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We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal–truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E−3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile. This article is protected by copyright. All rights reserved

OBJECTIVE As odontoid process fractures become increasingly common in the aging population, a technical understanding of treatment approaches is critical. 3D image guidance can improve the safety of posterior cervical hardware placement, but few studies have explored its utility in anterior approaches. The authors present in a stepwise fashion the technique of odontoid screw placement using the Medtronic O-arm navigation system and describe their initial institutional experience with this surgical approach. METHODS The authors retrospectively reviewed all cases of anterior odontoid screw fixation for Type II fractures at an academic medical center between 2006 and 2015. Patients were identified from a prospectively collected institutional database of patients who had suffered spine trauma. A standardized protocol for navigated odontoid screw placement was generated from the collective experience at the authors' institution. Secondarily, the authors compared collected variables, including presenting symptoms, injury mechanism, surgical complications, blood loss, operative time, radiographically demonstrated nonunion rate, and clinical outcome at most recent follow-up, between navigated and nonnavigated cases. RESULTS Ten patients (three female; mean age 61) underwent odontoid screw placement. Most patients presented with neck pain without a neurological deficit after a fall. O-arm navigation was used in 8 patients. An acute neck hematoma and screw retraction, each requiring surgery, occurred in 2 patients in whom navigation was used. Partial vocal cord paralysis occurred after surgery in one patient in whom no navigation was used. There was no difference in blood loss or operative time with or without navigation. One patient from each group had radiographic nonunion. No patient reported a worsening of symptoms at follow-up (mean duration 9 months). CONCLUSIONS The authors provide a detailed step-by-step guide to the navigated placement of an odontoid screw. Their surgical experience suggests that O-arm–assisted odontoid screw fixation is a viable approach. Future studies will be needed to rigorously compare the accuracy and efficiency of navigated versus nonnavigated odontoid screw placement.

Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks.

The hippocampus is integral to working and episodic memory and is a central region of interest in diseases affecting these processes. Pig models are widely used in translational research and may provide an excellent bridge between rodents and nonhuman primates for CNS disease models because of their gyrencephalic neuroanatomy and significant white matter composition. However, the laminar structure of the pig hippocampus has not been well characterized. Therefore, we histologically characterized the dorsal hippocampus of Yucatan miniature pigs and quantified the cytoarchitecture of the hippocampal layers. We then utilized stereotaxis combined with single-unit electrophysiological mapping to precisely place multichannel laminar silicon probes into the dorsal hippocampus without the need for image guidance. We used in vivo electrophysiological recordings of simultaneous laminar field potentials and single-unit activity in multiple layers of the dorsal hippocampus to physiologically identify and quantify these layers under anesthesia. Consistent with previous reports, we found the porcine hippocampus to have the expected archicortical laminar structure, with some anatomical and histological features comparable to the rodent and others to the primate hippocampus. Importantly, we found these distinct features to be reflected in the laminar electrophysiology. This characterization, as well as our electrophysiology-based methodology targeting the porcine hippocampal lamina combined with high-channel-count silicon probes, will allow for analysis of spike-field interactions during normal and disease states in both anesthetized and future awake behaving neurophysiology in this large animal.

Object Outcomes in clinical trials on trigeminal pain therapies require instruments with demonstrated reliability and validity. The authors evaluated the Brief Pain Inventory (BPI) in its existing form plus an additional 7 facial-specific items in patients referred to a single neurosurgeon for a diagnosis of facial pain. The complete 18-item instrument is referred to as the BPI-Facial. Methods This study was a cross-sectional analysis of patients who completed the BPI-Facial. The diagnosis of classic versus atypical trigeminal neuralgia (TN) was made before analyzing the questionnaire results. A hypothesis-driven factor analysis was used to determine the principal components of the questionnaire. Item reliability and questionnaire validity were tested for these specific constructs. Results Data from 156 patients were analyzed, including 114 patients (73%) with classic and 42 (27%) with atypical TN. Using orthomax rotation factor analysis, 3 factors with an eigenvalue > 1.0 were identified—pain intensity, interference with general activities, and facial-specific pain interference—accounting for 97.6% of the observed item variance. Retention of the 3 factors was confirmed via a Cattell scree plot. Internal reliability was demonstrated by calculating Cronbach's α: 0.86 for pain intensity, 0.89 for interference with general activities, 0.95 for facial-specific pain interference, and 0.94 for the entire instrument. Initial validity of the BPI-Facial instrument was supported by the detection of statistically significant differences between patients with classic versus atypical pain. Patients with atypical TN rated their facial pain as more intense (atypical 6.24 vs classic 5.03, p = 0.013) and as having greater interference in general activities (atypical 6.94 vs classic 5.43, p = 0.0033). Both groups expressed high levels of facial-specific pain interference (atypical 6.34 vs classic 5.95, p = 0.527). Conclusions The BPI-Facial is a rigorous measure of facial pain in patients with TN and appears to have sound psychometric properties and is responsive to differences between classic and atypical TN. Future studies must assess the instrument's test-retest reliability, validity in additional populations, and responsiveness with respect to changes in patient outcomes following neurosurgical interventions and medical therapies.

