Search

OBJECTIVE Chronic subdural hematoma (CSDH) is a common neurological disease among elderly adults. The progression of CSDH is an angiogenic process, involving inflammatory mediators that affect vascular permeability, microvascular leakage, and hematoma thickness. The authors aimed to identify biomarkers associated with angiogenesis and vascular permeability that might influence midline shift and hematoma thickness. METHODS Medical records and laboratory data of consecutive patients who underwent surgery for CSDH were analyzed. Collected data were basic demographic data, CSDH classification, CSDH thickness, midline shift, heme oxygenase–1 (HO-1) levels in hematomas, and common laboratory markers. Linear regression analysis was used to evaluate the relationship of CSDH thickness with characteristic variables. The chick chorioallantoic membrane (CAM) assay was used to test the angiogenic potency of identified variables in ex ovo culture of chick embryos. RESULTS In total, 93 patients with CSDH (71.0% male) with a mean age of 71.0 years were included. The mean CSDH thickness and midline shift were 19.7 and 9.8 mm, respectively. The mean levels of HO-1, ferritin, total bilirubin, white blood cells, segmented neutrophils, lymphocytes, platelets, international normalized ratio, and partial thromboplastin time were 36 ng/mL, 14.8 μg/mL, 10.5 mg/dL, 10.3 × 103 cells/μL, 69%, 21.7%, 221.1 × 109 cells/μL, 1.0, and 27.8 seconds, respectively. Pearson correlation analysis revealed that CSDH thickness was positively correlated with midline shift distance (r = 0.218, p < 0.05) but negatively correlated with HO-1 concentration (r = −0.364, p < 0.01) and ferritin level (r = −0.222, p < 0.05). Multivariate linear regression analysis revealed that HO-1 was an independent predictor of CSDH thickness (β = −0.084, p = 0.006). The angiogenic potency of HO-1 in hematoma fluid was tested with the chick CAM assay; topical addition of CSDH fluid with low HO-1 levels promoted neovascularization and microvascular leakage. Addition of HO-1 in a rescue experiment inhibited CSDH fluid–mediated angiogenesis and microvascular leakage. CONCLUSIONS HO-1 is an independent risk factor in CSDH hematomas and is negatively correlated with CSDH thickness. HO-1 may play a role in the pathophysiology and development of CSDH, possibly by preventing neovascularization and reducing capillary fragility and hyperpermeability.

Overdrainage of cerebrospinal fluid is one of the most notorious complications after ventriculoperitoneal shunt implantation. Siphon effect plays a major role in the development of overdrainage. Various overdrainage-preventing devices have been invented to counteract the siphon effect. Though some of the devices are designed to reduce the flow instead of providing antisiphoning effect, they are generally called antisiphon devices (ASDs). The basics of siphoning, the mechanisms and physical properties of currently available devices are described in this article. The clinical efficacy, shunt survival, and considerations on patient factors are also discussed. There are three kinds of ASD design, diaphragm, gravitational, and flow reducing devices. Flow reducing ASD is always open and the flow it controls is relatively stable. On the other hand, it may not provide sufficient flow in nocturnal intracranial pressure elevations. Diaphragm and gravitational devices are sensitive to the position of the patients. Diaphragm device is sensitive to the external pressure and the relative position of the device to the mastoid process. The gravitational device is sensitive to the angle between the axis of the device and the head. Many studies showed encouraging results with gravitational devices. Studies regarding diaphragm devices either showed better or similar outcomes comparing to differential pressure valves. Clinical studies regarding flow-reducing devices and head-to-head comparison between different mechanisms are warranted. This review aims to provide a useful reference for clinical practice of hydrocephalus.

