Morphological analysis of isolated hemivertebra: radiographic manifestations related to the severity of congenital scoliosis.

PURPOSE: The natural history of congenital scoliosis (CS) caused by hemivertebra varies greatly. This study aimed to explore the association between the morphology of hemivertebra and the severity of CS, since the diagnosis of the hemivertebra. METHODS: Patients with isolated (single fully segmented) hemivertebra were enrolled. The degree and progression of deformity were compared by three morphological parameters of hemivertebra, comprising whether the width of hemivertebra extends across the central vertical line of lower adjacent vertebra (midline); the lateral height ratio (LHR, lateral height of hemivertebra× 2/(lateral height of HV-1 plus HV + 1) with the cut-point being 0.9; and the sagittal position of hemivertebra that was divided into the lateral and posterolateral group. RESULTS: In total, 156 patients (mean age 9.7 ± 6.2 years, 81 males) were enrolled. The number of thoracic, thoracolumbar (T12/13-L1), and lumbar hemivertebrae were 63, 41, and 52, respectively. Hemivertebrae across the midline had larger scoliosis and kyphosis (58.3 ± 20.6° vs. 42.8 ± 15.0°, P <  0.001; 45.1 ± 32.5° vs. 29.5 ± 25.7°, P = 0.013, respectively). Hemivertebrae with LHR ≥0.9 was associated with larger scoliosis (55.7 ± 20.6° vs. 41.4 ± 13.3°, P <  0.001). Larger scoliosis and kyphosis were observed in posterolateral hemivertebrae (54.4 ± 21.0° vs. 44.4 ± 15.6°, P = 0.026; 51.4 ± 31.5° vs. 20.6 ± 17.1°, P <  0.001, respectively). Co-occurrence of more than one of the three positive parameters above indicated higher annual progression (5.0 ± 2.2° vs. 3.3 ± 1.3°, P <  0.001). CONCLUSION: Three positive parameters, width across the midline, LHR ≥0.9, and posterolateral position were associated with a more severe deformity in patients with isolated hemivertebra. Hemivertebrae with more than one positive parameter may cause progressive deformity, and thus need prompt surgery. LEVEL OF EVIDENCE: Prognostic, level IV.

Unilateral interlaminar fenestration on the convex side provides a reliable access for intrathecal administration of nusinersen in spinal muscular atrophy: a retrospective study.

BACKGROUND: As the first gene therapy for spinal muscular atrophy (SMA), nusinersen is supposed to be administrated via intrathecal injection regularly for a lifetime. However, for SMA patients with severe spinal deformities, bony fusion following posterior spinal instrumentation sets great obstacles for the application of nusinersen. Therefore, efforts have been devoted to the exploration of appropriate approach for nusinersen administration. This study aims to evaluate the safety and reliability of unilateral interlaminar fenestration on the convex side during spinal fusion surgery for intrathecal nusinersen injection in SMA. RESULTS: SMA patients receiving posterior spinal fusion and interlaminar fenestration in Peking Union Medical College Hospital from January 2020 to October 2021 were retrospectively analyzed. 13 patients were included. Of the 13 patients, 10 were classified into SMA type II and 3 into SMA type III. Distal fusion to pelvis was undertaken in 11 patients; while L5 was selected as the lowest instrumented vertebra in the other 2 patients. All patients received interlaminar fenestration on the convex side only with an area of about 15 mm × 20 mm. Fenestration at L2-L3 level was performed in 6 patients; while L3-L4 level was selected for windowing in the remaining 7 patients. 9 of the 13 patients received lumbar puncture and intrathecal nusinersen administration during the 1-year follow-up, with an accumulative total of 50 times. All injections were performed successfully under ultrasound guidance, with no one transferred to radiographic assistance. No severe complications occurred after injection. CONCLUSIONS: In SMA with severe scoliosis planning to receive posterior spinal fusion, unilateral lumbar interlaminar fenestration on the convex side provides a feasible and reliable access for intrathecal nusinersen administration after surgery.

Apical region correction and global balance: a 3-rods surgical strategy for the treatment of severe and rigid scoliosis.

