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Shanmukha Srinivas, Arvin R. Wali and Martin H. Pham

OBJECTIVE

Riluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.

METHODS

The PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.

RESULTS

A total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.

CONCLUSIONS

SCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

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Joshua D. Burks, Katie L. Gant, James D. Guest, Aria G. Jamshidi, Efrem M. Cox, Kim D. Anderson, W. Dalton Dietrich, Mary Bartlett Bunge, Barth A. Green, Aisha Khan, Damien D. Pearse, Efrat Saraf-Lavi and Allan D. Levi

OBJECTIVE

In cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors’ institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.

METHODS

The authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.

RESULTS

Imaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).

CONCLUSIONS

While screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

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Joseph P. Antonios, Ghassan J. Farah, Daniel R. Cleary, Joel R. Martin, Joseph D. Ciacci and Martin H. Pham

Spinal cord injury (SCI) has been associated with a dismal prognosis—recovery is not expected, and the most standard interventions have been temporizing measures that do little to mitigate the extent of damage. While advances in surgical and medical techniques have certainly improved this outlook, limitations in functional recovery continue to impede clinically significant improvements. These limitations are dependent on evolving immunological mechanisms that shape the cellular environment at the site of SCI. In this review, we examine these mechanisms, identify relevant cellular components, and discuss emerging treatments in stem cell grafts and adjuvant immunosuppressants that target these pathways. As the field advances, we expect that stem cell grafts and these adjuvant treatments will significantly shift therapeutic approaches to acute SCI with the potential for more promising outcomes.

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Paolo Belardinelli, Ramin Azodi-Avval, Erick Ortiz, Georgios Naros, Florian Grimm, Daniel Weiss and Alireza Gharabaghi

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson’s disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.

The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.

The authors identified coherent activity in the upper beta range (21–35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4–6 Hz) was detected in the ipsilateral prefrontal area.

These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.

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Sanjay S. Dhall, Shekar N. Kurpad, R. John Hurlbert and Praveen V. Mummaneni

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Francesco Sammartino, Dylan W. Beam, John Snell and Vibhor Krishna

Transcranial focused ultrasound (FUS) ablation is an emerging incision-less treatment for neurological disorders. The factors affecting FUS treatment efficiency are not well understood. Kranion is open-source software that allows the user to simulate the planning stages of FUS treatment and to “replay” previous treatments for off-line analysis. This study aimed to investigate the relationship between skull parameters and treatment efficiency and to create a metric to estimate temperature rise during FUS. CT images from 28 patients were analyzed to validate the use of Kranion. For stereotactic targets within each patient, individual transducer element incident angles, skull density ratio, and skull thickness measurements were recorded. A penetration metric (the “beam index”) was calculated by combining the energy loss from incident angles and the skull thickness. Kranion accurately estimated the patient’s skull and treatment parameters. The authors observed significant changes in incident angles with different targets in the brain. Using the beam index as a predictor of temperature rise in a linear-mixed-effects model, they were able to predict the average temperature rise at the focal point during ablation with < 21% error (55°C ± 3.8°C) in 75% of sonications, and with < 44% (55°C ± 7.9°C) in 97% of sonications. This research suggests that the beam index can improve the prediction of temperature rise during FUS. Additional work is required to study the relationship between temperature rise and lesion shape and clinical outcomes.

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Dmitriy Petrov, Michael Spadola, Connor Berger, Gregory Glauser, Ahmad F. Mahmoud, Bert O’Malley and Neil R. Malhotra

Chordomas are rare, locally aggressive neoplasms that develop from remnants of the notochord. The typical approach to chordomas of the clivus and axial cervical spine often limits successful en bloc resection. In this case report, authors describe the first-documented transoral approach using both transoral robotic surgery (TORS) for exposure and the Sonopet bone scalpel under navigational guidance to achieve en bloc resection of a cervical chordoma. This 27-year-old man had no significant past medical history (Charlson Comorbidity Index 0). During a trauma workup following a motor vehicle collision, a CT of the patient’s cervical spine demonstrated an incidental 2.2-cm lesion situated along the posterior aspect of the C2 vertebral body. Postoperative imaging showed successful en bloc resection with adequate placement of hardware, and the pathology report demonstrated negative resection margins. The patient tolerated the procedure well, and because of the successful en bloc resection, radiation has been deferred. At 7 months postoperatively, the patient returned to work in New York City. Contrasted MRI at 15 months postoperatively showed the patient to be disease free. This approach offers a promising way forward in the treatment of these complex tumors.

