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J Neurol 2018 Sep 27;265(9):2015-2022. Epub 2018 Jun 27.

Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.

Background: Friedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Read More

Mol Ther 2018 08 28;26(8):1940-1952. Epub 2018 May 28.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U1258, 67404 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Université de Strasbourg, 67000 Strasbourg, France. Electronic address:

Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Read More

J Neurol 2018 Jun 25;265(6):1454-1462. Epub 2018 Apr 25.

Service of Neurology, University Hospital "Marqués de Valdecilla (IDIVAL)", University of Cantabria, and "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)", Santander, Spain.

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Read More

Clin Neurophysiol 2018 Jun 27;129(6):1121-1129. Epub 2018 Mar 27.

Laboratory of Neurosensory Biophysics, UMR INSERM 1107, University Clermont Auvergne, Clermont-Ferrand, France; Centre Jean Perrin, Clermont-Ferrand, France. Electronic address:

Objectives: In patients with Friedreich ataxia (FRDA), mitochondrial failure leads to impaired cellular energetics. Since many FRDA patients have impaired hearing in noise, we investigated the objective consequences on standard auditory brainstem-evoked responses (ABRs).

Methods: In 37 FRDA patients, among whom 34 with abnormal standard ABRs, hearing sensitivity, speech-in-noise intelligibility and otoacoustic emissions were controlled. Read More

J Child Neurol 2018 05 2;33(6):397-404. Epub 2018 Apr 2.

1 Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Objective: To determine how mobility device use impacts quality of life in children with Friedreich ataxia.

Study Design: Data from 111 pediatric patients with genetically confirmed Friedreich ataxia were collected from a prospective natural history study utilizing standardized clinical evaluations, including health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Module. Read More

Muscle Nerve 2018 05 27;57(5):852-856. Epub 2017 Nov 27.

Department of Neurology, Auckland District Health Board, Auckland, New Zealand.

Introduction: Sensory impairment in Friedreich ataxia (FRDA) is generally accepted as being due to a ganglionopathy. The degree of contribution from axonal pathology remains a matter of debate. Nerve ultrasound may be able to differentiate these processes. Read More

J Neurosci Rural Pract 2017 Aug;8(Suppl 1):S117-S119

Department of Pediatric Neurosciences, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India.

Patients with Friedreich's ataxia (FA) are at an increased risk of developing diabetes mellitus and glucose intolerance. Diabetes usually develops many years after the initial presentation. We report an 8-year-old girl who initially presented with diabetic ketoacidosis and was treated as a case of insulin-dependent diabetes mellitus. Read More

Acta Med Iran 2017 Feb;55(2):128-130

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Friedreich's ataxia (FRDA) is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1) is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Read More

Parkinsonism Relat Disord 2017 01 19;34:71-72. Epub 2016 Oct 19.

Neuroscience Centre, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address:

Cerebellum 2017 04;16(2):599-601

Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil.

Herein, we report a patient that presented with late-onset progressive steppage gait, neuropathy and pes cavus, suggesting Charcot-Marie-Tooth (CMT) disease. Subsequent genetic investigation confirmed Friedreich's ataxia (FRDA). We demonstrate that late-onset Friedreich's ataxia (LOFA) may be a CMT mimicker. Read More

Case Rep Neurol Med 2016 7;2016:4515938. Epub 2016 Sep 7.

Suna and Inan Kıraç Foundation Neurodegeneration Research Laboratory, Molecular Biology and Genetics Department, Bogazici University, 34342 Istanbul, Turkey.

Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. Read More

Behav Brain Res 2017 01 26;316:183-188. Epub 2016 Aug 26.

Department of Molecular Biosciences, University of California, Davis, CA 95616, USA. Electronic address:

Friedreich's Ataxia (FA) is a pediatric neurodegenerative disease whose clinical presentation includes ataxia, muscle weakness, and peripheral sensory neuropathy. The KIKO mouse is an animal model of FA with frataxin deficiency first described in 2002, but neurobehavioral deficits have never been described in this model. The identification of robust neurobehavioral deficits in KIKO mice could support the testing of drugs for FA, which currently has no approved therapy. Read More

Muscle Nerve 2017 02 12;55(2):E7-E8. Epub 2016 Sep 12.

Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.

Rev Neurol (Paris) 2016 Aug - Sep;172(8-9):524-529. Epub 2016 Jul 28.

