DOCSLIB.ORG

An Approach to Late Onset Cerebellar Ataxia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Sixth Annual Intensive Update in Neurology 9/15-16/2016 THE WOBBLY PATIENT: ADULT ONSET ATAXIA Rosalind Chuang, M.D. Movement Disorders Swedish Neuroscience Institute September 15, 2016 Disclosure: none 1 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Objectives • Review algorithm for work up of patients with ataxia • Review common forms of genetic ataxia • Understand which genetic tests to obtain and rationale for genetic testing 2 Sixth Annual Intensive Update in Neurology 9/15-16/2016 What is ataxia? • Dysfunction of the cerebellum or cerebellar pathways • Core symptoms: • Balance & gait • Hand incoordination • Dysarthria • Oculo-motor abnormality 3 Sixth Annual Intensive Update in Neurology 9/15-16/2016 APPROACH TO THE ATAXIC PATIENT A detailed history and exam are always free! 4 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Question to self: “Is it ataxia?” Other causes of imbalance Visual: blindness Vestibular: BPPV, Ménière syndrome Cortical: dementia, medications Musculoskeletal: muscle weakness, hip/knee joint problems Proprioception/Sensory: sensory ataxia 5 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Drugs & Dementia are common cause of falls in elderly 6 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Cerebellar Exam: Scale for the assessment and rating of ataxia (SARA) 1. Gait 2. Stance 3. Sitting 4. Speech 5. Finger chase 6. Nose-finger 7. Fast alternating hand movements 8. Heel shin slide 7 Sixth Annual Intensive Update in Neurology 9/15-16/2016 8 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Questions to ask 1. Age of onset 2. Rate of disease progression 3. Family history 4. Systemic clues 9 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Approach to the ataxic patient • Family history • Not limited to ataxia • Consider: • Dementia • Other movement disorders: Tremors, parkinsonism, chorea, dystonia • Epilepsy • Mental retardation, learning disability, autism • Psychiatric disease, history of suicide or alcoholism • History of institutionalization • “Cerebral palsy” • Vision loss • Premature ovarian failure • Autonomic dysfunction • Other medical diseases: DM II , deafness 10 Sixth Annual Intensive Update in Neurology 9/15-16/2016 The detailed family pedigree • Don’t accept “old age” as cause of death • Did parent remain ambulatory throughout? • Aunts, uncles, first cousins • Why was someone “institutionalized?” • “Really alcoholics?” • Children: any difficulty learning to walk? Learning disability? • Ethnicity • Ashkenazi Jewish ancestry? • French Canadians? • Possibility of consanguinity? 11 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Approach to the ataxic patient • Cerebellar ataxia confirmed • Always do MRI brain to exclude structural causes • Additional clues for another cause of ataxia • Labs: (Fogel et al 2007) • Basic screen: Comprehensive metabolic panel, Vit B1, B12, E, CBC with smear, thyroid studies, ESR, CRP, ANA, immunofixation, RPR • Secondary screening labs: anti-GAD, cholesterol • If systemic clues are present: • paraneoplastic panel (with CT imaging), celiac, copper/ceruloplasmin • Imaging: MRI brain/C spine • Consults: neuro-ophtho, neuro-muscular 12 Sixth Annual Intensive Update in Neurology 9/15-16/2016 CASE PRESENTATION 65 year old male with progressive ataxia… 13 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case Presentation • 65 year old gentleman with ataxia • PMH: DM II, HTN • His wife noticed at breakfast that his speech was slightly slurred • Difficulty holding utensil at breakfast • Stumbled while walking • Stable for past 3 months • Walking/stumbling has improved • Occasionally drops cups • Slurred speech resolved 14 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Acute onset, no progression 3. Family history • None 4. Systemic clues • Stroke risk factors 15 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Acute onset cerebellar ataxia • Vascular (stroke) • Wernicke’s encephalopathy • Infections • More common in children • Trauma • Autoimmune: MS, ADEM, Miller-Fisher Syndrome) • Vestibular • Functional (psychogenic) Cerebellarand Afferent Ataxias. Pandolfo, Massimo; Manto, Mario; MD, PhD. CONTINUUM:, October 2013. 