DOCSLIB.ORG

A Case of MELAS Syndrome with Typical Cluster Headache

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Case of MELAS Syndrome with Typical Cluster Headache J Headache Pain (2002) 3:51–53 © Springer-Verlag 2002 BRIEF REPORT Bruno M. Fusco A case of MELAS syndrome with typical cluster Mario Giacovazzo headache attacks: is it a causal or coincindental association? Received: 7 June 2001 Abstract Many findings relate diagnosis was confirmed when a Accepted in revised form: 4 December 2001 migraine and cluster headaches to a point mutation (Leu mutation at genetic alteration, even if the site of position 3423 of mitochondrial the defect has not been identified. RNA) was found in the mitochondri- Some of these findings indicate an al gene. The recurrent periods, char- involvement of mitochondrial DNA, acterized by attacks of unilateral pain although some contrasting results and accompanied by homolateral ౧ B.M. Fusco ( ) have been reported. We describe a symptoms (e.g. tearing, palpebral Department of Pharmaceutical Science, University of Salerno, case of cluster headache occurring in ptosis, rhinorrea), did not leave any Via del Ponte Don Melillo, a patient with MELAS syndrome. doubt as to the diagnosis of cluster I-84084 Fisciano (SA), Italy The diagnosis of MELAS was sup- headache. We discuss whether the e-mail: [email protected] ported by the familiar anamnesis (the co-existence of MELAS and cluster Tel.: +39-089-962726 mother suffered from a similar headache was coincidental or causal. form), by the laboratory reports M. Giacovazzo Institute of Internal Medicine, (lacto-acidosis), by instrumental Key words Cluster headache • Second Faculty of Medicine, analysis (signs of encephalopathy on mtDNA • Lacto-acidosis • MELAS • La Sapienza University of Rome, magnetic resonance imaging) and by Mitochondrial disease Rome, Italy biopsy findings (myopathy). The cate metabolic process, disruption of any mitochondrial or Introduction nuclear gene by mutation is likely to have impact on that organism. mtDNA is particular vulnerable to mutations [3]. MELAS, a syndrome characterized by myopathy, The inheritance of mitochondria-related diseases is more encephalopathy, lactic acidosis and stroke-like episodes, has complex than that of diseases due to genetic alterations of been related to an alteration in mitochondrial DNA the nucleus. A zygote receives a large number of organelles (mtDNA). Mitochondria are intracellular organelles which through the egg. Only few of them contain a mutation. are the sites of the oxidative phases of cell respiration [1]. During the early phases of life, cell division disperses the Mitochondria have their own DNA. In most eukaryotes, initial population of the mitochondria and new populations mtDNA exists as a double-stranded, closed circle which has of the organelles are reproduced by the original. Therefore, the capability to replicate. Mitochondrial genes have been if a mutation is present in some of the initial populations of identified to code 13 proteins that are essential to the cellu- mitochondria, the adult cell will have a variety of lar respiratory functions of the mitochondria [2]. Protein organelles, both normal and abnormal. This condition is encoded by intra-organelle genes act, along with proteins of called heteroplasmy [4]. nuclear origin, to guarantee the respiratory function of the Human disorders that are attributable to mutations of the mitochondria. Because cellular respiration is such an intri- mtDNA have to meet several criteria. They can be either 52 sporadic, when mutations occur in somatic cells, or inherit- and spread to the maxillary area. Pain was described as ed when the gene alteration is present in oocytic organelles. excruciatingly sharp. Accompanying symptoms usually Inheritance must exhibit a maternal rather than a mendelian described for cluster headache occurred, along with other pattern. The mtDNA alteration must produce a deficit in the (stroke-like) symptoms not usually associated. In particular, bio-energetic function of the organelle [5]. On the other conjunctival hyperemia, tearing, palpebral ptosis, and nasal hand, a disruption of mitochondrial function could also arise obstruction were always present on the same side as the from a nuclear gene alteration. Mitochondrial disorders can pain. These episodes matched the diagnostic crteria outlined be categorized as due to: primary mutations of DNA, either by the Ad Hoc Committee of the International Headache sporadic or maternally inherited; nuclear mutations which Society (IHS). In addition, hemiplegia, aphasia, and blind- provoke