OBJECTIVE Leptomeningeal metastasis (LM) is a challenging scenario in non–small cell lung cancer (NSCLC). Considering that outcomes of treatment modalities stratified by LM chronological patterns related to brain metastasis (BM) are lacking, the aim of this study was to evaluate outcomes and explore prognostic factors. METHODS The authors retrospectively collected data of patients with NSCLC undergoing Ommaya reservoir implantation, ventriculoperitoneal shunt implantation, or lumboperitoneal shunt implantation. Based on radiographic findings and time from diagnosis of NSCLC to LM, the authors divided them into subtypes of LM as follows: LM without BM; LM concurrent with BM; or LM after BM. The Kaplan-Meier method was applied to analyze overall survival (OS) and multivariate Cox regression for prognostic factors. RESULTS Sixty-one patients with LM were included, with a median OS of 8.1 (range 0.2–70.0) months. Forty-three (70.5%) patients had EGFR-mutant disease. Forty-two (68.9%) patients had 19-del or L858R mutation, and one (1.6%) patient had G719A mutation. Fifty-seven (93.4%) patients had hydrocephalus. Twenty-one (34.4%) patients received whole-brain radiotherapy before LM diagnosis, 3 (4.9%) patients underwent operation for BMs before LM diagnosis, and 42 (68.9%) patients received EGFR tyrosine kinase inhibitor (TKI) therapy before LM diagnosis. Eleven patients were treated with chemotherapy, 10 patients were treated with TKIs, and 32 patients were treated with chemotherapy combined with TKIs before LM diagnosis. Patients with LM after BM had lower Karnofsky Performance Status (KPS) scores (KPS score 50) than did those with LM without BM (KPS score 80) or LM concurrent with BM (KPS score 70; p = 0.003). More patients with LM after BM received intrathecal methotrexate than in the other subgroups (p < 0.001). The median OS was significantly shorter in the LM after BM than in the concurrent LM and BM and the LM without BM subgroups (5.4 vs 5.5 vs 11.6 months; p = 0.019). Cox regression revealed that a KPS score ≥ 70 (HR 0.51; p = 0.027) and shunt implantation (HR 0.41; p = 0.032) were favorable prognostic factors. CONCLUSIONS Patients with NSCLC who had LM without BM had better survival outcomes (11.6 months) compared with those who had LM after BM or concurrent LM and BM. Aggressive shunt implantation may be favored for LM.

Pediatric spinal tumors are unique pathologies treated by pediatric neurosurgeons. Special attention is required for the preservation of neural function and bony alignment. We reported our experience in the management of these challenging lesions. A total of 75 pediatric patients with spinal tumors treated at the National Taiwan University Hospital from 1998 to 2018 were identified retrospectively. Clinical data, radiographic image, and pathological report were reviewed for analysis. There were 37 females and 38 males. The median age was 9 years. Thirty-eight tumors (50.6%) were extradural, 20 (26.7%) intradural extramedullary, and 17 (22.6%) intramedullary. The most common pathologies were glioma, ependymoma, and neuroblastoma. The rate of total and subtotal resection was 45.3% and 21.3%. Thirty-four patients (45.3%) required post-operative adjuvant therapy. Eight patients (10.6%) with spinal deformity had simultaneous tumor excision and spinal fusion surgery. Additional six (8%) patients had subsequent spinal fixation and fusion for deformity after primary tumor operation. Eighty-four percent of patients were ambulatory 3 years after operation. For patients with intradural extramedullary and intramedullary tumors, worse survival outcome was associated with tumor derived from CSF seeding and cranial involvement of spinal tumor, while poorer functional outcome was correlated with cranial involvement and adjuvant therapy with chemotherapy or radiotherapy. Pediatric spinal tumor surgery carries low surgical morbidity and mortality under current standard of neurosurgical practice. Post-operative adjuvant therapy is required for nearly half of the cases. Spinal deformity requires special attention and sometimes surgical correction. Contemporary management of pediatric spinal tumors enables effective ablation of the lesion and delivers favorable outcome for the majority of patients.

