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Joers JM, Adanyeguh IM, Deelchand DK, Hutter DH, Eberly LE, Iltis I, Bushara KO, Lenglet C, Henry PG. Spinal cord magnetic resonance imaging and spectroscopy detect early-stage alterations and disease progression in Friedreich ataxia. Brain Commun 2022; 4:fcac246. [PMID: 36300142 PMCID: PMC9581897 DOI: 10.1093/braincomms/fcac246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 06/04/2022] [Accepted: 09/23/2022] [Indexed: 02/01/2023] Open
Abstract
Friedreich ataxia is the most common hereditary ataxia. Atrophy of the spinal cord is one of the hallmarks of the disease. MRI and magnetic resonance spectroscopy are powerful and non-invasive tools to investigate pathological changes in the spinal cord. A handful of studies have reported cross-sectional alterations in Friedreich ataxia using MRI and diffusion MRI. However, to our knowledge no longitudinal MRI, diffusion MRI or MRS results have been reported in the spinal cord. Here, we investigated early-stage cross-sectional alterations and longitudinal changes in the cervical spinal cord in Friedreich ataxia, using a multimodal magnetic resonance protocol comprising morphometric (anatomical MRI), microstructural (diffusion MRI), and neurochemical (1H-MRS) assessments.We enrolled 28 early-stage individuals with Friedreich ataxia and 20 age- and gender-matched controls (cross-sectional study). Disease duration at baseline was 5.5 ± 4.0 years and Friedreich Ataxia Rating Scale total neurological score at baseline was 42.7 ± 13.6. Twenty-one Friedreich ataxia participants returned for 1-year follow-up, and 19 of those for 2-year follow-up (cohort study). Each visit consisted in clinical assessments and magnetic resonance scans. Controls were scanned at baseline only. At baseline, individuals with Friedreich ataxia had significantly lower spinal cord cross-sectional area (-31%, P = 8 × 10-17), higher eccentricity (+10%, P = 5 × 10-7), lower total N-acetyl-aspartate (tNAA) (-36%, P = 6 × 10-9) and higher myo-inositol (mIns) (+37%, P = 2 × 10-6) corresponding to a lower ratio tNAA/mIns (-52%, P = 2 × 10-13), lower fractional anisotropy (-24%, P = 10-9), as well as higher radial diffusivity (+56%, P = 2 × 10-9), mean diffusivity (+35%, P = 10-8) and axial diffusivity (+17%, P = 4 × 10-5) relative to controls. Longitudinally, spinal cord cross-sectional area decreased by 2.4% per year relative to baseline (P = 4 × 10-4), the ratio tNAA/mIns decreased by 5.8% per year (P = 0.03), and fractional anisotropy showed a trend to decrease (-3.2% per year, P = 0.08). Spinal cord cross-sectional area correlated strongly with clinical measures, with the strongest correlation coefficients found between cross-sectional area and Scale for the Assessment and Rating of Ataxia (R = -0.55, P = 7 × 10-6) and between cross-sectional area and Friedreich ataxia Rating Scale total neurological score (R = -0.60, P = 4 × 10-7). Less strong but still significant correlations were found for fractional anisotropy and tNAA/mIns. We report here the first quantitative longitudinal magnetic resonance results in the spinal cord in Friedreich ataxia. The largest longitudinal effect size was found for spinal cord cross-sectional area, followed by tNAA/mIns and fractional anisotropy. Our results provide direct evidence that abnormalities in the spinal cord result not solely from hypoplasia, but also from neurodegeneration, and show that disease progression can be monitored non-invasively in the spinal cord.
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Affiliation(s)
- James M Joers
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Isaac M Adanyeguh
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Dinesh K Deelchand
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Diane H Hutter
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Lynn E Eberly
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Isabelle Iltis
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Khalaf O Bushara
- Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Christophe Lenglet
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Pierre-Gilles Henry
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias. Tomography 2022; 8:423-437. [PMID: 35202200 PMCID: PMC8877967 DOI: 10.3390/tomography8010035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/16/2022] [Accepted: 02/02/2022] [Indexed: 11/18/2022] Open
Abstract
MRI shows the three archetypal patterns of CNS volume loss underlying progressive ataxias in vivo, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Friedreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, repurposing therapies or the enlargement of drug indications in progressive ataxias.
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Baviera-Muñoz R, Campins-Romeu M, Carretero-Vilarroig L, Sastre-Bataller I, Martínez-Torres I, Vázquez-Costa JF, Muelas N, Sevilla T, Vílchez JJ, Aller E, Jaijo T, Bataller L, Espinós C. Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations. J Neurol Sci 2021; 429:118062. [PMID: 34500365 DOI: 10.1016/j.jns.2021.118062] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/25/2021] [Accepted: 08/27/2021] [Indexed: 12/27/2022]
Abstract
Spastic paraplegia type 7 (SPG7) is one of the most common hereditary spastic paraplegias. SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes. We sought to clinically and genetically characterize a Spanish cohort of SPG7 patients. Patients were recruited from our HCA and HSP cohorts. We identified twenty-one patients with biallelic pathogenic SPG7 mutations. Mean age at onset was 37.4 years (SD ± 14.3). The most frequent phenotype was spastic ataxia (57%), followed by pure spastic paraplegia (19%) and complex phenotypes (19%). Isolated patients presented with focal or multifocal dystonia, subclinical myopathy or ophthalmoplegia. p.Ala510Val was the most frequent pathogenic variant encountered. Compound heterozygous for p.Ala510Val displayed younger onset (p < 0.05) and more complex phenotypes (p < 0.05) than p.Ala510Val homozygotes. Two novel variants were found: p.Lys559Argfs*33 and p.Ala312Glu. In conclusion, spastic ataxia is the most common phenotype found in Spanish patients. Nonetheless, SPG7 analysis should also be considered in patients with less frequent clinical findings such as dystonia or ophthalmoplegia especially when these symptoms are associated with mild spastic ataxia.
