Dysphagia Secondary to Myotonic Dystrophy Unveiled in a Case of Destructive Spondylitis With Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) Syndrome Presenting As Torticollis.

To report an instructive case involving destructive spondylitis and synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, presenting with torticollis and postoperative dysphagia without hoarseness, attributed to hidden myotonic dystrophy (DM). A 51-year-old male patient with a cervical deformity, who was previously managed conservatively for a metastatic tumor, underwent reconstruction surgery and subsequently experienced postoperative dysphagia. The presence of destructive spondylitis with torticollis, warranting prompt assessment to prevent paralysis, adds complexity to the delayed identification of DM. Given the rarity of DM, peculiar neurological symptoms and other systemic comorbidities did not lead to a preoperative diagnosis without prior knowledge. The patient's dysphagia induced respiratory arrest and required reintubation. Challenges in extubation and ventilator weaning arose due to hypercapnia. Superimposed COVID-19 infection elongated the duration of intubation. Extubation failed due to aspiration pneumonia and required a tracheotomy. Despite laryngeal elevation and preservation of the relaxation of the oesophageal entrance, the sensation and movement of the tracheopharynx were disturbed. The patient exhibited an oropharyngeal propulsive disorder, predominantly indicative of motor neuron disease. The patient's mother stated that his brother had been hospitalized for a long time after abdominal surgery. Finally, the patient was diagnosed with DM, which is known to cause post-anesthetic dysphagia. Recognizing the existence of severe destructive cervical spondylitis associated with SAPHO is crucial. Although DM is not very common, it is not classified as extremely rare. Therefore, surgeons should be mindful of the potential risks associated with general anesthesia in patients with DM. The complexity of preoperative conditions may hinder an accurate diagnosis. Recognizing and establishing preoperative expectations can assist surgeons in preventing complications, even if complex spinal surgery is required for patients with DM.

Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis.

Dysregulated oxidative stress plays a major role in cancer pathogenesis and some types of cancer cells are particularly vulnerable to inhibition of their cellular antioxidant capacity. Glutamate-cysteine ligase (GCL) is the first and rate-limiting step in the synthesis of the major cellular antioxidant glutathione (GSH). Developing a GCL inhibitor may be an attractive therapeutic strategy for certain cancer types that are particularly sensitive to oxidative stress. In this study, we reveal a cysteine-reactive ligand, EN25, that covalently targets an allosteric cysteine C114 on GCLM, the modifier subunit of GCL, and leads to inhibition of GCL activity. This interaction also leads to reduced cellular GSH levels and impaired cell viability in ARID1A-deficient cancer cells, which are particularly vulnerable to glutathione depletion, but not in ARID1A-positive cancer cells. Our studies uncover a novel potential ligandable site within GCLM that can be targeted to inhibit GSH synthesis in vulnerable cancer cell types.

Treatment of progressive paralysis associated with cervical myelopathy and suspected amyotrophic lateral sclerosis: A case report.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an intractable progressive disease, with an incidence of 2.2- 2.3 per 100,000 individuals, which is not extremely low. ALS symptoms are accompanied by spinal myeloradicular motor deficit; its differential diagnosis is must because progressive paralysis needs emergency surgery. CASE DESCRIPTION: A 64-year-old man with suspected ALS showing progressive paralysis with cervical myelopathy was diagnosed as normal after performing a nerve conduction study preoperatively. Postoperative diffuse fasciculation after posterior decompression allowed the diagnosis of ALS through needle electromyography (EMG). Thereafter, the patient's condition slowly deteriorated and he died after 16 months. CONCLUSION: Surgery might aggravate ALS symptoms; however, surgery for progressive paralysis in patients with suspected ALS is required for distinguishing patients with non-ALS paralysis. Approximately 70% of cases have spinal-onset ALS lacking typical cranial nerve symptoms; thus, to prevent unnecessary surgery, surgeons should at least know the characteristic features of ALS and should be aware that early diagnosis requires needle EMG for definitive diagnosis of ALS.

Pediatric spinal infection with epidural abscess: A report of two cases.

BACKGROUND: Pediatric spinal infections are rare and often accompanied by abscesses. Delayed diagnosis commonly leads to a poor neurological prognosis, emphasizing the need for early diagnosis and treatment. CASE DESCRIPTION: We report on two cases of spinal infection; one in a 5-year-old boy with a T8-11 epidural abscess and one in a 10-year-old boy with an L5-S1 epidural abscess. Both cases improved with conservative therapy. CONCLUSION: Early magnetic resonance imaging diagnosis and systemic treatment in collaboration with pediatricians are key factors in the successful management of children with spinal infections.

