Auditory independent low-intensity ultrasound stimulation of mouse brain is associated with neuronal ERK phosphorylation and an increase of Tbr2 marked neuroprogenitors.

Transcranial ultrasound stimulation is an emerging technique for the development of a non-invasive neuromodulation device for the treatment of various types of neurodegenerations and brain damages. However, there are very few studies that have quantified the optimal ultrasound dosage and the long-term associated effects of transcranial ultrasound treatments of brain diseases. In this study, we used a simple ex vivo hippocampal tissues stimulated by different dosages of ultrasound in combination with different chemical treatments to quantify the required energy for a measurable effect. After determining the most desirable ex vivo stimulation conditions, it was then replicated for the in vivo mouse brains. It was discovered that transcranial ultrasound promoted the increase of Tbr2-expressing neural progenitors in an ASIC1a-dependent manner. Furthermore, such effect was observable at least a week after the initial ultrasound treatments and was not abolished by auditory toxicity.

Low Intensity Ultrasound Induces Epithelial Cell Adhesion Responses.

In this study, we investigated the cellular mechanosensitive responses to a low intensity ultrasound (LIUS) stimulation (ISATA = 1 mW/cm2, pressure = 10 kPa). The dose and temporal effects at cell-substrate adhesion (CSA) at the basal level and cell-cell adhesion (CCA) at the apical level are reported in detail. A model of mouse mammary gland epithelial cells (EpH4) and the phosphorylation of mechanosensitive 130 kDa Crk-associated substrate (p130CAS) as an indicator for cellular responses were used. The intensity of phospho-p130CAS was found to be dependent on LIUS stress level, and the p130CAS was phosphorylated after 1 min stimulation at CSA. The phospho-p130CAS was also found to increase significantly at CCA upon LIUS stimulation. We confirmed that the cellular responses to ultrasound are immediate and dose dependent. Ultrasound affects not only CSA but also CCA. An E-cadherin knockout (EpH4ECad-/-) model also confirmed that phosphorylation of p130CAS at CCA is related to E-cadherins.

The responses of nucleus pulposus cells to pressure and ultrasound stimulation.

A cellular stimulation device with a pressurized chamber is developed to investigate the effect of ultrasound and pressure fluctuation on nucleus pulposus (NP) cells. The pressurized chamber is designed to emulate the in vivo environment of intervertebral discs, which are under dynamic pressure, and to emulate impact during sports and exercise. Both hydrostatic pressure and ultrasound stimulation increase phosphorylation of ERK (pERK) in NP cells, and promote its translocation into nucleus. This increase in pERK levels might be activated through calcium signaling pathways as intracellular calcium in NP cells was strongly elevated by pressure changes.

Piezoelectric stimulation by ultrasound facilitates chondrogenesis of mesenchymal stem cells.

A cellular stimulation device utilizing an AT-cut quartz coverslip mounted on an ultrasonic live imaging chamber is developed to investigate the effect of piezoelectric stimulation. Two types of chambers deliver ultrasound at intensities ranging from 1 to 20 mW/cm2 to mesenchymal stem cells (MSCs) seeded on the quartz coverslip. The quartz coverslip imposes additionally localized electric charges as it vibrates with the stimulation. The device was applied to explore whether piezoelectric stimulation can facilitate chondrogenesis of MSCs. The results suggest piezoelectric stimulation drove clustering of MSCs and consequently facilitated chondrogenesis of MSCs without the use of differentiation media.

