Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

STUDY DESIGN: Randomized controlled trial with single-blinded primary outcome assessment. OBJECTIVES: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). SETTING: Six SCI treatment centers in the United States and Israel. METHODS: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-B or better at ≥6 months. Safety was assessed by analysis of adverse events (AEs). RESULTS: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942). CONCLUSION: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

Atlantoaxial rotatory fixation after ventriculoperitoneal shunting.

Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in this same group. We present the first reported case of AARF following a VP shunt procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A second operation was performed 2 days later to optimize catheter placement. Postoperative neck pain was attributed to tunneling of the subcutaneous catheter. 2 months after surgery, the child had minimal neck discomfort but maintained his head in a "cock-robin" position. Plain radiographs and computed tomographic (CT) images confirmed AARF. The child was admitted and placed in halo traction. After 3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re-alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3 months of immobilization in a halo-vest apparatus, the halo was removed. At 8-year follow-up, the clinical examination is normal and repeat imaging studies remain normal. Due to surgical positioning, and postoperative signs attributed to normal postoperative pain, an AARF was not initially recognized. This case represents the first time that AARF has been reported following a VP shunt procedure.

Reduced expression of plasma membrane calcium ATPase 2 and collapsin response mediator protein 1 promotes death of spinal cord neurons.

The mechanisms underlying neuronal pathology and death in the spinal cord (SC) during inflammation remain elusive. We previously showed the important role of plasma membrane calcium ATPases (PMCAs) in the survival of SC neurons, in vitro. We also postulated that a decrease in PMCA2 expression could cause neuronal death during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The current studies were undertaken to define the specific contribution of PMCA2 to degeneration of SC neurons, the effectors downstream to PMCA2 mediating neuronal death and the triggers that reduce PMCA2 expression. We report that knockdown of PMCA2 in SC neurons decreases collapsin response mediator protein 1 (CRMP1) levels. This is followed by cell death. Silencing of CRMP1 expression also leads to neuronal loss. Kainic acid reduces both PMCA2 and CRMP1 levels and induces neuronal death. Administration of an alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor antagonist, at onset or peak of EAE, restores the decreased PMCA2 and CRMP1 levels to control values and ameliorates clinical deficits. Thus, our data link the reduction in PMCA2 expression with perturbations in the expression of CRMP1 and the ensuing death of SC neurons. This represents an additional mechanism underlying AMPA/kainate receptor-mediated excitotoxicity with relevance to neurodegeneration in EAE.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

STUDY DESIGN: Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). OBJECTIVES: Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. SETTING: Subjects were recruited to one of six international study centers. METHODS: Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. RESULTS: Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. CONCLUSION: The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Intradiscal electrothermal annuloplasty: the IDET procedure.

Intradiscal electrothermal annuloplasty is a minimally invasive procedure for the treatment of lumbar degenerative disc disease. This procedure has been used in the lumbar spine of patients who have failed conservative treatment regimens and who might otherwise be candidates for a spinal fusion procedure. As this is a new, recently developed procedure, there is only relatively short-term follow-up data available, and as such, the procedure has not been widely accepted.

Metastatic spinal tumors.

Metastatic spinal tumors are the most common type of malignant lesions of the spine. Prompt diagnosis and identification of the primary malignancy is crucial to overall treatment. Numerous factors affect outcome including the nature of the primary cancer, the number of lesions, the presence of distant nonskeletal metastases, and the presence and/or severity of spinal cord compression. Initial management consists of chemotherapy, external beam radiotherapy, and external orthoses. Surgical intervention must be carefully considered in each case. Patients expected to live longer than 12 weeks should be considered as candidates for surgery. Indications for surgery include intractable pain, spinal cord compression, and the need for stabilization of impending pathological fractures. Whereas various surgical approaches have been advocated, anterior-approach surgery is the most accepted procedure for spinal cord decompression. Posterior approaches have also been used with success, but they require longer-length fusion. To obtain a stable fixation, the placement of instrumentation, in conjunction with judicious use of polymethylmethacrylate augmentation, is crucial. Preoperative embolization should be considered in patients with extremely vascular tumors such as renal cell carcinoma. Vertebroplasty, a newly described procedure in which the metastatic spinal lesions are treated via a percutaneous approach, may be indicated in selected cases of intractable pain caused by non- or minimally fractured vertebrae.

