DOCSLIB.ORG

Small Fiber Neuropathy and Sodium Channels : a Paradigm Shift

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Small Fiber Neuropathy and Sodium Channels : a Paradigm Shift Small fiber neuropathy and sodium channels : a paradigm shift Citation for published version (APA): Hoeijmakers, J. G. J. (2014). Small fiber neuropathy and sodium channels : a paradigm shift. Datawyse / Universitaire Pers Maastricht. https://doi.org/10.26481/dis.20140214jh Document status and date: Published: 01/01/2014 DOI: 10.26481/dis.20140214jh Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.umlib.nl/taverne-license Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 11 Oct. 2021 Small fiber neuropathy and sodium channels a paradigm shift Janneke G. J. Hoeijmakers © J.G.J. Hoeijmakers, 2014 Lay-out: Jos Hendrix Cover: Gijs Hoeijmakers Production: Datawyse/Universitaire Pers Maastricht ISBN 978 94 6159 289 9 The studies described in this thesis were performed at the Department of Neurology of the Maastricht University Medical Center, Maastricht, the Netherlands and at the Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT 06516, USA The printing of this thesis was financially supported by Pfizer. Small fiber neuropathy and sodium channels a paradigm shift PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit Maastricht, op gezag van de Rector Magnificus, Prof. dr. L.L.G. Soete volgens het besluit van het College van Decanen, in het openbaar te verdedigen op vrijdag 14 februari 2014 om 14.00 uur door Janneke Gertrude Jacobine Hoeijmakers Promotiecommissie Promotor: Prof. dr. R.J. van Oostenbrugge Copromotoren: Dr. C.G. Faber Dr. I.S.J. Merkies Beoordelingscommissie: Prof. dr. M. Van Kleef, voorzitter Prof. dr. C.E.M. De Die-Smulders Prof. dr. I.N. van Schaik (Academisch Medisch Centrum, Amsterdam) Prof. dr. H.J.M. Smeets Dr. P.A.G. Volders Contents Abbreviations 6 Chapter 1 General introduction and outline of thesis 9 Chapter 2 Small-fiber neuropathies: advances in diagnosis, 23 pathophysiology and management Chapter 3 Gain-of-function NaV1.7 mutations in 51 idiopathic small fiber neuropathy Chapter 4 Intra- and interfamily phenotypic diversity in pain syndromes 79 associated with a gain-of-function variant of NaV1.7 Chapter 5 NaV1.7-related small fiber neuropathy: 99 impaired slow-inactivation and DRG neuron hyperexcitability Chapter 6 Functional profiles of SCN9A variants in dorsal root ganglion 115 neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fiber neuropathy Chapter 7 Small nerve fibers, small hands and small feet: 143 a new syndrome of pain, dysautonomia and acromesomelia in a kindred with a novel NaV1.7 mutation Chapter 8 Genetic aspects of sodium channelopathy 171 in small fiber neuropathy Chapter 9 Summary, general discussion and future perspectives 187 Chapter 10 Nederlandse samenvatting 211 Dankwoord 217 Curriculum vitae 222 List of publications 224 Abbreviations APs Action potentials ARFS Axon Reflex Flare Size CHEPs Contact heat-evoked potentials CIP Congenital insensitivity to pain DRG Dorsal root ganglion FAP Familial amyloid polyneuropathy GFP Green fluorescent protein HIV Human immunodeficiency virus IEM Inherited erythromelalgia IENF Intraepidermal nerve fiber IENFD Intraepidermal nerve fiber density IES Intraepidermal electrical stimulation IL Interleukin I-SFN Idiopathic small fiber neuropathy LEPs Laser-evoked potentials NaV1.3 Voltage-gated sodium channel 1.3 NaV1.6 Voltage-gated sodium channel 1.6 NaV1.7 Voltage-gated sodium channel 1.7 NaV1.8 Voltage-gated sodium channel 1.8 NaV1.9 Voltage-gated sodium channel 1.9 NCS Nerve conduction studies NGF Nerve growth factor NPS Neuropathic Pain Scale PEPD Paroxysmal extreme pain disorder PGP 9.5 Protein gene product 9.5 PREPs Pain-related evoked potentials QSART Quantitative Sudomotor Axon Reflex Test QST Quantitative sensory testing RMP Resting membrane potential SCN3A Sodium channel, voltage-gated, type