Reweighting of the sensory inputs for postural control in patients with cervical spondylotic myelopathy after surgery.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative cervical disease in which the spinal cord is compressed. Patients with CSM experience balance disturbance because of impaired proprioception. The weighting of the sensory inputs for postural control in patients with CSM is unclear. Therefore, this study investigated the weighting of sensory systems in patients with CSM. METHOD: Twenty-four individuals with CSM (CSM group) and 24 age-matched healthy adults (healthy control group) were analyzed in this observational study. The functional outcomes (modified Japanese Orthopaedic Association Scale [mJOA], Japanese Orthopaedic Association Cervical Myelopathy Questionnaire [JOACMEQ], Nurick scale) and static balance (eyes-open and eyes-closed conditions) were assessed for individuals with CSM before surgery, 3 and 6 months after surgery. Time-domain and time-frequency-domain variables of the center of pressure (COP) were analyzed to examine the weighting of the sensory systems. RESULTS: In the CSM group, lower extremity function of mJOA and Nurick scale significantly improved 3 and 6 months after surgery. Before surgery, the COP mean velocity and total energy were significantly higher in the CSM group than in the control group for both vision conditions. Compared with the control group, the CSM group exhibited lower energy content in the moderate-frequency band (i.e., proprioception) and higher energy content in the low-frequency band (i.e., cerebellar, vestibular, and visual systems) under the eyes-open condition. The COP mean velocity of the CSM group significantly decreased 3 months after surgery. The energy content in the low-frequency band (i.e., visual and vestibular systems) of the CSM group was closed to that of the control group 6 months after surgery under the eyes-open condition. CONCLUSION: Before surgery, the patients with CSM may have had compensatory sensory weighting for postural control, with decreased weighting on proprioception and increased weighting on the other three sensory inputs. After surgery, the postural control of the patients with CSM improved, with decreased compensation for the proprioceptive system from the visual and vestibular inputs. However, the improvement remained insufficient because the patients with CSM still had lower weighting on proprioception than the healthy adults did. Therefore, patients with CSM may require balance training and posture education after surgery. TRIAL REGISTRATION: Trial Registration number: NCT03396055 Name of the registry: ClinicalTrials.gov Date of registration: January 10, 2018 - Retrospectively registered Date of enrolment of the first participant to the trial: October 19, 2015.

Design of an ultrasound chamber for cellular excitation and observation.

In this work, a design of integrating ultrasonic transduction with live cell imaging chamber is introduced. The principle of a metal-incident-glass-output acoustic path was used to deliver a uniform energy profile into the imaging/incubation chamber in the form of leaky Lamb waves. The design was applied to examine living mouse mammary gland epithelial cells (EpH4). Significant changes in intracellular activities were observed even at a very low energy intensity level (1 MHz, ISATA = 1 mW/cm2, continuous wave). Live imaging with ultrasonic stimulation provides a different paradigm to interrogate cellular mechanosensitive responses in real time.

Intervertebral disc needle puncture injury can be repaired using a gelatin-poly (γ-glutamic acid) hydrogel: an in vitro bovine biomechanical validation.

PURPOSE: The subtle impairments of the disc due to anular punctures may have an immediate effect on the functional integrity due to the altered intradiscal pressure, hence the subsequent catabolic degradation. This study evaluates functional restoration of needle puncture injured intervertebral discs with a newly developed injectable hydrogel using the quantitative discomanometry (QD) test. The proposed hydrogel is composed of gelatin and poly (γ-glutamic acid) (γ-PGA) and crosslinked with 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC). METHODS: Thirty-six bovine motion segments were distributed into six groups. Needle puncture injured discs were created in all discs except for those in the first group (intact). The second group included injured discs that received no treatment (injury). The remaining four groups included injured discs repaired with injected hydrogels fabricated with different polymer solutions and EDC concentrations including: gelatin/γ-PGA solution crosslinked with the EDC solution at a 10:1 and 40:1 ratio to form the GP/E(10:1) and GP/E(40:1) groups, respectively, and gelatin and γ-PGA solution crosslinked with the EDC solution at a 10:1 ratio to form the G/E(10:1) or P/E(10:1) groups. The QD tests were performed to evaluate disc integrity of all six groups. RESULTS: Among all hydrogel repair groups, the GP/E(10:1) group was found to have the highest leakage and saturate pressure and was the only group comparable to the intact one. CONCLUSIONS: Restoration of disc integrity secondary to needle puncture injury can be achieved via the repair with the newly developed gelatin hydrogel incorporated with γ-PGA and EDC. These slides can be retrieved under Electronic Supplementary Material.

Identification of head control deficits following anterior cervical discectomy and fusion in patients with cervical spondylotic myelopathy.