16 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case Presentation • 65 year old male with progressive ataxia • Onset 4 months prior • Saw 2 prior physicians 2 months after onset of “dizziness” • Extensive work up… • No family history, no risk factors (no tobacco, illicit drugs or alcohol history) • On initial exam: • SARA score of ~10 • Dysarthria • Abnormal saccades • Review of past work up: • CT chest with nodule: scar tissue • FDG-PET scan: “possible cerebellitis” • CSF: +EBV IgG Referred for possible infectious cerebellitis 17 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Sub-acute, progressive with SARA of 10 over 4 month period 3. Family history • None 4. Systemic clues • None: no h/o fevers, chills, cough, malaise 18 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case presentation #2: conclusion • Referred to pulmonary consult for lung biopsy • Whole body PET scan positive • Biopsy: neuro-endocrine tumor Paraneoplastic cerebellar ataxia • Ataxia stable with chemotherapy/XRT • Had 3 rounds of IVIg with slight improvement with first round, no additional improvement with subsequent IVIg 19 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Paraneoplastic ataxia • Most common malignancies: • SCLC • Breast, ovarian • Hodgkin’s • Usually sub-acute • Ataxia can precede identification of underlying tumor by 4 years • Should everyone with ataxia have routine screening for paraneoplastic syndrome? • If rapid progression over months, yes. Also include CT Chest/abdomen/pelvis with contrast and whole body PET. • If negative initially, some still recommend Q6 month paraneoplastic panel 20 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case presentation: Patient #3 • 65 year old computer engineer with no PMH until September 2015 • Awoke in middle of night with chest pains and sensory symptoms described as “electrical impulses” • New onset headaches causing insomnia from 10/2015-12/2015 • Spontaneously resolved December 2015 • Hyperacusis • Cognitive decline-not noticeable to colleagues or family but it “hurt” to think • His wife started to notice short term memory changes in February 2016 • Handwriting changes: messy, clumsy 21 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case # 3 Physical exam February 2016 • Halting speech, repeating same stories, frequent word finding difficulties • CN: impaired smooth pursuit. But vertical gaze intact. No hypermetric saccades • Reflexes: areflexic • Sensation: Normal • Movement disorders: Excessive startle to facial stimuli No myoclonus UPDRS: slight neck rigidity, slight bradykinesia of all limbs, no tremors SARA 11.5 22 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case # 3 • Labs: • RA, CRP, ESR, Hashimoto's Ab negative • Paraneoplastic Panel (serum) #1: negative • RPR non reactive • CSF November 2015: • Glucose 53, Protein 25, WBC 2, RBC 6, CSF ACE 1.7 (normal), IgG Index 0.5 (normal), Lyme negative, Oligoclonal Bands negative, VDRL non-reactive • EMG/NCS: negative • DaT scan: February 2016 • “Scintigraphic findings indicate nigrostriatal degeneration indicating Parkinsonian syndrome” Referred to Movement Disorders for atypical parkinsonism 23 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Acute/Sub-acute, rapidly progressive with SARA of 11.5 3. Family history • None 4. Systemic clues • Sensory symptoms • Significant Cognitive changes 24 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Case # 3: Conclusion Additional labs • Whole body PET scan: • Progressive cognitive negative decline with agitation • CSF March 17, 2016 • Family consented for Brain • Paraneoplastic (Mayo Clinic) donation to Prion Center negative • Voltage gated K channel • Passed away May 11, requested, not done 2016 • CSF Tau total 6169 pg/ml • Autopsy confirmed prion • 14-3-3 to Prion Disease Center (Available April 2016) protein in brain tissue • Positive Sporadic CJD • RT-quic positive 25 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Sporadic CJD • Peak age ~55-75 years old • Prodromal symptoms • Survival <1 year • 300 cases in USA/year • First symptom: • Dementia (37 %) • Cerebellar (34 %) • Visual (15 %) • Psychiatric disturbances (14 %) • Extrapyramidal 4% (Krasniaski 2014) 26 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Sub-acute ataxia • Paraneoplastic • Potentially treatable! • Infection: • Prion disease • Infection precautions with brain biopsy/lumbar puncture • Send 14-3-3 to Case Western (Prion Surveillance Center) for RT-quic • Auto-immune • Anti-GAD • SREAT • Gluten Ataxia 27 Sixth Annual Intensive Update in Neurology 9/15-16/2016 Gluten Ataxia: brief word… • Controversial • Celiac related antibodies • Anti-gliadin (not recommended, high false positive) • Anti-TTG (tissue transglutaminase) • Anti-TG6 (transglutaminase 6) • Antibodies can also be present in ataxias with confirmed genetic cause • Gold standard: gut biopsy • Treatment: gluten free diet • European Consensus Statement on ataxia does NOT recommend routine testing for gluten antibodies • It is potentially treatable, so if sub-acute onset, I send labs after 3-4 weeks of high
Recommended publications
  • Rehabilitating Individuals with Spinocerebellar Ataxia: Experiences from Impairment-Based Rehabilitation Through Multidisciplinary Care Approach

