LC-MS/MS analysis of elastin crosslinker desmosines and microscopic evaluation in clinical samples of patients with hypertrophy of ligamentum flavum.

Ligamentum flavum (LF) pathologies often lead to severe myelopathy or radiculopathy characterized by reduced elasticity, obvious thickening, or worsened ossification. Elastin endows critical mechanical properties to tissues and organs such as vertebrae and ligaments. Desmosine (DES) and isodesmosine (IDES) are crosslinkers of elastin monomers called tropoelastin. These crosslinkers are potential biomarkers of chronic obstructive pulmonary disease. As a biological diagnostic tool that supplements existing symptomatic, magnetic resonance imaging scanning or radiological imaging diagnostic measures for LF hypertrophy and associated pathologies, an isotope-dilution liquid chromatography-tandem mass spectrometry method with selected reaction monitoring mode for the quantitation of DESs in human plasma, urine, cerebrospinal fluid (CSF), and yellow ligamentum was investigated. Isotopically labeled IDES-13C3,15N1 was used as an internal standard (ISTD) for DES quantitation for the first time. The samples plus ISTD were hydrolyzed with 6 N hydrochloric acid. Analytes and ISTD were extracted using a solid phase extraction cellulose cartridge column. The assays were repeatable, reproducible, and accurate with % CV ≤ 7.7, ISTD area % RSD of 7.6, and % AC ≤ (101.2 ± 3.90) of the calibrations. The ligamentum samples gave the highest average DES/IDES content (2.38 µg/mg) on a dry-weight basis. A high percentage of the CSF samples showed almost no DESs. Urine and plasma samples of patients showed no significant difference from the control (p-value = 0.0519 and 0.5707, respectively). Microscopy of the yellow ligamentum samples revealed dark or blue-colored zones of elastin fibers that retained the hematoxylin dye and highly red-colored zones of collagen after counterstaining with van Gieson solution. Thus, we successfully developed a method for DES/IDES quantitation in clinical samples.

Correction: Takeuchi et al. Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation. Medicina 2022, 58, 1868.

In the original publication [...].

Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation.

Background and Objectives: Condoliase, a chondroitin sulfate ABC endolyase, is a novel and minimally invasive chemonucleolytic drug for lumbar disc herniation. Despite the growing number of treatments for lumbar disc herniation, the predicting factors for poor outcomes following treatment remain unclear. The aim of this study was to determine the predictive factors for unsuccessful clinical outcome following condoliase therapy. Material and Methods: We performed a retrospective single-center analysis of 101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p < 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715−1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration.

Severe low back pain with mild leg symptoms due to lumbar spine stenosis.

BACKGROUND: Some patients with lumbar spine stenosis (LSS) have severe low back pain (LBP) with only mild leg symptoms. The effects of decompression surgery for such patients remain unknown. METHODS: Of 818 patients with LSS who underwent surgical treatment in our institution from 2011 to 2019, eight patients had a numeric rating scale (NRS) score of ≥7 for LBP and 3≤ for leg pain. The patients' age, sex, clinical characteristics, preoperative leg symptoms, and level of LSS were investigated. The detailed characteristics of LBP, such as the disease duration, location of LBP, and exacerbating factors, were obtained from each patient. The NRS and Japanese Orthopaedic Association (JOA) scores for LBP were evaluated on admission, at 1 and 3 months postoperatively, and at the final follow-up (>1 year postoperatively). RESULTS: All patients were male with a mean age of 71.5 years (range, 57-82 years). LBP was exacerbated during walking in six patients and during an extension posture in three patients. The median duration of LBP was 2.9 years (range, 0.3-7 years). The stenosis was located at L2/3 in three patients, L3/4 in five patients, and L4/5 in seven patients. The stenosis involved one level in three patients and more than two levels in five patients. Other pathologies, such as sacroiliac joint lesions, facet pain, superior/middle cluneal nerve pain, and discogenic pain, were excluded by diagnostic anesthetic block and detailed physical examination. All patients underwent posterior decompression surgery without fusion. In all eight patients, the NRS score for LBP significantly improved from 7.6 (range, 7-10) to 1.7 (range, 0-3) and the JOA score improved from 13.1 (range, 4-19) to 21.8 (range, 18-27). CONCLUSION: A low proportion of patients showed walking-evoked severe LBP with mild leg symptoms due to lumbar spine stenosis. The patients' pain was improved by decompression surgery with satisfactory results.

[What are the Indications and Points of Anterior Cervical Decompression Surgery?]

