Detection of Dural Defect Localization Using 4-Dimensional Dynamic Computed Tomography Myelography for Patients with Superficial Siderosis.

BACKGROUND: There are cases of superficial siderosis (SS) with spinal ventral fluid-filled collection in the spinal canal. In our previous study, the balanced steady-state free precession sequence magnetic resonance imaging is useful in identifying the location of dural defects. However, because of its narrow scan area and long scan time, it cannot easily detect the defect location in some patients with small dural defect. In this study, we applied 4-dimensional (4D) dynamic computed tomography (CT) imaging, including time-axis imaging, to myelography using the latest CT imaging equipment, which can perform short-time continuous imaging, to identify the dural defect site. METHODS: Twenty SS patients with ventral fluid-filled collection in the spinal canal (9 males, 11 females; mean age 61.6 years) underwent 4D dynamic CT myelography. A 192-row helical CT (SOMATOM Force, SIEMENS, Munich, Germany) with high-speed scanning capability was used to obtain 9-11 scans per minute at low dose while passing contrast medium into the subarachnoid space. Then, contrast leakage sites were identified. RESULTS: The contrast leakage sites could be identified in all 20 cases: C7/Th1, 2 cases; Th1/2, 5 cases; Th2/3, 9 cases; Th3/4, 1 case; Th5/6, 1 case; Th7/8, 1 case; and Th8/9, 1 case. Eighteen cases underwent surgical operation, and actual dural defects were confirmed at the contrast leakage sites. The mean ± standard deviation of leakage time from contrast agent injection was 19.0 ± 9.2 s. CONCLUSIONS: The 4D dynamic CT myelography can be used to reliably identify the location of spinal fluid leakage. In SS cases, dural defects could be visualized in an average of 19 seconds.

Comparison of Postoperative Complications and Outcomes in Anterior Cervical Spine Surgery: Ossification of the Posterior Longitudinal Ligament Versus Cervical Spondylotic Myelopathy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the frequency of complications and outcomes between patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine and those with cervical spondylotic myelopathy (CSM) who underwent anterior surgery. SUMMARY OF BACKGROUND DATA: Anterior cervical spine surgery for OPLL is an effective surgical procedure; however, it is complex and technically demanding compared with the procedure for CSM. Few reports have compared postoperative complications and clinical outcomes after anterior surgeries between the 2 pathologies. METHODS: Among 1434 patients who underwent anterior cervical spine surgery at 3 spine centers within the same spine research group from January 2011 to March 2021, 333 patients with OPLL and 488 patients with CSM were retrospectively evaluated. Demographics, postoperative complications, and outcomes were reviewed by analyzing medical records. In-hospital and postdischarge postoperative complications were investigated. Postoperative outcomes were evaluated 1 year after the surgery using the Japanese Orthopaedic Association score. RESULTS: Patients with OPLL had more comorbid diabetes mellitus preoperatively than patients with CSM ( P <0.001). Anterior cervical corpectomies were more often performed in patients with OPLL than in those with CSM (73.3% and 14.5%). In-hospital complications, such as reoperation, cerebrospinal fluid leak, C5 palsy, graft complications, hoarseness, and upper airway complications, occurred significantly more often in patients with OPLL. Complications after discharge, such as complications of the graft bone/cage and hoarseness, were significantly more common in patients with OPLL. The recovery rate of the Japanese Orthopaedic Association score 1 year postoperatively was similar between patients with OPLL and those with CSM. CONCLUSION: The present study demonstrated that complications, both in-hospital and after discharge following anterior spine surgery, occurred more frequently in patients with OPLL than in those with CSM.

Kinematic analysis of chewing and swallowing function after cervical spine surgery.

PURPOSE: Although movement of the hyoid bone is different for masticatory swallowing and liquid swallowing in normal subjects, it has not been studied after cervical spine surgery. Therefore, we analyzed the swallowing dynamics of masticatory swallowing in anterior cervical spine disease surgery using foods that require chewing close to actual meals. METHODS: A day before and one week after the surgery, a videofluoroscopic swallow study (VFSS) was performed, and the distance of hyoid bone movement in the anterior and superior directions, amount of opening of the upper esophageal sphincter (UES), time of passage through the pharynx, number of swallows, and amount of pharyngeal residual were measured on the VFSS images during a masticatory swallow of corn flakes. The swallowing function was evaluated by DSS (dysphagia severity scale) and FOIS (functional oral intake scale). Imaging software was used for the measurements. RESULTS: Postoperative hyoid movement during masticatory swallowing was not significantly different for anterior movement but significantly limited in upward movement (p = 0.002); UES opening volume was significantly decreased (p < 0.001), and bolus residue was significantly worse (p < 0.001), compared to preoperative. The pharyngeal transit time was not significantly different; the number of swallows increased (p < 0.001), along with DSS (p < 0.001) and FOIS (p < 0.001), with significant differences before and after surgery, indicating worsened swallowing function. CONCLUSIONS: Swallowing function worsened in masticatory swallowing after surgery for cervical spine disease, mainly due to the restriction of upward movement of the hyoid bone and the resulting increase in pharyngeal residuals after swallowing.