    Rehabilitating Individuals with Spinocerebellar Ataxia: Experiences from Impairment-Based Rehabilitation Through Multidisciplinary Care Approach

    Neurology Asia 2020; 25(1) : 75 – 80 Rehabilitating individuals with spinocerebellar ataxia: Experiences from impairment-based rehabilitation through multidisciplinary care approach 1,2Fatimah Ahmedy MBBCh MRehabMed, 1Yuen Woei Neoh MBBS, MRehabMed, 1Lydia Abdul Latiff MBBS MRehabMed 1Department of Rehabilitation Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur; 2Department of Surgery, Faculty of Medicine & Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia Abstract Spinocerebellar ataxia (SCA) is a rare neurodegenerative disease with progressive course and poor expected outcomes. Therefore, rehabilitation remains the principal form of management especially in advanced disease. Impairment-based rehabilitation through multidisciplinary care approach has proven benefits for functional improvement in individuals with advancing SCA. This concept is based on comprehensive assessments of individualised impairments and functional limitations while exploring contributing environmental and personal factors affecting the person as a whole. From this assessment, individualised rehabilitation goals can be formulated through a multidisciplinary care approach. Neurologists, rehabilitation physicians, physiotherapists, occupational therapists and speech and language pathologists are key individuals involved in the multidisciplinary care for individuals with SCA rehabilitation. Two cases of individuals at different stages of SCA are presented to highlight the rehabilitation approach in providing focused interventions
  • 2020 Question Book

    2020 Question Book

    2020 QUESTION BOOK 13TH EDITION WHO WE ARE Welcome to the thirteenth edition of the Ninja’s Guide to PRITE! Loma Linda University Medical Center is located in sunny Southern California. about 60 miles east of Los Angeles. A part of the Adventist Health System, we provide patient care in one of the largest non-profit health systems in the nation. Loma Linda's mission is to excel in medical education, global healthcare, and community outreach, all under a central tenant: "To Make Man Whole." At the Loma Linda Department of Psychiatry, our residents are trained in many diverse patient care settings. As an official World Health Organization Collaboration Center, our department funds resident electives in Global Mental Health at locations around the world. Additionally, our residents can participate in national and international disaster relief on the LLU Behavioral Health Trauma Team. We were proud to welcome our first group of Child and Adolescent Psychiatry fellows in the Summer of 2019 and work collaboratively with 3 other residency programs within the region. Our residency didactic education is constantly evolving based upon resident feedback, and our residents have the opportunity to aid in course development. More than anything, our residency fosters an environment where residents and faculty treat each other like family. Our faculty are dedicated to resident education and professional development. We believe in "taking 'No' off the table", encouraging innovative change, and passionately supporting our residents to achieve anything they set their minds to. For over a decade our residents have volunteered their time to create The Ninja's Guide to PRITE at our Annual Ninja PRITE Workshop.
  • Spinocerebellar Ataxia Genetic Testing

