(BQ) Part 1 book “Smell and taste disorders” has contents: Anatomy and physiology of olfaction, anatomy and physiology of gustation, measurement of olfaction, measurement of gustation.
Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information Smell and Taste Disorders © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information Smell and Taste Disorders Christopher H Hawkes, MD FRCP Honorary Professor of Neurology and Honorary Consultant Neurologist, Neuroscience Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK Richard L Doty, PhD FAAN Professor, Department of Otorhinolaryngology: Head and Neck Surgery, and Director, Smell and Taste Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information University Printing House, Cambridge CB2 8BS, United Kingdom One Liberty Plaza, 20th Floor, New York, NY 10006, USA 477 Williamstown Road, Port Melbourne, VIC 3207, Australia 314–321, 3rd Floor, Plot 3, Splendor Forum, Jasola District Centre, New Delhi – 110025, India 79 Anson Road, #06–04/06, Singapore 079906 Cambridge University Press is part of the University of Cambridge It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning, and research at the highest international levels of excellence www.cambridge.org Information on this title: www.cambridge.org/9780521130622 DOI: 10.1017/9781139192446 © Cambridge University Press 2017 This publication is in copyright Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press First published 2017 Printed in the United Kingdom by TJ International Ltd Padstow Cornwall A catalogue record for this publication is available from the British Library ISBN 978-0-521-13062-2 Paperback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication and does not guarantee that any content on such websites is, or will remain, accurate or appropriate Every effort has been made in preparing this book to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved Nevertheless, the authors, editors, and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation The authors, editors, and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information Contents Preface vii Acknowledgments ix Anatomy and Physiology of Olfaction Neurodegenerative Chemosensory Disorders 293 Anatomy and Physiology of Gustation 46 Assessment, Treatment, and Medicolegal Aspects of Chemosensory Disorders 387 Measurement of Olfaction 80 Measurement of Gustation 138 Non-neurodegenerative Disorders of Olfaction 182 Index Non-neurodegenerative Disorders of Gustation 248 Color plates are to be found between pp 214 and 215 406 v © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information Preface This smell and taste disorders aims to provide neuroscientists, physicians, dentists, and psychologists with concise, practical, and authoritative information for understanding, testing, and managing disorders of taste and smell Nearly percent of Americans under the age of 65 suffer from some form of chronic olfactory or gustatory dysfunction – a percentage that rises to more than 50 percent of those over 65 years of age and is likely much higher in areas of the world where air and water pollution are prevalent Despite such statistics, the chemical senses remain neglected by the majority of medical practitioners Such oversight stems from a number of sources, not least of which is the lack of understanding or trivialization of these senses and the belief that their accurate assessment cannot be made in the clinic Less-than-total dysfunction is rarely brought to the attention of the physician and, when aberrations are found, many are unsure of how to proceed Although practical quantitative tests of smell function are now widely available, the majority of neurologists test only cranial nerves II through XII This continues, despite the fact that olfactory testing has been recommended by the Quality Standards Committee of the American Academy of Neurology for inclusion in the diagnostic criteria for Parkinson’s disease (Suchowersky et al., 2006) Similar suggestions have been made for inclusion of smell testing as an aid in the diagnosis of Alzheimer’s disease (Foster et al., 2008) There is evidence that smell tests can be useful in differential diagnosis of several disorders (e.g., depression vs Alzheimer’s disease; Parkinson’s disease vs progressive supranuclear palsy and essential tremor) Moreover, they may assist the detection of malingering Loss of smell or taste has considerable medico-legal importance, commanding major financial compensation for those who are victims of head injury or exposure to toxic agents, particularly for the young and persons whose livelihoods depend upon chemosensation As this book emphasizes, there are no longer excuses for neglecting the chemical senses in medical practice Smell and taste are regularly lumped together, particularly by lay people While both are chemical senses and contribute to the flavor of foods and beverages, in the embryo these two systems develop independently and are completely separate at subcortical level and merge only at the anterior insula Olfaction is seemingly more ancient, developing first phylogenetically; taste, as an oral chemosensory system, is a relatively new thalamic-dependent system It is important to recognize, however, that both olfactory and gustatory receptor proteins are found outside of the nose and oral cavity, suggesting that these proteins are ubiquitous and have functions beyond those of transducing the conscious perception of tastes and smells For example, olfactory receptor proteins have been found in the tongue, brain, prostate, enterochromaffin cells, pulmonary