A Comparison of Spinopelvic Alignment and Quality of Life between Farmers and Non-Farmers: A Cross-Sectional Population-Based Study in a Japanese Rural Area.

BACKGROUND: It may be difficult to define what would constitute an abnormal spinal sagittal alignment. The same degree of malalignment may be found both in patients with pain and disability and in asymptomatic individuals. This study focuses on elderly farmers who characteristically have a kyphotic spine, in addition to local residents. It questions whether these patients experience cervical and lower back symptoms, respectively, more often than elderly people who never worked on a farm and do not have a kyphotic deformity. Previous research could have been biased by sampling patients who came to a spine clinic for treatment, whereas this study sampled asymptomatic elderly who may or may not have had kyphosis. METHODS: We studied 100 local residents at their annual health checkup (22 farmers and 78 non-farmers) with a median age of 71 years (range 65-84 years). Spinal radiographs were used to measure sagittal vertical axis, lumbar lordosis, thoracic kyphosis and other measurements of sagittal malalignment. Back symptoms were measured using Oswestry Disability Index (ODI) and Neck Disability Index (NDI). The association between alignment measures and back symptoms were calculated by bivariate comparison between patient groups and by Pearson's correlation. RESULTS: About 55% of farmers and 35% of non-farmers had abnormal radiographs (i.e., vertebral fracture). Farmers had higher measurements of sagittal vertical axis (SVA), compared to non-farmers, when measured from C7 (median 24.4 mm vs. 9.15 mm, p = 0.04) and from C2 (47.65 vs. 25.3, p = 0.03). Lumbar lordosis (LL) and thoracic kyphosis (TK) were significantly decreased in farmers vs. non-farmers (37.5 vs. 43.5, p = 0.04 and 32.5 vs. 39, p = 0.02, respectively). The ODI was likely to be higher among farmers compared to non-farmers while NDI scores showed no significant difference between farmers and non-farmers (median 11.7 vs. 6.0, p = 0.06 and median 13 vs. 12, p = 0.82, respectively). In terms of correlation among spinal parameters, LL had a higher correlation with SVA, but TK had less correlation with SVA among farmers compared to non-farmers. There was no significant correlation between disability scores and measurements of sagittal alignment. CONCLUSIONS: Farmers had higher measurements of sagittal malalignment, characterized by loss of LL, decreased TK and an increased forward translation of cervical vertebrae relative to sacrum. ODI was likely to higher in farmers compared to non-farmers although the association did not reach a significant level. These results probably indicate that the gradual development of spinal malalignment in agricultural workers does not result in excess morbidity compared to controls.

Analysis of swallowing function after anterior/posterior surgery for cervical degenerative disorders and factors related to the occurrence of postoperative dysphagia.

