Publications by authors named "Henrich Cheng"

186 Publications

Cortical Bone Trajectory-Based Dynamic Stabilization.

World Neurosurg 2021 Dec 22. Epub 2021 Dec 22.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Background: Cortical bone trajectory (CBT) screws have demonstrated similar biomechanical strength and fusion rates as conventional pedicle screws for short-segment lumbar fusion. However, very few studies have verified the viability of CBT screws in dynamic stabilization. In the present study, we compared the clinical outcomes of CBT-based Dynesys dynamic stabilization (CBT-DDS) with standard minimally invasive transforaminal lumbar interbody fusion (MI-TLIF).

Methods: Consecutive patients who had undergone CBT-DDS or MI-TLIF at L4-L5 or L3-L5 were retrospectively reviewed. All the radiological and clinical outcomes were compared between the 2 groups. The patient-reported outcomes included the visual analog scale scores for back and leg pain, Japanese Orthopaedic Association scores, and Oswestry disability index. The pre- and postoperative radiological evaluations were also reviewed.

Results: A total of 60 patients (20 patients in the CBT-DDS and 40 in the MI-TLIF groups) were analyzed. The MI-TLIF group had required a longer operation time (P = 0.010) than the CBT-DDS group but had had a similar estimated blood loss (P = 0.484). The perioperative complications, including screw loosening, wound infection, and radiculopathy, were similar in both groups (P > 0.05 for all). The degree of decreased range of motion after surgery was similar between the 2 groups (P = 0.781), and no pseudarthrosis developed in the MI-TLIF group.

Conclusions: Because the clinical and radiological outcomes of CBT-DDS were similar to those of MI-TLIF in patients with L4-L5 or L3-L5 spondylosis and spondylolisthesis, CBT-DDS appears to be a viable and effective alternative to MI-TLIF, with a shorter operation time and similarly limited segmental motility.
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http://dx.doi.org/10.1016/j.wneu.2021.12.061DOI Listing
December 2021

Cervical disc arthroplasty for Klippel-Feil syndrome.

Clin Neurol Neurosurg 2021 10 3;209:106934. Epub 2021 Sep 3.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan. Electronic address:

Objective: Klippel-Feil syndrome (KFS) is a congenital musculoskeletal condition characterized by improper segmentation of the cervical spine. This study aimed to evaluate outcomes of KFS patients who underwent cervical disc arthroplasty (CDA).

Methods: Consecutive patients who underwent anterior cervical surgery were retrospectively reviewed. Those patients with KFS who received discectomy adjacent to the congenitally fused vertebral segments were extracted and grouped into either the fusion or the CDA group. Clinical and radiological evaluations included visual analog scales, Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) scores, C2-7 range of motion (ROM), C2-7 Cobb angle, C2-7 sagittal vertical axis (SVA), and T1-slope.

Results: Among 2320 patients, there were 41 with KFS (prevalence = 1.77%), who were younger than the entire cohort (53.3 vs 56.4 years). Thirty KFS patients had adjacent discs and were grouped into the CDA and fusion groups (14 vs 16). Type-I KFS with C3-4 involvement was the most common for both groups (92.8% vs 81.2% with 57% vs 50%, respectively). Post-operation, both groups demonstrated improvement of all the patient reported outcomes. The C2-7 ROM significantly decreased in the fusion group than that of pre-operation (12.8 ± 6° vs 28.1 ± 11.5°). In contrast, the CDA group successfully preserved C2-7 and segmental ROM without additional complications.

Conclusions: KFS is rare (prevalence = 1.77%) among cervical spine surgery patients, and it rarely affects the overall cervical spinal alignment, except that it decreases segmental mobility. CDA is a feasible option for KFS because it not only avoids long-segment fusion but also preserves segmental and global mobility.
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http://dx.doi.org/10.1016/j.clineuro.2021.106934DOI Listing
October 2021

Correlation of bone density to screw loosening in dynamic stabilization: an analysis of 176 patients.

Sci Rep 2021 09 1;11(1):17519. Epub 2021 Sep 1.

Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Beitou District, Taipei, 112, Taiwan, ROC.

Although osteoporosis has negative impacts on lumbar fusion, its effects on screw loosening in dynamic stabilization remain elusive. We aimed to correlate bone mineral density (BMD) with screw loosening in Dynesys dynamic stabilization (DDS). Consecutive patients who underwent 2- or 3-level DDS for spondylosis, recurrent disc herniations, or low-grade spondylolisthesis at L3-5 were retrospectively reviewed. BMD was assessed by the Hounsfield Unit (HU) in vertebral bodies (VB) and pedicles with and without cortical bone (CB) on pre-operative computed tomography (CT). Screw loosening was assessed by radiographs and confirmed by CT. HU values were compared between the loosened and intact screws. 176 patients and 918 screws were analyzed with 78 loosened screws found in 36 patients (mean follow-up: 43.4 months). The HU values of VB were similar in loosened and intact screws (p = 0.14). The HU values of pedicles were insignificantly less in loosened than intact screws (including CB: 286.70 ± 118.97 vs. 297.31 ± 110.99, p = 0.45; excluding CB: 238.48 ± 114.90 vs. 240.51 ± 108.91, p = 0.88). All patients had clinical improvements. In conclusion, the HU values, as a surrogate for BMD, were unrelated to screw loosening in DDS. Therefore, patients with compromised BMD might be potential candidates for dynamic stabilization rather than fusion.
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http://dx.doi.org/10.1038/s41598-021-95232-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410763PMC
September 2021

The Application of an Omentum Graft or Flap in Spinal Cord Injury.

Int J Mol Sci 2021 Jul 25;22(15). Epub 2021 Jul 25.

Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Taipei 11217, Taiwan.

Background: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration.

Methods: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord.

Results: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, < 0.05). Furthermore, the reduction in cavity and the preservation of class III β-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers ( < 0.05) and a reduced injured cavity, though locomotor scores were similar.

Conclusions: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.
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http://dx.doi.org/10.3390/ijms22157930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347514PMC
July 2021

Stem cell transplantation and/or adenoviral glial cell line-derived neurotrophic factor promote functional recovery in hemiparkinsonian rats.

World J Stem Cells 2021 Jan;13(1):78-90

Department of Neurosurgery, Taipei Veterans General Hospital, Center for Neural Regeneration, Neurological Institute, Taipei 112, Taiwan.