Anterior cervical foraminotomy is a motion-preserving and precise decompressing surgery with minimal bone removal. As preserving the motion segment and maximizing decompression are contradictory concepts, proficiency is needed to balance these requirements. Anatomical knowledge and good intraoperative orientation are essential to reach the nerve roots accurately in a narrow surgical field.

Extraforaminal entrapment of the fifth lumbar spinal nerve by nearthrosis in patients with lumbosacral transitional vertebrae.

PURPOSE: Lumbosacral transitional vertebrae (LSTV) often have nearthrosis between the L5 transverse processes and the sacral ala; this causes the formation of new bone and synovial-like tissue, which can entrap L5 nerve root. The present study aimed to examine the role of nearthrosis in L5 nerve root compression in patients with LSTV. METHODS: From 2008 to 2018, 65 patients were surgically treated for severe leg pain/numbness caused by L5 extraforaminal stenosis. The patients were assessed regarding the presence of LSTV, radiographic features of nearthrosis, operative/radiological findings, and clinical outcomes. CT/MRI were used to classify the patients into three groups: group A had L5 nerve root compression that was not related to nearthrosis, group B had L5 nerve root impingement due to nearthrosis with new bone formation, and group C had L5 nerve root impingement due to nearthrosis with synovial-like tissue. The relationships between the type of LSTV (based on the Castellvi's classification) and these three groups were investigated. RESULTS: Although 26 of 65 patients had LSTV (40%), four were excluded because of less than 1-year follow-up. The 22 patients with LSTV were classified as type IA (n = 2), IIA (n = 13), and IIB (n = 7). In accordance with the radiological findings, there were eight patients in group A, six in group B, and eight in group C; the LSTV morphology did not significantly differ between groups. CONCLUSIONS: L5 nerve root was compressed by nearthrosis in 64% of symptomatic patients with LSTV; this region should be carefully assessed in all symptomatic patients with LSTV.

[Systematic review of complications for proper informed consent(12)decompression or fixation surgery of the lumbar spine].

A systematic review of the English- and Japanese-language literature related to complications and reoperation rates of spinal surgery for degenerative lumbar disease was undertaken for articles published between 1993 and 2012. From these references, key articles were selected to determine the incidence of clinical perioperative and postoperative adverse events for different types of degenerative lumbar diseases. The mortality rate after lumbar degenerative spinal surgery was 0.20% in the large-scale clinical studies evaluated. In this review series, the complication rates for lumbar canal stenosis(LCS), degenerative spondylolisthesis(DS), and lumbar disc herniation(LDH)were 7.6%, 8.5%, and 3.5%, respectively. The reoperation rates for LCS, DS, and LDH were 8.1%, 8.0%, and 6.2%, respectively. These data are helpful for spinal surgeons to apprise patients who have spinal surgery for degenerative lumbar disease of the possible risks of surgical procedures and reoperation rates.

[Evaluation of micturitional disturbance in spinal disorders: reproducibility of uroflowmetry].

Patients with spinal degenerative diseases suffer not only neuropathy in the extremities but also lower urinary tract dysfunction(LUTD). Patients with cauda equina syndrome generally need emergency decompression to pelvic visceral function, especially that of the urinary bladder. However, less prominent voiding symptoms can be missed in clinical settings. There is a discrepancy between lower urinary tract symptoms and LUTD. Therefore, urodynamic studies are needed to screen of patients with spinal diseases. Cystometry and urethral sphincter electromyography are useful for increasing our understanding of LUTD but are too invasive for screening. Our protocol for the evaluation of LUTD consists of residual urine measurement and uroflowmetry(UFM). UFM is the simplest and noninvasive urodynamic technique;however, it has the disadvantage of being nonreproducible, which depends on bladder volume, diurnal variation, presence of obstructive disease, and mental stress. UFM was reportedly reproducible in normal individuals in 1979, but was not evaluated in patients with spinal disease. This study examined the reproducibility of UFM in patients with spinal disease. UFM was performed twice in 26 male patients with cervical or lumbar degenerative disease. Maximum urinary flow rate corrected with Siroky's nomogram was reproducible in 23(88.5%)of the 26 patients. A urinary flow curve was reproducible in 25(96.2%)of the 26 patients, and only 1 patient had excessive urination at the 1st UFM and normal urination at the 2nd UFM. The reproducibility of UFM was high in patients with spinal degenerative disease.

Prevertebral Soft-tissue Swelling Following One-level Anterior Cervical Discectomy and Fusion: An Analysis Based on Surgical Level.