Ruptured intracranial aneurysm in an adolescent with Alport's syndrome--a new expression of type IV collagenopathy: case report.

BACKGROUND: Aneurysmal subarachnoid hemorrhage is uncommon in the pediatric and adolescent age groups. Collagenopathies, particularly of collagen type III and IV, have been recognized in the pathogenesis of intracranial (i.c.) aneurysms in recent studies of cerebrovascular immunoreactivity and the molecular architecture of the walls of cerebral blood vessels. Alport's syndrome is a genetic disease characterized by imperfect synthesis of type IV collagen leading to sensorineural hearing loss and hematuria. The hematuria results from an abnormal synthesis of the type IV collagen of the glomerular basement membrane. CASE DESCRIPTION: After a motor vehicle accident, this 14-year-old male driver presented with diffuse subarachnoid hemorrhage confirmed by computerized tomography. Subsequent cerebral angiography revealed a left carotid artery bifurcation aneurysm. A retrospective review of the patient's history disclosed renal biopsy-proven hereditary Alport's syndrome. The patient underwent left pterional craniotomy and clipping of the aneurysm, which had clearly ruptured. CONCLUSIONS: The authors present the first clinical observation of a ruptured cerebral aneurysm in an adolescent male with Alport's syndrome. In this case the type IV collagenopathy of Alport's syndrome may have contributed to the genesis of this adolescent's aneurysm. Intracranial aneurysms may be more common in the population of collagenopathies than previously suspected and non-invasive screening may be appropriate.

Acute pancreatitis complicating anterior lumbar interbody fusion.

Postoperative pancreatitis may occur following surgery in regions remote from the pancreas and the biliary tree. Though uncommon, it carries a high mortality rate. Pancreatitis complicating spinal surgery is extremely rare. This report describes a case of acute pancreatitis following an anterior lumbar interbody fusion and discusses the possible mechanisms of pancreatic cellular injury.

Visceral and vascular complications resulting from anterior lumbar interbody fusion.

OBJECT: The literature on abdominal and general surgery-related complications following anterior lumbar interbody fusion (ALIF) is scant. In this retrospective review of 60 patients in whom ALIF was performed at their institutions between 1996 and 1998, the authors detail the associated complications and their correlation with perioperative factors. The causes, strategies for their avoidance, and the clinical course of these complications are also discussed. METHODS: The study group was composed of 31 men and 29 women whose mean age was 42 years (range 29-71 years). The preoperative diagnosis was discogenic back pain in 33 patients (55%); failed back syndrome in 11 (18.3%); pseudarthrosis in five (8.3%); postlaminectomy syndrome in four (6.6%); spondylolisthesis in three (5%); burst fracture in two (3.3%); and malignancy in two (3.3%). A retroperitoneal approach to the spine was used in 57 of the 60 patients. One interspace was exposed in 28 patients (46.6%), two in 28 (46.6%), and three in four (6.6%). Discectomy and interbody fusion in which the authors placed titanium cages or bone dowels was performed in 56 patients and corpectomy with instrumentation in four. Seven (11.6%) of 60 patients had undergone previous abdominal surgery and 29 (48.3%) had undergone previous spinal surgery. The follow-up period averaged 12+/-4 months (mean+/-standard deviation). Twenty-four general surgery-related complications occurred in 23 patients (38.3%), including sympathetic dysfunction in six; vascular injury in four; somatic neural injury in three; sexual dysfunction in three; prolonged ileus in three; wound incompetence in two; and deep venous thrombosis, acute pancreatitis, and bowel injury in one patient each. There were no deaths. The incidence of complications was not associated with underlying diagnosis (p>0.1), age (p>0.5), previous abdominal or spinal surgery (p>0.1), or the number of levels exposed (p>0.1). CONCLUSIONS: This report provides a detailed analysis of the general surgery-related complications following ALIF. Although many of these complications have been recognized in the literature, the significance of sympathetic dysfunction appears to have been underestimated. The high incidence of complications in this series likely reflects the strict criteria. Many of these complications were minor and resolved over time without long-term sequelae.

