Superb microvascular ultrasound is a promising non-invasive diagnostic tool to assess a ventriculoperitoneal shunt system function: a feasibility study.

The objective of this pilot study was to assess the reliability of superb microvascular ultrasound (SMI) for the measurement of the cerebrospinal fluid (CSF) flow within VPS systems as an indirect sign for shunt dysfunction. Asymptomatic hydrocephalus patients, with a VPS system implanted between 2017 and 2021, were prospectively enrolled in the study. Using SMI, the CSF flow within the proximal and distal catheters were analysed. Before and after pumping the shunt reservoir, intraabdominal free fluid, optical nerve sheath diameter (ONSD), and papilla diameter (PD) were evaluated and correlated with the amount of valve activation. Nineteen patients were included. A flow was detectable in 100% (N = 19) patients in the proximal and in 89.5% (N = 17) in the distal catheter. The distal catheter tip was detectable in 27.7% (N = 5) patients. Free intraabdominal fluid was initially detected in 21.4% (N = 4) patients and in 57.9% (N = 11) at the end of the examination (P = 0.049). ONSD was significantly lower after pump activation (4.4 ± 0.9 mm versus 4.1 ± 0.8 mm, P = 0.049). Both peak velocity and flow volume per second were higher in proximal compared to distal catheters (32.2 ± 45.2 versus 5.6 ± 3.7 cm/sec, P = 0.015; 16.6 ± 9.5 ml/sec versus 5.1 ± 4.0 ml/sec, P = 0.001, respectively). No correlation was found between the number of pump activations and the changes in ONSD (P = 0.975) or PD (P = 0.820). SMI appears to be a very promising non-invasive diagnostic tool to assess CSF flow within the VPS systems and therefore affirm their function. Furthermore, appearance of free intraperitoneal fluid followed by repeated compression of a shunt reservoir indicates an intact functioning shunt system.

Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease.

BACKGROUND: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). METHODS: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. RESULTS: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. CONCLUSIONS: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting.

Lumbar Disc Herniation­the Significance of Symptom Duration for the Indication for Surgery.

BACKGROUND: Lumbar disc surgery is among the more common spinal procedures. In this paper, we report the current treatment recommendations for patients with symptomatic disc herniation. METHODS: This review is based on pertinent publications retrieved by a selective literature search in PubMed using the terms [timing] AND [lumbar disc herniation], supplemented by other relevant articles and guidelines. RESULTS: Symptoms resolve in 60% to 80% of patients with herniated discs in 6-12 weeks, and in 80% to 90% over the long term (≥ 1 year). According to the guidelines, 6-12 weeks of conservative treatment are recommended in the absence of significant neu - rologic deficits. Early surgery is indicated in case of worsening pain or new onset of neurologic deficits. Lumbar disc herniation associated bladder or bowel dysfunction (cauda equina syndrome) is considered an absolute surgical emergency that requires immediate decompression (within 24 to 48 hours). Patients with severe motor deficits (MRC ≤ 3/5) benefit from early intervention and should be offered surgery within three days, if possible, for the best chance of recovery. The degree of weakness and the duration of symptoms have been identified as risk factors for incomplete recovery. Early surgery can be considered in patients with mild paresis (MRC 4/5) in case of functional impairment (e.g., quadriceps paresis). CONCLUSION: Longer symptom duration and lower motor scores are associated with worse outcome and a lower chance of neurologic recovery. The recovery rate for motor deficits ranges from 33% to 75%, depending on the timing and modality of treatment as well as the motor score.

Intraoperative application of triamcinolone - a risk factor for delayed CSF fistula formation?

