Less Use of the Bipolar Cautery can Prevent Postlaminectomy Epidural Fibrosis: An Experimental Study in Rats.

AIM: To investigate the role of bipolar electrocautery in the occurrence of epidural fibrosis following lumbar spine laminectomy in a rat model. MATERIAL AND METHODS: Fourteen male Sprague-Dawley rats (age: 4-6 months, weight: 250-300 g) were randomly divided into two groups, a bipolar group (Group I) and a control group (Group II). Laminectomy was performed between the L1 and L3 levels. In Group I (n=7), a laminectomy was carried out and soft tissue around the spinal cord was coagulated by using a bipolar electrocautery. In the control group (n=7), only laminectomy was performed. The animals were sacrificed 4 weeks after surgery, and post-laminectomy epidural fibrosis (PLEF) was evaluated. Macropathological, qualitative and quantitative histological evaluations as well as immunohistochemical staining including transforming growth factor-ß (TGF-ß), collagen I and collagen III were performed. RESULTS: The numbers of TGF-ß positive cells staining (PCS) were 3.00 ± 0.46 for Group I and 1.00 ± 0.52 for Group II. The numbers of collagen I PCS were 2.00 ± 0.93 for Group I and 1.25 ± 0.46 for Group II. The numbers of collagen III PCS were 2.25 ± 0.76 for Group I, 1.25 ± 0.46 for Group II, and TGF-ß PCS than Group II (p≤0.05). Compared with the control group, Group I's formation of epidural fibrosis was significantly increased. CONCLUSION: Our study clearly demonstrated that the use of bipolar cauterisation is associated with increased PLEF in the experimental animal model. Thus, limiting the use of bipolar cauterisation may be effective in reducing this complication.

Effect of Cetuximab on the Development of Epidural Fibrosis Based on CD105 and Osteopontin Immunohistochemical Staining.

STUDY DESIGN: The effect of cetuximab on the development of epidural fibrosis (EF) was assessed using immunohistochemical methods as well as antibodies for CD105 and osteopontin (OPN). OBJECTIVE: The goal of this study was to assess of EGFR inhibition for the postoperative treatment of fibrosis. SUMMARY OF BACKGROUND DATA: EF is one of most common causes of failed back surgery syndrome, which occurs after laminectomy. Numerous causes and mechanisms have been proposed to explain its development after laminectomy. Many agents have been tested to prevent the development of EF. EGFR, a multi-functional transmembrane glycoprotein, causes cell growth, proliferation, and EF by interacting with epidermal growth factor and TGF-ß1. The inhibition of postoperative fibrosis using cetuximab, an epidermal growth factor receptor blocker, is theoretically possible. However, this has not been tested to date. METHODS: Sixteen Wistar-Albino rats were divided into two groups, namely, control and cetuximab groups. L1-2 laminectomy alone was performed in both groups, and topical cetuximab was applied to the treatment group. After 6 weeks, rats were sacrificed and examined histopathologically and immunohistochemically; EF tissue was also graded. Statistical significance was accepted at P < 0.05. RESULTS: Fibroblast counts and fibrosis density, determined by histopathologic examination, and EF, according to immunohistochemical assessment based on CD105, were found to be higher in the treatment group than in the control group, and this was statistically significant (P < 0.001). Based on OPN staining, the results were consistent with classical methods, and no significant difference was detected among the groups (P = 0.358). CONCLUSION: Our study revealed that cetuximab inhibits the development of EF and that CD105, and not OPN, is a reliable marker for grading EF. In addition, cetuximab did not result in toxic, systemic side effects in surrounding tissues. LEVEL OF EVIDENCE: N/A.

[Changes in Spinal MRI Findings for Epidural Fluid Collection in the Treatment of Intracranial Hypotension].

We have experienced 30 cases of intracranial hypotension in the last three years. Spinal MRI was performed in all cases, and 27 patients demonstrated epidural fluid collection(EFC). Of these 30 patients, 6 were treated conservatively with bed rest and hydration, and 24 were treated with epidural blood patch(EBP). Twenty-two patients were cured, 4 were improved significantly, and 4 were improved partially. We examined spinal MR images of 22 patients after 3 months of treatment. The EFC wasn't visible in 11 cases;however, residual EFC was found in the 11 remaining cases. The patients without EFC were cured. Of the 11 patients with residual EFC, 4 patients were cured, 4 were improved significantly, and 3 showed partial improvement. Furthermore, in subsequent spinal MRI of 7 patients, EFC wasn't visible in 2 patients;however the patients continued to experience moderate orthostatic headache. Therefore, while EFC is closely associated with spinal CSF leakage, the presence of CSF leakage doesn't necessitate the observation of EFC by current MRI. In post-treatment spinal MRI, we sometimes observed residual EFC in the ventro-lateral area of the spinal dural sac, especially in the thoracic region;hence, we speculated that CSF leakage may occur in the ventro-lateral aspect of spinal dural sac in many cases of intracranial hypotension. Moreover, in these cases, subsequent treatment with EBP cannot assure the delivery of autologous blood to the residual EFC. Therefore, we considered that the residual EFC in the ventro-lateral epidural space is often separated from its dorsal part.

