Do Tumour Size, Type and Localisation Affect Resection Rate in Patients with Spinal Schwannoma?

Background and Objectives: Spinal schwannomas are benign tumours that can present with various symptoms such as pain, radiculopathy and neurological deficit. Gross total resection (GTR) is of key importance for local recurrence. The aim of this study is to describe the clinical characteristics, resection rate, clinical outcome, as well as tumour recurrence, in patients with non-syndromic spinal schwannomas and to clarify which factors affect the resection rate. Materials and Methods: Patients with non-syndromic spinal schwannomas that underwent surgical resection between January 2009 and December 2018 at a single institution were included. Demographic parameters, clinical symptoms, tumour localisation and size, surgical approach and complications were noted. Factors influencing the extent of resection, the surgeon's decision regarding the approach and the occurrence of new postoperative deficits were evaluated. Results: Fifty patients (18 females) were included. The most common presenting symptom was radiculopathy (88%). The lumbar spine was the most commonly affected site (58%). Laminotomy (72%) was the preferred surgical approach overall and specifically for exclusively intraspinal schwannomas (p = 0.02). GTR was achieved in 76.0% (n = 38). In multivariate analysis, only tumour localisation within the spinal canal (p = 0.014) independently predicted GTR, whereas the type of approach (p = 0.50) and tumour volume (p = 0.072) did not. New postoperative persisting deficits could not be predicted by any factor, including the use and alteration of intraoperative neuromonitoring. Recurrence was observed in four cases (8%) and was significantly higher in cases with STR (p = 0.04). Conclusions: In this retrospective study, GTR was solely predicted by tumour localisation within the spinal canal. The decision regarding the utilisation of different surgical approaches was solely influenced by the same factor. No factor could predict new persisting deficits. Tumour recurrence was higher in STR.

First neurological symptoms in degenerative cervical myelopathy: does it predict the outcome?

PURPOSE: Degenerative cervical myelopathy (DCM) is the most common non-traumatic cause of spinal cord dysfunction. Prediction of the neurological outcome after surgery is important. The aim of this study was to analyze the relationship between first symptoms of DCM and the neurological outcome after surgery. METHODS: A retrospective analysis over a period of 10 years was performed. First symptoms such as cervicobrachial neuralgia, sensory and motor deficits and gait disturbances were evaluated regarding the postoperative neurological outcome. The modified Japanese Orthopedic Association Score (mJOA Score) was used to evaluate neurological outcome. RESULTS: In total, 411 patients (263 males, 64%) with a median age of 62.6 ± 12.1 years were included. Cervicobrachial neuralgia was described in 40.2%, gait disturbance in 31.6%, sensory deficits in 19% and motor deficits in 9.2% as first symptom. Patients with cervicobrachial neuralgia were significantly younger (median age of 58 years, p = 0.0005) than patients with gait disturbances (median age of 68 years, p = 0.0005). Patients with gait disturbances and motor deficits as first symptom showed significantly lower mJOA Scores than other patients (p = 0.0005). Additionally, motor deficits and gait disturbance were negative predictors for postoperative outcome according to the mJOA Score. CONCLUSION: Motor deficits and gait disturbances as the first symptom of DCM are negative predictors for postoperative neurological outcome. Nevertheless, patients with motor deficits and gait disturbance significantly profit from the surgical treatment despite poor preoperative mJOA Score.

Surgical outcome and prognostic factors in spinal cord ependymoma: a single-center, long-term follow-up study.

