The Findings of MR Imaging in Rett Syndrome

The Findings of Resting-state Functional Magnetic Resonance Imaging , Susceptibility Weighted Imaging and Diffusion Spectrum Imaging in Rett Syndrome

Introduction: Rett Syndrome is a neurodevelopmental disease that primarily affects girls. Clinically, patients are normal before six months to one and half years old, and then develop progressive severe problems with communication, learning, co-ordination and neurodevelopment, with loss of motor skills around the age of two. At the same time, stereotyped hand movement typically appears. However, some of them will improve the abilities in speech and eye gaze, and the repetitive hand movements may decrease after few years.

Background / hypothesis：Preliminary evidence suggests that there are many differences in brain structure between Rett syndrome and normal people including cerebral volume reduction in both white matter and gray matter, cerebral blood flow in the frontal area, and density of receptors in basal ganglia. In MR imaging studies, decreases in parietal lobe gray matter were found, and several reductions in cortical white matter were observed by DTI. However, the visual related pathway- posterior corona radiata in Rett syndrome girls was normal to be increased in FA values. The similar result was also discovered in the superior longitudinal fasciculus, associated with speech, which equal to control subjects and patients with preserved speech (phrases and sentences).Despite this, few studies mentioned comparison with brain microstructure in the different stage, especially in adult patients. Therefore, our prospective study will be planned to figure out the specific changing pattern of brain structure in different stages of Rett syndrome. And the trajectory of microstructure in brain is going to be in accordance with the functional improvement.

The investigators suppose that (1)there are different microstructural changes for patients with/without preserved mobility, verbal ability and communication skill; (2)there are a few specific brain microstructures changes in visual pathway; (3) there is a specific changing pattern of brain microstructure in different aging of Rett syndrome. To acquire more specific results, the investigators aim to apply conventional MRI, diffusion-spectrum imaging, and some clinical assessment tools like Rett syndrome -related questionnaire, SSI, PDMS-2 and six-minute walk test to investigate their correlation.

Study Overview

• Status: Unknown
• Conditions: Rett Syndrome
• Intervention / Treatment: Other: Rett Syndrome

Detailed Description

In this study we proposed to use conventional MR imaging, diffusion spectrum imaging(DSI), and susceptibility weighted imaging(SWI), to acquire the information of brain structure in neural tissue and the volume of blood vessels. Conventional MR imaging with 3T MR unit will consist of sagittal T1-weighted, axial T2 fast spin-echo, and thickness of transverse sections in 2.5 mm are obtained parallel to the anterior and posterior commissure line. Diffusion spectrum imaging(DSI), a more specific method to detects the fiber crossing of white matter, quantified by GFA value to investigate the tract-specific abnormalities with the growth trajectories and their correlations with clinical features in patients with RTT.DSI scans were acquired using a Siemens Tim Trio 3T scanner at NTUH. Diffusion spectrum imaging data were obtained in 32 channel head coil with following parameters: TE = 2.98 ms, TR = 2000 ms, slice per slab=208, slice thickness = 1.0mm, FoV read = 256mm, voxel size=2.5x2.5x2.5mm. Susceptibility weighted image(SWI), facilitated sensitivity to deposited hemosiderin, has improved the recognition of cerebral micro bleeds (CMB). Therefore, we plan to use the advancing techniques to gain the information about the multiple cortico-subcortical blood vessels from our patient.

Study subjects will be recruited from OPD in NTU hospital, age range 2 to 30 years, 45 diagnosed rett patients and 45 controls. All of the scanning will complete in NTU hospital. Before entering the scanning room, parents of patients will finish a questionnaire about the physical development in Rett syndrome, including gross motor, fine motor skills and speech ability. After then, DSI data are acquired at 3T MR unit and we will analysis the white matter data by DSI studio (http://dsi-studio.labsolver.org ) and perform the whole brain tracts in detail by TBAA which were reconstructed on the NTU-DSI-122 template. We will process and analyze the gray matter by using FreeSurfer (http://freesurfer.net) and the volume of cerebral micro bleeds by SWI data to find out the difference between Rett patients and control group. In order to obtain the results with reliability and validity, Peabody developmental motor scales (PDMS-2), a motor development program will be applied to assess the gross motor and fine motor skills objectively. PDMS-2 consists of 6 subjects: reflexes, stationary, locomotion, object manipulation, grasping, and visual-motor integration and can be used in clinical assessment and training. Finally, the brain structure data will be compared with the functional changes in Rett syndrome patients.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Department of Pediatrics, National Taiwan University Hospital
    • Contact: Wang Tso Lee; Phone Number: 71618 886-2-23123456

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 26 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Rett Syndrome is a neurodevelopmental disease that primarily affects girls. Clinically, patients are normal before six months to one and half years old, and then develop progressive severe problems with communication, learning, co-ordination and neurodevelopment, with loss of motor skills around the age of two. At the same time, stereotyped hand movement typically appears.

Description

Inclusion Criteria:

• Diagnosis: Rett Syndrome

Exclusion Criteria:

1. Psychiatric diagnoses
2. History of neurological impairment
3. Neuropsychiatric conditions
4. Clinical evidence of a genetic disorder

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rett Syndrome; Rett Syndrome is a neurodevelopmental disease that primarily affects girls. Clinically, patients are normal before six months to one and half years old, and then develop progressive severe problems with communication, learning, co-ordination and neurodevelopment, with loss of motor skills around the age of two. At the same time, stereotyped hand movement typically appears.	Other: Rett Syndrome; Diagnosis of Rett Syndrome
Control-normal; Healthy people	Other: Rett Syndrome; Diagnosis of Rett Syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DSI data	Diffusion spectrum imaging(DSI), a more specific method to detects the fiber crossing of white matter, quantified by GFA value to investigate the tract-specific abnormalities with the growth trajectories and their correlations with clinical features in patients with RTT.DSI scans were acquired using a Siemens Tim Trio 3T scanner at NTUH. Diffusion spectrum imaging data were obtained in 32 channel head coil with following parameters: TE = 2.98 ms, TR = 2000 ms, slice per slab=208, slice thickness = 1.0mm, FoV read = 256mm, voxel size=2.5x2.5x2.5mm.	40 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peabody developmental motor scales (PDMS-2),	A motor development program will be applied to assess the gross motor and fine motor skills objectively. PDMS-2 consists of 6 subjects: reflexes, stationary, locomotion, object manipulation, grasping, and visual-motor integration and can be used in clinical assessment and training.	within the first 90 days after scanning

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Wang Tso Lee, PhD, NTUH

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimate): September 16, 2016

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; functional Magnetic Resonance Imaging; Diffusion Spectrum Imaging; Susceptibility weighted imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: 201510011RINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No