Neurology Commons^™

Proteomic Profiling Of High Risk Medulloblastoma Reveals Functional Biology, Jerome A. Staal, Ling San Lau, Huizhen Zhang, Wendy J. Ingram, Andrew R. Hallahan, Roger J. Packer, Brian R. Rood, Kristy J. Brown, +6 Additional Authors

Neurology Faculty Publications

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation., Marta S Vismer, Patrick A Forcelli, Mark D Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are …

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …

Implications Of Epigenetic Variability Within A Cell Population For "Cell Type" Classification, I. Tabansky, J. N.H. Stern, D. W. Pfaff

Journal Articles

Here, we propose a new approach to defining nerve "cell types" in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A "cell type" could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be …

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial With Recombinant Anti-Il-20 Monoclonal Antibody In Patients With Psoriasis, A. B. Gottlieb, J. G. Krueger, M. Sandberg Lundblad, M. Gothberg, B. E. Skolnick

Journal Articles

BACKGROUND: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20. METHODS: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area >/=15% and physician global assessment score >/=3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 …

Reduced Functional Connectivity Of Default Mode And Set-Maintenance Networks In Ornithine Transcarbamylase Deficiency., Ileana Pacheco-Colón, Stuart D. Washington, Courtney Sprouse, Guy Helman, Andrea L. Gropman, John W. Vanmeter

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks-default mode and set-maintenance-between OTCD patients and healthy controls.

METHODS: Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.

RESULTS: Group comparisons revealed …

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 …

Hmgb1 Mediates Anemia Of Inflammation In Murine Sepsis Survivors, S. I. Valdes-Ferrer, J. Papoin, M. E. Dancho, L. P. S. Olofsson, J. Li, J. M. Lipton, P. Avancena, H. Yang, Y. R. Zou, S. S. Chavan, B. T. Volpe, S. Rivella, B. Diamond, B. M. Steinberg, L. Blanc, K. J. Tracey, +2 Additional Authors

Journal Articles

Patients surviving sepsis develop anemia but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial Gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating TNF and IL-6 are elevated for five days after the onset of sepsis, and serum HMGB1 levels are increased from day seven until at least day 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after …

Stress Induces The Danger-Associated Molecular Pattern Hmgb-1 In The Hippocampus Of Male Sprague Dawley Rats: A Priming Stimulus Of Microglia And The Nlrp3 Inflammasome, M. D. Weber, M. G. Frank, K. J. Tracey, L. R. Watkins, S. F. Maier

Journal Articles

Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the …

Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author

Journal Articles

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional …

Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey

Journal Articles

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin …

Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors

Journal Articles

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, …

Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey

Journal Articles

SIGNIFICANCE: High mobility group protein 1 (HMGB1) is an evolutionarily conserved and multi-functional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses. RECENT ADVANCES: Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in position 23, 45 and 106 determine the biological activity of …

A Unifying Principle Underlying The Extracellular Field Potential Spectral Responses In The Human Cortex, E. Podvalny, N. Noy, M. Harel, S. Bickel, G. Chechik, C. E. Schroeder, A. D. Mehta, M. Tsodyks, R. Malach

Journal Articles

Electrophysiological mass potentials show complex spectral changes upon neuronal activation. However, it is unknown to what extent these complex band-limited changes are interrelated or, alternatively, reflect separate neuronal processes. To address this question, intracranial electrocorticograms (ECoG) responses were recorded in patients engaged in visuomotor tasks. We found that in the 10- to 100-Hz frequency range there was a significant reduction in the exponent chi of the 1/f(chi) component of the spectrum associated with neuronal activation. In a minority of electrodes showing particularly high activations the exponent reduction was associated with specific band-limited power modulations: emergence of a high gamma (80-100 …

Clinical Reasoning: Worsening Neurologic Symptoms In A Brain Tumor Patient, G. Faivre, E. Pentsova, A. Demopoulos, S. Taillibert, M. Rosenblum, A. Omuro

Journal Articles

No abstract provided.

