Ethical clinical translation of stem cell interventions for neurologic disease.

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease.

Neurosurgery in Iraqi Kurdistan: An Example of International Neurosurgery Capacity Building.

The medical infrastructure of Iraqi Kurdistan, a semiautonomous region in the northern part of Iraq, lags disproportionately behind relative to the otherwise booming industrial advances of the region. Although neurosurgical training is available, the local population lacks trust in its own neurosurgeons. Medical facilities suffer from a lack of basic resources, such as high-speed drills, intracranial pressure monitoring, and stereotaxy to care for neurosurgical patients. Since 2012, American volunteer neurosurgeons have delivered lectures and mentored local neurosurgeons in performing neurosurgical procedures. Over the last 4 years, the visiting neurosurgical team has seen hundreds of patients in consultation and performed more than 50 complex cranial and spinal operations jointly with local neurosurgeons. This article discusses our experience as volunteer neurosurgeons in building neurosurgical capacity in Iraqi Kurdistan.

The impact of a standardized "spine damage-control" protocol for unstable thoracic and lumbar spine fractures in severely injured patients: a prospective cohort study.

BACKGROUND: In contrast to the established principles of "damage-control orthopedics" for temporary external fixation of long bone or pelvic fractures, the "ideal" timing and modality of fixation of unstable spine fractures in severely injured patients remains controversial. METHODS: A prospective cohort study was designed to evaluate the safety and efficacy of a standardized "spine damage-control" (SDC) protocol for the acute management of unstable thoracic and lumbar spine fractures in severely injured patients. A total of 112 consecutive patients with unstable thoracic or lumbar spine fractures and Injury Severity Score (ISS) of greater than 15 were prospectively enrolled in this study from October 1, 2008, to December 31, 2011. Acute posterior spinal fixation within 24 hours was performed in 42 patients (SDC group), and 70 patients underwent definitive operative spine fixation in a delayed fashion ("delayed surgery"[DS] group). Both cohorts were prospectively analyzed for baseline demographics, length of operative time, amount of intraoperative blood loss, total hospital length of stay, number of ventilator-dependent days, and incidence of early postoperative complications. RESULTS: The mean time to initial spine fixation was significantly decreased in the SDC group (8.9 [1.7] hours vs. 98.7 [22.4] hours, p < 0.01). The SDC cohort had a reduced mean length of operative time (2.4 [0.7] hours vs. 3.9 [1.3] hours), length of hospital stay (14.1 [2.9] days vs. 32.6 [7.8] days), and number of ventilator-dependent days (2.2 [1.5] days vs. 9.1 [2.4] days), compared with the DS group (p < 0.05). Furthermore, the complication rate was decreased in the SDC group with regard to wound complications (2.4% vs. 7.1%), urinary tract infections (4.8% vs. 21.4%), pulmonary complications (14.3% vs. 25.7%), and pressure sores (2.4% vs. 8.6%), compared with the DS cohort (p < 0.05). CONCLUSION: A standardized SDC protocol represents a safe and efficient treatment strategy for severely injured patients with associated unstable thoracic or lumbar fractures. LEVEL OF EVIDENCE: Therapeutic study, level III.

Cranioplasty after postinjury decompressive craniectomy: is timing of the essence?

BACKGROUND: The appropriate timing of cranioplasty after decompressive craniectomy for trauma is unknown. Potential benefits of delayed intervention (>6 weeks) for reducing the risk of infection must be balanced by persistent altered cerebrospinal fluid dynamics leading to hydrocephalus. We reviewed our recent 5-year experience in an effort to improve patient throughput and develop a rational decision making plan. METHODS: A 5-year query (2003-2007) of our level I neurotrauma database. From 2,400 head injuries, we performed a total of 350 craniotomies. Of the 350 patients who underwent craniotomy for trauma, 70 patients (20%) underwent decompressive craniectomy requiring cranioplasty. Timing of cranioplasty, cranioplasty material, postoperative infections, and incidence of hydrocephalus were evaluated with logistic regression to study potential associations between complications and timing, adjusted for risk factors. RESULTS: No specific time frame was predictive of hydrocephalus or infection, and logistic regression failed to identify significant predictors among the collected variables. CONCLUSION: In our experience, the prior practice of delayed cranioplasty (3-6 months postdecompressive craniectomy), requiring repeat hospital admission, does not seem to lower postcranioplasty infection rates nor the need for cerebrospinal fluid diversion procedures. Our current practice emphasizes cranioplasty during the initial hospital admission, as soon as there is resolution on computed tomography scan of brain swelling outside of the cranial vault with concurrent clinical examination. This occurs as early as 2 weeks postcraniectomy and should lower the overall cost of care by eliminating the need for additional hospital admissions.

Fatal outcome after insufficient spine fixation for pyogenic thoracic spondylodiscitis: an imperative for 360 degrees fusion of the infected spine.

