Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

The Scale for the Assessment and Rating of Ataxia (SARA) is an 8-item assessment measuring ataxia severity. Total scores are calculated as a sum of item scores and range 0-40, with higher scores indicating greater ataxia severity.

The Patient-Reported Outcome Measure of Ataxia (PROM-ataxia) is a 70-item questionnaire assessing the impact of ataxia on an individual's daily life. Items are rated 0-4, where 0 indicates no difficulty/symptoms and 4 indicates severe difficulty/symptoms. Total scores are a sum of item scores and range 0 to 280 with higher scores indicating greater impact of ataxia symptoms on daily life.

Pons volume will be measured using MRI and divided by normalized intracranial volume. This measure is a unitless ratio.

The Timed 25-Foot Walk (T25-FW) measures how fast participants can complete a 25-foot walk in seconds. The final score is an average of 2 trials. A higher scores indicates slower walking and greater gait impairment.

The modified Friedreich Ataxia Rating Scale - Part E (mFARS-E) is a 7-item comprehensive neurological assessment of upright stability. Item E1 (Sitting) is scored 0-4, Items E2-E5 (Stance) are scored 0-4 based on how many seconds a patient can maintain position without support, and Item E6 (Tandem Walk) is scored 0-3, and Item E7 (Gait) is scored 0-5. Participants may be given up to three attempts (trials) for Items E2-E5, with each attempt recording a score 0-4, and then averaging trial scores for the total Item score. Total score is a sum of item scores on a scale of 0 to 36 points, with higher scores indicating greater impairment and loss of balance.

The Friedrich's Ataxia Activities of Daily Living (FA-ADL) is a 9-item questionnaire measuring how ataxia affects everyday function. Items are rated 1-5 on an ordinal scale with higher scores indicating greater impairment during daily tasks. Total score is the sum of items scorings, ranging 0-36, with higher scores indicating greater impairment.

The Brief Ataxia Rating Scale (BARS) is a 5-item assessment measuring cerebellar ataxia severity. Items are scored 0-4. Total scores are a sum of item scores and range 0-20, with higher scores indicating greater ataxia severity.

The Cerebellar Cognitive Affective Syndrome (CCAS) Scale is a screening instrument to detect the cerebellar cognitive affective syndrome in patients with cerebellar injury. The 12-item scale assesses different cognitive domains. The total possible raw score is 120 points; the Pass/Fail measure provides a maximum fail score of 10 (i.e., 10 failed tests). A fail score of 0 is normal. A participant with a fail score of 1 indicates a Possible CCAS, a fail score of 2 indicates Probable CCAS, and a fail score of 3 or more indicate Definite CCAS.

The Nine-Hole Peg Test (9-HPT) assesses upper motor dexterity by having participants place and remove 9 pegs, one at a time, as quickly as possible, with one hand at a time. Scores are reported in seconds with higher scores indicated greater upper motor impairment.

The EuroQol 5-Dimension Questionnaire (EQ-5D) is a 6-item questionnaire used to assess a person's health-related quality of life. Items 1-3 are rated 1-3, items 4 and 5 are rated 1-5, and item 6 is a visual analog scale 0-100. Scores on questions 1-5 are converted into a single summary index value between 0 and 1, with lower scores indicating worse health-related quality of life.

The Fatigue Severity Scale is a 9-item scale that evaluates the impact of fatigue on a participant's life within the last week. Nine statements are rated on a scale of 1 to 7, where low values indicate strong disagreement with the statement and higher values indicate strong agreement with the statement. An additional item assess global fatigue on a scale 0 to 10, with 0 being the worst and 10 being normal. Total scores are calculated as the sum of ratings from Items 1-9, with higher scores indicating greater fatigue severity.

The Fall Questionnaire is a 5-item scale designed to monitor and capture a participant's number of falls, near-falls, and fall consequences based on the previous three months. Items 1-4 are rated on a scale of 0 to 3 points. Items 1-3 capture frequency of fall, near fall, and worry of falling, where a rating of 0 is Not at All in terms of frequency, up to a rating of 3 fora frequency of at least one time per week (over 13 or more times in 3 months). Item 4 is rated based on severity of injuries, if any, where 0 is Not at all for sustaining injuries, 1 is mild injuries, 2 is moderate injuries, and 3 is severe injuries. The scores from all four questions are summed to give a total score of 0-12 points, where higher scores indicate more severe fall history. Item 5 captures qualitative information on the circumstances of the fall and possible causes.