Neurology Commons^™

Polio Eradication And Health Systems In Karachi: Vaccine Refusals In Context, Svea Closser, Rashid Jooma, Emma Varley, Naina Qayyum, Sonia Rodrigues, Akasha Sarwar, Patricia Omidian

Section of Neurosurgery

Community and health worker engagement will be key to polio eradication in Karachi, Pakistan. In this study, the authors conducted participant observation, interviews, and a document review in SITE Town, Karachi, an area that in recent years has harbored poliovirus. SITE’s diverse population includes large numbers of internally displaced persons who are disproportionately affected by polio and are more likely than other populations to refuse the polio vaccine. Vaccine acceptance and worker motivation in SITE Town were shaped by the discrepancy in funding and attention for polio eradication campaigns as compared with routine services. Parental vaccine refusals stemmed from a …

Prospective Validation Of A Blood Ordering Protocol For Elective Spine Arthrodesis And Its Impact On Cost Reduction, Muhammad Waqas, Muhammad Shahzad Shamim, Badar Uddin Ujjan, Saqib Kamran Bakhshi

Section of Neurosurgery

Background: On the basis of an institutional audit, the authors published an individual patient-based protocol for preoperative arrangement of blood products in patients undergoing elective spine arthrodesis. The present study was conducted for the prospective validation of the proposed protocol in reducing cross match to transfusion ratio, and its implications on overall cost.
Methods: This cross-sectional study was conducted over 1 year (2012). All adult patients who underwent elective spinal arthrodesis were included and prospectively observed. The actual transfusion index was calculated for individual patients with the formula C1/T, where C1 is the number of units of packed RBCs cross …

Lumbar Morphometry: A Study Of Lumbar Vertebrae From A Pakistani Population Using Computed Tomography Scans, Muhammad M. Alam, Muhammad Waqas, Hussain Shallwani, Gohar Javed

Section of Neurosurgery

Study design: A cross-sectional study.
Purpose: To describe the characteristics of lumbar vertebrae of Pakistani patients reporting at a tertiary care hospital and compare with studies from other populations.
Overview of literature: Several studies have been conducted to determine morphometry of lumbar vertebrae. Most of the studies involve Caucasian populations, still data on other populations still sparse. This is the first study describing lumbar morphometry of a Pakistani population.
Methods: An observational study was conducted based on a review of thin-cut (3 mm) computed topographic images of lumbar vertebrae. Two-hundred and twenty vertebrae from forty-nine patients were studied, and various …

Polio Travel Restrictions: A Sledgehammer To Crack A Nut?, Rashid Jooma

Section of Neurosurgery

Imposition by WHO of mandatory vaccination for international travelers from Pakistan has caused confusion and panic amongst travelers besides the adverse effect on the country's image from the widely reported statement. It is felt that the announced measure is not primarily supported by science but is rather a response to disillusionment in the donors about the repeatedly missed eradication targets set by WHO. In the past few years, exportation of poliovirus from Pakistan has caused outbreaks in China, Iraq and Syria besides the ongoing two way transmission with Afghanistan, but the carriers in these spreads are mainly land route travelers. …

Kyphotic Progression After Thoracolumbar Burst Fractures Treated Conservatively, With Mis, Or Via Open Approach, Mark Rivkin, Howard Eisenbrock

Research Day

Management of thoracolumbar burst fractures (AO A3) without neurological deficit is subject to debate in the literature. While TLICS provides guidance for injuries necessitating intervention, it makes little mention of best surgical approaches. Furthermore, intact patients with suspected posterior ligamentous complex injury (TLICS 4) compose an additional level of management uncertainty. Present study examined outcomes for TL burst fractures in neurologically intact patients with suspected disruption of the PLC treated with bracing, MIS, or open fixation and fusion.

