Methylprednisolone Sodium Succinate Group Research Articles

Clinical Evaluation of the Effect of Methylprednisolone Sodium Succinate and Meloxicam in Experimental Acute Spinal Cord Injury

Background: Central nervous system (CNS) has limited repair capacity, and any spinal cord injury (SCI) can cause persistent disability in motor, sensory, and autonomic functions. The harmful reactions around the lesion must be stopped to prevent this consequence. Objectives: The present study compares the clinical effects of methylprednisolone sodium succinate (MPSS) and meloxicam in acute spinal cord injury in an animal model of rats. Methods: We randomly divided 24 male Wistar rats into 4 groups: 1) sham, 2) placebo, 3) SCI+MPSS (30 mg/kg, IV), and 4) SCI+meloxicam (1 mg/kg, SC). We used a Fogarty embolectomy catheter to induce a compression injury to the rats’ T8-T9 spinal cord segment. The drugs were injected one hour after surgery. Neurological evaluation was performed using BBB (Basso, Beattie, and Bresnahan) test immediately after recovery and then once a week for up to 6 weeks. Results: According to the BBB test results, single-dose administration of MPSS one hour after injury improved motor function significantly compared to placebo. But, there was no significant difference between MPSS and meloxicam groups and between meloxicam and placebo groups (P>0.01). Conclusion: In clinical evaluation, single-dose administration of MPSS one hour after injury improved motor function compared to meloxicam.

Comparative analysis of neurological recovery and adverse effects in chondrodystrophic dogs with thoracolumbar intervertebral disc herniation treated with methylprednisolone versus non-steroidal anti-inflammatory drugs

Thoracolumbar intervertebral disc herniation is a common neurological disease presented to the small-animal practitioner. The use of methylprednisolone sodium succinate (MPSS) as an adjunct to surgical decompression in cases of acute spinal cord injury following intervertebral disc extrusion is controversial. A prospective study was undertaken to compare the perioperative use of MPSS and non-steroidal anti-inflammatory drugs (NSAIDs) in 40 chondrodystrophic dogs presenting with similar signs and undergoing spinal decompressive surgery. Twenty dogs received MPSS and 20 had NSAIDs administered preoperatively. Dogs were administered with either MPSS intravenously 20 min before surgery (30 mg/kg) or NSAID (meloxicam 0.2 mg/kg or carprofen 4 mg/kg) subcutaneously 20 min before surgery. Dogs were evaluated by neurological examination of gait 24 h postoperatively, at time of discharge, and then at 8 weeks. The neurological recovery was similar in both groups, but the frequency of side effects such as vomiting (MPSS group: 90% vs NSAIDs group: 55%), and anorexia within the first three days (present in all 20 dogs pretreated with MPSS) was significantly different, with complications being more prevalent in the MPSS group. This study showed that side effects were significantly more evident with the MPSS treatment group than with the NSAID group, with a neurological recovery similar in both groups.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6h after the occurrence of facial paralysis and peaked after 2days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate.

Introduction:The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI).Methods:A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.”Results:The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) “We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI”; (2) “We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option”; and (3) “We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI.”Conclusions:These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients.

The dose-dependent neuroprotective effect of alpha-lipoic acid in experimental spinal cord injury