Service de neurologie, hôpital de Hautepierre, 1, avenue Molière, 67000 Strasbourg, France; Fédération de médecine translationnelle, 67000 Strasbourg, France.

Mitochondrial diseases (MIDs) are a large group of heterogeneous disorders due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes, the latter encoding proteins involved in mitochondrial function. A multisystem clinical picture that involves several organs, including both the peripheral and central nervous systems, is a common presentation of MID. Movement disorders, even isolated ones, are not rare. Read More

Neurologia 2016 Jul 23. Epub 2016 Jul 23.

Servicio de Neurología, Complexo Hospitalario Universitario, Santiago de Compostela, España. Electronic address:

Introduction: Autosomal recessive spinocerebellar ataxia refers to a large group of diseases affecting the cerebellum and/or its connections, although they may also involve other regions of the nervous system. These diseases are accompanied by a wide range of systemic manifestations (cardiopathies, endocrinopathies, skeletal deformities, and skin abnormalities).

Development: This study reviews current knowledge of the most common forms of autosomal recessive spinocerebellar ataxia in order to provide tips that may facilitate diagnosis. Read More

Brain 2016 07 19;139(Pt 7):e39. Epub 2016 Apr 19.

1 Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France 2 Faculté de Médecine Denis Diderot, Université Paris Diderot - Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France

Dis Model Mech 2016 06 14;9(6):647-57. Epub 2016 Apr 14.

Program in Rare and Genetic Diseases and IBV/CSIC Associated Unit at CIPF, Centro de Investigación Príncipe Felipe (CIPF), Valencia 46012, Spain CIBER de Enfermedades Raras (CIBERER), Valencia 28029, Spain Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia 46010, Spain

Frataxin (FXN) deficiency causes Friedreich's ataxia (FRDA), a multisystem disorder with neurological and non-neurological symptoms. FRDA pathophysiology combines developmental and degenerative processes of dorsal root ganglia (DRG), sensory nerves, dorsal columns and other central nervous structures. A dying-back mechanism has been proposed to explain the peripheral neuropathy and neuropathology. Read More

Mov Disord 2016 Jan 21;31(1):62-9. Epub 2015 Sep 21.

Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, France Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France; and Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.

Background: Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia. Read More

J Clin Neuromuscul Dis 2015 Sep;17(1):13-7

*The University of Tennessee Health Science Center, Memphis, TN; and †The University of Texas Southwestern Medical Center, Dallas, TX.

The classic phenotype of Friedreich ataxia is characterized by dysarthria, progressive limb and trunk ataxia, loss of reflexes, and gait disturbance with the onset of disease before the second decade. Homozygous trinucleotide repeat expansion of GAA in the FXN gene is found in 98% of patients. Two-5% of all patients have a repeat expansion on one allele and a point mutation on the other allele. Read More

Free Radic Biol Med 2015 Nov 12;88(Pt A):10-7. Epub 2015 Jun 12.

Department of Molecular Biosciences, University of California, Davis, CA 95616, USA. Electronic address:

Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Read More

Ann Indian Acad Neurol 2015 Apr-Jun;18(2):171-80

Department of Ear, Nose and Throat, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.

Aims: To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center.

Settings And Design: A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present. Read More

Neurodegener Dis 2015 17;15(2):114-20. Epub 2015 Mar 17.

Department of Neurosciences, University of Padova, Padova,Italy.

Background: Friedreich's ataxia (FRDA) is a degenerative disorder caused by mutations of the FXN gene. Sensorineural hearing loss is one of the clinical features of FRDA, and the majority of hearing-impaired patients have shown evidence of auditory neuropathy.

Objective: This study characterizes the cochlear receptor and auditory nerve potentials in a patient with FRDA who had the clinical profile of auditory neuropathy. Read More

Neurogenetics 2015 Jul 8;16(3):151-60. Epub 2015 Feb 8.

Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Pedro de Toledo 650 Vila Clementino, São Paulo, 04039-002, SP, Brazil,

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. Read More

J Mov Disord 2015 Jan 13;8(1):33-6. Epub 2015 Jan 13.

Department of Neurology, St. Olavs University Hospital, Trondheim, Norway ; Department of Neurology, Norwegian University of Science and Technology, Trondheim, Norway.

Objective: Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurological disorder which usually starts in childhood. The clinical presentation is very similar to Friedreich ataxia, most patients have progressive truncal and extremity ataxia, areflexia, positive Babinski sign, dysarthria and sensory neuropathy.

