The effectiveness of organic vegetable oils with high biocompatibility in preventing epidural fibrosis: An experimental study.

Background and purpose:

Epidural fibrosis after all spinal surgeries is an important surgical issue. Various biological and non-biological materials have been tried to inhibit epidural fibrosis, which is deemed to be the most important cause of pain after spinal surgery. Olive oil, nigella sativa oil and soybean oil employed in oral nutrition in clinics involving liquid fatty acids, palmatic acid, linoleic acid, stearic acid and palmitoleic acid. The effectiveness of olive oil, nigella sativa oil and soybean oil on epidural fibrosis was researched on for the first time in laminectomy model.

Fifty adult male Wistar albino rats weighing between 300 and 400 grams were used in the research. A total of 5 groups were formed: sham (Group I) (n = 10), no application was created; Group II (n = 10) 1 cc saline; Group III (n = 10) 1 cc olive oil; Group IV (n = 10) 1 cc nigella sativa oil; Group V (n = 10); 1 cc soybean oil was applied topically to the epidural region after laminectomy. The total spine of the rats was dissected, histopathological and immuno­chemical measurements were conducted. Neuro-histopathological results were scored semi-quantitatively in terms of vascular modification, neuron degeneration, gliosis and bleeding criteria.

The lowest level of fibrosis and connective tissue proliferation was observed in the group where nigella sativa oil was used after the operation, followed by the group treated with olive oil and lastly with the group given soybean oil.

Nigella sativa oil and olive oil are very efficient for lowering the degree of epidural fibrosis and adhesions following laminectomy and can be employed as a simple, inexpensive and highly biocompatible material in clinical practice.

Paralysis under pressure.

Treating cardiovascular paralysis with epidural electrical neuromodulation.

Effect of Ozone Therapy on Epidural Fibrosis in Rats.

OBJECTIVE: To demonstrate the effect of medical ozone therapy on the development of epidural fibrosis. METHODS: A total of 25 Sprague-Dawley male rats were randomly divided into 3 groups: a control group (L3-L4 laminectomy only), a systemic ozone therapy (SOT) group (L3-L4 laminectomy only + intraperitoneal 15 mL [30 µg/mL] ozone), and a local ozone therapy (LOT) group (L3-L4 laminectomy only + subcutaneous 15 mL [30 µg/mL] ozone). Ozone therapy was administered 4 times on a 3-day interval during the wound-healing process, with the first dose immediately administered after surgery. The effects of ozone therapy on vascular endothelial growth factor, inflammation, and epidural fibrosis between groups were evaluated. RESULTS: Staining with vascular endothelial growth factor was significantly less in the group that received SOT compared with the control group (P = 0.021). When the groups were compared in terms of inflammation, it was found that inflammation was less common in the SOT and LOT groups compared with the control group (SOT vs. control: P = 0.004 and LOT vs. control: P = 0.024), whereas inflammation was found to be significantly less in the SOT group compared with the LOT group (P = 0.008). In the histopathologic evaluation of epidural fibrosis, there was no significant difference between the SOT and LOT groups but less epidural fibrosis was observed in both groups compared to the control group (LOT vs. control: P = 0.037; SOT vs. control: P = 0.018). CONCLUSIONS: Medical ozone therapy may be an alternative method that can be used effectively and safely in the prevention of epidural fibrosis after laminectomy.

Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Importance: The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking. Objective: To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders. Design, Setting, and Participants: This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022. Interventions: Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold. Main Outcomes and Measures: The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events. Results: Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system. Conclusions and Relevance: Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability. Trial Registration: ClinicalTrials.gov Identifier: NCT03546738.

Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).

A man with severed spine is able to walk again following implantation of electrical stimulation device.

Patients with devastating spinal cord injuries regained the ability to stand, walk, and perform even more complex motor functions after receiving implants that deliver epidural electrical stimulation.

Abnormal motor blockade after epidural analgesia caused by pneumorrhachis and the role of hyperbaric oxygen treatment: a case report.

INTRODUCTION: Pneumorrhachis is a rare clinical entity that is usually asymptomatic. Previous reports have associated such events with epidural insertion using a loss of resistance (LOR) to air technique. This report describes a case of symptomatic epidural pneumorrhachis following epidural anaesthesia using LOR to saline. CASE REPORT: A 32-year-old American Society of Anesthesiologists (ASA) Classification II female patient was admitted for unplanned caesarean section. Epidural anaesthesia was performed at the L3-4 space using LOR to saline. The procedure, including delivery of the neonate, was uneventful. In the recovery room, a local anaesthetic infusion via an elastomeric pump (infusion 'balloon') was started. Two hours after initiation of the infusion the patient complained of motor blockade, so it was stopped. Two hours later she remained paraparetic, and a neurologist assessment was required. A computed tomography scan showed epidural pneumorrhachis at the L2-3 level. The patient was referred for emergent hyperbaric oxygen treatment (US Navy Treatment Table 5) and following one session the patient recovered completely. DISCUSSION: Anaesthetists should be aware of this rare complication, which is easily overlooked. Hyperbaric oxygen treatment is a first line treatment for gas-associated lesions with neurological impairment. Timely referral is essential to prevent irreversible deficits.