Background and purposeFree radical production after spinal cord injury (SCI) plays an important role in secondary damage. The aim of this study was to investigate neuroprotective effects of the powerful antioxidant alpha-lipoic acid (ALA) in a spinal cord clip compression injury model. Material and methodsFifty-six Sprague-Dawley rats, weighing between 210 and 300 g, were randomly divided into seven groups. Spinal cord injury was performed by an aneurysm clip placed extradurally at the level of T9. Group 1 (sham) received laminectomy only. Group 2 (control) received SCI; Group 3 received 30 mg/kg of methylprednisolone sodium succinate (MPSS); Groups 4, 5, 6 and 7 received ALA at doses of 50, 100, 150, 200 mg/kg, respectively, via the intraperitoneal route immediately after SCI. The rats were neurologically tested 24 hours after trauma. Spinal cord samples from injury sites were harvested for measurement of lipid peroxidation products and histopathological evaluation. ResultsSpinal cord malonyldialdehyde levels of rats in treatment groups decreased after administration of ALA. The difference between the trauma group and groups receiving MPSS-ALA was statistically significant. The difference between the ALA (50, 100, 150 mg/kg) and MPSS groups was insignificant. Group 7 (ALA 200 mg/kg) was excluded from the study because of the possible toxic effect. Alpha lipoic acid and MPSS had similar effects on spinal cord injury in terms of lipid peroxidation, neurological recovery and histopathological changes. ConclusionsAlpha lipoic acid at a dose range of 50–150 mg/kg is as effective as MPSS (30 mg/kg) in neuroprotection after SCI. Further, more detailed experimental studies are needed to determine the effects of ALA on the detrimental results of secondary SCI before its use in humans.

Does High Dose Methylprednisolone Sodium Succinate Really Improve Neurological Status in Patient With Acute Cervical Cord Injury?

Consecutive cohort study. To reconsider effects of the Second National Acute Spinal Cord Injury Study. High dose methylprednisolone sodium succinate (MPSS) for the patients with acute spinal cord injury has been considered standard treatment in the several countries. However, many authors have criticized the effect of MPSS because of lack of evidence about neurologic improvement and the high incidence of complications. During 2-year, all patients with cervical cord injury were treated with MPSS within 8 hours of their injuries based on the Second National Acute Spinal Cord Injury Study protocol (MPSS group). During the next 2-year, all patients were treated without MPSS (non-MPSS group). There were 38 patients in the MPSS group and 41 in the non-MPSS. Early spinal decompression and stabilization was performed as soon after injury in both the groups. According to The American Spinal Injury Association (ASIA) motor score, there was an average improvement by 3 months postinjury of 12.4 points in the MPSS group and 13.8 points in the non-MPSS group. In patients with complete motor loss, average ASIA motor score improved 9.0 points in the MPSS group and 12.6 points in the non-MPSS group. For patients with incomplete motor loss, average ASIA motor score improvement was 14.1 and 15.5 points in the MPSS and non-MPSS groups, respectively.In the MPSS group, 19 patients developed pneumonia, 13 developed urinary tract infections, and 5 developed wound infections. Incidence of pneumonia was significantly increased with the use of MPSS medication. We found no evidence supporting the opinion that high-dose MPSS administration facilitates neurologic improvement in patients with spinal cord injury. We believe MPSS should be used under limited circumstances because of the high incidence of pulmonary complication.

Effects of the Second National Acute Spinal Cord Injury Study of High-Dose Methylprednisolone Therapy on Acute Cervical Spinal Cord Injury–Results in Spinal Injuries Center

Retrospective single-center study. To evaluate the recovery of motor function and the early complications in patients with acute cervical spinal cord injury after receiving a high dose of methylprednisolone sodium succinate (MPSS) within 8 hours of injury. High-dose MPSS therapy has been demonstrated to improve the neurologic recovery in patients with acute spinal cord injury. However, it remains a controversial treatment. Seventy patients were included in this study: 37 in the MPSS group who were treated with MPSS within 8 hours of their injury according to the Second National Acute Spinal Cord Injury Study protocol, and 33 in non-MPSS group who were not administered with MPSS. Improvements in the American Spinal Injury Association motor score were compared between the MPSS group and the non-MPSS group. In patients with complete motor loss at admission and follow-up periods, improvements of myotomal levels between the MPSS (n = 15) and non-MPSS groups (n = 21) were compared. Early complications within 6 weeks of high-dose MPSS therapy were compared with those of no MPSS therapy. Among the patients with incomplete paralysis at admission, the American Spinal Injury Association motor scores in the MPSS group were improved more significantly than those in the non-MPSS group at 6 weeks and 6 months after injury. Meanwhile, among the patients with complete paralysis at admission, the patients in the MPSS group did not show significantly more change in motor score than those in the non-MPSS group. Improvement in myotomal level had no significant difference between the MPSS and non-MPSS groups. The MPSS group had 10 patients with early complications, while the non-MPSS group had 14. The differences between the 2 groups showed no statistical significance. MPSS should be administered to patients with incomplete cervical spinal cord injury according to the Second National Acute Spinal Cord Injury Study protocol.

