Martin H. Pham

Endovascular stenting of extracranial carotid and vertebral artery dissections: A systematic review of the literature

BACKGROUND:Carotid and vertebral artery dissections are a leading cause of stroke in young individuals. OBJECTIVE:To examine the published safety and efficacy of endovascular stenting for extracranial artery dissection. METHODS:We conducted a systematic review of the literature to identify all cases of endovascular management of extracranial carotid and vertebral artery dissections. RESULTS:For carotid dissections, our review yielded 31 published reports including 140 patients (153 vessels). Reported etiologies were traumatic (48%, n = 64), spontaneous (37%, n = 49), and iatrogenic (16%, n = 21). The technical success rate of stenting was 99%, and the procedural complication rate was 1.3%. Mean angiographic follow-up was 12.8 months (range, 2-72 months) and revealed in-stent stenosis or occlusion in 2% of patients. Mean clinical follow-up was 17.7 months (range, 1-72 months), and neurological events were seen in 1.4% of patients. For vertebral artery dissections, our review revealed 8 reports including 10 patients (12 vessels). Etiologies were traumatic (60%, n = 6), spontaneous (20%, n = 2), and iatrogenic (20%, n = 2). There was a 100% technical success rate. The mean angiographic follow-up period was 7.5 months (range, 2-12 months). No new neurological events were reported during a mean clinical follow-up period of 26.4 months (range, 3-55 months). CONCLUSION:Endovascular management of extracranial arterial dissection continues to evolve. Current experience shows that this treatment option is safe and technically feasible. Prospective randomized trials compared with medical management are needed to further elucidate the role of stenting.

Molecular genetics of meningiomas: a systematic review of the current literature and potential basis for future treatment paradigms.

Although a majority of meningiomas are benign neoplasms, those occurring at the cranial base may be challenging tumors to treat because of extensive tissue invasion, an inability to achieve gross-total microscopic resection, and local tumor recurrence and/or progression. A more comprehensive understanding of the genetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide novel targets for grading assessments and individualizing molecular therapies for skull base meningiomas. The authors performed a review of the current literature to identify genes that have been associated with the formation and/or progression of meningiomas. Mutations in the NF2 gene have been most commonly implicated in the formation of the majority of meningiomas. Inactivation of other tumor suppressor genes, including DAL-1 and various tissue inhibitors of matrix metalloproteinases, upregulation of several oncogenes including c-sis and STAT3, and signaling dysregulation of pathways such as the Wnt pathway, have each been found to play important, and perhaps, complementary roles in meningioma development, progression, and recurrence. Identification of these genetic factors using genome-wide association studies and high-throughput genomics may provide data for future individualized treatment strategies.

Ossification of the posterior longitudinal ligament: genetics and pathophysiology

Ossification of the posterior longitudinal ligament (OPLL) is a disease of progressive ectopic calcification of the PLL of the spine. It occurs most frequently in the cervical spine, followed by the thoracic spine. The disease was first described in the Japanese population, and the prevalence of OPLL is highest in Japan at a rate of 1.9%-4.3%. Note, however, that OPLL is also seen and is a known cause of cervical myelopathy in other Asian countries and in the white population. Research into the underlying cause of OPLL over the past few decades has shown that it is a multifactorial disease with significant genetic involvement. Genetic studies of OPLL have revealed several gene loci that may be involved in the pathogenesis of this disease. Genes encoding for proteins that process extracellular inorganic phosphate, collagen fibrils, and transcription factors involved in osteoblast and chondrocyte development and differentiation have all been implicated in the pathophysiology of OPLL. In this paper, the authors review current understanding of the genetics and pathophysiology of OPLL.

The indications and timing for operative management of spinal epidural abscess: literature review and treatment algorithm