Pulmonary complications are frequently observed after severe traumatic brain injury (TBI), but little is known about the consequences of lung injury on brain tissue oxygenation and metabolism.We examined the association between lung function and brain tissue oxygen tension (PbtO2) in patients with severe TBI.We analyzed data from 78 patients with severe, nonpenetrating TBI who underwent continuous PbtO2 and intracranial pressure monitoring. Acute lung injury was defined by the presence of pulmonary infiltrates with a PaO2/FiO2 (PF) ratio less than 300 and the absence of left ventricular failure. A total of 587 simultaneous measurements of PbtO2 and PF ratio were examined using longitudinal data analysis.PbtO2 correlated strongly with PaO2 and PF ratio (P.05) independent of PaCO2, brain temperature, cerebral perfusion pressure, and hemoglobin. Acute lung injury was associated with lower PbtO2 (34.6 +/- 13.8 mm Hg at PF ratio300 vs 30.2 +/- 10.8 mm Hg [PF ratio 200-300], 28.9 +/- 9.8 mm Hg [PF ratio 100-199], and 21.1 +/- 7.4 mm Hg [PF ratio100], all P values.01). After adjusting for intracranial pressure, Marshall computed tomography score, and APACHE II (Acute Physiology and Chronic Health Evaluation) score, acute lung injury was an independent risk factor for compromised PbtO2 (PbtO220 mm Hg; adjusted odds ratio: 2.13, 95% confidence interval: 1.21-3.77; P.01).After severe TBI, PbtO2 correlates with PF ratio. Acute lung injury is associated with an increased risk of compromised PbtO2, independent from intracerebral and systemic injuries. Our findings support the use of lung-protective strategies to prevent brain hypoxia in TBI patients.

The hypoxia and proliferation index increase with grade in human glial tumors, but there is no agreement whether either has prognostic importance in glioblastomas. We evaluated these end points individually and together in 16 de novo human glioblastomas using antibodies against the 2-nitmimidazole hypoxia detection agent EF5 and the proliferation detection agent Ki-67. Frozen tumor tissue sections were fluorescence-stained for nuclei (Hoechst 33342), hypoxia (anti-EF5 antibodies), and proliferation (anti-Ki-67 antibodies). EF5 binding adjacent to Ki-67+ cells, overall EF5 binding, the ratio of these values, and the proliferation indexwere evaluated. Patients were classified using recursive partitioning analysis and followed up until recurrence and/or death. Recursive partitioning analysis was statistically significant for survival ( P = .0026). Overall EF5 binding, EF5 binding near Ki-67+ cells, and proliferation index did not predict recurrence. Two additional survival analyses based on ratios of the overall EF5 binding to EF5 binding near Ki-67+ cells were performed. High and low ratio values were determined by two cutoff points: ( a ) the 50% value for the ratio [EF5/Ki-67 Binding ]/[Tumor binding ] = Ratio EF5 50% and ( b ) the median EF5 value (75.6%) of the ratio [EF5/Ki-67 Binding ]/[Tumor binding ] = Ratio patients median . On the basis of the Ratio EF5 50% , recurrence ( P = .0074) and survival ( P = .0196) could be predicted. Using the Ratio patients median , only survival could be predicted ( P = .0291). In summary, patients had a worse prognosis if the [EF5/Ki-67 Binding ]/[Tumor binding ] ratio was high. A hypothesis for the mechanisms and translational significance of these findings is discussed.