either direct alterations in mtDNA or intergenomic ness often occurred during the crises, and disappeared at the signalling defects; mendelian defects that affect the respira- end of the attacks. He reported that his mother suffered from tory chain in the absence of mtDNA mutations. The differ- an analogous form, with cluster headache-like attacks (even ence (if one exists) in the pathophysiology of these three if the pain intensity was described as significantly lighter) possibilities has not been determined [6]. accompanied by the same stroke-like symptoms (hemiple- MELAS is one of the major mitochondria-related gia, aphasia, amaurosis). It was not possible to evaluate if encephalomyopathies. MELAS has been related to a point other analogous cases occurred in his pedigree mutation resulting in the presence of leucine in position The personal anamnesis showed that before the occur- 3234 of mitochondrial tRNA [7]. rence of the cluster period, the patient had suffered from MELAS has been related to migraine, in as much as the stroke-like attacks that had the same duration as that of the symptomatology is often characterized by migraine-like accompanying headache. The chronological pattern of attacks (i.e. headache with nausea and vomiting). The rela- these pre-cluster episodes was not determined, occurring tionship between MELAS and migraine-like attacks and 5–6 times during a year. No other important pathologies the consideration that migraine could have a familiar were referred. The stroke-like attacks which occurred inheritance with a preferential maternal line have suggest- before the onset of the cluster headache-like disease were ed possible common elements at the basis of the two clin- similar to those present during the headache attacks. The ical entities [8]. One study showed that there was a high patient referred transitory (5–10 min) episodes of amauro- frequency of mitochondrial gene alterations (same Leu sis, with loss of coordination, hemiplegia and, sometimes, mutation) in a population of migraine patients [9]. These aphasia. findings were not confirmed by a subsequent investigation The general clinical investigation revealed a light [10], nor was an alteration in mtRNA found in cluster hypotrophy of the muscles with relative weakness. headache patients [11]. On the other hand Montagna [12] Neurological examination was normal. Neuroimaging tech- demonstrated, with spectroscopy resonance, an alteration niques documented the presence of encephalopathy, partic- of the neuronal cell respiratory function in cluster ularly at the posterior level (Fig. 1). No lesions were found headache patients, while Montagna et al. [13] described a in the hypothalamus. Electromyographic examination case of cluster headache with an extensive deletion of the demonstrated the myopathic alteration. Laboratory investi- mitochondrial genome. These findings support the hypoth- gation did not reveal any abnormal values. A significant esis of the hereditability of migraine and cluster headache. increase of lactic acid in the blood was found during the We described a case of a typical cluster headache feature in attacks. The basal values were 15 mg/dl 2 hours after the a subject with MELAS. crisis. They increased to 80–110 mg/dl during the crisis, and descended to 20 mg/dl at the end of the crisis Electrocardiographic features were not altered. A muscular biopsy was carried out in order to examine the mtDNA Case report along with the leucocytic mtDNA. The polymerase chain reaction (PCR) technique was applied to sequence the A 37-year-old man came to our observation at the headache DNA. A point mutation was found (cytosine to thymine). centre of Rome. He reported episodes of headache which The mutation was related to the Leu alteration in the tRNA occurred over a period of about 2 months. These periods re- at position 3243. occurred with a frequency of twice a year for 7 years. The last cluster headache-like period was treated with During these periods the occurrence of the headache attacks verapamil (oral dose of 80 mg, 3 times a day), which had an impressive chronological pattern: the attacks appeared to shorten the length of the florid phase (40 days). occurred every day at 1:00 a.m. and 4:00 p.m. Each attack The attacks were treated with oxygen, which only partially lasted about 45 minutes. The pain was localized in the left (30% as reported by the patient) attenuated the intensity of side, involved the orbit and the facial and parietal regions, the attack, whereas the duration was unaffected. 53 attacks were also characterized by an increase in lactic acid well above the normal level. The instrumental investiga- tion indicated the presence of encephalopathy and myopa- thy. The patient’s mother was affected by an analogous form of headache. The presence of a point mutation in the mtDNA confirmed the diagnosis of MELAS, with a possi- ble maternal inheritance. MELAS is often characterized by migraine-like attacks, and this had encouraged studies on the possible involvement of mtDNA in migraine. The only study which described an elevated frequency of mitochon-