OBJECT Delayed or inappropriate treatment of spinal epidural abscess (SEA) can lead to serious morbidity or death. It is a rare event with significant variation in its causes, anatomical locations, and rate of progression. Traditionally the treatment of choice has involved emergency surgical evacuation and a prolonged course of antibiotics tailored to the offending pathogen. Recent publications have advocated antibiotic treatment without surgical decompression in select patient populations. Clearly defining those patients who can be safely treated in this manner remains in evolution. The authors review the current literature concerning the treatment and outcome of SEA to make recommendations concerning what population can be safely triaged to nonoperative management and the optimal timing of surgery. METHODS A PubMed database search was performed using a combination of search terms and Medical Subject Headings, to identify clinical studies reporting on the treatment and outcome of SEA. RESULTS The literature review revealed 28 original case series containing at least 30 patients and reporting on treatment and outcome. All cohorts were deemed Class III evidence, and in all but two the data were obtained retrospectively. Based on the conclusions of these studies along with selected smaller studies and review articles, the authors present an evidence-based algorithm for selecting patients who may be safe candidates for nonoperative management. CONCLUSIONS Patients who are unable to undergo an operation, have a complete spinal cord injury more than 48 hours with low clinical or radiographic concern for an ascending lesion, or who are neurologically stable and lack risk factors for failure of medical management may be initially treated with antibiotics alone and close clinical monitoring. If initial medical management is to be undertaken the patient should be made aware that delayed neurological deterioration may not fully resolve even after prompt surgical treatment. Patients deemed good surgical candidates should receive their operation as soon as possible because the rate of clinical deterioration with SEA is notoriously unpredictable. Although patients tend to recover from neurological deficits after treatment of SEA, the time point when a neurological injury becomes irreversible is unknown, supporting emergency surgery in those patients with acute findings.

Conservative management of ossification of the posterior longitudinal ligament. A review

OBJECT Ossification of the posterior longitudinal ligament (OPLL) can result in significant myelopathy. Surgical treatment for OPLL has been extensively documented in the literature, but less data exist on conservative management of this condition. METHODS The authors conducted a systematic review to identify all reported cases of OPLL that were conservatively managed without surgery. RESULTS The review yielded 11 published studies reporting on a total of 480 patients (range per study 1-359 patients) over a mean follow-up period of 14.6 years (range 0.4-26 years). Of these 480 patients, 348 (72.5%) were without myelopathy on initial presentation, whereas 76 patients (15.8%) had signs of myelopathy; in 56 cases (15.8%), the presence of myelopathy was not specified. The mean aggregate Japanese Orthopaedic Association score on presentation for 111 patients was 15.3. Data available for 330 patients who initially presented without myelopathy showed progression to myelopathy in 55 (16.7%), whereas the other 275 (83.3%) remained progression free. In the 76 patients presenting with myelopathy, 37 (48.7%) showed clinical progression, whereas 39 (51.5%) remained clinically unchanged or improved. CONCLUSIONS Patients who present without myelopathy have a high chance of remaining progression free. Those who already have signs of myelopathy at presentation may benefit from surgery due to a higher rate of progression over continued follow-up.

Radiosurgery for angiographically occult vascular malformations.

The use of radiosurgery for angiographically occult vascular malformations (AOVMs) is a controversial treatment option for those that are surgically inaccessible or located in eloquent brain. To determine the efficacy of this treatment, the authors reviewed the literature reporting hemorrhage rates, seizure control, and radiation-induced morbidity. They found overall hemorrhage rates of 2-6.4%, overall postradiosurgery hemorrhage rates of 1.6-8%, and stratified postradiosurgery hemorrhage rates of 7.3-22.4% in the period immediately to 2 years after treatment; these latter rates declined to 0.8-5.2% > 2 years after treatment. Of 291 patients presenting with seizure across 16 studies, 89 (31%) attained a seizure-free status and 102 (35%) had a reduction in seizure frequency after radiosurgery. Overall radiation-induced morbidity ranged from 2.5 to 59%, with higher complication rates in patients with brainstem lesion locations. Researchers applying mean radiation doses of 15-16.2 Gy to the tumor margin saw both low radiation-induced complication rates (0-9.1%) and adequate hemorrhage control (0.8-5.2% > 2 years after treatment), whereas mean doses >or= 16.5 Gy were associated with higher total radiation-induced morbidity rates (> 17%). Although the use of stereotactic radiosurgery remains controversial, patients with AOVMs located in surgically inaccessible areas of the brain may benefit from such treatment.

A Perfusion-Based Human Cadaveric Model for Management of Carotid Artery Injury during Endoscopic Endonasal Skull Base Surgery

Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm.

