DOCSLIB.ORG

Case 38-2017: a 20-Year-Old Woman with Seizures and Progressive Dystonia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Case 38-2017: a 20-Year-Old Woman with Seizures and Progressive Dystonia The new england journal of medicine Case Records of the Massachusetts General Hospital Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Dennis C. Sgroi, M.D., Jo-Anne O. Shepard, M.D., Associate Editors Allison R. Bond, M.D., Case Records Editorial Fellow Emily K. McDonald, Sally H. Ebeling, Production Editors Case 38-2017: A 20-Year-Old Woman with Seizures and Progressive Dystonia Florian S. Eichler, M.D., Kathryn J. Swoboda, M.D., Ann L. Hunt, D.O., Dean M. Cestari, M.D., and Otto Rapalino, M.D.​​ Presentation of Case From the Departments of Neurology Dr. Andrew J. Cole (Neurology): A 20-year-old woman was seen in the neurology (F.S.E., K.J.S., A.L.H.) and Radiology (O.R.), clinic of this hospital because of seizures and progressive dystonia. Massachusetts General Hospital, the De- partments of Neurology (F.S.E., K.J.S., The patient had been well until she was 3 years of age, when she began to have A.L.H.), Ophthalmology (D.M.C.), and recurrent falls, difficulty walking, and seizures. A diagnostic evaluation at an- Radiology (O.R.), Harvard Medical School, other hospital included a muscle biopsy, electroencephalography, and electroretinog- and the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary raphy, as well as analysis of the carnitine profile, visual-evoked potentials, and (D.M.C.) — all in Boston. the enzymatic activity of the mitochondrial respiratory chain; the test results were N Engl J Med 2017;377:2376-85. reportedly interpreted as inconclusive. Magnetic resonance imaging (MRI) of the DOI: 10.1056/NEJMcpc1706109 head was performed; T2-weighted images reportedly showed areas of abnormal Copyright © 2017 Massachusetts Medical Society. hyperintensity in the basal ganglia bilaterally. Therapy with carbamazepine and a multivitamin was initiated. During the next 15 years, progressive stepwise deteriora- tion, including worsening dystonia and dysarthria, occurred; cognitive function was not affected. Exacerbations of her neurologic decline were precipitated by acute intercurrent illnesses and recurrent seizures from which she did not have complete recovery. Five years before the current presentation, anticonvulsant medications were stopped for 1 month. During that period, three flurries of generalized tonic– clonic seizures occurred. During admission to a second hospital, the complete blood count, oxygen saturation, blood levels of calcium and magnesium, and results of liver- and renal-function tests were normal. Medications on discharge included carbamazepine, L-carnitine, coenzyme Q10, and vitamin B complex. On follow-up at that hospital 2 months later, the patient reportedly had dysarthria, dystonic posturing of both arms (especially the hands), and an ataxic gait. Strength was 3+/5 in the distal arms and 5/5 in the proximal arms. Approximate- ly 2.8 years before the current presentation, the patient was evaluated at a third hospital. MRI of the head was performed; T2-weighted and fluid-attenuated inver- sion recovery (FLAIR) images again showed areas of abnormal hyperintensity in the basal ganglia bilaterally, with mild associated volume loss. The MRI was sig- 2376 n engl j med 377;24 nejm.org December 14, 2017 The New England Journal of Medicine Downloaded from nejm.org by LUIS ERNESTO GONZALEZ SANCHEZ on January 2, 2018. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital nificantly degraded by susceptibility artifacts showed nonenhancing areas of abnormal, diffuse that were produced by orthodontic braces. The hyperintensity in the cerebral cortex, basal gan- blood lactate level was 1.6 mmol per liter (14.4 glia, thalami, midbrain, and cerebellum. Repeat mg per deciliter; reference range at this hospi- imaging studies obtained 10 months later showed tal, 0.5 to 2.2 mmol per liter [4.5 to 19.8 mg per resolution of most of the signal abnormalities, deciliter]), and the cerebrospinal fluid (CSF) although residual signal abnormalities and vol- lactate level was 1.2 mmol per liter (10.8 mg per ume loss were present in the basal ganglia. deciliter; reference range at this hospital, 0.6 to On examination at this hospital, which was 2.2 mmol per liter [5.4 to 19.8 mg per deciliter]). performed with the assistance of an interpreter, A preliminary diagnosis of mitochondrial cy- the patient was alert and her mental status was topathy was made. normal. She had severe dysarthria, but her speech Between 17 and 11 months before the current was fluent, with no paraphasic errors. Cranial- presentation, examinations were performed at nerve function was intact, and visual acuity was the second hospital while the patient was receiv- 20/30 in both eyes. She had fluctuating dystonia ing levetiracetam and trihexyphenidyl. Speech of the