PURPOSE: Cerebrospinal fluid (CSF) leaks are a well-known complication in spinal surgery, caused mostly by incidental durotomy (ID). However, delayed pseudomeningocele formation has been described in patients following an unremarkable surgery - without ID. Intraoperative and epidural triamcinolone application has been suspected to be a potential risk factor. This study was conducted to evaluate the management of ID and identify further risk factors for secondary CSF fistula formation. METHODS: After obtaining approval from the institutional ethics committee, a total of about 5512 patients, who underwent spine surgery between January 2014 and December 2017, were retrospectively reviewed. Of those, 139 cases with intraoperative ID and 15 with delayed pseudomeningocele formation were extracted and analyzed to identify potential risk factors for a late presenting dural injury (LPDI). RESULTS: The incidence of delayed CSF fistulas was 0.27%, with 15 patients presenting with a secondary symptomatic CSF fistula following an unremarkable surgery. Triamcinolone was identified as a risk factor (p<0.001) for pseudomeningocele formation with an OR of 11.5, as it was applied in 80.0% (n=12) of these cases. Revision surgery was performed at a mean period of 6 weeks after initial surgery. CONCLUSION: In our retrospective analysis, intraoperative application of triamcinolone was significantly associated with a high rate of delayed CSF fistulas. It should therefore be used with caution and only after weighing in potential negative side effects.

Health-related quality of life 2 years after pedicle subtraction osteotomy for sagittal imbalance: a single-center experience of 65 patients.

PURPOSE: Pedicle subtraction osteotomy (PSO) as an invasive procedure with high reoperation and complication rates in an often elderly population has often been questioned. The purpose of our study was to evaluate the impact of PSO for sagittal imbalance (SI) on patient-reported outcomes including self-reported satisfaction and health-related quality of life 2 years postoperatively. METHODS: Consecutive patients who underwent correction of their spinal deformity by thoracolumbar PSO were assessed using self-reporting questionnaires 2 years postoperatively. Outcome was measured by visual analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EQ-5D scores. Additionally, a Patient Satisfaction Index (PSI) rated in four grades (A: very satisfied to D: not satisfied), walking range, and the Timed Up and Go (TUG) Test were evaluated. RESULTS: Sixty-five patients were included, and each parameter was assessed preoperatively and 24 months postoperatively. The intervention led to significant improvements in back pain (8.1 ± 1.2 vs. 2.9 ± 1.9; p < 0.001), as well as ODI scores (57.7 ± 13.9 vs. 32.6 ± 18.9; p < 0.001), walking range (589 ± 1676 m vs. 3265 ± 3405 m; p < 0.001), and TUG (19.2 s vs. 9.7 s; p < 0.05). 90.7% of patients (n = 59/65) reported a PSI grade "A" or "B" 24 months postoperatively. CONCLUSION: Patient satisfaction 24 months after PSO for SI is high. Quality of life improved significantly by restoring sagittal balance.

Bed rest after incidental durotomy in lumbar surgery: a redundant measure in case of watertight dural repair.

BACKGROUND: Cerebrospinal fluid (CFS) leaks are a well-known complication in spinal surgery, caused mostly by incidental durotomy (ID). Management of ID is a matter of ongoing debate. Different treatment strategies have been described ranging from no specific treatment to intraoperative suture or even complex reconstructive procedures. The role of bedrest has also been controversially discussed. The aim of this study was thus to evaluate a potential benefit of postoperative bedrest after ID. METHODS: ID management following lumbar spine surgery at a high-volume center between 01/2014 and 12/2017 was retrospectively assessed. Several risk factors such as type of surgery, size of dural lesion, intraoperatively chosen strategy, postoperative management (e.g., bedrest) and surgery-related complications were analyzed. Failure of the chosen strategy was defined as symptomatic CSF leakage, requiring revision surgery. RESULTS: Sufficient data was available for 135 patients with intraoperatively detected incidental durotomy. Eighty-seven patients with intraoperatively detected ID (64.4%) were additionally managed with bedrest, whereas 48 patients (35.6%) were immediately mobilized after surgery. Sixteen patients overall needed to be revised. However, patients treated with additional bedrest did not show a significant reduction of CSF fistula rate (P=0.27). The degree of laceration (>5mm) negatively affected the outcome (P=0.027). The hospital stay was significantly prolonged in patients, who were subjected to additional bedrest (P=0.001). CONCLUSIONS: Postoperative CSF leakage represents a serious postoperative complication of lumbar surgery. Intraoperative dural repair plays a crucial role to avoid further neurological morbidity. Postoperative bedrest might be spared in case of watertight dural closure.

FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease.

BACKGROUND: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. METHODS: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. RESULTS: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. CONCLUSIONS: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.

Motor Recovery Depends on Timing of Surgery in Patients With Lumbar Disk Herniation.

BACKGROUND: Although approximately half of the patients undergoing lumbar disk surgery present with motor deficits, timing of surgery for radicular weakness is largely unclear. OBJECTIVE: To evaluate the impact of surgical timing on motor recovery in patients with lumbar disk herniation (LDH) and to identify an ideal time window for intervention. METHODS: In a single-center observational trial, 390 patients with LDH-associated motor deficits were prospectively followed for a minimum of 12 months after nonelective microscopic disk surgery. The duration of motor deficit before surgery was documented. Motor function was graded according to the Medical Research Council (MRC) scale. Statistical analysis of motor recovery applied unbiased recursive partitioning conditional inference tree to determine cutoff times for optimal surgical intervention. The slope of recovery calculated as the change of the MRC grade over time served as the primary outcome. RESULTS: A preoperative motor deficit of MRC ≤2/5 and the duration of paresis were identified as the most important predictors of recovery ( P < .001). Surgery within 3 days was associated with a better recovery for both severe and moderate/mild deficits ( P = .017 for MRC ≤ 2/5; P < .001 for MRC > 2/5; number needed to treat [NNT] <2). A sensitivity analysis in mild motor deficits indicated a cutoff of 8 days. CONCLUSION: Timing of surgery is crucial for motor recovery in LDH-associated deficits. Immediate diagnosis, imaging, and referral should be aimed for to allow disk surgery within 3 days in patients with severe and moderate radicular weakness. If functionally disabling, even mild deficits may warrant decompression within a week.

Flexing a standard hinge-powered operating table for lumbosacral three-column osteotomy (3-CO) site closure in 84 consecutive patients.

Three-column osteotomy (3-CO) is a powerful technique in adult deformity surgery, and pedicle subtraction osteotomy (PSO) is the workhorse to correct severe kyphotic spinal deformities. Aging of the population, increasing cases of iatrogenic flat back deformities and understanding the importance of sagittal balance have led to a dramatic increase of this surgical technique. Surgery, however, is demanding and associated with high complication rates so that every step of the procedure requires meticulous technique. Particularly, osteotomy closure is associated with risks like secondary fracture, translation, or iatrogenic stenosis. This step is traditionally performed by compression or a cantilever maneuver with sometimes excessive forces on the screws or instrumentation. Implant loosening or abrupt subluxation resulting in construct failure and/or neurological deficits can result. The aim of this prospective registry study was to assess the efficacy and safety of our surgical PSO technique as well as the osteotomy closure by flexing a hinge-powered OR table. In a series of 84 consecutive lumbosacral 3-CO, a standardized surgical technique with special focus on closure of the osteotomy was prospectively evaluated. The surgical steps with the patients positioned prone on a soft frame are detailed. Osteotomy closure was achieved by remote controlled bending of a standard OR table without compressive or cantilever forces in all 84 cases. This technique carries a number of advantages, particularly the reversibility and the slow speed of closure with minimum force. There was not a single mechanical intraoperative complication such as vertebral body fracture, subluxation, or adjacent implant loosening during osteotomy closure, compared to external cohorts using the cantilever technique (p = 0.130). The feasibility of controlled 3-CO closure by flexing a standard OR table is demonstrated. This technique enables a safe, gentle closure of the osteotomy site with minimal risk of implant failure or accidental neurological injury.

Sacral fracture associated with a Tarlov cyst causing an anterior sacral CSF fistula and intraventricular fat emboli - a case report and review of the literature.

BACKGROUND: Sacral fractures are rare and either associated with high-energy trauma or osteoporosis in most cases. A search of the current literature on sacral fractures and cerebrospinal fluid fistula identified only few cases. Pathological fractures are uncommon and exceedingly rare in case of Tarlov cysts. Sacral fractures can be missed in oligosymptomatic patients. However, severe complications may emerge as shown by this case report. METHODS: We present the case of a pathological sacral fracture at the level S2/3 following a low-impact trauma, associated with a Tarlov cyst, which was complicated by an anterior CSF fistula and intraventricular fat emboli. RESULTS: The patient was treated conservatively with strict bedrest and a CT-guided blood patch. Postponed mobilization was successful with decreasing orthostatic symptoms. Follow-up MRI and CT imaging showed a complete resolution of the ventral CSF fistula and ossification of the fracture. The intraventricular fat did not resolve, however, there was no radiological sign of hydrocephalus with excellent clinical outcome at 6-months follow-up. CONCLUSION: Although exceedingly rare, sacral Tarlov cysts may be associated with pathological fractures of the sacrum. Relevant complications can emerge and need to be properly addressed.