Histologic changes in the intervertebral disc after intradiscal injections of methylprednisolone acetate in rabbits.

Histologic changes in the intervertebral disc were evaluated by light and electron microscopy after an intradiscal injection of methylprednisolone acetate. To evaluate the histologic changes that occur in the disc after an intradiscal injection of cortico steroids. Several orthopedic surgeons have managed lumbar disc herniation with intradiscal steroid injection. Few studies have addressed the histologic changes after this treatment. Thirty rabbits were surgically treated. Rabbits were divided into two groups. Group A: 25 rabbits underwent intradiscal steroid injections. Methylprednisolone acetate was injected into the L3-L4 disc, whereas methylprednisolone sodium succinate was injected into the L4-L5 disc. Physiologic saline was injected into the L5-L6 disc as a control. Groups of five rabbits were killed 1 day, 1, 4, 12, and 24 weeks after the injection and subjected to microscopic evaluation. Group B: Another five rabbits underwent an injection of polyethylene glycol 4000, a vehicle for methylprednisolone acetate, into the L3-L4 and L4-L5 discs. All five rabbits were killed 24 weeks after the injection and subjected to microscopic evaluation. Group A: Light microscopic evaluation showed tissue in the nucleus pulposus, and the inner layer of the anulus fibrosus had degenerated in the methylprednisolone acetate group killed 24 weeks after the injection. Matrix vesicles, an indication of primary tissue calcification, were observed by electron microscopy. In the methylprednisolone sodium succinate group and saline group, however, no histologic changes were observed. Group B: Degeneration of the nucleus pulposus and primary tissue calcification were observed in the discs of all rabbits. Methylprednisolone acetate and its vehicle polyethylene glycol cause degeneration and primary calcification in discs.

Modeling of Acute Spinal Cord Injury in the Rat: Neuroprotection and Enhanced Recovery with Methylprednisolone, U-74006F and YM-14673

We used a new injury device that produces consistent spinal cord contusion injuries (T8) in rats to compare the behavioral and histologic effects of methylprednisolone sodium succinate (MPSS) administration, the clinical standard of therapy after acute spinal cord injury (ASCI), with the 21-aminosteroid, U-74006F (U74), and the TRH analogue, YM-14673 (YM), at different trauma doses. Three sequential experiments were conducted: Experiment 1 . U74 (3.0/1.5/1.5 mg/kg; 10/5/5 mg/kg; 30/15/15 mg/kg), MPSS (30/15/15 mg/kg), or vehicle were administered intravenously (iv) at 5 min, 2 and 6 h after the injury (n = 8/group). U74 (10/5/5 mg/kg) and MPSS animals scored better than controls (Days 8-43) in open field walking (OFW); no other differences were seen between groups. Experiment 2. Dose-response evaluation of MPSS determined more effective doses. Groups (n = 16) receiving 30/30/30/30 mg/kg and 60/60/60/60 mg/kg iv at 5 min and 2, 4, and 6 h after the injury had better OFW scores than controls (Days 8-29; Day 29). Both groups performed better than controls (Days 8-29) on inclined plane (IP); 30 mg/kg animals scored higher on Day 29. Percentage tissue spared (%TS) at the lesion center was greater for 60 mg/kg animals (23.4%) than controls (17.3%). Experiment 3. Compounds were administered as in experiment 2 (n = 15/group); MPSS (60/30/30/30 mg/kg) and YM (1/1/1/1 mg/kg and 1 mg/kg/day ip) were most effective. YM and MPSS combination produced no additive effects. YM animals scored better than MPSS and control animals in OFW (Days 8-29) and better than controls on IP (Days 8-29; Day 29) and grid walking (Day 29), MPSS animals scored better than controls on IP (Days 8-29 ). YM and MPSS groups had greater %TS than controls.This series of experiments demonstrates the utility of this injury model and simple behavioral measures for preclinical assessment of pharmacologic agents. Under these experimental conditions, U74 demonstrated equivalent efficacy to MPSS, and YM demonstrated greater efficacy than MPSS in the treatment of ASCI.

