Unstable Pathologic Vertebral Fractures in Multiple Myeloma : Propensity Score Matched Cohort Study between Reconstructive Surgery with Adjuvant Radiotherapy and Radiotherapy Alone.

OBJECTIVE: Although radiotherapy (RT) is recommended for multiple myeloma (MM) involving spine, the treatment of choice between reconstructive surgery with RT and RT alone for pathologic vertebral fractures (PVFs) associated with structural instability or neurologic compromises remains controversial. The purpose of this study was to evaluate the clinical efficacies of reconstructive surgery with adjuvant RT for treatment of MM with PVFs by comparing with matched cohorts treated with RT alone. METHODS: Twenty-eight patients underwent reconstructive surgery followed by RT between 2008 and 2015 in a single institution, for management of PVFs associated with structural instability of the spine and/or neurologic compromises (group I). Twentyeight patients were treated with RT alone (group II) after propensity score matching in a 1-to-1 format based on instability of the spine, as well as age and performance. Clinical outcomes including the overall survival rates, duration of independent ambulation, neurological status, and numeric rating scale (NRS) for back pain were compared. RESULTS: Clinical and radiological features before treatment were similar in both groups. The median survival period was similar between the two groups. However, the mean duration of independent ambulation was significantly longer in group I (88.8 months; 95% confidence interval [CI], 66.0-111.5) than in group II (39.4 months; 95% CI, 25.2-53.6) (log rank test; p=0.022). Deterioration of Frankel grade (21.4% vs. 60.7%, p=0.024) and NRS for back pain (2.7±2.2 vs. 5.0±2.7, p=0.000) at the last follow-up were higher in the group II. Treatment-related complications were similar in both groups. CONCLUSION: In patients with unstable PVFs due to MM, reconstructive surgery may yield superior clinical outcomes compared with RT alone in maintaining independent ambulation and neurological status, as well as pain control despite similar median survival and complications.

No association between POU4F1, POU4F2, ISL1 polymorphisms and normal-tension glaucoma.

BACKGROUND: Normal-tension glaucoma (NTG) that occurs despite normal intraocular pressure has genetic predisposition. Since retinal ganglion cells (RGCs) are a key node in pathogenesis of glaucoma, neurodegeneration of RGCs is thought to be the main cause increasing the risk of NTG development. Here, we aimed to investigate the association of polymorphisms in RGC development genes with NTG development. MATERIALS AND METHODS: We performed a case-control association study of 435 patients with NTG and 419 normal controls. We genotyped four single nucleotide polymorphisms (SNPs) in genes responsible for RGC development, namely POU4F2 (rs13152799 and rs1504360), POU4F1 (rs9601092), and ISL1 (rs2288468), by either real-time PCR or PCR-RFLP, and evaluated its association with the risk of NTG development. RESULTS: No significant association was observed between the candidate SNPs and NTG development. CONCLUSIONS: To the best of our knowledge, this is the first report exploring the association between genes regulating RGC development and NTG susceptibility. Our data could provide a reference for further researches that focus on finding additional potential SNPs of POU4F2, POU4F1, ISL1 or other RGC development genes for NTG.

Genomic Characterization of TBK1 Duplication in Korean Normal-tension Glaucoma Patients.