BACKGROUND: The treatment of severe and rigid scoliosis is challenging. We developed a surgical strategy for severe and rigid scoliosis since 2014. This study aimed to retrospectively analyze the safety and efficacy of apical region correction and global balance with 3 rods as a surgical strategy for the treatment of severe and rigid scoliosis. METHODS: A retrospective study was performed for patients with severe and rigid scoliosis who underwent one-stage posterior corrective operation using the apical region correction and global balance with 3 rods surgical strategy between February 2014 and April 2020. The inclusion criteria were as follows: [1] Cobb angle > 90°; [2] flexibility < 30%; [3] a minimum 2-year follow-up. Patients were excluded if they had a history of traction or spinal surgery. Coronal and sagittal parameters, including Cobb angle, flexibility, apex vertebra translation, trunk shift (TS), thoracic kyphosis, lumbar lordosis, and sagittal vertical axis (SVA) were measured preoperatively, postoperatively and at the final follow-up. The Scoliosis Research Society 22-item questionnaire was administered preoperatively and at the final follow-up. During the operation, one slightly-bent short rod was placed into the concave side of apical region and correction was achieved by rod-rotation and distraction. Two pre-bent long rods were placed into both sides of the scoliosis and global balance was improved by leveling the proximal thoracic vertebrae and distal lumbar vertebrae. RESULTS: A total of 41 patients were included, with an average age of 20 years (range, 12-49 years) and follow-up of 34 months (range, 24-58 months). Postoperative correction rate was 53% for scoliosis. There were 14 patients with normal kyphosis before surgery, and 28 patients with normal kyphosis at the last follow-up. 88% of the patients (23/26) with preoperative coronal imbalance (TS > 20 mm) restored coronal balance at the final follow-up. 87% of the patients (14/16) with preoperative sagittal imbalance (SVA > 40 mm) restored sagittal balance at the final follow-up. The mean operation time and blood loss were 286 min and 941 mL, respectively. No patients had neurological complications or implant failure. CONCLUSION: The surgical strategy of apical region correction and global balance with 3 rods is a safe and effective alternative for the surgical treatment of severe and rigid scoliosis.

Surgical treatment of spinal deformities in spinal muscular atrophy: a single-center experience from China.

PURPOSE: To report the clinical characteristics and surgical outcomes of scoliosis in patients with spinal muscular atrophy (SMA) from Mainland China. METHODS: Nineteen patients were retrospectively analyzed. Demographic, anthropometric and respiratory parameters were collected preoperatively. Surgical program was analyzed. Radiographic data were measured perioperatively. Motor status, ventilation support, sitting ability and respiratory symptoms were evaluated preoperatively and at final follow-up. RESULTS: Age at surgery was 17.08 (12.83, 20.08) years. More than 40% of patients were diagnosed with low weight. Pulmonary dysfunction was observed in all patients. All patients received posterior spinal fusion (PSF). Sacroiliac fixation with sacral-2 alar iliac technique was used in 16 patients. Major curve correction rate was 54.87 ± 16.14%. Pelvic obliquity correction rate was 63.84 ± 23.70%. T1-T12 height, space-available-for-lung ratio and thoracic transverse diameter were increased (p < 0.001). Percentage of patients capable of sitting independently increased from 26.32% preoperatively to 73.68% at final follow-up. Cumulative scores of sitting-related items in muscular dystrophy spine questionnaire improved from 19.11 ± 5.40 preoperatively to 26.21 ± 5.20 at final follow-up. Total scores of symptomatic domains in St. George's Respiratory Questionnaire decreased from 4 (2, 12) preoperatively to 1 (0, 3) at final follow-up. CONCLUSIONS: SMA patients in China always present severe scoliosis at late adolescence, accompanied with high proportion of low weight and pulmonary dysfunction. PSF is effective for the correction of scoliosis and pelvic obliquity and the improvement of thoracic morphology. Sitting ability and respiratory symptoms were improved postoperatively.

The Effect of Traditional Single Growing Rod Technique on the Growth of Unsegmented Levels in Mixed-Type Congenital Scoliosis.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To present outcomes concerning patients with early-onset mixed-type congenital scoliosis (EOMTCS) treated with the traditional single growing rod (TSGR), focusing on the growth of unsegmented levels (USLs). METHODS: Patients with EOMTCS who underwent TSGR and had a minimum of 4 USLs, 4 distractions, and 3-year follow-up were enrolled. Spine radiographs before and after index surgery and at the latest follow-up were evaluated. The length of the concave and convex side of USLs and thoracic parameters were measured. The absolute value and percentage of growth were calculated. RESULTS: Fourteen patients (mean age, 7.3 ± 2.8 years) were enrolled. The average follow-up duration was 4.9 ± 1.2 years, during which time 84 distractions and 8 final fusions were performed. The average number of USLs was 6.3 ± 2.2. The total and annual percent growth of concave side of USLs was significantly higher than convex side (32.2 ± 13.3% vs. 23.9 ± 9.5%, p = 0.007; 6.8 ± 2.7%/year vs. 5.1% ± 2.2%/year, p = 0.007, respectively). The concave-to-convex ratio of USLs increased from 58.6 ± 6.4 ± 7.6% at baseline to 68.8 ± 9.3% at the latest follow-up (p < 0.001). The Campbell's space available for lung ratio increased from 74.9 ± 11.1% at baseline to 89.6 ± 7.0% at the latest follow-up (p < 0.001). CONCLUSIONS: In patients with EOMTCS, unilateral repetitive lengthening with TSGR can accelerate the growth of the concave side of USLs and improve the symmetry of the thorax.

