Characteristics of Episodic Ataxia Syndrome

Episodic Ataxia Syndrome: Genotype-phenotype Correlation and Longitudinal Study

Episodic ataxia (EA) is a rare genetic disease characterized by episodes of imbalance, incoordination, and slurring of speech. The underlying cause of EA is only partly understood, and currently there are no established treatments. There is also little information about the link between EA's clinical features and its genetic basis. The purpose of this study is to better characterize EA and disease progression. In turn, this may direct the development of future treatments.

Study Overview

• Status: Completed
• Conditions: Cerebellar Diseases; Episodic Ataxia Syndrome

Detailed Description

Attacks of ataxia, or the loss of ability to coordinate muscular movement, are often triggered by stress or exertion. EA is likely caused by an inherited genetic mutation; many individuals with EA have abnormalities in the KCNA1 or CACNA1A genes. To date, two known subtypes of EA have been identified, and other types likely exist. Specific characteristics of each EA subtype, however, have not been adequately described. The purpose of this study is to better define the clinical features and genetic basis of the various subtypes of EA and to evaluate disease progression. The study will also establish relevant study endpoints for use in future therapeutic trials.

This multi-center observational study will involve both a cross-sectional data analysis and a prospective longitudinal analysis. Participants will initially attend an outpatient study visit that will last 7 hours. This initial evaluation will include a medical history, a physical examination, neurological testing, and an ataxia assessment. Blood will be collected for genetic testing. Additionally, the following procedures may be conducted: ocular motor test, electromyography/nerve conduction study, electroencephalogram, MRI, and digital videotaping. Follow-up evaluations will occur on a yearly basis for at least 2 years; each will last 4 hours.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
• United Kingdom
  • London
    • Queen Square, London, United Kingdom, WC1N 3BG
      • Institute of Neurology, Center for Neuromuscular Disease
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Reed Neurological Research Center, UCLA
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with episodic ataxia

Description

Inclusion Criteria:

• A clinically confirmed diagnosis of episodic ataxia as defined by one of the following three features:

  1. Clear-cut episodes of recurrent, transient ataxia
  2. Mutation confirmed in KCNA1 or CACNA1A
  3. Ataxic features with a first degree relative with episodic ataxia

Exclusion Criteria:

• Any other disorder known to cause episodic ataxia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Rare Diseases Clinical Research Network; Office of Rare Diseases (ORD)
• Investigators: Study Chair: Robert W. Baloh, MD, University of California, Los Angeles; Principal Investigator: Joanna C. Jen, MD, PhD, University of California, Los Angeles; Principal Investigator: Tracey Graves, MD, Institute of Neurology and National Hospital for Neurology; Principal Investigator: Yoon-Hee Cha, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology. 2004 Jan 13;62(1):17-22. doi: 10.1212/01.wnl.0000101675.61074.50.
• Sasaki O, Jen JC, Baloh RW, Kim GW, Isawa M, Usami S. Neurotological findings in a family with episodic ataxia. J Neurol. 2003 Mar;250(3):373-5. doi: 10.1007/s00415-003-0994-3. No abstract available.
• Denier C, Ducros A, Vahedi K, Joutel A, Thierry P, Ritz A, Castelnovo G, Deonna T, Gerard P, Devoize JL, Gayou A, Perrouty B, Soisson T, Autret A, Warter JM, Vighetto A, Van Bogaert P, Alamowitch S, Roullet E, Tournier-Lasserve E. High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2. Neurology. 1999 Jun 10;52(9):1816-21. doi: 10.1212/wnl.52.9.1816.
• Graves TD, Cha YH, Hahn AF, Barohn R, Salajegheh MK, Griggs RC, Bundy BN, Jen JC, Baloh RW, Hanna MG; CINCH Investigators. Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation. Brain. 2014 Apr;137(Pt 4):1009-18. doi: 10.1093/brain/awu012. Epub 2014 Feb 26.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: December 16, 2005
• First Submitted That Met QC Criteria: December 16, 2005
• First Posted (Estimate): December 19, 2005

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Disease; Dyskinesias; Syndrome; Ataxia; Cerebellar Ataxia; Cerebellar Diseases
• Other Study ID Numbers: RDCRN 5302; U54RR019482-03 (U.S. NIH Grant/Contract)