The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH.Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured.There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p 0.001).The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Objectives Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery and researchers have recently focused on preserving nasal function. The transseptal approach is a promising procedure owing to its less injury to nasal mucosa. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Study design Retrospective chart review. Setting Single-institution tertiary care centre. Participants 25 patients of transseptal approach from January 2019 to December 2020 and 25 patients of transnasal approach from January 2017 to December 2018. Main outcome measures Lund-Kennedy endoscopic scores, 22-item sinonasal outcome test (SNOT-22) scores, TIB smell identification tests (TIBSIT®) scores, the rate of gross total resection, endocrine control, and postoperative complications were collected. Results The postoperative SNOT-22 (4.40 vs. 7.36, P =.005) and Lund-Kennedy endoscopic scores (2.72 vs, 5.08 at 2 weeks, 0.88 vs. 3.52 at 1 month, 0.48 vs. 2.12 at 3 months, 0.04 vs. 1.76 at 6 months, all adjusted P < .01) were significantly lower in the transseptal group, while the TIBSIT scores were not significantly different (41.6 vs. 42.4 preoperatively, P = .68; 41.6 vs. 40.2 postoperatively, P = .46). The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. In multivariate analysis, the transseptal approach remained an independent factor for lower SNOT-22 scores and Lund-Kennedy endoscopic scores. Conclusion The transseptal approach provides better recovery of nasal mucosa and intact olfactory function without compromising neurosurgical outcomes.

BACKGROUND Cerebrospinal fluid (CSF) venous fistulas are a recently discovered and underdiagnosed cause of spontaneous spinal CSF leak, which may lead to spontaneous intracranial hypotension. Most cases occur in the thoracic spine, and only 2 cases were reported in the cervical spine. Treatments include the epidural blood patch, fibrin glue injection, and surgical ligation of the fistula. OBSERVATIONS The authors report the treatment of a C6–7 CSF venous fistula, for which direct ligation was not feasible, with suboccipital decompression, leading to the complete resolution of the symptoms. Based on the clinical course and outcome in our patient, the authors summarize the previous theory and propose a hypothesis for the pathophysiology of headache and other symptoms in patients with CSF venous fistulas. LESSONS The symptoms of CSF venous fistulas may be linked not only to intracranial hypotension but also to the altered CSF dynamics induced by tonsillar herniation. Suboccipital decompression should be considered as a potential treatment option, especially in patients with Valsalva-induced headache who show a poor response to surgical ligation, patients in whom surgical ligation is not feasible, and patients with foramen magnum obstruction. Further investigation of the pathophysiology of CSF venous fistulas is warranted and should be performed in the future.

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.

Given the limited studies addressing the issue about the effect of different surgical modalities for metastatic spinal cord compression (MSCC) as the first malignancy manifestation, we conducted a retrospective case-control study to evaluate the surgical outcome of MSCC as the first malignancy manifestation. A total of 59 patients who were suspected of having metastatic spinal cord compression and underwent surgery from 2008 to 2017 were enrolled in the study. All patients were categorized into either ‘debulking group’ or ‘palliative group’. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), Frankel scale, and Karnofsky scores. All the outcomes were analyzed with a data cutoff of December 31, 2017. There was a significant difference between groups in progression-free survival (PFS) (p = 0.0036). However, there was no significant difference between groups in the overall survival (OS) (p = 0.8669). Age of onset, gender, duration of symptoms, and location of spinal metastasis, initial Frankel, initial Tomita scores, and initial Karnofsky performance scale showed no significant differences between groups. In conclusion, debulking surgery was shown to provide better neurological recoveries and could be considered first in patients with metastatic spinal cord compression as the first malignancy manifestation.

Lumbar degenerative spine disease (DSD) with neurological symptoms is the most common indication requiring lumbar surgery when nonoperative treatment is not effective. Individuals with lumbar DSD have sensory, proprioception, and musculoskeletal system alterations, which may result in balance impairment. However, evidence regarding balance recovery in individuals with lumbar DSD after lumbar surgery is limited.To evaluate balance control, pain, and functional activities in individuals with lumbar DSD after lumbar surgery.A prospective study with a cross-sectional control group.Seventy individuals with lumbar DSD (DSD group) and 30 age-matched healthy adults (control group) were recruited. Participants in the DSD group were diagnosed by a neurological surgeon and received lumbar surgery according to relevant imaging findings and neurological symptoms.Clinical assessments, including a visual analogue scale (VAS), the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RMDQ), were performed in the DSD group only. Balance control was assessed in all participants using the root mean square (RMS) distance of the center of pressure (COP) in anteroposterior and mediolateral directions.All participants were instructed to stand in natural stance and Romberg stance with eyes open and eyes closed on a force platform for 35 seconds, respectively. The assessments were performed in the DSD group at four time points: preoperative phase (baseline), 3 months, 6 months, and 12 months postoperatively. In the age-matched healthy control group, only one assessment on the recruitment day was performed.The VAS, ODI, and RMDQ scores of the DSD group significantly improved after lumbar surgery (p.001). The RMS distance of COP in the DSD group significantly decreased after lumbar surgery (p.017) compared with baseline in most of the testing conditions. However, the RMS distance of the COP in the DSD group after surgery was significantly greater than in the healthy control group (p.05), especially 6 months and 12 months postoperatively.Balance control, pain, and functional activities of individuals with lumbar DSD showed improvement after lumbar surgery. However, balance control in individuals with lumbar DSD was still less stable than in age-matched healthy adults from 6 to 12 months after surgery. Therefore, individuals with lumbar DSD require fall prevention programs after lumbar surgery, including balance assessments and postoperative balance training.

