Patients with Friedreich’s ataxia (FRDA) who have trouble standing upright are at greater risk of losing their ability to walk, a report based on a large natural history study found.
Standing and balance tests could be used to separate groups of patients at lower and higher risk of losing the ability to walk, or loss of ambulation (LOA), and to evaluate in clinical trials if new treatments can delay this loss, the researchers suggest.
The study, “Predictors of loss of ambulation in Friedreich’s ataxia,” was published in the journal EClinicalMedicine.
Friedreich’s ataxia (FRDA) is a rare inherited disease of the nerves and muscles that involves progressive loss of coordination and balance and eventual loss of walking ability.
Losing the ability to walk is a key event for those with FRDA, but predicting when this will happen is challenging because disease severity and progression varies among patients.
Large natural history studies have tried to identify predictors of FRDA progression based on neurological examinations or performance measures that quantify simple neurologic tasks. “In clinical reports, the time of loss of ambulation — a measure with intrinsic clinical meaning — has been documented and estimated, but only on much smaller sample sizes,” the researchers said.
To determine potential predictors of losing the ability to walk, three researchers — one at the Clinical Data Science GmbH, in Switzerland, one with the Friedreich’s Ataxia Research Alliance, and one at Children’s Hospital in Philadelphia — studied the progressive loss of specific functions related to walking and standing in participants enrolled in the Friedreich’s Ataxia Clinical Outcome Measures Study (FA-COMS).
To capture the worsening of those specific functions over time, researchers used parts of the Friedreich Ataxia Rating Scale (FARS), a physician-rated neurological scale used to measure FRDA progression.
To account for different disease severities, patients were grouped by age at disease onset in three categories — younger than 15 years old (703 patients), between 15 and 24 years old (211 patients), and older than 24 (107 patients). Loss of ambulation was defined as being unable to walk, even with assistance, and requiring the use of a wheelchair.
Patients with early onset disease — before the age of 15 — lost the ability to walk sooner, at a median of 11.5 years after they began experiencing the first symptoms. Researchers found that patients’ ability to stand and keep their balance could predict their future risk of losing the ability to walk, and the time to this loss was associated with how poorly they performed.
In these exams, upright stability was evaluated using six different tests — standing with feet apart, with feet apart and eyes closed, with feet together, with feet together and eyes closed, with feet in tandem (heel-to-toe placement), or using only the dominant foot.
Specifically looking at more severe cases (disease onset before 15 years old), researchers noted that each function is lost step by step, as the disease progresses.
First, patients lost the ability to stand with eyes closed (step 0), followed by the ability to stand with eyes open and feet together (step 1), and eventually that of standing with feet apart (steps 2 and 3), before they lost the ability to walk.
Participants on step 0 showed a median time to loss of walking ability of 10.3 years. Patients on step lost ambulation in a median of 6.1 years; patients on step 2 in 5.8 years; and patients on step 3 in 2.0 years.
After five years, the risk of LOA was 9%, 39%, 43%, and 90%, respectively, for patients on each of these steps.
“We propose a stratification paradigm for time to LoA in FRDA. Concurrently, each step [score of stance test] in a sequence of events represents a surrogate measure for future LoA. This will facilitate patient selection and stratification in clinical trials, and potentially enable study of LoA as a direct clinical outcome,” researchers said.