    Spinocerebellar Ataxia Genetic Testing

    Lab Management Guidelines V1.0.2020 Spinocerebellar Ataxia Genetic Testing MOL.TS.311.A v1.0.2020 Introduction Spinocerebellar ataxia (SCA) genetic testing is addressed by this guideline. Procedures addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedures addressed by this Procedure codes guideline ATXN1 gene analysis, evaluation to detect 81178 abnormal (eg,expanded) allele ATXN2 gene analysis, evaluation to detect 81179 abnormal (eg,expanded) allele ATXN3 gene analysis, evaluation to detect 81180 abnormal (eg,expanded) allele ATXN7 gene analysis, evaluation to detect 81181 abnormal (eg,expanded) allele ATXN8 gene analysis, evaluation to detect 81182 abnormal (eg, expanded) alleles ATXN10 gene analysis, evaluation to 81183 detect abnormal (eg, expanded) alleles CACNA1A gene analysis; evaluation to 81184 detect abnormal (eg, expanded) alleles CACNA1A gene analysis; full gene 81185 sequence CACNA1A gene analysis; known familial 81186 variant PPP2R2B gene analysis, evaluation to 81343 detect abnormal (eg, expanded) alleles TBP gene analysis, evaluation to detect 81344 abnormal (eg, expanded) alleles Unlisted molecular pathology procedure 81479 © 2020 eviCore healthcare. All Rights Reserved. 1 of 15 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2020 What is spinocerebellar ataxia Definition Spinocerebrallar ataxias (SCA) are a group of autosomal dominant ataxias that have a range of phenotypes. There are various subtypes of SCA, which are denoted by numbers (e.g. SCA1, SCA3, etc.) Incidence and Prevalence The prevalence of autosomal dominant cerebellar ataxias, as a whole, is 1-5:100,000.1 SCA3 is the most common autosomal dominant form of ataxia.
  • Friedreich Ataxia Mouse Models with Progressive Cerebellar and Sensory Ataxia Reveal Autophagic Neurodegeneration in Dorsal Root Ganglia

    Friedreich Ataxia Mouse Models with Progressive Cerebellar and Sensory Ataxia Reveal Autophagic Neurodegeneration in Dorsal Root Ganglia

    The Journal of Neuroscience, February 25, 2004 • 24(8):1987–1995 • 1987 Neurobiology of Disease Friedreich Ataxia Mouse Models with Progressive Cerebellar and Sensory Ataxia Reveal Autophagic Neurodegeneration in Dorsal Root Ganglia Delphine Simon,1 Herve´ Seznec,1 Anne Gansmuller,1 Nade`ge Carelle,1 Philipp Weber,1 Daniel Metzger,1 Pierre Rustin,2 Michel Koenig,1 and He´le`ne Puccio1 1Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Sante´ et de la Recherche Me´dicale (INSERM)/Universite´ Louis Pasteur, 67404 Illkirch cedex, CU de Strasbourg, France, and 2Unite´ de Recherches sur les Handicaps Ge´ne´tiques de l’Enfant, INSERM U393, Hoˆpital Necker-Enfants Malades, 75015 Paris, France Friedreich ataxia (FRDA), the most common recessive ataxia, is characterized by degeneration of the large sensory neurons of the spinal cord and cardiomyopathy. It is caused by severely reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster (ISC) biosynthesis. Through a spatiotemporally controlled conditional gene-targeting approach, we have generated two mouse models for FRDA that specifically develop progressive mixed cerebellar and sensory ataxia, the most prominent neurological features of FRDA. Histological studies showed both spinal cord and dorsal root ganglia (DRG) anomalies with absence of motor neuropathy, a hallmark of the human disease. In addition, one line revealed a cerebellar granule cell loss, whereas both lines had Purkinje cell arborization defects. These lines represent the first FRDA models with a slowly progressive neurological degeneration. We identified an autophagic process as the causative pathological mechanism in the DRG, leading to removal of mitochondrial debris and apparition of lipofuscin deposits.
  • Treatment of Autonomic Dysreflexia for Adults & Adolescents with Spinal

