Congenital scoliosis due to a hemivertebra requires surgical stabilization prior to skeletal maturity if rapidly progressive curve growth occurs. Here the authors present the unique case of a man who, at the age of 12 years, had undergone Harrington rod placement for stabilization of progressive congenital scoliosis due to a T-11 hemivertebra and then, at the age of 53 years, presented with acutely progressive myelopathy due to spinal cord compression from an arachnoid web at T-11 despite a solid fusion mass at the prior surgical site. The patient underwent a posterior midline approach for resection of the T-11 pedicle at the level of the hemivertebra, intradural spinal cord detethering with resection of the arachnoid web at T-11, and T2–L2 instrumented fusion with deformity correction, leading to subsequent resolution of his acute myelopathic symptoms. In conclusion, arachnoid web formation superimposed on preexisting tension on the thoracic spinal cord from congenital scoliosis due to a T-11 hemivertebra caused acute myelopathy in an adult with a previously solid fusion mass from childhood. The resolution of acute myelopathy and halting of further progression occurred with pedicle resection, arachnoid web fenestration, and spinal deformity correction.
Molly E. Hubbard, Matthew A. Hunt, Kristen E. Jones and David W. Polly
John L. Gainer, Jason P. Sheehan, James M. Larner and David R. Jones
A new drug, trans sodium crocetinate (TSC), has been developed to enhance the delivery of oxygen to hypoxic tissues. Cancerous tumors, such as glioblastoma multiforme (GBM), are very hypoxic, and it has been suggested that radiation therapy (RT) is more beneficial if tumors are better oxygenated. A Phase I/II clinical trial was conducted to determine the effect of adding TSC to RT sessions.
An open, single-arm clinical trial incorporating the standard of care (SOC) for GBM was conducted at 18 clinical sites. There were 6 weeks of RT consisting of 2 Gy/day for 5 days/week, beginning after an initial resection or stereotactic biopsy to confirm GBM. Temozolomide (TMZ), 75 mg/m2, was given before each RT session. The TSC, 0.25 mg/kg, was intravenously administered around 45 minutes before an RT session 3 days/week, usually on Monday, Wednesday, and Friday.
A Phase I run-in period included 2 cohorts. The first cohort contained 3 patients who were given a half dose of the intravenous TSC (that is, 0.25 mg/kg, 3 times per week for only the first 3 weeks of RT). After a Safety Monitoring Committee (SMC) had verified that no dose-limiting toxicity (DLT) had occurred, a second cohort of 6 patients was given the same dosage of TSC but for the full 6 weeks of RT. After the SMC verified that no DLTs had occurred, Phase II began, with the administration of the full 18 doses of TSC. Fifty additional patients were enrolled during Phase II.
Following the completion of RT, the patients rested for a month. After that, SOC TMZ chemotherapy (150–200 mg/m2) was administered for 5 days of the 1st week of 6 monthly cycles. No TSC was administered during this chemotherapy phase or later in the trial. Any other follow-up therapies were administered at the discretion of the individual investigators.
Kaplan-Meier analysis showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the SOC. Survival for the biopsy-only subset of patients was 40%, as compared with 42.9% for those patients having a complete resection before treatment. In addition, 2 of the 3 Phase I, Cohort 1 patients survived at 2 years. Contrast MRI data suggested that considerable pseudoprogression had occurred. Both Karnofsky Performance Status (KPS) scores and quality of life (QOL) questionnaires indicated that a good quality of life existed for most patients throughout the trial. No serious adverse events occurring in the trial were attributed to TSC.
This trial contained a single arm consisting of 59 patients. The results strongly suggested that adding TSC during RT is beneficial for the treatment of GBM. Trans sodium crocetinate offers a novel, easily implemented way to combat hypoxia in tumor tissue.
Clinical trial registration no.: NCT01465347 (clinicaltrials.gov)
Gerald A. Grant, Sohail K. Mirza, Jens R. Chapman, H. Richard Winn, David W. Newell, Dolors T. Jones and M. Sean Grady
Object. The authors retrospectively reviewed 121 patients with traumatic cervical spine injuries to determine the risk of neurological deterioration following early closed reduction.
Methods. After excluding minor fractures and injuries without subluxation, the medical records and imaging studies (computerized tomography and magnetic resonance [MR] images) of 82 patients with bilateral and unilateral locked facet dislocations, burst fractures, extension injuries, or miscellaneous cervical fractures with subluxation were reviewed. Disc injury was defined on MR imaging as the presence of herniation or disruption: a herniation was described as deforming the thecal sac or nerve roots, and a disruption was defined as a disc with high T2-weighted signal characteristics in a widened disc space. Fifty-eight percent of patients presented with complete or incomplete spinal cord injuries. Thirteen percent of patients presented with a cervical radiculopathy, 22% were intact, and 9% had only transient neurological deficits in the field.
