MRI Brain Studies in Patients With HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis

MRI Investigation Of The CNS In HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

This study will use three different magnetic resonance imaging (MRI) techniques to study HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/STP)-a disease of slowly progressive weakness in the legs. It is not known how the HTLV-1 virus causes this disease, but it is thought that as the body's immune system tries to destroy the virus, parts of the nervous system-primarily the spinal cord-are damaged.

Patients 18 years of age and older with HAM/TSP and healthy normal volunteers may be eligible for this study.

Participants will undergo diffusion tensor MRI, MR-spectroscopy, and magnetization transfer imaging to look at different compositional, architectural, and microscopic properties of the brain. All of these techniques are similar to conventional MRI, and like the conventional method they use a strong magnetic field and radio waves to measure structural and chemical changes in brain tissue. Each of the three scans will be done on separate days, each lasting about 1 hour. For the procedures, the patient or volunteer lies on a stretcher in a narrow metal cylinder (the scanner) and is asked to remain still for 15 to 30 minutes at a time. A special lightweight coil may be placed on the head to enhance the brain images. The subject can communicate with the person doing the scan at all times.

Study Overview

• Status: Completed
• Conditions: Tropical Spastic Paraparesis

Detailed Description

Magnetic Resonance Imaging (MRI) has become an important tool in the diagnosis of inflammatory CNS diseases such as Multiple Sclerosis (MS) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM-TSP). It is widely used as a marker for disease activity and progression. However, conventional MRI methods are only suitable to study gross anatomical features, such as size and shape of a particular area of the brain; questions regarding intrinsic microstructure and morphologic specificity cannot be addressed. But axonal damage or structural abnormalities even in normal appearing brain tissue may play an important role in the development of irreversible disability. Magnetization Transfer Imaging, Magnetic Resonance Spectroscopy and Diffusion Tensor MRI are imaging techniques described to be capable of the detection of such changes. Spectroscopy can detect molecular components in tissue, whereas the Magnetization Transfer Ratio (MTR) allows the measurement of water-macromolecule interactions. Diffusion Tensor MRI (DT-MRI) is an imaging modality that combines features of in vivo anatomical MRI and histopathology: it is an in vivo MRI method that provides information about tissue composition, microstructure, organization and architecture. This is possible because water diffusion properties in tissues, as measured by DT-MRI, are affected by tissue constituents, such as macromolecules, membranes, organelles, as well as by tissue microstructure, architecture and organization. A study comprising Magnetization Transfer-, Spectroscopy- and DT-MRI furnishes important information that cannot be obtained using conventional MRI methods.

• Study Type: Observational
• Enrollment: 40

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Neurological Disorders and Stroke (NINDS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

Patients:

A. Established Diagnosis of HAM/TSP as defined by Osame, Igata, and Matsumoto and subsequently confirmed by Gessain and Gout and the WHO.

B. Age 18 or older

C. An initial cohort of 5 HAM/TSP patients with established disease with EDSS levels of 6.0 or greater and duration of disease of 2 years or more will be investigated. If MRI abnormalities can be demonstrated, the group will be expanded to 20. Of this 20, at least 5 patients have been identified that will be HLA A201.

Healthy Controls:

A. No history of disease of the nervous system or autoimmune disease

B. Age 18 or older

C. Subjects shall be sex- and age-matched to our patients

EXCLUSION CRITERIA:

A subject will be excluded if he/she has a contraindication to MRI scanning such as the following: Aneurysm clip; Implanted neural stimulator; Implanted cardiac pacemaker or autodefibrillator; Cochlear implant; Ocular foreign body or implant (e.g. metal savings, retinal clips); breast implants; or Insulin pumps. Subjects will be excluded if they have claustrophobia. A pregnancy test will be administered to women of childbearing age. Pregnant women will be excluded from the studies.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

General Publications

• McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7. doi: 10.1002/ana.1032.
• Frank JA, McFarland HF. How to participate in a multiple sclerosis clinical trial. Neuroimaging Clin N Am. 2000 Nov;10(4):817-30 ,x.
• Gessain A, Gout O. Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). Ann Intern Med. 1992 Dec 1;117(11):933-46. doi: 10.7326/0003-4819-117-11-933.

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Study Completion: March 1, 2004

Study Registration Dates

• First Submitted: May 1, 2002
• First Submitted That Met QC Criteria: May 1, 2002
• First Posted (Estimate): May 2, 2002

Study Record Updates

• Last Update Posted (Estimate): March 4, 2008
• Last Update Submitted That Met QC Criteria: March 3, 2008
• Last Verified: March 1, 2004

More Information

Terms related to this study

• Keywords: HV; Healthy Volunteer; DTI; Normal Control; HTLV-1 Associated Myelopathy; HAM/TSP; MRSI; MTR; NAWN; Fiber-Tract; Tropical Spastic Paraparesis
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Retroviridae Infections; Neurologic Manifestations; Hematologic Diseases; Musculoskeletal Diseases; Muscular Diseases; Central Nervous System Infections; Neuromuscular Manifestations; Muscle Hypertonia; Paresis; Myelitis; Deltaretrovirus Infections; HTLV-I Infections; Spinal Cord Diseases; Bone Marrow Diseases; Muscle Spasticity; Paraparesis, Tropical Spastic; Paraparesis; Paraparesis, Spastic
• Other Study ID Numbers: 020180; 02-N-0180