Ximing Xu

Anterior controllable antidisplacement and fusion surgery for the treatment of multilevel severe ossification of the posterior longitudinal ligament with myelopathy: preliminary clinical results of a novel technique

PurposeAlthough anterior and posterior decompression surgery are both reported to treat patients with myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). The surgical strategy of the disease is still controversial when the OPLL is multilevel and severe. This present study reports the preliminary clinical results of a novel technique named anterior controllable antidisplacement and fusion (ACAF) for the treatment of multilevel-severe OPLL with myelopathy.MethodsA series of 15 patients with cervical myelopathy caused by compression of multilevel severe OPLL were enrolled. All the patients underwent ACAF after thorough surgical designing based on preoperative imaging. The patients were followed for a mean follow-up duration of 9xa0months in this study. The main surgical procedures include discectomy of the involved levels, thinning of the anterior part of the involved vertebrae, intervertebral cages, anterior plate and screws installation, bilateral osteotomies of the vertebrae, and antedisplacement of the vertebrae-OPLL complex (VOC). The Japanese Orthopaedic Association (JOA) scales, Visual Analog Scale (VAS) were studied. And the pre- and postoperative radiological parameters, and surgical complications were also investigated.ResultsPostoperative CT and MRI showed complete decompression of the cord by antidisplacement of the VOC. Restoration of neurological defects was confirmed at the last follow-up assessment. Bone fusion was confirmed by CT at 6xa0months follow-up. No specific complications were identified that were associated with this technique.ConclusionsThe present study demonstrates that excellent postoperative outcome can be achieved with the use of the ACAF. Though further study is required to confirm the conclusion, this novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

miR-32-5p-mediated Dusp5 downregulation contributes to neuropathic pain

Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1β, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.

Neuroprotective Effects of Valproic Acid in a Rat Model of Cauda Equina Injury

BACKGROUNDnHistone deacetylase inhibitors, including valproic acid (VPA), are promising therapeutic interventions in neurological disorders and play an important role in synaptic activity and neuronal function.nnnMETHODSnA total of 30 rats were randomly allocated to 3 groups: sham, control, and VPA. The rats in the VPA and control groups received laminectomy at the L4 level of the vertebrae and silicone gel implantation into the epidural spaces L5 and L6. Rats in the sham group only received laminectomy at the L4 level of vertebrae without any implantation. VPA (300 mg/kg in saline) was administered 2 hours before the surgery. After the surgery, the VPA group received further VPA injections at 300 mg/kg twice a day for 1 week. The same volume of saline was injected in the control group. Neurobehavioral tests using the Basso, Beattie, Bresnahan scale and the oblique board test were performed for 1 week starting at 2 hours before surgery up to day 7 after surgery. At day 7 after surgery, tissues from the compressed cauda equina (L5-L6) were subjected to hematoxylin and eosin, luxol fast blue, or immunofluorescence staining, whereas the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end label assay staining was performed on the tissue from the dorsal root ganglions and the lumbar segment of the spinal cord proximal to the compressed cauda equina (L5-L6).nnnRESULTSnThe behavioral results suggested a significant improvement in the lower limb motor function in the VPA group compared with controls (P < 0.05). Furthermore, histologic assessment revealed a significant reduction in nerve fibers showing Wallerian degeneration and demyelinating lesions in the VPA group, in addition to an increased myelination compared with the control group (Pxa0< 0.05). The terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end label assay staining revealed a significant decrease in the number of apoptotic neurons in the spinal cord anterior horn and dorsal root ganglions in the VPA group compared with controls (Pxa0<xa00.05).nnnCONCLUSIONSnOur data demonstrated that VPA could alleviate cauda equina injury, reduce apoptotic cells, and improve motor recovery, suggesting a neuroprotective effect in acute cauda equina syndrome.

Quantitative Anterior Enlargement of the Spinal Canal by Anterior Controllable Antedisplacement and Fusion for the Treatment of Cervical Ossification of the Posterior Longitudinal Ligament with Myelopathy

PURPOSEnThis retrospective study aimed to investigate the effect of quantitative enlargement of spinal canal by anterior controllable antedisplacement and fusion (ACAF) for cervical ossification of the posterior longitudinal ligament (OPLL).nnnMETHODSnForty-three patients with OPLL who underwent ACAF were enrolled. According to the use of a curvature ruler (CR), patients were divided into group A (CR used, nxa0= 21) and group B (CR not used, nxa0= 22). The average follow-up was 9.5 months. The occupation rate (OR) of the spinal canal and the curvature of the cervical plate were recorded. The Japanese Orthopedic Association (JOA) scores were analyzed, and the recovery rate (RR) was calculated. Surgical complications were also investigated.nnnRESULTSnThe OR of the spinal canal in group A decreased from 66.7% ± 12.8% to 19.1% ± 10.9% after surgery (P < 0.05). In group B, the preoperative and postoperative OR was 63.9% ± 11.7% and 21.2% ± 8.7%, respectively (P < 0.05). Patients in group A had higher agreement of the curvature of the cervical plate between preoperative planning and postoperative measurement. The RR of JOA scores in group A was 73.7% ± 19.7%, higher than in group B (70.9% ± 7.3%, Pxa0>xa00.05). Further comparison between the 2 groups, excluding those patients with OR <50%, showed that both JOA score and RR in group A were higher than in group B at the final follow-up (P < 0.05).nnnCONCLUSIONSnThe quantitative enlargement of the spinal canal by ACAF may provide a positive and favorable effect on enlarging the spinal canal and achieving better neurologic recovery for the treatment of cervical OPLL with myelopathy. CR can facilitate the achievement of better and more quantitative spinal canal enlargement.

