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Kelly Russell, Erin Selci, Brian Black and Michael J. Ellis

OBJECTIVE

The longitudinal effects of sports-related concussion (SRC) in adolescents on health-related quality of life (HRQOL) remain poorly understood. Hence, the authors established two objectives of this study: 1) compare HRQOL outcomes among adolescents with an acute SRC or a sports-related extremity fracture (SREF) who were followed up until physician-documented clinical recovery; and 2) identify the clinical variables associated with worse HRQOL among adolescent SRC patients.

METHODS

The authors conducted a prospective cohort study of adolescents with acute SRC and those with acute SREF who underwent clinical assessment and follow-up at tertiary subspecialty clinics. Longitudinal patient-reported HRQOL was measured at the time of initial assessment and at each follow-up appointment by using the adolescent version (age 13–18 years) of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale and Cognitive Functioning Scale.

RESULTS

A total of 135 patients with SRC (60.0% male; mean age 14.7 years; time from injury to initial assessment 6 days) and 96 patients with SREF (59.4% male; mean age 14.1 years; time from injury to initial assessment 8 days) participated in the study. At the initial assessment, the SRC patients demonstrated significantly worse cognitive HRQOL and clinically meaningful impairments in school and overall HRQOL compared to the SREF patients. Clinical variables associated with a worse HRQOL among SRC patients differed by domain but were significantly affected by the patients’ initial symptom burden and the development of delayed physician-documented clinical recovery (> 28 days postinjury). No persistent impairments in HRQOL were observed among SRC patients who were followed up until physician-documented clinical recovery.

CONCLUSIONS

Adolescent SRC is associated with temporary impairments in HRQOL that have been shown to resolve in patients who are followed up until physician-documented clinical recovery. Future studies are needed to identify the clinicopathological features that are associated with impaired HRQOL and to assess whether the initiation of multidisciplinary, targeted rehabilitation strategies would lead to an improvement in HRQOL.

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James R. Bean

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Chia-Hua Chen, Pin-Yuan Chen, You-Yu Lin, Li-Ying Feng, Shin-Han Chen, Chia-Yuan Chen, Yin-Cheng Huang, Chiung-Yin Huang, Shih-Ming Jung, Leslie Y. Chen and Kuo-Chen Wei

OBJECTIVE

Despite intensive medical treatment, patients with glioblastoma (grade IV glioma [GBM]) have a low 5-year survival rate of 5.5%. In this study, the authors tried to improve currently used therapies by identification of a therapeutic target, IGFBP3, for glioma treatment.

METHODS

IGFBP3 RNA expression in 135 patients newly diagnosed with glioma was correlated with clinicopathological factors. Immunohistochemical analysis was performed to determine IGFBP3 protein expression in glioma specimens. The effect of IGFBP3 depletion on cell proliferation was examined using IGFBP3 knockdown glioma cells. Intracranial infusion of IGFBP3 siRNAs was performed to evaluate the effect of IGFBP3 depletion in mouse intracranial xenograft models.

RESULTS

We demonstrated higher IGFBP3 expression in GBM than in tumor margin and grade II glioma. IGFBP3 expression was not only positively correlated with tumor grades but also associated with tumor histology and IDH1/2 mutation status. Additionally, higher IGFBP3 expression predicted shorter overall survival in glioma and GBM proneural subgroup patients. In vitro cell culture studies suggested IGFBP3 knockdown suppressed cell proliferation and induced cell cycle G2/M arrest as well as apoptosis in glioma cells. Also, accumulation of DNA double-strand breaks and γH2AX was observed in IGFBP3 knockdown cells. IGFBP3 knockdown delayed in vivo tumor growth in mouse subcutaneous xenograft models. Furthermore, convection-enhanced delivery of IGFBP3 siRNA to mouse brain suppressed intracranial tumor growth and prolonged survival of tumor-bearing mice.

CONCLUSIONS

Our findings suggest IGFBP3 predicts poor outcome of glioma patients and is a potential therapeutic target for which depletion of its expression suppresses tumor growth through inducing apoptosis and accumulation of DNA damage in glioma cells.

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Emerson Magno de Andrade, Raquel C. R. Martinez, Rosana L. Pagano, Patricia S. S. Lopes, Aline V. V. Auada, Flavia V. Gouveia, Geiza F. Antunes, Danielle V. Assis, Ivo Lebrun and Erich T. Fonoff

OBJECTIVE

Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings.

METHODS

Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS.

RESULTS

MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia.

CONCLUSIONS

These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

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Benedikt W. Burkhardt, Simon J. Müller, Anne-Catherine Wagner and Joachim M. Oertel

OBJECTIVE

Infection of the cervical spine is a rare disease but is associated with significant risk of neurological deterioration, morbidity, and a poor response to nonsurgical management. The ideal treatment for cervical spondylodiscitis (CSD) remains unclear.