Impact of appendicular and trunk skeletal muscle mass and back extensor strength on sagittal spinal alignment in Japanese women without vertebral fracture.

OBJECTIVES: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. METHODS: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4-71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann-Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. RESULTS: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. CONCLUSIONS: BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

Thin Cervical Spinal Cord Between Ossifications of the Ligamentum Flavum and the Posterior Longitudinal Ligament: Case Report and Literature Review.

BACKGROUND: Cervical ossification of the ligamentum flavum (OLF) is a rare condition; however, the coexistence of OLF and ossification of the posterior longitudinal ligament (OPLL) is extremely uncommon. These can exist simultaneously and cause thinning of the cervical spinal cord. Sufficient decompression, dural ossification, semispinalis dissection, and postoperative kyphosis were evaluated. We report the successful treatment of coexisting cervical OLF and OPLL. CASE DESCRIPTION: A 70-year-old man had been experiencing weakness in the left knee and clumsiness in the left hand for 6 months. Hemiparesis was considered; however, magnetic resonance imaging revealed a cervical spinal lesion. Hence a spine surgeon diagnosed the patient with severe stenosis with OLF at the C2-C3 levels and OPLL at the C2-C4 levels. The patient presented with spastic gait and left-hand motor weakness. Computed tomography scan revealed the disappearance of the black line, indicating dural ossification surrounding the OLF. OPLL was observed in 61.5% of the C2 spinal canal. The K-line was (-); however, the alternative K-line between the C1 and C7 level was (+). Posterior laminectomy at the C2-C3 levels and laminoplasty at the C4-C7 levels with muscle preservation resulted in sufficient decompression. The patient's symptoms improved, and cervical alignment was maintained 2 years after surgery. CONCLUSIONS: An alternative K-line comprised successful treatment for coexisting cervical OLF and OPLL. Surgeons must evaluate the severity of adhesion, damage of the paraspinal muscles, and necessity of posterior corrective surgery along with the patient's comorbidities and possible postoperative complications.

Locomotive Syndrome Is Associated with Health-Related Quality of Life and Low Back Pain in the Elderly, Including Individuals More Than 80 Years Old.

OBJECTIVES: The extent to which locomotive syndrome is associated with low back pain (LBP), health-related quality of life (HRQOL), and impairment of activities of daily living among elderly men and women remains poorly documented. This study evaluated associations between locomotive syndrome and both HRQOL and LBP as assessed using a questionnaire completed by elderly individuals, including some >80 years old. METHODS: We conducted a survey assessing locomotive syndrome using the loco-check, HRQOL using the Short-Form 36 questionnaire (SF-36), and LBP using the Roland-Morris Disability Questionnaire (RDQ) among individuals >60 years old. SF-36 and RDQ scores were compared between 253 subjects with and without locomotive syndrome. RESULTS: Fifty-seven men (48%) and 71 women (53%) were diagnosed with locomotive syndrome. Subjects of both sexes with locomotive syndrome scored significantly lower for eight items from SF-36. Physical and mental component summary scores were significantly worse in women with locomotive syndrome in their 60s and 70s. RDQ scores were significantly higher in participants with locomotive syndrome for men in their 60s and for both men and women in their 70s. CONCLUSIONS: Locomotive syndrome was associated with impaired HRQOL and worse LBP among men and women >60 years old. Differences in HRQOL and LBP between subjects with and without locomotive syndrome were significant for both men and women in their 60s and 70s, but not in their 80s. Locomotive syndrome should be prevented to maintain HRQOL, particularly for men and women in their 60s and 70s.

Diagnosis and Surgical Treatment of Thoracic Dorsal Arachnoid Web: A Report of Two Cases.

INTRODUCTION: An arachnoid web (AW) is a relatively rare disease and shows clinical symptoms and radiological findings similar to those of an arachnoid cyst (AC) or spinal cord herniation (SCH). Since the operative procedures for an AW are generally different from those intrathecal disorders, correct preoperative differential diagnosis is important. The purposes of this study were to report the usefulness of magnetic resonance imaging (MRI) and computed tomography (CT) myelography for diagnosing AW and to show the histological findings and clinical results. Case Description. Two patients, a 79-year-old man and a 43-year-old woman, are presented. The primary diagnoses were AC with ossification of the ligamentum flavum and epidural hematoma, respectively, in previous hospitals. They were finally diagnosed by the characteristic MRI and CT myelogram finding called the "scalpel sign." Histological findings showed epithelial cells and fibrous tissue derived from arachnoid tissues and microcalcifications. After surgery, the scalpel sign has vanished, and aggravation of their symptoms was prevented. CONCLUSION: An AW is refractory, but early detection by MRI and CT myelography and early treatment improve outcomes after surgery.