Object Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. Methods Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. Results Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94–0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95–0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96–0.99). Conclusions Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

Neural progenitor cells (NPCs) have been investigated as potential vehicles for brain tumor therapy because they have been shown to migrate toward central nervous system gliomas and can be genetically engineered to deliver cytotoxic agents to tumors. The mechanisms that regulate migration of NPCs to tumors are not fully understood. By means of microarray analysis, polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry, we found that monocyte chemoattractant protein-1 (MCP-1/CCL-2) was expressed in experimental brain tumor cells in vivo and in vitro. CCR2, the receptor for MCP-1, was expressed on C17.2 NPCs. We used a modified Boyden chamber assay and found increased migration of NPCs in vitro in response to MCP-1. By means of an in vivo model for NPC migration, we found evidence of NPC migration toward areas of MCP-1 infusion in rat brains. An understanding of NPC migration mechanisms may be used to enhance delivery of cytotoxic agents to brain tumor cells.

✓The authors report the case of an 18-month-old girl who presented with a ruptured anterior communicating artery aneurysm, and who was later diagnosed with Takayasu arteritis. Her initial aneurysm was successfully treated with clip application. However, over a 6-month period she had multiple ruptures from new and rapidly recurring aneurysms adjacent to the clips. These aneurysms were treated with repeated craniotomy and clip application and then with endovascular coil placement. Aneurysmal subarachnoid hemorrhage is a rare presentation of Takayasu arteritis. To the authors' knowledge, this is the youngest reported patient with Takayasu arteritis to present with a ruptured cerebral aneurysm.

Minichromosomes of wild-type polyomavirus were previously shown to be highly acetylated on histones H3 and H4 compared either to bulk cell chromatin or to viral chromatin of nontransforming hr-t mutants, which are defective in both the small T and middle T antigens. A series of site-directed virus mutants have been used along with antibodies to sites of histone modifications to further investigate the state of viral chromatin and its dependence on the T antigens. Small T but not middle T was important in hyperacetylation at major sites in H3 and H4. Mutants blocked in middle T signaling pathways but encoding normal small T showed a hyperacetylated pattern similar to that of wild-type virus. The hyperacetylation defect of hr-t mutant NG59 was partially complemented by growth of the mutant in cells expressing wild-type small T. In contrast to the hypoacetylated state of NG59, NG59 minichromosomes were hypermethylated at specific lysines in H3 and also showed a higher level of phosphorylation at H3ser10, a modification associated with the late G 2 and M phases of the cell cycle. Comparisons of virus growth kinetics and cell cycle progression in wild-type- and NG59-infected cells showed a correlation between the phase of the cell cycle at which virus assembly occurred and histone modifications in the progeny virus. Replication and assembly of wild-type virus were completed largely during S phase. Growth of NG59 was delayed by about 12 h with assembly occurring predominately in G 2 . These results suggest that small T affects modifications of viral chromatin by altering the temporal coordination of virus growth and the cell cycle.

One strategy for the use of neural stem cells (NSCs) in treating neurological disorders is as transplantable "biological minipumps", in which genetically engineered neural stem cells serve as sources of secreted therapeutic (neuroprotective or tumoricidal) agents. Neural stem cells are highly mobile within the brain and demonstrate a tropism for various types of central nervous system (CNS) pathology, making them promising candidates for targeted gene delivery vehicles. Although neural stem cells have also been proposed as a potential source of replacement neurons and astrocytes to repopulate injured or degenerating neural circuits, the challenges involved in rebuilding damaged brain architecture are substantial and remain an active area of investigation. In contrast, the use of NSCs as biological minipumps does not rely on neuronal differentiation, axonal targeting, or synaptogenesis. This strategy may be a faster route to cell-based therapy of the CNS and is poised to move into human clinical trials. This review considers two types of neurologic disease that may be suitable targets for this alternative approach to NSC therapy: glial brain tumors and traumatic brain injury. We examine some of the key scientific and technical issues that must be addressed for the successful use of NSCs as minipumps.