OBJECTIVE: Spinal cord ependymomas account for 3-6% of all central nervous system tumors and around 60% of all intramedullary tumors. The aim of this study was to analyze the neurological outcome after surgery and to determine prognostic factors for functional outcome. PATIENTS AND METHODS: Patients treated surgically due to a spinal cord ependymoma between 1990 and 2018 were retrospectively included. Demographics, neurological symptoms, radiological parameters, histopathology, and neurological outcome (using McCormick Score [MCS]) were analyzed. Possible prognostic factors for neurological outcome were evaluated. RESULTS: In total, 148 patients were included (76 males, 51.4%). The mean age was 46.7 ±â€„15.3 years. The median follow-up period was 6.8 ±â€„5.4 years. The prevalence was mostly in the lumbar spine (45.9%), followed by the thoracic spine (28.4%) and cervical spine (25.7%). Gross-total resection was achieved in 129 patients (87.2%). The recurrence rate was 8.1% and depended on the extent of tumor resection (p = 0.001). Postoperative temporary neurological deterioration was observed in 63.2% of patients with ependymomas of the cervical spine, 50.0% of patients with ependymomas of the thoracic spine, and 7.4% of patients with ependymomas of the lumbosacral region. MCS 1-2 was detected in nearly two-thirds of patients with cervical and thoracic spinal cord ependymoma 36 months after surgery. Neurological recovery was superior in thoracic spine ependymomas compared with cervical spine ependymomas. Poor preoperative functional condition (MCS >2), cervical and thoracic spine location, and tumor extension >2 vertebrae were independent predictors of poor neurological outcome. CONCLUSION: Neurological deterioration was seen in the majority of cervical and thoracic spine ependymomas. Postoperative improvement was less in thoracic cervical spine ependymomas compared with thoracic spine ependymomas. Poor preoperative status and especially tumor extension >2 vertebrae are predictors of poor neurological outcome (MCS >2).

Risk score for outcome prediction after microsurgical resection of spinal ependymoma (SOURSE score).

OBJECTIVE: Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma. MATERIALS AND METHODS: All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery. RESULTS: Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0-3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively. CONCLUSION: The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial.

Predictors of Brain Natriuretic Peptide Serum Level Elevation in Patients with Symptomatic Chronic Subdural Hematoma: A Prospective Study.

BACKGROUND: Brain natriuretic peptide serum levels (BNP) on admission are frequently elevated in patients with symptomatic chronic subdural hematoma (cSDH) and predict unfavorable long-term functional outcomes. However, the reasons for these elevated levels remain unclear. Therefore, we aimed to identify the predictors of BNP elevation. METHODS: Patients with unilateral symptomatic cSDH who were surgically treated in our department between November 2016 and May 2020 were enrolled. Patients' symptoms and neurological deficits were prospectively assessed using a study questionnaire. On initial computer tomography, hematoma volumes and midline shift (MLS) values were measured to analyze the degree of brain compression. RESULTS: In total, 100 patients were analyzed. Linear regression analysis showed that higher BNP levels were significantly associated with smaller hematoma volumes (p = 0.003) and littler MLS values (p = 0.022). Multivariate analysis revealed that presence of a neurological deficit (p = 0.041), a hematoma volume < 140 mL (p = 0.047), advanced age (p = 0.023), and head trauma within 24 h of admission (p = 0.001) were independent predictors of BNP elevation. CONCLUSION: In symptomatic cSDH, BNP elevation is related, among others, to the presence of neurological deficits and smaller hematoma volumes. Whether BNP elevation may coincide with the early stage of hematoma growth, i.e., immaturity of cSDH neomembrane, requires further investigations.

Role of new agents affecting NO/cGMP pathway on ovalbumin-sensitized guinea pig trachea.

Asthma is a chronic inflammatory disease in which cell components play important roles. We aimed to evaluate the effects of NO/cGMP cleavage at trachea preparations isolated from ovalbumin-sensitized guinea pigs in vitro. Trachea rings were exposed to 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-12), (±)-(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl-nicotinamide (NOR-4), 2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl)-8-(pyrimidin-2-yl) methoxy-1,2-dihydro-1-oxo-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride (T-0156), and electrical field stimulation (EFS). cGMP levels in trachea tissues were also measured. The relaxation responses of NOC-12, NOR-4, T-0156, and EFS were significantly decreased at ovalbumin-sensitized group. Nitric oxide (NO) donors significantly decreased the relaxation responses in the presence of 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ). L-Nitro-Arginine Methyl Ester (L-NAME) significantly decreased the EFS relaxation responses in both groups (experimental group and control group), but this effect was reversed by L-Arginine addition. In the experimental group, cGMP levels after EFS, carbachol, NOC-12, NOR-4, and T-0156 exposure were significantly lower than control group. In both groups, cGMP levels after NO donors' exposure were significantly lower in the presence of ODQ and the cGMP levels after EFS + L-NAME were significantly lower than EFS alone. These results may show the increased formation of NO because of the increased iNOS activity in airway sensitization leading to the inhibition of cNOS resulting in the decrease of endogen NO and decrease of activation of guanylyl cyclase.