Background: Parkinson's disease (PD) is a neurological disorder characterized by the progressive loss of midbrain dopamine (DA) neurons. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into multiple cell types including neurons and glia. Transplantation of BMSCs is regarded as a potential approach for promoting neural regeneration. Glial cell line-derived neurotrophic factor (GDNF) can induce BMSC differentiation into neuron-like cells. This work evaluated the efficacy of nigral grafts of human BMSCs (hMSCs) and/or adenoviral (Ad) GDNF gene transfer in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.

Aim: To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats.

Methods: We used immortalized hMSCs, which retain their potential for neuronal differentiation. hMSCs, preinduced hMSCs, or Ad-GDNF effectively enhanced neuronal connections in cultured neurons. , preinduced hMSCs and/or Ad-GDNF were injected into the substantia nigra (SN) after induction of a unilateral 6-OHDA lesion in the nigrostriatal pathway.

Results: Hemiparkinsonian rats that received preinduced hMSC graft and/or Ad-GDNF showed significant recovery of apomorphine-induced rotational behavior and the number of nigral DA neurons. However, DA levels in the striatum were not restored by these therapeutic treatments. Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN.

Conclusion: The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.
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http://dx.doi.org/10.4252/wjsc.v13.i1.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859988PMC
January 2021

Minocycline exhibits synergism with conditioned medium of bone marrow mesenchymal stem cells against ischemic stroke.

J Tissue Eng Regen Med 2021 03 9;15(3):279-292. Epub 2021 Feb 9.

Department of Pharmacology and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Several lines of evidence show that a conditioned medium of bone marrow mesenchymal stem cells (BM-MSCcm) improve functional recovery after ischemic stroke but do not reduce ischemic lesions. It is important to develop a treatment strategy that can exhibit a synergistic effect with BM-MSCcm against ischemic stroke. In this study, the effect of BM-MSCcm and/or minocycline was examined in culture and in a middle cerebral artery occlusion (MCAo) animal model. In neuron-glial cultures, BM-MSCcm and combined treatment, but not minocycline, effectively increased neuronal connection and oligodendroglial survival. In contrast, minocycline and combined treatment, but not BM-MSCcm, reduced toxin-induced free radical production in cultures. Either minocycline or BM-MSCcm, or in combination, conferred protective effects against oxygen glucose deprivation-induced cell damage. In an in vivo study, BM-MSCcm and minocycline were administered to rats 2 h after MCAo. Monotherapy with BM-MSCcm or minocycline after ischemic stroke resulted in 9.4% or 17.5% reduction in infarction volume, respectively, but there was no significant difference. Interestingly, there was a 33.9% significant reduction in infarction volume by combined treatment with BM-MSCcm and minocycline in an in vivo study. The combined therapy also significantly improved grasping power, which was not altered by monotherapy. Furthermore, combined therapy increased the expression of neuronal nuclei in the peri-infarct area and hippocampus, and concurrently decreased the expression of ED1 in rat brain and the peri-infarct zone. Our data suggest that minocycline exhibits a synergistic effect with BM-MSCcm against ischemic stroke not only to improve neurological functional outcome but also to reduce cerebral infarction.
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http://dx.doi.org/10.1002/term.3171DOI Listing
March 2021

Cranio-Vertebral Junction Triangular Area: Quantification of Brain Stem Compression by Magnetic Resonance Images.

Brain Sci 2021 Jan 6;11(1). Epub 2021 Jan 6.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

(1) Background: Most of the currently used radiological criteria for craniovertebral junction (CVJ) were developed prior to the popularity of magnetic resonance images (MRIs). This study aimed to evaluate the efficacy of a novel triangular area (TA) calculated on MRIs for pathologies at the CVJ. (2) Methods: A total of 702 consecutive patients were enrolled, grouped into three: (a) Those with pathologies at the CVJ ( = 129); (b) those with underlying rheumatoid arthritis (RA) but no CVJ abnormalities ( = 279); and (3) normal (control; = 294). TA was defined on T2-weighted MRIs by three points: The lowest point of the clivus, the posterior-inferior point of C2, and the most dorsal indentation point at the ventral brain stem. Receiver operating characteristic (ROC) analysis was used to correlate the prognostic value of the TA with myelopathy. Pre- and post-operative TA values were compared for validation. (c) Results: The CVJ-pathology group had the largest mean TA (1.58 ± 0.47 cm), compared to the RA and control groups (0.96 ± 0.31 and 1.05 ± 0.26, respectively). The ROC analysis calculated the cutoff-point for myelopathy as 1.36 cm with the area under the curve at 0.93. Of the 81 surgical patients, the TA was reduced (1.21 ± 0.37 cm) at two-years post-operation compared to that at pre-operation (1.67 ± 0.51 cm). Moreover, intra-operative complete reduction of the abnormalities could further decrease the TA to 1.03 ± 0.39 cm. (4) Conclusions: The TA, a valid measurement to quantify compression at the CVJ and evaluate the efficacy of surgery, averaged 1.05 cm in normal patients, and 1.36 cm could be a cutoff-point for myelopathy and of clinical significance.
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http://dx.doi.org/10.3390/brainsci11010064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825444PMC
January 2021

A Cylindrical Ion Sensor Tip with a Diameter of 1.5 mm for Potentially Invasive Medical Application.

ACS Omega 2020 Sep 2;5(36):23021-23027. Epub 2020 Sep 2.

Institute of Physics, National Chiao Tung University, Hsinchu 300, Taiwan.

A fine cylindrical chemical sensor tip is developed with optical fiber in the core, surrounded by a transparent cylinder of photopolymer Norland Optical Adhesive 61 (NOA 61), and covered by a polymer hydrogel mixed with sensing molecules. The overall diameter is as small as 1.5 mm. pH response is demonstrated using two approaches of sensing materials: (i) absorbing probe Phenol Red mixed with Rhodamine 6G fluorescent dye and (ii) 8-hydroxypyrene-1,3,6-trisulfonic acid fluorescent probe. Both the optical excitation and fluorescence signal collection are through the optical fibers. A time resolution of 10 s is achieved for pH variations. Good linearity is observed in the physiological range from pH 7.0 to pH 8.6 with reversible and reproducible outcomes. For urea measurement, the sensor tip can distinguish 1, 3, and 5 mM urea solution, which is a crucial range in saliva urea concentration. The miniaturized tip with such simple cylindrical symmetry is designed to detect vital signs during minimally invasive surgeries and can be potentially accompanied with endoscopes to enter human bodies.
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http://dx.doi.org/10.1021/acsomega.0c02725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495754PMC
September 2020

Minimally invasive dynamic screw stabilization using cortical bone trajectory.