PURPOSE: To investigate the presence of head control deficits and its course of recovery after anterior cervical discectomy and fusion (ACDF) surgery in cervical spondylotic myelopathy (CSM) patients. METHODS: Thirty-seven CSM patients were assessed for their C2-C7 cervical lordosis, neck Range of Motion (ROM), repositioning accuracy, neck strength as well as surface electromyography of the neck muscle activities during slow head motions. Assessments were performed preoperatively and then at 3- and 6-month postoperatively. RESULTS: No significant difference was found for the C2-C7 cervical lordosis postoperatively at 6-month. ROM was restricted immediately after surgery but recovered over time, however, neck strength remained significantly reduced postoperatively. Reposition accuracy improved immediately after surgery but declined again at 6-month follow-up. In addition, muscle activities required to control head motions showed a continuous reduction postoperatively. CONCLUSIONS: Adequate C2-C7 cervical lordosis was maintained in the current study with improvement of slow head motion control and ROM at 6-month. However, improvement in head position sense was not maintained and neck strength showed continuous declination overtime. Assessment and monitoring of head control deficits should be routinely considered in CSM patients.

Differential segmental motion contribution of single- and two-level anterior cervical discectomy and fusion.

PURPOSE: To determine and compare the biomechanical effects of single- and two-level anterior cervical decompression and fusion (ACDF) on the re-distribution of the segmental contribution to total cervical range of motion (ROM) in a prospective longitudinal design. METHODS: Fifty-one patients undergoing either a single- or two-level ACDF due to cervical disc disease were recruited. Functional radiographs were taken preoperatively and then at 3, 6 and 12-month follow-ups. Global ROM of C2-C7, ROM of the treated functional spinal unit (FSU) and the superior and inferior segmental ROMs were then measured. The relative contribution from the FSU and each of the adjacent segments to total cervical ROM were compared pre- and post-operatively within and between the two groups at each of the time points. RESULTS: Single-level ACDF patients demonstrated a significantly greater total cervical ROM at 6 and 12 months compared with the two-level ACDF group (p = 0.021 and 0.045, respectively). A significantly greater contribution from the FSU to the total ROM was found at 3 months in the two-level ACDF group (p = 0.016), but the greater contribution shifted to the superior adjacent segment at 6 and 12 months (p = 0.025 and 0.046). The two-level ACDF group did not demonstrate a significant difference at 3 months (p = 0.087), but a significant increase in contribution was found at 6 and 12 months (p < 0.01). CONCLUSIONS: Single-level ACDF maintains and restores a more physiological re-distribution of segmental contribution of ROM compared with two-level ACDF, which required longer time to achieve stable FSU immobilization and coupled with significantly increased superior segment contribution.

Biomechanical analysis between PEEK and titanium screw-rods spinal construct subjected to fatigue loading.

STUDY DESIGN: An in vitro fatigue loading test with porcine specimens. OBJECTIVES: To comparatively analyze the in vitro biomechanical performance of Polyetheretherketone (PEEK) and Titanium rods construct subjected to a battery of fatigue loading testing. SUMMARY OF BACKGROUND DATA: PEEK rods construct has been proposed to allow better load sharing among spinal components than the more traditional Titanium rods constructs. However, such proposal has largely derived from single-load in vitro testing and the biomechanical differences when subjected to fatigue loading remain unknown. METHODS: Twenty-four fresh 4-level motion segment were harvested from porcine. Specimens were randomly assigned into 3 groups: (1) intact, (2) destabilized group with Titanium alloy rods, and (3) destabilized group with PEEK rods. All specimens were subjected to a fatigue loading procedure with the disk height and intradiscal pressure (IDP) of the instrumented and adjacent levels were recorded and used for analysis. The stress levels on the rods and bone stress near the screw-bone interface were also collected to investigate the likely failure rates of the 2 constructs. RESULTS: Titanium rods construct demonstrated a minimum amount of loss of disk height and IDP at the instrumented level; however, a significant loss of the disk height and IDP at adjacent levels compared with the intact spine were identified. In contrast, the disk height and IDP of the PEEK rods were found to be comparable with those of the intact spine for all levels. The PEEK rods group also showed significantly less bone stress near the screw-bone interface compared with the Titanium rods group. CONCLUSIONS: The current study has demonstrated the differences in biomechanical characteristics of PEEK and Titanium rods construct when subjected to fatigue loading. More specifically, the result is indicative of the potential benefits of the PEEK rods construct in reducing the risks of adjacent segment disease and implant failure rates.