hands, arms, legs, and feet that was more difficulties, limb rigidity, and spasticity of the prominent on the left side than on the right side. left upper leg were noted. She was referred to the Strength was normal throughout. The plantar re- epilepsy clinic of this hospital. flex was extensor in the left foot and was mute in On presentation to this hospital, the patient the right foot; deep-tendon reflexes were normal. reported dysarthric speech and painful dystonia The gait was slow, wide-based, and dystonic, of her hands and limbs (particularly her legs). with inversion and internal rotation of both feet. The dystonia was associated with gait deteriora- The remainder of the examination was normal. tion that had led to use of a wheelchair. Cognitive MRI of the head was performed without the function was not affected. Her most recent sei- administration of intravenous contrast material. zure had occurred 1 year before this assessment. T2-weighted images showed persistent areas of The patient was the fourth child of healthy abnormal hyperintensity, volume loss, and sub- consanguineous parents (first cousins). She had tle abnormal mineralization in the basal ganglia been born after a full-term gestation, with no bilaterally. Electroencephalography, which was complications. Her birth weight was 3750 g. performed while the patient was awake and Medications were levetiracetam, pyridoxine, thia- while she was asleep, revealed excessive, diffuse mine, and trihexyphenidyl. She had no known beta activity, with no definitive evidence of epi- allergies. She lived with her family in the Arabian leptiform abnormalities. Peninsula; she spoke Arabic and some English, The younger sister was present during the attended a regular high school, and did not drink clinic visit and was also examined. She had mild alcohol, smoke tobacco, or use illicit drugs. dystonia of the right foot, an extensor plantar She had three older brothers who were healthy. reflex in the right foot, and a clumsy gait. She had a 6-year-old sister with a similar illness Dr. Ann L. Hunt: The patient was referred to the that had started when she was 3 years of age, movement disorders clinic of this hospital (see when she had an episode of bloody diarrhea and Video 1, available with the full text of this article A video showing then began to have dystonia of the right foot, at NEJM.org). She came to the visit in a wheel- the examination difficulty walking, and seizures. On evaluation chair. Her speech was dysarthric in both English is available at NEJM.org at that time, the sister had a peak blood lactate and Arabic. She had previously been a fluent Arabic level of 11.7 mmol per liter (105.4 mg per deciliter) speaker. While the patient was sitting quietly, and a peak CSF lactate level of 2.3 mmol per liter she had dystonic posturing of the left hand and (20.7 mg per deciliter). Genetic testing for the both feet. During any activation procedure, the MELAS syndrome (mitochondrial encephalomy- dystonic posturing of the left hand and left foot opathy, lactic acidosis, and strokelike episodes) increased. During rapid successive movements, and the Leigh syndrome was reportedly negative, slowness and dystonic posturing were more and levels of urinary organic acids were normal. prominent in the left hand and foot than in the The sister underwent MRI of the head during the right hand and foot. There was no rigidity of the acute phase of her disease. T2-weighted images arms or legs. When she walked, dystonic postur- n engl j med 377;24 nejm.org December 14, 2017 2377 The New England Journal of Medicine Downloaded from nejm.org by LUIS ERNESTO GONZALEZ SANCHEZ on January 2, 2018. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved. The new england journal of medicine A B C D E F Figure 1. Patient’s MRI Studies. An axial fluid-attenuated inversion recovery (FLAIR) image, a coronal T2-weighted image, and an axial T2-weighted image were obtained approximately 2.8 years before the current presentation (Panels A, B, and C, respectively). The images show areas of abnormal hyperintensity in the basal ganglia bilaterally (arrows). An axial FLAIR image and a coronal T2-weighted image were obtained on presentation (Panels D and E, respectively). The images show evidence of mild volume loss, with a slight increase in ventricular size. An axial susceptibility-weighted image (Panel F) shows bilateral areas of mineralization in the basal ganglia (arrows). ing was more prominent in the left hand and nence of the lateral ventricles) and abnormal foot than in the right hand and foot. A pull test mineralization of the basal ganglia (as com- revealed good postural stability. pared with the mineralization in age-matched A diagnostic test was performed. controls). The patient’s sister had undergone MRI twice: Differential Diagnosis approximately 3.5 years before the patient’s cur- rent presentation (when the sister was 3 years of Dr.