BMC Musculoskelet Disord 2020 Sep 10;21(1):605. Epub 2020 Sep 10.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Room 525, 17F, No. 201, Shih-Pai Road, Sec. 2, Beitou, Taipei, 11217, Taiwan.

Background: The conventional pedicle-screw-based dynamic stabilization process involves dissection of the Wiltse plane to cannulate the pedicles, which cannot be undertaken with minimal surgical invasion. Despite some reports having demonstrated satisfactory outcomes of dynamic stabilization in the management of low-grade spondylolisthesis, the extensive soft tissue dissection involved during pedicle screw insertion substantially compromises the designed rationale of motion (muscular) preservation. The authors report on a novel method for minimally invasive insertion of dynamic screws and a mini case series.

Methods: The authors describe innovations for inserting dynamic screws via the cortical bone trajectory (CBT) under spinal navigation. All the detailed surgical procedures and clinical data are demonstrated.

Results: A total of four (2 females) patients (mean age 64.75 years) with spinal stenosis at L4-5 were included. By a combination of microscopic decompression and image-guided CBT screw insertion, laminectomy and dynamic screw stabilization were achieved via one small skin incision (less than 3 cm). These patients' back and leg pain improved significantly after the surgery.

Conclusion: This innovative dynamic screw stabilization via the CBT involved no discectomy (or removal of sequestrated fragment only), no interbody fusion, and little muscle dissection (not even of the Wiltse plane). As a minimally invasive surgery, CBT appeared to be a viable alternative to the conventional pedicle-screw-based dynamic stabilization approach.
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http://dx.doi.org/10.1186/s12891-020-03629-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488542PMC
September 2020

The Effect of T1-Slope in Spinal Parameters After Cervical Disc Arthroplasty.

Neurosurgery 2020 11;87(6):1231-1239

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Although patients with cervical kyphosis are not ideal candidates for cervical disc arthroplasty (CDA), there is a paucity of data on patients with a straight or slightly lordotic neck.

Objective: To correlate cervical lordosis, T1-slope, and clinical outcomes of CDA.

Methods: The study retrospectively analyzed 95 patients who underwent 1-level CDA and had 2-yr follow-up. They were divided into a high T1-slope (≥28°) group (HTSG, n = 45) and a low T1-slope (<28°) group (LTSG, n = 50). Cervical spinal alignment parameters, including T1-slope, cervical lordosis (C2-7 Cobb angle), and segmental mobility (range of motion [ROM]) at the indexed level, were compared. The clinical outcomes were also assessed.

Results: The mean T1-slope was 28.1 ± 7.0°. After CDA, the pre- and postoperative segmental motility remained similar and cervical lordosis was preserved. All the clinical outcomes improved after CDA. The HTSG were similar to the LTSG in age, sex, segmental mobility, and clinical outcomes. However, the HTSG had higher cervical lordosis than the LTSG. Furthermore, the LTSG had increased cervical lordosis (ΔC2-7 Cobb angle), whereas the HTSG had decreased lordosis after CDA. Patients of the LTSG, who had more improvement in cervical lordosis, had a trend toward increasing segmental mobility at the index level (ΔROM) than the HTSG.

Conclusion: In this series, T1-slope correlated well with global cervical lordosis but did not affect the segmental mobility. After CDA, the changes in cervical lordosis correlated with changes in segmental mobility. Therefore, segmental lordosis should be cautiously preserved during CDA as it could determine the mobility of the disc.
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http://dx.doi.org/10.1093/neuros/nyaa271DOI Listing
November 2020

Hydrogel-based zinc ion sensor on optical fiber with high resolution and application to neural cells.

Biosens Bioelectron 2020 Aug 21;162:112230. Epub 2020 Apr 21.

Institute of Physics, National Chiao Tung University, Hsinchu, 300, Taiwan. Electronic address:

Solid-state zinc ion sensor is developed with high enough resolution and reproducibility for the potential application in brain injury monitoring. An optical diffuser is incorporated into the zinc ion sensor based on optical fiber and hydrogel doped with the fluorescent zinc ion probe molecule meso-2,6-Dichlorophenyltripyrrinone (TPN-Cl). The diffuser transforms the high-peak-intensity excitation light near the fiber end into a broad light with moderate local intensity to reduce the degradation of the probe molecule. Reversible detection can be reached for 1, 2, and 5 μM (10 Molar), with slopes 0.3, 0.6, and 0.8 respectively. This is the pathophysiological concentration range after brain injury. The sensor is applied to neuron-glial cultures and macrophage under the stimulation of lipopolysaccharide (LPS), KCl and oxygen/glucose deprivation (OGD) that reflect inflammation, depolarization and ischemia respectively, mimicking events after brain injury. The zinc ion level is raised to 4-5 μM after LPS treatment, and then reduced to <3 μM after the co-treatment with the herbal drug silymarin. The results suggest the conditions of the neural cells under stress can be monitored.
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http://dx.doi.org/10.1016/j.bios.2020.112230DOI Listing
August 2020

Effects of smoking on pedicle screw-based dynamic stabilization: radiological and clinical evaluations of screw loosening in 306 patients.

J Neurosurg Spine 2020 May 1:1-8. Epub 2020 May 1.

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: Cigarette smoking has been known to increase the risk of pseudarthrosis in spinal fusion. However, there is a paucity of data on the effects of smoking in dynamic stabilization following lumbar spine surgery. This study aimed to investigate the clinical outcomes and the incidence of screw loosening among patients who smoked.

Methods: Consecutive patients who had lumbar spondylosis, recurrent disc herniations, or low-grade spondylolisthesis that was treated with 1- or 2-level surgical decompression and pedicle screw-based Dynesys dynamic stabilization (DDS) were retrospectively reviewed. Patients who did not complete the minimum 2 years of radiological and clinical evaluations were excluded. All screw loosening was determined by both radiographs and CT scans. Patient-reported outcomes, including visual analog scale (VAS) scores of back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI), were analyzed. Patients were grouped by smoking versus nonsmoking, and loosening versus intact screws, respectively. All radiological and clinical outcomes were compared between the groups.

Results: A total of 306 patients (140 women), with a mean age of 60.2 ± 12.5 years, were analyzed during an average follow-up of 44 months. There were 34 smokers (9 women) and 272 nonsmokers (131 women, 48.2% more than the 26.5% of smokers, p = 0.017). Postoperatively, all the clinical outcomes improved (e.g., VAS back and leg pain, JOA scores, and ODI, all p < 0.001). The overall rate of screw loosening was 23.2% (71 patients), and patients who had loosened screws were older (61.7 ± 9.6 years vs 59.8 ± 13.2 years, p = 0.003) and had higher rates of diabetes mellitus (33.8% vs 21.7%, p = 0.038) than those who had intact DDS screws. Although the patients who smoked had similar clinical improvement (even better VAS scores in their legs, p = 0.038) and a nonsignificantly lower rate of screw loosening (17.7% and 23.9%, p = 0.416), the chances of secondary surgery for adjacent segment disease (ASD) were higher than for the nonsmokers (11.8% vs 1.5%, p < 0.001).

