Pathophysiology of Acute Coma and Disorders of Consciousness: Considerations for Diagnosis and Management

Abstract Disorders of consciousness are due to failure of the arousal system. In this review, the authors introduce the spectrum of disorders of consciousness and describe the structures, projections, and neurotransmitters involved in the generation and maintenance of arousal. Next, they discuss the neurologic diseases frequently associated with arousal failure. Evaluation of patients with disorders of arousal is summarized, including the neurologic exam, electrophysiological studies, biochemical testing, and imaging modalities. Finally, they review treatment options, including therapeutic hypothermia, medications, and deep brain and spinal cord stimulation.

[1]  Z. Odabaşı,et al.  Clinical properties of regional thalamic hemorrhages. , 2013, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[2]  Y. Katayama,et al.  Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state. , 2013, World neurosurgery.

[3]  H. Nawashiro,et al.  Prognostic factors in patients with primary brainstem hemorrhage , 2013, Clinical Neurology and Neurosurgery.

[4]  R. Delorenzo,et al.  Hypothermia reduces calcium entry via the N-methyl-D-aspartate and ryanodine receptors in cultured hippocampal neurons. , 2013, European journal of pharmacology.

[5]  S. Mayer,et al.  The Epidemiology of Intracerebral Hemorrhage in the United States from 1979 to 2008 , 2013, Neurocritical Care.

[6]  T. Beems,et al.  Outcome Prediction in Moderate and Severe Traumatic Brain Injury: A Focus on Computed Tomography Variables , 2013, Neurocritical Care.

[7]  Tao Yu,et al.  Global functional connectivity reveals highly significant differences between the vegetative and the minimally conscious state , 2013, Journal of Neurology.

[8]  A. Belousov.  Novel model for the mechanisms of glutamate-dependent excitotoxicity: Role of neuronal gap junctions , 2012, Brain Research.

[9]  Wenhua Zheng,et al.  Glutamate attenuates IGF-1 receptor tyrosine phosphorylation in mouse brain: Possible significance in ischemic brain damage , 2012, Neuroscience Research.

[10]  Yilong Wang,et al.  Epidemiology of Subarachnoid Hemorrhage, Patterns of Management, and Outcomes in China: A Hospital‐Based Multicenter Prospective Study , 2012, CNS neuroscience & therapeutics.

[11]  B. Jones,et al.  Immunohistochemical evidence for synaptic release of GABA from melanin-concentrating hormone containing varicosities in the locus coeruleus , 2012, Neuroscience.

[12]  R. Vertes,et al.  Projections of the central medial nucleus of the thalamus in the rat: Node in cortical, striatal and limbic forebrain circuitry , 2012, Neuroscience.

[13]  D. Smajlović,et al.  Stroke and Disorders of Consciousness , 2012, Cardiovascular psychiatry and neurology.

[14]  J. Rostas,et al.  αCaMKII is Differentially Regulated in Brain Regions that Exhibit Differing Sensitivities to Ischemia and Excitotoxicity , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  Michal A Miller.  Clinical Examination for Outcome Prediction in Nontraumatic Coma , 2012 .

[16]  H. Deng,et al.  Prediction of coma and anisocoria based on computerized tomography findings in patients with supratentorial intracerebral hemorrhage , 2012, Clinical Neurology and Neurosurgery.

[17]  Jon T. Willie,et al.  Controlled cortical impact traumatic brain injury acutely disrupts wakefulness and extracellular orexin dynamics as determined by intracerebral microdialysis in mice. , 2012, Journal of neurotrauma.

[18]  Sachie K. Ogawa,et al.  Whole-Brain Mapping of Direct Inputs to Midbrain Dopamine Neurons , 2012, Neuron.

[19]  S. Y. Chabok,et al.  Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury , 2012, The journal of trauma and acute care surgery.

[20]  B. Waterhouse,et al.  Evidence for Broad Versus Segregated Projections from Cholinergic and Noradrenergic Nuclei to Functionally and Anatomically Discrete Subregions of Prefrontal Cortex , 2012, Front. Behav. Neurosci..