Early, rapid closed reduction, using serial plain radiographs or fluoroscopy and Gardner—Wells craniocervical traction, was achieved in 97.6% of patients. In two patients (2.4%) closed reduction failed and they underwent emergency open surgical reduction. The average time to achieve closed reduction was 2.1 ± 0.24 hours (standard error of the mean).
The incidence of disc herniation and disruption in the 80 patients who underwent postreduction MR imaging was 22% and 24%, respectively. However, the presence of disc herniation or disruption did not affect the degree of neurological recovery, as measured by American Spinal Injury Association motor score and the Frankel scale following early closed reduction. Only one (1.3%) of 80 patients deteriorated, but that occurred more than 6 hours following closed reduction.
Conclusions. Although disc herniation and disruption can occur following all types of traumatic cervical fracture subluxations, the incidence of neurological deterioration following closed reduction in these patients is rare. The authors recommend early closed reduction in patients presenting with significant motor deficits without prior MR imaging.
Report of two cases
Lindsay I. G. Worthley, David J. Cooper and Nigel Jones
✓ The authors describe two patients with traumatic cerebral edema and intracranial hypertension in whom the continued use of mannitol and furosemide resulted in a progressive lessening of the effect of these agents on the intracranial pressure (ICP) and caused prerenal failure. Intravenous administration of hypertonic saline (50 ml and 20 ml of a 5-mmol/ml saline solution over 10 minutes in Cases 1 and 2, respectively) produced a prolonged reduction in the ICP and improved renal function in both cases. It is suggested that if a reduction in ICP without diuresis is required in patients with traumatic cerebral edema, treatment with intravenous hypertonic saline should be considered.
Dustin K. Ragan, Jonathon Cerqua, Tiffany Nash, Robert C. McKinstry, Joshua S. Shimony, Blaise V. Jones, Francesco T. Mangano, Scott K. Holland, Weihong Yuan and David D. Limbrick Jr.
Assessment of ventricular size is essential in clinical management of hydrocephalus and other neurological disorders. At present, ventricular size is assessed using indices derived from the dimensions of the ventricles rather than the actual volumes. In a population of 22 children with congenital hydrocephalus and 22 controls, the authors evaluated the relationship between ventricular volume and linear indices in common use, such as the frontooccipital horn ratio, Evans' index, and the bicaudate index. Ventricular volume was measured on high-resolution anatomical MR images. The frontooccipital horn ratio was found to have a stronger correlation with both absolute and relative ventricular volume than other indices. Further analysis of the brain volumes found that congenital hydrocephalus produced a negligible decrease in the volume of the brain parenchyma.
James P. McAllister II, Arcangela S. Wood, Martha J. Johnson, Robert W. Connelly, David J. Skarupa, Michelle Secic, Mark G. Luciano, Neil G. Harris and Hazel C. Jones
Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a “third messenger” to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.
Irene Meissner, James Torner, John Huston III, Michele L. Rajput, David O. Wiebers, Lyell K. Jones Jr., Robert D. Brown Jr. and the International Study of Unruptured Intracranial Aneurysms Investigators
Investigators conducting the International Study of Unruptured Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to evaluate predictors of future hemorrhage in patients who had unruptured mirror aneurysms. These paired aneurysms in bilateral arterial positions mirror each other; their natural history is unknown.
Centers in the US, Canada, and Europe enrolled patients for prospective assessment of unruptured intracranial aneurysms. Central radiological review confirmed the presence or absence of mirror aneurysms in patients without a history of prior subarachnoid hemorrhage (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are compared.
Of 3120 patients with aneurysms treated in 61 centers, 376 (12%) had mirror aneurysms, which are more common in women than men (82% [n = 308] vs 73% [n = 1992], respectively; p <0.001) and in patients with a family history of aneurysm or SAH (p <0.001).
Compared with patients with nonmirror saccular aneurysms, a greater percentage of patients with mirror aneurysms had larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p <0.001). The most common distribution for mirror aneurysms was the middle cerebral artery (34% [126 patients]) followed by noncavernous internal carotid artery (32% ), posterior communicating artery (16% ), cavernous internal carotid artery (13% ), anterior cerebral artery/anterior communicating artery (3% ), and vertebrobasilar circulation (2% ). When these patients were compared with patients without mirror aneurysms, no statistically significant differences were found in age (mean age 54 years in both groups), blood pressure, smoking history, or cardiac disease. Aneurysm rupture rates were similar (3.0% for patients with mirror aneurysms vs 2.8% for those without).