Thoracic And Lumbar Spinal Surgery Under Local Anesthesia For Patients With Multiple Comorbidities: A Consecutive Case Series, Muhammad Babar Khan, Rajesh Kumar, Ather Enam

Section of Neurosurgery

Background: Although some patients with symptomatic spinal disease may benefit greatly from surgery, their multiple attendant comorbidities may make general anesthesia risky or contraindicated. However, there is scarce literature describing the efficacy and safety of local anesthesia to perform these operations. Here we report seven patients who successfully underwent spinal surgery utilizing local anesthesia to limit the risks and complications of general anesthesia.
Methods: Seven patients for whom general anesthesia was contraindicated were prospectively followed for a minimum of 3 months following spinal surgery performed under local anesthesia. Pain and functional improvement were assessed utilizing the Visual Analog Scores (VAS) …

Critical Role Of Tnf-Α In Cerebral Aneurysm Formation And Progression To Rupture., Robert M Starke, Nohra Chalouhi, Md, Pascal Jabbour Md, Stavropoula Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasswer Md, Kosuke Wada, Kenji Shimada, David M Hasan, Nigel H Greig, Gary K Owens, Aaron Dumont

Department of Neurosurgery Faculty Papers

BACKGROUND: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established.

METHODS: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining.

RESULTS: …

Novel Anticancer Agents In Clinical And Preclinical Trials, Adnan Salim

Section of Neurosurgery

No abstract provided.

Is Surgical Spinal Decompression For Supratentorial Gbm Symptomatic Drop Down Metastasis Warranted? A Case Report And Review Of Literature, Muhammad Babar Khan, Muhammad Riaz, Muhammad Ehsan Bari

Medical College Documents

Background: Symptomatic spinal metastasis from an intracranial primary
glioblastoma multiforme (GBM) is very rare. Our literature search identified a total
of 42 such patients of which 11 were treated with surgical decompression for spinal metastasis with only one such report from the pediatric age group. Previous studies have reported variable outcomes after surgical management.

Case Description: We report the case of a 16‑year‑old boy who underwent
surgical spinal decompression for spinal metastasis after intracranial GBM. The
patient regained motor and autonomic function following surgery and reported
improvement in pain. We also present findings from a literature review using …

Consensus On Guidelines For Stereotactic Neurosurgery For Psychiatric Disorders, B. Nuttin, H. Wu, H. Mayberg, M. Hariz, L. Gabriels, T. Galert, R. Merkel, M. Schulder, Y. J. Li, T. Schlaepfer, +24 Additional Authors

Journal Articles

Background For patients with psychiatric illnesses remaining refractory to 'tandard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights …

Molecular Medicine Commemorates The Career And Science Of Anthony Cerami, K. J. Tracey

Journal Articles

No abstract provided.

Phase I/Ii Study Of Resection And Intraoperative Cesium-131 Radioisotope Brachytherapy In Patients With Newly Diagnosed Brain Metastases., A. G. Wernicke, B. Parashar, D. Nori, K. S. Clifford Chao, P. Christos, I. Kovanlikaya, S. Pannullo, J. A. Boockvar, P. E. Stieg, T. H. Schwartz

Journal Articles

OBJECT: Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS: After institutional review board approval was …

Sepsis: Current Dogma And New Perspectives, C. S. Deutschman, K. J. Tracey

Journal Articles

Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity andmortality worldwide. Current immunological mechanisms do not explain the basis of cellular dysfunction and organ failure, the ultimate cause of death. Here we review current dogma and argue that it is time to delineate novel immunometabolic and neurophysiological mechanisms underlying the altered cellular bioenergetics and failure of epithelial and endothelial barriers that produce organ dysfunction and death. These mechanisms might hold the key to future therapeutic strategies.

A Systematic Nomenclature For The Redox States Of High Mobility Group Box (Hmgb) Proteins, D. J. Antoine, H. E. Harris, U. Andersson, K. J. Tracey, M. E. Bianchi

Journal Articles

High mobility group box 1 (HMGB1) is a central mediator in inflammation and immunity. Recently, it was shown that different redox states of the three cysteines of HMGB1 endow it with mutually exclusive activities, such as inducing chemotaxis or the transcription of cytokines and chemokines, via the interaction with different receptors. The different HMGB1 redox forms can be identified by mass spectrometry in body fluids of patients and may hold promise as biomarkers. We propose here a systematic nomenclature of the different redox forms of HMGB1 and related proteins, to replace the conflicting names used so far by different laboratories.