Background We redesigned decompressive craniectomy and cranioplasty procedures to decrease the inherent risk of complications. This novel technique, called decompressive cranioplasty, not only may decrease the complication rate but also may improve the cosmetic result, obviate the need for artificial skull implant, and increase the decompressive volume compared with traditional craniectomy. Methods In decompressive cranioplasty, the Agnes Fast craniotomy was adopted without cutting the temporalis muscle from the underlying bone flap. After opening the dura with or without removal of intracranial hematomas, duraplasty was performed with an intracranial pressure monitor inserted. Four miniplates were bent into a “Z” shape, and the vascularized bone flap was elevated approximately 1.2–1.5 cm above the outer cortex of the skull and fixed with the miniplates. Subsequent cranioplasty was done with a mini-incision on the miniplate sites and reshaping of the miniplate to align the outer cortex of the bone flap. Results We successfully performed decompressive cranioplasty in 3 emergent cases—2 traumatic subdural hematomas and 1 malignant middle cerebral artery infarction. Postoperative brain computed tomography demonstrated adequate decompression in all cases. Cosmetic outcome was excellent, and there was no temporal hallowing. Mastication function was not affected. At 6-month follow-up, there was no bone flap shrinkage and no hydrocephalus. Conclusions Decompressive cranioplasty is a safe and effective method in the management of patients with brain edema and intracranial hypertension. It is simple to perform and may reduce the morbidity associated with traditional decompressive craniectomy and subsequent cranioplasty.

2057 Background: ADI-PEG 20 exploits the different metabolic ability for synthesizing arginine (Arg) between normal and neoplastic cells to reduce tumor cell growth. Preclinical and clinical studies have shown that cancers which are either Arg auxotrophic, with silencing of argininosuccinate synthetase ( ASS1), or Arg non-auxotrophic, respond to ADI-PEG 20 monotherapy or ADI-PEG 20 combined with various chemotherapies, respectively. ADI-PEG 20 has shown efficacy as monotherapy in ASS1 negative mouse glioblastoma (GBM) models and the combination of ADI-PEG 20 with temozolomide (TMZ) and with radiation (RT) in both ASS1 negative and ASS1 positive mouse GBM models. Based on these rationales, ADI-PEG 20 was added to standard RT + TMZ in patients with newly diagnosed GBM. This is the first clinical trial combining ADI-PEG 20 with RT. Methods: This phase IB, open-label, single-arm, standard 3+3 dose escalation with a recommended phase 2 dose (RP2D) expansion study (NCT04587830) was initiated in June 2020. Weekly ADI-PEG 20 is added to concurrent RT + TMZ and to 6 cycles of adjuvant TMZ (Stupp protocol). ADI-PEG 20 could be continued for up to 2 years. RANO criteria are used to determine response by evaluating MRI at 1, 3 and 6 months after RT, and every 3 months thereafter. Major eligibility criteria are age 20-75 years with newly diagnosed, histologically confirmed GBM with Karnofsky performance status ≥ 60. Endpoints include safety, pharmacodynamics, immunogenicity, progression free survival (PFS) and overall survival (OS). Results: Cohorts 1 (18 mg/m2) and 2 (36 mg/m2) were completed without dose limiting toxicity (DLT). Enrollment to cohort 3 (RP2D phase, 36 mg/m2) is ongoing with 23/26 patients. The major adverse events (AEs) were fatigue (52%), constipation (39%) and neutrophil decrease (39%). Dermatologic or allergic reactions occurred in 12/23 (52%), and all were grade 1-2 except for anaphylactic shock in 1 and vasculitis/rash in 1. 22/23 are alive, with median PFS = 9.5 months. The first 6 study patients are all alive for at least 11 months, with the longest at 1.5 years. 10 are off treatment due to progressive disease in 6, severe AE in 2, consent withdrawal in 1, and medical decision in 1. Mean peripheral blood Arg levels were suppressed ( < 10uM) for 4-6 weeks in most subjects, with a reciprocal elevation of citrulline levels. Anti-ADI-PEG 20 antibodies tended to increase as peripheral Arg levels increased. Conclusions: The addition of ADI-PEG 20 to RT + TMX was safe, and no DLT was observed. The RP2D of ADI-PEG 20 was determined to be 36mg/m2. AEs were those typically seen with RT + TMZ, with perhaps an increase in rash reported with the addition of ADI-PEG 20. Anaphylaxis and vasculitis were seen (1 subject with each), and have been observed previously with ADI-PEG 20. The preliminary OS data are encouraging. A registration phase 2/3 trial of this triplet is being considered. Clinical trial information: NCT04587830.