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Affiliation(s)
- Raquel Baviera-Muñoz
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain
| | - Marina Campins-Romeu
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain
| | - Lidón Carretero-Vilarroig
- Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Cell Biology Department, University of Valencia, Valencia, Spain
| | - Isabel Sastre-Bataller
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain
| | - Irene Martínez-Torres
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain
| | - Juan F Vázquez-Costa
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
| | - Nuria Muelas
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain
| | - Teresa Sevilla
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain; Department of Medicine, University of Valencia, Valencia, Spain
| | - Juan J Vílchez
- Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain
| | - Elena Aller
- Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain; Department of Genetics, Hospital Universitari I Politècnic La Fe, Valencia, Spain
| | - Teresa Jaijo
- Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain; Department of Genetics, Hospital Universitari I Politècnic La Fe, Valencia, Spain
| | - Luis Bataller
- Department of Neurology, Hospital Universitari I Politècnic La Fe, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain; Department of Medicine, University of Valencia, Valencia, Spain.
| | - Carmen Espinós
- Rare Diseases Joint Unit, CIPF-IIS La Fe, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain; Laboratory of Rare Neurodegenerative Diseases, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
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Mormina E, Petracca M, Bommarito G, Piaggio N, Cocozza S, Inglese M. Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging. World J Radiol 2017; 9:371-388. [PMID: 29104740 PMCID: PMC5661166 DOI: 10.4329/wjr.v9.i10.371] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 07/18/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique’s advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.
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Affiliation(s)
- Enricomaria Mormina
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Neuroradiology Unit, Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, 98100 Messina, Italy
| | - Maria Petracca
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80138 Naples, Italy
| | - Giulia Bommarito
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
| | - Niccolò Piaggio
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
- Department of Neuroradiology, San Martino Hospital, 16132 Genoa, Italy
| | - Sirio Cocozza
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80138 Naples, Italy
| | - Matilde Inglese
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
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Szmulewicz DJ, Roberts L, McLean CA, MacDougall HG, Halmagyi GM, Storey E. Proposed diagnostic criteria for cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Neurol Clin Pract 2016; 6:61-68. [PMID: 26918204 DOI: 10.1212/cpj.0000000000000215] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
PURPOSE OF REVIEW Diagnosis of ataxic disorders is an important clinical challenge upon which prognostication, management, patient solace, and, above all, the hope of future treatment all rely. Heritable diseases and the possibility of affected offspring carry the added burden of portending adverse health, social and financial ramifications. RECENT FINDINGS Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited multisystem ataxia compromising cerebellar, vestibular, and sensory function. It is not uncommon, but despite early attempts the genetic defect is yet to be identified. As the search for the causative gene continues, we have found it useful to further define this syndrome in terms of its likely phenotype. SUMMARY We propose staged diagnostic criteria based on the identified pathology in CANVAS. We envisage that these criteria will aid the clinician in diagnosing CANVAS and the researcher in further elucidating this complex disorder.
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Affiliation(s)
- David J Szmulewicz
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
| | - Leslie Roberts
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
| | - Catriona A McLean
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
| | - Hamish G MacDougall
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
| | - G Michael Halmagyi
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
| | - Elsdon Storey
- University of Melbourne (DJS), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Neuroscience (LR), St Vincent's Hospital, Melbourne, Australia; Department of Anatomical Pathology (CAL), Alfred Hospital, Melbourne, Australia; Vestibular Research Laboratory (HGM), School of Psychology, University of Sydney, Australia; Department of Neuroscience (GMH), Monash University, Melbourne, Australia; and Department of Neurology (ES), Royal Prince Alfred Hospital, Sydney, Australia
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Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias. THE CEREBELLUM 2015; 15:21-25. [DOI: 10.1007/s12311-015-0738-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Stefanescu MR, Dohnalek M, Maderwald S, Thürling M, Minnerop M, Beck A, Schlamann M, Diedrichsen J, Ladd ME, Timmann D. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia. Brain 2015; 138:1182-97. [PMID: 25818870 DOI: 10.1093/brain/awv064] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 01/21/2015] [Indexed: 02/07/2023] Open
Abstract
Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls (P < 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes.
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Affiliation(s)
- Maria R Stefanescu
- 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany
| | - Moritz Dohnalek
- 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany
| | - Stefan Maderwald
- 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany
| | - Markus Thürling
- 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany
| | - Martina Minnerop
- 3 Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany 4 Department of Neurology, University of Bonn, Bonn, Germany
| | - Andreas Beck
- 5 Department of Computer Sciences, University of Düsseldorf, Düsseldorf, Germany
| | - Marc Schlamann
- 6 Department of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Essen, Germany
| | - Joern Diedrichsen
- 7 Institute of Cognitive Neuroscience, University College London, London, UK
| | - Mark E Ladd
- 2 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany 6 Department of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Essen, Germany 8 Division of Medical Physics in Radiology, University of Heidelberg and German Cancer Research Centre, Heidelberg, Germany
| | - Dagmar Timmann
- 1 Department of Neurology, University of Duisburg-Essen, Essen, Germany
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Pedroso JL, Braga-Neto P, Ricarte IF, Albuquerque MVC, Barsottini OGP. Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed. ARQUIVOS DE NEURO-PSIQUIATRIA 2013; 71:345-8. [DOI: 10.1590/0004-282x20130036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Accepted: 11/21/2012] [Indexed: 11/21/2022]
Abstract
Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.