A review of epigenetic and gene expression alterations associated with intracranial meningiomas

OBJECT A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas. METHODS The authors performed a review of the current literature to identify the epigenetic modifications associated with the formation and/or progression of meningiomas. RESULTS Several epigenomic alterations, mainly pertaining to DNA methylation, have been associated with meningiomas. Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2 (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2, and TGF-β epigenetic modifications allow either upregulation or downregulation of critical pathways for meningioma development, progression, and recurrence. CONCLUSIONS Genome-wide methylation profiling demonstrated that global hypomethylation correlates with tumor grades and severity. Identification of additional epigenetic changes, such as histone modification and higher-order chromosomal structure, may allow for a more thorough understanding of tumorigenesis and enable future individualized treatment strategies for meningiomas.

Clinical Relevance of Magnetic Resonance Imaging in Cervical Spine Clearance: A Prospective Study

IMPORTANCE A missed cervical spine (CS) injury can have devastating consequences. When CS injuries cannot be ruled out clinically using the National Emergency X-Radiography Utilization Study low-risk criteria because of either a neurologic deficit or pain, the optimal imaging modality for CS clearance remains controversial. OBJECTIVE To investigate the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for CS clearance. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was conducted from January 1, 2010, through May 31, 2011, at a level I trauma center. Participants included 830 adults who were awake, alert, and able to be examined who experienced blunt trauma with resultant midline CS tenderness and/or neurologic deficits and were undergoing CT of the CS. Initial examinations, all CS imaging results, interventions, and final CS diagnoses were documented. The criterion standard for the sensitivity and specificity calculations was final diagnosis of CS injury at the time of discharge. MAIN OUTCOMES AND MEASURES Clinically significant CS injuries, defined as injuries requiring surgical stabilization or halo placement. RESULTS Overall, 164 CS injuries (19.8%) were diagnosed, and 23 of these (2.8%) were clinically significant. All clinically significant injuries were detected by CT. Fifteen of 681 patients (2.2%) with a normal CT scan had a newly identified finding on MRI; however, none of the injuries required surgical intervention or halo placement. There was no change in management on the basis of MRI findings. The sensitivity and specificity of CT for detecting CS injury was 90.9% and 100%, respectively. For clinically significant CS injuries, the sensitivity was 100% and specificity was 100%. CONCLUSIONS AND RELEVANCE Computed tomography is effective in the detection of clinically significant CS injuries in adults deemed eligible for evaluation who had a neurologic deficit or CS pain. Magnetic resonance imaging does not provide any additional clinically relevant information.

Endoscopic-Assisted Resection of Intracranial Epidermoid Tumors

OBJECTIVE Intracranial epidermoid tumors are epithelially derived lesions that may present particular challenges to neurosurgeons, often encasing critical neurovascular structures and extending into multiple subarachnoid cisterns. We aimed to evaluate our recent experience with endoscopic assistance to craniotomy with microsurgical resection of these lesions. METHODS A retrospective review of patients undergoing endoscopic-assisted craniotomy for resection of an epidermoid tumor at the Keck School of Medicine of University of Southern California between 2009 and 2012 was conducted. In all patients, the surgical approach and tumor resection were first performed microscopically. This was followed by use of an angled endoscope to facilitate further inspection and additional resection of tumor using a two-surgeon technique. RESULTS Twelve patients undergoing 13 consecutive endoscopic-assisted craniotomies were included in the analysis. The mean patient age was 45 years. The mean maximal tumor diameter was 4.0 cm (range, 2.4-5.8 cm). Surgery was for recurrent epidermoid in 6 of 13 cases (46%). Epidermoid tumor location included the cerebellopontine angle (9 patients, 75%), fourth ventricle (2 patients, 17%), and third ventricle (1 patient, 8%). Surgical approaches included retrosigmoid craniotomy (8 patients), suboccipital craniotomy (1 patient), suboccipital craniotomy with supracerebellar approach (1 patient), extradural temporopolar approach (1 patient), and subtemporal approach (1 patient). In 11 of 13 cases (85%), additional tumor was identified upon inspection with an angled endoscope, facilitating additional tumor resection in each case. Gross or deliberate near total resection was achieved in 7 of 13 cases (54%). Four patients (31%) had improvement of cranial nerve function. Postoperative neurological deficits included transient abducens and oculomotor nerve paresis in one patient each. CONCLUSIONS The endoscope is a safe and effective adjunct to the microscope in facilitating additional inspection and further resection of epidermoid tumors. Endoscopic-assisted surgery is particularly useful for identifying and removing additional tumor located around surgical corners.