Partial Pedicle Subtraction Osteotomy for Patients with Thoracolumbar Fractures : Comparative Study between Burst Fracture and Posttraumatic Kyphosis

ObjectiveTo evaluate the surgical outcomes of partial pedicle subtraction osteotomy (PPSO) in patients with thoracolumbar fractures and compare the outcomes of PPSO for burst fractures with those for posttraumatic kyphosis (PTK). MethodsFrom June 2013 to May 2019, 20 consecutive adult patients underwent PPSO for thoracolumbar fractures at the levels of T10 to L2. Of these patients, 10 underwent surgery for acute fractures (burst fractures), and 10 for sequelae of thoracolumbar fractures (PTK). Outcomes of PPSO were evaluated and compared between the groups. ResultsTwenty patients (each 10 patients of burst fractures and PTK) with a mean age of 64.7±11.1 years were included. The mean follow-up period was 21.8±11.0 months. The mean correction of the thoracolumbar angle was -34.9°±18.1° (from 37.8°±20.5°preoperatively to 2.8°±15.2° postoperatively). The mean angular correction at the PPSO site was -38.4°±13.6° (from 35.5°±13.6° preoperatively to -2.9°±14.1° postoperatively). The mean preoperative sagittal vertical axis was 93.5±6.7 cm, which was improved to 37.6±35.0 cm postoperatively. The mean preoperative kyphotic angle at the PPSO site was significant greater in patients with PTK (44.8°±7.2°) than in patients with burst fractures (26.2°±12.2°, p=0.00). However, the mean postoperative PPSO angle did not differ between the two groups (-5.9°±15.7° in patients with burst fractures and 0.2°±12.4° in those with PTK, p=0.28). The mean angular correction at the PPSO site was significantly greater in patients with PTK (-44.6°±10.7°) than in those with burst fractures (-32.1°±13.7°, p=0.04). The mean operation time was 188.1±37.6 minutes, and the mean amount of surgical bleeding was 1030.0±533.2 mL. There were seven cases of perioperative complications occurred in five patients (25%), including one case (5%) of neurological deficit. The operation time, surgical bleeding, and complication rates did not differ between groups. ConclusionIn cases of burst fracture, PPSO provided enough spinal cord decompression without corpectomy and produced sagittal correction superior to that achieved with corpectomy. In case of PTK, PPSO achieved satisfactory curve correction comparable to that achieved with conventional PSO, with less surgical time, less blood loss, and lower complication rates. PPSO could be a viable surgical option for both burst fractures and PTK.     

Limited Unilateral Decompression and Pedicle Screw Fixation with Fusion for Lumbar Spinal Stenosis with Unilateral Radiculopathy: A Retrospective Analysis of 25 Cases

ObjectiveLumbar spinal stenosis is conventionally treated with surgical decompression. However, bilateral decompression and laminectomy is more invasive and may not be necessary for lumbar stenosis patients with unilateral radiculopathy. We aimed to report the outcomes of unilateral laminectomy and bilateral pedicle screw fixation with fusion for patients with lumbar spinal stenosis and unilateral radiculopathy.MethodsPatients with lumbar spinal stenosis with unilateral lower extremity radiculopathy who received limited unilateral decompression and bilateral pedicle screw fixation were included and evaluated using visual analog scale (VAS) pain and the Oswestry Disability Index (ODI) scores preoperatively and at follow-up visits. Ligamentum flavum thickness of the involved segments was measured on axial magnetic resonance images.ResultsTwenty-five patients were included. The mean preoperative VAS score was 6.6±1.6 and 4.6±3.1 for leg and back pain, respectively. Ligamentum flavum thickness was comparable between the symptomatic and asymptomatic side (p=0.554). The mean follow-up duration was 29.2 months. The pain in the symptomatic side lower extremity (VAS score, 1.32±1.2) and the back (VAS score, 1.75±1.73) significantly improved (p=0.000 vs. baseline for both). The ODI improved significantly postoperatively (6.60±6.5; p=0.000 vs. baseline). Significant improvement in VAS pain and ODI scores were observed in patients receiving single or multi-segment decompression fusion with fixation (p<0.01).ConclusionLimited laminectomy and unilateral spinal decompression followed by bilateral pedicle screw fixation with fusion achieves satisfactory outcomes in patients with spinal stenosis and unilateral radiculopathy. This procedure is less damaging to structures that are important for maintaining posterior stability of the spine.     