[21]  D. Burdakov,et al.  Convergent inputs from electrically and topographically distinct orexin cells to locus coeruleus and ventral tegmental area , 2012, The European journal of neuroscience.

[22]  P. Kudenchuk,et al.  Impact of Changes in Resuscitation Practice on Survival and Neurological Outcome After Out-of-Hospital Cardiac Arrest Resulting From Nonshockable Arrhythmias , 2012, Circulation.

[23]  Shijie Sun,et al.  Therapeutic hypothermia after cardiac arrest in adults: mechanism of neuroprotection, phases of hypothermia, and methods of cooling. , 2012, Critical care clinics.

[24]  K. Suk,et al.  Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect , 2012, Current neuropharmacology.

[25]  John Whyte,et al.  Placebo-controlled trial of amantadine for severe traumatic brain injury. , 2012, The New England journal of medicine.

[26]  Mu‐Shun Huang,et al.  Emergency department neurologic deterioration in patients with spontaneous intracerebral hemorrhage: incidence, predictors, and prognostic significance. , 2012, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[27]  Donald H. Lee,et al.  Disruptions of functional connectivity in the default mode network of comatose patients , 2012, Neurology.

[28]  Yongfu Wang,et al.  Neuronal Gap Junction Coupling Is Regulated by Glutamate and Plays Critical Role in Cell Death during Neuronal Injury , 2012, The Journal of Neuroscience.

[29]  Harald Herkner,et al.  Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. , 2012, The Cochrane database of systematic reviews.

[30]  Y. Katayama,et al.  Spinal cord stimulation for treatment of patients in the minimally conscious state. , 2012, Neurologia medico-chirurgica.

[31]  T. Hodics.  Neurocritical care. , 2012, Archives of neurology.

[32]  Botros B. Kostandy.  The role of glutamate in neuronal ischemic injury: the role of spark in fire , 2012, Neurological Sciences.

[33]  R. Palmiter.  Dopamine signaling as a neural correlate of consciousness , 2011, Neuroscience.

[34]  K. Sakai,et al.  Sleep-waking discharge profiles of dorsal raphe nucleus neurons in mice , 2011, Neuroscience.

[35]  S. Datta,et al.  Calcium/Calmodulin Kinase II in the Pedunculopontine Tegmental Nucleus Modulates the Initiation and Maintenance of Wakefulness , 2011, The Journal of Neuroscience.

[36]  G. B. Young,et al.  Anoxic-ischemic encephalopathy and strokes causing impaired consciousness. , 2011, Neurologic clinics.

[37]  Yvonne Höller,et al.  Deactivation of the Default Mode Network as a Marker of Impaired Consciousness: An fMRI Study , 2011, PloS one.

[38]  A. Loewy,et al.  Serotonergic inputs to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei that project to the ventral tegmental area , 2011, Neuroscience.

[39]  M. Kawai,et al.  Outcome From Therapeutic Hypothermia and EEG , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[40]  J. Mnif,et al.  Diffuse axonal injury in patients with head injuries: an epidemiologic and prognosis study of 124 cases. , 2011, The Journal of trauma.

[41]  Timothy E. Ham,et al.  Default Mode Network Connectivity Predicts Sustained Attention Deficits after Traumatic Brain Injury , 2011, The Journal of Neuroscience.

[42]  P. Torterolo,et al.  A restricted parabrachial pontine region is active during non-rapid eye movement sleep , 2011, Neuroscience.

[43]  W. Haupt,et al.  Application of Electrophysiologic Techniques in Poor Outcome Prediction Among Patients With Severe Focal and Diffuse Ischemic Brain Injury , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[44]  M. Czisch,et al.  Development of the brain's default mode network from wakefulness to slow wave sleep. , 2011, Cerebral cortex.

[45]  Shi-ting Li,et al.  Spinal Cord Stimulation and Cerebral Hemodynamics: Updated Mechanism and Therapeutic Implications , 2011, Stereotactic and Functional Neurosurgery.

[46]  O. Etard,et al.  Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study , 2011, BMC cardiovascular disorders.