III, alpha subunit SCN8A Sodium channel, voltage-gated, type VIII, alpha subunit SCN9A Sodium channel, voltage-gated, type IX, alpha subunit SCN10A Sodium channel, voltage-gated, type X, alpha subunit SCN11A Sodium channel, voltage-gated, type XI, alpha subunit SFN Small fiber neuropathy SFN-SIQ SFN Symptom Inventory Questionnaire SGC Superior cervical ganglion SSR Sympathetic Skin Response SVR Skin Vasomotor Reflex TNF-α Tumor necrosis factor-α TRP Transient receptor potential TTX Tetrodotoxin VAS Visual Analogue Pain Scale VGSC Voltage-gated sodium channel WT Wild-type Chapter 1 General introduction and outline of thesis Introduction Small fiber neuropathy Small fiber neuropathy (SFN) is a condition characterized by neuropathic pain and autonomic symptoms, caused by dysfunction of the thinly myelinated Aδ-fibers and unmyelinated C-fibers. As early as 1868, Paul Langerhans made drawings of the small diameter nerve fiber extensions in the human epidermis.1 However, it took up until the last two decades, for SFN to be fully recognized as a distinct nosological entity. Despite debilitating symptoms, neurological examination and nerve conduction studies (NCS) are generally normal in the pure form of SFN. The introduction of specific diagnostic tests, such as quantitative sensory testing (QST)2 and, in particular, intraepidermal nerve fiber density (IENFD) quantification by skin biopsy,3 made it possible to establish a more reliable diagnosis.4, 5 After the diagnosis SFN is made, an underlying cause has to be searched for, as some are potentially treatable. Diabetes mellitus is most frequently associated with SFN5, but also a causal relationship with HIV, hyperlipidaemia, amyloidosis, Fabry disease, celiac disease, sarcoidosis and other systemic illnesses is suggested.6-8 However, the exact way in which these disorders results in the degeneration of the small nerve fibers is not elucidated yet. Besides, in a substantial proportion of patients diagnosed with SFN, ranging from 24% to 93% in different series, no underlying condition can be demonstrated.4, 7, 9 In this group of idiopathic SFN (I-SFN) patients causative treatment is impossible and therapy will mainly focus on neuropathic pain relief, unfortunately often with suboptimal effect. A better understanding of the pathophysiology of SFN is necessary to optimize patient management. Pathophysiology of peripheral neuropathies As with other peripheral neuropathies, multiple underlying conditions can cause SFN. The conditions that are associated with SFN can be classified into the following groups: metabolic, immune-mediated, toxic, infectious, hereditary and idiopathic. Many of these disorders also affect the large diameter nerve fibers, resulting in a mixed polyneuropathy. Several pathophysiological mechanisms have been proposed to cause peripheral neuropathies, usually related to the type of underlying condition. However, details about the degeneration of the small nerve fibers remain unknown. The pathophysiology of diabetic polyneuropathy has been studied most, especially in rat models. Hyperglycaemia might disturb the polyol pathway, which through various changes may result in production of nerve toxic reactive oxygen.10 Ischemia, in diabetes caused by vascular disease, may also induce reactive oxygen species. The smaller myelinated and unmyelinated fibers 10 11 appear to be most sensitive for this. Nerve growth factor (NGF) would Chapter protect the nerve fibers against oxidative stress. In diabetes, however, impaired 1. neurotrophic transport may lower the levels of NGF and could therefore indirect lead to nerve dysfunction.12 In addition, in two diabetes studies with capsaicin induced axotomy, a role for damaged axonal transport13 and impaired vascular regeneration14 was suggested. Besides diabetic polyneuropathy, the pathophysiology of peripheral neuropathy in immunological disorders has also been studied extensively. In some small studies immunomodulatory therapy showed reduction of SFN-related symptoms, supporting the presumption of a causal relationship between an activated immune system and nerve