Conclusions: Smoking had no adverse effects on the improvements of clinical outcomes in the pedicle screw-based DDS surgery. For smokers, the rate of screw loosening trended lower (without significance), but the chances of secondary surgery for ASD were higher than for the nonsmoking patients. However, the optimal surgical strategy to stabilize the lumbar spine of smoking patients requires future investigation.
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http://dx.doi.org/10.3171/2020.2.SPINE191380DOI Listing
May 2020

Comparison of Radiation Exposure Between O-Arm Navigated and C-Arm Guided Screw Placement in Minimally Invasive Transforaminal Lumbar Interbody Fusion.

World Neurosurg 2020 07 18;139:e489-e495. Epub 2020 Apr 18.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Instrumentation in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is highly dependent on image guidance. Guidance with fluoroscopy (C-arm) and cone-beam computed tomography (O-arm) with navigation are common options. The intraoperative radiation exposure to patients with the different image modalities has not been compared, however. The present study aimed to compare the radiation exposure of the C-arm guidance and O-arm navigation techniques during MIS-TLIF surgery.

Methods: Ninety consecutive patients who underwent MIS-TLIF for degenerative lumbar pathologies were retrospectively reviewed. The patients were divided into the C-arm guided (CG) and the O-arm navigated (ON) groups (45 patients in each group), and the radiation dosage reports were analyzed for comparison of radiation exposure.

Results: The ON group had a higher average effective radiation dose (1.99 ± 0.4 mSv vs. 0.91 ± 0.3 mSv). For patients with more than 2 interbody fusion levels (≥6 pedicle screws), the effective dose per screw was similar in the CG and ON groups (0.22 ± 0.08 mSv vs. 0.23 ± 0.05 mSv). As the body mass index increased, the per-screw effective dose of the CG group showed a significant positive trend, compared with a nonsignificant negative trend in the ON group.

Conclusions: For level 1 MIS-TLIF (4 percutaneous screws), patients in the ON group had almost double the radiation exposure as those in the CG group. For level ≥2 (≥6 screws) or obese patients, the O-arm with navigation has the advantage of similar radiation exposure to the patient and less (almost no) radiation to the operating room staff.
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http://dx.doi.org/10.1016/j.wneu.2020.04.052DOI Listing
July 2020

Neuroprotection in the Acute Stage Enables Functional Recovery Following Repair of Chronic Cervical Root Transection After a 3-Week Delay.

Neurosurgery 2020 09;87(4):823-832

Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery.

Objective: To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair.

Methods: First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury.

Results: Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance.

Conclusion: Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.
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http://dx.doi.org/10.1093/neuros/nyz572DOI Listing
September 2020

The superiority of conditioned medium derived from rapidly expanded mesenchymal stem cells for neural repair.

Stem Cell Res Ther 2019 12 16;10(1):390. Epub 2019 Dec 16.

Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, 11217, Taiwan.

Background: Spinal cord injury (SCI) is a complex and severe neurological condition. Mesenchymal stem cells (MSCs) and their secreted factors show promising potential for regenerative medicine. Many studies have investigated MSC expansion efficacy of all kinds of culture medium formulations, such as growth factor-supplemented or xeno-free medium. However, very few studies have focused on the potential of human MSC (hMSC) culture medium formulations for injured spinal cord repair. In this study, we investigated the effect of hMSC-conditioned medium supplemented with bFGF, EGF, and patient plasma, namely, neural regeneration laboratory medium (NRLM), on SCI in vitro and in vivo.

Methods: Commercial and patient bone marrow hMSCs were obtained for cultivation in standard medium and NRLM separately. Several characteristics, including CD marker expression, differentiation, and growth curves, were compared between MSCs cultured in standard medium and NRLM. Additionally, we investigated the effect of the conditioned medium (referred to as NRLM-CM) on neural repair, including inflammation inhibition, neurite regeneration, and spinal cord injury (SCI), and used a coculture system to detect the neural repair function of NRLM-MSCs.

Results: Compared to standard culture medium, NRLM-CM had superior in inflammation reduction and neurite regeneration effects in vitro and improved functional restoration in SCI rats in vivo. In comparison with standard culture medium MSCs, NRLM-MSCs proliferated faster regardless of the age of the donor. NRLM-MSCs also showed increased adipose differentiative potential and reduced CD90 expression. Both types of hMSC CM effectively enhanced injured neurite outgrowth and protected against HO toxicity in spinal cord neuron cultures. Cytokine arrays performed in hMSC-CM further revealed the presence of at least 120 proteins. Among these proteins, 6 demonstrated significantly increased expression in NRLM-CM: adiponectin (Acrp30), angiogenin (ANG), HGF, NAP-2, uPAR, and IGFBP2.

Conclusions: The NRLM culture system provides rapid expansion effects and functional hMSCs. The superiority of the derived conditioned medium on neural repair shows potential for future clinical applications.
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http://dx.doi.org/10.1186/s13287-019-1491-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916259PMC
December 2019

Radiological and clinical outcomes of 3-level cervical disc arthroplasty.

J Neurosurg Spine 2019 Nov;32(2):174-181

3Department of Biomedical Imaging and Radiological Sciences, and.

Objective: One- and two-level cervical disc arthroplasty (CDA) has been compared to anterior cervical discectomy and fusion (ACDF) in several large-scale, prospective, randomized trials that have demonstrated similar clinical outcomes. However, whether these results would be similar when treating 3-level disc herniation and/or spondylosis has remained unanswered. This study aimed to investigate the differences between 3-level CDA and ACDF.

Methods: A series of 50 patients who underwent 3-level CDA at C3-7 was retrospectively reviewed and compared with another series of 50 patients (age- and sex-matched controls) who underwent ACDF at C3-7. Clinical outcomes were measured using the visual analog scale (VAS) for neck and arm pain, the modified Japanese Orthopaedic Association (mJOA) scale, and the Neck Disability Index (NDI). Radiological outcomes included range of motion (ROM) at the index levels. Every patient was evaluated by CT for the presence of fusion in the ACDF group. Also, complication profiles were investigated.