Load more

Recommended publications
  • Cluster Headache: a Review MARILYN J
    • Cluster headache: A review MARILYN J. CONNORS, DO ID Cluster headache is a debilitat­ consists of episodes of excruciating facial pain that ing neuronal headache with secondary vas­ is generally unilateraP and often accompanied by cular changes and is often accompanied by ipsilateral parasympathetic phenomena including other characteristic signs and symptoms, such nasal congestion, rhinorrhea, conjunctival injec­ as unilateral rhinorrhea, lacrimation, and con­ tion, and lacrimation. Patients may also experi­ junctival injection. It primarily affects men, ence complete or partial Horner's syndrome (that and in many cases, patients have distinguishing is, unilateral miosis with normal direct light response facial, body, and psychologic features. Sever­ and mild ipsilateral ptosis, facial flushing, and al factors may precipitate cluster headaches, hyperhidrosis).4-6 These autonomic disturbances including histamine, nitroglycerin, alcohol, sometimes precede or occur early in the headache, transition from rapid eye movement (REM) adding credence to the theory that this constella­ to non-REM sleep, circadian periodicity, envi­ tion of symptoms is an integral part of an attack and ronmental alterations, and change in the level not a secondary consequence. Some investigators of physical, emotional, or mental activity. The consider cluster headache to exemplify a tempo­ pathophysiologic features have not been com­ rary and local imbalance between sympathetic and pletely elucidated, but the realms of neuro­ parasympathetic systems via the central nervous biology, intracranial hemodynamics, endocrinol­ system (CNS).! ogy, and immunology are included. Therapy The nomenclature of this form of headache in is prophylactic or abortive (or both). Treat­ the literature is extensive and descriptive, includ­ ment, possibly with combination regimens, ing such terminology as histamine cephalgia, ery­ should be tailored to the needs of the indi­ thromelalgia of the head, red migraine, atypical vidual patient.
    [Show full text]
  • Migraine; Cluster Headache; Tension Headache Order Set Requirements: Allergies Risk Assessment / Scoring Tools / Screening: See Clinical Decision Support Section
    Provincial Clinical Knowledge Topic Primary Headaches, Adult – Emergency V 1.0 © 2017, Alberta Health Services. This work is licensed under the Creative Commons Attribution-Non-Commercial-No Derivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Disclaimer: This material is intended for use by clinicians only and is provided on an "as is", "where is" basis. Although reasonable efforts were made to confirm the accuracy of the information, Alberta Health Services does not make any representation or warranty, express, implied or statutory, as to the accuracy, reliability, completeness, applicability or fitness for a particular purpose of such information. This material is not a substitute for the advice of a qualified health professional. Alberta Health Services expressly disclaims all liability for the use of these materials, and for any claims, actions, demands or suits arising from such use. Revision History Version Date of Revision Description of Revision Revised By 1.0 March 2017 Topic completed and disseminated See Acknowledgements Primary Headaches, Adult – Emergency V 1.0 Page 1 of 16 Important Information Before You Begin The recommendations contained in this knowledge topic have been provincially adjudicated and are based on best practice and available evidence. Clinicians applying these recommendations should, in consultation with the patient, use independent medical judgment in the context of individual clinical circumstances to direct care. This knowledge topic will be reviewed periodically and updated as best practice evidence and practice change. The information in this topic strives to adhere to Institute for Safe Medication Practices (ISMP) safety standards and align with Quality and Safety initiatives and accreditation requirements such as the Required Organizational Practices.