Hecht Syndrome is an autosomal dominant distal arthrogryposis caused by mutation in the MYH8 locus characterized by trismus and pseudocamptodactyly. Hecht-associated trismus is thought to result from bilateral hyperplasia of the mandibular coronoid processes. Although several interventions to address trismus have been pursued, no consensus exists regarding optimal management. In this report, the authors present a 7-month-old male with Hecht Syndrome referred for management of trismus. By age 2, interincisal opening had progressively decreased from 12 to 5 mm despite physical therapy. Nutrition was limited to liquids, oral hygiene was compromised, and aspiration risk was present. Computed tomography examination revealed enlarged coronoid processes extending medially and superiorly to the zygomatic arches. To release bony impaction of the coronoid processes against the zygoma and to prevent reossification of the temporalis tendon insertion, resection of the enlarged coronoids and distal temporalis muscles as well as placement of Alloderm spacers were performed via an open craniofacial transzygomatic approach. Jaw motion rehabilitation was used following surgery. Two years postoperatively, the patient had no signs of recurrence and good functional stability of jaw excursion. He was able to chew and swallow solid foods, protrude his tongue, use utensils, and perform regular oral hygiene, none of which were possible before surgery. This case demonstrates that open bilateral coronoidectomy can be a successful and durable management option for trismus in patients with Hecht Syndrome. The open transzygomatic approach is safe, has low morbidity, and provides direct access and adequate exposure for coronoid resection, spacer placement, and prevention of temporalis reinsertion.

Background/Aims: Transorbital approaches traditionally have focused on skull base and cavernous sinus lesions medial to the globe. Lateral orbital approaches to the temporal lobe have not been widely explored despite several theoretical advantages compared to open craniotomy. Recently, we demonstrated the feasibility of the lateral transorbital technique in cadaveric specimens with endoscopic visualization. We describe our initial clinical experience with the endoscope-assisted lateral transorbital approach to lesions in the temporal lobe. Methods: Two patients with mesial temporal lobe pathology presenting with seizures underwent surgery. The use of a transpalpebral or Stallard-Wright eyebrow incision enabled access to the intraorbital compartment, and a lateral orbital wall ‘keyhole' opening permitted visualization of the anterior temporal pole. Results: This approach afforded adequate access to the surgical target and surrounding structures and was well tolerated by the patients. To the best of our knowledge, this report constitutes the first case series describing the endoscope-assisted lateral transorbital approach to the temporal lobe. We discuss the limits of exposure, the nuances of opening and closing, and comparisons to open craniotomy. Conclusion: Further prospective investigation of this approach is warranted for comparison to traditional approaches to the mesial temporal lobe.

Grip force control involves mechanisms to adjust to unpredictable and predictable changes in loads during manual manipulation. Somatosensory feedback is critical not just to reactive, feedback control but also to updating the internal representations needed for proactive, feedforward control. The role of primary somatosensory cortex (S1) in these control strategies is not well established. Here we investigated grip force control in a rare case of acute central deafferentation following resection of S1. The subject had complete loss of somatosensation in the right arm without any deficit in muscle strength or reflexes. In the first task, the subject was asked to maintain a constant grip force with and without visual feedback. The subject was able to attain the target force with visual feedback but not maintain that force for more than a few seconds after visual feedback was removed. In the second task, the subject was asked to grip and move an instrumented object. The induced acceleration-dependent loads were countered by adjustments in grip force. Both amplitude and timing of the grip force modulation were not affected by deafferentation. The dissociation of these effects demonstrates the differential contribution of S1 to the mechanisms of grip force control.

Resection of the hippocampus is the standard of care for medically intractable epilepsy in patients with mesial temporal sclerosis. Although temporal craniotomy in this setting is highly successful, the procedure carries certain immutable risks and may be associated with cognitive deficits related to cortical and white matter disruption. Alternative surgical approaches may reduce some of these risks by preserving the lateral temporal lobe. This study examined the feasibility of transorbital endoscopic amygdalohippocampectomy (TEA) as an alternative to open craniotomy in cadaveric specimens.TEA dissections were performed in 4 hemispheres from 2 injected cadaveric specimens fixed in alcohol. Quantitative predictions of the limits of exposure based on predissection imaging were compared with intradissection measurements. The extent of resection and angles of exposure during the dissection and on postdissection imaging were recorded. These measurements were validated with MRI studies from 10 epilepsy patients undergoing standard surgical evaluations.The transorbital approach permitted direct access to the mesial temporal structures through the lateral orbital wall. Up to 97% of the hippocampal formation was resected with no brain retraction and minimal (mean 6.0 ± 1.4 mm) globe displacement. Lateral temporal lobe white matter tracts were preserved.TEA permits hippocampectomy comparable to standard surgical approaches without disrupting the lateral temporal cortex or white matter. This novel approach is feasible in cadaveric specimens and warrants clinical investigation in carefully selected cases.