Epidural space "ballooning" during local anaesthetic injection in infants and children: An ultrasound observational study.

BACKGROUND: Infants and children require a larger dose of a local anaesthetic (LA) to establish epidural analgesia than adults, but the reason for this remains unclear. We hypothesised that prominent ventro-dorsal expansion of the epidural space limits cranio-caudal spread of LA in infants. Accordingly, we studied the dimensions of the epidural space with real-time ultrasound (US) before and after epidural injection. METHODS: Ninety-six infants and children aged 0-12 years who underwent abdominal surgery under combined epidural and general anaesthesia were examined in this prospective observational study. Using a micro-convex probe, US recordings of the posterior epidural space were performed while a LA (0.5 ml kg-1 ) was infused at 0.54 ml s-1 . The width in the ventro-dorsal dimension (VDD) of the posterior epidural space before and after injection was recorded; the change in VDD was defined as "ballooning". Correlations between "ballooning" and patient age, body mass index, and volume and rate of LA administration were analysed. RESULTS: "Ballooning" correlated positively but weakly with age (R2  = 0.25; p < .001) and the infused LA volume (R2  = 0.32; p < .001). The "magnitude of ballooning" ("ballooning" per ml of injected LA) correlated negatively but weakly with age (R2  = 0.27; p < .001). CONCLUSIONS: "Magnitude of ballooning" of the epidural space become inconspicuous with growing during epidural injection. This effect may slow the cranio-caudal spread of LA and explain partially why larger volumes of LA are required to effect a block in children.

[Comparative study between electroacupuncture at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery].

OBJECTIVE: To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery. METHODS: Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (T0), skin incision (T1), extubation (T2) and 2 h after operation (T3); the dosage of anesthetics and extubation time were recorded; the plasma levels of ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were measured at the following time points: T0, T3, 12 h after operation (T4), 24 h after operation (T5) and 48 h after operation (T6). Visual analogue scale (VAS) was used to evaluate the analgesic effect. RESULTS: The MAP at T1 and T2 in the group A was lower than that in group B and control group (P<0.05), and HR at T1 and T2 was lower than that in control group (P<0.05). The MAP and HR at T1 and T2 in the group B were lower than those in the control group (P<0.05). The dosage of remifentanil in the group A and group B was lower than that in the control group (P<0.05), and extubation time was earlier than that in the control group (P<0.05). The content of ß-EP at T4, T5 and T6 in the group B was higher than that in the group A and control group (P<0.05); the contents of 5-HT and PGE2 at T3, T4 and T5 in the group A and group B were lower than those in the control group (P<0.05). The VAS scores at T3, T4 and T5 in the group A and group were lower than those in the control group (P<0.05). CONCLUSION: The preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.

Comparative study between electroacupuncture at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery / 中国针灸

OBJECTIVE@#To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery.@*METHODS@#Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (T@*RESULTS@#The MAP at T@*CONCLUSION@#The preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

Emodin promotes fibroblast apoptosis and prevents epidural fibrosis through PERK pathway in rats.

BACKGROUND: Laminectomy is usually classed as a common orthopedic surgery, but postoperative epidural fibrosis often leads to less-than-desirable clinical outcomes. As demonstrated by prior studies, emodin (EMO) exerts an anti-fibrotic effect. Here, we carried out investigation into the inhibitory effect created by EMO application on epidural fibrosis after laminectomy in rats. METHODS: The paper conducts a series of experiment. In vitro, we observed the effect of EMO on fibroblasts by Cell Counting Kit-8 (CCK-8) assay. Apoptosis of fibroblasts induced by EMO was detected by western blot, TUNEL assay, and flow cytometry. The results revealed that EMO was capable of inducing fibroblast apoptosis, and the proteins of PERK pathway also changed accordingly. In vivo, the effect of EMO on epidural fibrosis in 12 male Sprague-Dawley rats was observed by histological staining. RESULTS: CCK-8 assay indicated that EMO was effective in reducing fibroblast viability in a time- and a dose-dependent manner. TUNEL assay and flow cytometry analysis have demonstrated that the apoptotic rate of fibroblasts increased as the EMO concentration rose. Western blot analysis proved that EMO promoted the relative expression of p-perk and p-eIF2α and that the expression of its downstream proteins CHOP and GRP78 was also enhanced. The expression of apoptotic protein Bax and cleaved PARP was upregulated, whereas the expression of anti-apoptotic protein Bcl-2 was downregulated. In addition, histological and immunohistochemical analysis demonstrated that EMO functioned to inhibit epidural fibrosis and increase GRP78 expression in fibrous tissue by promoting apoptosis of fibroblasts. CONCLUSIONS: EMO could have inhibitory effect on epidural fibrosis in a concentration-dependent manner. The potential mechanism might be through PERK signaling pathway to promote fibroblast apoptosis. It has a possibility to be taken as a novel method for the treatment of epidural fibrosis.