Corticocortical Evoked Potentials Reveal Projectors And Integrators In Human Brain Networks, C. J. Keller, C. J. Honey, L. Entz, S. Bickel, D. M. Groppe, E. Toth, I. Ulbert, F. A. Lado, A. D. Mehta

Journal Articles

The cerebral cortex is composed of subregions whose functional specialization is largely determined by their incoming and outgoing connections with each other. In the present study, we asked which cortical regions can exert the greatest influence over other regions and the cortical network as a whole. Previous research on this question has relied on coarse anatomy (mapping large fiber pathways) or functional connectivity (mapping inter-regional statistical dependencies in ongoing activity). Here we combined direct electrical stimulation with recordings from the cortical surface to provide a novel insight into directed, inter-regional influence within the cerebral cortex of awake humans. These networks …

Evoked Effective Connectivity Of The Human Neocortex, L. Entz, E. Toth, C. J. Keller, S. Bickel, D. M. Groppe, D. Fabo, L. R. Kozak, L. Eross, I. Ulbert, A. D. Mehta

Journal Articles

The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an …

Exemplar Selectivity Reflects Perceptual Similarities In The Human Fusiform Cortex, I. Davidesco, E. Zion-Golumbic, S. Bickel, M. Harel, D. M. Groppe, C. J. Keller, C. A. Schevon, G. M. Mckhann, R. R. Goodman, G. Goelman, C. E. Schroeder, A. D. Mehta, R. Malach

Journal Articles

While brain imaging studies emphasized the category selectivity of face-related areas, the underlying mechanisms of our remarkable ability to discriminate between different faces are less understood. Here, we recorded intracranial local field potentials from face-related areas in patients presented with images of faces and objects. A highly significant exemplar tuning within the category of faces was observed in high-Gamma (80-150 Hz) responses. The robustness of this effect was supported by single-trial decoding of face exemplars using a minimal (n = 5) training set. Importantly, exemplar tuning reflected the psychophysical distance between faces but not their low-level features. Our results reveal …

Guanine Nucleotide Exchange Factor Dock7 Mediates Hgf- Induced Glioblastoma Cell Invasion Via Rac Activation, D. W. Murray, S. Didier, A. Chan, V. Paulino, L. Van Aelst, R. Ruggieri, N. L. Tran, A. T. Byrne, M. Symons

Journal Articles

Background: Glioblastoma multiforme (GBM), a highly invasive primary brain tumour, remains an incurable disease. Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs), have central roles in GBM invasion. Anti-angiogenic therapies may stimulate GBM invasion via HGF/c-Met signalling. We aim to identify mediators of HGF-induced GBM invasion that may represent targets in a combination anti-angiogenic/anti-invasion therapeutic paradigm. Methods: Guanine nucleotide exchange factor expression was measured by microarray analysis and western blotting. Specific depletion of proteins was accomplished using siRNA. Cell invasion was determined using matrigel and brain slice assays. Cell proliferation and survival were monitored using sulforhodamine B and …

Head Model And Electrical Source Imaging: A Study Of 38 Epileptic Patients, G. Birot, L. Spinelli, S. Vulliemoz, P. Megevand, D. Brunet, M. Seeck, C. M. Michel

Journal Articles

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from scalp EEG. When applied to interictal epileptiform discharges (IEDs), this technique is of great use for identifying the irritative zone in focal epilepsies. Inaccuracies in the modeling of electro-magnetic field propagation in the head (forward model) may strongly influence ESI and lead to mislocalization of IED generators. However, a systematic study on the influence of the selected head model on the localization precision of IED in a large number of patients with known focus localization has not yet been performed. We here present such a performance evaluation of …

Hmgb1 Enhances Immune Suppression By Facilitating The Differentiation And Suppressive Activity Of Myeloid-Derived Suppressor Cells, K. H. Parker, P. Sinha, L. A. Horn, V. K. Clements, H. Yang, J. H. Li, K. J. Tracey, S. Ostrand-Rosenberg

Journal Articles

Chronic inflammation often precedes malignant transformation and later drives tumor progression. Likewise, subversion of the immune system plays a role in tumor progression, with tumoral immune escape now well recognized as a crucial hallmark of cancer. Myeloid-derived suppressor cells (MDSC) are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. Thus, MDSCs may define an element of the pathogenic inflammatory processes that drives immune escape. The secreted alarmin HMGB1 is a proinflammatory partner, inducer, and chaperone for many proinflammatory molecules that MDSCs develop. Therefore, in this study, we examined HMGB1 as a potential …