Influences of Thoracic Spinal Deformity on Exercise Performance and Pulmonary Function: A Prospective Study of 168 Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the factors associated with cardiopulmonary exercise testing (CPET) measurements in patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Patients with AIS display restrictive pulmonary dysfunction on pulmonary function testing (PFT). It remains unknown whether thoracic spinal deformity affects exercise performance. METHODS: One hundred and sixty-eight patients with AIS from January 2014 to December 2019 were included. They underwent preoperative spinal radiological assessment, PFT, and CPET. The effects of the thoracic curve magnitude, body mass index, physical activity level and history of bracing on pulmonary function and exercise performance were analyzed. The Student t test and two-tailed Pearson test were used in data analysis. RESULTS: We found significantly reduced forced expiratory volume in 1second (FEV1) in patients with a larger magnitude of the proximal thoracic curve (P < 0.001) and the main thoracic curve (P < 0.001). There was a negative correlation between forced vital capacity (FVC) and the magnitude of the main thoracic curve (P < 0.001) and thoracic hypokyphosis (P < 0.001). In CPET, exercise capacity indicators such as the work rate, peak oxygen intake, and heart rate were not affected by the thoracic curve magnitude. Patients with moderate or severe pulmonary dysfunction had decreased tidal volume (P = 0.01) and ventilatory reserve (P < 0.001), as well as increased respiratory frequency at maximal exercise (P = 0.01). Patients with a moderate or high physical activity level had better exercise capacity, which was reflected by a higher work rate (P = 0.009) and oxygen intake (P < 0.001). CONCLUSION: There was no significant correlation between radiographic parameters and exercise capacity indicators. When the thoracic curve increased, patients had restrictive ventilatory dysfunction, which led to a tachypneic breathing pattern and reduction of ventilatory reserve during exercise. A physiological change of improved peak oxygen intake was demonstrated in patients with a moderate or high physical activity level.Level of Evidence: 3.

AMPK as a Potential Therapeutic Target for Intervertebral Disc Degeneration.

As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.

Melatonin Synergizes With Methylprednisolone to Ameliorate Acute Spinal Cord Injury.

Methylprednisolone (MP) is the drug of choice for treating spinal cord injury (SCI), but the aggressive dosage regimen used often results in adverse side effects. Therefore, MP should be combined with other drugs to lower the required dose. Melatonin is effective in alleviating nerve damage and inhibiting axonal degeneration. The combination of melatonin and half-dose methylprednisolone (HMP) for spinal cord injury treatment has never been reported. In this study, we established a rat model of T9 spinal cord injury by the Allen's method and assessed the synergistic therapeutic effects of melatonin and HMP by factorial design. Our results demonstrated that melatonin could synergize with HMP to ameliorate acute SCI through PI3K-AKT1 pathway. Combining melatonin with HMP significantly reduced the standard-dose of methylprednisolone and limited its adverse reactions, representing a promising option for treating acute SCI.

Bioinformatic analysis of SMN1-ACE/ACE2 interactions hinted at a potential protective effect of spinal muscular atrophy against COVID-19-induced lung injury.

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.

Surgical Scoliosis Correction in Chiari-I Malformation with Syringomyelia Versus Idiopathic Syringomyelia.

BACKGROUND: Both patients with Chiari-I malformation (CIM) with syringomyelia and those with idiopathic syringomyelia (ISm) have a syrinx and can have scoliosis as well. However, there is no literature regarding differences between CIM and ISm in terms of radiographic outcomes and surgical complications after posterior fusion, to our knowledge. The aim of the present study was to compare radiographic features, clinical outcomes, and surgical complications after posterior spinal fusion between patients with CIM-associated scoliosis and those with ISm-associated scoliosis. METHODS: One hundred and twenty patients with syringomyelia-associated scoliosis were retrospectively analyzed. Twenty-one patients with scoliosis secondary to CIM were enrolled and matched by sex, age, and the Cobb angle of the scoliotic curve with 21 patients with scoliosis secondary to ISm. All patients underwent 1-stage posterior fusion surgery. Coronal and sagittal radiographic parameters were evaluated before surgery, immediately after surgery, and at the final follow-up (at least 2 years). We also collected data regarding syringeal features, neurological deficits, intraoperative neuromonitoring, and complications. RESULTS: Sex, age, preoperative coronal/sagittal scoliosis parameters, and neurological deficits were similar between the matched CIM and ISm groups. On average, the CIM group had a longer syrinx (12.3 ± 3.6 versus 8.9 ± 4.5 vertebral levels, p = 0.010) than the ISm group. The CIM and ISm groups showed similar correction rates for primary curves (70.9% ± 10.6% versus 69.5% ± 16.3%, p = 0.739). There were no significant differences in coronal/sagittal correction, intraoperative neuromonitoring abnormalities, surgical complications, or Scoliosis Research Society-22 questionnaire scores between the 2 groups. CONCLUSIONS: Despite matched demographic and scoliotic coronal parameters, patients with CIM had longer syrinxes compared with patients with ISm. One-stage posterior fusion achieved comparable clinical and radiographic outcomes for both CIM- and ISm-associated scoliosis without significant differences in neurological complications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.