BACKGROUND: Pyogenic spondylodiscitis represents a potentially life-threatening condition. Due to the low incidence, evidence-based surgical recommendations in the literature are equivocal, and the treatment modalities remain controversial. CASE PRESENTATION: A 59 year-old patient presented with a history of thoracic spondylodiscitis resistant to antibiotic treatment for 6 weeks, progressive severe back pain, and a new onset of bilateral lower extremity weakness. Clinically, the patient showed a deteriorating spastic paraparesis of her lower extremities. An emergent MRI revealed a kyphotic wedge compression fracture at T7/T8 with significant spinal cord compression, paravertebral and epidural abscess, and signs of myelopathy. The patient underwent surgical debridement with stabilization of the anterior column from T6-T9 using an expandable titanium cage, autologous bone graft, and an anterolateral locking plate. The patient recovered well under adjunctive antibiotic treatment. She presented again to the emergency department 6 months later, secondary to a repeat fall, with acute paraplegia of the lower extremities and radiographic evidence of failure of fixation of the anterior T-spine. She underwent antero-posterior revision fixation with hardware removal, correction of kyphotic malunion, evacuation of a recurrent epidural abscess, decompression of the spinal canal, and 360 degrees fusion from T2-T11. Despite the successful salvage procedure, the patient deteriorated in the postoperative phase, when she developed multiple complications including pneumonia, acute respiratory distress syndrome, bacterial meningitis, abdominal compartment syndrome, followed by septic shock with multiple organ failure and a lethal outcome within two weeks after revision surgery. CONCLUSION: This catastrophic example of a lethal outcome secondary to failure of anterior column fixation for pyogenic thoracic spondylodiscitis underlines the notion that surgical strategies for the infected spine must be aimed at achieving absolute stability by a 360 degrees fusion. This aggressive - albeit controversial - concept allows for an adequate infection control by adjunctive antibiotics and reduces the imminent risk of a secondary loss of fixation due to compromises in initial fixation techniques.

Unilateral cervical facet fractures with subluxation: injury patterns and treatment.

STUDY DESIGN: This is a retrospective study of patients with unilateral cervical facet fractures from a Level I academic trauma center. OBJECTIVE: We sought to examine fracture patterns involving only the facets, to examine the incidence of associated neurologic and vascular injuries, and to determine optimum management strategies for these injuries. SUMMARY OF BACKGROUND DATA: Most of the literature regarding unilateral cervical facet injuries has resulted from studies evaluating dislocated locked facets, "fracture-dislocations," or fractures of the lateral mass and pedicle. METHODS: We retrospectively reviewed our experience with unilateral fractures of the facets, identifying 25 cases over a 5-year period. Presenting history, neurologic examination, imaging findings, method of reduction, interval to surgery, type of surgery, and evaluation for vascular injuries were recorded. Fusion was assessed by plain radiographs and computed tomography scans at follow-up. RESULTS: All 25 patients were treated operatively. Ten of the fractures involved the superior articular process, 13 involved the inferior articular process, and 2 cases involved both. The most commonly affected level was at C6/7. Twenty-one of the 25 patients underwent anterior stabilization, 3 underwent posterior stabilization, and 1 underwent anterior-posterior stabilization. Eleven patients underwent diagnostic 4-vessel angiography, revealing 2 patients with vertebral artery injuries. Average follow-up was 11.5 months. There were no identifiable nonunions. CONCLUSIONS: We conclude the following: (a) anterior discectomy and fusion with a static (constrained) plating system is appropriate treatment for this type of injury, (b) in the absence of significant neurologic deficit with residual canal or foraminal stenosis, preoperative closed reduction is not necessary, (c) a small percentage of these patients will have vertebral artery injury, thus warranting screening with 16-slice computed tomographic angiography.

Are upright lateral cervical radiographs in the obtunded trauma patient useful? A retrospective study.

BACKGROUND: The best method for radiographic "clearance" of the cervical spine in obtunded patients prior to removal of cervical immobilization devices remains debated. Dynamic radiographs or MRI are thought to demonstrate unstable injuries, but can be expensive and cumbersome to obtain. An upright lateral cervical radiograph (ULCR) was performed in selected patients to investigate whether this study could provide this same information, to enable removal of cervical immobilization devices in the multiple trauma patient. METHODS: We retrospectively reviewed our experience with ULCR in 683 blunt trauma victims who presented over a 3-year period, with either a Glasgow Coma Score <13 or who were intubated at the time of presentation. RESULTS: ULCR was performed in 163 patients. Seven patients had studies interpreted to be abnormal, of which six were also abnormal, by either CT or MRI. The seventh patient's only abnormality was soft tissue swelling; MRI was otherwise normal. Six patients had ULCR interpreted as normal, but had abnormalities on either CT or MRI. None of the missed injuries required surgical stabilization, although one had a vertebral artery injury demonstrated on subsequent angiography. ULCR had an apparent sensitivity of 45.5% and specificity of 71.4%. CONCLUSION: ULCR are inferior to both CT and MRI in the detection of cervical injury in patients with normal plain radiographs. We therefore cannot recommend the use of ULCR in the obtunded trauma patient.