[47]  J. Monti,et al.  Serotonin control of sleep-wake behavior. , 2011, Sleep medicine reviews.

[48]  Robert Leech,et al.  Default mode network functional and structural connectivity after traumatic brain injury. , 2011, Brain : a journal of neurology.

[49]  Ralph Lydic,et al.  Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation , 2011, Journal of neurochemistry.

[50]  S. Naruse,et al.  Temporal and sequential changes of glial cells and cytokine expression during neuronal degeneration after transient global ischemia in rats , 2011, Journal of Neuroinflammation.

[51]  A. Rossetti,et al.  Predicting neurological outcome after cardiac arrest , 2011, Current opinion in critical care.

[52]  D. Brealey,et al.  Outcome in Poor Grade Subarachnoid Hemorrhage Patients Treated with Acute Endovascular Coiling of Aneurysms and Aggressive Intensive Care , 2011, Neurocritical care.

[53]  S. Sesack,et al.  Projections from the rat pedunculopontine and laterodorsal tegmental nuclei to the anterior thalamus and ventral tegmental area arise from largely separate populations of neurons , 2011, Brain Structure and Function.

[54]  H. S. Lee,et al.  Retrograde study of projections from the tuberomammillary nucleus to the mesopontine cholinergic complex in the rat , 2011, Brain Research.

[55]  Jun Lu,et al.  Reassessment of the structural basis of the ascending arousal system , 2011, The Journal of comparative neurology.

[56]  Randy M. Bruno,et al.  Effects and Mechanisms of Wakefulness on Local Cortical Networks , 2011, Neuron.

[57]  M. Garzón,et al.  Hypocretin1/OrexinA‐containing axons innervate locus coeruleus neurons that project to the Rat medial prefrontal cortex. Implication in the sleep‐wakefulness cycle and cortical activation , 2011, Synapse.

[58]  María C. García-Roca,et al.  Autonomic, EEG, and Behavioral Arousal Signs in a PVS Case After Zolpidem Intake , 2011, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[59]  R. Lundy,et al.  Terminal field specificity of forebrain efferent axons to the pontine parabrachial nucleus and medullary reticular formation , 2011, Brain Research.

[60]  Wakako Fujita-Hamabe,et al.  RETRACTED: Effect of Orexin-A on Post-ischemic Glucose Intolerance and Neuronal Damage. , 2011, Journal of pharmacological sciences.

[61]  J. Bolam,et al.  Phasic modulation of cortical high-frequency oscillations by pedunculopontine neurons. , 2011, Progress in brain research.

[62]  A. Mahapatra,et al.  Single photon emission computed tomography scanning: A predictor of outcome in vegetative state of head injury , 2011, Journal of neurosciences in rural practice.

[63]  H. Haas,et al.  Waking with the hypothalamus , 2011, Pflügers Archiv - European Journal of Physiology.

[64]  Jean-Yves Fagon,et al.  Can fast-component of nystagmus on caloric vestibulo-ocular responses predict emergence from vegetative state in ICU? , 2011, Journal of Neurology.

[65]  David M Devilbiss,et al.  Phasic and tonic patterns of locus coeruleus output differentially modulate sensory network function in the awake rat. , 2011, Journal of neurophysiology.

[66]  Steven Laureys,et al.  Resting state activity in patients with disorders of consciousness. , 2011, Functional neurology.

[67]  M. Boly,et al.  Brain Connectivity in Pathological and Pharmacological Coma , 2010, Front. Syst. Neurosci..

[68]  John E Billi,et al.  Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. , 2010, Circulation.

[69]  M. Oertel,et al.  Spontaneous Intracerebral Hemorrhage With Ventricular Extension and the Grading of Obstructive Hydrocephalus: The Prediction of Outcome of a Special Life-Threatening Entity , 2010, Neurosurgery.

[70]  R. Berg,et al.  Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies. , 2010, Resuscitation.

[71]  Walter G Sannita,et al.  Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome , 2010, BMC medicine.

[72]  T. Tsumori,et al.  Glutamatergic lateral parabrachial neurons innervate orexin-containing hypothalamic neurons in the rat , 2010, Brain Research.