PRéCIS:: One (0.2%) of 418 Korean normal-tension glaucoma (NTG) patients had TBK1 duplication. The putative mechanism of TBK1 duplication in Korean NTG patients is the nonhomologous end-joining. PURPOSE: TBK1 duplication is a genomic cause of familial NTG. NTG accounts for up to 90% of primary open-angle glaucoma in Koreans, with genetic tendency. We aimed to investigate the prevalence of TBK1 duplication in Korean NTG patients and to identify their genomic structure and duplication mechanism. MATERIALS AND METHODS: We obtained DNA samples from 418 NTG patients and 195 healthy controls for evaluating TBK1 copy number variations using a semiquantitative polymerase chain reaction (PCR). The samples with TBK1 gene duplication were further confirmed using droplet digital PCR. The whole-genome sequencing of patient samples with duplications was performed to identify the accurate breakpoints and to elucidate the genomic structure. Ophthalmic evaluation and confirmation of TBK1 duplication using junction PCR were performed in families of positive patients. RESULTS: TBK1 duplication was found in 1 of 418 NTG cases (0.2%). The duplication range was from g.64,803,151 to g.64,927,214 (124,063 bp). It is the smallest region of overlapping duplication in TBK1. Any repetitive sequences were not found near the breakpoints of our case. Inserted sequences were found within the breakpoints. A brother and a niece of the positive case appeared the typical clinical features of NTG and shared the same TBK1 duplications with the index case. CONCLUSIONS: In Korea, the prevalence of TBK1 duplication was 0.2% and the smallest reported TBK1 duplication associated with NTG was found. The mechanism of TBK1 duplication was suggested to be nonhomologous end-joining while a previous report pointed out the mechanism of TBK1 duplications as nonallelic homologous recombination.

Clinical Significance of Preoperative Embolization for Non-Hypervascular Metastatic Spine Tumors.

OBJECTIVE: The efficacy of preoperative embolization for hypervascular metastatic spine disease (MSD) such as renal cell and thyroid cancers has been reported. However, the debate on the efficacy of preoperative embolization for non-hypervascular MSD still remains unsettled. The purpose of this study is to determine whether preoperative embolization for non-hypervascular MSD decreases perioperative blood loss. METHODS: A total of 79 patients (36 cases of preoperative embolization and 43 cases of non-embolization) who underwent surgery for metastatic spine lesions were included. Representative hypervascular tumors such as renal cell and thyroid cancers were excluded. Intraoperative and perioperative estimated blood losses (EBL), total number of transfusion and calibrated EBL were recorded in the embolization and non-embolization groups. The differences in EBL were also compared along with the type of surgery. In addition, the incidence of Adamkiewicz artery and complications of embolization were assessed. RESULTS: The average age of 50 males and 29 females was 57.6±13.5 years. Lung (30), hepatocellular (14), gastrointestinal (nine) and others (26) were the primary cancers. The demographic data was not significantly different between the embolization and the non-embolization groups. There were no significant differences in intraoperative EBL, perioperative EBL, total transfusion and calibrated EBL between two groups. However, intraoperative EBL and total transfusion in patients with preoperative embolization were significantly lower than in non-embolization in the corpectomy group (1645.5 vs. 892.6 mL, p=0.017 for intraoperative EBL and 6.1 vs. 3.9, p=0.018 for number of transfusion). In addition, the presence of Adamkiewicz artery at the index level was noted in two patients. Disruption of this major feeder artery resulted in significant changes in intraoperative neuromonitoring. CONCLUSION: Preoperative embolization for non-hypervascular MSD did not reduce perioperative blood loss. However, the embolization significantly reduced intraoperative bleeding and total transfusion in corpectomy group. Moreover, the procedure provided insights into the anatomy of tumor and spinal cord vasculature.

Jack-knife Posture After Correction Surgery for Degenerative Sagittal Imbalance-Does Spinopelvic Parameter Always Matter in Preventing Stooping Posture?