Comparison between Anterior Cervical Decompression with Fusion and Posterior Cervical Fusion with Wide Facetectomy for Treatment of Severe Bony Foraminal Stenosis

ObjectiveTo compare the anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF) with wide facetectomy in the treatment of parallel-shaped bony foraminal stenosis (FS). MethodsThirty-six patients underwent surgery due to one-or-two levels of parallel-shaped cervical FS. ACDF was performed in 16 patients, and PCF using CPS was performed in 20 patients. All patients were followed up at 1, 3, 6, and 12 months postoperatively. Standardized outcome measures such as Numeric rating scale (NRS) score for arm/neck pain and Neck disability index (NDI) were evaluated. Cervical radiographs were used to compare the C2–7 Cobb’s angle, segmental angle, and fusion rates. ResultsThere was an improvement in NRS scores after both approaches for radicular arm pain (mean change -6.78 vs. -8.14, p=0.012), neck pain (mean change -1.67 vs. -4.36, p=0.038), and NDI score (-19.69 vs. -18.15, p=0.794). The segmental angle improvement was greater in the ACDF group than in the posterior group (9.4°±2.7° vs. 3.3°±5.1°, p=0.004). However, there was no significant difference in C2–7 Cobb angle between groups (16.2°±7.9° vs. 14.8°±8.5°, p=0.142). As a complication, dysphagia was observed in one case of the ACDF group. ConclusionIn the treatment of parallel-shaped bony FS up to two surgical levels, segmental angle improvement was more favorable in patients who underwent ACDF. However, PCF with wide facetectomy using CPS should be considered as an alternative treatment option in cases where the anterior approach is burdensome.     

Usefulness of Simple Rod Rotation to Correct Curve of Adolescent Idiopathic Scoliosis

ObjectiveTo correct apical vertebral rotation for adolescent idiopathic scoliosis (AIS), direct vertebral derotation (DVD) or simple rod rotation (SRR) might be considered. The aim of the present study is to introduce the surgical experiences of AIS by a Korean neurosurgeon and to evaluate the effectiveness of SRR for apical vertebral rotation.MethodsA total of 9 patients (1 male and 8 females) underwent scoliosis surgery by a neurosurgeon of our hospital. The Lenke classifications of the patients were 1 of 1B, 2 of 1C, 1 of 2A, 1 of 2C, 3 of 5C and 1 of 6C. Surgery was done by manner of simple rod rotation on the concave side and in situ coronal bending. Coronal Cobb''s angles, vertebral rotation angles and SRS-22 were measured on a plain standing X-ray and CT before and after surgery.ResultsThe mean follow up period was 25.7 months (range : 5–52). The mean number of screw positioning level was nine (6–12). The mean age was 16.4 years (range : 13–25) at surgery. The mean Risser grade was 3.7±0.9. The apical vertebral rotation measured from the CT scans was 25.8±8.5° vs. 9.3±6.7° (p<0.001) and the Coronal Cobb''s angle was 53.7±10.4° vs. 15.4±6.5° (p<0.001) preoperatively and postoperative, respectively. The SRS-22 improved from 71.9 preoperatively to 90.3 postoperatively. There were no complications related with the operations.ConclusionSRR with pedicle screw instrumentation could be corrected successfully by axial rotation without complications. SRR might serve as a good option to correct AIS deformed curves of AIS.     