Cervical meningioma resection including the inner dura through an open-door laminoplasty using hydroxyapatite spacers: A case report.

BACKGROUND: The ideal surgery for spinal cord tumors is complete resection to prevent recurrence. However, it should be accomplished safely/effectively without risking increased morbidity. Here, we report a cervical meningioma that was totally resected, including the inner dura, through a laminoplasty performed with hydroxyapatite (HA) spacers. CASE DESCRIPTION: A 61-year-old Asian male presented with a symptomatic intradural extramedullary C4-C6 cervical meningioma. At surgery, this required resection of the inner dural layer through an open-door laminoplasty. Preservation of the outer dural layer facilitated a watertight closure and the avoidance of a postoperative cerebrospinal fluid (CSF) fistula. Notably, the laminoplasty utilized HA spacers which were magnetic resonance (MR) compatible allowing for future follow-up studies to evaluate for tumor recurrence. At 5-year follow-up, the tumor had not recurred, the patient was asymptomatic, and alignment was maintained. CONCLUSION: Gross total resection of an intradural extramedullary C4-C6 cervical meningioma was performed with removal of just the inner dural layer. Preservation of the outer dural layer allowed for a watertight closure and the avoidance of a postoperative CSF leak. Further, laminoplasty using HA spacers allowed for successful tumor resection, adequate fusion/stabilization, while not interfering with future MR studies (e.g., HA MR compatible).

Pyogenic Atlantoaxial Rotational Dislocation Representing Adult Torticollis with Vertebral Artery Occlusion: A Case Report and Review.

BACKGROUND: Pyogenic atlantoaxial rotational dislocation is a rare but life-threatening condition. Disease progression damages the soft tissue and bony structure, resulting in spinal cord or brain stem compression. Rapid and correct diagnosis could enable successful treatment. However, few studies have been reported, and the characteristics of a successful treatment course are not well known. In addition, our case presented with vertebral artery (VA) occlusion. Here we present a report of successful treatment of pyogenic atlantoaxial rotational dislocation representing adult torticollis with VA occlusion. CASE DESCRIPTION: A 67-year-old woman with neck pain and high fever was treated for suspected meningitis. Although her fever improved, pain persisted for several weeks. Examinations mostly showed characteristics of an infection with destructive atlantoaxial rotational dislocation; however, positive uptake with positron emission tomography, no anomalies with diffusion-weighted magnetic resonance imaging, and VA occlusion indicated the presence of a tumor lesion. After VA embolization and Halo reduction/stabilization, biopsy and blood culture revealed pyogenic infection. Antibiotics with rigid stabilization improved the inflammation and allowed definitive occipitocervical fixation, resulting in an uneventful postoperative course and painless bony fusion 2 years postoperatively. CONCLUSIONS: VA involvement should be examined for safe treatment. Stabilization is warranted to improve chronic inflammation. Knowledge regarding the characteristic treatment course could enable successful treatment planning and may prove to be lifesaving.

Growing Rod Surgery for Early-Onset Scoliosis in an Osteogenesis Imperfecta Patient.

BACKGROUND: Osteogenesis imperfecta (OI) is characterized by bone fragility and is often accompanied by spinal deformity. Surgical treatment for early-onset scoliosis in patients with OI is hazardous and difficult due to the bone fragility and rigidity of the deformity. A case of early-onset scoliosis with OI that was treated using growing-rod surgery is presented. CASE DESCRIPTION: The patient was an 11-year-old girl with type 4 OI. At the age of 4 years, she was noted to have scoliosis. Preoperative radiographs showed that the Cobb angle, thoracic kyphosis angle, and T1-S1 height were 94°, 77°, and 258 mm, respectively. One year before the operation, she underwent cyclic intravenous pamidronate disodium treatment. Three months after the pedicle screws were inserted, the growing rods were placed with pedicle screws and sublaminar polyethylene tape. The patient had intraoperative traction for correction. At 13 years and 11 months, the patients underwent posterior instrumentation and spinal fusion. Postoperative radiographs showed that the Cobb angle, thoracic kyphosis angle, and T1-S1 height were 29°, 29°, and 405 mm, respectively. Three months after the operation, she was well, and there have been no spine-related problems. CONCLUSIONS: This case demonstrates the successful use of the growing rod for early-onset scoliosis in patients with OI. The treatment strategy, which included pedicle screw insertion as anchors to create the foundations in advance, sublaminar tape, intraoperative traction, and preoperative bisphosphonate administration, might have led to the good outcome.