STUDY DESIGN: A retrospective comparative cohort study. OBJECTIVE: To investigate the causes of jack-knife posture (JKP) without proximal junctional kyphosis (PJK) and to compare the causes of PJK and JKP without PJK. SUMMARY OF BACKGROUND DATA: PJK causing stooping posture could be inevitable after long instrumented lumbar fusion for degenerative sagittal imbalance. However, few studies have addressed JKP without PJK, which is a different type of sagittal malalignment. METHODS: Ninety-four adult patients who underwent long instrumented lumbar fusion for degenerative sagittal imbalance were divided into three groups depending on the presence of a postoperative sagittal deformity: JKP, PJK, or none. JKP was defined as a sagittal vertical axis of at least 8 cm anterior to the posterosuperior corner of S1 upper endplate without PJK. PJK was defined as a proximal kyphotic angle ≥10° and at least 10° greater than the preoperative measurement. RESULTS: Seventeen patients (18.1%) showed JKP, and 39 patients (41.5%) showed PJK. The mean age at the surgery of JKP and PJK patients was 70.0 and 65.5 years, respectively (p = .05). JKP developed more frequently if the preoperative pelvic tilt was <25° or the sagittal vertical axis was >8 cm (p = .048, 0.004, respectively). PJK developed more frequently if the preoperative pelvic tilt was >25°, surgically corrected lumbar lordosis was >30°, or the lumbar lordosis to thoracic kyphosis angle was <0° (p = .002, .010, .031, respectively). JKP was more likely to develop in patients without sacropelvic fixation (p = .042), although they had a more degenerative L5-S1 segment (p = .010). CONCLUSIONS: Postoperative sagittal deformity can be classified into two types: JKP and PJK. JKP is caused mainly by hip and back extensor muscle weakness even though the cause of postoperative sagittal decompensation could be multifactorial. However, PJK developed mainly due to spinopelvic malalignment. Therefore, hip and back extensor weakness, which is age-dependent, may explain why older patients experienced more postoperative sagittal deformity. LEVEL OF EVIDENCE: Level IV.

Clinical and Radiologic Features of Osteoporotic Spine Fracture with Delayed Neurologic Compromises.

OBJECTIVES: Osteoporotic spine fractures (OSFs) with delayed neurologic compromises (NCs) have been increasingly reported. Although several studies have addressed that the pathologic mechanism of NC involves nonunion and segmental instability, the risk factors remain unclear. Therefore, the purpose of this study was to assess the radiologic and clinical features of OSFs with delayed NC. METHODS: Thirty patients with delayed NC (group 1) were matched in a 1-to-1 format with 30 patients without delayed NC (group 2) by age, bone mineral density, body mass index, and medical treatment for osteoporosis. Clinical and radiologic parameters were assessed to determine the risk factors related to delayed NC. Clinical outcomes were also compared between the 2 groups. RESULTS: Neurologic compromises were presented as myelopathy in 20 patients and radiculopathy in 10 patients. Initial kyphotic angle (KA) and height loss (HL) were significantly greater in group 1 (21.6 ± 12.9 degrees vs. 10.5 ± 8.6 degrees, P = 0.0001 for KA; 55.8% ± 15.2% vs. 19.9% ± 10.9%, P = 0.0001 for HL). Fracture instability with intravertebral cleft, posterior wall involvement, midportion type of magnetic resonance classification, thoracolumbar level, and aortic calcification were significantly correlated with delayed NC. In multivariate analysis, initial HL (hazard ratio = 1.24; P = 0.012) and midportion-type fracture (hazard ratio = 14.9: P = 0.03) were the independent risk factors related to delayed NC. In addition, clinical outcomes at the last follow-up were significantly better in group 2. CONCLUSIONS: Initial HL and midportion-type fracture were correlated with delayed NC following OSFs. Moreover, pre-existing stenotic lesions might be associated with delayed NC.

Minimally Invasive Lateral Lumbar Interbody Fusion for Adult Spinal Deformity: Clinical and Radiological Efficacy With Minimum Two Years Follow-up.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To evaluate the clinical and radiological efficacies of supplementing minimally invasive lateral lumbar interbody fusion (LLIF) with open posterior spinal fusion (PSF) in adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: Minimally invasive techniques have been increasingly applied for surgery of ASD. Few reports have been published that directly compare LLIF combined with PSF to conventional PSF for ASD. METHODS: To evaluate the advantages of minimally invasive LLIF for ASD, patients who underwent minimally invasive LLIF followed by open PSF (combined group) were compared with patients who only underwent PSF (only PSF group). The clinical and radiological outcomes for deformity correction and indirect decompression were assessed. The occurrence of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) were also evaluated. RESULTS: No significant differences were observed in the clinical outcomes of the Oswestry Disability Index (ODI), visual analog scale, and major complications including reoperations between the groups. No additional advantage was found for coronal deformity correction, but the restoration of lumbar lordosis in the combined group was significantly higher postoperatively (15.3° vs. 8.87°, P = 0.003) and last follow-up (6.69° vs. 1.02°, P = 0.029) compared to that of the only PSF group. In the subgroup analysis for indirect decompression for the combined group, a significant increase of canal area (104 vs. 122 mm) and foraminal height (16.2 vs. 18.5 mm) was noted. The occurrence of PJK or PJF was significantly higher in the combined group than in the only PSF group (P = 0.039). CONCLUSION: LLIF has advantages of indirect decompression and greater improvements of sagittal correction compared to only posterior surgery. LLIF should be conducted considering the above-mentioned benefits and complications including PJK or PJF in ASD. LEVEL OF EVIDENCE: 4.