Load more

Recommended publications
  • 1 Cerebrospinal Fluid Neurofilament Light Is Associated with Survival In
    1 Cerebrospinal fluid Neurofilament Light is associated with survival in mitochondrial disease patients Kalliopi Sofou†,a, Pashtun Shahim†, b,c, Már Tuliniusa, Kaj Blennowb,c, Henrik Zetterbergb,c,d,e, Niklas Mattssonf, Niklas Darina aDepartment of Pediatrics, University of Gothenburg, The Queen Silvia’s Children Hospital, Gothenburg, Sweden bInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. cClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden dDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK eUK Dementia Research Institute at UCL, London, UK fClinical Memory Research Unit, Lund University, Malmö, Sweden, and Lund University, Skåne University Hospital, Department of Clinical Sciences, Neurology, Lund, Sweden †Equal contributors Correspondence to: Kalliopi Sofou, MD, PhD Department of Pediatrics University of Gothenburg, The Queen Silvia’s Children Hospital SE-416 85 Gothenburg, Sweden Tel: +46 (0) 31 3421000 E-mail: [email protected] Abbreviations Ab42 Amyloid-b42 AD Alzheimer’s disease AUROC Area under the receiver operating-characteristic curve CNS Central nervous system CSF Cerebrospinal fluid DWI Diffusion weighted imaging FLAIR Fluid attenuated inversion recovery GFAp Glial fibrillary acidic protein KSS Kearns-Sayre syndrome LP Lumbar puncture ME Mitochondrial encephalopathy Mitochondrial encephalomyopathy, lactic acidosis and MELAS stroke-like
    [Show full text]
  • Drugs for Orphan Mitochondrial Disease
    Drugs for Orphan Mitochondrial Disease Gino Cortopassi, CEO Ixchel:Mayan goddess of health www.ixchelpharma.com Davis, CA Executive Summary • Ixchel is a clinical stage company focused on developing IXC-109 as therapeutic for mitochondrial diseases: 109 increases mitochondrial activities in cells & mice. • XC-109 is an NCE prodrug of the active moiety Mono-methylfumarate (MMF) upon which a Composition-of-Matter patent has been applied for. • IP: rights to 5 patent families, including composition of matter, method of use, formulation and 2 granted orphan drug designations. • Efficacy: demonstrated efficacy in preclinical mouse models with IXC-109 in Leigh’s Syndrome, Friedreich’s ataxia cardiac defects. • Patient advocacy groups & KOLs: Ixchel developed a 10-year relationship with patient advocacy groups FARA, Ataxia UK, UMDF & MDA, and networks with 8 Key Opinion Leaders in Mitochondrial Research and Mitochondrial Disease clinical development • Proven path and comps – Valuation of other MMF prodrugs: Vumerity/Alkermes 8700, Xenoport/Dr. Reddy’s – Valuation of Reata FA – IXC-109 is pharmacokinetically superior to Biogen’s DMF and Vumerity 2 Ixchel’s pipeline in orphan mitochondrial disease Benefits in Benefits in Patient Cells Target Identified Orphan Mitochondrial: Mouse models POC clinical trial Friedreich’s Ataxia, IXC103 Leigh’s Syndrome, LHON Mitochondrial Myopathy, IXC109 Duchenne’s Muscular Dystrophy 3 Defects of mitochondria are inherited and cause disease Neurodegeneration Friedreich’s ataxia Mitochondrial defect Genetics Leber’s (LHON) Myopathy Leigh Syndrome Muscle Wasting MELAS 4 Friedreich’s Ataxia as mitochondrial disease target for therapy FA as an orphan therapeutic target: § FA is the most prevalent inherited ataxia: ~6000 in North America, 15,000 Europe.