Lactulose, as a prebiotic, can be utilized by human gut microbiota and stimulate their growth. Although microbiota modulation has become an emerging approach to manage many diseases and can be achieved by the administration of prebiotics, fewer investigations have been carried out on the therapeutic mechanism of lactulose. Two trehalose analogs, lactulose and melibiose, were identified as having a neuroprotective effect in polyglutamine and Parkinson disease models. In this study, we examined lactulose and melibiose in a mouse primary hippocampal neuronal culture under the toxicity of oligomeric Aβ25-35. Lactulose was further tested in vivo because its effective concentration is lower than that of melibiose. Lactulose and trehalose were applied individually to mice before a bilateral intrahippocampal CA1 injection of oligomeric Aβ25-35. The administration of lactulose and trehalose attenuated the short-term memory and the learning retrieval of Alzheimer's disease (AD) mice. From a pathological analysis, we found that the pretreatment of lactulose and trehalose decreased neuroinflammation and increased the levels of the autophagic pathways. These results suggest that the neuroprotective effects of both lactulose and trehalose are achieved through anti-inflammation and autophagy. In addition, lactulose was better than trehalose in the enhancement of the synaptic protein expression level in AD mice. Therefore, lactulose could potentially be developed into a preventive and/or therapeutic disaccharide for AD.