Results: The demographics and levels of distribution in both groups were very similar. During the follow-up period of 24 months, clinical outcomes improved (overall and respectively in each group) for both the CDA and ACDF patients when compared with the patients' preoperative condition. There were essentially few differences between the two groups in terms of neck and arm pain VAS scores, mJOA scores, and NDI scores preoperatively and at 3, 6, 12, and 24 months postoperatively. After the 3-level surgery, the CDA group had an increased mean ROM of approximately 3.4°, at 25.2° ± 8.84°, compared to their preoperative ROM (21.8° ± 7.20°) (p = 0.001), whereas the ACDF group had little mobility (22.8° ± 5.90° before and 1.0° ± 1.28° after surgery; p < 0.001). The mean operative time, estimated blood loss, and complication profiles were similar for both groups.

Conclusions: In this selectively matched retrospective study, clinical outcomes after 3-level CDA and ACDF were similar during the 2-year follow-up period. CDA not only successfully preserved but slightly increased the mobility at the 3 index levels. However, the safety and efficacy of 3-level CDA requires more long-term data for validatation.
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http://dx.doi.org/10.3171/2019.8.SPINE19545DOI Listing
November 2019

The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from to .

Ther Adv Chronic Dis 2019 19;10:2040622319875305. Epub 2019 Sep 19.

Department of Basic Medical Science, Center for Transitional Medicine, Xiamen Medical College, Xiamen, 361023, China.

Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects. In this review, we highlight various strategies, namely computational biology (), enzymatic and cell assays, and animal tests, for seeking natural DPP-4 inhibitors from botanic sources including herbs and plants. The pros and cons of all approaches for new inhibitor candidates or hits will be under discussion.
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http://dx.doi.org/10.1177/2040622319875305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753520PMC
September 2019

Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence.

Br J Pharmacol 2020 03 27;177(6):1409-1423. Epub 2019 Nov 27.

Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan.

Traditional chemotherapy is being considered due to hindrances caused by systemic toxicity. Currently, the administration of multiple chemotherapeutic drugs with different biochemical/molecular targets, known as combination chemotherapy, has attained numerous benefits like efficacy enhancement and amelioration of adverse effects that has been broadly applied to various cancer types. Additionally, seeking natural-based alternatives with less toxicity has become more important. Experimental evidence suggests that herbal extracts such as Solanum nigrum and Claviceps purpurea and isolated herbal compounds (e.g., curcumin, resveratrol, and matairesinol) combined with antitumoral drugs have the potential to attenuate resistance against cancer therapy and to exert chemoprotective actions. Plant products are not free of risks: Herb adverse effects, including herb-drug interactions, should be carefully considered. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
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http://dx.doi.org/10.1111/bph.14816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056458PMC
March 2020

Suture Repair in Endoscopic Surgery for Craniovertebral Junction.

Neurospine 2019 Jun 30;16(2):257-266. Epub 2019 Jun 30.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: Endoscopic approaches to the craniovertebral junction (CVJ) have been established as viable and effective surgical treatments in the past decade. One of the major complications is leakage of the cerebrospinal fluid (CSF). This study aimed to investigate the efficacy and feasibility of suture closure at the nasopharyngeal mucosa upon durotomy.

Methods: A series of consecutive patients who underwent different endoscopic approaches to the CVJ were retrospectively reviewed. The pathologies, surgical corridors, neurological and functional outcomes, radiological evaluations, and complications were analyzed. Different strategies of repair for the intraoperative CSF leakage were described and compared.

Results: A total of 22 patients covering 13 years were analyzed. There were 12, 2, and 8 patients who underwent transnasal, transoral, and combined approaches, respectively. There were 8 patients (36.4%) who experienced intraoperative CSF leakage, and were grouped into 2: 4 in the nonsuture (NS) group and 4 in the suture-repaired (SR) group. The NS group had 3 (75%) persistent CSF leakages postoperation that caused 1 mortality, whereas patients of the SR group had only 1 minor CSF rhinorrhea that healed spontaneously within days.

Conclusion: In this series of 22 patients who required anterior endoscopic resection of pathologies at the CVJ, there was 1 (4.5%) serious complication related to CSF leakage. For patients who had no durotomy, the mucosal incision at the nasopharynx usually healed rapidly and there were few procedure-related complications. For patients with intraoperative CSF leakage, suture closure was technically challenging but could significantly lower the risks of postoperative complications.
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http://dx.doi.org/10.14245/ns.1938174.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603818PMC
June 2019

Monkey Recovery from Spinal Cord Hemisection: Nerve Repair Strategies for Rhesus Macaques.

World Neurosurg 2019 Sep 25;129:e343-e351. Epub 2019 May 25.

Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: Repair of spinal cord injury (SCI) using peripheral nerve graft (PNG) and acidic fibroblast growth factor (aFGF) has shown promising results in rats and a few human patients, but not in nonhuman primates. The aim of this study was to verify the effective use of PNG and aFGF for repairing incomplete SCI in nonhuman primates.

Methods: Six adult rhesus macaques received spinal cord hemisection at T8 level and were grouped into repair and control groups (n = 3 in each). Animals in the repair group underwent nerve repair with autologous PNG plus aFGF immediately after lesioning. The control group received exactly the same operation for lesioning but no treatment. Postoperative behavioral evaluations, electrophysiologic tests (including motor and somatosensory evoked potentials), and magnetic resonance imaging were performed and compared between the 2 groups as well as histologic examination of the spinal cord cephalic to, at, and caudal to the lesion site after sacrifice.

Results: Animals in the repair group had better motor function in the lower limbs at every observed time point and demonstrated more improvement on electrophysiologic examinations than the control group. The repair group had smaller areas of myelomalacia on magnetic resonance imaging around the lesion compared with the control group, suggesting diminished inflammatory responses with the repair strategy.

Conclusions: PNG plus aFGF for SCI in nonhuman primates yielded improvements in clinical behavior, electrophysiologic tests, and magnetic resonance imaging. This study suggests that the repair strategy is feasible and effective for nonhuman primate SCI. Further investigations are warranted to corroborate its effectiveness for clinical application.
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http://dx.doi.org/10.1016/j.wneu.2019.05.145DOI Listing
September 2019

Characterizing the Neuroprotective Effects of S/B Remedy ( Georgi and Willd) in Spinal Cord Injury.