Spine surgery in pregnant women: a multicenter case series and proposition of treatment algorithm.

PURPOSE: Spinal diseases requiring urgent surgical treatment are rare during pregnancy. Evidence is sparse and data are only available in the form of case reports. Our aim is to provide a comprehensive guide for spinal surgery on pregnant patients and highlight diagnostic and therapeutic aspects. METHODS: The study included a cohort of consecutive pregnant patients who underwent spinal surgery at five high-volume neurosurgical centers between 2010 and 2017. Perioperative and perinatal clinical data were derived from medical records. RESULTS: Twenty-four pregnant patients were included. Three underwent a preoperative cesarean section. Twenty-one patients underwent surgery during pregnancy. Median maternal age was 33 years, and median gestational age was 13 completed weeks. Indications were: lumbar disk prolapse (n = 14; including cauda equina, severe motor deficits or acute pain), unstable spine injuries (n = 4); intramedullary tumor with paraparesis (n = 1), infection (n = 1) and Schwann cell nerve root tumor presenting with high-grade paresis (n = 1). Two patients suffered transient gestational diabetes and 1 patient presented with vaginal bleeding without any signs of fetal complications. No miscarriages, stillbirths, or severe obstetric complications occurred until delivery. All patients improved neurologically after the surgery. CONCLUSION: Spinal surgical procedures during pregnancy seem to be safe. The indication for surgery has to be very strict and surgical procedures during pregnancy should be reserved for emergency cases. For pregnant patients, the surgical strategy should be individually tailored to the mother and the fetus.

A Case Series of Surgically Treated Spinal Dumbbell Tumors of Critical Parent Nerve Roots: To Cut or Not to Cut?

BACKGROUND: Dumbbell tumors present challenging cases, with either an incomplete tumor resection or a need to sacrifice nerve roots. Published literature suggests encouraging neurological outcomes after nerve root amputation. OBJECTIVE: To determine the incidence of postoperative neurological deficits after amputating the parent nerve root. METHODS: A retrospective consecutive analysis of all patients treated for dumbbell nerve sheet tumors with a reported amputation of the functional relevant parent nerve roots C5-Th1 and L3-S1. RESULTS: Among 21 evaluated patients, minor postoperative neurological motor function deterioration occurred in 4 patients (19%). Most patients recovered to the preoperative level at the follow-up examination, and only one patient retained a new Medical Research Council (MRC) scale of 4/5 for deltoid weakness. The majority of tumors were resected at the lumbar level (nerve root L3: 28.6%, L5: 19%). Gross total resection was achieved in 90.5% of patients. Neuropathic pain was reported in one third of the patients during the long-term follow-up. CONCLUSION: Amputating critical parent nerve roots during the dumbbell tumor resections seems to result in a low incidence of postoperative motor deficits and may offer an acceptable sacrifice in otherwise only incompletely resectable dumbbell tumors. The cross-innervation of neighboring nerve roots and its, probably, per-se-reduced functionality may be a possible mechanism for maintaining motor function.

Early surgery determines recovery of motor deficits in lumbar disc herniations-a prospective single-center study.

BACKGROUND: Patients with intervertebral disc herniation undergo surgical removal of herniated disc material in cases of persisting symptoms and/or neurologic deficits. While motor deficits often prompt surgery, little is known about the optimal timing of surgery in these cases. The aim of this study was to prospectively evaluate the impact of timing of disc surgery on motor recovery. Does postponing surgical treatment worsen outcome? METHOD: In total, 120 patients with sciatica and/or sensorimotor deficits due to a lumbar disc herniation were surgically treated at the authors' center within a 3-month period. In 60 patients, motor deficits were present at the time of admission. Motor function was assessed using manual muscle testing and subdivided according to the Medical Research Council (MRC) scale. Patient demographics, neurologic deficits, duration of motor deficits, treatment characteristics, and outcome were assessed. At a minimum follow-up of 1 year, functional recovery and complications were collated. Patients were subdivided into groups according to the severity of the paresis (MRC ≤ 3/5 vs. MRC 4/5). Intra-group differences were compared based on the duration of the neurologic deficits. RESULTS: Patients with moderate and severe paresis (MRC ≤ 3/5) benefit from treatment within 72 h as they were shown to have a significantly higher complete recovery rate at 1-year follow-up (75% vs. 0%; p < 0.001). CONCLUSION: Immediate surgery should be offered to patients with moderate and severe motor deficits to increase the likelihood of neurologic recovery. This prospective data may have an impact on emergency triage in these patients.