    [Show full text]
  • Autonomic Headache with Autonomic Seizures: a Case Report
    J Headache Pain (2006) 7:347–350 DOI 10.1007/s10194-006-0326-y BRIEF REPORT Aynur Özge Autonomic headache with autonomic seizures: Hakan Kaleagasi Fazilet Yalçin Tasmertek a case report Received: 3 April 2006 Abstract The aim of the report is the criteria for the diagnosis of Accepted in revised form: 18 July 2006 to present a case of an autonomic trigeminal autonomic cephalalgias, Published online: 25 October 2006 headache associated with autonom- and was different from epileptic ic seizures. A 19-year-old male headache, which was defined as a who had had complex partial pressing type pain felt over the seizures for 15 years was admitted forehead for several minutes to a with autonomic complaints and left few hours. Although epileptic hemicranial headache, independent headache responds to anti-epilep- from seizures, that he had had for tics and the complaints of the pre- 2 years and were provoked by sent case decreased with anti- watching television. Brain magnet- epileptics, it has been suggested ౧ A. Özge ( ) • H. Kaleagasi ic resonance imaging showed right that the headache could be a non- F. Yalçin Tasmertek hippocampal sclerosis and elec- trigeminal autonomic headache Department of Neurology, troencephalography revealed instead of an epileptic headache. Mersin University Faculty of Medicine, Mersin 33079, Turkey epileptic activity in right hemi- e-mail: [email protected] spheric areas. Treatment with val- Keywords Headache • Non-trigemi- Tel.: +90-324-3374300 (1149) proic acid decreased the com- nal autonomic cephalalgias • Fax: +90-324-3374305 plaints. The headache did not fulfil Autonomic seizure • Valproic acid lateral autonomic phenomena and/or restlessness or agita- Introduction tion [3].
    [Show full text]
  • Leigh Disease Associated with a Novel Mitochondrial DNA ND5 Mutation
    European Journal of Human Genetics (2002) 10, 141 ± 144 ã 2002 Nature Publishing Group All rights reserved 1018-4813/02 $25.00 www.nature.com/ejhg SHORT REPORT Leigh disease associated with a novel mitochondrial DNA ND5 mutation Robert W Taylor*,1, Andrew AM Morris2, Michael Hutchinson3 and Douglass M Turnbull1 1Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK; 2Department of Metabolic Medicine, Great Ormond Street Hospital, London, WC1N 3JH, UK; 3Department of Neurology, St Vincent's University Hospital, Dublin, Republic of Ireland Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome. Here, we report the molecular genetic findings in a patient with neuropathological hallmarks of Leigh disease and complex I deficiency. Direct sequencing of the seven mitochondrial DNA (mtDNA)-encoded complex I (ND) genes revealed a novel missense mutation (T12706C) in the mitochondrial ND5 gene. The mutation is predicted to change an invariant amino acid in a highly conserved transmembrane helix of the mature polypeptide and was heteroplasmic in both skeletal muscle and cultured skin fibroblasts. The association of the T12706C ND5 mutation with a specific biochemical defect involving complex I is highly suggestive of a pathogenic role for this mutation. European Journal of Human Genetics (2002) 10, 141 ± 144. DOI: 10.1038/sj/ejhg/5200773 Keywords: Leigh disease; complex I; mitochondrial DNA; mutation; heteroplasmy Introduction mutations in the tRNALeu(UUR) gene,3 and a G14459A Leigh disease is a neurodegenerative condition with a variable transition in the ND6 gene that has previously been clinical course, though it usually presents during early characterised in patients with Lebers hereditary optic childhood.
    [Show full text]
  • Headache: a Patient's Guide (Pdf)
    Headache A Patient’s Guide Kathleen Digre, MD • Susan Baggaley, APRN • K.C. Brennan, MD • Seniha Ozudogru, MD 729 Arapeen Drive Salt Lake City, Utah 84108 801.585.7575 headache.uofuhealth.org Headache: A Patient’s Guide eadache is an extremely common problem. It is estimated that 10-20% of all people have migraine. Headache is one of the most common reasons H people visit the doctor’s office. Headache can be the symptom of a serious problem, or it can be recurrent, annoying and disabling, without any underlying structural cause. WHAT CAUSES HEAD PAIN? Pain in the head is carried by certain nerves that supply the head and neck. The trigeminal system impacts the face as well as the cervical (neck) 1 and 2 nerves in the back of the head. Although pain can indicate that something is pushing on the brain or nerves, most of the time nothing is pushing on anything. We think that in migraine there may be a generator of headache in the brain which can be triggered by many things. Some people’s generators are more sensitive to stimuli such as light, noise, odor, and stress than others, causing a person to have more frequent headaches. THERE ARE MANY TYPES OF HEADACHES! Most people have more than one type of headache. The most common type of headache seen in a doctor's office is migraine (the most common type of headache in the general population is tension headache). Some people do not believe that migraine and tension headaches are different headaches, but rather two ends of a headache continuum.