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Teive HAG. Early onset cerebellar ataxia with retained reflexes: a clinical and genetic conundrum. ARQUIVOS DE NEURO-PSIQUIATRIA 2013; 71:341-342. [PMID: 23828530 DOI: 10.1590/0004-282x20130089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 05/07/2013] [Indexed: 06/02/2023]
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Spinal Cord Atrophy Correlates with Disability in Friedreich’s Ataxia. THE CEREBELLUM 2012; 12:43-7. [DOI: 10.1007/s12311-012-0390-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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De Michele G, Filla A. Other autosomal recessive and childhood ataxias. HANDBOOK OF CLINICAL NEUROLOGY 2012; 103:343-57. [PMID: 21827899 DOI: 10.1016/b978-0-444-51892-7.00021-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The label of "early-onset cerebellar ataxia with retained tendon reflexes" (EOCA) has been created to differentiate it from Friedreich ataxia (FRDA) patients with preserved knee jerks and absence of cardiomyopathy, optic atrophy, and diabetes mellitus. However, EOCA is a heterogeneous syndrome and several FRDA patients present with an EOCA-like phenotype. Cerebellar ataxia with hypogonadism is another heterogeneous syndrome for which no locus has been mapped yet. Two peculiar ataxic syndromes have been identified in genetically isolated populations: autosomal recessive ataxia of Charlevoix-Saguenay (ARSACS) in Quebec and infantile-onset spinocerebellar ataxia (IOSCA) in Finland. Both conditions present usually within the second year of life. ARSACS is characterized by marked spasticity and IOSCA by a complex phenotype which includes, besides ataxia, epilepsy, optic atrophy, ophthalmoplegia, hearing loss, and areflexia. The responsible genes are SACS, encoding sacsin, a protein which may act as a chaperone, and C10orf2, encoding Twinkle, a mitochondrial DNA-specific helicase. Marinesco-Sjögren syndrome, clinically characterized by cerebellar ataxia, cataracts, myopathy, and mental retardation, is genetically heterogeneous. One gene, SIL1, encodes a nucleotide exchange factor for the heat-shock protein 70 chaperone HSPA5. Five conditions account for most cases of progressive myoclonic ataxia: Unverricht-Lundborg disease, Lafora disease, myoclonic epilepsy with ragged-red fibers, neuronal ceroid lipofuscinoses, and sialidoses.
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Mascalchi M, Vella A. Magnetic resonance and nuclear medicine imaging in ataxias. HANDBOOK OF CLINICAL NEUROLOGY 2012; 103:85-110. [PMID: 21827882 DOI: 10.1016/b978-0-444-51892-7.00004-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET) have been widely applied to the investigation of patients with acute or chronic ataxias. Fundamentally, CT has a role in the emergency evaluation of the patient with acute ataxia to ascertain brainstem or cerebellar hemorrhage and to exclude a mass lesion in the posterior cranial fossa. Conventional MRI is the most frequently performed imaging investigation in patients with ataxia. It can support the diagnosis of acute cerebellitis and Wernicke encephalopathy by revealing T2 signal changes with a typical distribution. In patients with inherited or sporadic chronic ataxia it reveals three fundamental patterns of atrophy of the brainstem, cerebellum, and spinal cord which match the gross neuropathological descriptions. These are represented by olivopontocerebellar atrophy (OPCA), cortical cerebellar atrophy (CCA), and spinal atrophy (SA). A substantial correspondence exists among these patterns of atrophy shown by MRI and the etiological classification of inherited or acquired chronic ataxias. This, along with demonstration of T2 signal changes characteristic of some diseases, makes conventional MRI potentially useful for the diagnostic work-up of the single patient, especially in the case of a sporadic disease. Non-conventional MR techniques including diffusion MR, spectroscopy, and functional MR have been used in patients with acute or chronic ataxia, but their exact role in the evaluation of the single patient is not established yet. They are currently investigated as potential tools to monitor progression of neurodegeneration in chronic ataxia and to serve as "surrogate markers" in clinical trials. Several radiotracers have been utilized in combination with SPECT and PET in patients with ataxia. Perfusion SPECT can reveal cerebellar blood flow abnormalities early in the course of cerebellitis. It has also been utilized to investigate perfusion of the brain in several inherited or sporadic chronic ataxic diseases, contributing to improved understanding of the pathophysiology of these conditions. Recently, perfusion SPECT has been tested as a "surrogate marker" to verify the effects of newly developed therapies in patients with a variety of chronic ataxias. Whole-body FDG-PET is recommended in patients with suspected paraneoplastic cerebellar degeneration to detect the primary malignancy. Brain FDG-PET has provided important information on the pathophysiology of several acquired and inherited conditions. PET and SPECT with radiotracers able to assess the nigrostriatal system or the density of D2 dopamine receptors in the striatum are increasingly used in patients with adult-onset sporadic ataxia for the differential diagnosis between multiple system atrophy in which overt striatal abnormalities are found and idiopathic late-onset cerebellar ataxia in which no abnormality is detected.
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Affiliation(s)
- Mario Mascalchi
- Radiodiagnostic Section, Department of Clinical Physiopathology, University of Florence, Italy.
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Werneck LC, Cousseau VA, Graells XS, Werneck MC, Scola RH. Muscle study in experimental scoliosis in rabbits with costotransversectomy: evidence of ischemic process. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2008; 17:726-33. [PMID: 18210168 DOI: 10.1007/s00586-008-0598-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2007] [Revised: 12/10/2007] [Accepted: 12/21/2007] [Indexed: 11/25/2022]
Abstract
Scoliosis involves the central nervous system diseases, ligaments, articulations and skeletal muscles, but there is no consensus on its pathogeny and progression of muscle abnormalities. In this study, we investigate the morphologic changes in the muscle of rabbit submitted to experimental scoliosis, with special emphasis on abnormalities related to blood supply. We studied 26 rabbits subjected to costotransversectomy by pulling out six transverse processes at thoracic level and six rabbits were used as controls. All the animals operated upon developed scoliosis showing an average angle of 29.1 degrees on the 60th day, with its apices located at T4 and T12 when they were subjected to paraspinal muscle biopsy on both sides. The muscle biopsies were subjected to histological stains and histochemical reactions, as well as to a morphometric study. On the concave side, the changes were not statistically significant regarding the control group. On the convex side conjunctive tissue proliferation, infiltration by adipose tissue, central nucleus excess, inflammatory reaction, segmental fibrosis, type 1 fiber hypertrophy, type 2 fiber hypertrophy and atrophic angular dark fibers in the unspecific esterase were statistically significant. The segmental fibrosis reached a circumscribed muscle segment, compatible with an ischemic phenomenon. The histological diagnoses on the concave side of the animals had unspecific alterations (atrophy and hypertrophy) in 13, myopathy in 3, denervation in 3 and normal in 7. The convex side diagnoses were myopathy in 14, denervation in 8, mixed in 3 and normal in 1. The procedure determined morphologic changes on the convex side indicating possible denervation or myopathy of ischemic origin.
