Eric A. Sribnick

Recent developments in clinical trials for the treatment of traumatic brain injury

The clinical understanding of traumatic brain injury (TBI) and its manifestations is beginning to change. Both clinicians and research scientists are recognizing that TBI and related disorders such as stroke are complex, systemic inflammatory and degenerative diseases that require an approach to treatment more sophisticated than targeting a single gene, receptor, or signaling pathway. It is becoming increasingly clear that TBI is a form of degenerative disorder affecting the brain and other organs, and that its manifestations can unfold days, weeks, and years after the initial damage. Until recently, and despite numerous industry- and government-sponsored clinical trials, attempts to find a safe and effective neuroprotective agent have all failed - probably because the research and development strategies have been based on an outdated early 20th century paradigm seeking a magic bullet that will affect a narrowly circumscribed target. We propose that more attention be given to the development of drugs, given alone or in combination, that are pleiotropic in their actions and that have systemic as well as central nervous system effects. We review current Phase II and Phase III trials for acute pharmacologic treatments for TBI and report on their aims, methods, status, and important associated research issues.

Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

Purpose Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormones effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. Methods Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28. Results The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. Conclusion Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

Surgical technique for spinal cord delivery of therapies: demonstration of procedure in gottingen minipigs.

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use. The size, anatomy, and general vulnerability of the spine and spinal cord of the swine are recognized to better model the human. Moreover, the surgical process of exposing and manipulating the spinal cord as well as closing the wound in the pig is virtually indistinguishable from the human. We believe that the healthy pig model represents a critical first step in the study of procedural safety.

Traumatic High-Grade Cervical Dislocation: Treatment Strategies and Outcomes

OBJECTIVE Traumatic high-grade cervical spinal dislocations are rare injuries, generally associated with severe neurological compromise. In particular, cervical spondyloptosis (>100% subluxation) is rarely reported. The object of our study is to present a case series describing presentation, management, and outcome in traumatic high-grade cervical spinal dislocations. METHODS Retrospective analysis was performed involving two level 1 trauma centers. Patients with a high-grade traumatic cervical subluxation were selected from a database, and these patients were admitted between August 2007 and July 2011. RESULTS Fifteen patients were identified; three had spondyloptosis. The admission American Spinal Injury Association Impairment Scale (AIS) grade varied (A = 9; B = 2; C = 1; D = 2; E = 1). Fourteen patients underwent attempted closed reduction with six (43%) failing closed reduction. High-dose methylprednisolone was administered in nine patients (60%). All patients underwent surgical stabilization: three underwent anterior only, three underwent posterior only, and nine underwent a combined anterior-posterior approach. Postoperatively, one patient improved two AIS grades, three improved one AIS grade, nine maintained their preoperative score, and two patients worsened. CONCLUSIONS In this series, 26.7% of patients had improvement in their AIS grade postoperatively, and the majority of patients (60%) maintained their preoperative AIS grade. In 57% of patients placed in traction, reduction was possible. Likely due to the severity of these injuries, there was a high incidence of complications. However, review of patient outcomes reveals that these patients can have improvement of neurological function. We recommend aggressive reduction and surgical stabilization. Our preference is either a combined anterior-posterior approach or a posterior-only approach.

Treatment of Harlequin syndrome by costotransversectomy and sympathectomy: case report.

BACKGROUND AND IMPORTANCE:Harlequin syndrome is a rare neurological condition involving various degrees of unilateral hyperhidrosis and erythema of the head and neck. We present a clinical presentation and description of curative therapy in a patient with a sudden onset of Harlequin syndrome following a thoracotomy. CLINICAL PRESENTATION:A 42-year-old female with a history of mastectomy for right-sided breast cancer subsequently had a left partial pneumonectomy for a metastasis. Postoperatively, she had onset of contralateral neck and facial flushing and sweating. Flushing was triggered by emotion and exercise, but also occurred spontaneously at random intervals. Magnetic resonance imaging of the brain, cervical spine, and thoracic spine were negative for pathology. Because of the patients surgical history and negative workup, she was given a diagnosis of Harlequin syndrome. Surgical intervention consisted of a partial right T3 costotransversectomy with T2 sympathectomy. Postoperatively, the patients symptoms of Harlequin syndrome resolved. The procedure was complicated by T1 radicular pain, which responded well to Gabapentin. CONCLUSION:The diagnosis of Harlequin syndrome is relatively new, and the majority of the scientific literature is concerned with descriptive case presentations. We present a surgical technique for the treatment of Harlequin syndrome.