    [Show full text]
  • Primary Headaches and Their Relationship with Sleep Cefaleias Primárias E Sua Relação Com O Sono
    Yagihara F, Lucchesi LM‚ Smith AKA, Speciali JG 28 REVIEW ARTICLE Primary headaches and their relationship with sleep Cefaleias primárias e sua relação com o sono Fabiana Yagihara1, Ligia Mendonça Lucchesi1, Anna Karla Alves Smith1, José Geraldo Speciali2 ABSTRACT pain control systems. In general, pain affects sleep and vice There is a clear association between primary headaches and sleep versa(1,2). We found that primary headaches with no clear disorders, especially when these headaches occur at night or upon etiology by clinical and laboratory tests can be triggered by waking. The primary headaches most commonly related to sleep either short or long periods of sleep, or by interrupted or are: migraine, cluster headache, tension type, hypnic headache and (3) chronic paroxysmal hemicrania. The objective of this review was to non-restorative sleep . Sleep is also effective in relieving describe the relationship between these types of headaches and sle- symptoms: 85% of individuals with migraine report that ep and to address sleep apnea headaches. There are various types of they choose to sleep or rest because of a headache, and demonstrated associations between sleep and headache disorders, many are forced to do it(4). Therefore, headaches and sleep and the mechanisms underlying these associations are complex, multi-factorial and poorly understood. Moreover, all sleep disorders disturbances are common and often coexist in the same may be related to headaches to some degree; therefore, the evalua- individual(3,5), and this association is especially observed tion of patients with headaches should include a brief investigation when these headaches occur at night or upon waking(6,7).
    [Show full text]
  • Headaches and Sleep
    P1: KWW/KKL P2: KWW/HCN QC: KWW/FLX T1: KWW GRBT050-134 Olesen- 2057G GRBT050-Olesen-v6.cls August 17, 2005 2:18 ••Chapter 134 ◗ Headaches and Sleep Poul Jennum and Teresa Paiva Headache and sleeping problems are both some of the maintaining sleep), hypersomnias (with excessive day- most commonly reported problems in clinical practice and time sleepiness), parasomnias (disorders of arousal, par- cause considerable social and family problems, with im- tial arousal, and sleep stage transition), or circadian portant socioeconomic impacts. There is a clear associa- disturbances. tion between headache and sleep disturbances, especially Sleep is regulated by a complex set of mechanisms headaches occurring during the night or early morning. including the hypothalamus and brainstem and involv- The prevalence of chronic morning headache (CMH) is ing a large number of neurotransmitters including sero- 7.6%; CMH is more common in females and in subjects tonin, adenosine, histamine, hypocretin, γ -aminobutyric between 45 and 64 years of age; the most significant asso- acid (GABA), norepinephrine, and epinephrine (65). How- ciated factors are anxiety, depressive disorders, insomnia, ever, the specific roles in the relation between sleep and and dyssomnia (75). headache disorders are only partly known. However, the cause and effect of this relation are not clear. Patients with headache also report more daytime symptoms such as fatigue, tiredness, or sleepiness and COMMON HEADACHE TYPES sleep-related problems such as insomnia (77,52). Identi- AND THE RELATION TO SLEEP fication of sleep disorders in chronic headache patients is worthwhile because identification and treatment of sleep Commonly reported headache disorders that show rela- disorders among chronic headache patients may be fol- tion to sleep are migraine, tension-type headache, cluster lowed by improvement of the headache.