BACKGROUND Anterior cervical discectomy and fusion (ACDF) with a rigid interbody spacer is commonly used in the treatment of cervical degenerative disc disease. Although ACDF relieves clinical symptoms, it is associated with several complications such as pseudoarthrosis and adjacent segment degeneration. The concept of dynamic fusion has been proposed to enhance fusion and reduce implant subsidence rate and post-fusion stiffness; this pilot preclinical animal study was conducted to begin to compare rigid and dynamic fusion in ACDF. QUESTIONS/PURPOSES Using a pig model, we asked, is there (1) decreased subsidence, (2) reduced axial stiffness in compression, and (3) improved likelihood of bone growth with a dynamic interbody cage compared with a rigid interbody cage in ACDF? METHODS ACDF was performed at two levels, C3/4 and C5/6, in 10 pigs weighing 48 to 55 kg at the age of 14 to 18 months (the pigs were skeletally mature). One level was implanted with a conventional rigid interbody cage, and the other level was implanted with a dynamic interbody cage. The conventional rigid interbody cage was implanted in the upper level in the first five pigs and in the lower level in the next five pigs. Both types of interbody cages were implanted with artificial hydroxyapatite and tricalcium phosphate bone grafts. To assess subsidence, we took radiographs at 0, 7, and 14 weeks postoperatively. Subsidence less than 10% of the disc height was considered as no radiologic abnormality. The animals were euthanized at 14 weeks, and each operated-on motion segment was harvested. Five specimens from each group were biomechanically tested under axial compression loading to determine stiffness. The other five specimens from each group were used for microCT evaluation of bone ingrowth and ongrowth and histologic investigation of bone formation. Sample size was determined based on 80% power and an α of 0.05 to detect a between-group difference of successful bone formation of 15%. RESULTS With the numbers available, there was no difference in subsidence between the two groups. Seven of 10 operated-on levels with rigid cages had subsidence on a follow-up radiograph at 14 weeks, and subsidence occurred in two of 10 operated-on levels with dynamic cages (Fisher exact test; p = 0.07). The stiffness of the unimplanted rigid interbody cages was higher than the unimplanted dynamic interbody cages. After harvesting, the median (range) stiffness of the motion segments fused with dynamic interbody cages (531 N/mm [372 to 802]) was less than that of motion segments fused with rigid interbody cages (1042 N/mm [905 to 1249]; p = 0.002). Via microCT, we observed bone trabecular formation in both groups. The median (range) proportions of specimens showing bone ongrowth (88% [85% to 92%]) and bone volume fraction (87% [72% to 100%]) were higher in the dynamic interbody cage group than bone ongrowth (79% [71% to 81%]; p < 0.001) and bone volume fraction (66% [51% to 78%]; p < 0.001) in the rigid interbody cage group. The percentage of the cage with bone ingrowth was higher in the dynamic interbody cage group (74% [64% to 90%]) than in the rigid interbody cage group (56% [32% to 63%]; p < 0.001), and the residual bone graft percentage was lower (6% [5% to 8%] versus 13% [10% to 20%]; p < 0.001). In the dynamic interbody cage group, more bone formation was qualitatively observed inside the cages than in the rigid interbody cage group, with a smaller area of fibrotic tissue under histologic investigation. CONCLUSION The dynamic interbody cage provided satisfactory stabilization and percentage of bone ongrowth in this in vivo model of ACDF in pigs, with lower stiffness after bone ongrowth and no difference in subsidence. CLINICAL RELEVANCE The dynamic interbody cage appears to be worthy of further investigation. An animal study with larger numbers, with longer observation time, with multilevel surgery, and perhaps in the lumbar spine should be considered.

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive, because the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions.In vitrocalcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and the tether-mode mechanotransduction were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not affect the ultrasound-mediated neuronal activation.SIGNIFICANCECNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show the reactions of CNS neurons to ultrasound is through ASIC1a channels, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same ultrasound stimulation, suggesting potential therapeutic translation.

Patients with cervical myelopathy may manifest impairments in functional activities and balance control caused by compression of the spinal cord. The objective of the current study was to determine long-term changes in the upright balance control of patients with cervical myelopathy who had undergone cervical decompression surgery. This is a prospective cohort study from the preoperative phase to 3 months, 6 months, and 1 year postsurgery. Fifty-three patients with cervical myelopathy were recruited for the cervical myelopathy group and 22 age-matched healthy controls were recruited for the control group. Functional assessments including Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire-Lower Extremity Function (JOACMEQ-LEF) and 10-second step test; as well as balance assessments including postural sway (center-of-pressure: COP) were performed for both groups. The JOACMEQ-LEF (p = 0.036) scores of the myelopathy group improved postoperatively, and a significant decrease in COP variables of postural sway was observed. The upright posture was less stable in the myelopathy group than in the control group (p

Adequate decompression is the primary goal during surgical management of patients with traumatic brain injury (TBI). Therefore, it may seem counterintuitive to use minimally-invasive strategies to treat these patients. However, recent studies show that endoscopic-assisted minimally-invasive neurosurgery (MIN) can provide both adequate decompression (which is critical for preserving viable brain tissue) and maximize neurological recovery for patients with TBI. Hence, we reviewed the pertinent literature and shared our experiences on the use of MIN.This was a retrospective multi-center study. We collected data of 22 TBI patients receiving endoscopic-assisted MIN within 72 hours after the onset, with Glasgow Coma Scale (GCS) scores of 6-14 and whose hemorrhage volume ranging from 30 to 70 mL.We have applied MIN techniques to a group of 22 patients with traumatic ICH (TICH), epidural hematoma (EDH), and subdural hematoma (SDH). The mean pre-operative GCS score was 7.5 (median 7), and mean hemorrhage volume was 57.14 cmEndoscopic-assisted MIN in TBI is safe and effective in a carefully selected group of patients.