The Effect of the Pedicle-Facet Angle on Degenerative Cervical Spondylolisthesis

ObjectiveTo measure the orientation of the facet joints of cervical spine (C-spine) segments in the sagittal plane, known as the pedicle-facet (P-F) angle, and to use these measurements to evaluate the relationship between the P-F angle and the amount of vertebral anterolisthesis in patients with degenerative cervical spondylolisthesis (DCS).MethodsA retrospective case-control study was performed including 30 age- and sex-matched patients with DCS and 30 control participants. Anterior-posterior and lateral view radiographs of the C-spine were obtained in a standing position. The P-F angle at all cervical levels and the amount of anterolisthesis at C4-5 were measured from lateral view plain radiographs.ResultsThe P-F angles at C4-5 were 141.14±7.14° for the DCS group and 130.53±13.50° (p=0.012) for the control group, and at C5-6 were 137.46±8.53° for the DCS group and 128.53±16.01° for the control group (p=0.001). The mean P-F angle at C4-5 did not correlate with the amount of anterolisthesis (p=0.483). The amount of anterior slippage did correlate with age (p<0.001).ConclusionThe P-F angle was intrinsically higher at C4-5, compared to C5-6, in both the DCS and control groups, which might explain the increased likelihood for anterolisthesis of C4. Higher P-F angles in the DCS group may be a predisposing factor to slippage. The P-F angle may interact with age to increase incidence of anterolisthesis with increasing age.     

The Fate of Proximal Junctional Vertebral Fractures after Long-Segment Spinal Fixation : Are There Predictable Radiologic Characteristics for Revision surgery?

ObjectiveTo investigate the radiographic characteristics of the uppermost instrumented vertebrae (UIV) and UIV+1 compression fractures that are predictive of revision surgery following long-segment spinal fixation. MethodsA total 27 patients who presented newly developed compression fracture at UIV, UIV+1 after long segment spinal fixation (minimum 5 vertebral bodies, lowest instrumented vertebra of L5 or distal) were reviewed retrospectively. Patients were divided into two groups according to following management : revisional surgery (group A, n=13) and conservative care (group B, n=14). Pre- and postoperative images, and images taken shortly before and after the occurrence of fracture were evaluated for radiologic characteristics ResultsDespite similar degrees of surgical correction of deformity, the fate of the two groups with proximal junctional compression fractures differed. Immediately after the fracture, the decrement of adjacent disc height in group A (32.3±7.6 mm to 23.7±8.4 mm, Δ=8.5±6.9 mm) was greater than group B (31.0±13.9 mm to 30.1±15.5 mm, Δ=0.9±2.9 mm, p=0.003). Pre-operative magnetic resonance imaging indicated that group A patients have a higher grade of disc degeneration adjacent to fractured vertebrae compared to group B (modified Pfirrmann grade, group A : 6.10±0.99, group B : 4.08±0.90, p=0.004). Binary logistic regression analysis indicated that decrement of disc height was the only associated risk factor for future revision surgery (odds ratio, 1.891; 95% confidence interval, 1.121–3.190; p=0.017). ConclusionProximal junctional vertebral compression fractures with greater early-stage decrement of adjacent disc height were associated with increased risk of future neurological deterioration and necessity of revision. The condition of adjacent disc degeneration should be considered regarding severity and revision rate of proximal junctional kyphosis/proximal junction failures.     

Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

BackgroundVasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β‐catenin signaling.MethodsWe evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV‐induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β‐catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.ResultsLithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm³ vs. 19.97 ± 3.20 mm³ in vehicle controls, p = 0.0016) and improved the neurological outcomes of mice following ICH. Importantly, lithium significantly increased the BBB integrity, as evidenced by reductions in the levels of brain edema (p = 0.0312), Evans blue leakage (p = 0.0261), and blood IgG extravasation (p = 0.0009) into brain tissue around the hematoma. Mechanistically, lithium upregulated the activity of endothelial Wnt/β‐catenin signaling in mice and increased the levels of tight junction proteins (occludin, claudin‐5 and ZO‐1). Furthermore, the protective effect of lithium on cerebral damage and BBB integrity was abolished in endothelial Gpr124 knockout mice, suggesting that its protective effect on BBB function was mainly dependent on Gpr124‐mediated endothelial Wnt/β‐catenin signaling.ConclusionOur findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.     