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Angela G. Viers, Khoi D. Nguyen, Perounsack X. Moon, Scott E. Forseen and Ian M. Heger

OBJECTIVE

Occipitocervical fusions in the pediatric population are rare but can be challenging because of the smaller anatomy. The procedure is even more exacting in patients with prior suboccipital craniectomy. A proposed method for occipitocervical fusion in such patients is the use of occipital condyle screws. There is very limited literature evaluating the pediatric occipital condyle for screw placement. The authors examined the occipital condyle in pediatric patients to determine if there was an age cutoff at which condylar screw placement is contraindicated.

METHODS

The authors performed a retrospective morphometric analysis of the occipital condyle in 518 pediatric patients aged 1 week–9 years old. Patients in their first decade of life whose occipital condyle was demonstrated on CT imaging in the period from 2009 to 2013 at the Augusta University Medical Center and Children’s Hospital of Georgia were eligible for inclusion in this study. Exclusion criteria were an age older than 10 years; traumatic, inflammatory, congenital, or neoplastic lesions of the occipital condyles; and any previous surgery of the occipitocervical junction. Descriptive statistical analysis was performed including calculation of the mean, standard deviation, and confidence intervals for all measurements. Probability values were calculated using the Student t-test with statistical significance determined by p < 0.05.

RESULTS

Overall, male patients had statistically significantly larger occipital condyles than the female patients, but this difference was not clinically significant. There was no significant difference in left versus right occipital condyles. There were statistically significant differences between age groups with a general trend toward older children having larger occipital condyles. Overall, 20.65% of all patients evaluated had at least one measurement that would prevent occipital condyle screw placement including at least one patient in every age group.

CONCLUSIONS

Occipital condyle screw fixation is feasible in pediatric patients younger than 10 years. More importantly, all pediatric patients should undergo critical evaluation of the occipital condyle in the axial, sagittal, and coronal planes preoperatively to determine individual suitability for occipital condyle screw placement.

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Cecilia L. Dalle Ore, Christopher P. Ames, Vedat Deviren and Darryl Lau

OBJECTIVE

Spinal deformity causing spinal imbalance is directly correlated to pain and disability. Prior studies suggest adult spinal deformity (ASD) patients with rheumatoid arthritis (RA) have more complex deformities and are at higher risk for complications. In this study the authors compared outcomes of ASD patients with RA following thoracolumbar 3-column osteotomies to outcomes of a matched control cohort.

METHODS

All patients with RA who underwent 3-column osteotomy for thoracolumbar deformity correction performed by the senior author from 2006 to 2016 were identified retrospectively. A cohort of patients without RA who underwent 3-column osteotomies for deformity correction was matched based on multiple clinical factors. Data regarding demographics and surgical approach, along with endpoints including perioperative outcomes, reoperations, and incidence of proximal junctional kyphosis (PJK) were reviewed. Univariate analyses were used to compare patients with RA to matched controls.

RESULTS

Eighteen ASD patients with RA were identified, and a matched cohort of 217 patients was generated. With regard to patients with RA, 11.1% were male and the mean age was 68.1 years. Vertebral column resection (VCR) was performed in 22.2% and pedicle subtraction osteotomy (PSO) in 77.8% of patients. Mean case length was 324.4 minutes and estimated blood loss (EBL) was 2053.6 ml. Complications were observed in 38.9% of patients with RA and 29.0% of patients without RA (p = 0.380), with a trend toward increased medical complications (38.9% vs 21.2%, p = 0.084). Patients with RA had a significantly higher incidence of deep vein thrombosis (DVT)/pulmonary embolism (PE) (11.1% vs 1.8%, p = 0.017) and wound infections (16.7% vs 5.1%, p = 0.046). PJK occurred in 16.7% of patients with RA, and 33.3% of RA patients underwent reoperation. Incidence rates of PJK and reoperation in matched controls were 12.9% and 25.3%, respectively (p = 0.373, p = 0.458). At follow-up, mean sagittal vertical axis (SVA) was 6.1 cm in patients with RA and 4.5 cm in matched controls (p = 0.206).

CONCLUSIONS

Findings from this study suggest that RA patients experience a higher incidence of medical complications, specifically DVT/PE. Preoperative lower-extremity ultrasounds, inferior vena cava (IVC) filter placement, and/or early initiation of DVT prophylaxis in RA patients may be indicated. Perioperative complications, morbidity, and long-term outcomes are otherwise similar to non-RA patients.