Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion.

Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-lying cerebellar tonsils (LLCT). CCI is characterized by severe headache and neck pain, cervical medullary syndrome, lower cranial nerve deficits, myelopathy, and radiological metrics, for which occipital cervical fusion (OCF) has been advocated. We conducted a retrospective analysis of patients with CCI and Ehlers-Danlos syndrome (EDS) to determine whether the surgical outcomes supported the criteria by which patients were selected for OCF. Fifty-three consecutive subjects diagnosed with EDS, who presented with severe head and neck pain, lower cranial nerve deficits, cervical medullary syndrome, myelopathy, and radiologic findings of CCI, underwent open reduction, stabilization, and OCF. Thirty-two of these patients underwent suboccipital decompression for obstruction of cerebral spinal fluid flow. Questionnaire data and clinical findings were abstracted by a research nurse. Follow-up questionnaires were administered at 5-28 months (mean 15.1). The study group demonstrated significant improvement in headache and neck pain (p < 0.001), decreased use of pain medication (p < 0.0001), and improved Karnofsky Performance Status score (p < 0.001). Statistically significant improvement was also demonstrated for nausea, syncope (p < 0.001), speech difficulties, concentration, vertigo, dizziness, numbness, arm weakness, and fatigue (p = 0.001). The mental fatigue score and orthostatic grading score were improved (p < 0.01). There was no difference in pain improvement between patients with CMI/LLCT and those without. This outcomes analysis of patients with disabling CCI in the setting of EDS demonstrated significant benefits of OCF. The results support the reasonableness of the selection criteria for OCF. We advocate for a multi-center, prospective clinical trial of OCF in this population.

Atlanto-axial rotary instability (Fielding type 1): characteristic clinical and radiological findings, and treatment outcomes following alignment, fusion, and stabilization.

Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament. This retrospective, IRB-approved study examines 20 subjects with Fielding type 1 rotary subluxation, characterized by anterior subluxation of the facet on one side, with a normal atlanto-dental interval. Subjects diagnosed with a heritable connective tissue disorder, and AAI had failed non-operative treatment and presented with severe headache, neck pain, and characteristic neurological findings. Subjects underwent a modified Goel-Harms posterior C1-C2 screw fixation and fusion without complication. At 15 months, two subjects underwent reoperation following a fall (one) and occipito-atlantal instability (one). Patients reported improvement in the frequency or severity of neck pain (P < 0.001), numbness in the hands and lower extremities (P = 0.001), headaches, pre-syncope, and lightheadedness (all P < 0.01), vertigo and arm weakness (both P = 0.01), and syncope, nausea, joint pain, and exercise tolerance (all P < 0.05). The diagnosis of Fielding type 1 AAI requires directed investigation with dynamic imaging. Alignment and stabilization is associated with improvement of pain, syncopal and near-syncopal episodes, sensorimotor function, and exercise tolerance.

Cervical medullary syndrome secondary to craniocervical instability and ventral brainstem compression in hereditary hypermobility connective tissue disorders: 5-year follow-up after craniocervical reduction, fusion, and stabilization.