METHODS

Hospital records of patients who underwent acute surgical management for CSD were reviewed. Information about preoperative neurological status, surgical treatment, peri- and postoperative processes, antibiotic treatment, repeated procedure, and neurological status at follow-up examination were analyzed.

RESULTS

A total of 30 consecutive patients (17 male and 13 female) were included in this retrospective study. The mean age at procedures was 68.1 years (range 50–82 years), with mean of 6 coexisting comorbidities. Preoperatively neck pain was noted in 21 patients (70.0%), arm pain in 12 (40.0%), a paresis in 12 (40.0%), sensory deficit in 8 (26.7%), tetraparesis in 6 (20%), a septicemia in 4 (13.3%). Preoperative MRI scan revealed a CSD in one-level fusion in 21 patients (70.0%), in two-level fusions in 7 patients (23.3%), and in three-level fusions in 2 patients (6.7%). In 16 patients an antibiotic treatment was initiated prior to surgical treatment. Anterior cervical discectomy and fusion with cervical plating (ACDF+CP) was performed in 17 patients and anterior cervical corpectomy and fusion (ACCF) in 12 patients. Additional posterior decompression was performed in one case of ACDF+CP and additional posterior fixation in ten cases of ACCF procedures. Three patients died due to multiple organ failure (10%). Revision surgery was performed in 6 patients (20.7%) within the first 2 weeks postoperatively. All patients received antibiotic treatment for 6 weeks. At the first follow-up (mean 3 month) no recurrent infection was detected on blood workup and MRI scans. At final follow-up (mean 18 month), all patients reported improvement of neck pain, all but one patients were free of radicular pain and had no sensory deficits, and all patients showed improvement of motor strength. One patient with preoperative tetraparesis was able to ambulate.

CONCLUSIONS

CSD is a disease that is associated with severe neurological deterioration. Anterior cervical surgery with radical debridement and appropriate antibiotic treatment achieves complete healing. Anterior cervical plating with the use of polyetheretherketone cages has no negative effect of the healing process. Posterior fixation is recommended following ACCF procedures.

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Jacob Cherian, Thomas P. Madaelil, Frank Tong, Brian M. Howard, C. Michael Cawley and Jonathan A. Grossberg

The video highlights a challenging case of bilateral vertebral artery dissection presenting with subarachnoid hemorrhage. The patient was found to have a critical flow-limiting stenosis in his dominant right vertebral artery and a ruptured pseudoaneurysm in his left vertebral artery. A single-stage endovascular treatment with stent reconstruction of the right vertebral artery and coil embolization sacrifice of the left side was performed. The case highlights the rationale for treatment and potential alternative strategies.

The video can be found here: https://youtu.be/e0U_JE2jISw.

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Chih-Hsiang Liao, Wen-Hsien Chen, Nien-Chen Liao and Yuang-Seng Tsuei

This video presents a case of new-onset visual blurring, diplopia, and conjunctival injection after head injury. CTA of the brain revealed a direct carotid-cavernous fistula (dCCF) of the right side. Careful evaluation of CTA source images revealed that the fistula point was at the ventromedial aspect of the right cavernous internal carotid artery (ICA), about 3.6 × 3.6 mm2 in size, with 3 main outflow channels (2 intracranial and 1 extracranial) (CTA-guided concept). DSA of the brain also confirmed the diagnosis but was unable to locate the fistula point in a large-sized dCCF. Through a transfemoral artery approach, 3 microcatheters were navigated to each peripheral channel to initiate outflow-targeted embolization. Intracranial refluxes were blocked first to avoid cerebral hemorrhages, followed by the extracranial outflow. During embolization, accidental dislodge of one coil into the sphenoparietal vein occurred, but no attempt of coil retrieval was made. Complete obliteration of the dCCF was achieved, and the patient recovered well without new neurological deficits. 4D MRA at the 3-month follow-up showed no residual dCCF.

The video can be found here: https://youtu.be/LH2lNVRZSPk.

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Kunal Vakharia, Stephan A. Munich, Muhammad Waqas, Swetadri Vasan Setlur Nagesh and Elad I. Levy

Progressive deconstruction with flow diversion using a Pipeline embolization device (PED; Medtronic) can be utilized to promote thrombosis of broad-based fusiform aneurysms. Current flow diverters require a 0.027-inch microcatheter for deployment. The authors present a patient with a fusiform P2–3 junction posterior cerebral artery aneurysm in which they demonstrate the importance of haptics in microwire manipulation to recognize large-vessel anatomy versus perforator anatomy that may overlap, especially when access is needed in distal tortuous circulations. In addition, the authors demonstrate the need for appropriate visualization before PED deployment. Postembolization runs demonstrated optimal wall apposition with contrast stasis within the aneurysm dome.

The video can be found here: https://youtu.be/8kfsSvN3XqM.