BACKGROUND CONTEXT: Dysphagia is one of the postoperative complications of cervical degenerative disorders. However, few studies have evaluated the pre- and postoperative swallowing function in detail. PURPOSE: To analyze pre- and postoperative swallowing dynamics kinetically and investigate factors associated with postoperative dysphagia in patients with cervical degenerative disorders. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: A total of 41 consecutive patients who underwent an anterior approach (anterior cervical discectomy/corpectomy and fusion (ACDF, ACCF), hybrid surgery (ACDF+ACCF) and total disc replacement) and 44 consecutive patients who underwent a posterior approach (laminoplasty and laminoplasty/laminectomy with fusion). OUTCOME MEASURES: We compared the pre- and postoperative functional oral intake scale (FOIS), dysphagia severity scale (DSS), esophageal dysphagia, anterior/superior hyoid movement, upper esophageal sphincter (UES) opening, pharyngeal transit time, bolus residue scale (BRS), and the number of swallows. METHODS: Videofluoroscopy was performed on the day before surgery and within two weeks after surgery. Data related to age, gender, disease, surgical procedure, surgical site, operative time, and blood loss were collected from the medical records. Pre- and postoperative data were compared for each item in the anterior and posterior approaches. The odds ratio of dysphagia after an anterior approach was also calculated. RESULTS: In the anterior approach, DSS, FOIS, the anterior and superior hyoid movements, maximum UES opening, BRS, and number of swallows worsened postoperatively (p<.05, respectively). In the posterior approach, DSS, FOIS, the anterior hyoid movement, and BRS worsened postoperatively (p<.05, respectively). The factors associated with dysphagia were a proximal surgical site above C3 (OR: 14.40, CI: 2.84-73.02), blood loss >100 mL (OR: 9.60, CI: 2.06-44.74), an operative time >200 minutes (OR: 8.18, CI: 1.51-44.49), and an extensive surgical field of more than three intervertebral levels (OR: 6.72, CI: 1.50-30.07). The decline in swallowing function after the posterior approach was related to aging (p=.045). CONCLUSIONS: Each approach may decrease swallowing function, especially because of the limitation on the anterior hyoid movement. Dysphagia after anterior approaches was associated with the operative site, operative time, and blood loss.

Risk factors for recurrence and regrowth of spinal schwannoma.

BACKGROUND: Spinal schwannoma recurs after initial surgery at a rate of 4%-6%, with known risk factors including subtotal resection, multilevel involvement, large tumor size, and malignant histopathology. This study examined risk factors for schwannoma recurrence and residual tumor regrowth. METHODS: Sixty-five patients who underwent resection of spinal schwannoma in our department between July 2010 and December 2018 and were followed up for more than 1 year were retrospectively analyzed for age, sex, follow-up duration, imaging and surgical data, recurrence, reoperation, and Japanese Orthopaedic Association scores before and 1 year after surgery. Patients with postoperative recurrence or residual tumor regrowth of >10% at the final visit (R+ group) were compared with patients without recurrence or regrowth (R- group). Multivariate logistic regression analysis was performed to analyze concurrent effects of risk factors on recurrence and regrowth. RESULTS: The 65 patients (mean age 52.4 years at surgery) had schwannomas involving cervical (n = 14), thoracic (n = 25), and lumbar (n = 26) spinal levels. Mean follow-up duration was 58 months. Location was intradural in 65%, extradural in 17%, and both intradural and extradural in 18%. There were 4 recurrences (6.2%), and the mean interval between surgery and recurrence was 18.8 months. Seven patients (10.8%) experienced regrowth. Comparing group R+ (n = 11) and group R- (n = 54), univariate analysis showed significant differences in Sridhar tumor classification, giant tumor (Sridhar classification II, IVb, and V), left-right and cranial-caudal tumor size, largest diameter, operative time, blood loss, subtotal resection, reoperation, fusion surgery, and follow-up duration. Multivariate logistic regression analysis revealed giant tumor (Sridhar classification types II, IVb, and V) as an independent risk factor for recurrence and regrowth. CONCLUSIONS: This retrospective review of 65 consecutive patients with spinal schwannoma in a single institution demonstrated that 16.9% had recurrence or regrowth, demonstrating that this potential risk should be kept in mind.

Case Report: Dural Dissection With Ventral Spinal Fluid-Filled Collection in Superficial Siderosis: Insights Into the Pathology From Anterior-Approached Surgical Cases.

Superficial siderosis (SS) of the central nervous system is a rare disease caused by chronic and repeated hemorrhages in the subarachnoid space. Recently, attention has been paid on the association of SS and dural defect with ventral fluid-filled collection in the spinal canal (VFCC). The pathophysiology of hemosiderin deposition in patients with SS and dural defects is still unclear. However, previous studies have suggested the possible mechanism: cerebrospinal fluid (CSF) leaks into the epidural space through the ventral dural defect, and repetitive bleeding occurs from the epidural vessels that circulate back to the subarachnoid space through the dural defect, leading to hemosiderin deposition on the surface of the brain, the central nerves, and the spinal cord. Previously, the surgical closure of dural defect via the posterior approach has been reported to be effective in arresting the continued subarachnoid bleeding and disease progression. Herein, we describe SS cases whose dural defects were repaired via the anterior approach. From the direct anterior approach to the ventral dural defect findings, we confirmed that the outer fibrous dura layer is intact, and the defect is localized in the inner thin layer. From the findings of this study, our proposed theory is that dural tear at the inner dural layer causes "dural dissection," which is likely to occur between the outer fibrous layer and inner dural border cellular layer. Bleeding from the vessels between the inner and outer Line 39-40 dural layers seems to be the pathology of SS with dural defect.