A great deal of literature has drawn attention to the "complex Chiari," wherein the presence of instability or ventral brainstem compression prompts consideration for addressing both concerns at the time of surgery. This report addresses the clinical and radiological features and surgical outcomes in a consecutive series of subjects with hereditary connective tissue disorders (HCTD) and Chiari malformation. In 2011 and 2012, 22 consecutive patients with cervical medullary syndrome and geneticist-confirmed hereditary connective tissue disorder (HCTD), with Chiari malformation (type 1 or 0) and kyphotic clivo-axial angle (CXA) enrolled in the IRB-approved study (IRB# 10-036-06: GBMC). Two subjects were excluded on the basis of previous cranio-spinal fusion or unrelated medical issues. Symptoms, patient satisfaction, and work status were assessed by a third-party questionnaire, pain by visual analog scale (0-10/10), neurologic exams by neurosurgeon, function by Karnofsky performance scale (KPS). Pre- and post-operative radiological measurements of clivo-axial angle (CXA), the Grabb-Mapstone-Oakes measurement, and Harris measurements were made independently by neuroradiologist, with pre- and post-operative imaging (MRI and CT), 10/20 with weight-bearing, flexion, and extension MRI. All subjects underwent open reduction, stabilization occiput to C2, and fusion with rib autograft. There was 100% follow-up (20/20) at 2 and 5 years. Patients were satisfied with the surgery and would do it again given the same circumstances (100%). Statistically significant improvement was seen with headache (8.2/10 pre-op to 4.5/10 post-op, p < 0.001, vertigo (92%), imbalance (82%), dysarthria (80%), dizziness (70%), memory problems (69%), walking problems (69%), function (KPS) (p < 0.001). Neurological deficits improved in all subjects. The CXA average improved from 127° to 148° (p < 0.001). The Grabb-Oakes and Harris measurements returned to normal. Fusion occurred in 100%. There were no significant differences between the 2- and 5-year period. Two patients returned to surgery for a superficial wound infections, and two required transfusion. All patients who had rib harvests had pain related that procedure (3/10), which abated by 5 years. The results support the literature, that open reduction of the kyphotic CXA to lessen ventral brainstem deformity, and fusion/stabilization to restore stability in patients with HCTD is feasible, associated with a low surgical morbidity, and results in enduring improvement in pain and function. Rib harvest resulted in pain for several years in almost all subjects.

Neuronal activity organization features in human consciousness: summary of introductory remarks in a dialogue with neurological surgery residents.

Agreeing with Damasio's statement defining the "process" of consciousness, we propose the self as created by mind-based knowledge and a combination of images of an organism's intentional motor responses interacting with its environment. The lemniscal system, with plastic capabilities, manages gravity in voluntary movement. The spinal segment motor reflex represents the schema of gravity-managing neuronal activity, and it can become "nested" in cortical areas participating in consciousness-building, allowing consideration of the brain as a hyper-evolved nervous system segment harboring atavic spinal organization. Consciousness' capability to change itself makes humans co-participants in their own mental and consciousness evolution.

Utility of the clivo-axial angle in assessing brainstem deformity: pilot study and literature review.

There is growing recognition of the kyphotic clivo-axial angle (CXA) as an index of risk of brainstem deformity and craniocervical instability. This review of literature and prospective pilot study is the first to address the potential correlation between correction of the pathological CXA and postoperative clinical outcome. The CXA is a useful sentinel to alert the radiologist and surgeon to the possibility of brainstem deformity or instability. Ten adult subjects with ventral brainstem compression, radiographically manifest as a kyphotic CXA, underwent correction of deformity (normalization of the CXA) prior to fusion and occipito-cervical stabilization. The subjects were assessed preoperatively and at one, three, six, and twelve months after surgery, using established clinical metrics: the visual analog pain scale (VAS), American Spinal InjuryAssociation Impairment Scale (ASIA), Oswestry Neck Disability Index, SF 36, and Karnofsky Index. Parametric and non-parametric statistical tests were performed to correlate clinical outcome with CXA. No major complications were observed. Two patients showed pedicle screws adjacent to but not deforming the vertebral artery on post-operative CT scan. All clinical metrics showed statistically significant improvement. Mean CXA was normalized from 135.8° to 163.7°. Correction of abnormal CXA correlated with statistically significant clinical improvement in this cohort of patients. The study supports the thesis that the CXA maybe an important metric for predicting the risk of brainstem and upper spinal cord deformation. Further study is feasible and warranted.

Neurological and spinal manifestations of the Ehlers-Danlos syndromes.

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression. This report also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto-occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS. © 2017 Wiley Periodicals, Inc.

Chemokine CXCL16 expression suppresses migration and invasiveness and induces apoptosis in breast cancer cells.