Surgical Indications and Operative Results of Lumbosubarachnoid-Lumboepidural Shunting in 29 Patients with Idiopathic Normal Pressure Hydrocephalus under Local Anesthesia.

This study consisted of 29 patients with idiopathic normal pressure hydrocephalus (iNPH) who underwent lumbosubarachnoid-lumboepidural (L-L) shunting under local anesthesia in accordance with our surgical indications of L-L shunting. (1) CSF absorption within the lumbar epidural space and shunt clearance were confirmed in all patients after operation. (2) Shunt responders (R) were 25 of 29 cases (86.2%) 3 months after surgery. Among the R, symptom exacerbation was confirmed in three patients (12%) within the follow-up period (mean, 25.1 months). In each of these patients, shunt function were maintained and remained unchanged even with pressure resetting, the cause being an intracranial/extracranial disease other than iNPH. (3) The initial pressure setting for this method was 8 cmH2O, with gradual change to higher pressures, such that the setting for Patient 11 and thereafter became 20 cmH2O. (4) As postsurgical complications, subcutaneous cerebral spinal fluid collection (SCC) was confirmed in five patients (17.2%). In high-pressure resetting and follow-up observation, SCC was not observed in all patients. Epidural catheter displacement was confirmed in three patients (10.3%). No recurrence was noted after the secure fixation of the catheter at the fascia insertion portion and 2 days' postsurgical bed rest. Hence, L-L shunting is an effective shunt therapy for iNPH.

Negative regulation of PI3K/AKT/mTOR axis regulates fibroblast proliferation, apoptosis and autophagy play a vital role in triptolide-induced epidural fibrosis reduction.

Fibroblasts excessive proliferation was considered as a decisive reason for epidural fibrosis, which was known as a serious complication of lumbar laminectomy. As a traditional Chinese medicine, triptolide (TP) was used to be proved effective in preventing several fibrosis scar formation diseases. However, little is known about the effect of TP on preventing epidural fibrosis and its possible mechanism. Here, we performed in vitro and in vivo experiments to detect the possible mechanism of TP in preventing epidural fibrosis. In vitro, the effect of TP on impacting fibroblasts proliferation activities was detected by CCK-8, cell cycle assay and EdU incorporation assay. Also, the expressions of cell proliferation protein markers and the expressions of p-PI3K, p-AKT, p-mTOR were detect by Western blot. Besides, the effect of TP on inducing fibroblast apoptosis and autophagy was tested by Western blots, flow cytometry, TUNEL staining, Transmission electron microscope (TEM) analysis and LC3 immunofluorescent staining. The results suggested that TP could suppress the activation of PI3K/AKT/mTOR signaling pathway. Meanwhile, TP could inhibit fibroblast proliferation and induce fibroblast apoptosis as well as autophagy, which was known as two cellular self-destructions. Furthermore, we speculated the possible molecular pathway, through which that TP could inhibit fibroblast proliferation, induce fibroblast apoptosis and autophagy. We used PI3-kinase activator (740Y-P) to activate the PI3K/AKT/mTOR signaling. Activation of PI3K/AKT/mTOR signaling pathway increase the proliferation of fibroblasts and suppressed the autophagy and apoptosis induced by TP. In vivo, we built epidural fibrosis models in rats and locally applied TP of various concentrations. Hematoxylin-eosin (HE) and Masson's trichrome were used to detect the effect of TP on reducing epidural fibrosis. And the results showed that TP could significantly reduce the surgery-induced epidural fibrosis. In conclusion, the results above shown that TP could reduce epidural fibrosis formation, and the potential mechanism might through inhibiting fibroblast proliferation and stimulating apoptosis and autophagy via suppressing PI3K/AKT/mTOR signaling pathway. It might provide a novel thought for reducing surgery-induced epidural fibrosis.

Cervical epidural hematoma following interlaminar epidural steroid injection via the contralateral oblique view in patient taking omega-3 fatty acids.