Assessing Cerebral Glucose Metabolism In Patients With Idiopathic Rapid Eye Movement Sleep Behavior Disorder, J. Ge, P. Wu, S. Peng, H. Yu, H. Zhang, Y. Guan, D. Eidelberg, C. Zuo, Y. L. Ma, J. Wang

Journal Articles

Idiopathic rapid eye movement sleep behavior disorder (RBD) is a risk marker for subsequent development of neurodegenerative parkinsonism. In this study, we aimed to investigate whether regional cerebral metabolism is altered in patients with RBD and whether regional metabolic activities are associated with clinical measurements in individual patients. Twenty-one patients with polysomnogram-confirmed RBD and 21 age-matched healthy controls were recruited to undertake positron emission tomography imaging with [18F]fluorodeoxyglucose. Differences in normalized regional metabolism and correlations between metabolic activity and clinical indices in RBD patients were evaluated on a voxel basis using statistic parametric mapping analysis. Compared with controls, patients with …

Effects Of Levodopa On Regional Cerebral Metabolism And Blood Flow, J. H. Ko, R. P. Lerner, D. Eidelberg

Journal Articles

Levodopa (l-dopa) has been at the forefront of antiparkinsonian therapy for a half century. Recent advances in functional brain imaging have contributed substantially to the understanding of the effects of l-dopa and other dopaminergic treatment on the activity of abnormal motor and cognitive brain circuits in Parkinson's disease patients. Progress has also been made in understanding the functional pathology of dyskinesias, a common side effect of l-dopa treatment, at both regional and network levels. Here, we review these studies, focusing mainly on the new mechanistic insights provided by metabolic brain imaging and network analysis. (c) 2014 International Parkinson and Movement …

Reproducibility Of A Parkinsonism-Related Metabolic Brain Network In Non-Human Primates: A Descriptive Pilot Study With Fdg Pet, Y. L. Ma, T. H. Johnston, S. C. Peng, C. T. Zuo, J. B. Koprich, S. H. Fox, Y. H. Guan, D. Eidelberg, J. M. Brotchie

Journal Articles

Background: We have previously defined a parkinsonism-related metabolic brain network in rhesus macaques using a high-resolution research positron emission tomography camera. This brief article reports a descriptive pilot study to assess the reproducibility of network activity and regional glucose metabolism in independent parkinsonian macaques using a clinical positron emission tomography/CT camera. Methods: [F-18]fluorodeoxyglucose PET scans were acquired longitudinally over 3 months in three drug-naive parkinsonian and three healthy control cynomolgus macaques. Group difference and test-retest stability in network activity and regional glucose metabolism were evaluated graphically, using all brain images from these macaques. Results: Comparing the parkinsonian macaques with the …

Abnormal Metabolic Pattern Associated With Cognitive Impairment In Parkinson's Disease: A Validation Study, S. K. Meles, C. C. Tang, L. K. Teune, R. A. Dierckx, V. Dhawan, P. J. Mattis, K. L. Leenders, D. Eidelberg

Journal Articles

Cognitive deficits in Parkinson's disease (PD) have been associated with a specific metabolic covariance pattern. Although the expression of this PD cognition-related pattern (PDCP) correlates with neuropsychological performance, it is not known whether the PDCP topography is reproducible across PD populations. We therefore sought to identify a PDCP topography in a new sample comprised of 19 Dutch PD subjects. Network analysis of metabolic scans from these individuals revealed a significant PDCP that resembled the original network topography. Expression values for the new PDCP correlated (P = 0.001) with executive dysfunction on the Frontal Assessment Battery (FAB). Subject scores for the …

The Visual Perception Of Natural Motion: Abnormal Task-Related Neural Activity In Dyt1 Dystonia, W. Sako, K. Fujita, A. Vo, J. C. Rucker, J. R. Rizzo, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg

Journal Articles

Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of …

Developments In Intervertebral Disc Disease Research: Pathophysiology, Mechanobiology, And Therapeutics, K. T. Weber, T. D. Jacobsen, R. Maidhof, J. Virojanapa, C. Overby, O. Bloom, S. Quraishi, M. Levine, N. O. Chahine