Pseudosparing of the endplate: a potential pitfall in using MR imaging to diagnose infectious spondylitis.

OBJECTIVE: The objective of this study was to describe a potential pitfall in using MR imaging to diagnose infectious spondylitis called "pseudosparing" of the endplate, in which the diseased endplate appears to be better defined than a healthy endplate. CONCLUSION: Poor definition of the endplate is a classic radiographic finding in infectious spondylitis; on MR imaging, however, increased conspicuity, or "pseudosparing," was common in our study. Pseudosparing occurs when the normal chemical shift artifact seen in healthy endplates is lost as a result of infiltration of the bone marrow by a pathologic process.

Type A immunoglobulin deficiency presenting as a mixed polymicrobial brain abscess: case report.

OBJECTIVE AND IMPORTANCE: We present a case report of a patient with a left frontal brain abscess. Cultures obtained from the abscess at the time of surgery were identified as dental flora known to establish a synergistic relationship in polymicrobial infections. This type of synergistic relationship makes the clearance of an infection more difficult for an intact immune system. A serum immunoglobulin (Ig) Type A deficiency was identified postoperatively. This immunodeficiency may have contributed to the development of the abscess. CLINICAL PRESENTATION: The patient presented with headaches and photophobia. Computed tomography of the head performed with intravenously administered contrast demonstrated a left frontal brain abscess. INTERVENTION: The patient was operated on through a left frontal approach, carefully avoiding the frontal sinus. The abscess was aspirated, and the patient was treated with intravenous antibiotics for several weeks. Postoperatively, the patient did well. There were no signs of enhancement on follow-up computed tomographic scans at 7 and 12 months postoperatively. CONCLUSION: Through a comprehensive immunological workup, an IgA deficiency was identified postoperatively. Although the deficiency of a single type of Ig may be asymptomatic, complications from recurrent or chronic bacterial infections may occur. The deficiency of IgA, combined with a synergistic polymicrobial infection, contributed to the development of an intracranial abscess. A patient presenting with a brain abscess without any predisposing medical history should be evaluated for an underlying immune deficiency.

"En-bloc" vertebrectomy in the mobile lumbar spine.

BACKGROUND: Primary tumors of the vertebral bodies have previously been treated with total or subtotal excision in a piecemeal fashion (intralesional excision). Radiation therapy has been used to help control tumor growth. Recurrence rates with an intralesional, piecemeal removal of vertebral tumors have been unacceptably high. This study describes a method to excise a lumbar vertebra "en-bloc," and in the process, to perform a marginal (extralesional) resection of a primary tumor of the mobile lumbar spine that allows for a potential surgical cure. METHODS: A combined posterior-anterior procedure allows for an extralesional, marginal resection of the tumor and the involved vertebra. All posterior bony elements, including the pedicles and the adjacent intervertebral discs, are removed via a posterior approach. An anterior, retroperitoneal approach is then used to remove the vertebral body/tumor as a single specimen. The nerve roots at the involved levels are spared and the spine is instrumented and fused both posteriorly and anteriorly. RESULTS: Three patients successfully had combined posterior-anterior resections of lumbar vertebral chordomas. No permanent neurological complications occurred. Overall morbidity of the procedure was acceptable. At 31-month follow-up, no tumor recurrence has been detected. CONCLUSIONS: "En-bloc" resection of a primary vertebral tumor of the lumbar spine is technically demanding, but potentially curative. The alternative approaches-intralesional excision, radiation therapy, or a combination-are unable to cure these tumors. Long-term, 10-year follow-up will be necessary to confirm whether this en-bloc approach provides a surgical cure.

Psychopharmacologic treatment of acquired attention disorders in children with brain injury.