BACKGROUND: The purposes of this study were to identify the primary level at which PSTS occurs following one level anterior cervical discectomy and fusion (ACDF) based on surgical level, and to quantify the degree to which it occurs. Although prevertebral tissue swelling (PSTS) peaks at day 2 or 3 after ACDF, with swelling noted to be prominent at levels C2-4, the way in which the features of PSTS vary according to surgical level has not been examined. METHODS: 37 patients who underwent one-level ACDF were reviewed and classified into retropharyngeal and retrotracheal group based on surgical level. PSTS occurring at C2-C6 and the width of airway (WA) at C2-C4 was assessed using plain radiographs before surgery and at 1, 3, 5, and 7 days postoperatively. RESULTS: The retropharyngeal group comprised 10 patients while the retrotracheal group comprised 27 patients. Retropharyngeal group had the most severe PSTS on day 3 after surgery. C4 showed PSTS peaked on day 3, with a value of 3.26 times the preoperative prevertebral tissue thickness. WA at C4 was narrowest on day 1, with a value of 0.74 times and remained narrow until day 3. The retrotracheal group showed the most severe PSTS on day 1 at level C3:2.81 times. WA at C4 was narrowest on day 1 with a value of 0.78 times and increased thereafter. CONCLUSIONS: PSTS following one-level ACDF for both retropharyngeal and retrotracheal lesions was greatest at the C3 and C4 levels, with peaks on the third day after operation for the former, and the first day for the latter. WA at C4 was narrowest from day 1 in both groups. In the retrophyaryngeal group, narrowing remained until day 3.

The Effectiveness of Tritanium Cages in Preventing Osteolytic Vertebral Endplate Cysts After Lumbar Interbody Fusion.

OBJECTIVE: Lumbar interbody fusion (LIF) is a common surgical procedure, but postoperative complications, such as osteolytic vertebral endplate cysts, can adversely affect patient outcomes. This study aims to investigate whether tritanium cages (Stryker, Mahwah, New Jersey, USA) are effective in preventing osteolytic vertebral endplate cysts after LIF. METHODS: Clinical data from 8 years (2013-2020) of LIF procedures at our hospital were analyzed. Computed tomography was used to assess the formation of osteolytic vertebral endplate cysts 6 months after surgery. Clinical factors potentially associated with cyst formation were compared among 3 different interbody spacer materials: tritanium, titanium, and polyetheretherketone. RESULTS: LIF was performed for 169 patients at 205 spinal levels, employing tritanium cages in 56 levels (48 patients), titanium in 103 levels (86 patients), and polyetheretherketone in 46 levels (35 patients). At 6 months after LIF, 27.3% of patients showed worsening of osteolytic vertebral endplate cysts. Multivariate logistic regression analysis showed that tritanium cages (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.46-10.21) and titanium (OR, 2.55; 95% CI, 1.13-5.75), and posterior LIF (OR, 5.74; 95% CI, 2.24-14.74) were associated with a reduced risk of postoperative osteolytic vertebral endplate cysts. CONCLUSIONS: Tritanium cages have shown promise in preventing postoperative osteolytic vertebral endplate cysts, suggesting their potential as a stable and effective choice in LIF procedures. These findings have significant implications for improving patient outcomes and warrant further investigation to optimize surgical techniques and materials.

Long-term survival following molecular-targeted therapy for intramedullary non-small-cell lung cancer metastasis.

Background: Intramedullary spinal cord metastases (ICSMs) are very rarely curable; these patients typically have very short-term survival rates. Here, a 22-year-old male with non-small-cell lung cancer (NSCLC) later developed ICSM twice; the first C4-C7 tumor responded well to surgery, radiation, and alectinib molecular-targeted therapy. The secondary ICSM C1 lesion seen years later (i.e., likely due to alectinib having been stopped) resolved once alectinib was again administered. Case Description: A 22-year-old male with a limited smoking history presented with advanced non-small-cell lung cancer (NSCLC) treated with pulmonary surgery followed by radiotherapy and chemotherapy. Four years later, he developed cervical myelopathy attributed to a C4-C7 stage IV NSCLC ICSM (i.e., notably associated with an anaplastic lymphoma kinase [ALK] rearrangement). After cervical surgery and irradiation (40 Gy/20 fr) of the resection cavity, he was also given alectinib; the patient remained disease-free for the next 7 years, remaining on alectinib. However, 1 year after alectinib was discontinued, he experienced a newly occurrent C1 ICSM lesion; the alectinib was restarted, and his tumor regressed over the next 3 years. At present, 14 years after the original ICSM surgery, the patient remains disease free but continued alectinib (Karnofsky Performance Scale: 90%). Conclusion: Although the prognosis for ICSM is generally poor, molecular-targeted therapies, such as alectinib, as administered in this case, may provide long-term survival for patients with ALK-positive NSCLC tumors.