Nonfusion Intracorporeal Enhancement System for the Treatment of Osteoporotic Vertebral Compression Fractures–Preliminary Clinical Result of a Novel Technique

OBJECTIVEnThis study sought to determine whether implantation of a newly designed nonfusion intracorporeal enhancement (NICE) system is an effective and safe way to treat osteoporotic vertebral compression fracture (OVCF).nnnMETHODSnThirteen patients with OVCF (10 women, 3 men; mean age 69 years, T11-L4) were included. From June 2014 to June 2016, all patients were treated with the NICE system. The clinical and radiologic results were evaluated preoperatively, postoperatively, and at 24 months follow-up based on the visual analog scale and the Oswestry Disability Index, radiography, magnetic resonance imaging, and computed tomography (height of fractured body and kyphosis Cobb angle).nnnRESULTSnThere was a significant improvement in pain intensity (visual analog scale score decreased from 8.3xa0preoperatively to 2.2 postoperatively, and decreased to 1.5 twenty-four months postoperatively). Also, a significant reduction was observed in that the mean Oswestry Disability Index decreased from 71.9% preoperatively to 17.6% after 24 months. The mean Cobb angle had a significant improvement, which decreased from 6.6° preoperatively to 1.3° postoperatively and then decreased to 1.2° after 24 months. Height of fractured body improved significantly from 66.4% to 86.5% and slightly decreased to 82.4% after 24 months. No specific complications were identified to be associated with this technique.nnnCONCLUSIONSnWith a low complication rate, the clinical midterm results are satisfactory. The treatment of symptomatic OVCF with the NICE system is a safe and effective procedure.

Segmental characteristics of main thoracic curves in patients with severe adolescent idiopathic scoliosis

OBJECTIVEnSegmental flexibility in adolescent idiopathic scoliosis is crucial for the development of nonfusion and osteotomy technology. However, only global curve flexibility has been assessed in previous studies. Knowledge about segmental characteristics is absent.nnnMETHODSnTwenty patients with severe adolescent idiopathic scoliosis were enrolled in the present study. The vertebral and disc wedge angles were measured, and the segmental flexibility index was assessed by the correction rate of disc wedging on the traction film. Least significant difference analysis was used to compare the distribution of the variable. The patients were divided into 2 groups according to the stiffness of the global curves, and their relative wedging was compared.nnnRESULTSnVertebral wedging decreased from the apex toward the end. The apical and adjacent vertebrae accounted for 67.44% ± 8.05% of the total vertebral wedging deformities. Disc wedging significantly decreased upward and downward from the apex. Disc wedging demonstrated no significant differences between U1 (first above the apex) and U2 or L1 (first below the apex) and L2, and these 4 discs accounted for 75.47% ± 9.25% of the total disc wedging deformities. The levels close to the apical discs (U2 and L2) had the smallest extent of limited correctability. Segment disc flexibility showed a W-shaped distribution. The disc angle in the non-stiff group was significantly larger than the vertebral angle (40.13° ± 4.67° vs. 26.62° ± 6.99°; P < 0.001); however, similar results were not noted in the stiff group.nnnCONCLUSIONSnSignificant apical tethering in both vertebral body and disc wedging occurred, and the relative wedging changed significantly according to the rigidity of the main thoracic curves.

The clinical outcomes of primary and revision untethering surgery in patients with tethered cord syndrome and spinal bifida

BACKGROUNDnTethered cord syndrome (TCS) is an increasingly recognized clinical condition, with untethering surgery considered the classically effective treatment. Yet, as evidence has aggregated, the surgical outcomes of untethering remain controversial. This study aimed to systematically evaluate the clinical outcomes in patients who underwent primary or revision untethering.nnnMETHODSnThis retrospective study was conducted at the Department of Spine Surgery of Changzheng Hospital between January and December 2016. Patients with TCS who underwent untethering surgery were recruited for the study. Information collected included demographic data, main clinical manifestations, and outcomes after untethering surgery.nnnRESULTSnA total of 112 patients (60 males and 52 females) were included in this study, with mean follow-up of 13.7 years. The surgical outcomes of the primary untethering varied among symptoms, with remission rates of 30.0% for pain, 24.4% for paresthesia, 18.6% for motor deficit, 12.6% for bladder dysfunction, and 21.2% for bowel dysfunction. Moreover, 23.3%-40.2% of patients suffered deterioration after surgery during the follow-up period. Twenty-eight patients underwent revision untethering surgery. In these patients, the remission rate decreased by 5.6%-16.7% compared with the primary operation. Moreover, most patients (58.8%-70.6%) experienced no benefits after revision surgery.nnnCONCLUSIONSnWith a possible high risk of recurrence, further exploration of the indications and timing of the untethering surgery is needed. Conservative treatment and omnidirectional care might be a better choice for patients with retethering with recurrent symptoms.

