Cognitive Dysfunction in MS: Using Altered Brain Oscillation to Link Molecular Mechanisms With Clinical Outcomes

Up to 65% of patients with multiple sclerosis (MS) experience cognitive dysfunction. Diminution of mental capacity has a pervasive and profound impact on their quality of life. Subtle changes in white matter predict cognitive changes in these patients but how this disrupts brain function remains unclear. Development of effective therapeutics to restore normal cognition hinges on elucidating these functional changes. The investigators seek to uncover the patho-physiological basis for cognitive decline in MS. The investigators hypothesize that cognitive decline originates from disrupted gamma oscillations and that gamma oscillations are disrupted by molecular changes triggered by demyelination.

Study Overview

• Status: Completed
• Conditions: Pediatric Multiple Sclerosis

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Seven patients who have pediatric-onset multiple sclerosis and 7 healthy (non-patient) children are expected to participate in this study.

Description

Inclusion Criteria (*applicable to controls):

1. Must be between 6 and 17 years and 11 months of age*;
2. Have a diagnosis of MS according to the revised McDonald diagnostic criteria and/or International Pediatric MS Study Group criteria;
3. Has English language knowledge at the level needed to complete clinical questionnaires (4th grade level).*

Exclusion Criteria (*applicable to controls):

1. Neurological comorbidity.*;
2. Relapses or requires treatment with steroids within 30 days from enrollment;
3. Is pregnant at the time of enrollment.*;
4. Has any metal parts in their body (i.e. Cochlear (ear) implant, metal braces (dental fillings are o.k.).*;
5. Is younger than 6 years of age.*;
6. Is older than 18 years of age.*;
7. Has prior history of traumatic brain injury, neurological disorder, cerebral palsy, developmental delay or learning disability.*;
8. Requires sedation for brain scanning.*;
9. Is claustrophobic, as brain scanning requires children to enter a tunnel in the MRI machine.*

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
7 pediatric-onset multiple sclerosis
7 non-patient healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI scans of the brain, including Diffusion Tensor Imagine (DTI)		90 minutes
Neuronal responses during simple and choice reaction time tasks	Video-based eye tracking in the MEG	60 minutes
Neurocognitive Testing	Penn Computerized Neurocognitive Battery	90 minutes
Neurological Exam - Standard physical exam performed by the neurologist to determine the Expanded Disability Status Scale (EDSS) score.		20 minutes
Clinical Interview	Series of questions about the participant's demographic and clinical information including, current and past health, family history, and medications.	10 minutes

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): November 24, 2017
• Study Completion (Actual): November 24, 2017

Study Registration Dates

• First Submitted: January 3, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurocognitive Disorders; Cognition Disorders; Multiple Sclerosis; Cognitive Dysfunction
• Other Study ID Numbers: 1000054117

Plan for Individual participant data (IPD)

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