Exercise training for non-operative and post-operative patient with cervical radiculopathy: a literature review.

[Purpose] Cervical radiculopathy is a clinical condition associated with pain, numbness and/or muscle weaknesses of the upper extremities due to a compression or irritation of the cervical nerve roots. It is usually managed conservatively but surgical intervention is sometimes required for those who fail to respond adequately. This study performed a literature review to determine the effects of exercise on non-operative and post-operative cervical radiculopathy patients. [Methods] The PubMed, MEDLINE, CINAHL and Scopus databases were searched to identify relevant articles published from January 1997 to May 2014, which explicitly stated that an exercise program was employed as an intervention for cervical radiculopathy. The therapeutic effectiveness and outcomes were then classified based on the International Classification of Functioning, Disability and Health (ICF) model. [Results] Eleven studies were identified and included in the final analysis. In these studies, the main forms of exercise training were specific strengthening and general stretching exercises. Levels of evidence were graded as either I or II for all studies according to the Oxford Centre for Evidence-based Medicine. The PEDro Scale score of these studies ranged from 5 to 8. [Conclusion] A review of eleven high-level evidence and high-quality studies revealed that, based on the ICF model, exercise training is beneficial for improving the body function as well as activity participation of cervical radiculopathy patients.

Clinical significance of postdecompression facet joint effusion after minimally invasive decompression for degenerative lumbar spinal stenosis.

STUDY DESIGN: A retrospective case series study. OBJECTIVE: To investigate the clinical significance of postdecompression facet effusion (PDFE) after microendoscopic decompressive laminotomy (MEDL). SUMMARY OF BACKGROUND DATA: The facet joint effusion noted on magnetic resonance imaging was considered as an indicator of degeneration of the facet joints and segmental instability. PDFE occurring after MEDL might imply postdecompression segmental instability. Its clinical significance has not yet been clarified. MATERIALS AND METHODS: From 2005 to 2010, 165 patients with degenerative lumbar spinal stenosis (average age: 64.5, average follow-up: 25.8 mo) who received MEDL were reviewed. We investigated the incidence of PDFE with preoperative and repetitive magnetic resonance imaging at 6 months postoperatively. The clinical data and treatment courses were reviewed. The treatment outcomes were evaluated with Oswestry Disability Index and Japanese Orthopedic Association scores. RESULTS: The incidence of PDFE was 17.0% (n=28), which was significantly higher in patients receiving multilevel decompression and patients with scoliosis or spondylolisthesis. The intensity of low back pain was similar between patients with and without PDFE, but "mechanical" low back pain was only noted in patients with PDFE. Of the 28 patients with PDFE, only 9 symptomatic patients required invasive treatment (5 facet joint steroid injection, 3 revision MEDL, and 1 spinal fusion). Although the postoperative Oswestry Disability Index and Japanese Orthopedic Association scores were significantly worse these 9 patients, the final outcomes were good. Progression of spondylolisthesis was noted in 2 patients without PDFE but no patients with PDFE during the follow-up period. CONCLUSIONS: The relatively high incidence of PDFE after MEDL suggests that injury to the integrity of facet joint is inevitable during decompression of the stenosis, even using minimally invasive techniques. However, the overall stability is well preserved with very rare progression of spondylolisthesis. Most patients with PDFE are asymptomatic. The prognosis of PDFE is very good. Spinal fusion is rarely indicated.

Pullout strength of thoracic pedicle screws improved with cortical bone ratio: a cadaveric study.