    [Show full text]
  • Mitochondrial Genome Changes and Neurodegenerative Diseases☆
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1842 (2014) 1198–1207 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbadis Review Mitochondrial genome changes and neurodegenerative diseases☆ Milena Pinto a,c,CarlosT.Moraesa,b,c,⁎ a Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA b Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA c Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA article info abstract Article history: Mitochondria are essential organelles within the cell where most of the energy production occurs by the oxida- Received 31 July 2013 tive phosphorylation system (OXPHOS). Critical components of the OXPHOS are encoded by the mitochondrial Received in revised form 6 November 2013 DNA (mtDNA) and therefore, mutations involving this genome can be deleterious to the cell. Post-mitotic tissues, Accepted 8 November 2013 such as muscle and brain, are most sensitive to mtDNA changes, due to their high energy requirements and non- Available online 16 November 2013 proliferative status. It has been proposed that mtDNA biological features and location make it vulnerable to mu- tations, which accumulate over time. However, although the role of mtDNA damage has been conclusively con- Keywords: Mitochondrion nected to neuronal impairment in mitochondrial diseases, its role in age-related neurodegenerative diseases mtDNA remains speculative. Here we review the pathophysiology of mtDNA mutations leading to neurodegeneration Encephalopathy and discuss the insights obtained by studying mouse models of mtDNA dysfunction.
    [Show full text]
  • Defined Neuronal Populations Drive Fatal Phenotype in a Mouse Model
    RESEARCH ARTICLE Defined neuronal populations drive fatal phenotype in a mouse model of Leigh syndrome Irene Bolea1,2†*, Alejandro Gella2,3†, Elisenda Sanz2,4,5†, Patricia Prada-Dacasa2,5, Fabien Menardy2, Angela M Bard4, Pablo Machuca-Ma´ rquez2, Abel Eraso-Pichot2, Guillem Mo` dol-Caballero2,5,6, Xavier Navarro2,5,6, Franck Kalume4,7,8, Albert Quintana1,2,4,5,9‡* 1Center for Developmental Therapeutics, Seattle Children’s Research Institute, Seattle, United States; 2Institut de Neurocie`ncies, Universitat Auto`noma de Barcelona, Bellaterra, Spain; 3Department of Biochemistry and Molecular Biology, Universitat Auto`noma de Barcelona, Bellaterra, Spain; 4Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States; 5Department of Cell Biology, Physiology and Immunology, Universitat Auto`noma de Barcelona, Bellaterra, Spain; 6Centro de Investigacio´n Biome´dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain; 7Department of Neurological Surgery, University of Washington, Seattle, United States; 8Department of Pharmacology, University of Washington, Seattle, United States; 9Department of Pediatrics, University of Washington, Seattle, United States *For correspondence: [email protected] (IB); [email protected] (AQ) Mitochondrial deficits in energy production cause untreatable and fatal pathologies † Abstract These authors contributed known as mitochondrial disease (MD). Central nervous system affectation is critical in Leigh equally to this work Syndrome (LS), a common MD presentation, leading to motor and respiratory deficits, seizures and Present address: ‡Institut de premature death. However, only specific neuronal populations are affected. Furthermore, their Neurocie`ncies, Universitat molecular identity and their contribution to the disease remains unknown. Here, using a mouse Auto`noma de Barcelona, model of LS lacking the mitochondrial complex I subunit Ndufs4, we dissect the critical role of Bellaterra (Barcelona), Spain genetically-defined neuronal populations in LS progression.