Spontaneous intracerebral hemorrhage (ICH) is a common disease associated with high mortality and morbidity. The treatment of patients with ICH includes medical and surgical interventions. New areas of surgical intervention have been focused on the evacuation of hematoma through minimally invasive neurosurgery. In contrast, there have been no significant advances in the development of medical interventions for functional recovery after ICH. Stem cells exert multiple therapeutic functions and have emerged as a promising treatment strategy. Herein, we summarized the pathophysiology of ICH and its treatment targets, and we introduced the therapeutic mechanisms of stem cells (e.g. neutrotrophy and neuroregeneration). Moreover, we reviewed and summarized the experimental designs of the preclinical studies, including the types of cells and the timing and routes of stem cell administration. We further listed and reviewed the completed/published and ongoing clinical trials supporting the safety and efficacy of stem cell therapy in ICH. The limitations of translating preclinical studies into clinical trials and the objectives of future studies were discussed. In conclusion, current literatures showed that stem cell therapy is a promising treatment in ICH and further translation research on judiciously selected group of patients is warranted before it can be extensively applied in clinical practice.

Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell-derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)-expressing or osterix (Osx)-expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult-stage deletion of Cxcl12 in Osx-expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1-expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC-secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell-autonomous and non-autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research.

Background/Purpose Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. Methods The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Results Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. Conclusion This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings.

Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five coagulopathy-related ICH patients were retrospectively reviewed to compare the surgical outcomes between craniotomy (n = 52) and MIN (n = 23). Postoperative rebleeding rates, morbidity rates, and mortality at 1 month were analyzed. Postoperative Glasgow Outcome Scale Extended (GOSE) and modified Rankin Scale (mRS) scores at 1 year were assessed for functional outcomes. Morbidity, mortality, and rebleeding rates were all lower in the MIN group than the craniotomy group (8.70% vs. 30.77%, 8.70% vs. 19.23%, and 4.35% vs. 23.08%, respectively). The 1-year GOSE score was significantly higher in the MIN group than the craniotomy group (3.96 ± 1.55 vs. 3.10 ± 1.59, p = 0.027). Multivariable logistic regression analysis also revealed that MIN contributed to improved GOSE (estimate: 0.99650, p = 0.0148) and mRS scores (estimate: −0.72849, p = 0.0427) at 1 year. MIN, with low complication rates and improved long-term functional outcome, is feasible and favorable for coagulopathy-related ICH. This promising result should be validated in a large-scale prospective study.

Traumatic cerebral contusion and intracerebral hemorrhages (ICH) commonly result from traumatic brain injury and are associated with high morbidity and mortality rates. Current animal models require craniotomy and provide less control over injury severity. This study proposes a highly reproducible and controllable traumatic contusion and ICH model using non-invasive extracorporeal shockwaves (ESWs). Rat heads were exposed to ESWs generated by an off-the-shelf clinical device plus intravenous injection of microbubbles to enhance the cavitation effect for non-invasive induction of injury. Results indicate that injury severity can be effectively adjusted by using different ESW parameters. Moreover, the location or depth of injury can be purposefully determined by changing the focus of the concave ESW probe. Traumatic contusion and ICH were confirmed by H&E staining. Interestingly, the numbers of TUNEL-positive cells (apoptotic cell death) peaked one day after ESW exposure, while Iba1-positive cells (reactive microglia) and GFAP-positive cells (astrogliosis) respectively peaked seven and fourteen days after exposure. Cytokine assay showed significantly increased expressions of IL-1β, IL-6, and TNF-α. The extent of brain edema was characterized with magnetic resonance imaging. Conclusively, the proposed non-invasive and highly reproducible preclinical model effectively simulates the mechanism of closed head injury and provides focused traumatic contusion and ICH.