This investigation examined the efficacy of psychostimulant therapy in alleviating neurobehavioral dysfunction attendant to pediatric brain injury. The most commonly reported neurobehavioral sequelae associated with head injury in the pediatric population involve deficits along the attentional matrix. This is also the most common objectively documented neurobehavioral finding among children as well as adults. There are several investigations in the adult literature which have employed the use of psychostimulants in treating both psychiatric and neuropsychological residua associated with head injury. Overall, the results of these studies are equivocal, but suggest a beneficial impact on general functioning. The present prospective investigation utilized a double-blind, placebo-controlled, cross-over experimental design to examine the efficacy of methylphenidate in treating children with acquired attentional disorders secondary to brain injury. A cohort of 14 children with varying degrees of head injury were recruited for participation. As expected, differences between drug and placebo conditions uniformly achieved statistical significance. Additionally, there were no differences in performance between baseline and placebo conditions on neurobehavioral tasks of attention and concentration. Current findings suggest that methylphenidate (and probably other psychostimulants such as Cylert, Adderal, Wellbutrin and dextroamphetamine sulfate) is an extremely effective agent in treating attentional disorders secondary to brain injury in children.

Steroids and gunshot wounds to the spine.

OBJECTIVE: The second National Acute Spinal Cord Injury Study demonstrated that there were neurological benefits from "spinal cord injury" doses of methylprednisolone for blunt spinal cord injuries. In this review, we examined the relative risk/benefit ratio of intravenously treating spinal gunshot wound victims with steroids. METHODS: A retrospective review was conducted of 254 consecutive patients who were treated between 1979 and 1994 for gunshot wounds to the spine (C1-L1) and a spinal cord injury. Three subgroups were established based on the administration of the steroids methylprednisolone (National Acute Spinal Cord Injury Study 2 protocol), dexamethasone (initial dose, 10-100 mg), and no steroids. All patients who received steroids were initially treated at another hospital and then transferred. No patients received steroids at our institution. The data analyzed included neurological outcome and infectious and noninfectious complications. RESULTS: No statistically significant neurological benefits were demonstrable from the use of steroids (methylprednisolone, dexamethasone). Infectious complications were increased in both groups receiving steroids (not statistically significant). Gastrointestinal complications were significantly increased in the dexamethasone group (P = 0.021), and pancreatitis was significantly increased in the methylprednisolone group (P = 0.040). The mean duration of follow-up was 56.3 months. CONCLUSION: In this retrospective, nonrandomized review, no neurological benefits were detectable from intravenously administered steroids after a gunshot wound to the spine. Both infectious and noninfectious complication rates were higher in the groups receiving steroids. Patients who sustain a spinal cord injury secondary to a gunshot wound to the spine should not be treated with steroids until the efficacy of such treatment is proven in a controlled study.

MRI of pituitary abscess: two cases and review of the literature.

Pituitary abscesses, rare lesions, may be divided into primary and secondary types. Primary pituitary abscesses occur within a previously healthy gland, while secondary abscesses arise within an existing lesion, such as an adenoma, craniopharyngioma, or Rathke's cleft cyst. Secondary abscesses share radiologic characteristics with the lesions from which they arise. There has been no review of the MRI characteristics of primary pituitary abscesses. We report two cases and review the literature. The typical primary pituitary abscess gives the same or slightly lower signal than brain on T1-weighted images, and could be mistaken for a solid mass or presumed to represent a pituitary adenoma. Contrast-enhanced images are useful, demonstrating absence of central enhancement, suggesting a fluid or necrotic center. In one of our cases, meningeal enhancement was obvious; this has not been reported previously and may be diagnostic, when associated with a rim-enhancing pituitary mass.

Surgical anatomy of the vertebral arteries.

