Doniel Drazin

INTRODUCTION: Spinal ankylosing disorders encompass ankylosing spondylitis (AS), disseminated hyperostosis of the spine, and end-stage spondylosis. All these result in a stiffened and frequently deformed spinal column. This makes the spinal column highly susceptible to severe injuries that are commonly associated with unfavorable outcomes. Improved understanding of the underlying disease processes and clinical comorbidities may alter the poor injury related morbidity and mortality outcomes. METHODS: A systematic review of the MEDLINE and PubMed databases was performed using the following key words to identify articles published between 2001 and 2016: "ankylosing spondylitis," "epidemiology," "DISH," "treatment," "outcome," and/or "fracture." Articles were read for data on methodology (retrospective vs. prospective), type of treatment, number of patients, mean patient age, and mean follow-up. RESULTS: Twenty-one identified articles were analyzed. Average age was 63.4 years. Most patients were men. Ground level fall or low energy trauma caused most injuries. Diagnosis was delayed in 15%-41% cases. Hyperextension fracture patterns were most common. Cervical spine fractures were more common than thoracolumbar fractures, with the highest prevalence between C5 and C7. Neurologic deficits were encountered in 21%-100% of patients. Operative fixation and fusion were performed in 40%-100% of patients. Mortality was reported between 0% and 32% at 1 year postinjury. Complications were encountered in 84% of patients, mostly in the form of pneumonia, respiratory failure, and pseudoarthrosis. Neurologic deterioration has been reported in 16% of patients. Fusion was successful in 87%-100% of patients. Neurologic deficits improved in function in 6%-66% at the final follow-up. CONCLUSIONS: Because of the stiffening of the spinal column, patients with spinal ankylosing disorders are preferably evaluated for spinal fractures and ligamentous injuries after even trivial trauma. Spinal injuries in patients with AS are difficult to diagnose on plain radiographs; computed tomography and magnetic resonance imaging are recommended instead. The entire spine should be scanned for multilevel involvement. Although osteoporosis makes fixation of spine implants a significant concern, the literature has reported that most patients with AS treated surgically had good outcomes. Numerous studies have reported risks associated with conservative management.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

OBJECT: The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG. The authors present a novel proof-of-concept near-infrared (NIR) imaging system using a standard charge-coupled device (CCD) camera for visualizing low levels of ICG attached to the tumors. This system is small, inexpensive, and sensitive. The imaging system uses a narrow-band laser at 785 nm and a notch filter in front of the sensor at the band. The camera is a 2-CCD camera, which uses identical CCDs for both visible and NIR light. METHODS: The NIR system is tested with serial dilution of BLZ-100 from 1 μM to 50 pM in 5% Intralipid solution while the excitation energy is varied from 5 to 40 mW/cm(2). The analog gain of the CCD was changed from 0, 6, and 12 dB to determine the signal-to-noise ratio. In addition to the Intralipid solution, BLZ-100 was injected 48 hours before euthanizing the mice that were implanted with the human glioma cell line. The brain was removed and imaged using the NIR imaging system. RESULTS: The authors' results show that the NIR imaging system using a standard CCD is able to visualize the ICG down to 50 nM of concentration with a high signal-to-noise ratio. The preliminary experiment on human glioma implanted in mouse brains demonstrated that BLZ-100 has a high affinity for glioma compared with normal brain tissue. Additionally, the results show that NIR excitation is able to penetrate deeply and has a potential to visualize metastatic lesions that are separate from the main tumor. CONCLUSIONS: The authors have seen that BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. The authors hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits.

OBJECT Anterior cervical discectomy and fusion (ACDF) is an effective procedure for the treatment of cervical radiculopathy and/or myelopathy; however, postoperative dysphagia is a significant concern. Dexamethasone, although potentially protective against perioperative dysphagia and airway compromise, could inhibit fusion, a generally proinflammatory process. The authors conducted a prospective, randomized, double-blinded, controlled study of the effects of steroids on swallowing, the airway, and arthrodesis related to multilevel anterior cervical reconstruction in patients who were undergoing ACDF at Albany Medical Center between 2008 and 2012. The objective of this study was to determine if perioperative steroid use improves perioperative dysphagia and airway edema. METHODS A total of 112 patients were enrolled and randomly assigned to receive saline or dexamethasone. Data gathered included demographics, functional status (including modified Japanese Orthopaedic Association myelopathy score, neck disability index, 12-Item Short-Form Health Survey score, and patient-reported visual analog scale score of axial and radiating pain), functional outcome swallowing scale score, interval postoperative imaging, fusion status, and complications/reoperations. Follow-up was performed at 1, 3, 6, 12, and 24 months, and CT was performed 6, 12, and 24 months after surgery for fusion assessment. RESULTS Baseline demographics were not significantly different between the 2 groups, indicating adequate randomization. In terms of patient-reported functional and pain-related outcomes, there were no differences in the steroid and placebo groups. However, the severity of dysphagia in the postoperative period up to 1 month proved to be significantly lower in the steroid group than in the placebo group (p = 0.027). Furthermore, airway difficulty and a need for intubation trended toward significance in the placebo group (p = 0.057). Last, fusion rates at 6 months proved to be significantly lower in the steroid group but lost significance at 12 months (p = 0.048 and 0.57, respectively). CONCLUSIONS Dexamethasone administered perioperatively significantly improved swallowing function and airway edema and shortened length of stay. It did not affect pain, functional outcomes, or long-term swallowing status. However, it significantly delayed fusion, but the long-term fusion rates remained unaffected. Clinical trial registration no.: NCT01065961 (clinicaltrials.gov).