BACKGROUND: The application of pedicle screw constructs for the osteoporotic vertebrae remains a serious clinical challenge for spinal surgeons and has been intensely studied recently. However, the exact role of the pedicular cortical bone composition and the screw-bone gap on the screw fixation failure has yet to be quantitatively documented. The current study aims to address this gap in our knowledge and elucidate possible relationships. METHODS: Twelve fresh-frozen human cadaveric thoracic spine vertebrae (T9-T12) were harvested from six human cadavers (five males; one female; 63.5 ± 17 years). A three-dimensional reconstruction of the individual vertebrae was firstly rendered from computed tomography (CT) scan images to allow calculation of the cortical bone ratio. Specimens were then subdivided into three groups: Intact, 1-mm screw-bone gap, and 2-mm screw-bone gap. The gap groups were subjected to a standard cyclic fatigue-loading protocol. The pullout strength of the pedicle screws for all specimens were then determined. RESULTS: The pullout strength of the 1-mm and 2-mm groups were significantly reduced when compared with the intact group. A moderate to excellent positive correlation was identified between the cortical bone area ratio and pullout strength for all groups (r > 0.55). A cortical shell ratio of 0.73 or higher was also found to be a safe cut-off index for screw fixation failure, even with an observable 1-mm screw-bone gap. CONCLUSIONS: The current in vitro cadaveric spine study identified a significant correlation between cortical bone area ratio and the thoracic pedicle screw pullout strength. The presented results also demonstrate that the fatigue-loading-induced screw-bone gap of 1-mm was sufficient to cause a significant decrease in the pullout strength. However, a cortical bone area ratio of 0.73 or higher in this group was able to preserve most of the screw-bone interfacial strength, and subsequently may prevent a complete implant failure.

Enzymatic denaturation versus excessive fatigue loading degeneration: Effects on the time-dependent response of the intervertebral disc.

Degenerative disc disease (DDD), regardless of its phenotype and clinical grade, is widely associated with low back pain (LBP), which remains the single leading cause of disability worldwide. This work provides a quantitative methodology for comparatively investigating artificial IVD degeneration via two popular approaches: enzymatic denaturation and fatigue loading. An in-vitro animal study was used to study the time-dependent responses of forty fresh juvenile porcine thoracic IVDs in conjunction with inverse and forward finite element (FE) simulations. The IVDs were dissected from 6-month-old-juvenile pigs and equally assigned to 5 groups (intact, denatured, low-level, medium-level, high-level fatigue loading). Upon preloading, a sinusoid cyclic load (Peak-to-peak/0.1-to-0.8 MPa) was applied (0.01-10 Hz), and dynamic-mechanical-analyses (DMA) was performed. The DMA outcomes were integrated with a robust meta-model analysis to quantify the poroelastic IVD characteristics, while specimen-specific FE models were developed to study the detailed responses. The results demonstrated that enzymatic denaturation had a more significantly pronounced effect on the resistive strength and shock attenuation capabilities of the intervertebral discs. This can be attributed to the simultaneous disruption of the collagen fibers and water-proteoglycan bonds induced by trypsin digestion. Fatigue loading, on the other hand, primarily influenced the disc's resistance to deformation in a frequency-dependent pattern, where alterations were most noticeable at low loading frequencies. This study confirms the intricate interplay between the biochemical changes induced by enzymatic processes and the mechanical behavior stemming from fatigue loading, suggesting the need for a comprehensive approach to closely mimic the interrelated multifaceted processes of human disc degeneration.

Effects of pilates exercises on radiographic lumbo-pelvic alignment and range of motion in non-specific low back pain patients.

OBJECTIVES: To determine the effects of Pilates exercises on lumbo-pelvic alignment in non-specific low back pain (NSLBP) patients. METHODS: Twenty-two patients (Male:7; Female:15) with NSLBP aged 20-65 years were recruited and classified based on a modified O'Sullivan's classification system into flexion pattern (FP) or active extension pattern (EP) groups. Oswestry Disability index (ODI), Roland-Morris Disability Questionnaire (RMDQ) as well as radiographic lumbar global range of motion (ROM) and lumbo-pelvic alignment were measured Pre- and immediately post-intervention and at 6- and 12-month. The intervention included supervised six-weeks Pilates program with 60 min per session and up to two sessions per week. RESULTS: Lumbar lordosis, sacral slope and sacral inclination were found to be significantly different between the FP and EP groups based on the O'Sullivan's classification system. However, despite the significant changes in RMDQ (p = 0.001), no significant changes were found for any of the alignment parameters (p > 0.05) post intervention for both groups. For lumbar global ROM, a statistically significant change was observed for the EP group (p = 0.028) but not for the FP group (p = 0.249). No significant correlations were identified between any of the self-reported outcomes, radiographic alignment and ROM parameters. CONCLUSIONS: Patients self-perceived long-term functional improvements based on responding to questionnaires after Pilates exercises were not reflected in significant changes in lumbo-pelvic alignment or lumbar ROM. This may be due to the current cohort demonstrating within normal ranges due to the lesser severity of their condition, but further research is needed for clarification.