Acute cervical epidural abscess with concurrent calcium pyrophosphate deposition after cervical spinal surgery: A case report.

Background: Spinal epidural abscess (SEA) is a rare condition that may result in catastrophic outcomes. On the other hand, calcium pyrophosphate (CPP) deposition disease (CPPD) causes inflammatory arthritis. Spinal involvement of a crystal-induced inflammation caused by CPPD is also common. Surgery is a common risk factor for both SEA and CPPD; however, the postoperative acute onset of SEA complicated with CPPD is extremely rare. Case Description: A man in his 70s presented to our hospital, complaining of right upper limb weakness, loss of dexterity, and gait disturbance. The diagnosis of cervical spondylotic myelopathy was made, and he performed laminectomy at C3, C4, and C5 levels. Four days after the laminectomy, he suffered from acute neck pain, weakness, and hypoesthesia in his arms and legs. Magnetic resonance imaging revealed a mass occupying the dorsal epidural space of C6 and C7, compressing the cervical spinal cord. Considering the acute symptomatology, an acute spinal epidural hematoma after surgery was suspected; therefore, emergency C6 and C7 laminectomy was performed. Surgical findings indicated that the pressure inside the spinal canal was elevated, and the mass was purulent exudate. Pathological examination showed suppurative inflammation with concomitant deposition of CPP. SEA complicated with CPPD was considered; therefore, antibiotics and non-steroidal anti-inflammatory drugs were administered. The motor weakness and hypoesthesia were improved despite a slight residual deficit in his dexterity. Conclusion: An acute onset of SEA complicated with CPPD after cervical surgery has rarely been reported. The suppurative inflammation fostered by the crystal-induced inflammation may account for the acute symptomatology.

Prognostic Factors Associated with Poor Treatment Outcomes After Balloon Kyphoplasty in Elderly Patients Aged ≥81 years.

OBJECTIVE: Balloon kyphoplasty (BKP) is an effective procedure for osteoporotic vertebral compression fractures; however, there is limited data regarding its outcomes in patients aged ≥81 years. This study investigated the treatment outcomes and prognostic factors for BKP in this age group. METHODS: A retrospective analysis was conducted on 115 patients with osteoporotic vertebral compression fracture undergoing single-level BKP after failed conservative treatment, classified into the <81 years (n=70) and ≥81 years (n=45) groups. Surgical results were evaluated as good outcomes (independent indoors 1 year postoperatively) and poor outcomes, followed by univariate and multivariate analyses to determine prognostic factors correlating with these outcomes. RESULTS AND CONCLUSION: The majority of patients (<81 years: 85.7%; ≥81 years: 73.3%) had a good degree of independence at 1 year postoperatively, which was comparable in both groups. Further analysis of patients aged ≥81 years showed that longer duration from onset to surgery, more subsequent vertebral fractures, and lower preoperative body mass index were correlated with poorer outcomes postoperatively, and low body mass index, time from onset to surgery, and female sex were independent risk factors for these outcomes (area under the receiver operating characteristics curve: 0.91).

Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes.

STUDY DESIGN: Retrospective observational study. PURPOSE: To evaluate the modified osteoporotic fracture (mOF) scores in three treatment groups and compare imaging findings in patients treated and not treated according to the mOF score-based treatment recommendation. OVERVIEW OF LITERATURE: The osteoporotic fracture (OF) score was established by the AO Spine to guide therapeutic decisions. To enhance its applicability, a mOF score was recently introduced. METHODS: Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. RESULTS: In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF scorebased treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. CONCLUSIONS: In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs.

Unilateral Lumbosacral Facet Abnormality Resembling Facet Interlocking: A Case Report.

We report a rare case presenting radiculopathy caused by unilateral lumbosacral facet abnormality resembling facet interlocking. The patient was a 57-year-old man with no medical and traumatic history. He began to exhibit numbness below his left ankle followed by pain at the left buttock with no obvious causes. He visited our hospital approximately 1 year after the onset of his symptom. Preoperative images revealed a left lumbosacral facet abnormality resembling facet interlocking. His left S1 nerve root was compressed by the dislocated left L5 inferior articular process and bone fragment. His symptom was consistent with left S1 radiculopathy without an obvious stenosis of the left L5 intervertebral foramen; thus, we performed partial facetectomy of the left L5/S1, posterior decompression of the S1 nerve root tunnel, and removal of bone fragment. After the operation, his symptom completely disappeared with satisfactory result. There are several types of congenital facet anomalies in the lumbosacral facet joint; however, congenital unilateral lumbosacral facet abnormality resembling facet interlocking described in this paper has not been reported. His clinical symptom was completely recovered after simple decompression surgery. In this paper, we report the interesting and unique findings of facet abnormality resembling facet interlocking.