Occurrence of substance P and neurokinin receptors during the early phase of spinal fusion

Spinal fusion is widely used for patients with spinal disorders; however, patients often suffer from back pain following fusion surgery. Substancexa0P (SP) acts as a pain neurotransmitter via the sensory nerve afferent fibres up to the spinal cord, and is involved in the conduction and modulation of pain. The use of specific SP neurokinin receptor (NKR) antagonists may decrease postoperative pain. In the present study, the effects of alterations in the quantity of SP and NKRs in the early spinal fusion process were investigated. The results of the present study revealed that SP and NKRs began to appear 1xa0week post‑surgery in fibrous tissues. The abundance of SP and NKRs peaked at 3xa0weeks post‑surgery; the majority of SP and NKRs were distributed around the allograft and the new microvessels. In conclusion, SP and NKRs are involved in early spinal fusion, a finding that may facilitate the development of novel strategies to promote spinal fusion from a neurogenesis perspective.

Surgical results and complications of anterior controllable antedisplacement fusion as a revision surgery after initial posterior surgery for cervical myelopathy due to ossification of the posterior longitudinal ligament

Posterior surgery has been widely used as an initial surgery for cervical ossification of the posterior longitudinal ligament (OPLL). However, some patients require revision surgery because of failure of symptom relief or late neurological deterioration after posterior surgery. The aim of this study is to retrospectively investigated the surgical results and complications of anterior controllable antedisplacement fusion (ACAF) as a revision surgical technique after initial posterior surgery for OPLL. The present study concluded 13 patients. The operation duration, blood loss and hospital stay was estimated. Radiologic assessment included type and extent of OPLL, decompression width and antero-posterior (AP) diameter of the spinal cord. The JOA scoring system was used to evaluate the neurological status. Surgery- and implant-related complications such as cerebrospinal fluid (CSF) leakage, spinal cord or nerve injury, subsidence and pseudoarthrosis were all recorded. The results showed that nine patients undergoing revision ACAF because of residual stenosis after initial posterior surgery, two because of OPLL progression, one because of lamina closure, one because of a blind man requiring better neurological function of both hands. The mean decompression width and AP diameter of the spinal cord was 20.3u202f±u202f2.1u202fmm and 5.8u202f±u202f1.1u202fmm respectively. The mean postoperative JOA score at last follow-up was significantly better than preoperation (14.8u202f±u202f2.5 vs. 8.5u202f±u202f2.7 points, Pu202f<u202f0.01), with a mean improvement rate of 75.3%u202f±u202f12.2%. No complication such as CSF leakage, spinal cord or nerve injury, subsidence and pseudoarthrosis occurred. In conclusion, ACAF is a well choice for revision surgery after initial posterior surgery for OPLL.

Protective effect of epigenetic silencing of CyclinD1 against spinal cord injury using bone marrow-derived mesenchymal stem cells in rats

This study focuses on the protective effect of epigenetic silencing of CyclinD1 against spinal cord injury (SCI) using bone marrow‐derived mesenchymal stem cells (BMSCs) in rats. Eighty‐eight adult female Wistar rats were randomly assigned into the sham group, the control group, the si‐CyclinD1u2009+u2009BMSCs group and the BMSCs group. CyclinD1 protein and mRNA expressions after siRNA transfection were detected by Western blotting and qRT‐PCR. The siRNA‐CyclinD1 BMSCs were transplanted into rats in the si‐CyclinD1u2009+u2009BMSCs group using stereotaxic method 6u2009hr after SCI. Hindlimb locomotor performance was determined using inclined plane test and Basso‐Beattie‐Bresnahan (BBB) locomotor rating scale. Expressions of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were detected by immunohistochemistry. Inclined plane and BBB scores in the control, si‐CyclinD1u2009+u2009BMSCs, and BMSCs groups were significantly lower than the sham group, but these scores were evidently decreased in the control group and increased in the si‐CyclinD1u2009+u2009BMSCs group compared with the BMSCs group. The repair degree of spinal cord tissues of rats in the si‐CyclinD1u2009+u2009BMSCs group was obvious than the BMSCs group. GFAP and NGF protein expressions were markedly decreased in the control, si‐CyclinD1u2009+u2009BMSCs and BMSCs groups when compared with the sham group. GFAP‐ and NGF‐positive cells were significantly increased in the si‐CyclinD1u2009+u2009BMSCs group while decreased in the control group. Our study provides evidence that epigenetic silencing of CyclinD1 using BMSCs might accelerate the repair of SCI in rats.