[73]  B. Schofield,et al.  Cholinergic and Non-Cholinergic Projections from the Pedunculopontine and Laterodorsal Tegmental Nuclei to the Medial Geniculate Body in Guinea Pigs , 2010, Front. Neuroanat..

[74]  A. Yamatodani,et al.  Modanifil activates the histaminergic system through the orexinergic neurons , 2010, Neuroscience Letters.

[75]  A. Scheinberg,et al.  Zolpidem for Persistent Vegetative State – A Placebo-Controlled Trial in Pediatrics , 2010, Neuropediatrics.

[76]  F. Sakai,et al.  The effect of orexin-A on the pathological mechanism in the rat focal cerebral ischemia , 2010, Neuroscience Research.

[77]  Ralph Lydic,et al.  GABAA Receptors in the Pontine Reticular Formation of C57BL/6J Mouse Modulate Neurochemical, Electrographic, and Behavioral Phenotypes of Wakefulness , 2010, The Journal of Neuroscience.

[78]  P. Henny,et al.  Immunohistochemical evidence for synaptic release of glutamate from orexin terminals in the locus coeruleus , 2010, Neuroscience.

[79]  M. Xi,et al.  The injection of hypocretin-1 into the nucleus pontis oralis induces either active sleep or wakefulness depending on the behavioral state when it is administered. , 2010, Sleep.

[80]  C. Callaway,et al.  Association between clinical examination and outcome after cardiac arrest. , 2010, Resuscitation.

[81]  O. Hassani,et al.  GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep , 2010, The European journal of neuroscience.

[82]  Roland Bammer,et al.  Temporal and Spatial Profile of Brain Diffusion-Weighted MRI After Cardiac Arrest , 2010, Stroke.

[83]  Toshio Matsuda,et al.  Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice , 2010, Journal of neurochemistry.

[84]  J. Brubacher,et al.  Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review. , 2010, CJEM.

[85]  Francois Pomerleau,et al.  Diffuse brain injury elevates tonic glutamate levels and potassium-evoked glutamate release in discrete brain regions at two days post-injury: an enzyme-based microelectrode array study. , 2010, Journal of neurotrauma.

[86]  Fang Sun,et al.  Willful modulation of brain activity in disorders of consciousness. , 2010, The New England journal of medicine.

[87]  C. Doherty,et al.  The value of motor response versus neuroimaging in predicting outcome post cardiac arrest: a retrospective study , 2010, Journal of Neurology.

[88]  E. Arrigoni,et al.  Activation of the basal forebrain by the orexin/hypocretin neurones , 2010, Acta physiologica.

[89]  M. Castro-Alamancos,et al.  Neocortex network activation and deactivation states controlled by the thalamus. , 2010, Journal of neurophysiology.

[90]  E. Garcia-Rill,et al.  Cholinergic modulation of fast inhibitory and excitatory transmission to pedunculopontine thalamic projecting neurons. , 2010, Journal of neurophysiology.

[91]  C. Kamei,et al.  Studies on wakefulness-promoting effect of memantine in rats , 2010, Behavioural Brain Research.

[92]  K. Hattori,et al.  Consciousness recovery induced by intrathecal baclofen administration after subarachnoid hemorrhage -two case reports-. , 2010, Neurologia medico-chirurgica.

[93]  G. Marks,et al.  A novel GABAergic afferent input to the pontine reticular formation: The mesopontine GABAergic column , 2009, Brain Research.

[94]  T. Scammell,et al.  Loss of hypocretin (orexin) neurons with traumatic brain injury , 2009, Annals of neurology.

[95]  Paul S. Morgan,et al.  In vivo mapping of the human locus coeruleus , 2009, NeuroImage.

[96]  P. Onorati,et al.  Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses. , 2009, Archives of physical medicine and rehabilitation.

[97]  N. Miyamatsu,et al.  A priority treatment of the intraventricular hemorrhage (IVH) should be performed in the patients suffering intracerebral hemorrhage with large IVH , 2009, Clinical Neurology and Neurosurgery.