    [Show full text]
  • Blueprint Genetics Leukodystrophy and Leukoencephalopathy Panel
    Leukodystrophy and Leukoencephalopathy Panel Test code: NE2001 Is a 118 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. Is ideal for patients with a clinical suspicion of leukodystrophy or leukoencephalopathy. The genes on this panel are included on the Comprehensive Epilepsy Panel. About Leukodystrophy and Leukoencephalopathy Leukodystrophies are heritable myelin disorders affecting the white matter of the central nervous system with or without peripheral nervous system myelin involvement. Leukodystrophies with an identified genetic cause may be inherited in an autosomal dominant, an autosomal recessive or an X-linked recessive manner. Genetic leukoencephalopathy is heritable and results in white matter abnormalities but does not necessarily meet the strict criteria of a leukodystrophy (PubMed: 25649058). The mainstay of diagnosis of leukodystrophy and leukoencephalopathy is neuroimaging. However, the exact diagnosis is difficult as phenotypes are variable and distinct clinical presentation can be present within the same family. Genetic testing is leading to an expansion of the phenotypic spectrum of the leukodystrophies/encephalopathies. These findings underscore the critical importance of genetic testing for establishing a clinical and pathological diagnosis. Availability 4 weeks Gene Set Description Genes in the Leukodystrophy and Leukoencephalopathy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ABCD1*
    [Show full text]
  • Adult Leigh Disease Without Failure to Thrive
    Title Adult Leigh Disease Without Failure to Thrive Author(s) Sakushima, Ken; Tsuji-Akimoto, Sachiko; Niino, Masaaki; Saitoh, Shinji; Yabe, Ichiro; Sasaki, Hidenao Neurologist, 17(4), 222-227 Citation https://doi.org/10.1097/NRL.0b013e318217357a Issue Date 2011-07 Doc URL http://hdl.handle.net/2115/49478 Rights This is a non-final version of an article published in final form in Neurologist, Jul. 2011, 17(4), 222-227. Type article (author version) File Information Neu17-4_222-227.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Case report Title: Adult Leigh disease without failure to thrive : a case report and review of the literatures Authors: Ken Sakushima, M.D., M.P.H., 1 Sachiko Tsuji-Akimoto, M.D., Ph. D.,1 Masaaki Niino, M.D., Ph.D.,1 Shinji Saitoh, M.D., Ph.D., 2 Ichiro Yabe, M.D., Ph.D.,1 and Hidenao Sasaki, M.D., Ph. D.1 1. Department of Neurology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan. 2. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido, Japan. Correspondence: Ichiro Yabe, M.D., Ph.D. Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638 Japan e-mail; [email protected] short title: Adult Leigh disease Disclosure of funding: None Conflict of interest: 1 None 2 Abstract Introduction: Most Leigh disease (LD) patients die before reaching adulthood, but there are reports of ‘adult LD’. The clinical features of adult LD were quite different from those in infant or childhood cases.
    [Show full text]
  • Vaccination Triggering Onset of M.8993T > G Associated Leigh
    Vaccination triggering onset of m.8993T > G associated Leigh syndrome Josef Finsterer, Sinda Zarrouk-Mahjoub To cite this version: Josef Finsterer, Sinda Zarrouk-Mahjoub. Vaccination triggering onset of m.8993T > G associated Leigh syndrome. Molecular Genetics and Metabolism Reports, Elsevier, 2018, 15, pp.127-128. 10.1016/j.ymgmr.2018.04.001. pasteur-02009084 HAL Id: pasteur-02009084 https://hal-riip.archives-ouvertes.fr/pasteur-02009084 Submitted on 6 Feb 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives| 4.0 International License Molecular Genetics and Metabolism Reports 15 (2018) 127–128 Contents lists available at ScienceDirect Molecular Genetics and Metabolism Reports journal homepage: www.elsevier.com/locate/ymgmr Correspondence Vaccination triggering onset of m.8993T > G associated Leigh syndrome T ARTICLE INFO Keywords: Renal mtDNA Mutation Mitochondrial Lactate Multisystem disease Letter to the Editor. may be hypocitrullinemia. Were any of these phenotypic features de- tected in the index case? We read with interest the article by Uittenbogaard et al. about a 2yo In summary, additional data about the cause of hydrocephalus, the male with maternally-inherited Leigh syndrome (MILS) due to the ATP6 treatment of epilepsy, and the phenotypic spectrum are eligible.