Molecules 2019 May 16;24(10). Epub 2019 May 16.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

The main causes of dysfunction after a spinal cord injury (SCI) include primary and secondary injuries that occur during the first minutes, hours, to days after injury. This treatable secondary cascade provides a window of opportunity for delivering therapeutic interventions. An S/B remedy ( Georgi and Willd) has anti-inflammatory, cytoprotective, and anticarcinogenic effects in liver or neurodegenerative diseases. The present work examined the effect of S/B on injured spinal cord neurons in cultures and in vivo. S/B effectively reduced peroxide toxicity and lipopolysaccharide stimulation in both spinal cord neuron/glial and microglial cultures with the involvement of PKC and HSP70. The effect of S/B was further conducted in contusive SCI rats. Intraperitoneal injections of S/B to SCI rats preserved spinal cord tissues and effectively attenuated microglial activation. Consistently, S/B treatment significantly improved hindlimb functions of SCI rats. In the acute stage of injury, S/B treatment markedly reduced the levels of ED1 expression and lactate and had a tendency to decrease lipid peroxidation. Taken together, we demonstrated long-term hindlimb restoration alongside histological improvements with systemic S/B remedy treatment in a clinically relevant model of contusive SCI. Our findings highlight the potential of an S/B remedy for acute therapeutic intervention after SCI.
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http://dx.doi.org/10.3390/molecules24101885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571778PMC
May 2019

Cervical disc arthroplasty for less-mobile discs.

J Neurosurg Spine 2019 May;31(3):310-316

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: The published clinical trials of cervical disc arthroplasty (CDA) have unanimously demonstrated the success of preservation of motion (average 7°-9°) at the index level for up to 10 years postoperatively. The inclusion criteria in these trials usually required patients to have evident mobility at the level to be treated (≥ 2° on lateral flexion-extension radiographs) prior to the surgery. Although the mean range of motion (ROM) remained similar after CDA, it was unclear in these trials if patients with less preoperative ROM would have different outcomes than patients with more ROM.

Methods: A series of consecutive patients who underwent CDA at the level of C5-6 were followed up and retrospectively reviewed. The indications for surgery were medically refractory cervical radiculopathy, myelopathy, or both, caused by cervical disc herniation or spondylosis. All patients were assigned to 1 of 2 groups: a less-mobile group, which consisted of those patients who had an ROM of ≤ 5° at C5-6 preoperatively, or a more-mobile group, which consisted of patients whose ROM at C5-6 was > 5° preoperatively. Clinical outcomes, including visual analog scale, Neck Disability Index, and Japanese Orthopaedic Association Scale scores, were evaluated at each time point. Radiological outcomes were also assessed.

Results: A total of 60 patients who had follow-up for more than 2 years were analyzed. There were 27 patients in the less-mobile group (mean preoperative ROM 3.0°) and 33 in the more-mobile group (mean ROM 11.7°). The 2 groups were similar in demographics, including age, sex, diabetes, and cigarette smoking. Both groups had significant improvements in clinical outcomes, with no significant differences between the 2 groups. However, the radiological evaluations demonstrated remarkable differences. The less-mobile group had a greater increase in ΔROM than the more-mobile group (ΔROM 5.5° vs 0.1°, p = 0.001), though the less-mobile group still had less segmental mobility (ROM 8.5° vs 11.7°, p = 0.04). The rates of complications were similar in both groups.

Conclusions: Preoperative segmental mobility did not alter the clinical outcomes of CDA. The preoperatively less-mobile (ROM ≤ 5°) discs had similar clinical improvements and greater increase of segmental mobility (ΔROM), but remained less mobile, than the preoperatively more-mobile (ROM > 5°) discs at 2 years postoperatively.
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http://dx.doi.org/10.3171/2019.2.SPINE181472DOI Listing
May 2019

Effects of smoking on cervical disc arthroplasty

J Neurosurg Spine 2019 02;30(2):168-174

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: Cigarette smoking can adversely affect bone fusion in patients who undergo anterior cervical discectomy and fusion. However, there is a paucity of data on smoking among patients who have undergone cervical disc arthroplasty (CDA). The present study aimed to compare the clinical and radiological outcomes of smokers to those of nonsmokers following CDA.

Methods: The authors retrospectively reviewed the records of consecutive patients who had undergone 1- or 2-level CDA for cervical disc herniation or spondylosis and had a minimum 2-year follow-up. All patients were grouped into a smoking group, which consisted of those who had consumed cigarettes within 6 months prior to the CDA surgery, or a nonsmoking group, which consisted of those who had not consumed cigarettes at all or within 6 months of the CDA. Clinical outcomes were evaluated according to the visual analog scale for neck and arm pain, Neck Disability Index, Japanese Orthopaedic Association Scale, and Nurick Scale at each time point of evaluation. Radiological outcomes were assessed using radiographs and CT for multiple parameters, including segmental range of motion (ROM), neutral lordotic curve, and presence of heterotopic ossification (HO).

Results: A total of 109 patients completed at least 2 years of follow-up and were analyzed (mean follow-up 42.3 months). There were 89 patients in the nonsmoking group and 20 in the smoking group. The latter group was younger and predominantly male (both p < 0.05) compared to the nonsmoking group. The two groups had similar improvements in all clinical outcomes after CDA compared to preoperatively. Radiological evaluations were also very similar between the two groups, except for two factors. The smoking group had well-preserved segmental ROM after CDA at an average of 8.1° (both pre- and postoperation). However, while the nonsmoking group remained mobile, segmental ROM decreased significantly (8.2° to 6.9°, p < 0.05) after CDA. There was a trend toward more HO development in the nonsmoking group than in the smoking group, but the difference was without significance (59.6% vs 50.0%, p = 0.43).

Conclusions: During an average 3.5 years of follow-up after 1- and 2-level CDA, cigarette smokers and nonsmokers had similar improvements in clinical outcomes. Moreover, segmental mobility was slightly better preserved in smokers. Since smoking status did not negatively impact outcomes, CDA may be a reasonable option for selected patients who have smoked.

Abbreviations: ACDF = anterior cervical discectomy and fusion; ASD = adjacent-segment degeneration; CDA = cervical disc arthroplasty; FDA = Food and Drug Administration; HO = heterotopic ossification; JOA = Japanese Orthopaedic Association; NDI = Neck Disability Index; ROM = range of motion; VAS = visual analog scale.
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http://dx.doi.org/10.3171/2018.7.SPINE18634DOI Listing
February 2019

Disappearance of Anterior Cervical Corpectomy Cage.

Cureus 2019 Jan 30;11(1):e3985. Epub 2019 Jan 30.

Neurosurgery, Taipei Veterans General Hospital, Taipei, TWN.