Load more

Recommended publications
  • Evaluation of Symptom Heterogeneity in Neuropathic Pain Using Assessments of Sensory Functions
    Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics Evaluation of Symptom Heterogeneity in Neuropathic Pain Using Assessments of Sensory Functions Kathrin Arning and Ralf Baron Division of Neurological Pain Research and Therapy, Department of Neurology, Christian-Albrechts-Universität Kiel, Germany Summary: Classification of neuropathic pain has been based can be elucidated in each patient. Moreover, in questionnaires on disease entities, anatomical localization, or histological ob- the verbal descriptors can depict the quality and intensity of the servations. Over the past decade, there has been an explosion in individual pain. The approach of classifying and subgrouping our understanding of the basic mechanisms of neuropathic pain. patients with neuropathic pain on the basis of symptoms or The exciting advances in basic science are paralleled by the signs opens up new possibilities for stratifying patients in clin- recognition from clinical investigations that neuropathic pain is ical trials. First, in clinical proof-of-concept trials the study not a monolithic entity, but instead presents as a composite of population can be enriched prospectively on the basis of entry pain and other sensory symptoms. Attempts are under way to criteria defined a priori. This enrichment with patients who supplement the traditional classification with a classification potentially require a specific treatment should increase the like- that links pain and sensory symptoms with neurobiological lihood for positive trial outcomes. Second, in clinical practice it mechanisms. This mechanism- or symptom-based classifica- becomes possible to establish an individualized therapy—that tion takes both negative and positive sensory symptoms into is, to identify the particular patients who require a specific account.
    [Show full text]
  • Restless Legs Syndrome in Adults
    The night time hustle: managing restless legs syndrome in adults 18 BPJ Issue 49 Restless legs syndrome is a common condition that Approximately four in five people with restless legs syndrome can significantly affect a patient’s quality of life. It also experience periodic limb movement of sleep (PLMS). is a neurological disorder, which can be diagnosed This is characterised by involuntary leg movement while the on the basis of the patient’s description of their person is asleep. The condition can cause repeated waking and poor sleep quality. The presence of PLMS in a person symptoms. Lifestyle modification is the mainstay with restless legs syndrome is likely to increase the severity of of treatment for patients with mild or infrequent impact on the person’s quality of life through the combination symptoms. Pharmacological treatments, starting of delayed sleep onset from restless legs syndrome and poor with dopamine agonists, should be reserved for quality sleep from PLMS. people with more severe symptoms. A diagnosis is made based on description of What is restless legs syndrome? symptoms Restless legs syndrome is a neurological disorder characterised There is no specific examination or test that will confirm a by throbbing, pulling, creeping or other unpleasant sensations diagnosis of restless legs syndrome. The patient’s description in the legs and an uncontrollable, usually overwhelming, urge of their symptoms, combined with a brief history, is sufficient to move them. Symptoms occur primarily in the evening when to make a diagnosis. a person is relaxing, and can increase in severity throughout the night. Both legs may be affected or one may be worse than The diagnostic criteria for restless legs syndrome is a history the other.