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Affiliation(s)
- Lineu C Werneck
- Department of Internal Medicine/Neurology, Universidade Federal do Paraná, Rua Gal. Carneiro 181-3 Andar, Curitiba, PR 80060-900, Brazil.
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14
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Shimazaki H, Sakoe K, Niijima K, Nakano I, Takiyama Y. An unusual case of a spasticity-lacking phenotype with a novel SACS mutation. J Neurol Sci 2007; 255:87-9. [PMID: 17349660 DOI: 10.1016/j.jns.2007.02.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2006] [Revised: 01/31/2007] [Accepted: 02/01/2007] [Indexed: 10/23/2022]
Abstract
The authors describe an unusual case of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) without leg spasticity, which is a core clinical feature of ARSACS. This is the second family with a spasticity-lacking phenotype in ARSACS. A peripheral nerve conduction study disclosed decreases in motor and sensory nerve conduction velocities with the disease progression. Although the leg spasticity is reported to become progressively worse during the disease and is prevalent in older patients, we first observed that the symptom had disappeared, probably due to the progressive peripheral nerve degeneration in the disease course. Thus, we should analyze the SACS gene even in cases of early-onset cerebellar ataxia without spasticity. The patient had a novel homozygous 2-base pair deletion mutation (c.5988-9 del CT) of the SACS gene, but the genotype was different from that in our first family of this phenotype. A further genotype-phenotype correlation study is required to clarify the molecular mechanism underlying 'sacsinopathies'.
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Affiliation(s)
- Haruo Shimazaki
- Division of Neurology, Department of Internal Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan
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Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.
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Affiliation(s)
- Yoshihisa Takiyama
- Division of Neurology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
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16
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Palau F, Espinós C. Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis 2006; 1:47. [PMID: 17112370 PMCID: PMC1664553 DOI: 10.1186/1750-1172-1-47] [Citation(s) in RCA: 119] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2006] [Accepted: 11/17/2006] [Indexed: 02/06/2023] Open
Abstract
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia.
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Affiliation(s)
- Francesc Palau
- Genetics and Molecular Medicine Unit, Instituto de Biomedicina, CSIC, Jaume Roig, 11 46010 Valencia, Spain
- Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
| | - Carmen Espinós
- Genetics and Molecular Medicine Unit, Instituto de Biomedicina, CSIC, Jaume Roig, 11 46010 Valencia, Spain
- Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Valencia, Spain
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Mantovan MC, Martinuzzi A, Squarzanti F, Bolla A, Silvestri I, Liessi G, Macchi C, Ruzza G, Trevisan CP, Angelini C. Exploring mental status in Friedreich's ataxia: a combined neuropsychological, behavioral and neuroimaging study. Eur J Neurol 2006; 13:827-35. [PMID: 16879292 DOI: 10.1111/j.1468-1331.2006.01363.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Despite much evidence of cognitive and affective disorders in Friedreich's ataxia (FRDA), the nature of mental status in FRDA has received little systematic attention. It has been proposed that the cerebellum may interfere indirectly with cognition through the cerebello-cortical loops, whereas the role of pathological changes in different areas of the central nervous system is still undetermined. In the present study, 13 patients with molecularly determined FRDA and a group of matched controls were evaluated by a comprehensive battery of neuropsychological tests and the Minnesota Multiphasic Personality Inventory. A repetitive task of simple visual-reaction times was used to investigate implicit learning in all subjects. Pathological changes in cortical areas were explored comparing cerebral activations of patients and controls during finger movements (functional MRI). The intelligence profile of FRDA patients is characterized by concrete thinking, poor capacity in concept formation and visuospatial reasoning. FRDA patients show reduced speed of information processing. The learning effect seen in controls was notably absent in patients with FRDA. The patients' personality is characterized by some pathological aspects and reduced defensiveness. Patterns of cortical activation during finger movements are heterogeneous in patients compared to controls. Cognitive impairment, mood disorders and motor deficits in FRDA patients may be the result of the cumulative damage caused by frataxin deficiency not only in the cerebellum and spinal cord but also in other brain areas.
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Affiliation(s)
- M C Mantovan
- Department of Neurology, Venice Hospital, University of Padua, Padua, Italy
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18
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Approach to the patient with ataxia. NEURODEGENER DIS 2005. [DOI: 10.1017/cbo9780511544873.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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van de Warrenburg BPC, Sinke RJ, Kremer B. Recent advances in hereditary spinocerebellar ataxias. J Neuropathol Exp Neurol 2005; 64:171-80. [PMID: 15804048 DOI: 10.1093/jnen/64.3.171] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
In recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinician, the expanding number of genes and genetic loci in these diseases and the enormous clinical heterogeneity of specific ataxia subtypes complicate management of ataxia patients. In this review, the clinical and neuropathologic features of the recently identified spinocerebellar ataxias are described, and the various molecular mechanisms that have been demonstrated to be involved in these disorders are discussed.