Although cage subsidence and dislodgement are not uncommon in anterior cervical spine surgery, missing cages have seldom been reported. This is the first report of the disappearance of a metallic corpectomy cage after anterior cervical fusion. A 63-year-old man, who had a history of ankylosing spondylitis and diabetes mellitus, was involved in a motor vehicle accident that broke his neck. The traumatic C6 burst fracture caused myelopathy and instability, which required surgery. He then underwent anterior C6 corpectomy with circumferential fixation, including anterior plating and posterior lateral mass screws from C5-C7. There was a significant improvement in neurological function after the surgery and he could ambulate independently. However, upon a visit at six months postoperation, there was dislodgement of the anterior cervical plate and cage. An attempt to revise the anterior fusion construct was made subsequently, but this surgery could only remove the plate. The metallic cage was left in place during the revision surgery because it was firmly incorporated into the C5 and C7 vertebra and could hardly be adjusted intraoperatively. There were no other interventions during the interval. Upon his visit at 23 months after the initial surgery, the metallic cage was missing. No examinations could locate the cage anywhere in the body, including 36-inch radiographs that demonstrated completely the disappearance of the metallic corpectomy cage. The posterior arthrodesis seemed stable and the patient had no dysphagia or any other gastrointestinal symptoms. The process of the disappearance of the corpectomy cage was never noticed by the patient and he remains free of symptoms to date. The complete dislodgement of a cervical corpectomy cage that was placed anteriorly could happen without symptoms. The cage might have been expelled during bowel movements and caused little problem. Failure to achieve arthrodesis in anterior cervical fusion, therefore, must be closely monitored.
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http://dx.doi.org/10.7759/cureus.3985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443108PMC
January 2019

Radiological and clinical outcomes of cervical disc arthroplasty for the elderly: a comparison with young patients.

BMC Musculoskelet Disord 2019 Mar 18;20(1):115. Epub 2019 Mar 18.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Room 525, 17F, #201, Shih-Pai Road, Sec. 2, Beitou District, Taipei, 11217, Taiwan.

Background: This study aimed to investigate whether cervical disc arthroplasty (CDA) would be equally effective in elderly patients as in the young. The inclusion criteria of published clinical trials for CDA-enrolled patients covered the ages from 18 to 78 years. However, there was a paucity of data addressing the differences of outcomes between older and the younger patients.

Methods: A series of consecutive patients who underwent one- or two-level CDA were retrospectively reviewed. Patients at the two extreme ends of the age distribution (≥65 and ≤ 40 years) were selected for comparison. Clinical outcome parameters included visual analog scale (VAS) of neck and arm pain, neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores. Radiographic outcomes included range of motion (ROM) at the indexed level and evaluation of heterotopic ossification (HO) by computed tomography (CT). Complication profiles were also investigated.

Results: There were 24 patients in the elderly group (≥65 years old) and 47 patients in the young group (≤40 years old) with an overall mean follow-up of 28.0 ± 21.97 months. The elderly group had more two-level CDA, and thus the mean operative time was longer (239 vs. 179 min, p < 0.05) than the young group. Both groups had similarly significant improvement in clinical outcomes at the final follow-up. All the replaced disc segments remained mobile on post-operative lateral flexion and extension radiographs. However, the elderly group had a slight decrease in mean ROM (- 0.32° ± 3.93°) at the index level after CDA when compared to that of pre-operation. In contrast, the young group had an increase in mean ROM (+ 0.68° ± 3.60°). The complication profiles were not different, though a trend toward dysphagia was noted in the elderly group (p = 0.073). The incidence or severity (grading) of HO was similar between the two groups.

Conclusions: During the follow-up of two years, CDA was equally effective for patients over 65 years old and those under 40 years in clinical improvement. Although the elderly group demonstrated a small reduction of mean ROM after CDA, in contrast to the young group which had a small increase, the segmental mobility was well preserved at every indexed level for each group.
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http://dx.doi.org/10.1186/s12891-019-2509-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421705PMC
March 2019

Acidic Fibroblast Growth Factor in Spinal Cord Injury.

Neurospine 2019 Dec 15;16(4):728-738. Epub 2019 Jan 15.

Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.

Spinal cord injury (SCI), with an incidence rate of 246 per million person-years among adults in Taiwan, remains a devastating disease in the modern day. Elderly men with lower socioeconomic status have an even higher risk for SCI. Despite advances made in medicine and technology to date, there are few effective treatments for SCI due to limitations in the regenerative capacity of the adult central nervous system. Experiments and clinical trials have explored neuro-regeneration in human SCI, encompassing cell- and molecule-based therapies. Furthermore, strategies have aimed at restoring connections, including autologous peripheral nerve grafts and biomaterial scaffolds that theoretically promote axonal growth. Most molecule-based therapies target the modulation of inhibitory molecules to promote axonal growth, degrade glial scarring obstacles, and stimulate intrinsic regenerative capacity. Among them, acidic fibroblast growth factor (aFGF) has been investigated for nerve repair; it is mitogenic and pluripotent in nature and could enhance axonal growth and mitigate glial scarring. For more than 2 decades, the authors have conducted multiple trials, including human and animal experiments, using aFGF to repair nerve injuries, including central and peripheral nerves. In these trials, aFGF has shown promise for neural regeneration, and in the future, more trials and applications should investigate aFGF as a neurotrophic factor. Focusing on aFGF, the current review aimed to summarize the historical evolution of the utilization of aFGF in SCI and nerve injuries, to present applications and trials, to summarize briefly its possible mechanisms, and to provide future perspectives.
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http://dx.doi.org/10.14245/ns.1836216.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944993PMC
December 2019

Taiwan Neurosurgical Spine Society: The New Shining Star.

Neurospine 2018 Dec 19;15(4):285-295. Epub 2018 Nov 19.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

As spine surgery flourished in Taiwan and neurosurgeons became more involved in spine surgery towards the end of the 20th century, the Taiwan Neurosurgical Spine Society (TNSS), earlier named the Taiwan Neurospinal Society, was established on March 11, 2001. As its main founder, Dr. Chun-I Huang was elected as the first president of the TNSS. The goals of the TNSS were to promote research, to hold academic seminars, to participate in international conferences, and to exchange clinical experiences. The mission of the TNSS was successful, and the profession of spine surgery in Taiwan advanced during the first decade of the 21st century, culminating in the TNSS joining ASIA SPINE in 2010. Since its establishment, the TNSS has always been supportive of collaboration and communication with the Korean Spinal Neurosurgery Society and the Neurospinal Society of Japan. Through periodical meetings, supported by the TNSS, surgeons worldwide have enjoyed a platform of sharing and mutual learning. To further promote academic research, the TNSS has officially supported the journal Neurospine since 2018. With extensive efforts from local and international surgeons, the TNSS will continue to adhere to its mission and to advance the profession of spine surgery.
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http://dx.doi.org/10.14245/ns.1836194.097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347352PMC
December 2018

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells.