BACKGROUND: Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. METHODS: Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. RESULTS: We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. CONCLUSIONS: Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

Operative Epidemiology of the First Five Years in a New African Neurosurgery Training Center: The Experience in Rural Kenya at Tenwek Hospital 2016 to 2021.

BACKGROUND: One strategy to increase the availability of neurosurgical services in underserved regions within Sub-Saharan African countries is to create new residency training programs outside of cosmopolitan cities where programs may already exist. In 2016 Tenwek Hospital in rural western Kenya began offering full-time neurosurgical services and in 2020 inaugurated a residency training program. This review highlights the operative epidemiology of the first 5 years of the hospital's neurosurgical department. METHODS: A retrospective review of all cases performed by a neurosurgeon at Tenwek Hospital between September 2016 and February 2022 was performed. Patient demographics, surgical indications, length of stay, and in-hospital mortality rates were collected. RESULTS: A total of 1756 cases were retrievable. Of these, 1006 (57.3%) were male and mean age was 30 years (range 1 day to 97 years). Mean length of stay was 11 ± 2 days and in-hospital mortality rate was 4.4% (77 patients). The most common pathologies in children comprised hydrocephalus and spina bifida (42.5% and 21.1%, respectively); in adults, cranial trauma (28.2%), oncology (25.2%), and degenerative spine (18.5%) were most common. Trauma was the leading cause of death. CONCLUSIONS: The neurosurgical caseload of a rural hospital in an underserved area can provide not only an adequate neurosurgical volume, but a robust and varied exposure that is necessary for training safe and competent surgeons who are willing to remain in their countries of origin.

An early case of successful peripheral nerve repair in 1880: Francis L. Parker, MD.

The modern technique of epineural suture repair, along with a detailed reporting of functional restoration, came from Carl Hueter in 1873. While there is extensive information on peripheral nerve surgery throughout recorded history leading up to the 1800s, little early American scientific literature is available. While Schwann, Nissl, and Waller were publishing their work on nerve anatomy and physiology, Francis LeJau Parker was born. The South Carolina native would go on to describe one of the first American cases of peripheral nerve repair with the restoration of function. Francis Parker was born in 1836 in Abbeville, South Carolina. He gained local notoriety as one of the first American surgeons to suture a severed nerve, resulting in restored function. The case dates back to 1880, when a patient presented to his clinic with severing of the posterior interosseous nerve. The details of this case come from the archives of the South Carolina Medical Association. The authors reviewed these records in detail and provide a case description of nerve repair not previously reported in the modern literature. The history, neurological examination, and details of the case provide insight into the adroit surgical skills of Dr. Parker.

Safety and outcomes analysis: transcatheter implantation of autologous angiogenic cell precursors for the treatment of cardiomyopathy.

