Neurology Commons^™

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …

Two Distinct Dynamic Modes Subtend The Detection Of Unexpected Sounds, Jean-Rémi King, Alexandre Gramfort, Aaron Schurger, Lionel Naccache, Stanislas Dehaene

Psychology Faculty Articles and Research

The brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stable set of brain areas. Here we test this temporal dissociation by showing how the generalization of brain activity patterns across time can characterize the dynamics of the underlying …

Pb Neurotoxicity: Neuropsychological Effects Of Lead Toxicity, Lisa H. Mason, Jordan P. Harp, Dong Y. Han

Neurology Faculty Publications

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Paraoxon Toxicity, Laxmikant Sudhir Deshpande, Kristin Phillips, Beverly Huang, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure …

Acute Cranial Neuropathies Heralding Neurosyphilis In Human Immunodeficiency Virus-Infected Patient., Saeed Alqahtani

Neurology Faculty Publications

No abstract provided.

Is There Chronic Brain Damage In Retired Nfl Players? Neuroradiology, Neuropsychology, And Neurology Examinations Of 45 Retired Players, I. Casson, D. C. Viano, E. M. Haacke, Z. Kou, D. G. Lestrange

Journal Articles

BACKGROUND: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. HYPOTHESIS: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. STUDY DESIGN: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility …

Juvenile Myoclonic Epilepsy-What Does The Future Look Like?, C. Harden

Journal Articles

No abstract provided.

Topiramate, Zonisamide And Small For Gestational Age: Maternal Factors, Timing Of Exposure And Baby Fat, C. L. Harden

Journal Articles

No abstract provided.

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.

The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith

Journal Articles

Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer's disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n = 16) was correlated with PET scans of cerebral glucose metabolism …

Thiamine Pyrophosphokinase Deficiency Causes A Leigh Disease Like Phenotype In A Sibling Pair: Identification Through Whole Exome Sequencing And Management Strategies, Jamie L. Fraser, Adeline Vanderver, Sandra Yang, Taeun Chang, Laura Cramp, Gilbert Vezina, Uta Lichter-Konecki, Kristina Cusmano-Ozog, Patroula Smpokou, Kimberly A. Chapman, Dina Zand

Neurology Faculty Publications

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation …

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, …

Carotid-Cavernous Fistula As A Mimicker Of Myasthenia Gravis, A. Eswar, H. D. Pomeranz, S. M. Vishnubhakat, M. Oller-Cramsie

Journal Articles

BACKGROUND: A carotid-cavernous fistula (CCF) is an abnormal communication between the carotid arterial system and the cavernous sinus. Common symptoms of CCFs include proptosis and ophthalmoplegia, but fluctuating diplopia and presence of ptosis are not typical. CASE DESCRIPTION: We present an unusual case of CCF with fluctuating binocular diplopia and ptosis, mimicking myasthenia gravis. Electrodiagnostic testing, which included repetitive nerve stimulation and single-fiber electromyography, was normal. Magnetic resonance imaging of the brain and orbits was initially normal, but later magnetic resonance angiography revealed enlargement of the left superior ophthalmic vein along with a left CCF. Patient underwent a successful left …

The Utility Of Neuroimaging In The Differential Diagnosis Of Parkinsonian Syndromes, F. Holtbernd, D. Eidelberg

Journal Articles

The differential diagnosis of parkinsonian syndromes can be challenging, particularly in early disease stages. However, prognosis and therapeutic regimes are not alike in Parkinson disease and atypical parkinsonism, and thus a correct diagnosis at the earliest possible stage is desirable. Over the past two decades, magnetic resonance imaging and radiotracer-based imaging techniques have proven to be helpful tools to enhance the accuracy of clinical diagnosis in these disorders. Here, we review recent advances in neuroimaging for the differential diagnosis of parkinsonian syndromes.