Journal Articles

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in …

Exploratory Study For Identifying Systemic Biomarkers That Correlate With Pain Response In Patients With Intervertebral Disc Disorders, K. T. Weber, S. Satoh, D. O. Alipui, J. Virojanapa, M. Levine, C. Sison, S. Quraishi, O. Bloom, N. O. Chahine

Journal Articles

Molecular events that drive disc damage and low back pain (LBP) may precede clinical manifestation of disease onset and can cause detrimental long-term effects such as disability. Biomarkers serve as objective molecular indicators of pathological processes. The goal of this study is to identify systemic biochemical factors as predictors of response to treatment of LBP with epidural steroid injection (ESI). Since inflammation plays a pivotal role in LBP, this pilot study investigates the effect of ESI on systemic levels of 48 inflammatory biochemical factors (cytokines, chemokines, and growth factors) and examines the relationship between biochemical factor levels and pain or …

A Rare Case Of Aortic Dissection Presenting As Pure Transient Global Amnesia, H. Kaveeshvar, R. Kashouty, V. Loomba, N. Yono

Journal Articles

Transient global amnesia (TGA) is a well-described neurological phenomenon. Clinically, it manifests with the sudden onset of a paroxysmal, transient loss of anterograde memory and disorientation but with intact consciousness. Typically, symptoms last for only a few hours. We present an unusual case of aortic dissection presenting with pure TGA in a patient, who had a positive outcome. This is the second case report of a patient with aortic dissection presenting with pure TGA syndrome, but it is the first case in which the patient survived.

Selective Impairment Of Spatial Cognition Caused By Autoantibodies To The N-Methyl-D-Aspartate Receptor, E. H. Chang, B. T. Volpe, M. Mackay, C. Aranow, C. Kowal, P. Mattis, R. Berlin, S. Mader, T. S. Huerta, P. T. Huerta, B. Diamond, +3 Additional Authors

Journal Articles

Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at …

Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors

Journal Articles

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited …

Laminar Profile And Physiology Of The Alpha Rhythm In Primary Visual, Auditory, And Somatosensory Regions Of Neocortex, S. Haegens, A. Barczak, G. Musacchia, M. L. Lipton, A. D. Mehta, P. Lakatos, C. E. Schroeder

Journal Articles

The functional significance of the alpha rhythm is widely debated. It has been proposed that alpha reflects sensory inhibition and/or a temporal sampling or "parsing" mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate alpha rhythms and whether the generation of alpha is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed alpha current generators in …

Neural Circuitry And Immunity, V. Pavlov, K. J. Tracey

Journal Articles

No abstract provided.

Accuracy Of The Abc/2 Score For Intracerebral Hemorrhage: Systematic Review And Analysis Of Mistie, Clear-Ivh, And Clear Iii, A. J. Webb, N. L. Ullman, T. C. Morgan, J. Muschelli, J. Kornbluth, I. A. Awad, S. Mayo, M. Rosenblum, R. Narayan, D. F. Hanley, +14 Additional Authors

Journal Articles

BACKGROUND AND PURPOSE: The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP). METHODS: In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 …

Hbsc Disease And Spontaneous Epidural Hematoma With Kernohan's Notch Phenomena, M. Yogarajah, C. C. Agu, B. Sivasambu, M. A. Mittler

Journal Articles

Spontaneous (nontraumatic) acute epidural hematoma is a rare and poorly understood complication of sickle cell disease. A 19-year-old African American male with hemoglobin SC disease (HbSC) presented with generalized body aches and was managed for acute painful crisis. During his hospital stay he developed rapid deterioration of his mental status and computed topography revealed a spontaneous massive epidural hematoma with mass effect and midline shift with Kernohan's notch phenomena for which urgent craniotomy and evacuation was done. We report the first case of HbSC disease associated with catastrophic epidural hematoma progressing to transtentorial herniation and Kernohan's notch phenomena within few …