Overall, patients with mirror aneurysms were more likely to be women, to report a family history of aneurysmal SAH, and to have larger aneurysms. The presence of a mirror aneurysm was not an independent predictor of future SAHs.
Robert T. Buckley, Weihong Yuan, Francesco T. Mangano, Jannel M. Phillips, Stephanie Powell, Robert C. McKinstry, Akila Rajagopal, Blaise V. Jones, Scott Holland and David D. Limbrick Jr.
The authors report the case of a 25-month-old boy who underwent endoscopic third ventriculostomy (ETV) for hydrocephalus resulting from aqueductal stenosis. The patient's recovery was monitored longitudinally and prospectively using MR diffusion tensor imaging (DTI) and formal neuropsychological testing. Despite minimal change in ventricle size, improvement in the DTI characteristics and neurodevelopmental trajectory was observed following ETV. These data support the use of DTI as a biomarker to assess therapeutic response in children undergoing surgical treatment for hydrocephalus. In the patient featured in this report, DTI appeared to provide more information regarding postoperative neurodevelopmental outcome than ventricle size alone.
Victor Chang, Jason M. Schwalb, David R. Nerenz, Lisa Pietrantoni, Sharon Jones, Michelle Jankowski, Nancy Oja-Tebbe, Stephen Bartol and Muwaffak Abdulhak
Given the scrutiny of spine surgery by policy makers, spine surgeons are motivated to demonstrate and improve outcomes, by determining which patients will and will not benefit from surgery, and to reduce costs, often by reducing complications. Insurers are similarly motivated. In 2013, Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network (BCN) established the Michigan Spine Surgery Improvement Collaborative (MSSIC) as a Collaborative Quality Initiative (CQI). MSSIC is one of the newest of 21 other CQIs that have significantly improved—and continue to improve—the quality of patient care throughout the state of Michigan.
MSSIC focuses on lumbar and cervical spine surgery, specifically indications such as stenosis, disk herniation, and degenerative disease. Surgery for tumors, traumatic fractures, deformity, scoliosis, and acute spinal cord injury are currently not within the scope of MSSIC. Starting in 2014, MSSIC consisted of 7 hospitals and in 2015 included another 15 hospitals, for a total of 22 hospitals statewide. A standardized data set is obtained by data abstractors, who are funded by BCBSM/BCN. Variables of interest include indications for surgery, baseline patient-reported outcome measures, and medical history. These are obtained within 30 days of surgery. Outcome instruments used include the EQ-5D general health state score (0 being worst and 100 being the best health one can imagine) and EQ-5D-3 L. For patients undergoing lumbar surgery, a 0 to 10 numeric rating scale for leg and back pain and the Oswestry Disability Index for back pain are collected. For patients undergoing cervical surgery, a 0 to 10 numeric rating scale for arm and neck pain, Neck Disability Index, and the modified Japanese Orthopaedic Association score are collected. Surgical details, postoperative hospital course, and patient-reported outcome measures are collected at 90-day, 1-year, and 2-year intervals.
As of July 1, 2015, a total of 6397 cases have been entered into the registry. This number reflects 4824 eligible cases with confirmed surgery dates. Of these 4824 eligible cases, 3338 cases went beyond the 120-day window and were considered eligible for the extraction of surgical details, 90-day outcomes, and adverse events. Among these 3338 patients, there are a total of 2469 lumbar cases, 862 cervical cases, and 7 combined procedures that were entered into the registry.
In addition to functioning as a registry, MSSIC is also meant to be a platform for quality improvement with the potential for future initiatives and best practices to be implemented statewide in order to improve quality and lower costs. With its current rate of recruitment and expansion, MSSIC will provide a robust platform as a regional prospective registry. Its unique funding model, which is supported by BCBSM/BCN, will help ensure its longevity and viability, as has been observed in other CQIs that have been active for several years.
Kristen E. Jones, Ava M. Puccio, Kathy J. Harshman, Bonnie Falcione, Neal Benedict, Brian T. Jankowitz, Martina Stippler, Michael Fischer, Erin K. Sauber-Schatz, Anthony Fabio, Joseph M. Darby and David O. Okonkwo
Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI.
Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency.
Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003).
Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis.