C9ORF72 Mutations Limit ALS Patients’ Ability to Use Communications Devices, Study Suggests

Mutations in the C9ORF72 gene of people with amyotrophic lateral sclerosis (ALS) might make it more difficult for them to use brain-computer interfaces, says a study published in the journal Scientific Reports.

The study, “Expansion of C9ORF72 in amyotrophic lateral sclerosis correlates with brain-computer interface performance,” suggests not only that doctors might need to perform personalized assessments of a patient’s suitability to use communication-enabling devices, but that such devices might also help in diagnosis or early detection of non-motor manifestations of ALS.

Repeat expansion mutations in the C9ORF72 gene have been linked to earlier onset and more aggressive disease progression in ALS. Previous studies show that brain damage in people with such mutations extends beyond neural pathways that control movement. Such structural brain changes may be linked to reduced cognition.

Researchers at Penn State College of Medicine had earlier noted that cognitive decline predicts performance when using brain-computer interface devices such as the P300 speller. The device translates brain signals that are emitted when a person looks at the correct letter among several letters on a screen.

To test whether the mutation hurts performance when using a P300 device, researchers enrolled 25 ALS patients and 14 neurologically healthy controls matched for age and sex. Four of the ALS patients turned out to have a mutated C9ORF72 gene. This mutation is composed of repeated stretches of six DNA building blocks — the letters GGGGCC — that are expanded in an abnormal way.

Healthy people might have up to 30 copies of the sequence, while ALS patients can carry hundreds of such repeats. The mutation is the most common genetic flaw causing both ALS and related frontotemporal dementia.

The study showed that control individuals had 12 or fewer repeats of the sequence. The mutation was not linked to disease severity, assessed by the ALS Functional Rating Scale score, age at symptom onset, or with cognitive or behavioral assessments in the four affected patients.

Nevertheless, those with the mutation performed significantly worse on a spelling task using a brain-computer interface device. Patients carrying C9ORF72 mutations had a median spelling accuracy of 23.4 percent. Patients without the mutations were correct 78.1 percent of the time, and controls had an accuracy of 90.6 percent.

Researchers admit that their study has some limitations. For instance, they did not measure vision or eye movement control, which studies show are critical factors for ALS patients successfully using a P300 speller. The study suggests more research is needed to understand how C9ORF72 mutations affect the brain, and hence disease progression, in ALS.