ASIC3 roles in mechanosensitive elongation of nucleus pulposus cells.

Morphological changes of the nucleus pulposus (NP) cells occur concomitantly as part of the intervertebral disc (IVD) degeneration and excessive mechanical loading has been speculated as a significant key factor for contributing to such morphological changes. Therefore, we hypothesize that stress exerted on NP cells can cause a deformity of nucleus in response. The changes of cell morphology is observed in degenerative nucleus pulposus. One of the reasons for degeneration of NP is due to overloading of NP especially in the obese population. So the nucleus deformity caused by stress/force is of our study interest. To delineate the effects and role of mechanical stress, we developed a 3D assay using hydrogel cultures with a circular hole generated with needle indentation to simulate a local stress concentration along the edge of the hole. A stressed zone, encompassing 100 µm of range from the circular edge, is defined based on stress concentration calculation to enable quantitative analysis against the control zone. Our results demonstrated that the circular hole produces stress-induced morphological changes in NP cells. The tangential elongation of NP cells and their nucleus shape changes in the stressed zone are significantly increased compared to the non-stressed control zone. It is proposed that the cell elongation is a direct response to elevated stress within the stressed zone. Subsequently we found the stress induced morphological changes of the NP cells can be significantly reduced by inhibiting ASIC3. This suggests ASIC3 plays an important role of play in mechano-signaling of NP cells.

On minimal focal distance of a focused ultrasound probe for neuromodulation.

Focal distance is a key parameter for a focused ultrasound probe, especially in mouse brain stimulation where targets are right below the skull. A closed-form solution for the minimal focal distance with a given transducer size was derived in this study to facilitate precise focal spot alignment with targets in the mouse brain. The spherical profile corresponding to the minimal focal distance does not produce accurate focusing. An iterative algorithm based on Snell's law was introduced for lens profile calculation. With a suitable step size, an accurate lens profile can be obtained for the minimal focal distance.

Involvement of ASIC3 and Substance P in Therapeutic Ultrasound-Mediated Analgesia in Mouse Models of Fibromyalgia.

Therapeutic ultrasound (tUS) is widely used in chronic muscle pain control. However, its analgesic molecular mechanism is still not known. Our objective is to reveal the mechanism of the tUS-induced analgesia in mouse models of fibromyalgia. We applied tUS in mice that have developed chronic hyperalgesia induced by intramuscular acidification and determined the tUS frequency at 3 MHz, dosage at 1 W/cm2 (measured output as 6.3 mW/cm2) and 100% duty cycle for 3 minutes having the best analgesic effect. Pharmacological and genetic approaches were used to probe the molecular determinants involved in tUS-mediated analgesia. A second mouse model of fibromyalgia induced by intermittent cold stress was further used to validate the mechanism underlying the tUS-mediated analgesia. The tUS-mediated analgesia was abolished by a pretreatment of NK1 receptor antagonist-RP-67580 or knockout of substance P (Tac1-/-). Besides, the tUS-mediated analgesia was abolished by ASIC3-selective antagonist APETx2 but not TRPV1-selective antagonist capsazepine, suggesting a role for ASIC3. Moreover, the tUS-mediated analgesia was attenuated by ASIC3-selective nonsteroid anti-inflammation drugs (NSAIDs)-aspirin and diclofenac but not by ASIC1a-selective ibuprofen. We next validated the antinociceptive role of substance P signaling in the model induced by intermittent cold stress, in which tUS-mediated analgesia was abolished in mice lacking substance P, NK1R, Asic1a, Asic2b, or Asic3 gene. tUS treatment could activate ASIC3-containing channels in muscle afferents to release substance P intramuscularly and exert an analgesic effect in mouse models of fibromyalgia. NSAIDs should be cautiously used or avoided in the tUS treatment. PERSPECTIVE: Therapeutic ultrasound showed analgesic effects against chronic mechanical hyperalgesia in the mouse model of fibromyalgia through the signaling pathways involving substance P and ASIC3-containing ion channels in muscle afferents. NSAIDs should be cautiously used during tUS treatment.