Difference of Sagittal Spinopelvic Alignments between Degenerative Spondylolisthesis and Isthmic Spondylolisthesis

Objective

The purpose of this study was to analyze the differences of spinopelvic parameters between degenerative spondylolisthesis (DSPL) and isthmic spondylolisthesis (ISPL) patients.

Methods

Thirty-four patients with DSPL and 19 patients with ISPL were included in this study. Spinopelvic parameters were evaluated on whole spine X-rays in a standing position. The following spinopelvic parameters were measured : pelvic incidence (PI), sacral slope, pelvic tilt (PT), lumbar lordosis (LL), and sagittal vertical axis from C7 plumb line (SVA). The population of patients was compared with a control population of 30 normal and asymptomatic adults.

Results

There were statistically significant differences in LL (p=0.004) and SVA (p=0.005) between the DSPL and ISPL group. The LL of DSPL (42±13°) was significantly lower than that of the control group (48±11°; p=0.029), but that of ISPL (55±6°) was significantly greater than a control group (p=0.004). The SVA of DSPL (55±49 mm) was greater than that of a control group (<40 mm), but that of ISPL (21±22 mm) was within 40 mm as that of a control group. The PT of DSPL (24±7°) and ISPL (21±7°) was significantly greater than that of a control group (11±6°; p=0.000).

Conclusion

Both symptomatic DSPL and ISPL patients had a greater PI than that of the asymptomatic control group. In conclusion, DSPL populations are likely to have global sagittal imbalance (high SVA) compared with ISPL populations because of the difference of lumbar lordosis between two groups.     

Changes in striatal dopamine transporters in bipolar disorder and valproate treatment

BackgroundPrevious studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA.MethodsWe enrolled community-dwelling controls (N = 18) and BD patients (N = 23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350 mg/kg VPA for 3 weeks. Behavioral tests were administered, and striatal DAT expression levels were determined.ResultsIn humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52 ± 0.17 and 1.37 ± 0.23, p = 0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r = −0.653, p = 0.003). In SD mice, the expression of striatal DAT significantly increased (p < 0.001), and the SD effect on DAT expression was rescued by VPA treatment.ConclusionsThe striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.     

Early Vertebroplasty versus Delayed Vertebroplasty for Acute Osteoporotic Compression Fracture : Are the Results of the Two Surgical Strategies the Same?

Objective

In Korea, early vertebroplasty (EVP) or delayed vertebroplasty (DVP, which is performed at least 2 weeks after diagnosis) were performed for the treatment of acute osteoporotic compression fracture (OCF) of the spine. The present study compared the outcomes of two surgical strategies for the treatment of single-level acute OCF in the thoracolumbar junction (T12-L2).

Methods

From 2004 to 2010, 23 patients were allocated to the EVP group (EVPG) and 27 patients to the DVP group (DVPG). Overall mean age was 68.3±7.9 and minimum follow-up period was 1.0 year. Retrospective study of clinical and radiological results was conducted.

Results

No significant differences in baseline characteristics were observed between the two groups. As expected, mean duration from onset to vertebroplasty and mean duration of hospital stay were significantly longer in the DVPG (17.1±2.1 and 17.5±4.2) than in the EVPG (3.8±3.3 and 10.8±5.1, p=0.001). Final clinical outcome including visual analogue scale (VAS), Oswestry Disability Index, and Odom''s criteria did not differ between the two groups. However, immediate improvement of the VAS after vertebroplasty was greater in the EVPG (5.1±1.3) than in the DVPG (4.0±1.0, p=0.002). The proportion of cement leakage was lower in the EVPG (30.4%) than in the DVPG (59.3%, p=0.039). In addition, semiquantitative grade of cement interdigitation was significantly more favorable in the EVPG than in the DVPG (p=0.003). Final vertebral body collapse and segmental kyphosis did not differ significantly between the two groups.

Conclusion

Our findings suggest that EVP achieves a better immediate surgical effect with more favorable cost-effectiveness.     