    Treatment of Autonomic Dysreflexia for Adults & Adolescents with Spinal

    Treatment of Autonomic Dysreflexia for Adults & Adolescents with Spinal Cord Injuries Authors: Dr James Middleton, Director, State Spinal Cord Injury Service, NSW Agency for Clinical Innovation. Dr Kumaran Ramakrishnan, Honorary Fellow, Rehabilitation Studies Unit, Sydney Medical School Northern, The University of Sydney, and Consultant Rehabilitation Physician & Senior Lecturer, Department of Rehabilitation Medicine, University Malaya. Dr Ian Cameron, Head of the Rehabilitation Studies Unit, Sydney Medical School Northern, The University of Sydney. Reviewed and updated in 2013 by the authors. AGENCY FOR CLINICAL INNOVATION Level 4, Sage Building 67 Albert Avenue Chatswood NSW 2067 PO Box 699 Chatswood NSW 2057 T +61 2 9464 4666 | F +61 2 9464 4728 E [email protected] | www.aci.health.nsw.gov.au Produced by the NSW State Spinal Cord Injury Service. SHPN: (ACI) 140038 ISBN: 978-1-74187-972-8 Further copies of this publication can be obtained from the Agency for Clinical Innovation website at: www.aci.health.nsw.gov.au Disclaimer: Content within this publication was accurate at the time of publication. This work is copyright. It may be reproduced in whole or part for study or training purposes subject to the inclusion of an acknowledgment of the source. It may not be reproduced for commercial usage or sale. Reproduction for purposes other than those indicated above, requires written permission from the Agency for Clinical Innovation. © Agency for Clinical Innovation 2014 Published: February 2014 HS13-136 ACKNOWLEDGEMENTS This document was originally published as a fact sheet for the Rural Spinal Cord Injury Project (RSCIP), a pilot healthcare program for people with a spinal cord injury (SCI) conducted within New South Wales involving the collaboration of Prince Henry & Prince of Wales Hospitals, Royal North Shore Hospital, Royal Rehabilitation Centre Sydney, Spinal Cord Injuries Australia and the Paraplegic & Quadriplegic Association of NSW.
  • Scienti®C Review Spastic Movement Disorder

    Scienti®C Review Spastic Movement Disorder

    Spinal Cord (2000) 38, 389 ± 393 ã 2000 International Medical Society of Paraplegia All rights reserved 1362 ± 4393/00 $15.00 www.nature.com/sc Scienti®c Review Spastic movement disorder V Dietz*,1 1Paracare, Paraplegic Centre of the University Hospital Balgrist, ZuÈrich, Switzerland This review deals with the neuronal mechanisms underlying spastic movement disorder, assessed by electrophysiological means with the aim of ®rst, a better understanding of the underlying pathophysiology and second, the selection of an adequate treatment. For the patient usually one of the ®rst symptoms of a lesion within the central motor system represents the movement disorder, which is most characteristic during locomotion in patients with spasticity. The clinical examination reveals exaggerated tendon tap re¯exes and increased muscle tone typical of the spastic movement disorder. However, today we know that there exists only a weak relationship between the physical signs obtained during the clinical examination in a passive motor condition and the impaired neuronal mechanisms being in operation during an active movement. By the recording and analysis of electrophysiological and biomechanical parameters during a functional movement such as locomotion, the signi®cance of, for example, impaired re¯ex behaviour or pathophysiology of muscle tone and its contribution to the movement disorder can reliably be assessed. Consequently, an adequate treatment should not be restricted to the cosmetic therapy and correction of an isolated clinical parameter but should be based on the pathophysiology and signi®cance of the mechanisms underlying the disorder of functional movement which impairs the patient. Spinal Cord (2000) 38, 389 ± 393 Keywords: spinal cord injury; spasticity; electrophysiological recordings; treatment Introduction Movement disorders are prominent features of impaired strength of electromyographic (EMG) activation of function of the motor systems and are frequently best antagonistic leg muscles as well as intrinsic and passive re¯ected during gait.
  • Spinocerebellar Ataxia 17 (SCA17) and Huntington’S Disease-Like 4 (HDL4)