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20
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Viau M, Boulanger Y. Characterization of ataxias with magnetic resonance imaging and spectroscopy. Parkinsonism Relat Disord 2004; 10:335-51. [PMID: 15261875 DOI: 10.1016/j.parkreldis.2004.02.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2003] [Revised: 02/17/2004] [Accepted: 02/26/2004] [Indexed: 11/19/2022]
Abstract
A wide variety of autosomal transmitted ataxias exist and their ultimate characterization requires genetic testing. Common clinical characteristics among different ataxia types complicate the choice of the appropriate genetic test. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) generally show cerebellar or cerebral atrophy and perturbed metabolite levels which differ between ataxias. In order to help the clinician accurately identify the ataxia type, reported MRI and MRS data in different brain regions are summarized for more than 60 different types of autosomal inherited and sporadic ataxias.
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Affiliation(s)
- Martin Viau
- Département de Radiologie, Hôpital Saint-Luc, Centre Hospitalier de l'Université de Montréal, 1058 St-Denis, Montréal, Québec, Canada H2X 3J4
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21
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Mascalchi M, Cosottini M, Lolli F, Salvi F, Tessa C, Macucci M, Tosetti M, Plasmati R, Ferlini A, Tassinari CA, Villari N. Proton MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia. Radiology 2002; 223:371-8. [PMID: 11997539 DOI: 10.1148/radiol.2232010722] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To investigate whether proton magnetic resonance (MR) spectroscopy is a useful complement to MR imaging in patients with degenerative ataxia. MATERIALS AND METHODS Brain MR imaging and single-voxel proton MR spectroscopy of the right cerebellar hemisphere and pons were performed in 30 patients with sporadic (n = 16) or inherited (n = 14) degenerative ataxia and in 20 healthy control subjects. Several indexes of brainstem and cerebellar atrophy were measured on MR images, as well as the N-acetylaspartate/creatine (NAA/Cr), choline/Cr (Cho/Cr), and myo-inositol/Cr (mI/Cr) ratios in the MR spectra. Differences between patients and subjects were evaluated with the Kruskal-Wallis and Mann-Whitney tests, whereas correlation of clinical, MR imaging, and spectroscopic data was assessed with nonparametric Spearman rank correlation. RESULTS Measurements of brainstem and cerebellar atrophy obtained from MR images revealed patients had olivopontocerebellar atrophy (OPCA) (n = 11), spinal atrophy (SA) (n = 8), or corticocerebellar atrophy (CCA) (n = 4). Seven patients did not fulfill the criteria for any group and were considered undefined. In patients with OPCA, the pontine and cerebellar NAA/Cr and Cho/Cr ratios were significantly decreased when compared with those of the control subjects. Pontine and cerebellar NAA/Cr ratios were also significantly reduced in patients with SA and CCA. Five patients with undefined ataxia had a substantial decrease of pontine or cerebellar NAA/Cr ratio when compared with that of the control subjects. In patients with OPCA, the pontine NAA/Cr ratio (but not the atrophy measurements) showed a correlation (P =.04) with disability. CONCLUSION MR spectroscopy is a useful complement to MR imaging in patients with degenerative ataxia.
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Affiliation(s)
- Mario Mascalchi
- Section of Diagnostic Radiology, Department of Clinical Physiopathology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy
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22
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Marzouki N, Belal S, Benhamida C, Benlemlih M, Hentati F. Genetic analysis of early onset cerebellar ataxia with retained tendon reflexes in four Tunisian families. Clin Genet 2001; 59:257-62. [PMID: 11298681 DOI: 10.1034/j.1399-0004.2001.590407.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Spinocerebellar ataxias comprise a poorly understood group of inherited degenerative neurological diseases. Attempts to classify hereditary ataxias on the basis of the neurological features or specific clinical signs such as tendon reflex changes have proven to be unsatisfactory. Early onset cerebellar ataxia (EOCA) is generally inherited as an autosomal-recessive trait. Thus far, we do not have accurate answers to several questions about its classification. However, significant clinical heterogeneity observed in four Tunisian families with typical EOCA clinical features reinforces the hypothesis of genetic heterogeneity underlying this phenotype. We have demonstrated that three of the four families studied were not linked to Friedreich's ataxia (FA), vitamin E deficiency ataxia (AVED), and autosomal dominant cerebellar ataxia (ADCA) loci. The fourth family showed homozygosity for a large pathological expansion of GAA repeat in all patients, the parents being heterozygous for this mutation. We have also noted, in the case of the family studied, that there was instability in the transmission of the mutation, along with a phenomenon of anticipation comparable to that observed in dominant triplet repeat diseases. EOCA is thus clinically indistinguishable from FA, yet genetically independent of all known candidate genes. Genetic mapping is required for research into the causal gene and an understanding of the disease's physiopathologic mechanisms.
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Affiliation(s)
- N Marzouki
- Labratoire de Génétique Moléculaire, Université Mohamed Ben Abdellah, Faculté des Sciences, Fes, Morocco.
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23
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Vielhaber S, Ebert AD, Feistner H, Herrmann M. Frontal-executive dysfunction in early onset cerebellar ataxia of Holmes' type. Clin Neurol Neurosurg 2000; 102:102-5. [PMID: 10817897 DOI: 10.1016/s0303-8467(00)00068-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
We report the case of a 29-year-old male patient with cerebellar ataxia of Holmes' type. The combination of progressive cerebellar ataxia and hypogonadotrophic hypogonadism is a rare distinctive syndrome which was first described by Holmes in 1907. Early diagnosis is desirable because replacement of testosterone may allow normal sexual development. MRI showed severe combined superior vermian and cerebellar hemisphere atrophy. Comprehensive neuropsychological testing pointed to a more widespread cerebellar mediated functional CNS involvement in the earlier stages of this ataxic syndrome than previously described in mentally not retarded subjects.
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Affiliation(s)
- S Vielhaber
- Department of Neurology II, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120, Magdeburg, Germany.