Usefulness of Fracture Risk Assessment Tool Using Lumbar Bone Mineral Density in Prediction of Osteoporotic Vertebral Fracture

ObjectiveTo investigate the value of lumbar bone mineral density (BMD) in fracture risk assessment (FRAX) tool.MethodsOne hundred and ten patients aged over 60 years were enrolled and divided into 2 groups as non-osteoporotic vertebral fracture (OVF) and OVF groups. The 10-year-risk of major osteoporotic vertebral fracture of each group was calculated by FRAX tool with femoral and lumbar spine BMDs to compare the usefulness of lumbar spine BMD in prediction of OVF. The blood level of osteocalcin and C-terminal telopeptide (CTX) as markers of activities of osteoblast and osteoclast, respectively were analyzed using the institutional database.ResultsIn the OVF group, the ratio of patients with previous fracture history or use of glucocorticoid was higher than those in non-OVF group (p=0.000 and 0.030, respectively). The levels of T-score of femur neck and lumbar spine in OVF group were significantly lower than those in non-OVF group (p=0.001 and 0.000, respectively). The risk of OVF in FRAX using femur BMD in non-OVF and OVF groups was 6.7±6.13 and 11.4±10.06, respectively (p=0.007). The risk of using lumbar BMD in the 2 groups was 6.9±8.91 and 15.1±15.08, respectively (p=0.002). The areas under the receiver operator characteristic curve in the FRAX risk with lumbar and femur neck BMD were 0.726 and 0.684, respectively. The comparison of osteocalcin and CTX was not significant (p=0.162 and 0.369, respectively).ConclusionIn our study, the 10-year risk of major osteoporotic fracture in the OVF group of our study was lower than the recommended threshold of intervention for osteoporosis. Hence, a lower threshold for the treatment of osteoporosis may be set for the Korean population to prevent OVF. In the prediction of symptomatic OVF, FRAX tool using lumbar spine BMD may be more useful than that using femur neck BMD.     

Chronological Changes of C-Reactive Protein Levels Following Uncomplicated,Two-Staged,Bilateral Deep Brain Stimulation

ObjectiveThe occurrence of acute cerebral infection following deep brain stimulation (DBS) is currently being reported with elevation of C-reactive protein (CRP) level. The aim of the present study was to establish normal range of the magnitude and time-course of CRP increases following routine DBS procedures in the absence of clinical and laboratory signs of infection.MethodsA retrospective evaluation of serial changes of plasma CRP levels in 46 patients undergoing bilateral, two-staged DBS was performed. Because DBS was performed as a two-staged procedure involving; implantation of lead and internal pulse generator (IPG), CRP was measured preoperatively and postoperatively every 2 days until normalization of CRP (post-lead implantation day 2 and 4, post-IPG implantation day 2, 4, and 6).ResultsCompared with preoperative CRP levels (0.12±0.17 mg/dL, n=46), mean CRP levels were significantly elevated after lead insertion day 2 and 4 (1.68±1.83 mg/dL, n=46 and 0.76±0.38 mg/dL, n=16, respectively, p<0.001). The mean CRP levels at post-lead implantation day 2 were further elevated at post-IPG implantation day 2 (3.41±2.56 mg/dL, n=46, respectively, p<0.01). This elevation in post-IPG day 2 rapidly declined in day 4 (1.24±1.29 mg/dL, n=46, p<0.05) and normalized to preoperative value at day 6 (0.42±0.33 mg/dL, n=46, p>0.05). Mean CRP levels after IPG implantation were significantly higher in patients whose IPGs were implanted at post-lead day 3 than those at post-lead day 5-6 (3.99±2.80 mg/dL, n=30, and 2.31±1.56 mg/dL, n=16, respectively, p<0.05). However, there was no difference in post-IPG day 2 and 4 between them (p>0.05).ConclusionThe mean postoperative CRP levels were highest on post-IPG insertion day 2 and decreased rapidly, returning to the normal range on post-IPG implantation day 6. The duration of post-lead implantation period influenced the magnitude of CRP elevation at post-IPG insertion day 2. Information about the normal response of CRP following DBS could help to avoid unnecessary diagnostic and therapeutic efforts.     