    Spinocerebellar Ataxia 17 (SCA17) and Huntington’S Disease-Like 4 (HDL4)

    Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4). Giovanni Stevanin, Alexis Brice To cite this version: Giovanni Stevanin, Alexis Brice. Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4).. The Cerebellum, Springer, 2008, 7 (2), pp.170-8. 10.1007/s12311-008-0016-1. inserm- 00293796 HAL Id: inserm-00293796 https://www.hal.inserm.fr/inserm-00293796 Submitted on 26 Mar 2009 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Stevanin & Brice, SCA7 and HDL4 1 SPINOCEREBELLAR ATAXIA 17 (SCA17) AND HUNTINGTON’S DISEASE-LIKE 4 (HDL4) GIOVANNI STEVANIN1,2,3 & ALEXIS BRICE1,2,3 1INSERM, U679, 75013 Paris, France; 2Université Pierre et Marie Curie – Paris 6, UMR S679, Institut Fédératif de Recherche en Neurosciences, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France; 3APHP, Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique et Cytogénétique, 75013 Paris, France Correspondence: Giovanni Stevanin, PhD, INSERM U679, Groupe Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail: [email protected] Running title: SCA7 and HDL4 Stevanin & Brice, SCA7 and HDL4 2 Abstract Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like-4 is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene leading to an abnormal expansion of a polyglutamine stretch in the corresponding protein.
  • Cerebellar Ataxia

    Cerebellar Ataxia

    CEREBELLAR ATAXIA Dr. Waqar Saeed Ziauddin Medical University, Karachi, Pakistan What is Ataxia? ■ Derived from a Greek word, ‘A’ : not, ‘Taxis’ : orderly Ataxia is defined as an inability to maintain normal posture and smoothness of movement. Types of Ataxia ■ Cerebellar Ataxia ■ Sensory Ataxia ■ Vestibular Ataxia Cerebellar Ataxia Cerebrocerebellum Spinocerebellum Vestibulocerebellum Vermis Planning and Equilibrium balance Posture, limb and initiating and posture eye movements movements Limb position, touch and pressure sensation Limb ataxia, Eye movement dysdiadochokinesia, disorders, Truncal and gait Dysmetria dysarthria nystagmus, VOR, ataxia hypotonia postural and gait. Gait ataxia Types of Cerebellar Ataxia • Vascular Acute Ataxia • Medications and toxins • Infectious etiologies • Atypical Infectious agents • Autoimmune disorders • Primary or metastatic tumors Subacute Ataxia • Paraneoplastic cerebellar degeneration • Alcohol abuse and Vitamin deficiencies • Systemic disorders • Autosomal Dominant Chronic • Autosomal recessive Progressive • X linked ataxias • Mitochondrial • Sporadic neurodegenerative diseases Vascular Ataxia ▪ Benedikt Syndrome It is a rare form of posterior circulation stroke of the brain. A lesion within the tegmentum of the midbrain can produce Benedikt Syndrome. Disease is characterized by ipsilateral third nerve palsy with contralateral hemitremor. Superior cerebellar peduncle and/or red nucleus damage in Benedikt Syndrome can further lead in to contralateral cerebellar hemiataxia. ▪ Wallenberg Syndrome In
  • Spinocerebellar Ataxia Type 29 Due to Mutations in ITPR1: a Case Series and Review of This Emerging Congenital Ataxia Jessica L