Unintentional Infusion of Phenylephrine into the Epidural Space.

We describe a patient who received an unintentionally prolonged epidural infusion of phenylephrine. The patient experienced no major morbidity. However, this case highlights the continuing problem of wrong-route drug administration and the urgent need to adopt route-specific connections.

An experimental novel study: hyperbaric oxygen treatment on reduction of epidural fibrosis via down-regulation of collagen deposition, IL-6, and TGF-ß1.

OBJECTIVE: To investigate the effect of hyperbaric oxygen treatment (HBO) on prevention of epidural fibrosis in laminectomy rats. METHODS: A controlled, double-blinded study was performed in sixty healthy adult Wistar rats, mean weight 250 g. L1-L2 levels laminectomy were performed. Randomly, all rats were divided into three groups, with 20 in each group: (1) short-term HBO treatment group; (2) long-term HBO treatment (LHBO) group; and (3) Sham group (laminectomy without treatment). Four weeks post-operation, all rats were killed. The Rydell classification, hydroxyproline content, vimentin cells density, capillary density, and inflammatory factors expression were evaluated. RESULTS: The histological evaluation showed less epidural scar adhesions in LHBO group than other two groups. The hydroxyproline content, Rydell score, vimentin cells density, capillary density, and inflammatory factors expression all suggested better results in LHBO group than other two groups. CONCLUSION: It was concluded that HBO treatment might be beneficial in inhibiting collagen deposition and inflammatory activity and prevent epidural scar adhesion in laminectomy rat and, therefore, shows potential for clinical use.

Quantifying subtle but persistent peri-spine inflammation in vivo to submicron cobalt-chromium alloy particles.

PURPOSE: We evaluated the consequences of cobalt-chromium alloy (CoCr) wear debris challenge in the peri-spine region to determine the inflammation and toxicity associated with submicron particulates of CoCr-alloy and nickel on the peri-spine. METHODS: The lumbar epidural spaces of (n = 50) New Zealand white rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy and Ni particles had a mean diameter of 0.2 and 0.6 µm, respectively. Five rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues were analyzed histologically and quantitatively analyzed immunohistochemically (TNF-α and IL-6). RESULTS: Histologically, wear particles were observed in all animals. There was no evidence of toxicity or local irritation noted during macroscopic observations in any CoCr-dosed animals. However, Ni-treated control animals experienced bilateral hind leg paralysis and were euthanized at Day 2. Histopathology of the Ni particle-treated group revealed severe neuropathy. Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent increase in cytokines (IL-6, TNF-α, p < 0.05) at 12 and 24 weeks. CONCLUSIONS: Subtle peri-spine inflammation associated with CoCr-alloy implant particles was dose dependent and persistent. Neuropathy can be induced by highly reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant debris (e.g., TDA) is consistent with past reports using titanium alloy particles, i.e., mild persistent inflammation.

Excrescence of neurotransmitter glutamate from disc material has nociceptive qualities: evidence from a rat model.

BACKGROUND CONTEXT: The authors have previously demonstrated that herniated human lumbar disc is rich in free glutamate from degradation of aggrecan. Prior data have suggested that free glutamate could contribute to a nociceptive state. PURPOSE: Previous behavioral experiments suggested glutamate-related nociception by comparing pre- and postglutamate infusion responses only. This indirectly suggested nociceptive effects of epidural glutamate but was not a definitive evidence. Now, by using larger numbers of subjects, we have demonstrated that lumbar epidural glutamate infusion causes significant left-to-right differences in hind paw response during treatment, demonstrating more directly the focal nociceptive effects of glutamate. STUDY DESIGN: Behavioral studies and immunohistochemistry were used to assess for evidence of a nociceptive state. All researchers were blinded to infusion solution. METHODS: Via an implanted mini osmotic pump, the epidural space of rats was infused with 0.02 mM glutamate or normal saline for 72 hours. Signs of nociception were assessed by von Frey and plantar thermal stimulation testing and by glutamate receptor expression in the corresponding dorsal horn of the spinal cord and dorsal root ganglion. RESULTS: Both von Frey mechanical and plantar thermal stimulations showed differences in hind paw reactivity depending on whether it was on the ipsilateral or contralateral side of glutamate infusion. Saline infusion had no significant behavioral effects. Dorsal horn expression of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid and N-methyl-d-aspartic acid receptors was significantly increased in glutamate-infused animals, further indicative of a nociceptive state related to glutamate infusion. CONCLUSIONS: Elevated epidural glutamate concentrations caused a focal hyperesthetic state. Increased epidural glutamate concentration could be a driving force or "chemical" component of disc-related radiculopathy.