[98]  John Whyte,et al.  Incidence of Clinically Significant Responses to Zolpidem Among Patients with Disorders of Consciousness: A Preliminary Placebo Controlled Trial , 2009, American journal of physical medicine & rehabilitation.

[99]  B. Jones,et al.  Activity Profiles of Cholinergic and Intermingled GABAergic and Putative Glutamatergic Neurons in the Pontomesencephalic Tegmentum of Urethane-Anesthetized Rats , 2009, The Journal of Neuroscience.

[100]  A. Algra,et al.  Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial , 2009, The Lancet Neurology.

[101]  O. Hassani,et al.  Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep–wake cycle , 2009, Proceedings of the National Academy of Sciences.

[102]  Nicola J. Ray,et al.  Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus , 2009, Movement disorders : official journal of the Movement Disorder Society.

[103]  J. Pineda,et al.  Glutamate‐induced post‐activation inhibition of locus coeruleus neurons is mediated by AMPA/kainate receptors and sodium‐dependent potassium currents , 2009, British journal of pharmacology.

[104]  B. Biswal,et al.  Functional connectivity of default mode network components: Correlation, anticorrelation, and causality , 2009, Human brain mapping.

[105]  S. Mayer,et al.  Predicting long-term outcome in poor grade aneurysmal subarachnoid haemorrhage patients utilising the Glasgow Coma Scale , 2009, Journal of Clinical Neuroscience.

[106]  J. Weyler,et al.  The Prognostic Value of the EEG in Postanoxic Coma , 2009, Neurocritical care.

[107]  D. Schneider,et al.  Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care , 1998, Intensive Care Medicine.

[108]  T. Rothstein.  The Utility of Median Somatosensory Evoked Potentials in Anoxic-Ischemic Coma , 2009, Reviews in the neurosciences.

[109]  Steven Laureys,et al.  Neuroimaging after coma , 2009, Neuroradiology.

[110]  F. Brischoux,et al.  Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control , 2008, The Journal of comparative neurology.

[111]  C. Leonard,et al.  Dual orexin actions on dorsal raphe and laterodorsal tegmentum neurons: noisy cation current activation and selective enhancement of Ca2+ transients mediated by L-type calcium channels. , 2008, Journal of neurophysiology.

[112]  J. Siegel,et al.  Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[113]  R. Tamargo,et al.  VALIDATION OF AN ANEURYSMAL SUBARACHNOID HEMORRHAGE GRADING SCALE IN 1532 CONSECUTIVE PATIENTS , 2008, Neurosurgery.

[114]  F. Reinoso-suárez,et al.  GABAergic and non-GABAergic thalamic, hypothalamic and basal forebrain projections to the ventral oral pontine reticular nucleus: Their implication in REM sleep modulation , 2008, Brain Research.

[115]  F. Plum,et al.  Behavioural improvements with thalamic stimulation after severe traumatic brain injury , 2008, Nature.

[116]  Hao Chen,et al.  Risk factors related to hydrocephalus after traumatic subarachnoid hemorrhage. , 2008, Surgical neurology.

[117]  L. Naccache,et al.  A combined clinical and MRI approach for outcome assessment of traumatic head injured comatose patients , 2008, Journal of Neurology.

[118]  H. Ring,et al.  Transient reversal of anoxic brain injury-related minimally conscious state after zolpidem administration: a case report. , 2008, Archives of physical medicine and rehabilitation.

[119]  W. Liao,et al.  Effects of electrical cervical spinal cord stimulation on cerebral blood perfusion, cerebrospinal fluid catecholamine levels, and oxidative stress in comatose patients. , 2008, Acta neurochirurgica. Supplement.

[120]  Raminder Kumar.  Approved and investigational uses of modafinil : an evidence-based review. , 2008, Drugs.

[121]  J. Adair,et al.  Amnesic Syndrome in a Mammillothalamic Tract Infarction , 2007, Journal of Korean medical science.

[122]  A. Arboix,et al.  Thalamic haemorrhage vs internal capsule-basal ganglia haemorrhage: clinical profile and predictors of in-hospital mortality , 2007, BMC neurology.