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24
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Schelhaas HJ, Hulst MV, Ippel E, Prevo RL, Hageman G. Early onset cerebellar ataxia with retained tendon reflexes: foot deformity in a first grade family member. Clin Neurol Neurosurg 1999; 101:253-5. [PMID: 10622455 DOI: 10.1016/s0303-8467(99)00051-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich's ataxia (FA) mainly by the preservation of tendon reflexes, a better prognosis, and the absence of GAA expansion in the frataxin gene. Although EOCA is thought to be a hereditary disorder with an autosomal recessive mode of inheritance, genetic heterogeneity might underlie the spectrum of clinical features. In this case report we describe a patient with EOCA accompanied by pes cavus, hammer toes and peripheral neuropathy. The patient's father did not have any ataxia, but had the same foot deformities as his daughter and a slight peripheral neuropathy. The possible relationship between these clinical features is discussed.
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Affiliation(s)
- H J Schelhaas
- Department of Neurology and Radiology, Medisch Spectrum Twente, Enschede, The Netherlands
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25
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Abstract
Japanese encephalitis (JE) is associated with varying degrees of coma and brainstem involvement is frequent which can be evaluated and monitored by brainstem auditory evoked potential (BAEP). The present study has been undertaken to evaluate the BAEP changes and their role in predicting the outcome. Twelve adult patients with JE were subjected to CT scan, MRI and BAEP studies after detailed neurological evaluation. The severity of coma was assessed by Glasgow coma scale and outcome was defined at the end of 3 months into good and poor recovery on the basis of Barthel Index score (BI). The mean age of the patients was 28.3 years (range 14-50), and four of them were females. Most of the patients were comatose. The mean Glasgow coma scale (GCS) score was 7 (range 4-11). There were no brainstem signs or cranial nerve palsy. Cranial CT scan revealed thalamic hypodensity in four, whitematter oedema in three and left putaminal hypodensity in one patient. Cranial MRI was carried out in eight patients which revealed bilateral thalamic lesions in all, basal ganglia and midbrain lesions in three each and pontine and cerebellar lesions in one patient each. Brainstem auditory evoked potentials were recordable bilaterally. The absolute latency of wave I, II, III, IV and V and interpeak latencies (IPL) of I-V, III-V, and I-III were normal. The V/I amplitude ratio were significantly reduced in five patients. The BAEP abnormalities correlated with brainstem lesions on CT or MRI but not with severity of coma or outcome. The reduced amplitude ratio of wave V/I may be due to raised intracranial tension or brainstem involvement in JE.
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Affiliation(s)
- J Kalita
- Department of Neurology, Sanjay Gandhi PGIMS, Lucknow, India
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Terakawa H, Abe K, Watanabe Y, Nakamura M, Fujita N, Hirabuki N, Yanagihara T. Proton magnetic resonance spectroscopy (1H MRS) in patients with sporadic cerebellar degeneration. J Neuroimaging 1999; 9:72-7. [PMID: 10208103 DOI: 10.1111/jon19999272] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
The authors studied 23 patients with cerebellar degeneration including multiple systemic atrophy (MSA) and cerebellar cortical atrophy (CCA) by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS allowed noninvasive measurement of the signal intensities derived from N-acetylaspartate (NAA), creatine + phosphocreatine (CRE), and choline-containing compounds (CHO). There was significant reduction of the NAA/CRE level in the frontal cortex, putamen, cerebellar hemisphere and cerebellar vermis of patients with MSA, and in the frontal cortex, cerebellar hemisphere and cerebellar vermis of patients with CCA as compared with those of normal controls. There was significant reduction of the NAA/CRE level also in the putamen of patients with MSA as compared with that of patients with CCA. These results indicated the presence of a degenerative process and/or functional impairment in the frontal cortex and putamen of patients with MSA and in the frontal cortex of patients with CCA, in addition to a degenerative process in the cerebellum. There was a significant correlation between the NAA/CRE level and the severity of clinical signs. 1H-MRS is valuable in providing information regarding the pathophysiology and the progress of cerebellar degenerative diseases.
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Affiliation(s)
- H Terakawa
- Department of Neurology, Osaka University Medical School, Japan
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27
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Cossée M, Dürr A, Schmitt M, Dahl N, Trouillas P, Allinson P, Kostrzewa M, Nivelon-Chevallier A, Gustavson KH, Kohlschütter A, Müller U, Mandel JL, Brice A, Koenig M, Cavalcanti F, Tammaro A, De Michele G, Filla A, Cocozza S, Labuda M, Montermini L, Poirier J, Pandolfo M. Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes. Ann Neurol 1999; 45:200-6. [PMID: 9989622 DOI: 10.1002/1531-8249(199902)45:2<200::aid-ana10>3.0.co;2-u] [Citation(s) in RCA: 270] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in the first intron of the frataxin gene. The remaining cases are compound heterozygotes for a GAA expansion and a frataxin point mutation. We report here the identification of 10 novel frataxin point mutations, and the detection of a previously described mutation (G130V) in two additional families. Most truncating mutations were in exon 1. All missense mutations were in the last three exons coding for the mature frataxin protein. The clinical features of 25 patients with identified frataxin point mutations were compared with those of 196 patients homozygous for the GAA expansion. A similar phenotype resulted from truncating mutations and from missense mutations in the carboxy-terminal half of mature frataxin, suggesting that they cause a comparable loss of function. In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function. The incidence of optic disk pallor was higher in compound heterozygotes than in expansion homozygotes, which might correlate with a very low residual level of normal frataxin produced from the expanded allele.
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Affiliation(s)
- M Cossée
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Hôpitaux Universitaires de Strasbourg, Illkirch, France
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Zouari M, Feki M, Ben Hamida C, Larnaout A, Turki I, Belal S, Mebazaa A, Ben Hamida M, Hentati F. Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency. Neuromuscul Disord 1998; 8:416-25. [PMID: 9713861 DOI: 10.1016/s0960-8966(98)00051-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreich's ataxia and 15 patients with Friedreich's ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreich's ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreich's ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreich's ataxia and central distal axonopathy in Friedreich's ataxia phenotype with selective vitamin E deficiency.