    [Show full text]
  • Siegenthaler, Differential Diagnosis in Internal Medicine (ISBN9783131421418), © 2007 Georg Thieme Verlag Index
    Index Notes: Please note that entries in bold and italics represent tables and figures respectively A parapharyngeal space, 479 acromegaly, 81, 82, 743−744 acute renal failure (ARF), 852−857 spleen, 151 hands, 90 angiography, 854 Abciximab, thrombocytopenia, teeth, 212 hypertension, 738 causes, 853 459 tuberculous paravertebral, skin changes, 66 classification, 852 abdomen 597−599 ACTH-dependent Cushing definition, 852 acute see acute abdomen absolute pupillary areflexia, 97 syndrome, 742 diagnostic procedure, 855−857 angina, mesenteric infarction, Abt−Letterer−Siwe disease, 445 ACTH-independent Cushing blood analysis, 856 266 Acanthamoeba infection, syndrome, 742−743 glomerular filtration rate, 855 blood vessels, polyarteritis meningitis, 135 Actinomyces infection see main laboratory nodosa, 179 acanthocytes actinomycosis investigations, 856 pain see abdominal pain liver cirrhosis, 398 Actinomyces israelii, 131 physical examination, physical examination, 30−31 urinary sediment analysis, 847, actinomycosis, 71, 526 855−856 pleural effusion, 248 848 neck swelling, 131 radiologic examinations, 857 ultrasound, secondary acanthocytosis, 417 activated partial thromboplastin renal biopsy, 857 hypertension, 733 acanthosis nigricans, 55, 55 time (aPTT), 452, 1052−1053 urinalysis, 856 abdominal organs, nervous accelerated junctional rhythms, acute abdomen, 257−259 differential diagnosis, 855, system, 256 719 causes, 257, 257−258 855−857 abdominal pain acetaminophen chronic renal failure, 861 acute tubular necrosis vs., acute, 257−273 analgesic
    [Show full text]
  • Gain of Function Nav1.7 Mutations in Idiopathic Small Fiber Neuropathy
    ORIGINAL ARTICLE Gain of Function NaV1.7 Mutations in Idiopathic Small Fiber Neuropathy Catharina G. Faber, MD, PhD,1 Janneke G. J. Hoeijmakers, MD,1 Hye-Sook Ahn, PhD,2,3 Xiaoyang Cheng, PhD,2,3 Chongyang Han, PhD,2,3 Jin-Sung Choi, PhD,2,3* Mark Estacion, PhD,2,3 Giuseppe Lauria, MD, PhD,4 Els K. Vanhoutte, MD,1 Monique M. Gerrits, PhD,5 Sulayman Dib-Hajj, PhD,2,3 Joost P. H. Drenth, MD, PhD,6 Stephen G. Waxman, MD, PhD,2,3 and Ingemar S. J. Merkies, MD, PhD1,7 Objective: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage- gated sodium channel NaV1.7, which is preferentially expressed in small diameter peripheral axons. Methods: Patients referred with possible I-SFN, who met the criteria of 2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. Results: Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable.
    [Show full text]
  • Erythromelalgia - an Uncommon Challenging Entity
    Data da submissão: 6 de Março de 2021 CARTA AO EDITOR Data da aprovação: 17 de Março de 2021 ERYTHROMELALGIA - AN UNCOMMON CHALLENGING ENTITY ERITROMELALGIA - UMA ENTIDADE DESAFIADORA INCOMUM Vitorino Modesto dos Santos, Laura Campos Modesto DOI - 10.5935/2236-5117.2021v58a44 small fiber neuropathies, neurofibromatosis, and Vitorino Modesto dos Santos – Armed Forces Hospital and Catholic University, multiple sclerosis), diabetes gout, astrocytoma, Brasília-DF, Brazil, Internal Medicine - Brasília - DF, Brasil. colon cancer, thyroid cancer, and breast cancer, Laura Campos Modesto – University Center of Brasília (Uniceub), Brasília-DF, medications (bromocriptine, nifedipine, verapamil, Brazil, Medical Course - Brasília - DF, Brasil. topical isopropanol, pergolide, and simvastatin), arterial hypertension, venous insufficiency, pregnancy, Correspondência: Vitorino Modesto dos Santos. Quadra SMPW 1-5 Quadra 14 Conjunto 2, Lote 7, Casa A, Park Way, Brasília - DF, Brasil alcohol abuse, and mercury poisoning. The common - CEP: 71741402 hypothesis for both types of EM is that symptoms occur Internet: [email protected] by skin hypoxia due to increased arteriovenous shunting and imbalance between thermoregulatory and nutritive perfusion.1 The symptoms of EM typically appear under influence of warm or exercise and improve by cooling Conflito de interesses: não existem conflitos de interesse. the affected regions; the episodes commonly occur at night periods and the affected regions characteristically remain normal between the acute crises.