    [Show full text]
  • Cluster Headacheheadache
    ClusterCluster HeadacheHeadache 1 OBJECTIVESOBJECTIVES Describe the clinical features and diagnosis of cluster headache Discuss the pathogenesis of cluster pain and autonomic features Review acute and preventive therapy Overview of new treatment horizons for refractory chronic cluster 2 IHSIHS CLASSIFICATIONCLASSIFICATION Cluster headache n Episodic type (80%) n Chronic type (20%) (Cluster period lasts for more than one year without remission or remission lasts less than 14 days) Episodic Chronic IHS Headache Classification Committee. Cephalalgia. 2004. Although the unique clinical features of cluster headache (CH) have been recognized since the 17th century, the striking periodicity was not articulated until the 1940s. The term “cluster headache” was coined in the 1950s, and since then the International Headache Society (IHS) has identified and classified two major temporal patterns of CH (1). The episodic type (ECH), by far the most common (90%), is characterized by discrete attack and remission phases. The chronic type (CCH) is defined by attacks that occur daily for more than one year without remission or with remission periods lasting less than 14 days. Cluster headache is rare (about 0.4% of the general population), and it predominates in males, although recent studies indicate that the rate in females is rising (2). Onset can occur at any age but usually begins between 30 and 50 years of age (3). In contrast to migraine headache, genetics in cluster headache is not thought to be important, although recent studies have shown a positive family history in about 7% of patients with cluster headache. When compared with prevalence of CH in the general population, first-degree relatives have about a 14-fold increased risk of developing CH.
    [Show full text]
  • Consensus-Based Statements for the Management of Mitochondrial Stroke-Like Episodes[Version 1; Peer Review: 2 Approved]
    Wellcome Open Research 2019, 4:201 Last updated: 02 OCT 2020 RESEARCH ARTICLE Consensus-based statements for the management of mitochondrial stroke-like episodes [version 1; peer review: 2 approved] Yi Shiau Ng 1-3, Laurence A. Bindoff4,5, Gráinne S. Gorman1-3, Rita Horvath1,6, Thomas Klopstock7-9, Michelangelo Mancuso 10, Mika H. Martikainen 11, Robert Mcfarland 1,3,12, Victoria Nesbitt13,14, Robert D. S. Pitceathly 15,16, Andrew M. Schaefer1-3, Doug M. Turnbull1-3 1Wellcome Centre for Mitochondrial Research, Newcastle University, UK, Newcastle upon Tyne, Tyne and Wear, NE2 4HH, UK 2Directorate of Neurosciences, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, Tyne and Wear, NE1 4LP, UK 3NHS Highly Specialised Service for Rare Mitohcondrial Disorders, Royal Victoria Infirmary, Newcastle upon Tyne, UK 4Department of Clinical Medicine, University of Bergen, Bergen, Norway 5Department of Neurology, Haukeland University Hospital, Bergen, Norway 6Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 7Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-Universität München, Munich, Germany 8German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 9Munich Cluster for Systems Neurology (SyNergy), Munich, Germany 10Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy 11Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Turku, Finland 12Great North Children Hospital, Newcastle
    [Show full text]
  • Understanding and Coping with Mitochondrial Disease
    From the parents’ view … When we first heard that our daughter, Alexis, was diagnosed with Mitochondrial disease, we really didn't know what it was. We also learned that not too many people had heard of it before. Our daughter had many tests performed to reach the diagnosis of Mitochondrial disease. So once we received the news we were actually glad to finally have some answers. No parent wants their child to be ill, but we have learned to accept the disease and live with it on a day to day basis. We also learned that each person with Mitochondrial disease is affected differently by it. Alexis is severely affected by the disease, so each day with her is special. Meeting other children with Mitochondrial disease and their families have become a great support for us. We can relate to their daily struggles and if we need advice, they are there for us. My advice that I would give to others affected by Mitochondrial disease is to not give up. We can all fight this disease together. The hardest part sometimes is people not knowing enough about the disease. We really need to start educating people about it. Chris and Stephanie Understanding and coping with Mitochondrial disease A guide for parents The health care team at the Neuromuscular and Neurometabolic Centre wrote this book to answer some common questions about Mitochondrial disease. We hope that you will find it helpful. During your child’s care, you will meet the members of our team. We will work closely with you and your child to meet your needs.