    [Show full text]
  • Leigh Syndrome
    Leigh syndrome What is Leigh syndrome? Leigh syndrome is an inherited progressive neurodegenerative disease characterized by developmental delays or regression, low muscle tone, neuropathy, and severe episodes of illness that can lead to early death.1,2 Individuals with Leigh syndrome have defects in one of many proteins involved in the mitochondrial respiratory chain complexes that produce energy in cells.1 These protein defects cause lesions in tissues that require large amounts of energy, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord.1 Clinical symptoms depend on which areas of the central nervous system are involved.1,2 Leigh syndrome is also known as subacute necrotizing encephalomyelopathy.3 What are the symptoms of Leigh syndrome and what treatment is available? Leigh syndrome is a disease that varies in age at onset and rate of progression. Signs of Leigh syndrome can be seen before birth, but are usually noticed soon after birth. Signs and symptoms may include: 2,3,4 • Hypotonia (low muscle tone) • Intellectual and physical developmental delay and regression • Digestive problems and failure to thrive • Cerebellar ataxia (difficulty coordinating movements) • Peripheral neuropathy (disease affecting nerves) • Hypertrophic cardiomyopathy • Breathing problems, leading to respiratory failure • Metabolic or neurological crisis (serious episode of illness) often triggered by an infection During a crisis, symptoms can progress to respiratory problems, seizures, coma, and possibly death. There is no cure for Leigh syndrome. Treatment is supportive. Approximately 50% of affected individuals die by three years of age, although some patients may survive beyond childhood.4 How is Leigh Syndrome inherited? Autosomal recessive Leigh syndrome is caused by mutations in at least 36 different genes,3 including FOXRED1, NDUFAF2, NDUFS4, NDUFS7, NDUFV1, COX15, SURF1 and LRPPRC.
    [Show full text]
  • Exploring Alternative Therapeutic Interventions for the Treatment of Leigh Syndrome
    University of South Carolina Scholar Commons Theses and Dissertations 2018 Exploring Alternative Therapeutic Interventions For The rT eatment Of Leigh Syndrome Stephanie Martin University of South Carolina Follow this and additional works at: https://scholarcommons.sc.edu/etd Part of the Biomedical and Dental Materials Commons Recommended Citation Martin, S.(2018). Exploring Alternative Therapeutic Interventions For The Treatment Of Leigh Syndrome. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/4615 This Open Access Thesis is brought to you by Scholar Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. EXPLORING ALTERNATIVE THERAPEUTIC INTERVENTIONS FOR THE TREATMENT OF LEIGH SYNDROME by Stephanie Martin Bachelor of Science University of South Carolina, 2015 Submitted in Partial Fulfillment of the Requirements For the Degree of Master of Science in Biomedical Science School of Medicine University of South Carolina 2018 Accepted by: Norma Frizzell, Director of Thesis Gerardo Piroli, Reader Jack Goldsmith, Reader Cheryl L. Addy, Vice Provost and Dean of the Graduate School © Copyright by Stephanie Martin, 2018 All Rights Reserved. ii DEDICATION I would like to dedicate this thesis to my parents, who have always encouraged me to push farther and harder than I believed possible. Thank you for supporting me in everything through all of these years. I would also like to dedicate this to my amazing fiancé for being so thoughtful and helping me through the process of obtaining my master’s degree. iii ACKNOWLEDGEMENTS Thank you so very much to my incredible friends and family for pushing me and always believing in me.