Prostanoid production and pulmonary hypertension after fat embolism are not modified by methylprednisolone

Bilateral cemented arthroplasty (BCA) in anaesthetized mongrel dogs produces particulate fat and marrow embolism of the lung. Methylprednisolone sodium succinate (MPSS) has been advocated for post-traumatic fat embolism to prevent acute lung injury. We used the BCA procedure to produce acute fat and marrow embolism, and tested the efficacy of MPSS (30 mg.kg-1) in preventing physiological and pathological markers of acute lung injury. Dogs (n = 6) pre-treated with MPSS demonstrated similar acute increases in pulmonary artery pressure (PAP) within one minute of BCA (17.8 +/- 7.3 mmHg) as the untreated (control n = 7) dogs (18.6 +/- 12.6). Pulmonary vascular resistance (PVR) increased to the same degree in both groups (455 +/- 323 and 319 +/- 137 dyne.sec.cm-5) and PaO2 decreased by 18.3 +/- 6.4 mmHg in the control group as opposed to 12.4 +/- 7.7 mmHg in the MPSS group within five minutes of BCA. Circulating arterial and mixed venous plasma concentrations of thromboxane B2 (TxB2) increased within one minute of BCA in both groups with no increase in the transpulmonary gradient. Arterial plasma 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) increased (0.91 +/- 0.29 ng.ml-1 and 0.87 +/- 0.43 ng.ml-1) in both groups one minute after BCA. Mixed venous 6-keto PGF1 alpha plasma concentration also increased, but a significant transpulmonary 6-keto PGF1 alpha gradient was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Early Methylprednisolone Treatment for Septic Syndrome and the Adult Respiratory Distress Syndrome

From November 1, 1982 through December 31, 1985, there were 19 centers and 382 patients that evaluated the effect of methylprednisolone sodium succinate (MPSS) on the septic syndrome. Seventeen of these centers enrolled 304 patients in a prospective, randomized, double-blind, placebo-controlled study to determine if early treatment with MPSS would decrease the incidence of severity of the adult respiratory distress syndrome (ARDS) in patients at risk of ARDS from sepsis. To ensure early institution of the MPSS or placebo therapy (PLA), patients with the presumptive diagnosis of sepsis were identified. That diagnosis was based on the presence of fever or hypothermia (temperature greater than 38.3 degrees C or less than 35.5 degrees C, rectal), tachypnea (greater than 20 bpm), tachycardia (greater than 90 bpm) and the presence of one of the following indices of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels or oliguria. The treatment, either MPSS 30 mg/kg or PLA, was given in four 20-minute infusions six hours apart and was initiated within two hours of the presumptive diagnosis of sepsis. The development and reversal of the adult respiratory distress syndrome (ARDS) was followed and resulted in data on 304 of the 382 randomized patients. A trend toward increased incidence of ARDS was seen in the MPSS group 50/152 (32 percent) compared to the placebo group 38/152(25 percent) p = 0.10. Significantly fewer MPSS patients reversed their ARDS 15/50 (31 percent) compared to placebo 23/38 (61 percent) p = 0.005. The 14-day mortality in patients with ARDS treated with MPSS was 26/50 (52 percent) compared to placebo 8/22 (22 percent) p = 0.004. We conclude that early treatment of septic syndrome with MPSS does not prevent the development of ARDS. Additionally, MPSS treatment impedes the reversal of ARDS and increases the mortality rate in patients with ARDS.

Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury.

We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)--0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)--on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss, even though pulmonary capillary permeability was maintained near base line rates.

Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury

We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)—0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)—on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss. even though pulmonary capillary permeability was maintained near base line rates. (Neurosurgery 19:36-40, 1986)