Large Deletions of TSPAN12 Cause Familial Exudative Vitreoretinopathy (FEVR).

Purpose: Familial exudative vitreoretinopathy (FEVR) is a rare, hereditary visual disorder. The gene TSPAN12 is associated with autosomal dominant inheritance of FEVR. The prevalence and impact of large deletions/duplications of TSPAN12 on FEVR patients is unknown. To glean better insight of TSPAN12 on FEVR pathology, herein, we describe three FEVR patients with TSPAN12 deletions. Methods: Thirty-three Korean FEVR patients, who previously screened negative for TSPAN12 mutations, mutations in other FEVR-associated genes such as NDP, FZD4, LRP5, and large deletions and duplications of NDP, FZD4, and LRP5, were selected for TSPAN12 large deletion and duplication analyses. Semiquantitative multiplex PCR for TSPAN12 gene dosage analyses were performed, followed by droplet digital PCR (ddPCR) for validation. Results: Among the 33 patients, three patients were confirmed to carry large TSPAN12 deletions. Two of them had whole-gene deletions of TSPAN12, and the other patient possessed a deletion of TSPAN12 in exon 4. FEVR severity detected in these patients was not more severe than in a patient with TSPAN12 point mutation. Conclusions: Regarding previously reported proportions of FEVR-associated genes contributing to the disorder's autosomal dominant inheritance pattern in Korea, we determined that patients with TSPAN12 large deletions were more common than patients with single nucleotide variants in TSPAN12. Evaluating TSPAN12 large deletions and duplications should be considered in FEVR screening and diagnosis as well as in routine genetic workups for FEVR patients.

Foreign Body Reaction after Implantation of a Device for Intervertebral Assisted Motion.

The device for intervertebral assisted motion (DIAM) is a dynamic implant that consists of a silicone bumper enveloped by a polyethylene terephthalate (PET) fiber sack. Silicone and PET were used because of their biological inertness, but repetitive motion of the spine can cause wear on the implant nonetheless. The purpose of this study is to report a case of foreign body reaction (FBR) against a DIAM. A 72-year-old female patient presented with lower back pain and both legs radiating pain. She had undergone DIAM implantation at L4-5 for spinal stenosis 5 years previously. The intervertebral disc space of L4-5, where the DIAM was inserted, had collapsed and degenerative scoliosis had developed due to left-side collapse. MRI showed L3-4 thecal sac compression and left L4-5 foraminal stenosis. The patient underwent removal of the DIAM and instrumented fusion from L3 to L5. During surgery, fluid and granulation tissue were evident around the DIAM. Histopathology showed scattered wear debris from the DIAM causing chronic inflammation due to the resulting FBR. A FBR due to wear debris of a DIAM can induce a hypersensitivity reaction and bone resorption around the implant, causing it to loosen.

Bone cement augmentation procedures for spinal pathologic fractures by multiple myeloma.