BACKGROUND AND OBJECTIVES: We sought to describe a case of an epidural hematoma after a cervical interlaminar epidural steroid injection (ILESI) performed using contralateral oblique view. We also discuss factors that could have placed this patient at increased risk, including concurrent use of omega-3 fatty acids and non-steroidal anti-inflammatory medications. CASE REPORT: A 74-year-old woman returned to the pain clinic, within 15 min of discharge, after an apparent uncomplicated cervical ILESI using the contralateral oblique technique with severe periscapular pain and muscle spasms. Cervical MRI showed a large epidural hematoma which was subsequently emergently evacuated. On postoperative examination, the patient had no neurologic deficits and full resolution of her painful symptoms. CONCLUSIONS: To our knowledge, this is the first reported case of cervical epidural hematoma in which the contralateral oblique technique was used. Also, this is the second case in which the combination of non-steroidal anti-inflammatory medications and omega-3 fatty acids has been considered as a contributor to increased hematoma risk. This case underscores the risk of epidural hematoma using a novel fluoroscopic technique and the need for potential discontinuation of supplements like omega-3 fatty acids.

Pseudomeningocele and percutaneous intrathecal lead placement complication for spinal cord stimulator.

The incidence of symptomatic percutaneous intrathecal subarachnoid lead placement for spinal cord stimulator is almost an unheard of complication in the literature. We present the first case of a spinal cord stimulator implant with a complication of symptomatic intrathecal subarachnoid lead placement with a pseudomeningocele. This complication was found with myelogram and addressed by replacement with a new spinal cord stimulator implant with paddle leads instead of percutaneous leads and obliterating the pseudomeningocele tract. Technique for epidural lead placement is discussed. This case illustrates a spinal cord stimulator implant complication of intrathecal percutaneous lead placement with pseudomeningocele and its recognition and treatment involving replacement of the system while minimizing risk of postoperative cerebrospinal fluid leakage. Intraoperative neuromonitoring and interrogation of the spinal cord stimulator system during implantation are effective tools for accurate epidural lead placement.

Artesunate inhibits fibroblasts proliferation and reduces surgery-induced epidural fibrosis via the autophagy-mediated p53/p21waf1/cip1 pathway.

Fibroblast proliferation is considered to be a major cause in the process of epidural fibrosis formation. Autophagy is a tightly-regulated catabolic process in charge of degrading intracellular components. Although autophagy has been associated with fibrosis of different tissues, the effect of autophagy on epidural fibrosis is still unknown. The aim of this study was to investigate the function and mechanism of autophagy induced by Artesunate (ART), a classical antimalarial agent extracted from the Chinese medicinal herb. In vitro, the effect of ART on inducing fibroblast autophagy was evaluated via LC3 immunofluorescent staining, Transmission Electron Microscopy (TEM) and western blotting analysis. Moreover, the effect of ART on inhibiting fibroblast proliferation was investigated by CCK-8 assay, EdU incorporation assay, flow cytometry and western blotting analysis. Results indicated that ART could induce autophagy and inhibit proliferation in fibroblasts. The inhibitory effect of ART on fibroblast proliferation was associated with the upregulation of p53 and p21waf1/cip1 proteins. Intriguingly, 3-MA, a classical autophagy inhibitor, attenuated ART-induced p53/p21waf1/cip1 pathway activation and fibroblast proliferation inhibition. In vivo, the effect of ART on reducing epidural fibrosis was detected by histological macroscopic assessment, hydroxyproline content analysis, histological and immunohistochemical staining. The results revealed that ART had significant suppressive effects on epidural fibrosis following laminectomy in rats. In conclusion, this research demonstrated that ART could inhibit fibroblast proliferation and reduce epidural fibrosis formation after laminectomy, and the potential mechanism might through autophagy cascade-mediated p53/p21waf1/cip1 pathway. It might provide a novel reagent for reducing epidural fibrosis after spinal laminectomy surgery.

Intracranial abscess from facial cellulitis

Cellulitis, one of most common diseases of everyday life, is often overlooked for its significance. Although cellulitis does not cause or lead to serious problems usually, its possibility to cause life-threatening problem should be known. In present case, a patient who had received acupuncture treatment a week earlier presented to the clinic with symptoms of facial cellulitis. The disease resolved within few weeks under empirical antibiotic treatment but recurred after 3 months. Under close history review of the patient, we found out that the patient had received craniectomy 20 years ago. The patient had blunt headache with no other neurological symptoms that could suspect cranial infection, but considering the risk originating from the patient’s surgical history, brain computed tomography (CT) was taken. CT images revealed abscess formation in the subgaleal and epidural spaces. Craniotomy with abscess evacuation was done promptly. With additional antibiotic treatment postoperatively, the disease resolved, and the 1-month postoperative follow-up brain CT showed no signs of abscess formation.