Rho-kinase inhibitors Y-27632 and fasudil prevent agonist-induced vasospasm in human radial artery.

Radial artery (RA) vasospasm remains a potential cause of early graft failure after coronary artery bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. Our aim was to investigate the mechanism of the vasorelaxant effects of Rho-kinase inhibitors (Y-27632 and fasudil) on the human RA. Segments were obtained from 30 patients undergoing coronary artery bypass graft and were divided into 3-4 mm vascular rings. The rings were stimulated with 10(-5) mol/L phenylephrine (PE) by using the isolated tissue bath technique and were relaxed with 10(-6) mol/L acetylcholine. Relaxation responses were recorded for Y-27632 (10(-9)-10(-4) mol/L), fasudil (10(-9)-10(-4) mol/L), and sodium nitroprusside (SNP) (10(-9)-10(-5) mol/L). Y-27632 and fasudil relaxation responses were repeated in either N(G)-nitro-L-arginine (L-NNA), which is a specific endothelial nitric oxide synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which is a guanylate cyclase inhibitor. SNP relaxation responses were repeated in 10(-8) mol/L Y-27632 and 10(-8) mol/L fasudil. Y-27632 and fasudil caused concentration-dependent vasorelaxation in RA rings precontracted with PE, and maximal relaxation (100%) was recorded at the highest concentration used (10(-4) mol/L). The vasorelaxant effects of Y-27632 and fasudil were significantly reduced in the presence of L-NNA and ODQ, and the pD2 values of Y-27632 and fasudil were not changed. The vasorelaxant effects of SNP were significantly increased in the presence of Y-27632 and fasudil, and the pD(2) values of SNP were not changed. These findings indicate that Y-27632 and fasudil caused concentration-dependent vasorelaxation in the RA rings. Because this effect was decreased in a dose-dependent manner by L-NNA and ODQ, the relaxant effects of Y-27632 and fasudil could be due to stimulation by nitric oxide that is being released. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.

Nifedipine enhances the relaxant effects of cyclo-oxygenase inhibitors on the bovine ciliary muscle.

BACKGROUND/AIMS: The inhibition of cyclo-oxygenase (COX) enzymes and the blockade of Ca (2+) channels play an important role in the regulation of smooth muscle relaxation. This study was designed to investigate the relaxant effects of celecoxib, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), and indomethacin, cyclo-oxygenase (COX-1 and -2) inhibitors, in the absence or presence of a nifedipine, L-type Ca(2+) channel blocker, on bovine ciliary muscle. METHODS: Ciliary muscle strips (n = 12) were mounted in organ baths and tested for changes in isometric tension in response to celecoxib, DFU, and indomethacin. The relaxant effects of celecoxib, DFU, and indomethacin on carbachol-induced contractions in the presence or absence of nifedipine were investigated. RESULTS: Celecoxib (10(-7)-10(-4) M), DFU (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M), and nifedipine (10(-7)-10(-4) M) inhibited the carbachol-induced contractions in a concentration-dependent manner. The E(max) value of indomethacin was significantly higher than the E(max) values of celecoxib and DFU in ciliary muscle (P < 0.05), with no significant change in pD(2) values (P > 0.05). The relaxation responses by celecoxib, DFU, and indomethacin were significantly increased in the presence of nifedipine (10(-6) M). There were no significant differences between pEC50 and values of celecoxib, DFU, and indomethacin in the absence of nifedipine (10(-6) M) (P > 0.05), but E(max)values were significantly increased (P < 0.05). CONCLUSIONS: These results suggest that the celecoxib, DFU, and indomethacin cause relaxation in ciliary muscle precontracted with carbachol. Blockade of calcium channels with nifedipine in ciliary muscle may increase the relaxant effect of celecoxib, DFU, and indomethacin. The topical or systemic use of celecoxib, DFU, and indomethacin with nifedipine can cause blurred near vision due to ciliary muscle relaxation, and in ocular pain conditions caused by ciliary spasm, the pain can be decreased more easily by combined use of these drugs.

