Magnetic Resonance Imaging to Detect Brain Damage in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      This study will test the ability of magnetic resonance imaging (MRI) to detect damage in
      different parts of the brain in patients with multiple sclerosis and to see if cognitive
      problems in patients can be correlated with the presence of lesions or reduction in the size
      of certain part of the brain. Healthy subjects will also be studied to compare findings in
      patients with those of normal volunteers.

      Healthy subjects and patients with multiple sclerosis who are between 18 and 60 years of age
      may be eligible for this study. Patients must not have severe clinical disability and must
      have been receiving and responding to Interferon beta for at least 6 months prior to
      enrollment. Candidates are screened with a medical history, physical examination, MRI and
      possibly evoked potential testing, which measures the nervous system response to visual,
      auditory and somatosensory stimulation.

      Participants have two MRI scans within 1 week (inclusive of the one performed for screening).
      MRI uses a magnetic field and radio waves to obtain images of body tissues and organs. The
      scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, the
      subject lies on a table that can slide in and out of the cylinder. Participants will be
      tested with magnet strengths of 1.5 and 3 Tesla; the higher the Tesla, the greater the
      ability to see brain changes. Each scan may last up to 90 minutes. In addition to the MRI
      scans, participants undergo cognitive testing that measures memory and thought processes and
      complete forms that test and quantify fatigue level, stress, anxiety and depression
    

Detailed description: 
      OBJECTIVE: The study will evaluate cognitive impairment in patients with multiple sclerosis
      (MS) and correlate the degree of cognitive dysfunction as identified by scores obtained in
      multiple cognitive tests with measurements of cortical thickness, cortical lesions and white
      matter disease on magnetic resonance imaging of brains of MS individuals.

      STUDY POPULATION: Study population will consist of 49 patients with relapsing remitting or
      secondary progressive MS with superimposed relapses who have been treated with Interferon
      beta at fully tolerated dosages for at least six months, and 49 healthy volunteers matched
      for gender, age and educational level. We expect to screen 65 individuals per arm in order to
      be able to enroll 49 individuals per arm, thus meeting the requirements of the sample size
      calculations.

      DESIGN: After screening clinical (rating disability by the means of the Expanded Disability
      Status Scale [EDSS] score), neurophysiological (e.g. evoked potential tests) and imaging
      examinations, MS patients and healthy subjects will undergo a neuropsychological evaluation
      using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and the
      Automated Neuropsychological Assessment Metrics (ANAM), and also a 3 Tesla magnetic resonance
      imaging (MRI). After 25% and after 50% of projected patients have been enrolled, distribution
      in MACFIMS will be evaluated to ensure that a broad spectrum of cognitive ability is
      represented. Cortical thickness, cortical lesions and white matter damage metrics (e.g.
      lesion load, diffusion tensor and magnetization transfer MRI measures) will be computed. In
      order to exclude the hypothesis that the presence of fatigue, anxiety and depression,
      normally occurring in MS patients, might interfere with their cognitive performance, thus
      acting as confounding factors, scales measuring fatigue and mental status will be
      administered in all subjects. Scores obtained on these scales will be used as covariates in
      each of the statistical analyses performed in the present study to account for their possible
      effects.

      OUTCOME MEASURES: The first outcome measure will be the MACFIMS and cortical thickness
      values. Correlation between these two metrics will be initially performed. Secondly, cortical
      lesions as well as white matter lesions on T1 and T2 weighted images, magnetization transfer
      ratios and diffusion tensor imaging metrics of lesional and normal appearing brain tissues
      will be computed and their impact in determining cognitive impairment will be determined.
      Thirdly, deep gray matter, white matter and total brain volume measures will be computed and
      correlated with cognitive function measured by the MACFIMS. Similarly, correlations between
      clinical disability, as measured by the EDSS score and cognitive impairment, as well as
      between EDSS score and each of the RMI variables explored in the study will be performed.
      Finally, the level of correlation between MACFIMS and ANAM tests will be investigated.
    

Keywords: Brain; Cognitive Deficits; Cognitive Testing; MRI; Multiple Sclerosis; MS; Healthy Volunteer; HV