neuroendocrine cells, and spermatozoa Taste receptors have now been reported in the epiglottis, larynx, respiratory epithelium, stomach, pancreas, and colon, where they influence such processes as digestion, chemical absorption, insulin release, and protection of the epithelium from xenobiotic agents Olfaction is more plastic than taste, and it is damaged more readily from head trauma, viruses, and exposure to xenobiotics Inborn mechanisms largely determine the meaning of taste experiences, whereas learning plays a much greater role for the sense of smell Nonetheless, these primary sensory modalities intermingle both with each other and other sensory systems at the cortical level – interactions that in some cases are influenced greatly by learning Such interplay is only just beginning to be understood vii © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information viii Preface Many chemosensory systems have evolved in mammals, including the vomeronasal system, but the senses of taste and smell are the most prominent in humans In Chapters and we emphasize the anatomy and physiology of these two modalities, beginning with olfaction, which as noted above is typically more compromised than taste by injury and disease In subsequent chapters we review methods to measure smell (Chapter 3) and taste (Chapter 4), what factors influence these modalities, and, from a clinical perspective, the nature and major causes of their dysfunction with an emphasis on neurological disorders (Chapters 5, 6, and 7) Our goal is to provide up-to-date information about these senses in health and disease, and to guide the practitioner in the assessment, treatment, and management of patients with chemosensory disturbances (Chapter 8) We express our gratitude to the editors of Cambridge University Press who agreed to an update of our earlier work The Neurology of Olfaction (2009) and to include taste complaints We hope that this compendium will serve the needs of a broad array of clinicians and scientists who recognize the unique role that the chemical senses play in medicine and everyday life References Foster, J., Sohrabi, H., Verdile, G and Martins, R., 2008 Research criteria for the diagnosis of Alzheimer’s disease: Genetic risk factors, blood biomarkers and olfactory dysfunction International Psychogeriatrics 20(4), 853–855 Hawkes, C.H., Doty, R.L., 2009 The Neurology of Olfaction Cambridge, UK: Cambridge University Press © in this web service Cambridge University Press Suchowersky, O., Reich, S., Perlmutter, J., Zesiewicz, T., Gronseth, G., Weiner, W.J., 2006 Practice parameter: Diagnosis and prognosis of new onset Parkinson disease (an evidence-based review) Report of the quality standards subcommittee of the American Academy of Neurology Neurology 66(7), 968–975 www.cambridge.org Cambridge University Press 978-0-521-13062-2 — Smell and Taste Disorders Christopher H Hawkes , Richard L Doty Frontmatter More Information Acknowledgments We owe a debt of gratitude to the following who have helped with various sections of this volume: Professor Kailash Bhatia, National Hospital for Neurology and Neurosurgery, Queen Square, London Professor Jay Gottfried, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania Professor John Hardy, National Hospital for Neurology and Neurosurgery, Queen Square, London Dr Isabel Ubeda-Banon, Universidad de Castilla-La Mancha, Avda de Moledores s/n, 13071, Ciudad Real, Spain Professor Jason Warren, National Hospital for Neurology and Neurosurgery, Queen Square, London ix © in this web service Cambridge University Press www.cambridge.org Chapter Anatomy and Physiology of Olfaction Introduction The evolution of life required organisms to sense chemicals suspended or dissolved in water Some of these chemicals provided nourishment, whereas others were destructive and had to be avoided Single-celled organisms, such as Escherichia coli, developed multiple chemical receptors critical for such survival The rotatory direction of their flagellae – whip-like appendages used to propel them through their environment – is altered by the type of chemical encountered Thus, chemicals important for sustenance induce a counterclockwise rotation of the flagella, facilitating a smooth and somewhat linear swimming path, whereas toxic chemicals provoke a clockwise flagellar rotation, resulting in tumbling and turning away from the offending stimulus (Larsen et al., 1974) The sense of smell is one of nature’s true wonders, being ubiquitous within the animal kingdom and capable of detecting and differentiating thousands of diverse odorants at very low concentrations Humans possess far more odorant receptor types than any other sensory system, which explains, in part, their ability to perceive such a large number of stimuli It is now well established, as described in subsequent chapters of this book, that the olfactory system provides a unique probe into the general health of the brain Thus, smell loss is among the first signs of neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease and provides insight into elements of brain development Importantly, smell loss is one of the best predictors of future mortality in older populations, being a stronger predictor than cognitive deficits, cancer, stroke, lung disease, or hypertension even after controlling for the effects of age, sex, race, education, socioeconomic status, smoking behavior, alcohol use, cardiovascular disease, diabetes, and liver damage (Wilson et al., 2011; Gopinath et al., 2012; Pinto et al., 2014; Devanand et al., 2015) In the future, screening for a range of neurological disorders by