Unrecognized dural tear during percutaneous endoscopic lumbar surgery confirmed with myelography.

Iatrogenic dural tear is usually recognized during the surgery. We describe a rare case of unrecognized dural tear caused by percutaneous endoscopic lumbar surgery at another hospital clearly confirmed with dynamic myelography. Although magnetic resonance imaging of the lumbar spine showed no obvious fluid collection suggesting dural tear, dynamic myelography revealed leakage of intradural subarachnoid contrast medium along root sleeve into the intervertebral disc space. In the setting of endoscopic spine surgery, incidental dural tear might be overlooked due to the narrow and fluid-filled surgical field. Dynamic myelography is useful to evaluate the precise condition caused by unrecognized dural tear.

Postoperative intractable leg pain caused by dislocation of drainage tube.

Background: A wide variety of conditions can cause recurrent postoperative lumbar radiculopathy. Case Description: A 49-year-old female developed sudden recurrent postoperative right leg pain after a right-sided L5S1 microdiskectomy for a herniated disc. Emergent magnetic resonance and computed tomography studies demonstrated migration of the drainage tube into the right L5S1 lateral recess compromising the S1 nerve root. Following drain removal, the patient's right reg pain immediately resolved. Conclusion: Migration of a lumbar wound drain into the operated lateral recess following a lumbar diskectomy may result in acute, recurrent/intractable radicular pain that was readily resolved with drain removal.

Analysis of Neurogenic Bowel and Bladder Dysfunction Following Decompression Surgery for Cervical Spondylotic Myelopathy: A Prospective Cohort Study.

STUDY DESIGN: A prospective observational study. OBJECTIVES: To investigate preoperative prevalence of neurogenic bowel dysfunction and neurogenic bladder in patients with degenerative cervical myelopathy (DCM) and examine the degree and timing of symptom improvement after cervical decompression surgery. Factors contributing to symptom improvement were also analyzed. METHODS: Among 75 patients with DCM who underwent cervical decompression, Constipation Scoring System (CSS) score, International Prostate Symptoms Score (IPSS), and Japanese Orthopaedic Association (JOA) score were assessed before surgery and 1, 3, 6, and 12 months after. Prevalence rates were calculated. Data regarding patient age, sex, disease status, disease duration, lesion level, and score changes was prospectively recorded and analyzed. RESULTS: The prevalence rates of defecation and urinary dysfunction before surgery were 41.3% and 34.7%, respectively. Among the patients with defecation dysfunction, the number of patients who improved 1, 3, 6, and 12 months after surgery was 10, 9, 9, and 6, respectively. Among the patients with urinary dysfunction, the corresponding number of patients was 12, 10, 11, and 11, respectively. None of the factors we examined were significantly associated with improvement in either CSS or IPSS score; however, improvement of lower extremity JOA score tended to be associated with improvement in both. CONCLUSIONS: The prevalence of symptoms of defecation and urinary dysfunction in patients with DCM was 41.3% and 34.7%, respectively. Decompression surgery improved symptoms in 20% to 46% of patients.

Intraoperative complications of vertebral body stenting system.

Background: Vertebral body stenting systems (VBSs) are superior to balloon kyphoplasty for performing vertebral augmentation and height restoration. However, VBS may likely result in more material-related complications that have been under-reported. Here, an 84-year-old female's vertebral stents "toppled over" before the filling cement was fully applied, thus necessitating an additional posterior fusion. Case Description: An 84-year-old female presented with low back pain after a fall. Dynamic standing and decubitus X-rays revealed a vertebral compression fracture at T12 resulting in an intravertebral vacuum cleft (i.e., the lowermost level of diffuse idiopathic skeletal hyperostosis). When the VBS was performed, the stents "toppled over" just after removing the balloon catheters; we successfully restored with the cement volume in one stent but not the other, thus warranting an additional posterior fusion to maintain stability. Conclusion: The proper injection of cement into a VBS requires dual correct stent positioning, and careful control of requisite stent expansion. In an 84-year-old female with a T12 vertebral body fracture and a remarkable vacuum cleft, the VBS procedure resulted in an inadvertent injection into one stent thus warranting a secondary posterior fusion.