Efficacy and safety of bone cement augmentations for spinal pathologic fractures related to multiple myeloma, and usefulness of radionuclide studies for surgical decision were retrospectively evaluated. Forty eight vertebrae from 27 patients for bone cement augmentation procedures and 48 vertebrae from 29 patients for conservative treatment were enrolled. Clinical results using visual analogue scale (VAS) and Oswestry disability index (ODI), and radiologic results were assessed. For clinical decisions on treatment of spinal pathologic fracture, bone scan or single photon emission computed tomography was done for 20 patients who underwent surgery. Mean follow-up was 16.8 months. In terms of clinical results, immediate pain relief was superior in the operated group to that in the conservative group. ODI, maintenance of vertebral height and local kyphotic angle at the last follow-up were superior in the operated group in comparison to the conservative group. At one year follow-up, cumulative survival rate were 77.4% and 74.7% in the operated and conservative groups, respectively (log rank test> 0.05). Leakage of bone cement was noted at 10 treated vertebrae. Bone cement augmentations presented short-term pain relief for spinal pathologic fractures by myeloma with relative safety in highly selected patients, and radionuclide imaging studies were useful for the surgical decision on these procedures.

Fate of osteophytes and sclerosis in fused segments after lumbar fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the fate of sclerosis and anterior osteophytes in the fused segments after instrumented lumbar fusion for degenerative lumbar disorders. SUMMARY OF BACKGROUND DATA: Sclerosis and osteophytosis are well-known radiographical findings, but little is known of their significance with regard to spontaneous resorption after spine fusion. METHODS: Thirty patients (9 males, 21 females; 60 vertebra; mean age of 66.9 yr [45-86 yr]) were divided into a posterolateral fusion group (n = 14, 28 vertebrae) and a posterior lumbar interbody fusion group (n = 16, 32 vertebrae). Using serial radiographs obtained preoperatively; postoperatively at 3, 6, 12, and 24 months; and last follow-up, sclerotic areas of each involved vertebra were mapped and osteophyte lengths were measured. RESULTS: Sclerosis and osteophytes decreased with time for the instrumented fusion. The decrease in sclerotic areas and osteophytes length was observed as early as 3 months postoperatively, and the significant changes between each time point were noted in initial 3- and 6-month intervals. In terms of the type of surgery, similar changes were noted in the posterolateral fusion and posterior lumbar interbody fusion groups. CONCLUSION: Resorption of osteophytes and sclerosis after instrumented spine fusion were observed. Significant resorption was noted at 3 and 6 months postoperatively. As well, most graft bone would be incorporated in postoperative 6 months. Resorption of osteophytes and sclerosis after instrumented spine fusion could be helpful to confirm the successful union. LEVEL OF EVIDENCE: 4.

Is it real adjacent segment pathology by stress concentration after limited fusion in degenerative lumbar scoliosis?

STUDY DESIGN: A retrospective comparative study. OBJECTIVE: To investigate adjacent segment pathology (ASP) after limited lumbar fusion in the treatment of degenerative lumbar scoliosis (DLS). SUMMARY OF BACKGROUND DATA: The assessment of appropriate surgical techniques for DLS remains one of the most controversial topics in spinal surgery. So far, there has been no study specifically addressing why ASP shows different patterns with respect to different fusion levels after instrumented lumbar fusion for DLS. METHODS: Fifty-nine patients were enrolled and divided into 2 groups with respect to the proximal fusion level: group I consisted of 29 patients who underwent fusion below the proximal neutral vertebrae, and group II consisted of 30 patients who underwent fusion to the proximal neutral vertebrae. Clinical and radiological assessments were performed with an average of 59.4 months of follow-up. The number of radiological findings for ASP was determined on the basis of a 7-point scale that gave 1 point for each radiological finding. The 2 groups were analyzed according to radiological ASP (RASP). The Oswestry Disability Index and visual analogue scale scores were recorded prospectively. RESULTS: Overall, RASP developed in 16 (27.1%) patients. In group I, 12 (41.4%) of 29 patients, and in group II, 4 (13.3%) of 30 patients showed RASP. Group I yielded an average of 4.5 points, and group II, 1.8 points. RASP scores were much higher in group I than in group II, with statistical significance (P = 0.000). In group I, 4 patients underwent revision surgery, but in group II, only 1 patient did so. CONCLUSION: RASP displayed variance according to different fusion levels. RASP in group I showed similar patterns to the natural progression of DLS. It is suggested that fusion be included at least at the proximal neutral vertebrae to reduce RASP although RASP with different patterns is unavoidable. LEVEL OF EVIDENCE: 4.