STUDY DESIGN: This study compared direct measurements of the distances between the vertebral arteries in the cervical spines of human cadaver specimens with data obtained from axial computed tomography images of these specimens. OBJECTIVE: To determine whether the information obtained from a computed tomography scan can be used reliably to predict the true anatomic location of the vertebral arteries and, in so doing, provide accurate guidelines for the lateral extent of anterior cervical decompressive procedures. SUMMARY OF BACKGROUND DATA: Iatrogenic vertebral artery injury during anterior cervical surgery is uncommon, potentially catastrophic, and avoidable. METHODS: The means and standard deviation of measurements of the location of the cervical segment of the vertebral arteries obtained with high-precision, digital calipers by direct gross anatomic dissection of 16 adult (eight male, eight female) cadaver specimens were recorded. These measurements were compared with computed tomography scan data obtained on the same specimens. RESULTS: The mean distances between the vertebral arteries progressively increased from C3 to C6. Computed tomography scan measurements of the distance between the cervical foramina transversaria were consistently smaller than direct measurements of the gross specimens. At C6, the computed tomography scan data were significantly less than the gross anatomic data. CONCLUSIONS: According to these data, computed tomography scan measurements may be used safely and accurately to plan the lateral extent of anterior cervical decompressive surgical procedures. Although the data obtained from the gross anatomic dissections may serve as guidelines to assist the surgeon, the authors recommend a careful review of the preoperative computed tomography scan on an individual case-by-case basis as the safest method to plan for anterior cervical surgery.

Thoracolumbar infections in penetrating injuries to the spine.

A detailed review of the TJUH experience and the published literature on gunshot and stab wounds to the spine has been presented. The following statements are supported. (1) Military (high-velocity) gunshot wounds are distinct entities, and the management of these injuries cannot be carried over to civilian (low-velocity) handgun wounds. (2) Gunshot wounds with a resultant neurologic deficit are much more common than stab wounds and carry a worse prognosis. (3) Spinal infections are rare following a penetrating wound of the spine and a high index of suspicion is needed to detect them. (4) Extraspinal infections (septic complications) are much more common than spinal infections following a gunshot or stab wound to the spine. (5) Steroids are of no use in gunshot wounds to the spine. In fact, there was an increased incidence of spinal and extraspinal infections without a difference in neurologic outcome compared with those who did not receive steroids. (6) Spinal surgery is rarely indicated in the management of penetrating wounds of the spine. The recommendations for treatment at TJUH of victims of gunshot or stab wounds with a resultant neurologic deficit are as follows. (1) Spine surgery is indicated for progressive neurologic deficits and persistent cerebrospinal fluid leaks (particularly if meningitis is present), although these situations rarely occur. (2) Consider spine surgery for incomplete neurologic deficits with radiographic evidence of neural compression. Particularly in the cauda equina region, these surgeries may be technically demanding because of frequent dural violations and nerve root injuries/extrusions. These cases must be evaluated in an individual case-by-case manner. The neurologic outcomes of patients with incomplete neurologic deficits at TJUH who underwent acute spine surgery (usually for neural compression secondary to a bullet) were worse than the outcomes for the patients who did not have spine surgery. A selection bias against the patients undergoing spine surgery was likely present as these patients had evidence of ongoing neural compression. (3) A high index of suspicion is necessary to detect spinal and extraspinal infections. (4) Do not use glucorticoid steroids for gunshot wound victims. (5) Conservative (nonoperative) treatment with intravenous broad spectrum antibiotics and tetanus prophylaxis is the sole therapy indicated in the majority of patients who sustain a penetrating wound to the thoracic or lumbar spines.

Giant paraganglioma of the cauda equina in adolescence: magnetic resonance imaging demonstration.

A case of giant paraganglioma of the cauda equina is presented. This is only the second reported case in a minor and the first with magnetic resonance imaging. At 13 cm long, this is the largest paraganglioma of the cauda equina ever recorded.

Candidal pituitary abscess: case report.

We report a case of a culture-proven intrasellar Candida albicans abscess. A 36-year-old woman presented with a history of headaches, menstrual irregularities, and mild symptoms of diabetes insipidus. She was neurologically intact at the time of a transsphenoidal surgery for a presumed pituitary adenoma. An extensive work-up revealed that although the patient was seronegative for human immunodeficiency virus, she was immunocompromised with a T-cell dysfunction. Fungal abscesses of the pituitary gland have rarely been reported. This is the first documented case of a patient who is seronegative for human immunodeficiency virus who becomes infected by an ordinarily innocuous fungus, Candida albicans.