Blink reflex test may be biomarker to diagnose, monitor ALS

Assessing electrical activity may hasten diagnosis and track disease progression

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A test that assesses the electrical activity associated with blinking may help speed the diagnosis of amyotrophic lateral sclerosis (ALS) and monitor disease progression in people with the condition, a study found.

Findings showed that certain electrical waves can significantly distinguish people with ALS from healthy controls or people with diseases affecting the nerves outside the brain and spinal cord.

Also, among those with the disease, the timing of these waves was associated significantly with their disability status and ALS clinical subtype, which can meaningfully affect prognosis.

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“[Blink reflex] might help with earlier interventions in order to maintain a better functional status in ALS patients,” the researchers wrote in the study, “Blink Reflex Examination in Patients with Amyotrophic Lateral Sclerosis Compared to Diseases Affecting the Peripheral Nervous System and Healthy Controls,” published in the journal Brain Sciences.

ALS is caused by the progressive dysfunction of motor neurons, the nerve cells that control voluntary movements. This renders the brain unable to control muscles, and patients progressively lose their ability to perform everyday tasks.

Diagnosing the disease in its early stages is critical to ensure patients receive timely treatments before significant disability sets in. Current ALS therapies can slow the progression of the disease, but they cannot reverse damage that has already occurred.

But because ALS symptoms can overlap with a number of other neurological conditions, it often takes several months before patients receive a formal diagnosis and begin appropriate treatments.

How the blink reflex test works

The blink reflex test is a simple, noninvasive, and inexpensive test that can detect alterations in the brainstem, an area at the base of the brain that connects to the spinal cord. The test measures the electrical activity of facial nerves involved in blinking after being stimulated, but it’s unknown if it could serve as an easy-to-use diagnostic tool in ALS.

To find out, researchers in Hungary examined blink reflex parameters in 29 people with ALS, 50 healthy controls, and 61 people with other diseases affecting the peripheral nervous system — the nerves that branch out from the brain and spinal cord and into all body parts.

The test is based on an electric stimulus applied to the supraorbital nerve (a facial nerve located above the eye) and responses are obtained from electrodes placed over the muscle that closes the eyelid, namely in the lower lid.

Generally, patients experience an initial, rapid blink reflex on the side where the stimulus was applied, whose corresponding electrical signal is called R1. This is followed by a more sustained and prolonged closure of both eyelids, measured as R2 waves. There are two R2 waves: one on the stimulated side, called the ipsilateral R2 or R2i, and one on the opposite side, called contralateral R2 or R2c.

Different latencies for different waves

Results showed that the timing of the R1 wave, called latency, was similar for ALS patients and healthy controls, but patients had longer latencies of both R2i and R2c, indicating they took longer to close both eyelids after the stimulus.

There were six patients for whom no R2c wave was recorded, suggesting the  blinking response did not occur. This supports the loss of neuronal connectivity in ALS, according to the researchers.

The latencies of these R-waves also were different between ALS patients and people with diseases of the peripheral nervous system. A particular difference was the normal R1 wave in ALS patients, which was altered in at least one eye in people with all other examined conditions.

“The pathological latencies were increased and showed a pattern that could be well distinguished from the ‘ALS pattern,’” the researchers wrote.

Results also showed notable differences in R-wave latencies in ALS patients whose symptoms first began the muscles around the face and throat — called bulbar-onset disease — from those with spinal-onset ALS, where symptoms of muscle weakness are first evident in the arms and legs.

More precisely, the latencies of R1, R2i, and R2c were all higher in people with bulbar-onset ALS, which typically have a faster disease progression and worse prognosis, than in those with spinal-onset.

Consistently, higher latencies in all three waves were associated with a more severe functional disability, as measured by the ALS Functional Rating Scale—Revised (ALSFRS-R), regardless of clinical onset.

Promising tool to diagnose, monitor disease progression

The findings point to the blink reflex as a promising tool to diagnose and monitor disease progression in people with ALS, according to the researchers.

“[Blink reflex] examination might be a promising tool to monitor the course of the disease and to serve as a biomarker in patients with ALS, due to its correlation with ALSFRS-R score,” the researchers wrote.

However, its use as a prognosis ALS biomarker should be assessed in more studies, including in larger samples of ALS patients who would be followed for longer periods.