Background/Aims: Microvascular decompression (MVD) of the trigeminal nerve is a widely accepted treatment for patients with trigeminal neuralgia caused by vascular compression. The neuroendoscope is rapidly becoming a complementary tool in minimally invasive neurosurgery of the ventral anterior skull base. Its adoption in the lateral approach to the posterior fossa has been slower and has been used primarily as an adjunct to conventional microscopic surgical techniques, e.g. endoscope-assisted microsurgery. Methods: In this paper, we describe a stepwise, technical commentary on a purely endoscopic MVD of the trigeminal nerve via the retrosigmoid route. Results: From our experience, the endoscope provides excellent visualization of the neurovascular relationship. By allowing full visualization of the trigeminal nerve, endoscopy may likely lead to an increase in the number of successful MVDs and a decrease in the number of complications. Conclusion: We believe endoscopic MVD is a safe and effective method of accessing the trigeminal nerve in the cerebellopontine angle and of performing MVD. This endoscopic technique can be implemented in other neurosurgical and neuro-otological procedures such as resection of cerebellopontine angle masses.

Objective Intramedullary spinal sarcoidosis is a difficult diagnosis to make because of its nonspecific clinical and imaging features and its imitation of other common spine disorders. We present a patient with intramedullary spinal sarcoidosis that mimicked spinal cord injury from a cervical disk herniation. Methods Relevant information was extracted from the patient's medical and imaging records. A thorough literature review subsequently was performed. Results A 59-year-old woman presented to our institution with several months of intermittent parathesias, pain, and subjective weakness in her right upper and lower extremities. Magnetic resonance imaging of the cervical spine demonstrated a large osteophyte-disk complex at C4-5 adjacent to a small area of intramedullary spinal cord enhancement. The patient underwent C4-5 anterior cervical diskectomy and fusion for the osteophyte-disk complex. She initially improved postoperatively but subsequently worsened after a few months. Because of more prominent spinal cord enhancement, a posterior laminectomy and biopsy of the enhancing lesion was performed. Intramedullary spinal sarcoidosis was diagnosed, and she was treated medically with steroids and immunosuppressive agents. Conclusion Spinal sarcoidosis can mimic more common disease processes, such as cervical spondylosis. It is an important consideration in the diagnosis of intramedullary or intradural lesions of the spinal cord because early medical treatment may improve the course of the disease process. Surgery should be limited to biopsy for diagnostic purposes.

Outcomes in clinical trials on trigeminal pain therapies require instruments with demonstrated reliability and validity. The authors evaluated the Brief Pain Inventory (BPI) in its existing form plus an additional 7 facial-specific items in patients referred to a single neurosurgeon for a diagnosis of facial pain. The complete 18-item instrument is referred to as the BPI-Facial.This study was a cross-sectional analysis of patients who completed the BPI-Facial. The diagnosis of classic versus atypical trigeminal neuralgia (TN) was made before analyzing the questionnaire results. A hypothesis-driven factor analysis was used to determine the principal components of the questionnaire. Item reliability and questionnaire validity were tested for these specific constructs.Data from 156 patients were analyzed, including 114 patients (73%) with classic and 42 (27%) with atypical TN. Using orthomax rotation factor analysis, 3 factors with an eigenvalue1.0 were identified-pain intensity, interference with general activities, and facial-specific pain interference-accounting for 97.6% of the observed item variance. Retention of the 3 factors was confirmed via a Cattell scree plot. Internal reliability was demonstrated by calculating Cronbach's alpha: 0.86 for pain intensity, 0.89 for interference with general activities, 0.95 for facial-specific pain interference, and 0.94 for the entire instrument. Initial validity of the BPI-Facial instrument was supported by the detection of statistically significant differences between patients with classic versus atypical pain. Patients with atypical TN rated their facial pain as more intense (atypical 6.24 vs classic 5.03, p = 0.013) and as having greater interference in general activities (atypical 6.94 vs classic 5.43, p = 0.0033). Both groups expressed high levels of facial-specific pain interference (atypical 6.34 vs classic 5.95, p = 0.527).The BPI-Facial is a rigorous measure of facial pain in patients with TN and appears to have sound psychometric properties and is responsive to differences between classic and atypical TN. Future studies must assess the instrument's test-retest reliability, validity in additional populations, and responsiveness with respect to changes in patient outcomes following neurosurgical interventions and medical therapies.

Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial.Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques.Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94-0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95-0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96-0.99).Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

Background and Purpose— The optimal hemoglobin (Hgb) target after aneurysmal subarachnoid hemorrhage is not precisely known. We sought to examine the threshold of Hgb concentration associated with an increased risk of cerebral metabolic dysfunction in patients with poor-grade subarachnoid hemorrhage. Methods— Twenty consecutive patients with poor-grade subarachnoid hemorrhage who underwent multimodality neuromonitoring (intracranial pressure, brain tissue oxygen tension, cerebral microdialysis) were studied prospectively. Brain tissue oxygen tension and extracellular lactate/pyruvate ratio were used as markers of cerebral metabolic dysfunction and the relationship between Hgb concentrations and the incidence of brain hypoxia (defined by a brain tissue oxygen tension 40) was analyzed. Results— Compared with higher Hgb concentrations, a Hgb concentration P =0.02), higher lactate/pyruvate ratio (29 [interquartile range, 25 to 38] versus 36 [interquartile range, 26 to 59], P =0.16), and an increased incidence of brain hypoxia (21% versus 52%, P P =0.03). On multivariable analysis, a Hgb concentration P P =0.02) after adjusting for cerebral perfusion pressure, central venous pressure, PaO 2 /FIO 2 ratio, and symptomatic vasospasm. Conclusions— A Hgb concentration

Background and Purpose— The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). Methods— Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature ≥38.3°C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). Results— Compared to fever, induced normothermia resulted in lower LPR (40±24 versus 32±9, P P P P Conclusions— Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

OBJECTIVE: Barbiturate-induced coma can be used in patients to treat intractable intracranial hypertension when other therapies, such as osmotic therapy and sedation, have failed. Despite control of intracranial pressure, cerebral infarction may still occur in some patients, and the effect of barbiturates on outcome remains uncertain. In this study, we examined the relationship between barbiturate infusion and brain tissue oxygen (PbtO 2 ). METHODS: Ten volume-resuscitated brain-injured patients who were treated with pentobarbital infusion for intracranial hypertension and underwent PbtO 2 monitoring were studied in a neurosurgical intensive care unit at a university-based Level I trauma center. PbtO 2 , intracranial pressure (ICP), mean arterial pressure, cerebral perfusion pressure (CPP), and brain temperature were continuously monitored and compared in settings in which barbiturates were or were not administered. RESULTS: Data were available from 1595 hours of PbtO 2 monitoring. When pentobarbital administration began, the mean ICP, CPP, and PbtO 2 were 18 ± 10, 72 ± 18, and 28 ± 12 mm Hg, respectively. During the 3 hours before barbiturate infusion, the maximum ICP was 24 ± 13 mm Hg and the minimum CPP was 65 ± 20 mm Hg. In the majority of patients (70%), we observed an increase in PbtO 2 associated with pentobarbital infusion. Within this group, logistic regression analysis demonstrated that a higher likelihood of compromised brain oxygen (PbtO 2 < 20 mm Hg) was associated with a decrease in pentobarbital dose after controlling for ICP and other physiological parameters (P < 0.001). In the remaining 3 patients, pentobarbital was associated with lower PbtO 2 levels. These patients had higher ICP, lower CPP, and later initiation of barbiturates compared with patients whose PbtO 2 increased. CONCLUSION: Our preliminary findings suggest that pentobarbital administered for intractable intracranial hypertension is associated with a significant and independent increase in PbtO 2 in the majority of patients. However, in some patients with more compromised brain physiology, pentobarbital may have a negative effect on PbtO 2 , particularly if administered late. Larger studies are needed to examine the relationship between barbiturates and cerebral oxygenation in brain-injured patients with refractory intracranial hypertension and to determine whether PbtO 2 responses can help guide therapy.

The authors report the case of an 18-month-old girl who presented with a ruptured anterior communicating artery aneurysm, and who was later diagnosed with Takayasu arteritis. Her initial aneurysm was successfully treated with clip application. However, over a 6-month period she had multiple ruptures from new and rapidly recurring aneurysms adjacent to the clips. These aneurysms were treated with repeated craniotomy and clip application and then with endovascular coil placement. Aneurysmal subarachnoid hemorrhage is a rare presentation of Takayasu arteritis. To the authors' knowledge, this is the youngest reported patient with Takayasu arteritis to present with a ruptured cerebral aneurysm.