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Affiliation(s)
- M Zouari
- Institut National de Neurologie, Tunis, Tunisia
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Mielke R, Hilker R, Weber-Luxenburger G, Kessler J, Heiss WD. Early-onset cerebellar ataxia (EOCA) with retained reflexes: reduced cerebellar benzodiazepine-receptor binding, progressive metabolic and cognitive impairment. Mov Disord 1998; 13:739-45. [PMID: 9686785 DOI: 10.1002/mds.870130423] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
A family with two members who had early-onset cerebellar ataxia (EOCA) with retained tendon reflexes had, in addition to their motor deficits, a progressive impairment of cognitive and visuospatial abilities. We used positron emission tomography (PET) with 11C-flumazenil to study gamma-aminobutyric type A/benzodiazepine receptor binding (BZR) and 18F-2-fluoro-2-deoxy-D-glucose to analyze longitudinally regional cerebral glucose metabolism. Flumazenil-PET demonstrated loss of BZR binding that has not been shown in Friedreich's ataxia and olivopontocerebellar atrophy. These findings may be useful for differentiation of EOCA from other types of cerebellar ataxia. In comparison to age-matched control subjects, these patients showed a global metabolic decline and predominant hypometabolism in the thalamus and cerebellum. The progressive metabolic derangement may be explainable by a disturbed integrity of cognition-related networks resulting from secondary degeneration of cerebello-thalamo-cortical projections.
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Affiliation(s)
- R Mielke
- Max-Planck-Institut für Neurologische Forschung and Universitätsklinik für Neurologie, Köln, Germany
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30
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Klockgether T, Dichgans J. The genetic basis of hereditary ataxia. PROGRESS IN BRAIN RESEARCH 1997; 114:569-76. [PMID: 9193167 DOI: 10.1016/s0079-6123(08)63387-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- T Klockgether
- Department of Neurology, University of Tübingen, Germany
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31
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Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med 1996; 335:1169-75. [PMID: 8815938 DOI: 10.1056/nejm199610173351601] [Citation(s) in RCA: 700] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function. METHODS We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease. RESULTS One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs. The GAA repeats were unstable during transmission. CONCLUSIONS The clinical spectrum of Friedreich's ataxia is broader than previously recognized, and the direct molecular test for the GAA expansion on chromosome 9 is useful for diagnosis, determination of prognosis, and genetic counseling.
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Affiliation(s)
- A Dürr
- Fédération de Neurologie and INSERM Unité 289, Hôpital de la Saltpétriere, Paris, France
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32
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Perretti A, Santoro L, Lanzillo B, Filla A, De Michele G, Barbieri F, Martino G, Ragno M, Cocozza S, Caruso G. Autosomal dominant cerebellar ataxia type I: multimodal electrophysiological study and comparison between SCA1 and SCA2 patients. J Neurol Sci 1996; 142:45-53. [PMID: 8902719 DOI: 10.1016/0022-510x(96)00140-2] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.
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Affiliation(s)
- A Perretti
- Department of Clinical Neurophysiology, Università degli studi di Napoli "Federico II", Italy
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Scrimgeour EM, Krishna AG, Gasim A, Zawawi TH, Johnston WJ, Barron L, Brock DJ. Friedreich's ataxia, with retained lower limb tendon reflexes, in a Saudi Arabian family. Clin Neurol Neurosurg 1996; 98:8-11. [PMID: 8681484 DOI: 10.1016/0303-8467(95)00070-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Friedreich's ataxia (FA) was studied in a large inbred Arab family living near Jeddah, Saudi Arabia, in which DNA linkage studies localised the disease gene to 9q13-q21.1. Five siblings (aged 19-35 years), and their 27 year old cousin, had the typical features of FA, however in two patients, tendon reflexes were retained and were indeed brisk in the lower limbs, 13 and 19 years respectively after onset of symptoms: retention of lower limb tendon reflexes is exceptional in FA. Another 6 deceased individuals from two related families are presumed to have had FA.
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Affiliation(s)
- E M Scrimgeour
- Department of Medicine, National Guard King Khalid Hospital, Jeddah, Saudi Arabia
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34
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Abe K, Nishikawa Y, Fujimura H, Toyooka K, Kaido M, Yorifuji S, Yanagihara T. Clinical and magnetic resonance image correlation in idiopathic cerebellar ataxia. J Neurol Sci 1995; 133:53-60. [PMID: 8583232 DOI: 10.1016/0022-510x(95)00133-m] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Sixty-one patients who fulfilled the clinical criteria for idiopathic cerebellar ataxia and who had symptoms at least for 3 years were examined clinically and by magnetic resonance imaging (MRI). Based on the clinical signs, they were divided into patients with pure cerebellar signs (Group 1), patients with additional mild rigidity and/or hyperreflexia (Group 2) and patients with additional severe rigidity and hypokinesia (Group 3). Patients in Group 1 had milder disability and better prognosis than patients in Group 2 or Group 3 (ataxic score: 14.9 vs. 28.6 and 36.0; annual progression ratio: 0.26 vs. 0.65 and 0.70, respectively). We measured the area of the cerebellar vermis, ventral pons and dorsal brainstem on midsagittal T1-weighted MR images for all patients and age- and sex-matched controls. The cerebellar vermis as well as the ventral pons of patients were significantly smaller than corresponding structures in controls (p < 0.001). The ventral pons of patients in Group 2 and Group 3 was significantly smaller than that of patients in Group 1 (p < 0.0001, respectively), and the dorsal brainstem of patients in Group 2 and Group 3 was also significantly smaller than that of patients in Group 1 (p < 0.001, respectively). The ventral pons of patients in Group 3 was significantly smaller than that of patients in Group 2 (p < 0.05) as well. There was a significant correlation between the area of the ventral pons and the annual progression ratio (p < 0.001). With MRI, slight but definite hyperintensities were demonstrated in the pontine base and the medulla of 22 patients on proton density images. In the longitudinal study, patients in Group 2 and Group 3 had atrophy of the ventral pons already at an early stage. The ventral pons of patients in Group 3 was smaller at the initial MR examination than that of patients in Group 2. These observations suggest that patients with smaller ventral pons may have rapid progression and poor prognosis. Thus, even a relatively simple quantitation of the area of the ventral pons may be useful to predict the prognosis of patients, in addition to neurologic assessment at intervals.