    [Show full text]
  • National Consensus on Diagnosis and Treatment of Pain of Neurological Origin
    National Consensus on Diagnosis and Treatment of Pain of Neurological Origin Under the supervision of Acad. Prof. I. Milanov, MD, PhD, DSc. By initiative of the Bulgarian Headache and Pain Association 3 Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Classification By its duration pain is classified as acute and chronic. Acute pain is a symptom, chronic pain is a disease. Acute pain is related to clearly identified tissue injury and lasts no more than 1 month from its onset. It is protective and gradually resolves as the injured tissues heal, when the environment surrounding the nociceptors is normalized and their hyperactivity resolved. Chronic pain persists for more than 3 months. It is caused by tissue damage but continues even after the causative lesion heals. It is not due to activation of nociceptors and has no protective effect. According to the underlying pathophysiological mechanisms pain is classified as nociceptive or neuropathic. The combination of both types (mixed) pain is common. According to its anatomical location pain is classified as head, face and mouth pain; cervical pain; pain in shoulders and arms; thoracic; abdominal; lumbar pain; pain in lower limbs; pelvic; anal, perianal and genital pain. Nociceptive pain It is caused by injury to any organ or system other than the nervous system, and its diagnosis and treatment is associated with a number of medical specialties. It is subdivided into physiological nociceptive pain, caused by temporary dysfunction (cramps, colics), and pathological nociceptive pain, caused by tissue injury. Neuropathic pain It is pain caused by dysfunction, lesion or disease directly affecting the somatosensory nervous system.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0157405 A1 White, III (43) Pub
    US 2012O157405A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0157405 A1 White, III (43) Pub. Date: Jun. 21, 2012 (54) METHODS AND COMPOSITIONS FOR THE A63L/488 (2006.01) TREATMENT OF "BURNING FEET A 6LX 3/59 (2006.01) SYNDROME" A63L/385 (2006.01) A6II 3/525 (2006.01) (76) Inventor: John B. White, III, Hurricane, WV (US) (52) U.S. Cl. ........... 514/52: 514/440, 514/276; 514/251: 514/89: 514/387: 514/249 (21) Appl. No.: 13/229,860 (57) ABSTRACT (22) Filed: Sep. 12, 2011 A composition for the treatment of “Burning Feet Syndrome' Related U.S. Application Data includes pantothenic acid or its analogs, or its derivatives, or its synonyms, alpha-lipoic acid or its analogs, or its deriva (63) Continuation-in-part of application No. 12/972.499. tives, or its synonyms, and L-arginine or its analogs, or its filed on Dec. 19, 2010. derivatives, or its synonyms. The composition may also include at least one Substance selected from the group con Publication Classification sisting of B1, B2, B3, B6, B7, B9, B12, Acetly-L-Carnitine, (51) Int. Cl. N-acetlycystein, Omega-3 fatty acids, Omega-6 fatty acids, A6 IK3I/7064 (2006.01) Vitamin E, and Taurine or any of their analogs, derivatives, or A6 IK3I/SI (2006.01) synonyms. The composition is used in a method for the treat A6IP 25/02 (2006.01) ing of “Burning Feet Syndrome' by administering to a human A6 IK3I/675 (2006.01) Such a composition. US 2012/O157405 A1 Jun.
    [Show full text]
  • Vol 27, No 05 | May 2013
    PEDIATRIC NEUROLOGY BRIEFS A MONTHLY JOURNAL REVIEW J. GORDON MILLICHAP, M.D., F.R.C.P., EDITOR Vol. 27, No. 5 May 2013 NEUROMUSCULAR DISORDERS SMALL-FIBER POLYNEUROPATHY AND PAIN SYNDROMES Investigators at the Massachusetts General Hospital, Boston, MA, tested the hypothesis that acquired small-fiber polyneuropathy (SFPN) contributes to unexplained widespread pain syndromes in children and adolescents. Medical records of 41 consecutive patients were analyzed for objective diagnostic test data for SFPN. These included skin biopsy, nerve biopsy, and autonomic function testing, plus histories, symptoms and signs, and treatments. Healthy matched volunteers acted as normal controls for SFPN tests. In this polyethnic patient sample, age at illness onset averaged 12.3 +/- 5.7 years; 73% were female, 68% chronically disabled, and 68% had been hospitalized. Objective diagnostic test results were definite for SFPN in 59%, probable in 17%, and possible in 22%. Only 1 had normal SFPN test results. Somatic complaints other than pain were reported in 98% patients and were consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urological). Chronic fatigue was reported in 83% and chronic headache in 63%. Neurological examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including erythromelalgia in 23%. Tests for causality of pain revealed only a history of autoimmune disease elicited in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or IV immunoglobulin benefited 80% of patients (12/15), both objectively and subjectively. (Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics 2013 Apr;131(4):e1091-e1100).