    [Show full text]
  • How Do We Manage Stroke-Like Episodes?
    Mitochondrial diseases in adults: how do we manage stroke-like episodes? Dr Robert Pitceathly Senior Clinical Research Associate MRC Centre for Neuromuscular Diseases UCL, London Overview • Mitochondria and mitochondrial disease • What are stroke-like episodes? • Recognition of stroke-like episodes • Management of stroke-like episodes Mitochondria and mitochondrial disease The mitochondrion mtDNA and mitochondrial diseases 0 16,569 >250 pathogenic mutations Genetics of mitochondrial disease 37 genes > 1000 genes Genes of mitochondria-localised proteins linked to human disease Koopman WJ et al. N Engl J Med 2012;366:1132-1141 Genetic variability nDNA mtDNA 13 polypeptide subunits 7/44 0/4 1/11 3/14 2/16 Clinical variability Respiratory Failure Optic Atrophy / Retinitis Pigmentosa / Cataracts Cardiomyopathy / Conduction Defects CVA / Seizures / Developmental Delay Liver / Renal Failure Deafness Short stature / Marrow Failure Peripheral Diabetes Neuropathy Hypothyroidism Myopathy Clinical variability Age of onset Neonate Infant Child Adolescent Adult Elderly Congenital Lactic LS Acidosis PMPS HCM Alpers KSS MELAS CPEO MERRF NARP Exercise intolerance Myopathy How common is Mitochondrial Disease? Minimum point prevalence (mtDNA mutations): 1, in 5,000 Overt disease due to nDNA mutations: 2.9 per 100,000 Prevalence (total): 1 in 4,300 Mutation Affected ‘At Risk’ per 100,000 (CI) LHON 3.7 (2.9-4.6) 4.4 (3.7-5.3) m.3243A>G 3.5 (2.7-4.4) 4.4 (3.7-5.3) mtDNA 1.5 (1.0-2.1) 0 deletion m.8344A>G 0.2 (0.1-0.5) 0.5 (0.2-0.8) SPG7, ar 0.8 (0.5-1.3) 1.3
    [Show full text]
  • Migraines: Genetic Studies Pietro Cortelli Mirella Mochi and Some Practical Considerations
    J Headache Pain (2003) 4:47–56 DOI 10.1007/s10194-003-0030-0 EDITORIAL Pasquale Montagna The “typical” migraines: genetic studies Pietro Cortelli Mirella Mochi and some practical considerations Abstract Epidemiological genetic, in the inflammation cascade; etc.) family and twin studies show that the did not result in uniformely accepted typical migraines carry a substantial findings. Linkage and genome wide genetic risk; they are currently con- scans gave evidence for several ceptualized as complex genetic dis- genetic susceptibility loci, still how- ౧ P. Montagna ( ) • M. Mochi eases. Several genetic association ever in need of confirmation. Careful Department of Clinical Neurosciences, University of Bologna Medical School, and linkage studies have been per- dissection of the clinical phenotypes Via Ugo Foscolo 7, I-40123 Bologna, Italy formed in the typical migraines. and trigger factors shall greatly help e-mail: [email protected] Candidate gene studies based on “a future efforts in the quest for the Tel.: +39-051-6442179 priori” pathogenic models of genetic basis of the typical Fax: +39-051-6442165 migraine (migraine as a calcium migraines. P. Cortelli channelopathy; a mitochondrial Department of Neurology, DNA disorder; a disorder in the University of Modena and Reggio Emilia, metabolism of serotonin or Key words Migraine • Aura • Modena, Italy dopamine; in vascular risk factors or Genetics • Cardiovascular risk prove heritability, since it may result from shared envi- “Typical” migraine as a complex disease: genetic ronmental factors. It is therefore interesting to note that at epidemiology, twin and segregation analysis studies least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives com- That migraine runs in families is an ancient observation.
    [Show full text]