Local Suppression Effect of Paclitaxel-Impregnated Hydroxyapatite/Collagen on Breast Cancer Bone Metastasis in a Rat Model.

Introduction: Breast cancer is one of the most frequent primary tumors that cause spinal metastases. Metastasis consequences impair both the patient's overall prognosis and quality of life. We previously developed a porous hydroxyapatite collagen composite (HAp/Col) as an osteoconductive scaffold. HAp/Col is a commercially available artificial bone that is frequently utilized in spinal fusion. Because of its high absorbance capacity, HAp/Col is regarded as a good chemical carrier. Methods: This study investigated the effect of local administration of paclitaxel combined with HAp/Col scaffold on breast cancer metastasis. High-performance liquid chromatography was used to assess the in vitro release of paclitaxel from HAp/Col. In an in vivo rat model, the inhibitory effects of paclitaxel-impregnated scaffolds on local osteogenesis was examined, and then the local suppression effects on metastatic cancer were investigated. Results: In vitro testing revealed that roughly 30% of the paclitaxel was released within 96 hours. Paclitaxel-impregnated HAp/Col inhibited local osteogenesis for the first 8 weeks in a rat femur. However, at 12 weeks following surgery, this negative effect appeared to have subsided. In the metastatic model, all rats in the control group reached the humane endpoint 14 days after surgery. On the other hand, the average time to the endpoint in the paclitaxel group was 26.5 days, which was substantially longer than that in the control group. Long-term survivors treated with paclitaxel had no remaining tumor cells in the femoral bone, and osteogenesis was seen surrounding the HAp/Col. Conclusions: Paclitaxel-impregnated HAp/Col reduced local tumor development and extended the time to the target endpoint in rats with metastases from breast cancer. This study shows that local implantation of paclitaxel-impregnated HAp/Col may be a viable therapeutic option for the management of breast cancer metastases.

Detecting ossification of the posterior longitudinal ligament on plain radiographs using a deep convolutional neural network: a pilot study.

BACKGROUND CONTEXT: Its rare prevalence and subtle radiological changes often lead to difficulties in diagnosing cervical ossification of the posterior longitudinal ligament (OPLL) on plain radiographs. However, OPLL progression may lead to trauma-induced spinal cord injury, resulting in severe paralysis. To address the difficulties in diagnosis, a deep learning approach using a convolutional neural network (CNN) was applied. PURPOSE: The aim of our research was to evaluate the performance of a CNN model for diagnosing cervical OPLL. STUDY DESIGN AND SETTING: Diagnostic image study. PATIENT SAMPLE: This study included 50 patients with cervical OPLL, and 50 control patients with plain radiographs. OUTCOME MEASURES: For the CNN model performance evaluation, we calculated the area under the receiver operating characteristic curve (AUC). We also compared the sensitivity, specificity, and accuracy of the diagnosis by the CNN with those of general orthopedic surgeons and spine specialists. METHODS: Computed tomography was used as the gold standard for diagnosis. Radiographs of the cervical spine in neutral, flexion, and extension positions were used for training and validation of the CNN model. We used the deep learning PyTorch framework to construct the CNN architecture. RESULTS: The accuracy of the CNN model was 90% (18/20), with a sensitivity and specificity of 80% and 100%, respectively. In contrast, the mean accuracy of orthopedic surgeons was 70%, with a sensitivity and specificity of 73% (SD: 0.12) and 67% (SD: 0.17), respectively. The mean accuracy of the spine surgeons was 75%, with a sensitivity and specificity of 80% (SD: 0.08) and 70% (SD: 0.08), respectively. The AUC of the CNN model based on the radiographs was 0.924. CONCLUSIONS: The CNN model had successful diagnostic accuracy and sufficient specificity in the diagnosis of OPLL.

Anterior Cervical Corpectomy with Fusion versus Anterior Hybrid Fusion Surgery for Patients with Severe Ossification of the Posterior Longitudinal Ligament Involving Three or More Levels: A Retrospective Comparative Study.

