along the implants and across ribs. The avoidance of repetitive surgical implant lengthening with the availability of motorized distraction-based implants has further diminished the use of VEPTR, especially in the absence of volume-depletion deformities of the thorax. In view of the still scarce reporting on the ultimate strategy of VEPTR treatment and the lack of long-term follow-up of patients receiving growth-sparing surgery, only limited conclusions can be drawn so far. Based on the available reports, however, the intended deformity corrections with final fusion surgeries can be achieved to a rather limited extent, while the complication and reoperation rates are still very high.

Radiographic Outcome and Complication Rate of 34 Graduates After Treatment With Vertical Expandable Prosthetic Titanium Rib (VEPTR): A Single Center Report.

BACKGROUND: The final strategy for graduates from growth-sparing surgery is challenging. The purpose of this study was to evaluate the radiographic outcome and complications of patients with early onset scoliosis (EOS) who have graduated from vertical expandable prosthetic titanium rib (VEPTR) treatment, either undergoing final fusion surgery or following a nonfusion approach. METHODS: Final treatment for VEPTR graduates was divided in "VEPTR in situ without final fusion," "removal of VEPTR without final fusion," and "removal of VEPTR with instrumented final fusion." Radiographic evaluations included main coronal Cobb angle and main kyphosis pre and post VEPTR implantation, at the end of implant lengthening, after final fusion (if applicable), and at latest follow-up. Complications during VEPTR treatment and in case of final fusion were reported. RESULTS: In total, 34 VEPTR graduates were included; 17 underwent final fusion surgery, and 17 followed a nonfusion strategy. Average coronal Cobb angle before VEPTR implantation was 70±23 degrees (range, 21 to 121 degrees), and 65±22 degrees (range, 17 to 119 degrees) at latest follow-up. Average main kyphosis angle was 53±27 degrees (range, 6 to 137 degrees) before VEPTR, and 69±34 degrees (range, 10 to 150 degrees) at latest follow-up. There was a 41% complication rate with final fusion surgery. CONCLUSIONS: There is a high complication rate during VEPTR treatment and with final fusion surgery. The stiffness of the spine and thorax allow for only limited correction when performing a final instrumented spondylodesis. Avoiding final fusion may be a viable alternative in case of good coronal and sagittal alignment. LEVEL OF EVIDENCE: Level IV-therapeutic.

Spinal Surgery With Electrically Evoked Potential Monitoring and Monopolar Electrocautery: Is Prior Removal of a Cochlear Implant Necessary?

: Transcranial electric stimulation to generate motor evoked potentials in lower limb muscles is the standard technique used to monitor spinal cord efferent pathways during surgical correction for spinal deformities. Monopolar electrical cauterization is also used by default in the thoracic and lumbar area of the spine during this kind of surgery to prevent major blood loss. Owing to the high levels of current used, both techniques are considered contraindicative if the patient has a cochlear implant (CI). Here, we present a CI patient who underwent corrective spinal fusion surgery for a severe kyphoscoliotic spinal deformity on whom both techniques were used without any negative effects on the CI function. A major improvement in sagittal body balance was achieved with no loss in implant-aided hearing levels. These results add to reports that CI manufactures should review their evidence underlying recommendations that transcranial electric stimulation and upper thoracic monopolar electrical cauterization are high risk for CI users, possibly initiating verification studies.

Delayed diagnosis of fractured anterior arch of the atlas in a young child.

A 2-year-old girl fell off a bunk bed onto a parquet floor. She immediately reported neck pain and presented with muscle spasm and limited motion of the cervical spine (C-spine). Plain X-rays of the C-spine showed no osseous lesion. Owing to persisting pain and limited motion in the neck, MRI of the C-spine was obtained which revealed intact ligaments and cervical spinal cord, as well as soft tissue swelling in front of the anterior arch of the atlas. Subsequent CT of the C-spine confirmed a complete, undisplaced fracture of the anterior arch of the atlas (Gehweiler type I fracture). A Minerva cast was applied for 2 months, followed by a soft cervical collar. Persistent neck pain and limited range of motion of the neck after a fall may be indicative of atlas fracture that should be ruled out by CT.