Intraoperative myelography in minimally invasive decompression for degenerative lumbar spinal stenosis.

STUDY DESIGN: A retrospective comparative series study. OBJECTIVE: To develop an intraoperative myelography protocol and determine its value on the treatment results in microendoscopic decompressive laminotomy (MEDL) for degenerative lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: The MEDL is a minimally invasive but technically demanding technique for decompressing spinal stenosis. An intraoperatively assessing method for adequate decompression is lacking, but may be helpful and has positive value on the treatment results. METHODS: Forty consecutive degenerative lumbar spinal stenosis patients receiving MEDL were included in this study. The earlier 20 patients received MEDL without myelography (the traditional group); the later 20 patients received MEDL with the myelography protocol (the myelography group). An additional intraoperative myelography was performed in the myelography group to help localizing the stenosis before decompression and verifying adequate decompression after decompression. Any residual filling defects identified in the postdecompression myelogram were considered signs of inadequate decompression and additional decompression was performed until they resolved. RESULTS: Inadequate decompression was identified in 4 of 20 patients in the myelography group, but none in the traditional group. Both groups had significant improvement after surgery. However, the myelography group had significantly better results with lower 6-month Oswestry Disability Index (ODI) (6 vs. 10, P=0.049), more ODI improvement (44 vs. 28, P=0.009), higher Japanese Orthopedic Association (JOA) scores (27.5 vs. 24, P=0.043), a higher JOA improvement rate (92.8% vs. 73.2%, P=0.013), and greater decompression effect (56.8% vs. 41.4% cross-sectional dural area, P=0.024). The myelography group also had a higher proportion of patients to have "significant ODI improvement," "JOA success," and "JOA good-to-excellent results." There were no myelography-related complications. CONCLUSIONS: The intraoperative myelography protocol provides a simple method to precisely localize the stenosis and verifies the adequacy of decompression; hence, improves the treatment result of MEDL.

Activation of Mechanosensitive Ion Channels by Ultrasound.

Mechanosensitive channels (MSCs) play an important role in how cells transduce mechanical stimuli into electrical or chemical signals, which provides an interventional possibility through the manipulation of ion channel activation using different mechanical stimulation conditions. With good spatial resolution and depth of penetration, ultrasound is often proposed as the tool of choice for such therapeutic applications. Despite the identification of many ion channels as mechanosensitive in recent years, only a limited number of MSCs have been reported to be activated by ultrasound with substantial evidence. Furthermore, although many therapeutic implications using ultrasound have been explored, few offered insights into the molecular basis and the biological effects induced by ultrasound in relieving pain and accelerate tissue healing. In this review, we examined the literature, in particular studies that provided evidence of cellular responses to ultrasound, with and without the target ion channels. The ultrasound activation conditions were then summarized for these ion channels, and these conditions were related to their mode of activation based on the current biological concepts. The overall goal is to bridge the results relating to the activation of MSCs that is specific for ultrasound with the current knowledge in molecular structure and the available physiological evidence that may have facilitated such phenomena. We discussed how collating the information revealed by available scientific investigations helps in the design of a more effective stimulus device for the proposed translational purposes. Traditionally, studies on the effects of ultrasound have focused largely on its mechanical and physical interaction with the targeted tissue through thermal-based therapies as well as non-thermal mechanisms including ultrasonic cavitation; gas body activation; the direct action of the compressional, tensile and shear stresses; radiation force; and acoustic streaming. However, the current review explores and attempts to establish whether the application of low-intensity ultrasound may be associated with the activation of specific MSCs, which in turn triggers relevant cell signaling as its molecular mechanism in achieving the desired therapeutic effects. Non-invasive brain stimulation has recently become an area of intense research interest for rehabilitation, and the implication of low-intensity ultrasound is particularly critical given the need to minimize heat generation to preserve tissue integrity for such applications.