    Spinocerebellar Ataxia Type 29 Due to Mutations in ITPR1: a Case Series and Review of This Emerging Congenital Ataxia Jessica L

    Zambonin et al. Orphanet Journal of Rare Diseases (2017) 12:121 DOI 10.1186/s13023-017-0672-7 RESEARCH Open Access Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this emerging congenital ataxia Jessica L. Zambonin1*, Allison Bellomo2, Hilla Ben-Pazi3, David B. Everman2, Lee M. Frazer2, Michael T. Geraghty4, Amy D. Harper5, Julie R. Jones2, Benjamin Kamien6, Kristin Kernohan1,4, Mary Kay Koenig7, Matthew Lines4, Elizabeth Emma Palmer8,9, Randal Richardson10, Reeval Segel11, Mark Tarnopolsky12, Jason R. Vanstone4, Melissa Gibbons13, Abigail Collins14, Brent L. Fogel15, Care4Rare Canada Consortium, Tracy Dudding-Byth16 and Kym M. Boycott1,4 Abstract Background: Spinocerebellar ataxia type 29 (SCA29) is an autosomal dominant, non-progressive cerebellar ataxia characterized by infantile-onset hypotonia, gross motor delay and cognitive impairment. Affected individuals exhibit cerebellar dysfunction and often have cerebellar atrophy on neuroimaging. Recently, missense mutations in ITPR1 were determined to be responsible. Results: Clinical information on 21 individuals from 15 unrelated families with ITPR1 mutations was retrospectively collected using standardized questionnaires, including 11 previously unreported singletons and 2 new patients from a previously reported family. We describe the genetic, clinical and neuroimaging features of these patients to further characterize the clinical features of this rare condition and assess for any genotype-phenotype correlation for this disorder. Our cohort consisted of 9 males and 12 females, with ages ranging from 28 months to 49 years. Disease course was non-progressive with infantile-onset hypotonia and delays in motor and speech development. Gait ataxia was present in all individuals and 10 (48%) were not ambulating independently between the ages of 3–12 years of age.
  • Diagnostic Clues in Multiple System Atrophy

    Diagnostic Clues in Multiple System Atrophy

    DO I:10.4274/Tnd.82905 Case Report / Olgu Sunumu Diagnostic Clues in Multiple System Atrophy: A Case Report and Literature Review Multisistem Atrofi Tanısında İpuçları: Bir Olgu Sunumu ve Literatürün Gözden Geçirilmesi Mehmet Yücel, Oğuzhan Öz, Hakan Akgün, Semai Bek, Tayfun Kaşıkçı, İlter Uysal, Yaşar Kütükçü, Zeki Odabaşı Gülhane Military Medical Academy, Ankara, Turkey Sum mary Multiple system atrophy (MSA) is an adult-onset, sporadic, progressive neurodegenerative disease. Based on the consensus criteria, patients with MSA are clinically classified into cerebellar (MSA-C) and parkinsonian (MSA-P) subtypes. In addition to major diagnostic criteria including poor response to levodopa, and presence of pyramidal or cerebellar signs (ataxia) or autonomic failure, certain clinical features or ‘‘red flags’’ may raise the clinical suspicion for MSA. In our case report we present a 67-year-old female patient admitted to our hospital due to inability to walk, with poor response to levodopa therapy, whose neurological examination revealed severe Parkinsonism, ataxia and who fulfilled all criteria for MSA, as rarely seen in clinical practice.(Turkish Journal of Neurology 2013; 19:28-30) Key Words: Multiple system atrophy, autonomic failure, diagnostic criteria Özet Multisistem atrofi (MSA) erişkin dönemde başlayan, ilerleyici, nedeni bilinmeyen sporadik nörodejeneratif bir hastalıktır. MSA kabul görmüş tanı kriterlerine göre klinik olarak serebellar (MSA-C) ve parkinsoniyen (MSA-P) alt tiplerine ayrılmaktadır. Düşük levadopa yanıtı, piramidal, serebellar bulguların (ataksi) ya da otonomik bozukluk olması gibi majör tanı kriterlerininin yanında “red flags” olarak isimlendirilen belirgin klinik bulgular ya da uyarı işaretlerinin olması MSA tanısı için klinik şüpheyi oluşturmalıdır. Olgu sunumunda 67 yaşında yürüyememe şikayeti ile polikliniğimize müracaat eden ve levadopa tedavisine düşük yanıt gösteren ciddi parkinsonizm bulguları ile ataksi bulunan kadın hasta MSA tanı kriterlerini tam olarak karşıladığı ve klinik pratikte nadir görüldüğü için sunduk.
  • Molecular Diagnostics of Charcot-Marie-Tooth Disease and Related Peripheral Neuropathies