Quantifying spinal gait kinematics using an enhanced optical motion capture approach in adolescent idiopathic scoliosis.

BACKGROUND AND PURPOSE: The pathogenesis of adolescent idiopathic scoliosis (AIS) remains poorly understood. Previous research has indicated possible relationships between kinematics of the spine, pelvis and lower extremities during gait and the progression of AIS, but adequate evidence on spinal kinematics is lacking. The aim of this study was to provide a detailed assessment of spinal gait kinematics in AIS patients compared to asymptomatic controls. METHODS: Fourteen AIS patients and 15 asymptomatic controls were included. Through introducing a previously validated enhanced trunk marker set, sagittal and frontal spinal curvature angles as well as general trunk kinematics were measured during gait using a 12-camera Vicon motion capture system. Group comparisons were conducted using T-tests and relationships between kinematic parameters and severity of scoliosis (Cobb angle) were investigated using regression analyses. RESULTS: The sagittal thoracic curvature angle in AIS patients showed on average 10.7° (4.2°, 17.3°) less kyphosis but 4.9° (2.3°, 7.6°) more range of motion (Cobb angle-dependent (R(2)=0.503)). In the frontal plane, thoracic and thoracolumbar/lumbar curvature angles indicated average lateral deviations in AIS patients. General trunk kinematics and spatio-temporal gait parameters, however, did not show any clinically relevant differences between the groups. CONCLUSIONS: This demonstrates that the dynamic functionality of the scoliotic spine can be assessed using advanced non-invasive optical approaches and that these should become standard in clinical gait analysis. Furthermore, curvature angle data might be used to drive sophisticated computer simulation models in order to gain an insight into the dynamic loading behavior of the scoliotic spine during gait.

Bacterial colonization of VEPTR implants under repeated expansions in children with severe early onset spinal deformities.

PURPOSE: Historically, severe spinal and thoracic deformities in children were treated with early long spinal fusions. This prevented further growth of the spine and thorax and often led to small stiff thoraces. Therefore, growth-retaining implants, like vertical expandable titanium ribs (VEPTR), were developed to stimulate thoracic and spinal growth. To accommodate growth, these implants have to be expanded every 6 months. Infection rates of up to 2 % per procedure are reported. Exchange of implant parts allows analyzing the development of implant-related infections and subclinical colonizations. METHODS: In this prospective study, all patients undergoing repeat VEPTR expansion procedures at our institution were included. Preoperatively, clinical signs of infection were documented, and blood samples were taken. The removed implants were treated by sonication and microbiologically analyzed. The clinical follow-up was documented. RESULTS: From January 2009 to May 2012, 39 children with 163 re-operations were included. Four of the 39 patients (10 %) developed clinical apparent infections and had implant removal. These were excluded and analyzed separately. Of 144 procedures, implant parts were eligible for analysis. Implant colonization was detected by sonication in 24 of 144 (16 %) operations in 18 out of 39 (46 %) patients. Repeated detection occurred in 5 (14 %) patients. No risk factors for colonization could be identified. CONCLUSION: The rate of implant colonization is 4.5 times higher than the rate of manifest infections in VEPTR patients. Colonization may lead to a manifest infection over time. The knowledge of persistent implant colonization may change the treatment algorithm in patients with growth-retaining implants.

Patella instability in children and adolescents.