    [Show full text]
  • Biomarkers in Rare Demyelinating Disease of the Central Nervous System
    International Journal of Molecular Sciences Review Biomarkers in Rare Demyelinating Disease of the Central Nervous System Marina Boziki , Styliani-Aggeliki Sintila, Panagiotis Ioannidis and Nikolaos Grigoriadis * 2nd Neurological University Department, Aristotle University of Thessaloniki, AHEPA General Hospital, 54634 Thessaloniki, Greece; [email protected] (M.B.); [email protected] (S.-A.S.); [email protected] (P.I.) * Correspondence: [email protected]; Tel.: +30-2310994683 Received: 14 October 2020; Accepted: 7 November 2020; Published: 9 November 2020 Abstract: Rare neurological diseases are a heterogeneous group corresponding approximately to 50% of all rare diseases. Neurologists are among the main specialists involved in their diagnostic investigation. At the moment, a consensus guideline on which neurologists may base clinical suspicion is not available. Moreover, neurologists need guidance with respect to screening investigations that may be performed. In this respect, biomarker research has emerged as a particularly active field due to its potential applications in clinical practice. With respect to autoimmune demyelinating diseases of the Central Nervous System (CNS), although these diseases occur in the frame of organ-specific autoimmunity, pathology of the disease itself is orchestrated among several anatomical and functional compartments. The differential diagnosis is broad and includes, but is not limited to, rare neurological diseases. Multiple Sclerosis (MS) needs to be differentially diagnosed from rare MS variants, Acute Disseminated Encephalomyelitis (ADEM), the range of Neuromyelitis Optica Spectrum Disorders (NMOSDs), Myelin Oligodendrocyte Glycoprotein (MOG) antibody disease and other systemic inflammatory diseases. Diagnostic biomarkers may facilitate timely diagnosis and proper disease management, preventing disease exacerbation due to misdiagnosis and false treatment. In this review, we will describe advances in biomarker research with respect to rare neuroinflammatory disease of the CNS.
    [Show full text]
  • Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology, 7 and Clinical Management
    Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology, 7 and Clinical Management Omar Hussein and Alireza Minagar Introduction ADEM is a presumably immune-mediated multifocal or diffuse inflammatory demyelinating disease of the brain and the spinal cord that, often but not always, occurs para-infection or postvaccination. It affects children more commonly than adults but that might be attributed to the more clearly defined diagnostic criteria available for children more than adults who might also have pre-existing white mat- ter lesion(s) secondary to a different pathology leading to underscoring adult ADEM [1]. From certain viewpoints, ADEM resembles MS and other demyelinating dis- eases; however, significant differences do exist. ADEM occurs worldwide and usu- ally males and females are affected equally, unlike relapsing-remitting MS that is more common among females. However few studies suggested slight male pre- dominance [2–4]. A cornerstone landmark for the diagnosis of ADEM, especially in children, is encephalopathy in the absence of fever along with other manifestation [1]. This is attributed to the early involvement of the cortical gray matter in the course of the disease unlike most other demyelinating conditions in which cortical involvement usually occurs latter as the disease progresses. Gray matter involve- ment also causes dystonia and other movement disorders [3]. ADEM rarely exists in multiphasic and recurrent forms, but if occurred, encephalopathy remains the cornerstone. To date, there is no unique biomarker that exists to distinguish ADEM from other demyelinating or non-demyelinating conditions making it mostly a diag- nosis of exclusion [3]. Pathological differences also do exist between the different autoimmune demyelinating conditions according to biopsy and postmortem tissue analysis [5].
    [Show full text]
  • Diagnostic Approach in Infants and Children with Mitochondrial Diseases Ching-Shiang Chi*
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Pediatrics and Neonatology (2015) 56,7e18 Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.pediatr-neonatol.com INVITED REVIEW ARTICLE Diagnostic Approach in Infants and Children with Mitochondrial Diseases Ching-Shiang Chi* Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan Received Mar 17, 2014; accepted Mar 27, 2014 Available online 20 August 2014 Key Words Mitochondrial diseases are a heterogeneous group of disorders affecting energy production in diagnosis; the human body. The diagnosis of mitochondrial diseases represents a challenge to clinicians, infants and children; especially for pediatric cases, which show enormous variation in clinical presentations, as well mitochondrial as biochemical and genetic complexity. diseases; Different consensus diagnostic criteria for mitochondrial diseases in infants and children are Taiwan available. The lack of standardized diagnostic criteria poses difficulties in evaluating diag- nostic methodologies. Even though there are many diagnostic tools, none of them are sensitive enough to make a confirmative diagnosis without being used in combination with other tools. The current approach to diagnosing and classifying mitochondrial diseases incorporates clin- ical, biochemical, neuroradiological findings, and histological criteria, as well as DNA-based molecular diagnostic testing. The confirmation or exclusion of
    [Show full text]