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Affiliation(s)
- K Abe
- Department of Neurology, Osaka University Medical School, Japan
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35
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Affiliation(s)
- E Dirik
- Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, Izmer, Türkiye
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Lanzillo B, Perretti A, Santoro L, Pelosi L, Filla A, De Michele G, Caruso G. Evoked potentials in inherited ataxias: a multimodal electrophysiological study. ITALIAN JOURNAL OF NEUROLOGICAL SCIENCES 1994; 15:25-37. [PMID: 8206744 DOI: 10.1007/bf02343494] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
A multimodal electrophysiological study, including median nerve somatosensory evoked potentials (SSEPs), motor cortical stimulation (CS) and brainstem evoked potentials (BAEPs), was performed on 34 patients with hereditary ataxias (HAs): 15 with Friedreich's disease (FD), 10 with early onset cerebellar ataxia (EOCA), and 9 with autosomal dominant cerebellar ataxia (ADCA). A higher incidence of abnormal central motor conduction was observed in FD than in EOCA patients, but was never observed in ADCA. A relationship between central motor conduction abnormalities and disease duration and clinical impairment was found only in FD patients. All FD patients showed severe impairment of the SSEPs that was not related to disease duration. In EOCA patients, less frequent and more variable SSEP abnormalities were observed. The lowest incidence of central SSEP abnormalities was observed in ADCA. The BAEP findings in all 3 groups of patients (but particularly those with EOCA) suggest prevalent brainstem damage.
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Affiliation(s)
- B Lanzillo
- Fondazione Clinica del Lavoro, Centro Medico di Campoli-IRCCS, Campoli, Benevento
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Ormerod IE, Harding AE, Miller DH, Johnson G, MacManus D, du Boulay EP, Kendall BE, Moseley IF, McDonald WI. Magnetic resonance imaging in degenerative ataxic disorders. J Neurol Neurosurg Psychiatry 1994; 57:51-7. [PMID: 8301305 PMCID: PMC485039 DOI: 10.1136/jnnp.57.1.51] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
MRI of the brain was performed in 53 patients with a variety of degenerative ataxias and related disorders and 96 control subjects. Atrophy of intracranial structures was not seen in patients with the pure type of hereditary spastic paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's ataxia there was atrophy of the vermis and medulla. The MRI features of early onset cerebellar ataxia with retained reflexes were variable, and suggest heterogeneity. In autosomal dominant cerebellar ataxias, most patients had cerebellar and brainstem atrophy, probably reflecting the pathological process of olivopontocerebellar atrophy; there was no clearly defined group with both clinical and imaging features of isolated cerebellar involvement. The MRI abnormalities in idiopathic late onset cerebellar ataxia were predominantly those of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and imaging features of brainstem abnormalities were discordant in several patients. Pure cerebellar atrophy was associated with slower progression of disability. Cerebral atrophy was common in the late onset ataxias. Cerebral white matter lesions, although usually few in number, were observed in significantly more patients than controls, particularly those aged over 50 years.
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Chiò A, Orsi L, Mortara P, Schiffer D. Reduced life expectancy in 40 cases of early onset cerebellar ataxia with retained tendon reflexes: a population-based study. Acta Neurol Scand 1993; 88:358-62. [PMID: 8296536 DOI: 10.1111/j.1600-0404.1993.tb05358.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
A survival analysis of 40 cases of early onset cerebellar ataxia (EOCA) with retained tendon reflexes was performed. They represent all cases of EOCA diagnosed between 1945 and 1990 among residents of a defined area of Northwestern Italy, followed up to December 31, 1990. The survival rates were respectively 92%, 87% and 77% at 10, 20 and 30-years, worse than expected in a disease which is usually considered benign. The relative death rate was 4 times higher than expected for the general population. Prognosis was significantly worse for males than for females, whereas the age of onset and the calendar year of onset did not affect survival.
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Affiliation(s)
- A Chiò
- Clinica Neurologica II, University of Turin, Italy
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39
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Chiò A, Orsi L, Mortara P, Schiffer D. Early onset cerebellar ataxia with retained tendon reflexes: prevalence and gene frequency in an Italian population. Clin Genet 1993; 43:207-11. [PMID: 8330454 DOI: 10.1111/j.1399-0004.1993.tb04450.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
A genetic epidemiologic analysis of early onset cerebellar ataxias (EOCA) with retained tendon reflexes was performed in a defined area of Northwestern Italy. Forty cases diagnosed from 1940 to 1990 were ascertained. The ascertainment probability was 85.7%. The segregation analysis (Weinberg's proband method and 'singles' method under incomplete ascertainment) is compatible with autosomal recessive inheritance. The point prevalence ratio was 1.0/100,000 population. The birth incidence rate was 1/48,000 live births. Gene frequency was estimated to be 1/218. The ratio of first-cousin marriages among parents of EOCA (4.5%) was lower than expected using Dahlberg's formula (8.9%).
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Affiliation(s)
- A Chiò
- II Neurological Department, University of Torino, Italy
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40
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Santoro L, Perretti A, Filla A, De Michele G, Lanzillo B, Barbieri F, Crisci C, Rippa PG, Caruso G. Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia. J Neurol Sci 1992; 113:43-9. [PMID: 1469454 DOI: 10.1016/0022-510x(92)90263-k] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.
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Affiliation(s)
- L Santoro
- Department of Clinical Neurophysiology, Second School of Medicine, University of Naples, Italy
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