Patellar instabilities are the most common knee pathologies during growth. Congenital dislocations are rare. Extensive, early soft tissue releases relocate the extensor mechanism and may enable normal development of the femoro-patellar anatomy.Conservative management is the preferred strategy after a 'first-time' traumatic dislocation. In cases with concomitant anatomical predisposing factors such as trochlear dysplasia, malalignment, malrotation or ligamentous laxity, surgical reconstruction must be considered. The same applies to recurrent dislocations with pain, a sense of instability or re-dislocations which may also lead to functional compensatory mechanisms (quadriceps-avoiding gait in knee extension) or cartilaginous lesions with subsequent patello-femoral osteoarthritis. The decision-making process guiding surgical re-alignment includes analysis with standard radiographs and MRI of the trochlear groove, joint cartilage and medial patello-femoral ligament (MPFL). Careful evaluation of dynamic and static stabilisers is essential: the medial patello-femoral ligament provides stability during the first 20° of flexion, and the trochlear groove thereafter.Excessive femoral anteversion, general ligamentous laxity with increased femoro-tibial rotation, patella alta and increased distance between the tibial tuberosity and the trochlear groove must also be taken into account and surgically corrected.In cases with ongoing dislocations during skeletal immaturity, soft tissue procedures must suffice: reconstruction of the medial patello-femoral ligament as a standalone procedure or in conjuction with more complex distal realignment of the quadriceps mechanism may lead to a permanent stable result, or at least buys time until a definitive bony procedure is performed. Cite this article: Hasler CC, Studer D. Patella instability in children and adolescents. EFORT Open Rev 2016;1:160-166. DOI: 10.1302/2058-5241.1.000018.

Using Skin Markers for Spinal Curvature Quantification in Main Thoracic Adolescent Idiopathic Scoliosis: An Explorative Radiographic Study.

BACKGROUND AND PURPOSE: Although the relevance of understanding spinal kinematics during functional activities in patients with complex spinal deformities is undisputed among researchers and clinicians, evidence using skin marker-based motion capture systems is still limited to a handful of studies, mostly conducted on healthy subjects and using non-validated marker configurations. The current study therefore aimed to explore the validity of a previously developed enhanced trunk marker set for the static measurement of spinal curvature angles in patients with main thoracic adolescent idiopathic scoliosis. In addition, the impact of inaccurate marker placement on curvature angle calculation was investigated. METHODS: Ten patients (Cobb angle: 44.4±17.7 degrees) were equipped with radio-opaque markers on selected spinous processes and underwent a standard biplanar radiographic examination. Subsequently, radio-opaque markers were replaced with retro-reflective markers and the patients were measured statically using a Vicon motion capture system. Thoracolumbar/lumbar and thoracic curvature angles in the sagittal and frontal planes were calculated based on the centers of area of the vertebral bodies and radio-opaque markers as well as the three-dimensional position of the retro-reflective markers. To investigate curvature angle estimation accuracy, linear regression analyses among the respective parameters were used. The impact of inaccurate marker placement was explored using linear regression analyses among the radio-opaque marker- and spinous process-derived curvature angles. RESULTS AND DISCUSSION: The results demonstrate that curvatures angles in the sagittal plane can be measured with reasonable accuracy, whereas in the frontal plane, angles were systematically underestimated, mainly due to the positional and structural deformities of the scoliotic vertebrae. Inaccuracy of marker placement had a greater impact on thoracolumbar/lumbar than thoracic curvature angles. It is suggested that spinal curvature measurements are included in marker-based clinical gait analysis protocols in order to enable a deeper understanding of the biomechanical behavior of the healthy and pathological spine in dynamic situations as well as to comprehensively evaluate treatment effects.

Metamorphosis of human lumbar vertebrae induced by VEPTR growth modulation and stress shielding.

