New Endurance Tests Can Measure Fatigue in SMA Patients Types 2-4, Study Reports

Endurance tests that capture upper and lower body fatigue in spinal muscular atrophy patients — across ages, from children to adults, and degrees of disease severity — was proposed in a new study.

These tests, combined, are intended to help researchers and clinicians better evaluate and treat fatigue, so as to address a central complaint of SMA patients — the decline in their physical abilities due to how easily they tire doing even simple tasks, like lifting an arm repeatedly to eat or walking a short distance.

The study, “Assessment of fatigability in patients with spinal muscular atrophy: development and content validity of a set of endurance tests,” was published in BMC Neurology.

In addition to muscle weakness, fatigue is  a fairly common but often overlooked complaint, with patients noting they tire easily when going about even basic daily chores.

Exactly how SMA leads to disabling fatigue is not fully understood. Studies on animal models and post-mortem patients provide clues,  homing in on the abnormal development and maturation of the neuromuscular junction. This is the site of communication for nerve fiber and muscle cells that mainly controls when and how muscles contract. What is called “neuromuscular dysfunction” has been found in at least half of the patients with SMA, suggesting that problems with the neuromuscular junction contribute to fatigue.

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Tests that are sensitive enough to measure fatigue in SMA patients, however, are lacking.

Researchers with the University Medical Center Utrecht and the Netherlands Institute for Health Services Research (NIVEL) worked on identifying endurance tests that provide clinical methods for studying this problem in SMA patients.

They collected information from existing literature and current perspectives of patients, researchers, and clinicians dealing with SMA.

Researchers then analyzed information using a five-step method for clinical testing development called the “Consensus-based Standards for the selection of health Measurement Instruments” (COSMIN). These steps address:

1. Test definition: what is fatigue?
2. Choice of measurement method: how is fatigue measured?
3. Selecting formulating items: what activities can be used to study and measure fatigue?
4. Scoring issues: how can the results be best used?
5. Pilot testing: does this fatigability test work?

With an expert panel they assembled — researchers, clinicians, pediatric physical therapists, exercise psychologists, and neurologists — they examined these issues. Fatigue they defined as a “decline in performance such as peak force, power, speed and accuracy.”

Next, they broke down specific areas in which to measure performance and their related activities, based partly on patient answers to questionnaires on daily life activities that lead to feelings of fatigue:

• Leg function: walking, climbing stairs, showering, and running;
• Upper arm function: cooking, lifting a cup, washing hair, and brushing teeth;
• Hand function: using cutlery, typing, driving a car with a mini joy stick, and taking money out of a wallet.

“Patients with SMA reported a great number of different activities on the domains of leg function, upper arm function and hand function,” the study noted. “The expert panel therefore decided that all domains should be included in the development of the set of outcome measures for fatigability.”

Researchers and the expert panel then assembled a new comprehensive exam to measure fatigue in each area.

One test was selected to evaluate leg function in ambulatory SMA patients — the Endurance Shuttle Walking Test (ESWT), which the team adapted to SMA — and two tests to measure upper arm and hand strength and fatigue points: the repeated Nine Hole Peg Test (rNHPT) and the Box and Block Test (BBT), respectively. Together, these tests were called the Endurance Shuttle Box and Block Test and Nine Hole Peg Test.

The Endurance Shuffle Walking Test is a constant-load exercise test that measures how long a person can walk at a set constant endurance speed. The repeated Nine Hole Peg Test measures measure finger dexterity, and consists on taking pegs from a container, one by one, and placing them into holes on the board as quickly as possible. The Box and Block Test measures gross manual dexterity, and consists of a box with a partition in the middle — using only one hand at a time, the person has to move as many blocks as possible from one side of the partition to the other in 60 seconds.

Sixteen SMA patients — eight with type 2, and eight with type 3 — were recruited from the Dutch SMA registry, ranging in ages from 10 to 49, to assess the tests. Nine healthy adults and one teenager served as controls for a pilot run. Fatigue was measured both in physical terms — an evaluation of motor function such as “peak force, power, speed and accuracy”  in performing test task — and in cognitive terms, by assessing declines in attention and processing speed.

Patients completed all tests with a “lower than expected” dropout rate due to fatigue, the study noted — a 31% dropout rate for the repeated Nine Hole Peg Test, 45% on the  Box and Block Test, and 50% — the expected dropout rate across all tests — on the Walking Test.

However, “[i]t was observed that during the ESBBT [Box and Block test] subjects were actively compensating for fatigability by leaning on the box,” and that should not be allowed in testing, the researchers said.

All three tests were safe and helped to evaluate fatigue in SMA patients in slightly different ways.

“We developed a set of endurance tests for both non-ambulatory and ambulatory children and adults with spinal muscular atrophy which meet predefined specific criteria to achieve three main objectives: 1) quantify endurance; 2) generate clinical relevant outcome parameters and; 3) cover a large part of the clinical spectrum of spinal muscular atrophy,” the researchers wrote.

As such, the study established criteria to evaluate fatigue in SMA patients with a range of severity (types 2-4) and ages, using endurance tests representative of daily life activities. Researchers recommended these tests be further evaluated in larger and more varied patient groups.

“Based on our clinical experience and an upcoming large study on validity and reliability, we expect the endurance tests to be suitable for subjects aged 6 years and older for those being able to move around their dominant hand on their wheelchair table as minimal motor function,” the study concluded.