Inhibition of Autograft Bone Resorption by Antibone Resorptive Agents After Spinal Reconstruction Surgery for Extensive Cervical Chondrosarcoma: A Case Report with a 10-Year Follow-Up.

BACKGROUND: For the surgical treatment of spinal malignant tumor, spinal reconstruction with bone graft and instrumentation is necessary after tumor resection, but postoperative complications, including grafted bone resorption, may arise. CASE DESCRIPTION: A 42-year-old Asian woman presented with neck pain, tumorous masses on the neck, and left arm pain. Magnetic resonance imaging and computed tomography of the cervical spine showed extensive malignant spinal tumor. Histological examination of tumor biopsy revealed grade I chondrosarcoma. Complete resection of the tumor was performed using an anterior-posterior approach, followed by anterior iliac bone grafting and posterior spinal instrumentation. No tumor recurrence was observed on magnetic resonance imaging at final follow-up after 10 years. However, grafted bone resorption was identified immediately after surgery due to stress shielding by robust spinal instrumentation. To inhibit resorption of grafted bone, the bisphosphonate minodronate was administered for 5 years from 3 years postoperatively, before being replaced by denosumab from 8 years postoperatively. After use of these antibone resorptive agents, grafted bone resorption stopped. CONCLUSIONS: Anteriorly grafted bone resorption due to stress shielding may occur after reconstructive cervical spine surgery with robust posterior spinal instrumentation. Bisphosphonates and denosumab may be considered to inhibit grafted bone resorption.

Recurrent dysphagia after lower posterior cervical fusion.

BACKGROUND: Although dysphagia following posterior craniocervical fixation is well known, the incidence after mid-lower posterior cervical fixation is not well described. Here, we presented a case of recurrent dysphagia in a 72-year-old male following C3-T3 posterior cervical fixation and discussed its etiology. CASE DESCRIPTION: A 72-year-old male sustained a cervical fracture in a fall; he was neurologically intact. The cervical/thoracic MR and CT studies documented ankylosing spondylitic changes in the cervicothoracic spine, a C5/6 disc herniation, and a C7 vertebral fracture. He underwent posterior cervical C3 to T3 fusion without decompression. For the 1st postoperative day, he complained of dysphagia without hoarseness, and fiberoptic endoscopy revealed poor esophageal mobility. For the next 6 postoperative years, he continued to require repeated attempts at the dilation of the esophageal entrance but remained reliant on a feeding tube. CONCLUSION: Posterior cervical fixation restricts cervical motion and may restrict expansion of the esophageal duct leading to permanent postoperative dysphagia requiring continued feeding tube utilization.

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.

Author Correction: Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Surgical treatment of complete fifth lumbar osteoporotic vertebral burst fracture: A retrospective case report of three patients.

BACKGROUND: Due to its rarity, surgical treatments for a complete fifth lumbar osteoporotic vertebral burst fracture (L5 OVBF) have yet to be well documented as compared to that for osteoporotic vertebral fractures of the thoracolumbar spine. The current case report discusses details of the surgical outcomes following posterior decompression and fusion for a complete L5 OVBF. CASE DESCRIPTION: Three women, ranging in age from 69 years to 82 years, were surgically treated for a complete L5 OVBF. Two of these patients were being treated for rheumatoid arthritis. Surgery was performed using the L5 shortening osteotomy or vertebroplasty, with one- or two-level posterior lumbar interbody fusion, and posterior spinal fixation for the L2 or L3 to the pelvis. Although the spinal alignment parameters, which included lumbar lordosis (LL), pelvic incidence-lumbar lordosis, T1 pelvic angle, and sagittal vertical axis, were better as compared to that observed before the surgery, these worsened at the final follow-up due to clinical fractures that occurred at the adjacent vertebral body and proximal junctional kyphosis. Compared to preoperative Japanese Orthopaedic Association (JOA) scores, postoperative JOA scores were improved and maintained at the final follow-up. CONCLUSION: Posterior surgery of a complete L5 OVBF led to improvement of both the JOA score and spinal alignment after the surgery. Despite a worsening of the spinal alignment parameters, the JOA score was maintained at the final follow-up.