Methods: We made an inquiry to our colleagues in Norway, we included information from a prevalence study published southern Norway and added data from our own known case. Read More

J Child Neurol 2015 May 3;30(6):741-8. Epub 2014 Sep 3.

Division of Pediatric Neurology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.

As part of a natural history study of giant axonal neuropathy, we hypothesized that the Friedreich Ataxia Rating Scale and the Gross Motor Function Measure would show a significant change over 6 months, reflecting subjects' decline in motor function. The Friedreich Ataxia Rating Scale was performed on 11 subjects and the Gross Motor Function Measure was performed on 10 subjects twice with a six-month interval. A paired two-tailed t-test was used to assess the difference in each subject's score. Read More

Front Cell Neurosci 2014 13;8:124. Epub 2014 May 13.

Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe Valencia, Spain ; IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe Valencia, Spain ; CIBER de Enfermedades Raras Valencia, Spain.

Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems. Dorsal root ganglia (DRG) are the major target tissue structures. This neuropathy is caused by mutations in the FXN gene that encodes frataxin. Read More

Neurology 2014 Apr 28;82(16):1410-5. Epub 2014 Mar 28.

From the University of Melbourne (D.J.S.), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Anatomical Pathology (C.A.M.), Alfred Hospital, Melbourne, Australia; Department of Forensic Medicine (M.L.R.), New South Wales Pathology, New South Wales, Australia; Department of Medicine (A.M.C.), Tauranga Hospital, Wellington, New Zealand; Department of Neurology (S.M.), Capital Coast Health, Wellington, New Zealand; Pathology (D.L.), Waikato Hospital, Hamilton, Waikato, New Zealand; Department of Neuroscience (L.R.), St Vincent's Hospital, Melbourne, Australia; Department of Neuroscience (E.S.), Monash University, Melbourne, Australia; and Department of Neurology (G.M.H.), Royal Prince Alfred Hospital, Sydney, Australia.

Objective: To elucidate the neuropathology in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia comprised of the triad of cerebellar impairment, bilateral vestibular hypofunction, and a peripheral sensory deficit.

Method: Brain and spinal neuropathology in 2 patients with CANVAS, together with brain and otopathology in another patient with CANVAS, were examined postmortem.

Results: Spinal cord pathology demonstrated a marked dorsal root ganglionopathy with secondary tract degeneration. Read More

Wien Med Wochenschr 2013 Nov 24;163(21-22):505-13. Epub 2013 Oct 24.

Krankenanstalt Rudolfstiftung, Postfach 20, 1180, Vienna, Austria,

Objectives: Unclassified cardiomyopathies (CMPs) include left ventricular hypertrabeculation or noncompaction (LVHT) and Takotsubo syndrome (TTS). Unclassified CMPs are frequently associated with noncardiac disease, including neuromuscular disorders (NMDs). This review aims at summarizing and discussing recent findings concerning the association of NMDs with unclassified CMPs. Read More

Medicina (B Aires) 2013 ;73 Suppl 1:38-48

Neurología pediátrica, Universidad de Chile, Chile. E-mail:

Chronic ataxias are an heterogeneous group of disorders that affect the child at different ages. Thus, the congenital forms, generally non progressive are observed from first months of life and are expressed by hypotonia and motor delay long before the ataxia became evident. The cerebral magnetic resonance images (MRI) may be diagnostic in some pictures like Joubert syndrome. Read More

J Neurosci Res 2013 Nov 30;91(11):1483-91. Epub 2013 Aug 30.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

Friedreich's ataxia (FRDA) is an autosomal recessive ataxia, characterized by progressive gait ataxia, limb ataxia, dysarthria, and areflexia associated with diabetes and hypertrophic cardiomyopathy. The primary cause of FRDA is the presence of expanded DNA triplet (GAA) repeats in the first intron of the fxn gene on chromosome 9q13. The expanded DNA repeats in fxn inhibit expression of the protein frataxin, which leads to neuronal degeneration. Read More

Handb Clin Neurol 2013 ;113:1869-78

Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address:

The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. Read More

Cochlear Implants Int 2013 Nov 9;14(5):287-90. Epub 2013 Mar 9.

Addenbrooke's Hospital, Cambridge, UK.