Investigation of acute effects of aflatoxin on rat proximal and distal colon spontaneous contractions.

Aflatoxins are one of the most potent toxic, mutagenic, teratogenic, cancerogenic, and immunosuppresive substances that naturally occurring contaminants of food. There are some studies in various animal species that have reported aflatoxin effects on gastrointestinal systems, but acute effects of aflatoxins have not been clearly investigated. In this study, we aimed to investigate the acute gastrointestinal effects of total aflatoxin on rat isolated proximal and distal colon. Aflatoxin was given cumulatively at 10(-8)-10(-5)M concentrations and the amplitude and frequency of proximal and distal colon contractions were increased significantly. In the presence of atropine sulfate (23.6 nM) and morphine (0.3 microM) the amplitude and frequency of aflatoxin induced spontan contractions in the proximal and distal colon decreased significantly, on the other hand, L-NNA (0.3 microM) increased contractions' amplitude and frequency significantly in the proximal colon but not in the distal colon. In conclusion, aflatoxin may increase the amplitude and frequency of contractions by increasing muscarinic activity or by decreasing NO synthase and/or release in proximal colon and by increasing muscarinic activity in the distal colon. These findings of aflatoxin on isolated rat proximal and distal colon may explain their acute gastrointestinal effects in humans and animals.

Changes in spontaneous contractions of rat ileum by aflatoxin in vitro.

Aflatoxins are a group of mycotoxins produced by toxigenic strains of Aspergillusflavus, Aspergillusparasiticus and Aspergillusnomius as secondary metabolites. Most of the studies on the aflatoxins have focused mainly on their chronic toxic effects but aflatoxins have also a lot of acute effects on the respiratory, cardiovascular and gastrointestinal systems. In this study the acute gastrointestinal effects of the aflatoxins on rat isolated ileum and the possible mechanisms underlying contractile responses to them were investigated. Aflatoxin increased both of the amplitude and the frequency of spontaneous contractions in a dose-dependent manner. Pretreatment with a cholinergic system inhibitor, atropine sulfate (23.6nM), a specific sodium-channel blocker, tetrodotoxin (0.3microM) and an inhibitor of ACh release from terminal motor neurons, morphine (0.3microM) decreased both of aflatoxin induced spontaneous contractions' amplitude and frequency, in contrast a nicotinic ganglionic blocker, hexamethonium chloride (55microM) did not change the aflatoxin effect. But the decrease of amplitude was more than the frequency in the presence of these antagonists. In conclusion, these findings of aflatoxin on isolated rat ileum may explain their acute gastrointestinal effects in humans and animals.

Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized guinea-pig trachea.

Nicotine is an irritant molecule in the cigarette that contributes airway hyper-reactivity. The aim of this study was to investigate the mechanism of these effects and effects of nicotine on the isolated trachea preparations from control and ovalbumin-sensitized guinea-pigs. Nicotine (3x10(-5) to 3x10(-4) M) produced concentration-dependent relaxation on isolated trachea preparations precontracted by carbachol (10(-6) M) in both groups. We found that the relaxant effect of nicotine decreased in the presence of N(w)-nitro L-arginine methyl ester (L-NAME) (10(-6) M), and hexamethonium (10(-2) M) but not in the presence of alpha-bungarotoxin (10(-3) M), and tetrodotoxin (3.1x10(-6) M) in isolated trachea preparations in both groups. The relaxant effect of nicotine was less significant in isolated trachea preparations from ovalbumin-sensitized guinea-pigs than from control guinea-pigs (P<0.05). The contractions elicited by carbachol (10(-6) M) were not significantly different in the ovalbumin-sensitized group than in the control group. Nicotine (10(-4) M) significantly increased the cGMP levels in trachea preparations compared with the control preparations.(P<0.05). These results suggest that nicotine-induced relaxation response in normal and ovalbumin sensitized guinea-pigs trachea is at least in part mediated by nitric oxide (NO) since it was significantly reduced in the presence of L-NAME. The decreased relaxation response to nicotine in ovalbumin sensitized guinea-pigs trachea may be due to impaired production and/or liberation of NO.

Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in normotensive and pre-eclamptic pregnancy.

Alterations in vascular responses to beta-adrenoceptor agonists in normotensive pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in vasodilator responses to beta(2)-adrenoceptor agonist formoterol and beta(3)-adrenoceptor agonist BRL 37344 on umbilical arteries isolated from normotensive (n=12) and pre-eclamptic (n=12) pregnant women. Changes in the relaxant effect of formoterol and BRL 37344 were investigated by measuring isometric tensions in endothelium-denuded strips of umbilical arteries in the presence or absence of metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor antagonists, respectively, 10(-6) mol/L). Effects of formoterol and BRL 37344 on cAMP levels of umbilical arteries were evaluated by radioimmunoassay kits. Formoterol (10(-10)-10(-4) mol/L) and BRL 37344 (10(-10)-10(-4) mol/L) caused concentration-dependent relaxation of the contraction induced by phenylephrine (10(-5) mol/L) in umbilical artery strips isolated from both groups. E(max) values of formoterol and BRL 37344 (for normotensive pregnant women: 87.33+/-0.87 and 53.25+/-1.17 vs. for pre-eclampsia: 73.68+/-1.58 and 43.64+/-1.19, n=12, P>0.05, respectively) were significantly smaller in strips from pre-eclamptic women (P<0.05), with no significant change in pD(2) values. E(max) values of formoterol were significantly higher than those of BRL 37344 in both tissue (P<0.05). ICI 118.551 and SR 59230A, but not metoprolol, antagonized the relaxant effects of formoterol and of BRL 37344 on umbilical artery strips isolated from normotensive and pre-eclamptic pregnant women. Formoterol and BRL 37344 increased cAMP levels in both groups, but less significant in pre-eclamptic strips (P<0.05). These results suggest that the relaxation caused in human umbilical arteries by formoterol and BRL 37344 is mediated by a mixed population of beta(2)- and beta(3)-adrenoceptor subtypes, with contribution of cAMP. Umbilical arteries from subjects with pre-eclampsia showed a weaker beta(2)- and beta(3)-receptor-mediated relaxation to formoterol and BRL 37344, suggesting that the reduced action of formoterol and BRL 37344 may be partly due to a decreased effect of cAMP.

Additive interaction of intraperitoneal dexmedetomidine and topical nimesulide, celecoxib, and DFU for antinociception.

Nimesulide, celecoxib, and DFU (5, 5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) are nonsteroidal anti-inflammatory drugs (NSAIDs) with selective cyclo-oxygenase (COX)-2 blocking properties and have potent analgesic and anti-inflammatory activities in oral and parenteral administrations. Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is an extremely potent antinociceptive agent. The present study was conducted to evaluate the antinociception induced by nimesulide, celecoxib, and DFU when topically applied on the tail in the absence or presence of intraperitoneal dexmedetomidine. Antinociception was measured in the radiant tail-flick test after immersion of the tail of rat into a solution of dimethyl sulfoxide (DMSO) containing nimesulide, celecoxib, or DFU. Antinociceptive effect of all drugs peaked at 60 min and decreased gradually to baseline levels at 240 min. Nimesulide had a potency lower than those of celecoxib, and DFU. The antinociceptive effect of dexmedetomidine was blocked by systemic pretreatment of selective alpha(2)-adrenoceptor antagonist, atipamezole. This suggests that antinociceptive effects of dexmedetomidine involve alpha(2)-adrenoceptors. Combination of topical COX-2 inhibitors with intraperitoneal dexmedetomidine yielded additive analgesic effect. These results demonstrate an additive interaction between topical COX-2 inhibitors with intraperitoneal dexmedetomidine. These observations are significant for physicians to combine selective COX-2 inhibitors and dexmedetomidine in the management of pain.