    [Show full text]
  • MAYO CLINIC ESSENTIAL NEUROLOGY Covers the Full Scope of Neurology by Combining a Focused Need-To-Know Format with Core Knowledge Andrea C
    A Concise and Succinct Guide to Neurology! Illustrated in Full Color This full-color guide to the essentials of neurology provides Adams Mayo Clinic practicing clinicians and students with one of the most focused Throughout presentations in the field today. Essential Neurology MAYO CLINIC ESSENTIAL NEUROLOGY covers the full scope of neurology by combining a focused need-to-know format with core knowledge Andrea C. Adams, MD as well as diagnosis and treatment guidelines. More than 75 color illustrations and numerous therapeutic tables help you diagnose, treat, and manage the Clinic Essential Neurology Mayo most commonly encountered neurologic problems. TOPICS INCLUDE: • The Neurologic Examination • Cognitive Loss • Diagnostic Tests • Spells • Headache • Pain • Spine and Limb Pain • Cerebrovascular Disease • Dizziness • Movement Disorders • Sensory Loss and Paresthesias • Immune and Infectious Diseases • Weakness • Neuro-oncology The perfect introduction for medical students, and a great daily reference for residents and clinicians, Mayo Clinic Essential Neurology’s current and consultative full-color format provides a fresh alternative to the current library of neurology references in print today. ABOUT THE AUTHOR ANDREA C. ADAMS, M.D., is a Consultant, Department of Neurology, Mayo Clinic, Rochester, Minnesota, and Assistant Professor of Neurology, College of Medicine, Mayo Clinic. MAYO CLINIC SCIENTIFIC PRESS Mayo Clinic Essential Neurology Andrea C. Adams, MD Mayo Clinic Essential Neurology Andrea C. Adams, MD Consultant, Department of Neurology, Mayo Clinic, Rochester, Minnesota; Assistant Professor of Neurology, College of Medicine, Mayo Clinic MAYO CLINIC SCIENTIFIC PRESS AND INFORMA HEALTHCARE USA, INC ISBN-13 9781420079739 The triple-shield Mayo logo and the words MAYO, MAYO CLINIC, and MAYO CLINIC SCIENTIFIC PRESS are marks of Mayo Foundation for Medical Education and Research.