With an incidence of 1:29 000 among Caucasians, Friedreich's ataxia (FRDA) is the most common inherited ataxia, leading to both sensory and motor degeneration. Despite many FRDA patients exhibiting normal or near normal sound detection thresholds, many individuals show abnormal neural conduction along their central auditory pathways. Electrophysiological testing can show abnormal or absent cochlear nerve and auditory brainstem recordings in the presence of normal pre-neural cochlear function (otoacoustic emissions or cochlear microphonics). Read More

J Neuropathol Exp Neurol 2013 Feb;72(2):78-90

Research Service, Veterans Affairs Medical Center, Albany, New York 12208, USA.

Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome-encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. Read More

Diagn Mol Pathol 2012 Dec;21(4):241-5

National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Ataxia with oculomotor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia caused by mutations in the SETX gene. It is a rare monogenic disease characterized by progressive cerebellar ataxia, oculomotor apraxia, axonal sensorimotor neuropathy, and an elevated serum α-fetoprotein level. To date, >100 AOA2 patients have been described and 75 different mutations in the SETX gene have been identified. Read More

Neuroscience 2012 Dec 13;226:227-35. Epub 2012 Sep 13.

The University of Melbourne, Department of Audiology & Speech Pathology, Parkville, Melbourne, Australia.

Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Read More

J Child Neurol 2012 Sep 29;27(9):1197-203. Epub 2012 Jun 29.

Department of Audiology & Speech Pathology, University of Melbourne, Parkville, VIC, Australia.

Friedreich ataxia is a neurodegenerative disease with an average age of onset of 10 years. The authors sought to investigate the presence and functional consequences of auditory neuropathy in a group of affected children and to evaluate the ability of personal FM-listening systems to improve perception. Nineteen school-aged individuals with Friedreich ataxia and a cohort of matched control subjects underwent a battery of auditory function tests. Read More

J Child Neurol 2012 Sep 29;27(9):1133-7. Epub 2012 Jun 29.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, VIC, Australia.

Friedreich ataxia, the most common hereditary ataxia, affects approximately 1 per 29,000 white individuals. In about 98% of these individuals, it is due to homozygosity for a GAA trinucleotide repeat expansion in intron 1 of FXN; in the other 2%, it is due to compound heterozygosity for a GAA expansion and point mutation or deletion. The condition affects multiple sites in the central and peripheral nervous system as well as a number of other organ systems, resulting in multiple signs and symptoms. Read More

Cerebellum 2012 Dec;11(4):1002-11

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.

Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Read More

Neurobiol Dis 2013 Mar 9;51:56-65. Epub 2012 Mar 9.

Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada.

Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). Read More

J Child Neurol 2012 Aug 12;27(8):1056-8. Epub 2012 Jan 12.

Department of Pediatrics, Division of Child and Adolescent Neurology, University of Texas Health Science Center, Houston, TX, USA.

A previously healthy 10-year-old girl presented with subacute onset of ataxia and acute-onset cardiac and pulmonary failure. Magnetic resonance imaging (MRI) of the brain showed symmetric T2 fluid-attenuated inversion recovery hyperintensities in the dorsal pons, medulla, and inferior cerebellar peduncles; nerve conduction velocities and electromyography demonstrated a sensorimotor axonal neuropathy consistent with Friedreich ataxia. Within 12 months, the patient fully recovered and molecular testing of the frataxin gene was unremarkable. Read More

Cerebellum 2011 Mar;10(1):9-13

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany.

Friedreich's ataxia (FA) is a multisystemic degenerative disease, but the prevalence of restless legs syndrome (RLS) is unknown. FA patients might be particularly susceptible to develop RLS as FA presents with features commonly associated with RLS, e.g. Read More

Neuroscience 2010 Dec 17;171(2):552-5. Epub 2010 Sep 17.

Department of Otolaryngology, The University of Melbourne, Parkville, Victoria 3010, Australia.

Friedreich ataxia (FRDA) is a neurodegenerative disease affecting motor and sensory systems. This study aimed to investigate the presence and perceptual consequences of auditory neuropathy (AN) in affected individuals and examine the use of personal-FM systems to ameliorate the resulting communication difficulties. Ten individuals with FRDA underwent a battery of auditory function tests and their results were compared with a cohort of matched controls. Read More

J Neurosci 2010 Aug;30(34):11369-78

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.