Pre‐ and post‐conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta‐analysis

BackgroundToll‐like receptor (TLR) agonist polyinosinic–polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.MethodsWe evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion.ResultsPoly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre‐ and post‐conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor‐κB (NF‐κB) [SMD = −1.78; CIs (−2.67, −0.88); p = 0.0)], and tumor necrosis factor alpha (TNF‐α) [SMD = −16.83; CIs (−22.63, −11.02); p = 0.00].ConclusionWe showed that poly I:C is neuroprotective and acts via the TLR3/NF‐κB/TNF‐α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.     

Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

BackgroundIndividuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.Methods“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.ResultsNinety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).ConclusionsThere is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.     

Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation

BackgroundQuestions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.MethodsUsing data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.ResultsExternalizing was heritable (h² = 0.46, p = 1 × 10⁻⁶), but not anxious-misery (h² = 0.09, p = 0.183), fear (h² = 0.04, p = 0.337), psychosis-spectrum (h² = 0.00, p = 0.494), or general psychopathology (h² = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρ_g = −0.412, p = 0.004), verbal reasoning (ρ_g = −0.485, p = 0.001), spatial reasoning (ρ_g = −0.426, p = 0.010), motor speed (ρ_g = 0.659, p = 1x10⁻⁴), verbal knowledge (ρ_g = −0.314, p = 0.002), and general cognitive ability (g)(ρ_g = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γ_g = −0.146, p = 0.004) and increasing environmental variance (γ_e = 0.059, p = 0.009) on externalizing.ConclusionsCognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.     

Long-Term Outcome of Posterior Cervical Inclinatory Foraminotomy

ObjectiveA modified surgical technique of posterior cervical foramintomy called posterior cervical inclinatory foraminotomy (PCIF) was introduced in previous preliminary article. PCIF allows better preservation of facet joint and capsule than conventional techniques. The authors conducted a study to investigate long-term outcomes of PCIF.MethodsWe retrospectively reviewed demographic, radiologic, and clinical data from the patients who underwent PCIFs at our institution. Criteria included a minimum of 48 month follow-up and PCIFs for patients with radiculopathy from foraminal stenosis (C2–T1; single or multilevel) with persistent or recurrent root symptoms despite conservative treatment for more than 3 months. Patients who had undergone previous cervical operation were excluded. The visual analogue scale (VAS) score was used for clinical follow-up, and radiologic follow-up was performed to compare the changes of cervical sagittal alignment, focal angle and disc-space height of treated segment.ResultsThe PCIFs were performed between April 2007 and March 2011 on 46 patients (32 males and 14 females) with a total of 73 levels affected. The average duration of follow-up was 74.4 months. Improvements in radiculopathic pain were seen in 39 patients (84.7%), and VAS score decreased from 6.82±1.9 to 2.19±1.9. Posterior neck pain also improved in 25 patients (71.4%) among 35 patients, and VAS score decreased from 4.97±2.0 to 2.71±1.9. The mean disc-space heights of treated segment were 5.41±1.03 mm preoperatively and decreased to 5.17±1.12 mm postoperatively. No statistically significant changes in cervical sagittal alignment, focal angle were seen during the follow-up period (Cox proportional hazards analysis and Student t-test, p>0.05).ConclusionThe PCIF is highly effective in treating patients with cervical spondylotic radiculopathy, leading to long-lasting relief in pain. Long-term radiologic follow-up showed no significant spinal angular imbalance.     