Lumbar medial branch cryoneurolysis under ultrasound guidance: initial report of five cases.

AIMS: To assess the feasibility and preliminary results of ultrasound guided medial branch cryoneurolysis in the management of facet joint syndrome. MATERIAL AND METHODS: Between March 2017 and August 2017, a total of 20 patients underwent medial branch blocks, 12 of which were positive. Five patients chose to participate in the study and 8 medial branch cryoneurolysis were performed. The primary endpoint of the study was the feasibility of the procedure. The secondary endpoint was the efficacy on pain assessed over the following year after the procedure. RESULTS: Technical feasibility of cryoneurolysis under ultrasound guidance was 100%. Accurate needle positioning at the accurate target in the angle between the posterior aspect of the transverse process and the lateral aspect of the facet joint was achieved in all cases. Needle progression could be depicted with US guidance in all cases. Mean pre-procedural Visual Analogue Scale and Oswestry disability Index scores were 6.8 (range 5-8) and 20.6 (range 12- 31), respectively. Follow up showed a decrease of Visual Analogue Scale score at one month (1.75, range 0-7), and at three months (1.75 range 0-3), Mean self-reported improvement at 6 months was 76% (60- 100%) and 77% at 12 months (50-100%). We report one case of failure at one month. No complications were noted during or after the procedure. CONCLUSION: Our findings suggest that ultrasound is a valid imaging modality to perform lumbar medial branch cryoneurolysis. Initial results show that cryoneurolysis under ultrasound guidance appears as a safe and effective procedure in patients suffering for facet joint pain.

Traction screws to reduce a bilateral pedicle fracture of L5: a case report.

Pedicle fractures are rare and usually associated with repetitive stress, high-speed trauma, osteoporosis, unilateral spondylolysis, or instrumentation surgery. A review of the current literature on bilateral pedicle fractures of the lumbar spine revealed only a few cases listed as a complication of instrumentation or excessive decompression surgery. The authors present the clinical case of a 49-year-old man with exacerbating low-back pain and intermittent L5 radicular pain. The known comorbidities were rather remarkable for systemic lupus erythematosus and osteopenia. Radiological investigations revealed an acute bilateral pedicle fracture of L5 without any evidence of preexisting spondylolysis. An off-label minimally invasive fracture reduction and fixation was performed using traction screws and intraoperative navigation. The patient reported instant pain relief and did not show any sensorimotor deficits at discharge. The postoperative CT scan revealed an ossification of the former fracture after 3 months, with great 1-year follow-up outcome. This is the first documented report on the effectiveness of traction screws used in a patient with bilateral pedicle fractures of the L5 vertebra. This minimally invasive technique represents a promising treatment option in selected cases by sparing segmental fusion.

The European Robotic Spinal Instrumentation (EUROSPIN) study: protocol for a multicentre prospective observational study of pedicle screw revision surgery after robot-guided, navigated and freehand thoracolumbar spinal fusion.

INTRODUCTION: Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting. METHODS AND ANALYSIS: Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan. ETHICS AND DISSEMINATION: The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage.

Thymic stromal lymphopoietin is expressed in the intact central nervous system and upregulated in the myelin-degenerative central nervous system.

Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase. At these sites, it is important for the generation and maintenance of non-inflammatory, tissue-resident dendritic cell responses. We show here that TSLP is also expressed in the central nervous system (CNS) where it is produced by choroid plexus epithelial cells and astrocytes in the spinal cord. Under conditions of low-grade myelin degeneration, the numbers of TSLP-expressing astrocytes increase, and microglia express transcripts for the functional TSLP receptor dimer indicating that these cells are targets for TSLP in the myelin-degenerative CNS.