Inflammation Induces Irreversible Biophysical Changes In Isolated Nucleus Pulposus Cells, R. Maidhof, T. Jacobsen, A. Papatheodorou, N. O. Chahine

Journal Articles

Intervertebral disc degeneration is accompanied by elevated levels of inflammatory cytokines that have been implicated in disease etiology and matrix degradation. While the effects of inflammatory stimulation on disc cell metabolism have been well-studied, their effects on cell biophysical properties have not been investigated. The hypothesis of this study is that inflammatory stimulation alters the biomechanical properties of isolated disc cells and volume responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine discs were isolated and treated with either lipopolysaccharide (LPS), an inflammatory ligand, or with the recombinant cytokine TNF-alpha for 24 hours. We measured cellular …

Jak/Stat1 Signaling Promotes Hmgb1 Hyperacetylation And Nuclear Translocation, B. Lu, K. Kwan, M. Robinson, M. A. D. Van Zoelen, H. Yang, J. Li, S. S. Chavan, H. Wang, U. Andersson, K. J. Tracey, +5 Additional Authors

Journal Articles

Extracellular high-mobility group box (HMGB)1 mediates inflammation during sterile and infectious injury and contributes importantly to disease pathogenesis. The first critical step in the release of HMGB1 from activated immune cells is mobilization from the nucleus to the cytoplasm, a process dependent upon hyperacetylation within two HMGB1 nuclear localization sequence (NLS) sites. The inflammasomes mediate the release of cytoplasmic HMGB1 in activated immune cells, but the mechanism of HMGB1 translocation from nucleus to cytoplasm was previously unknown. Here, we show that pharmacological inhibition of JAK/STAT1 inhibits LPS-induced HMGB1 nuclear translocation. Conversely, activation of JAK/STAT1 by type 1 interferon (IFN) stimulation …

Mapping Epileptic Activity: Sources Or Networks For The Clinicians?, F. Pittau, P. Megevand, L. Sheybani, E. Abela, F. Grouiller, L. Spinelli, C. M. Michel, M. Seeck, S. Vulliemoz

Journal Articles

Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize …

O-020 Modifying Flow In The Ica Bifurcation: Pipeline Deployment From The Supraclinoid Ica Extending Into The M1 Segment: Clinical And Anatomical Results, E. Nossek, D. J. Chalif, S. Chakraborty, A. Setton

Journal Articles

BACKGROUND: Utility of the pipeline embolization device (PED) extending to the M1 segment as well as its clinical and flow consequences at the ICA bifurcation, has not clearly described. We describe clinical and anatomical flow modifications results at the ICA bifurcation. METHODS: In this retrospective analysis of patients treated for distal supraclinoid carotid aneurysms, a single PED was deployed from the proximal M1 segment to the distal supraclinoid carotid. Flow assessment prior to the procedure, to predict the competence of the ACA/AcomA complex, was achieved by formal DSA angiography and occasional manual cross compression. In all cases a single PED …

The Regulation Of Rhoa At Focal Adhesions By Stard13 Is Important For Astrocytoma Cell Motility, B. D. Khalil, S. Hanna, B. A. Saykali, S. El-Sitt, A. Nasrallah, D. Marston, M. El-Sabban, K. M. Hahn, M. Symons, M. El-Sibai

Journal Articles

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Forster Resonance Energy Transfer (FRET), we show that RhoA activity …

Semapimod Sensitizes Glioblastoma Tumors To Ionizing Radiation By Targeting Microglia, I. S. Miller, S. Didier, D. W. Murray, T. H. Turner, M. Issaivanan, R. Ruggieri, Y. Al-Abed, M. Symons

Journal Articles

Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 …

Terror Medicine As Part Of The Medical School Curriculum, L. A. Cole, K. Wagner, S. Scott, N. D. Connell, A. Cooper, C. A. Kennedy, B. Natal, S. Lamba

Journal Articles

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, …

Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey

Journal Articles

Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …

Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia

Journal Articles

The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha 7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility …

High-Mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline By Engaging Bone Marrow-Derived Macrophages, S. Vacas, V. Degos, K. J. Tracey, M. Maze

Journal Articles

Background: Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods: The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results: A single …