olfactory biomarkers may be commonplace and may encourage the development of protective measures that delay or prevent central nervous system (CNS) degeneration We now describe the detailed anatomy, physiology, and pharmacology of the olfactory pathway, followed by factors that influence olfactory input and its interpretation Nasal Cavity During normal inspiration, only 5–10 percent of inhaled air reaches the olfactory epithelium This specialized pseudostratified neuroepithelium harbors the olfactory receptors It is found high within the nasal vault, lining sectors of the upper nasal septum, cribriform plate, superior turbinates, and, to a lesser extent, the anterior aspect of the middle turbinates 14:54:42 02 Smell and Taste Disorders Olfactory bulb Cribriform plate Olfactory epithelium Superior Inferior l sa na nt tro a nx or Re ary ph so Na Turbinates Od O Od r th or on a No as nt str al il Middle Palate Figure 1.1 This figure shows the human nasal cavity and extent of the olfactory epithelium Note the extension of the epithelium onto the anterior part of the middle turbinate Odorants access the olfactory epithelium either directly through the orthonasal route (anterior arrow) or indirectly through the retronasal route as in chewing or swallowing (posterior arrow) Reproduced with permission from Rawson, N (2000), Chapter 11, Human olfaction (Figure 1.1) The existence of olfactory receptor neurons (ORN) on the middle turbinate is a useful aspect of applied anatomy for those wishing to biopsy olfactory receptor cells (ORC) for culture, histology, or patch clamp studies, as it is more accessible and less risky to sample than the main olfactory area Sniffing Although sniffing assists smell recognition and identification, the first awareness of a new odor can be passive; sniffing then follows in an attempt to analyze the odor further and assess its behavioral significance Sniffing redirects up to 15 percent of the inhaled air through the olfactory meatus, a ~1 mm-wide opening leading to the uppermost sector of the nose that contains most of the olfactory epithelium Sniffing helps to increase the number of odorous molecules that ultimately reach this region However, molecules must absorb into the mucus that forms across the nasal mucosa to make contact with the olfactory receptor cells In some cases – particularly in the case of hydrophobic odorants – stimuli may be carried through this mucus by specialized “odorant carrier” proteins to the receptors (Pelosi et al., 1990) It should be emphasized that without a moist mucosal surface, detection of odors is largely impossible As mentioned in Chapter 5, diseases with excessive nasal dryness such as Sjögren’s syndrome are often accompanied by smell dysfunction Nasal Turbinates The nasal turbinates are highly vascularized structures that extend into the nasal cavity from its lateral wall (Figure 1.2) They can rapidly expand or contract, depending upon autonomic nervous system tone and stimulation Exercise, hypercapnia, and increased sympathetic tone constrict their engorgement, whereas cold air, irritants, hypocapnia, and 14:54:42 02 Anatomy and Physiology of Olfaction Figure 1.2 Coronal T1–weighted MRI scan to show the main structures around the nose increased parasympathetic tone can induce such engorgement Turbinate engorgement can be influenced by pressure on sectors of the body, body position, or ambient temperature Leftto-right fluctuations in relative engorgement, termed the nasal cycle, occur in many people over time, although these change with age and reciprocity is frequently the exception rather than the rule (Mirza et al., 1997) These fluctuations relate to changes in lateralized blood flow to various paired organs, including the two brain hemispheres, and belong to the basic restactivity cycle, a continuation of the REM/non-REM sleep cycle that occurs during the daytime Although the turbinates have never been thought relevant to the clinical neurologist, this concept may need to change given the recent suggestion that rhinorrhea, secondary to relative parasympathetic overactivity, may be a prodromal sign of Parkinson’s disease (see Chapter and Bower et al., 2006) Innervation of the Nasal Cavity In common with the nasal and oral mucosae, the olfactory epithelium also contains free nerve endings from the trigeminal nerve (CN V) Nonolfactory elements of nasal chemosensation, e.g., sharpness, coolness, warmth, and pungency, are mediated via free nerve endings of this nerve (Figure 1.3) These free nerve endings are supplied to the upper part of the nasal cavity by the anterior and posterior ethmoid nerves – branches of the nasociliary nerve which come from the ophthalmic (first division) of the trigeminal nerve The nasopalatine nerve, a branch of the maxillary nerve (second division of the trigeminal nerve) is the source of the CN V fibers innervating the posterior nasal cavity Most odorous compounds stimulate CN I and CN V, at least at higher 14:54:42 02 ... L&R 10 14 10 .6 (8.8) 13 .0 (9.2) 11 .7 13 .0 (9 .1) 12 .1 (9 .1) 12 .5 15 19 12 .2 (8.8) 12 .7 (9 .1) 12 .4 12 13 .0 (9.2) 12 .9 (9.2) 12 .9 20–29 10 15 .2 (10 .0) 14 .0 (9.3) 14 .6 11 16 .5 (9.6) 15 .6 (9.4) 16 .0... (10 .2) 10 2.4 (10 .3) 10 4.4 60–69 10 13 2.0 (10 .3) 11 6.0 (10 .3) 12 3.7 10 12 8.8 (10 .4) 12 4.0 (10 .0) 12 6.4 >70 14 6.4 (10 .4) 16 2.4 (10 .6) 15 4.2 17 1.2 (10 .0) 16 2.4 (10 .8) 16 6.7 16 6 Smell and Taste Disorders... 19 91) This superfamily comprises 18 gene families and 300 14 :54:42 02 10 Smell and Taste Disorders 6 11 10 14 N 7 G 16 15 16 15 P 11 15 II R 17 N I 25 25 D 14 21 24 13 15 D 11 * * 15 * * 24 13