J Clin Med 2018 Dec 25;8(1). Epub 2018 Dec 25.

Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Spinal cord injury (SCI) is a devastating neurological condition and might even result in death. However, current treatments are not sufficient to repair such damage. Bone marrow mesenchymal stem cells (BM-MSC) are ideal transplantable cells which have been shown to modulate the injury cascade of SCI mostly through paracrine effects. The present study investigates whether systemic administration of conditioned medium from MSCs (MSCcm) has the potential to be efficacious as an alternative to cell-based therapy for SCI. In neuron-glial cultures, MSC coculture effectively promoted neuronal connection and reduced oxygen glucose deprivation-induced cell damage. The protection was elicited even if neuron-glial culture was used to expose MSCcm, suggesting the effects possibly from released fractions of MSC. In vivo, intravenous administration of MSCcm to SCI rats significantly improved behavioral recovery from spinal cord injury, and there were increased densities of axons in the lesion site of MSCcm-treated rats compared to SCI rats. At early days postinjury, MSCcm treatment upregulated the protein levels of Olig 2 and HSP70 and also increased autophage-related proteins in the injured spinal cords. Together, these findings suggest that MSCcm treatment promotes spinal cord repair and functional recovery, possibly via activation of autophagy and enhancement of survival-related proteins.
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http://dx.doi.org/10.3390/jcm8010023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352201PMC
December 2018

Unintended facet fusions after Dynesys dynamic stabilization in patients with spondylolisthesis.

J Neurosurg Spine 2018 12;30(3):353-361

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

OBJECTIVEThe pedicle screw-based Dynesys dynamic stabilization (DDS) has reportedly become a surgical option for lumbar spondylosis and spondylolisthesis. However, it is still unclear whether the dynamic construct remains mobile or eventually fuses. The aim of this study was to investigate the incidence of unintended facet arthrodesis after DDS and its association with spondylolisthesis.METHODSThis retrospective study was designed to review 105 consecutive patients with 1- or 2-level lumbar spondylosis who were treated with DDS surgery. The patients were then divided into 2 groups according to preexisting spondylolisthesis or not. All patients underwent laminectomies, foraminotomies, and DDS. The clinical outcomes were measured using visual analog scale (VAS) scores for back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores. All medical records, including pre- and postoperative radiographs, CT scans, and MR images, were also reviewed and compared.RESULTSA total of 96 patients who completed the postoperative follow-up for more than 30 months were analyzed. The mean age was 64.1 ± 12.9 years, and the mean follow-up duration was 46.3 ± 12.0 months. There were 45 patients in the spondylolisthesis group and 51 patients in the nonspondylolisthesis group. The overall prevalence rate of unintended facet fusion was 52.1% in the series of DDS. Patients with spondylolisthesis were older (67.8 vs 60.8 years, p = 0.007) and had a higher incidence rate of facet arthrodesis (75.6% vs 31.4%, p < 0.001) than patients without spondylolisthesis. Patients who had spondylolisthesis or were older than 65 years were more likely to have facet arthrodesis (OR 6.76 and 4.82, respectively). There were no significant differences in clinical outcomes, including VAS back and leg pain, ODI, and JOA scores between the 2 groups. Furthermore, regardless of whether or not unintended facet arthrodesis occurred, all patients experienced significant improvement (all p < 0.05) in the clinical evaluations.CONCLUSIONSDuring the mean follow-up of almost 4 years, the prevalence of unintended facet arthrodesis was 52.1% in patients who underwent DDS. Although the clinical outcomes were not affected, elderly patients with spondylolisthesis might have a greater chance of facet fusion. This could be a cause of the limited range of motion at the index levels long after DDS.
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http://dx.doi.org/10.3171/2018.8.SPINE171328DOI Listing
December 2018

Differences in fixation strength among constructs of atlantoaxial fixation.

J Neurosurg Spine 2018 10;30(1):52-59

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei.

OBJECTIVETo avoid jeopardizing an aberrant vertebral artery, there are three common options in placing a C2 screw, including pedicle, pars, and translaminar screws. Although biomechanical studies have demonstrated similar strength among these C2 screws in vitro, there are limited clinical data to address their differences in vivo. When different screws were placed in each side, few reports have compared the outcomes. The present study aimed to evaluate these multiple combinations of C2 screws.METHODSConsecutive adult patients who underwent posterior atlantoaxial (AA) fixation were retrospectively reviewed. Every patient uniformly had bilateral C1 lateral mass screws in conjunction with 2 C2 screws (1 C2 screw on each side chosen among the three options: pedicle, pars, or translaminar screws, based on individualized anatomical consideration). These patients were then grouped according to the different combinations of C2 screws for comparison of the outcomes.RESULTSA total of 63 patients were analyzed, with a mean follow-up of 34.3 months. There were five kinds of construct combinations of the C2 screws: 2 pedicle screws (the Ped-Ped group, n = 24), 2 translaminar screws (the La-La group, n = 7), 2 pars screws (the Pars-Pars group, n = 6), 1 pedicle and 1 pars screw (the Ped-Pars group, n = 7), and 1 pedicle and 1 translaminar screw (the Ped-La group, n = 19). The rate of successful fixation in each of the groups was 100%, 57.1%, 100%, 100%, and 78.9% (Ped-Ped, La-La, Par-Par, Ped-Par, and Ped-La, respectively). The patients who had no translaminar screw had a higher rate of success than those who had 1 or 2 translaminar screws (100% vs 73.1%, p = 0.0009). Among the 5 kinds of construct combinations, 2 C2 pedicle screws (the Ped-Ped group) had higher rates of success than 1 C2 pedicle and 1 C2 translaminar screw (the Ped-La group, p = 0.018). Overall, the rate of successful fixation was 87.3% (55/63). There were 7 patients (4 in the Ped-La group and 3 in the La-La group) who lost fixation/reduction, and they all had at least 1 translaminar screw.CONCLUSIONSIn AA fixation, C2 pedicle or pars screws or a combination of both provided very high success rates. Involvement of 1 or 2 C2 translaminar screws in the construct significantly lowered success rates. Therefore, a C2 pars screw is recommended over a translaminar screw.
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http://dx.doi.org/10.3171/2018.6.SPINE171390DOI Listing
October 2018
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