[123]  J. Stein,et al.  Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. , 2007, Journal of neurosurgery.

[124]  R. T. Martin,et al.  The Effects of Methylphenidate on Command Following and Yes/No Communication in Persons with Severe Disorders of Consciousness: A Meta-Analysis of n-of-1 Studies , 2007, American journal of physical medicine & rehabilitation.

[125]  R. Llinás,et al.  Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling , 2007, Proceedings of the National Academy of Sciences.

[126]  S. Tufik,et al.  The Role of the Substantia Nigra Pars Compacta in Regulating Sleep Patterns in Rats , 2007, PloS one.

[127]  E. Chiquete,et al.  Grading Scale for Prediction of Outcome in Primary Intracerebral Hemorrhages , 2007, Stroke.

[128]  D. Monti,et al.  The involvement of dopamine in the modulation of sleep and waking. , 2007, Sleep medicine reviews.

[129]  E. Vicaut,et al.  Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials , 2007, The Lancet Neurology.

[130]  Diederik Dippel,et al.  Therapeutic hypothermia in acute ischemic stroke , 2007, Expert review of neurotherapeutics.

[131]  P. Onorati,et al.  An unexpected recovery from permanent vegetative state , 2007, Brain injury.

[132]  T. Taira,et al.  Intrathecal baclofen in the treatment of post-stroke central pain, dystonia, and persistent vegetative state. , 2007, Acta neurochirurgica. Supplement.

[133]  P. Pévet,et al.  The serotonergic inhibition of slowly bursting cells in the intergeniculate leaflet of the rat , 2006, The European journal of neuroscience.

[134]  E. Ely,et al.  Brain dysfunction: another burden for the chronically critically ill. , 2006, Archives of internal medicine.

[135]  Kamyar Keramatian,et al.  Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury , 2006, Clinical Neurology and Neurosurgery.

[136]  P. Henny,et al.  Vesicular glutamate (VGlut), GABA (VGAT), and acetylcholine (VACht) transporters in basal forebrain axon terminals innervating the lateral hypothalamus , 2006, The Journal of comparative neurology.

[137]  C. Saper,et al.  A putative flip–flop switch for control of REM sleep , 2006, Nature.

[138]  R. Llinás,et al.  Bursting of thalamic neurons and states of vigilance. , 2006, Journal of neurophysiology.

[139]  G Keir,et al.  Axonal damage and outcome in subarachnoid haemorrhage , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[140]  C. Berridge,et al.  Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area , 2006, Neuropsychopharmacology.

[141]  J. Langlois,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths , 2006 .

[142]  R. Clauss,et al.  Drug induced arousal from the permanent vegetative state. , 2006, NeuroRehabilitation.

[143]  D. Mochly‐Rosen,et al.  The Role of Protein Kinase C in Cerebral Ischemic and Reperfusion Injury , 2005, Stroke.

[144]  G. Kirouac,et al.  Orexin (hypocretin) innervation of the paraventricular nucleus of the thalamus , 2005, Brain Research.

[145]  Robyn L McClelland,et al.  Validation of a new coma scale: The FOUR score , 2005, Annals of neurology.

[146]  B. Ang,et al.  Cerebrospinal fluid orexin in aneurysmal subarachnoid haemorrhage – a pilot study , 2005, Journal of Clinical Neuroscience.

[147]  V. Rivera.  Modafinil for the treatment of diminished responsiveness in a patient recovering from brain surgery , 2005, Brain injury.

[148]  O. Hassani,et al.  Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle , 2005, The Journal of Neuroscience.

[149]  M. Hersberger,et al.  Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury , 2005, Neurology.

[150]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[151]  J. Kalita,et al.  Prognostic predictors of thalamic hemorrhage , 2005, Journal of Clinical Neuroscience.

[152]  Jon W. Johnson,et al.  Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block , 2005, Journal of Neuroscience.

[153]  G. Rinkel,et al.  Disorders of Sleep and Wake in Patients After Subarachnoid Hemorrhage , 2005, Stroke.

