Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2

Raw scores of Dimensional Card Sorting will be compared between groups. The higher score, the better executive function.

Raw scores of Flanker Inhibitory Control and Attention will be compared between groups. The higher score, the better attention and executive function.

Raw scores of Pattern Comparison Processing Speed Test will be compared between groups. The higher score, the better processing speed.

Raw scores of Oral Reading Recognition Test will be compared between groups. The higher score, the better language domain.

Raw scores of List Sorting Test will be compared between groups. The higher score, the better working memory.

Raw scores of Picture Sequence Memory Test will be compared between groups. The higher score, the better working memory.

Scores of TMT - Part B is based on time to complete the test (seconds). The lower scores of TMT-B, the better executive function. For TMT-B, an average score is 75 seconds and a deficient score is greater than 273 seconds. Maximum score is 300 seconds (5 minutes).

The Digit Span score is the length of the longest correctly repeated number sequence. Digit Span Score is an indication of intelligence among other tests. The average digit span for normal adults without error is seven plus or minus two (a span of 5 to 9 digits).

Scores of TMT-Part A is based on time taken to complete the test (seconds). An average score for TMT-A is 29 seconds and a deficient score is greater than 78 seconds.

Rey Auditory Verbal Learning Test (RAVLT) scores will be compared between groups - Scoring: Different summary scores are derived from raw RAVLT scores. These include RAVLT Immediate (the sum of scores from 5 first trials, i.e., Trials 1 to 5), Learning (the score of Trial 5 minus the score of Trial 1), and Forgetting (the score of Trial 5 minus score of the delayed recall).

Scores of COWA will count up the total number of words that the individual is able to produce within 60 seconds. A score of under 17 indicates concern, although some practitioners use 14 as a cutoff for abnormal.

Scores of verbal fluency will count up the total number of animals that the individual is able to produce within 60 seconds. A score of under 17 indicates concern, although some practitioners use 14 as a cutoff for abnormal.

The BDI is a widely used 21-item standardized self-report questionnaire measuring depression on a 4-point scale ranging from 0 to 3. Scores are interpreted as follows: 1-9, minimal depression; 10-16, mild depression; 17-29, moderate depression; 30-63, severe depression. BDI-II scores will be compared between groups.

The BAI is a 21-item self-report scale typically surveys features of anxiety. In using the BAI, patients rate the severity of each symptom on a 4-point scale ranging from 0 (not at all) to 3 (severely - I could barely stand it). A total score ranging from 0 to 63 is calculated by summing the severity ratings for all 21 items. BAI scores will be compared between groups.

AES was built based on the definition of apathy: syndrome of loss of motivation as reflected by acquired changes in affect (mood), behavior, and cognition. The AES is a four-point Likert-Scale response measure (0 = not at all true/characteristic to 3 = very much true/characteristic), composed of 18 items that assess and quantify emotional, behavioral, and cognitive aspects of apathy. We will evaluate AES in both participants and informants.

The possible score ranges from 0 to 20 points in each case. 0 points represent the patient's most severe physical and/or mental impairment, while 20 points represent the best possible state of health.

The SF-36 was used to assess the generic quality of life (QoL). It is a self-report measure with established reliability and validity across a wide range of clinical populations. Scores of SF-36 in each sub-scale will be compared between groups - SF-36 scores range from 0 (worst) to 100 (best)

The short-form BPI is designed to measure the interference pain has on the patient's daily activities. These scales were selected based on their validity, simplicity, ability to detect the change in pain with treatment, patient relevance, reliability, test-retest scores, and their previous use in pain studies of the myotonic dystrophy population. BDI scores will be compared between groups - Worst Pain Score: 1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain.

PSQI is a self-reported questionnaire that measures seven components of sleep over a 1-month time interval: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. PSQI scores will be collected and compared between groups - The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality.

The CIS-fatigue severity sub-scale contains eight items scored on a 7-point Likert scale. Scores can range between 8 and 56 with higher scores indicating higher levels of fatigue and scores of 35 or more are considered to indicate severe fatigue. Fatigue scores will be compared between groups.

The N4PE assay simultaneously measures four biomarkers in plasma. The targets are Abeta 40 (Aβ40), Abeta 42 (Aβ42), Glial Fibrillary Acidic Protein (GFAP™), and Neurofilament light (Nf-L).

The N4PE assay simultaneously measures four biomarkers in CSF. The targets are Abeta 40 (Aβ40), Abeta 42 (Aβ42), Glial Fibrillary Acidic Protein (GFAP™), and Neurofilament light (Nf-L).

Plasma P-tau 181 will be measured in DM2 and control groups. Relationships between plasma and CSF biomarkers will also be determined within the DM2 group. Plasma p-tau181 is categorized into three categories: low < 12.03 pg/ml, medium 12.04-19.63 pg/ml, and high > 19.65 pg/ml. High level of plasma P-tau 181 is correlated with neurodegenerative diseases.

The P-tau-181 assay will be measured in CSF samples. A maximum concentration of CSF P-tau of 60 pg/ml or lower is considered normal.

Among the tools that assess walking ability in muscular dystrophies, the 6MWT offers a good combination of reliability, sensitivity, clinical significance, and feasibility for multi-center trials. We will compared 6MWT between groups.

Subjects will be instructed to walk at maximum speed in a long corridor with an even surface over 10 meters with a still-standing start and a "flying" finish. Time to complete 10-meter will be measured between groups.

The SPPB measures physical function using three components: usual gait speed over 4-meters time to complete five chair rises, and standing balance with a progressively narrow base of support. Each component is scored on a 0-4 scale and summed for an overall score range of 0-12. SPPB scores will be compared between groups.

Participants will be instructed to make as many "full steps" as possible in 15 seconds. Both legs will be tested, one foot at the time. The number of the step will be compared between groups.

Handgrip dynamometer will be used to test grip strength. The subject will also perform quantitative pinch strength testing with a pinch gauge. Average grip and pinch strength (kg) will be measured and compared between groups.

The test will evaluate upper extremity function, specifically fine dexterity, and coordination. We will test each subject twice, starting with a dominant hand first, then a non-dominant hand. One practice trial (per hand) should be provided before timing the test. Average time to complete the 9HPT will be compared between groups.