Various studies have found a high incidence of early graft dislodgement after multilevel corpectomy. Although a hybrid fusion technique was developed to resolve implant failure, the hybrid and conventional techniques have not been clearly compared in terms of perioperative complications in patients with severe ossification of the posterior longitudinal ligament (OPLL) involving three or more levels. The purpose of this study was to compare clinical and radiologic outcomes between anterior cervical corpectomy with fusion (ACCF) and anterior hybrid fusion for the treatment of multilevel cervical OPLL. We therefore retrospectively reviewed the clinical and radiologic data of 53 consecutive patients who underwent anterior fusion to treat cervical OPLL: 30 underwent ACCF and 23 underwent anterior hybrid fusion. All patients completed 2 years of follow-ups. Implant migration was defined as subsidence > 3 mm. There were no significant differences in demographics or clinical characteristics between the ACCF and hybrid groups. Early implant failure occurred significantly more frequently in the ACCF group (5 cases, 16.7%) compared with the hybrid group (0 cases, 0%). The fusion rate was 80% in the ACCF group and 100% in the hybrid group. Although both procedures can achieve satisfactory neurologic outcomes for multilevel OPLL patients, hybrid fusion likely provides better biomechanical stability than the conventional ACCF technique.

Hydroxyapatite/collagen composite graft for posterior lumbar interbody fusion: a comparison with local bone graft.

BACKGROUND: Autologous bone has been used for posterior lumbar intervertebral fusion (PLIF). However, harvesting autologous bone graft is associated with donor site complications. We previously developed a hydroxyapatite/collagen (HAp/Col) composite as an osteoconductive artificial bone, characterized by having a highly porous structure with sponge-like elasticity. This study aims to investigate the effectiveness of HAp/Col composite with bone marrow aspirate (BMA) as a graft substitute in PLIF for the treatment of lumbar spinal diseases. METHODS: This study prospectively investigated patients who received one-level PLIF. For the interbody fusion, two titanium cages were inserted. On the one side of interbody space, HAp/Col composite incorporated with BMA filling the titanium cage was grafted. On the other side, local bone graft (LBG) harvested during decompressive laminotomy was grafted and then one-level instrumentation using pedicle screws was performed. The target levels were at L2/3 in 2 cases, L3/4 in 3 cases, L4/5 in 36 cases, and L5/S in 5 cases. We evaluated clinical symptoms and radiological outcomes of 46 patients and compared the fusion status of HAp/Col composite with that of LBG. RESULTS: The 1-year postoperative CT evaluation demonstrated that, in the HAp/Col, a complete fusion was observed in 38 patients (82.6%), whereas in the LBG, a complete fusion was observed in 35 patients (76.1%). There were no statistical differences between the HAp/Col and LBG. In the HAp/Col, incomplete fusion was observed in five patients (10.9%) and non-fusion in two patients (4.3%), and in the LBG, incomplete fusion was observed in nine patients (19.6%) and non-fusion in two patients (4.3%). At 2 years after the surgery, complete fusion increased to 44 patients (95.7%) in the HAp/Col and 41 patients (89.1%) in the LBG. There were no significant differences in the clinical scores for lumbar spine between patients with fusion and non-fusion. CONCLUSIONS: The HAp/Col composite with BMA in the titanium cage can be effectively used as an alternative to conventional autologous LBG for intervertebral spinal fusion. Trial registration University hospital Medical Information Network, UMIN000045010, July 30th, 2021, Retrospectively registered, https://www.umin.ac.jp/english/ .

Airway and circulatory collapse due to retropharyngeal hematoma after blunt vertebral artery injury.

Retropharyngeal hematoma following blunt cervical spine injury is a known cause of airway obstruction, but it is not known to cause hemorrhagic shock. We report the case of a massive retropharyngeal hematoma caused by a blunt vertebral artery transection leading simultaneously to airway obstruction and hemorrhagic shock. An 83-year-old woman was injured in a motorcycle accident. In the field, the patient exhibited paradoxical breathing with no breath sounds, and her blood pressure could not be measured. Therefore, emergency intubation and fluid resuscitation were initiated and the patient was transferred to the emergency department. Computed tomography angiography revealed a massive retropharyngeal hematoma with contrast extravasation from the right vertebral artery, which caused airway obstruction and hemorrhagic shock. The right vertebral artery was transected at the C5 level, which was associated with C4/C5 dislocation. Vertebral artery transection was successfully treated by endovascular embolization, which was followed by complication of asymptomatic posterior circulation stroke. Blunt vertebral artery transection can cause massive retropharyngeal hematoma, which can rapidly expand and lead to hemorrhagic shock in addition to airway obstruction. In cases of massive retropharyngeal hematoma with hemorrhagic shock following blunt cervical spine injury, blunt vertebral artery transection should be suspected. If blunt vertebral artery transection is detected and hemorrhagic shock is persistent, endovascular embolization should be performed immediately in addition to emergency intubation.