    [Show full text]
  • Copyrighted Material
    1 Index Note: Page numbers in italics refer to figures, those in bold refer to tables and boxes. References are to pages within chapters, thus 58.10 is page 10 of Chapter 58. A definition 87.2 congenital ichthyoses 65.38–9 differential diagnosis 90.62 A fibres 85.1, 85.2 dermatomyositis association 88.21 discoid lupus erythematosus occupational 90.56–9 α-adrenoceptor agonists 106.8 differential diagnosis 87.5 treatment 89.41 chemical origin 130.10–12 abacavir disease course 87.5 hand eczema treatment 39.18 clinical features 90.58 drug eruptions 31.18 drug-induced 87.4 hidradenitis suppurativa management definition 90.56 HLA allele association 12.5 endocrine disorder skin signs 149.10, 92.10 differential diagnosis 90.57 hypersensitivity 119.6 149.11 keratitis–ichthyosis–deafness syndrome epidemiology 90.58 pharmacological hypersensitivity 31.10– epidemiology 87.3 treatment 65.32 investigations 90.58–9 11 familial 87.4 keratoacanthoma treatment 142.36 management 90.59 ABCA12 gene mutations 65.7 familial partial lipodystrophy neutral lipid storage disease with papular elastorrhexis differential ABCC6 gene mutations 72.27, 72.30 association 74.2 ichthyosis treatment 65.33 diagnosis 96.30 ABCC11 gene mutations 94.16 generalized 87.4 pityriasis rubra pilaris treatment 36.5, penile 111.19 abdominal wall, lymphoedema 105.20–1 genital 111.27 36.6 photodynamic therapy 22.7 ABHD5 gene mutations 65.32 HIV infection 31.12 psoriasis pomade 90.17 abrasions, sports injuries 123.16 investigations 87.5 generalized pustular 35.37 prepubertal 90.59–64 Abrikossoff
    [Show full text]
  • The Night Time Hustle: Managing Restless Legs Syndrome in Adults
    The night time hustle: managing restless legs syndrome in adults 18 Restless legs syndrome is a common condition that Approximately four in five people with restless legs syndrome can significantly affect a patient’s quality of life. It also experience periodic limb movement of sleep (PLMS). is a neurological disorder, which can be diagnosed This is characterised by involuntary leg movement while the on the basis of the patient’s description of their person is asleep. The condition can cause repeated waking and poor sleep quality. The presence of PLMS in a person symptoms. Lifestyle modification is the mainstay with restless legs syndrome is likely to increase the severity of of treatment for patients with mild or infrequent impact on the person’s quality of life through the combination symptoms. Pharmacological treatments, starting of delayed sleep onset from restless legs syndrome and poor with dopamine agonists, should be reserved for quality sleep from PLMS. people with more severe symptoms. A diagnosis is made based on description of What is restless legs syndrome? symptoms Restless legs syndrome is a neurological disorder characterised There is no specific examination or test that will confirm a by throbbing, pulling, creeping or other unpleasant sensations diagnosis of restless legs syndrome. The patient’s description in the legs and an uncontrollable, usually overwhelming, urge of their symptoms, combined with a brief history, is sufficient to move them. Symptoms occur primarily in the evening when to make a diagnosis. a person is relaxing, and can increase in severity throughout the night. Both legs may be affected or one may be worse than The diagnostic criteria for restless legs syndrome is a history the other.
    [Show full text]
  • Burning Feet Syndrome a Clinical Review
    CLINICAL PRACTICE: Clinical review Burning feet syndrome A clinical review Ravinder P S Makkar, MD, is Medical Advisor, Department of Medical Assistance, International SOS, New Delhi, India. Anju Arora, MD, is attending physician, Department of Medicine, Sitaram Bhartia Institute of Science and Research, New Delhi, India. Amitabh Monga, MD, is attending physician, Department of Medicine, Sitaram Bhartia Institute of Science and Research, New Delhi, India. Ajay Kr Gupta, MD, is attending physician, Department of Medicine, Sitaram Bhartia Institute of Science and Research, New Delhi, India. Surabhi Mukhopadhyay, MD, is attending physician Department of Medicine, Sitaram Bhartia Institute of Science and Research, New Delhi, India. BACKGROUND Burning pain in the feet has been known to occur as a distinct clinical symptom for almost two centuries. Despite being a common and fascinating clinical entity, this syndrome has received scant attention in the medical literature and has been described only in anecdotal reports. OBJECTIVE This article describes and discusses the various aspects of this intriguing syndrome. DISCUSSION Burning feet syndrome (BFS) is a common disorder especially among the elderly and is frequently encountered in general practice. There is no specific aetiology and it can occur as an isolated symptom or as part of a symptom complex in a variety of clinical settings. In contrast to the presence of distressing subjective symptoms, the physical examination is marked by a paucity of objective signs. The pathophysiology of BFS is not very clear and treatment varies depending on the aetiology. urning feet syndrome (BFS), which is be divided into the following categories ciency related neuropathy before frank Bcharacterised by a sensation of (Table 1).
    [Show full text]