Dislocation of the mandibular condyle into the middle cranial fossa is a rare event due to anatomical and biomechanical factors. The authors report the case of a 12-year-old girl who presented with this condition after colliding with a classmate. One day after her injury, the patient demonstrated an inability to close her mouth completely, and she had minor tenderness to palpation anterior to the tragus, without neurological deficits. Imaging studies demonstrated a fractured glenoid fossa with intrusion of the mandible into the cranial cavity. Open reduction of the mandibular condyle was performed, and the glenoid fossa was reconstructed with a split-thickness bone graft and titanium screws. Several dural tears noted at the time of surgery were repaired primarily. Mandibular condyle dislocation into the middle cranial fossa is often misdiagnosed initially because of its low incidence and nonspecific symptoms. Computed tomography scanning is the most sensitive diagnostic study for detecting this injury. Closed reduction after induction of general anesthesia has been recommended in recently suffered injuries without neurological deficits, but this approach may overlook damage to intracranial structures. Surgical repair is recommended if neurological injury is suspected. Treatment options should be tailored to the individual factors of each case.

✓Vertebral hemangiomas are common entities that rarely present with neurological deficits. The authors report the unusual case of a large L-3 vertebral hemangioma with epidural extension in a 27-year-old woman who presented with hip flexor and quadriceps weakness, foot drop, and leg pain. The characteristics of the mass on magnetic resonance imaging suggested an aggressive, hypervascular lesion. The patient underwent embolization of the lesion followed by direct intralesional injection of ethanol. Significant resolution of clinical symptoms was observed immediately after the procedure and at her follow-up visits. Follow-up imaging studies obtained 9 months after the procedure also documented a considerable reduction in the size of the hemangioma with minimal loss of vertebral height and a mild kyphosis at the affected level. On repeated imaging studies obtained 21 months postoperatively, the size of the hemangioma and the degree of vertebral body compression were stable. As demonstrated in this case, patients with vertebral hemangiomas can present with acute nerve root compression and signs and symptoms similar to those of disc herniation. Vertebral hemangiomas can be treated effectively with interventional techniques such as embolization and ethanol injection.

Traumatic brain injury (TBI) causes selective hippocampal cell death which is believed to be associated with the cognitive impairment observed in both clinical and experimental settings. The endogenous neurotrophin-4/5 (NT-4/5), a TrkB ligand, has been shown to be neuroprotective for vulnerable CA3 pyramidal neurons after experimental brain injury. In this study, infusion of recombinant NT-4/5 increased survival of CA2/3 pyramidal neurons to 71% after lateral fluid percussion brain injury in rats, compared with 55% in vehicle-treated controls. The functional outcome of this NT-4/5-mediated neuroprotection was examined using three hippocampal-dependent behavioral tests. Injury-induced impairment was evident in all three tests, but interestingly, there was no treatment-related improvement in any of these measures. Similarly, injury-induced decreased excitability in the Schaffer collaterals was not affected by NT-4/5 treatment. We propose that a deeper understanding of the factors that link neuronal survival to recovery of function will be important for future studies of potentially therapeutic agents.

523 Background: A pathological complete response rate of 10% to 30% has been noted to occur following preoperative chemoradiation with CT-based treatment planning in patients with rectal cancer. Fusion of the treatment planning CT with other imaging modalities like MRI or PET may help identify tumor location and improve tumor coverage. This retrospective study sought to evaluate the effect of adding MRI or PET imaging to CT-based treatment planning and its impact on pathological complete response rates in patients with rectal cancer. Methods: A retrospective analysis was performed on 39 patients, who received neoadjuvant chemoradiation for rectal adenocarcinoma from February 2009 to September 2013. Patients were divided into two groups. The first group was treated using CT-only based treatment 3D-Conformal or IMRT planning (n=9) and the second was treated using either PET or MRI fusion with the simulation CT scan (n=30). Patients were treated to a total of 5,040 cGy in 28 fractions. Pathological complete response rates (ypT0N0M0) were assessed using postoperative pathologic reports following resection. Results: 39 patients with a median age of 62 received preoperative chemoradiation with an interval to surgery ranging from 34-162 days and a median of 70 days. Patients treated with PET or MRI fusion treatment planning showed a complete pathological response rate at the primary site of 60% and a complete lymph node pathological response rate of 70.83% compared to 22.22% at the primary site and 66.66% at lymph node sites in patients with CT-only treatment planning. In patients treated using MRI or PET fusion, middle rectal cancer showed the best complete pathological response rate at 80%, followed by lower rectal cancer at 41.66%, and upper rectal cancer at 37.5%. Conclusions: Although the sample size was small, utilization of MRI or PET fusion resulted in a higher pathological complete response rate when compared to CT-only based treatment planning, especially in middle rectal cancers. Further studies are needed to accurately identify those patients with a complete pathologic response which may ultimately alter their treatment course.