BACKGROUND: Stem cell transplantation is an emerging therapy for severe cardiomyopathy, proffering stem cell recruitment, anti-apoptosis, and proangiogenic capabilities. Angiogenic cell precursors (ACP-01) are autologous, lineage-specific, cells derived from a multipotent progenitor cell population, with strong potential to effectively engraft, form blood vessels, and support tissue survival and regeneration. METHODS: This IRB approved outcome analysis reports upon 74 consecutive patients who failed medical management for severe cardiomyopathy, and were selected to undergo transcatheter intramyocardial or intracoronary implantation of ACP-01. Serious adverse events (SAEs) were reported. Cell analysis was conducted for each treatment. The left ventricular ejection fraction (LVEF) was measured by multi-gated acquisition scan (MUGA) or echocardiogram at 4 months ± 1.9 months and 12 months ± 5.5 months. Patients reported quality of life statements at 6 months (± 5.6 months). RESULTS: Fifty-four of 74 patients met requirements for inclusion (48 males and five females; age 68.1 ± 11.3 years). The mean treatment cell number of 57 × 106 ACP-01 included 7.7 × 106 CD34 + and 21 × 106 CD31 + cells with 97.6% viability. SAEs included one death (previously unrecognized silent MI), ventricular tachycardia (n = 2) requiring cardioversion, and respiratory infection (n = 2). LVEF in the ischemic subgroup (n = 41) improved by 4.7% ± 9.7 from pre-procedure to the first follow-up (4 months ± 1.9 months) (p < 0.004) and by 7.2% ± 10.9 at final follow-up (n = 25) at average 12 months (p < 0.004). The non-ischemic dilated cardiomyopathy subgroup (n = 8) improved by 7.5% ± 6.0 at the first follow-up (p < 0.017) and by 12.2% ± 6.4 at final follow-up (p < 0.003, n = 6). Overall improvement in LVEF from pre-procedure to post-procedure was significant (Fisher's exact test p < 0.004). LVEF improvement was most marked in the patients with the most severe cardiomyopathy (LVEF < 20%) improving from a mean 14.6% ± 3.4% pre-procedurally to 28.4% ± 8% at final follow-up. Quality of life statements reflected improvement in 33/50 (66%), no change in 14/50 (28%), and worse in 3/50 (6%). CONCLUSION: Transcatheter implantation of ACP-01 for cardiomyopathy is safe and improves LVEF in the setting of ischemic and non-ischemic cardiomyopathy. The results warrant further investigation in a prospective, blinded, and controlled clinical study. TRIAL REGISTRATION: IRB from Genetic Alliance #APC01-001, approval date July 25, 2022. Cardiomyopathy is common and associated with high mortality. Stem cell transplantation is an emerging therapy. Angiogenic cell precursors (ACP-01) are lineage-specific endothelial progenitors, with strong potential for migration, engraftment, angiogenesis, and support of tissue survival and regeneration. A retrospective outcomes analysis of 53 patients with ischemic and non-ischemic dilated cardiomyopathy undergoing transcatheter implantation of ACP-01 demonstrated improvements in the left ventricular ejection fraction of 7.2% ± 10.9 (p < 0.004) and 12.2% ± 6.4, respectively, at 12 months (± 5) follow-up. Quality of life statements reflected improvement in 33/50 (66%) patients.

Refractory Syncope and Presyncope Associated with Atlantoaxial Instability: Preliminary Evidence of Improvement Following Surgical Stabilization.

BACKGROUND: The proclivity to atlantoaxial instability (AAI) has been widely reported for conditions such as rheumatoid arthritis and Down syndrome. Similarly, we have found a higher than expected incidence of AAI in hereditary connective tissue disorders. We demonstrate a strong association of AAI with manifestations of dysautonomia, in particular syncope and lightheadedness, and make preliminary observations as to the salutary effect of surgical stabilization of the atlantoaxial motion segment. METHODS: In an institutional review board-approved retrospective study, 20 subjects (16 women, 4 men) with hereditary connective tissue disorders had AAI diagnosed by computed tomography. Subjects underwent realignment (reduction), stabilization, and fusion of the C1-C2 motion segment. All subjects completed preoperative and postoperative questionnaires in which they were asked about performance, function, and autonomic symptoms, including lightheadedness, presyncope, and syncope. RESULTS: All patients with AAI reported lightheadedness, and 15 had refractory syncope or presyncope despite maximal medical management and physical therapy. Postoperatively, subjects reported a statistically significant improvement in lightheadedness (P = 0.003), presyncope (P = 0.006), and syncope (P = 0.03), and in the frequency (P < 0.05) of other symptoms related to autonomic function, such as nausea, exercise intolerance, palpitations, tremors, heat intolerance, gastroesophageal reflux, and sleep apnea. CONCLUSIONS: This study draws attention to the potential for AAI to present with syncope or presyncope that is refractory to medical management, and for surgical stabilization of AAI to lead to improvement of these and other autonomic symptoms.

Molecular Correlates of Long Survival in IDH-Wildtype Glioblastoma Cohorts.

IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or undersampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a "molecular grade IV" astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.

Sciatica Caused by Venous Varix Compression of the Sciatic Nerve.

BACKGROUND: The authors report the case of a 76-year-old woman presenting with leg pain, numbness, and weakness mimicking a lumbosacral radiculopathy. CASE DESCRIPTION: Initial lumbar spine magnetic resonance imaging demonstrated mild root compression, but lumbar decompression afforded only transient symptomatic relief. Postoperative magnetic resonance imaging of the lumbosacral plexus and sciatic nerve revealed a gluteal venous varix compressing the sciatic nerve just distal to the piriformis muscle. Neurolysis and surgical resection of the offending varix resulted in resolution of her symptoms. CONCLUSIONS: Variceal compression is a rare cause of extraspinal origin of lower extremity radicular pain. It should be considered if there is lack of correlation between radiologic findings and the clinical picture or if there is a failure of response to treatment of the assumed spinal cause.

Giant sacral meningeal diverticula: surgical implications of the "thecal tip" sign. Report of two cases.

The surgical anatomy of giant sacral meningeal diverticula varies greatly depending on whether they develop ventral or dorsal to the thecal sac and spinal nerve roots. The ability to distinguish between the two lesion types preoperatively is therefore advantageous. The authors present a method of distinguishing ventral from dorsal meningeal diverticula on magnetic resonance imaging using the "thecal tip sign." They also describe the differences in operative technique required for resection of each type of diverticular cyst.

CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life.

OBJECT: The authors conducted a study to assess safety, pain, and quality of life (QOL) outcomes following CyberKnife radiosurgical treatment of spinal tumors. METHODS: Data obtained in all patients with spinal tumors who underwent CyberKnife radiosurgery at Georgetown University Hospital between March 2002 and March 2003 were analyzed. Patients underwent examination, visual analog scale (VAS) pain assessment, and completed the 12-item Short Form Health Survey (SF-12) before treatment and at 1, 3, 6, 8, 12, 18, and 24 months following treatment. Fifty-one patients with 72 lesions (58 metastatic and 14 primary) were treated. The mean follow-up period was 1 year. Pain was improved, with the mean VAS score decreasing significantly from 51.5 to 21.3 at 4 weeks (p < 0.001). This effect on pain was durable, with a mean score of 17.5 at 1 year, which was still significantly decreased (p = 0.002). Quality of life was maintained throughout the study period. After 18 months, physical well-being was 33 (initial score 32; p = 0.96) and mental well-being was 43.8 (initial score 44.2; p = 0.97). (The mean SF-12 score is 50 +/- 10 [standard deviation].) Adverse effects included self-limited dysphagia (three cases), diarrhea (two cases), lethargy (three cases), paresthesias (one case), and wound dehiscence (one case). CONCLUSIONS: CyberKnife radiosurgery improves pain control and maintains QOL in patients treated for spinal tumors. Early adverse events are infrequent and minor. The authors await long-term follow-up data to determine late complications and tumor control rates.

Use of the telescopic plate spacer in treatment of cervical and cervicothoracic spine tumors.

OBJECTIVE: We investigated the mechanical and in vivo properties of a novel device, called the telescopic plate spacer (TPS), designed to promote restoration of height, alignment, and stability after cervical corpectomy for tumor. METHODS: The device first underwent mechanical testing. Comparisons were made with a commercially available anterior cervical plate. A caprine study was then performed. Twelve goats underwent a cervical corpectomy and placement of either a TPS filled with autograft or a plate and autograft. The animals were killed at 28 weeks and assessed for fusion. A prospective human study was then conducted. Fifteen patients with cervical or cervicothoracic tumors underwent corpectomy and placement of allograft-filled TPS. End points included pain scores and radiographic assessment of vertebral height, alignment, and stability. RESULTS: In the mechanical study, the TPS outperformed the anterior cervical plate in all modalities except for torsion stiffness and tension-bending failure load. The caprine study demonstrated fusion in six of six cases at 28 weeks in the TPS group, compared with four of six cases in the plate and autograft group. In the human study, patients (n = 15) were stabilized with the TPS after corpectomy (range, 1-3 levels; average, 1.7 levels). There were no failures of instrumentation or neurological deterioration. Stability was achieved in all patients, with an average follow-up of 9 months. Durable improvements in pain scores (P = 0.001), vertebral height (P = 0.002), and reduction of kyphosis (P = 0.046) were achieved. CONCLUSION: The TPS can be used to restore height, alignment, and stability after corpectomy.