True Posterior Communicating Artery Aneurysms with High Risk of Rupture despite Very Small Diameter

ObjectiveThis retrospective study investigated the clinical and angiographic characteristics of ruptured true posterior communicating artery (PCoA) aneurysms in comparison with junctional PCoA aneurysms presenting with a subarachnoid hemorrhage. MethodsThe medical records and radiological data of 93 consecutive patients who underwent three-dimensional rotational angiography and surgical or endovascular treatment for a ruptured junctional or true PCoA aneurysm over an 8-year period were examined. ResultsThe maximum diameter of the ruptured true PCoA aneurysm (n=13, 14.0%) was significantly smaller than that of the ruptured junctional PCoA aneurysms (n=80, 4.45±1.44 vs. 7.68±3.36 mm, p=0.001). In particular, the incidence of very small aneurysms <4 mm was 46.2% (six of 13 patients) in the ruptured true PCoA aneurysm group, yet only 2.5% (two of 80 patients) in the ruptured junctional PCoA aneurysm group. Meanwhile, the diameter of the PCoA was significantly larger in the true PCoA aneurysm group than that in the junctional PCoA aneurysm group (1.90±0.57 vs. 1.15±0.49 mm, p<0.001). In addition, the ipsilateral PCoA/P1 ratio was significantly larger in the true PCoA aneurysm group than that in the group of a junctional PCoA aneurysm (mean PCoA/P1 ratio±standard deviation, 2.67±1.22 vs. 1.14±0.88; p<0.001). No between-group difference was identified for the modified Fisher grade, clinical grade at admission, and 3-month modified Rankin Scale score. ConclusionA true PCoA aneurysm was found to be associated with a larger PCoA and ruptured at a smaller diameter than a junctional PCoA aneurysm. In particular, the incidence of a ruptured aneurysm with a very small diameter <4 mm was significantly higher among the patients with a true PCoA aneurysm.     

Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients

Background and PurposeWe investigated ¹⁸F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis.MethodsThis study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA).ResultsTwenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension.ConclusionsStroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.     

The association between C-reactive protein,mood disorder,and cognitive function in UK Biobank

BackgroundSystemic inflammation has been linked with mood disorder and cognitive impairment. The extent of this relationship remains uncertain, with the effects of serum inflammatory biomarkers compared to genetic predisposition toward inflammation yet to be clearly established.MethodsWe investigated the magnitude of associations between C-reactive protein (CRP) measures, lifetime history of bipolar disorder or major depression, and cognitive function (reaction time and visuospatial memory) in 84,268 UK Biobank participants. CRP was measured in serum and a polygenic risk score for CRP was calculated, based on a published genome-wide association study. Multiple regression models adjusted for sociodemographic and clinical confounders.ResultsIncreased serum CRP was significantly associated with mood disorder history (Kruskal–Wallis H = 196.06, p < 0.001, η² = 0.002) but increased polygenic risk for CRP was not (F = 0.668, p = 0.648, η² < 0.001). Compared to the lowest quintile, the highest serum CRP quintile was significantly associated with both negative and positive differences in cognitive performance (fully adjusted models: reaction time B = −0.030, 95% CI = −0.052, −0.008; visuospatial memory B = 0.066, 95% CI = 0.042, 0.089). More severe mood disorder categories were significantly associated with worse cognitive performance and this was not moderated by serum or genetic CRP level.ConclusionsIn this large cohort study, we found that measured inflammation was associated with mood disorder history, but genetic predisposition to inflammation was not. The association between mood disorder and worse cognitive performance was very small and did not vary by CRP level. The inconsistent relationship between CRP measures and cognitive performance warrants further study.     

Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression

BackgroundDepression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC).MethodsThe GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS.ResultsTwo genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p = 1.54 × 10⁻⁸, OR = 0.29) locate in PIEZO2, and rs6046722 (p = 2.52 × 10⁻⁸, OR = 1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (p_{replication GWAS1} = 0.02, p_{replication GWAS2} = 2.71 × 10⁻³) in CFAP61, and rs11661122 (p_{replication GWAS1} = 8.16 × 10⁻³, p_{replication GWAS2} = 8.08 × 10⁻³) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p < 0.001), such as marital separation/divorce (rg = 0.45, SE = 0.15).ConclusionsOur findings provide novel clues for understanding of the complex genetic architecture of depression.