    Molecular Diagnostics of Charcot-Marie-Tooth Disease and Related Peripheral Neuropathies

    17_Lupski 3/30/06 1:47 PM Page 243 NeuroMolecular Medicine Copyright © 2006 Humana Press Inc. All rights of any nature whatsoever reserved. ISSN0895-8696/06/08:243–254/$30.00 doi: 10.1385/NMM:8:1:243 REVIEW ARTICLE Molecular Diagnostics of Charcot-Marie-Tooth Disease and Related Peripheral Neuropathies Kinga Szigeti,1 Eva Nelis,2,3 and James R. Lupski*,1,4 1Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; 2Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium; 3Laboratory of Neurogenetics, Institute Born-Borge, University of Antwerp, Antwerpen, Belgium; and 4Pediatrics, Baylor College of Medicine, and Texas Children Hospital, Houston, TX 77030 Received January 10, 2006; Revised January 13, 2006; Accepted January 13, 2006 Abstract DNAdiagnostics plays an important role in the characterization and management of patients manifesting inherited peripheral neuropathies. We describe the clinical integration of molecular diagnostics with medical history, physical examination, and electrophysiological studies. Mole- cular testing can help establish a secure diagnosis, enable genetic counseling regarding recurrence risk, potentially provide prognostic information, and in the near future may be important for the choice of therapies. doi: 10.1385/NMM:8:1:243 Index Entries:Molecular diagnostics; Charcot-Marie-Tooth disease; CMT; hereditary neuropathy with liability to pressure palsies; HNPP; Dejerine-Sottas neuropathy; DSN; congenital hypomyelinating neuropathy; CHN; CMT1A duplication; HNPP deletion. Introduction genetic testing, one needs to be familiar with the diagnostic tests available, choose the appropriate Molecular genetic diagnosis has become an inte- patients for testing, and utilize the diagnostic tools gral part of the evaluation of patients with hered- in a logical fashion to optimize the use of resources.
  • Neuromuscular Disorders Neurology in Practice: Series Editors: Robert A

    Neuromuscular Disorders Neurology in Practice: Series Editors: Robert A

    Neuromuscular Disorders neurology in practice: series editors: robert a. gross, department of neurology, university of rochester medical center, rochester, ny, usa jonathan w. mink, department of neurology, university of rochester medical center,rochester, ny, usa Neuromuscular Disorders edited by Rabi N. Tawil, MD Professor of Neurology University of Rochester Medical Center Rochester, NY, USA Shannon Venance, MD, PhD, FRCPCP Associate Professor of Neurology The University of Western Ontario London, Ontario, Canada A John Wiley & Sons, Ltd., Publication This edition fi rst published 2011, ® 2011 by Blackwell Publishing Ltd Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientifi c, Technical and Medical business to form Wiley-Blackwell. Registered offi ce: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial offi ces: 9600 Garsington Road, Oxford, OX4 2DQ, UK The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offi ces, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell The right of the author to be identifi ed as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.