Repulsive guidance molecule b inhibits neurite growth and is increased after spinal cord injury.

Neuronal axons are guided by attractive and repulsive cues in their local environment. Since the identification of the repulsive guidance molecule (RGM) a (RGMa) as an axon repellent in the visual system, diverse functions, as part of the developing and adult central nervous system (CNS), have been ascribed to it. The binding of RGMa to its receptor neogenin has been shown to induce RhoA activation, leading to inhibitory/repulsive behavior and the collapse of the neuronal growth cone. In this paper, we provide evidence to suggest the involvement of RGMb, another member of the RGM family, in the rat CNS. RGMb inhibits neurite outgrowth in postnatal cerebellar granule neurons (CGNs) in vitro. RGMb is expressed by oligodendrocytes and neurons in the adult rat CNS, and the expression of this molecule is upregulated around the site of spinal cord injury. RGMb is present in myelin isolated from an adult rat brain. RGMb and neogenin are coexpressed in CGNs and entorhinal cortex neurons. These findings suggest that RGMb is a myelin-derived inhibitor of axon growth in the CNS. Inhibition of RGMb may provide an alternative approach for the treatment of spinal injuries.

Amyloid formation in rat transthyretin: effect of oxidative stress.

BACKGROUND: Transgenic mice carrying a human mutant transthyretin (TTR) gene are too small for in vivo experiments. It is necessary to have rat TTR protein and its antibody to overcome this problem. METHODS: Posttranslational modification of purified TTR was analyzed by means of matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS). Production of amyloid fibrils in vitro was confirmed by thioflavin T test and electron microscopy. Amyloidogenicity of rat TTR from rats with or without challenging paraquat was compared in vitro by thioflavin T test. RESULTS: MALDI/TOF-MS for rat TTR revealed three major modified forms-sulfate-conjugated, Cys-conjugated and glutathione-conjugated-in addition to the unconjugated (free) form of TTR. Although rat TTR in buffer of pH 7.0 could not make amyloid fibrils, rat TTR at pH 2.0-3.5 significantly formed amyloid fibrils, as confirmed by the thioflavin T test and electron microscopy. TTR purified from rats administered 4 mg/kg of paraquat formed much more amyloid fibrils than that from normal rats at pH 2.0-3.5 and significant amyloid fibrils were confirmed even at pH 7.0. CONCLUSIONS: Rat TTR may be a valuable experimental tool for examination of the amyloidogenicity of senile systemic amyloidosis (SSA) as well as familial amyloidotic polyneuropathy (FAP) both in vitro and in vivo.

[Neutralizing activity of human immunoglobulin preparation against toxic shock syndrome toxin-1].

Human intravenous immunoglobulin (IVIG) preparation containing a variety of antibodies is widely used against severe infectious diseases. Although IVIG is supposed to promote phagocytosis of opsonized bacteria and neutralize several bacterial toxins, it is unclear what antibodies are responsible for the effect in clinical use. In this study, we found that IVIG showed neutralizing activity against toxic shock syndrome toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). Whereas intravenous inoculation with culture medium of MRSA 1945 strain into ICR mice causes immediate death, all of the mice survived in case of previous administration of IVIG. Such effect might be attributed to neutralization of TSST-1. Murine splenocytes incubated with TSST-1 (1.0 ng/mL) for 48 hours produced IFN-gamma. By addition of IVIG at 100 micrograms/mL into culture medium, production of IFN-gamma was completely inhibited. From IVIG, anti-TSST-1 antibody was purified by affinity chromatography as one of the effective antibodies. MRSA 1945 mixed with dextran-based microcarrier beads and injected subcutaneously into mice resulted in the formation of abscess and excretion of TSST-1 in serum for 14 days. IVIG and anti-TSST-1 antibody neutralized TSST-1 in blood 24 hours after infection, although bacterial count was kept constant. Experimental rabbit TSS model was established by synergism with lipopolysaccharide (LPS) of Escherichia coli. Anti-TSST-1 antibody protected NZW rabbits from lethal challenge with TSST-1 (1 microgram/kg, i.v.) 4 hours before LPS in a dose-dependent manner (10 micrograms/kg, i.v.), whereas all of the NZW rabbits died in the control group. Thus, IVIG may be a useful tool in the prevention and perhaps therapy of staphylococcal infections and TSS.