Friedreich ataxia, a neurodegenerative disorder resulting from frataxin deficiency, is thought to involve progressive cellular damage from oxidative stress. In Drosophila larvae with reduced frataxin expression (DfhIR), we evaluated possible mechanisms of cellular neuropathology by quantifying mitochondrial axonal transport, membrane potential (MMP), and reactive oxygen species (ROS) production in the DfhIR versus wild-type nervous system throughout development. Although dying-back neuropathy in DfhIR larvae did not occur until late third instar, reduced MMP was already apparent at second instar in the cell bodies, axons and neuromuscular junctions (NMJs) of segmental nerves. Read More

Acta Neuropathol 2010 Jul 26;120(1):97-108. Epub 2010 Mar 26.

VA Medical Center, Albany, NY 12208, USA.

Friedreich's ataxia (FRDA) causes a complex neuropathological phenotype with characteristic lesions of dorsal root ganglia (DRG); dorsal spinal roots; dorsal nuclei of Clarke; spinocerebellar and corticospinal tracts; dentate nuclei; and sensory nerves. This report presents a systematic morphological analysis of sural nerves obtained by autopsy of six patients with genetically confirmed FRDA. The outstanding lesion consisted of lack of myelinated fibers whereas axons were present in normal numbers. Read More

Neurogenetics 2010 May 17;11(2):261-5. Epub 2010 Feb 17.

National Hospital for Neurology and Neurosurgery, London, UK.

Friedreich ataxia (FRDA) is typically characterized by slowly progressive ataxia, depressed tendon reflexes, dysarthria, pyramidal signs, and loss of position and vibration sense with onset before 25 years. While several atypical forms of FRDA are recognized, profound vision deficit is rare. We describe here a 41-year-old man with profound vision deficit and episodic complete blindness associated with marked optic atrophy, spastic paraparesis, and sensory neuropathy without ataxia whose diagnostic evaluation revealed compound heterozygosity for two frataxin mutations, a 994 GAA repeat intronic expansion and c. Read More

Neurosci Lett 2010 Mar 28;472(2):85-9. Epub 2010 Jan 28.

Center of Medical Genetics, Holguín, Cuba.

This report describes two families who presented with autosomal recessive ataxia. By means of Polymerase Chain Reaction (PCR) molecular testing we identified expansions in the gene encoding Frataxin (FTX) that is diagnostic of Friedreich ataxia. A history of reproductive loss in the two families, prominent scoliosis deformity preceding the onset of ataxic gait, the presence of a sensitive axonal neuropathy, as well as the common origin of ancestors are unusual features of these families. Read More

Mol Genet Metab 2010 Mar 26;99(3):246-55. Epub 2009 Nov 26.

Department of Pediatrics,Center for Inherited Disorders of Metabolism, University Hospitals Case Medical Center, Rainbow Babies and Childrens Hospital, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-6004, USA.

While many treatments for mitochondrial electron transport (respiratory) chain disorders have been suggested, relatively few have undergone controlled clinical trials. This review focuses on the recent history of clinical trials of dichloroacetate (DCA), arginine, coenzyme Q(10), idebenone, and exercise in both primary (congenital) disorders and secondary (degenerative) disorders. Despite prior clinical impressions that DCA had a positive effect on mitochondrial disorders, two trials of diverse subjects failed to demonstrate a clinically significant benefit, and a trial of DCA in MELAS found a major negative effect of neuropathy. Read More

Brain 2009 Oct 20;132(Pt 10):2688-98. Epub 2009 Aug 20.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, Université de Strasbourg, INSERM, Illkirch, France.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. Read More

Can J Neurol Sci 2009 Jul;36(4):409-28

Krankenanstalt Rudolfstiftung, Vienna, Austria, Europe.

Heredoataxias are a group of genetic disorders with a cerebellar syndrome as the leading clinical manifestation. The current classification distinguishes heredoataxias according to the trait of inheritance into autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias. The autosomal dominant heredoataxias are separated into spinocerebellar ataxias (SCA1-8, 10-15, 17-23, 25-30, and dentato-rubro-pallido-luysian atrophy), episodic ataxias (EA1-7), and autosomal dominant mitochondrial heredoataxias (Leigh syndrome, MIRAS, ADOAD, and AD-CPEO). Read More

Acta Neurol Scand Suppl 2009 (189):42-5

Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Ataxia with vitamin E deficiency (AVED) is a rare cause of hereditary ataxia in north European countries with unknown prevalence. Few cases are reported from these countries.

Methods: Through a systematic population based study of hereditary ataxia in southeast Norway subjects were classified and investigated. Read More