Impact of sagittal spine-pelvis-leg alignment and muscle strength on quality of life and low back pain in rural Japanese community- dwelling middle-aged and elderly persons.

BACKGROUND: Lower limb compensation for spinal sagittal malalignment and its impact on quality of life (QOL) and low back pain (LBP) have not been well studied. OBJECTIVE: To clarify postural compensation and the impact of spinal and lower limb sagittal alignment and muscle strength on QOL and LBP in persons > 50 years old. METHODS: In this cross-sectional study, 122 rural community-dwelling, healthy adults (56 males, 66 females; average age 71.1 years; age range, 52-88 years) underwent assessments of QOL (36-Item Short-Form Health Survey; SF-36), LBP (Roland-Morris Disability Questionnaire; RDQ), thoracic kyphosis (TK), lumbar lordosis (LL), sacral inclination (SI), grip strength, lower limb strength, and back extensor strength (BES). On univariate and multivariate analyses, variables that correlated with QOL and the RDQ were identified. RESULTS: LL was moderately correlated with SI and weakly correlated with the knee flexion angle (KFA). LL, KFA, C7-L5D, and BES were correlated with SF-36 subscales and the RDQ. KFA contributed to the physical component summary of the SF-36. Female sex and BES contributed to the RDQ. CONCLUSIONS: Knee flexion compensated for lumbar kyphosis, but affected physical QOL scores negatively; BES was the most reliable contributor to QOL and the RDQ.

Lumbar spinal stenosis associated with progression of locomotive syndrome and lower extremity muscle weakness.

PURPOSE: The purpose of this study was to evaluate the association between the early stages of lumbar spinal stenosis (LSS) and the risk of locomotive syndrome, as well as its effect upon muscle strength of the back, upper extremities, and lower extremities. PATIENTS AND METHODS: LSS was diagnosed with a self-administered, self-reported history questionnaire. Participants (n=113) who agreed to be tested by the diagnostic support tool for LSS underwent three risk tests for locomotive syndrome: a stand-up test, a two-step test, and a 25-question Geriatric Locomotive Function Scale (GLFS-25), as well as measurements of the strength of their grip, back extensor, hip flexor, and knee extensor muscles. RESULTS: Twenty-three participants were diagnosed with LSS by the questionnaire. Results of the stand-up test in the LSS group were significantly worse than those in the no-LSS group (P=0.003). The results of the two-step test and the total score on the GLFS-25 in the LSS group were significantly worse than those in the no-LSS group (P=0.002 and P<0.0001, respectively). The stages of locomotive syndrome assessed by the stand-up test, two-step test, and the GLFS-25 were significantly worse in the LSS group than in the no-LSS group (P=0.0004, P=0.0007, and P<0.0001, respectively). Hip flexor and knee extensor strength, but not grip and back extensor strength, in the LSS group were significantly lower than that in the no-LSS group. CONCLUSIONS: LSS diagnosed using the self-reported support tool worsened the stage of locomotive syndrome in older people. Furthermore, participants with LSS had significant lower extremity weakness.

Rapidly Progressing Symptomatic Calcification of Ligamentum Flavum in Thoracic Spine After Osteoporotic Vertebral Fractures.

BACKGROUND: Symptomatic calcification of the ligamentum flavum (CLF) is common in the cervical spine but rare in the thoracic spine. Rapidly progressing CLF in the thoracic spine has not been reported in the literature. CASE DESCRIPTION: A 76-year-old Asian male experienced back pain after a fall and was diagnosed with osteoporotic vertebral fractures at T11 and L1. He was treated conservatively because of the lack of neurologic deficits. Nine months after the initial visit, he complained of progressive incomplete paraplegia. Magnetic resonance imaging and computed tomography of the thoracic spine showed CLF at T11-T12 severely compressing the spinal cord. This finding had not been seen on imaging studies at the initial visit. The patient underwent surgical resection of CLF and posterior instrumented spine fusion. Symptoms of muscle weakness recovered postoperatively. CONCLUSIONS: In this case, sequential imaging studies with a 9-month interval showed evidence of rapidly progressing thoracic CLF. The preceding osteoporotic vertebral fracture may have triggered the development of CLF.