[154]  M. Xi,et al.  Interactions between GABAergic and Cholinergic Processes in the Nucleus Pontis Oralis: Neuronal Mechanisms Controlling Active (Rapid Eye Movement) Sleep and Wakefulness , 2004, The Journal of Neuroscience.

[155]  R. Clauss,et al.  Effect of Zolpidem on Brain Injury and Diaschisis as Detected by 99mTc HMPAO Brain SPECT in Humans , 2004, Arzneimittelforschung.

[156]  John H. Zhang,et al.  Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[157]  C. Leonard,et al.  Hypocretin/orexin peptide signaling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum. , 2004, Journal of Neurophysiology.

[158]  Theodore Speroff,et al.  Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. , 2004, JAMA.

[159]  J. Noth,et al.  CT findings and clinical features as markers for patient outcome in primary pontine hemorrhage. , 2004, AJNR. American journal of neuroradiology.

[160]  S. Hughes,et al.  Synchronized oscillations at alpha and theta frequencies in the lateral geniculate nucleus. , 2004, Neuron.

[161]  B. Siesjö,et al.  The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia , 2004, Acta Neuropathologica.

[162]  D. Krieger,et al.  Hypothermia for Acute Ischemic Stroke: Not Just Another Neuroprotectant , 2003, The neurologist.

[163]  D. Meaney,et al.  Diffuse Axonal Injury in Head Trauma , 2003, The Journal of head trauma rehabilitation.

[164]  A. Damasio,et al.  Neuroanatomical correlates of brainstem coma. , 2003, Brain : a journal of neurology.

[165]  I. Silver,et al.  Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[166]  H. Haas,et al.  The role of histamine and the tuberomamillary nucleus in the nervous system , 2003, Nature Reviews Neuroscience.

[167]  E. G. Jones,et al.  Thalamic circuitry and thalamocortical synchrony. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[168]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[169]  G. Berntson,et al.  Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour , 2002, The European journal of neuroscience.

[170]  B. Jennett.  The vegetative state , 2002, Journal of neurology, neurosurgery, and psychiatry.

[171]  M. Witter,et al.  The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness , 2002, Brain Research Reviews.

[172]  G. Hervieu,et al.  Protein distribution of the orexin-2 receptor in the rat central nervous system , 2002, Regulatory Peptides.

[173]  G. Murray,et al.  Traumatic Subarachnoid Hemorrhage: Demographic and Clinical Study of 750 Patients from the European Brain Injury Consortium Survey of Head Injuries , 2002, Neurosurgery.

[174]  A. Demchuk,et al.  Predictors of Fatal Brain Edema in Massive Hemispheric Ischemic Stroke , 2001, Stroke.

[175]  C. Saper,et al.  Narcolepsy and low CSF orexin (hypocretin) concentration after a diencephalic stroke , 2001, Neurology.

[176]  E. Wijdicks,et al.  Can We Predict Poor Outcome at Presentation in Patients with Lobar Hemorrhage? , 2001, Cerebrovascular Diseases.

[177]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[178]  D. Choi,et al.  Brain tissue responses to ischemia. , 2000, The Journal of clinical investigation.

[179]  G. B. Young,et al.  The EEG in Coma , 2000, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[180]  D F Meaney,et al.  Immediate coma following inertial brain injury dependent on axonal damage in the brainstem. , 2000, Journal of neurosurgery.

[181]  M. Mase,et al.  Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage. , 2000, Journal of neurotrauma.

[182]  R. Clauss,et al.  Extraordinary arousal from semi-comatose state on zolpidem. A case report. , 2000, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[183]  M. Xi,et al.  A GABAergic pontine reticular system is involved in the control of wakefulness and sleep. , 1999, Sleep research online : SRO.

[184]  T. Hökfelt,et al.  Hypocretin/Orexin‐ and melanin‐concentrating hormone‐expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene‐related protein systems , 1998, The Journal of comparative neurology.