INTRODUCTION: Distraction-based spinal growth modulation by growing rods or vertical expandable prosthetic titanium ribs (VEPTRs) is the mainstay of instrumented operative strategies to correct early onset spinal deformities. In order to objectify the benefits, it has become common sense to measure the gain in spine height by assessing T1-S1 distance on anteroposterior (AP) radiographs. However, by ignoring growth changes on vertebral levels and by limiting measurement to one plane, valuable data is missed regarding the three-dimensional (3D) effects of growth modulation. This information might be interesting when it comes to final fusion or, even more so, when the protective growing implants are removed and the spine re-exposed to physiologic forces at the end of growth. METHODS: The goal of this retrospective radiographic study was to assess the growth modulating impact of year-long, distraction-based VEPTR treatment on the morphology of single vertebral bodies. We digitally measured lumbar vertebral body height (VBH) and upper endplate depth (VBD) at the time of the index procedure and at follow-up in nine patients with rib-to-ileum constructs (G1) spanning an anatomically normal lumbar spine. Nine patients with congenital thoracic scoliosis and VEPTR rib-to-rib constructs, but uninstrumented lumbar spines, served as controls (G2). All had undergone more than eight half-yearly VEPTR expansions. A Wilcoxon signed-rank test was used for statistical comparison of initial and follow-up VBH, VBD and height/depth (H/D) ratio (significance level 0.05). RESULTS: The average age was 7.1 years (G1) and 5.2 year (G2, p > 0.05) at initial surgery; the average overall follow-up time was 5.5 years (p = 1). In both groups, VBH increased significantly without a significant intergroup difference. Group 1 did not show significant growth in depth, whereas VBD increased significantly in the control group. As a consequence, the H/D ratio increased significantly in group 1 whereas it remained unchanged in group 2. The growth rate for height in mm/year was 1.4 (group 1) and 1.1 (group 2, p = 0.45), and for depth, it was -0.3 and 1.1 (p < 0.05), respectively. CONCLUSIONS: VEPTR growth modulating treatment alters the geometry of vertebral bodies by increasing the H/D ratio. We hypothesize that the implant-related deprivation from axial loads (stress-shielding) impairs anteroposterior growth. The biomechanical consequence of such slender vertebrae when exposed to unprotected loads in case of definitive VEPTR removal at the end of growth is uncertain.

Patient-specific spinal stiffness in AIS: a preoperative and noninvasive method.

INTRODUCTION: The clinical tests currently used to assess spinal biomechanics preoperatively are unable to assess true mechanical spinal stiffness. They rely on spinal displacement without considering the force required to deform a patient's spine. We propose a preoperative method for noninvasively quantifying the three-dimensional patient-specific stiffness of the spines of adolescent idiopathic scoliosis patients. METHODS: The technique combines a novel clinical test with numerical optimization of a finite element model of the patient's spine. RESULTS: A pilot study conducted on five patients showed that the model was able to provide accurate 3D reconstruction of the spine's midline and predict the spine's stiffness for each patient in flexion, bending, and rotation. Statistically significant variation of spinal stiffness was observed between the patients. CONCLUSION: This result confirms that spinal biomechanics is patient-specific, which should be taken into consideration to individualize surgical treatment.

Fine structure of synapses on dendritic spines.

Camillo Golgi's "Reazione Nera" led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM) they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF), which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP) at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin), an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as an appropriate method for studying the fine structure and molecular composition of synapses on dendritic spines.

Direct observation of liquid crystals using cryo-TEM: specimen preparation and low-dose imaging.

Liquid crystals (LCs) represent a challenging group of materials for direct transmission electron microscopy (TEM) studies due to the complications in specimen preparation and the severe radiation damage. In this paper, we summarize a series of specimen preparation methods, including thin film and cryo-sectioning approaches, as a comprehensive toolset enabling high-resolution direct cryo-TEM observation of a broad range of LCs. We also present comparative analysis using cryo-TEM and replica freeze-fracture TEM on both thermotropic and lyotropic LCs. In addition to the revisits of previous practices, some new concepts are introduced, e.g., suspended thermotropic LC thin films, combined high-pressure freezing and cryo-sectioning of lyotropic LCs, and the complementary applications of direct TEM and indirect replica TEM techniques. The significance of subnanometer resolution cryo-TEM observation is demonstrated in a few important issues in LC studies, including providing direct evidences for the existence of nanoscale smectic domains in nematic bent-core thermotropic LCs, comprehensive understanding of the twist-bend nematic phase, and probing the packing of columnar aggregates in lyotropic chromonic LCs. Direct TEM observation opens ways to a variety of TEM techniques, suggesting that TEM (replica, cryo, and in situ techniques), in general, may be a promising part of the solution to the lack of effective structural probe at the molecular scale in LC studies.

Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue.

Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in ∼50 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION: An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS: A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS: Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS: In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.