✓Late cerebral radiation necrosis usually occurs within 3 years of stereotactic radiosurgery. The authors report on a case of recurrent radiation necrosis with rapid clinical deterioration and imaging findings resembling those of a malignant glioma. This 68-year-old man, who had a history of a left posterior temporal and thalamic arteriovenous malformation (AVM) treated with linear accelerator radiosurgery 13 years before presentation and complicated by radiation necrosis 11 years before presentation, exhibited new-onset mixed aphasia, right hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and an enlarging, heterogeneously enhancing mass in the region of the previously treated AVM. The patient was treated medically with corticosteroid agents, and stabilized temporarily. Unfortunately, his condition worsened precipitously soon thereafter, requiring the placement of a shunt for relief of obstructive hydrocephalus. Further surgical intervention was offered, but the patient’s family opted for hospice care instead. The patient died 10 weeks after initially presenting to the authors’ institution, and the results of an autopsy demonstrated radiation necrosis. Symptomatic radiation necrosis can occur more than a decade after stereotactic radiosurgery, necessitating patient follow up during a longer period of time than currently practiced. Furthermore, there is a need for more careful reporting on the natural history of such cases to clarify the pathogenesis of very late and recurrent radiation necrosis after radiosurgery and to define patient groups with a higher risk for these entities.

OBJECTIVE: Dystrophic calcification refers to heterotopic formation of calcium in soft tissue. There have been few reports that describe dystrophic calcification causing brachial plexopathies. We describe a unique case ofdystrophic calcification that caused entrapment of the posterior cord of the brachial plexus, something not previously described in the literature. CLINICAL PRESENTATION: We report the case of a 43-year-old woman with a medical history of congenital lymphangiomas of the left chest wall and axilla, for which she had undergone multiple surgeries and radioactive seed implantation. She presented 41 years later with progressive left arm paresthesias, pain, and weakness. Neurological findings were confined to the distribution of the posterior cord of the plexus. Radiographic evaluation demonstrated a 3 x 3 x 4-cm calcified mass in the axilla and proximal arm. INTERVENTION: A careful neurolysis and mass resection was performed. At exploration, the posterior cord, proximal radial nerve, and brachial artery were found to be densely adherent to a calcified mass. Reconstruction of the brachial artery and free tissue transfer were required for healing of the severely scarred wound. Pathological examination revealed dense, calcified connective tissue consistent with dystrophic calcification. She made an excellent recovery. CONCLUSION: We describe a rare case of dystrophic calcification of the proximal arm causing symptomatic brachial plexopathy, with onset many years after surgery and radiation. Diagnostic evaluation and surgical management are discussed.

To assess the efficacy and monitor serious adverse events in patients with rheumatoid arthritis (RA) switching treatment from infliximab to etanercept.Adult patients with active RA who were discontinuing treatment with infliximab were eligible to enroll in this prospective, 12-week, open label, single-arm, observational study. Four to 10 weeks after their last infusion of infliximab, patients began treatment with etanercept (twice weekly subcutaneous injections of 25 mg). Clinical assessments using the American College of Rheumatology (ACR) criteria for improvement were performed at baseline and at Weeks 6 and 12, and serious adverse events were monitored throughout the study.Twenty-five patients were enrolled, 18 of whom had discontinued infliximab because of lack of efficacy, and 22 completed 12 weeks of etanercept treatment. After 12 weeks, 14 of 22 patients (64%) achieved at least a 20% improvement in ACR criteria (ACR20), 13 (59%) experienced improvements in physical function that were considered clinically important (or = 0.22 point decrease in overall Health Assessment Questionnaire score), and mean values of all individual components of the ACR criteria had improved. No serious adverse events were reported during the study and no patient discontinued because of lack of efficacy.Etanercept, a soluble tumor necrosis factor (TNF) receptor, provided a well tolerated and effective treatment option for some patients even when infliximab, a monoclonal antibody to TNF, had been ineffective.