Neuroendoscopic Colloid Cyst Resection: A Case Cohort with Follow-Up and Patient Satisfaction

OBJECTIVE To analyze the safety and efficacy of neuroendoscopic colloid cyst resection and to assess patient satisfaction. METHODS A retrospective analysis of a single surgeons experience with neuroendoscopic resection of colloid cysts was performed. Surgeries performed in 56 patients were reviewed. Surgeries involved an anterolateral neuroendoscopic technique. Patients were followed postoperatively for an average of 14.9 months. Patients were also interviewed regarding their preoperative symptoms, resolution of symptoms postoperatively, and their degree of satisfaction. RESULTS The median operative time was 82 minutes, and the median duration of hospital stay was 5 days. During surgery, the ventricles were explored for residual cyst wall or cyst content, and none were encountered. On immediate postoperative imaging, cyst recurrence was not noted for any patient, and only 1 patient has had evidence of recurrence on long-term follow-up. Various preoperative symptoms were described by patients; depending on the specific symptoms, 70%-100% resolution of symptoms was shown after surgery. Along with clinical follow-up, patients were interviewed regarding their perception of surgery and recovery. Of the patients contacted, 100% reported satisfaction with the surgery, and 91% noted satisfaction with their recovery. Reported complications included memory loss, infection, deep vein thrombosis, and postoperative hematoma. There were 2 perioperative deaths (3.5%) related to surgery. CONCLUSIONS Neuroendoscopic colloid cyst resection can reliably achieve complete lesion removal with short operative times. In addition, there is a high level of reported patient satisfaction. To our knowledge, this is the largest case series of neuroendoscopic colloid cyst resections from a single surgeon.

The use of inside-outside screws for occipitocervical fusion in pediatric patients.

OBJECT The authors describe the use of inside-outside occipital screws in 21 children with occipitocervical instability requiring occipitocervical fusion. METHODS The ages of the patients were from 2 to 15 years, and patients presented with a variety of causes of occipitocervical instability, including congenital disorders, posttraumatic instability, idiopathic degeneration, and postoperative instability. Surgeries frequently included foramen magnum decompression, duraplasty, and laminectomy, but all patients required occipitocervical instrumentation and arthrodesis. Postoperative orthosis included the use of either a cervical collar or halo device. In all but one case, patients were followed postoperatively for at least 12 months. RESULTS The mean age of patients was 9.93 years. Inside-outside screws were used in all reported cases. Rib autograft was used in all patients. In addition, demineralized bone matrix was used in 2 cases, and bone morphogenetic protein was used in 2 patients. Two patients required halo placement, and the other 19 were placed in cervical collars. The average time postoperative orthotics were used was 2.82 months. Arthrodesis was determined radiographically and was noted in all patients. No operative complications were noted; however, postoperative complications included 1 wound infection, 2 cases of hardware loosening, and the need for tracheostomy in 2 patients. CONCLUSIONS Inside-outside screws were found to be a useful component of occipitocervical instrumentation in pediatric patients ranging from 2 to 15 years of age. Arthrodesis was demonstrated in all cases.

Complete neurologic recovery of spinal cord injury after posterior transpedicular reconstruction for traumatic lumbar burst fracture.

1529-9430/

Clinical outcome of children with suspected shunt malfunction evaluated in the emergency department.

see front matter 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spinee.2012.11.028 tomography scan demonstrated 50% loss of height at L1 with focal kyphosis and near complete obliteration of the spinal canal (Fig. 1, Left and Top Right). Initial evaluation revealed an incomplete spinal cord injury (American Spinal Injury Association D) characterized by hypesthesia below the L1 dermatome and four (minus) out of five strength of all major muscle groups of the lower extremities bilaterally. Rectal tone and continence were preserved. Injury to the conus medullaris was clinically suspected because the patient suffered urinary retention that required bladder catheterization throughout his hospitalization. Preoperative magnetic resonance imaging confirmed compression of the conus medullaris (Fig. 1, Bottom Right). The patient was

379 Communicating a Traumatic Brain Injury Patient's Potential Need for Operative Intervention: The Surgical Intervention for Traumatic Injury Scale.

BACKGROUND Patients with cerebrospinal fluid shunts frequently present to the emergency department (ED) with suspected shunt malfunction. The outcome of those patients who were discharged from ED when shunt malfunction was deemed unlikely has not been previously documented. OBJECTIVE To demonstrate there is no increase in severity or likelihood of harm for patients who are discharged directly from the ED after adequate evaluation, as compared to patients who were selected for inpatient hospitalization. METHODS The report screens 3080 ED visits between 2010 and 2013 made by patients with shunted hydrocephalus. ED visits preceded by another ED visit or neurosurgical procedures within 60 days were excluded. ED visits for reasons unrelated to shunt function were excluded, and 1943 visits met the inclusion criteria. Final dispositions from the ED included home (n = 1176), admission to neurosurgery service (n = 550), and admission to other services (n = 217). Subsequent events within 30 days, including ED visits and elective and nonelective shunt-related surgery, were reviewed. RESULTS The clinical characteristics of the 3 groups were similar. Of patients discharged home from the ED, 19.0% returned to ED, and 4.5% required shunt-related surgeries. Of the patients admitted for observation, 18.7% returned to ED and 14.2% required shunt-related surgery. Of the patients admitted to other hospital services, 19.6% patients returned to the ED, with 2.0% requiring surgical intervention. There were no shunt-related mortalities in any of the 3 groups. CONCLUSION Children with cerebrospinal fluid shunts are often evaluated in the ED. Discharge from the ED, when suspicion for shunt malfunction is low, is an appropriate practice.