Molecular biology of cervical myelopathy and spinal cord injury: role of oligodendrocyte apoptosis.

BACKGROUND CONTEXT: Rational design of treatment strategies for cervical myelopathy and spinal cord injury requires a working knowledge of the molecular biology underlying these pathological processes. The cellular process of apoptosis is an important component of tissue and organ development as well as the natural response to disease and injury. Recent studies have convincingly demonstrated that apoptosis also plays a pivotal role in numerous pathological processes, contributing to the adverse effects of various diseases and traumatic conditions. A growing body of evidence has implicated apoptosis as a key determinant of the extent of neurological damage and dysfunction after acute spinal cord injury and in chronic cervical myelopathy. PURPOSE: To provide clinicians and research investigators interested in spinal cord injury and myelopathy with a practical and up-to-date basic science review of cellular apoptosis in the context of spinal cord pathology. STUDY DESIGN/SETTING: A review of recently published or presented data from molecular biological, animal model and human clinical studies. METHODS: A computer-based comprehensive review of the English-language scientific and medical literature was performed in order to identify relevant publications with emphasis given to more recent studies. RESULTS: Investigation into the role of apoptosis in spinal cord injury and myelopathy has drawn the interest of an increasing number of researchers and has yielded a substantial amount of new information. CONCLUSIONS: Apoptosis is a fundamental biological process that contributes to preservation of health as well as development of disease. There is now strong evidence to support a significant role for apoptosis in secondary injury mechanisms after acute spinal cord injury as well in the progressive neurological deficits observed in such conditions as spondylotic cervical myelopathy.

Deformative stress associated with an abnormal clivo-axial angle: A finite element analysis.

BACKGROUND: Chiari malformation, functional cranial settling and subtle forms of basilar invagination result in biomechanical neuraxial stress, manifested by bulbar symptoms, myelopathy and headache or neck pain. Finite element analysis is a means of predicting stress due to load, deformity and strain. The authors postulate linkage between finite element analysis (FEA)-predicted biomechanical neuraxial stress and metrics of neurological function. METHODS: A prospective, Internal Review Board (IRB)-approved study examined a cohort of 5 children with Chiari I malformation or basilar invagination. Standardized outcome metrics were used. Patients underwent suboccipital decompression where indicated, open reduction of the abnormal clivo-axial angle or basilar invagination to correct ventral brainstem deformity, and stabilization/ fusion. FEA predictions of neuraxial preoperative and postoperative stress were correlated with clinical metrics. RESULTS: Mean follow-up was 32 months (range, 7-64). There were no operative complications. Paired t tests/ Wilcoxon signed-rank tests comparing preoperative and postoperative status were statistically significant for pain, bulbar symptoms, quality of life, function but not sensorimotor status. Clinical improvement paralleled reduction in predicted biomechanical neuraxial stress within the corticospinal tract, dorsal columns and nucleus solitarius. CONCLUSION: The results are concurrent with others, that normalization of the clivo-axial angle, fusion-stabilization is associated with clinical improvement. FEA computations are consistent with the notion that reduction of deformative stress results in clinical improvement. This pilot study supports further investigation in the relationship between biomechanical stress and central nervous system (CNS) function.