[185]  R. Spetzler,et al.  Characterization of Neuroprotection from Excitotoxicity by Moderate and Profound Hypothermia in Cultured Cortical Neurons Unmasks a Temperature-Insensitive Component of Glutamate Neurotoxicity , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[186]  J. Hobson,et al.  Cholinergic and non-cholinergic afferents of the caudolateral parabrachial nucleus: a role in the long-term enhancement of rapid eye movement sleep , 1998, Neuroscience.

[187]  E. Wijdicks,et al.  Clinical profiles predictive of outcome in pontine hemorrhage , 1997, Neurology.

[188]  K. Lovblad,et al.  Hypersomnia following paramedian thalamic stroke: A report of 12 patients , 1996, Annals of neurology.

[189]  HidekazuTomimoto,et al.  Induction of c-fos and c-jun Gene Products and Heat Shock Protein After Brief and Prolonged Cerebral Ischemia in Gerbils , 1995 .

[190]  R. Nair,et al.  Diffuse axonal injury: A clinical and computerised tomography study of 128 patients , 1995 .

[191]  Y. Iwasaki,et al.  Hypoxic brain damage: cortical laminar necrosis and delayed changes in white matter at sequential MR imaging. , 1993, Radiology.

[192]  F. Cohadon,et al.  [Deep cerebral stimulation in patients with post-traumatic vegetative state. 25 cases]. , 1993, Neuro-Chirurgie.

[193]  D. McCormick.  Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity , 1992, Progress in Neurobiology.

[194]  E. Levine,et al.  Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[195]  B. Jacobs,et al.  Structure and function of the brain serotonin system. , 1992, Physiological reviews.

[196]  T A Gennarelli,et al.  Diffuse axonal injury in non-missile head injury. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[197]  B. Crain,et al.  Selective neocortical and thalamic cell death in the gerbil after transient ischemia , 1990, Neuroscience.

[198]  T Hirayama,et al.  Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. , 1990, Brain injury.

[199]  E. Benveniste,et al.  Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. , 1990, Journal of immunology.

[200]  U. Pirvola,et al.  Histamine-immunoreactive nerve fibers in the rat brain , 1989, Neuroscience.

[201]  K. Takakura,et al.  Effect of cervical spinal cord stimulation (cSCS) on cerebral glucose metabolism and blood flow in a vegetative patient assessed by positron emission tomography (PET) and single photon emission computed tomography (SPECT). , 1989, Radiation medicine.

[202]  M. Jouvet,et al.  A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats , 1989, Brain Research.

[203]  L. Symon,et al.  Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery Occlusion , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[204]  W. Hassler,et al.  The critical first minutes after subarachnoid hemorrhage. , 1988, Neurosurgery.

[205]  F. Plum,et al.  Outcome prediction in comatose patients: significance of reflex eye movement analysis. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[206]  D. Sherman,et al.  Predicting outcome from hypoxic-ischemic coma. , 1985, JAMA.

[207]  M. Mesulam,et al.  Cortical projections arising from the basal forebrain: A study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase , 1984, Neuroscience.

[208]  J. Adams,et al.  Diffuse axonal injury and traumatic coma in the primate , 1982, Annals of neurology.

[209]  J. Posner.  Plum and Posner's Diagnosis of Stupor and Coma , 1982 .

[210]  J. Deck,et al.  Selective traumatic infarction of the human anterior hypothalamus. Clinical anatomical correlation. , 1979, Journal of neurosurgery.

[211]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[212]  T. Milhorat,et al.  Experimental hydrocephalus. 3. Light microscopic findings in acute and subacute obstructive hydrocephalus in the monkey. , 1970, Journal of neurosurgery.

[213]  T. Milhorat,et al.  Experimental hydrocephalus. 2. Gross pathological findings in acute and subacute obstructive hydrocephalus in the dog and monkey. , 1970, Journal of neurosurgery.

[214]  W. Hunt,et al.  Surgical risk as related to time of intervention in the repair of intracranial aneurysms. , 1968, Journal of neurosurgery.

[215]  G. Moruzzi,et al.  Brain stem reticular formation and activation of the EEG. , 1949, Electroencephalography and clinical neurophysiology.