Wider Vagus Nerve May Be Early Sign of Autonomic Neuropathy

Margarida Maia PhD avatar

by Margarida Maia PhD |

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The vagus nerve, the longest cranial nerve running from the brain through to the abdomen, is wider in people with familial amyloid polyneuropathy (FAP) than in people without the disease, a small study in China found.

Researchers also observed that its dimensions, measured by ultrasound imaging, correlated with the disease’s course and some of its symptoms.

According to the scientists, an ultrasound of the vagus nerve “may be a useful tool for evaluation of disease progression and an early sign of autonomic neuropathy,” or damage to the nerves that control involuntary bodily functions, as it is non-invasive and easier than other tests of such neuropathy.

The study, “Vagus nerve ultrasound in transthyretin familial amyloid polyneuropathy: A pilot study,” was published in the Journal of Neuroimaging.

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Symptoms of autonomic neuropathy are common among people with FAP and include an irregular heartbeat, a fall in blood pressure upon standing, cold extremities, incontinence, and constipation. Their identification is an essential step in distinguishing FAP from other neuropathies — disorders resulting from nerve damage and dysfunction — that affect adults.

“Early differentiation … is of vital importance for early treatment,” the researchers wrote.

One of the nerves thought to be involved in autonomic neuropathy is the vagus nerve. To understand if abnormalities in the vagus nerve could be an early sign of autonomic neuropathy, researchers worked with ultrasound — which uses sound waves to create images of internal body structures — to determine if differences exist in the dimensions of the left and right vagus nerve between people with or without the disease.

Their study included 18 FAP patients (14 men and four women) with a mean age of 50.4. Ten of the patients (55.6%)  had Coutinho stage 1 disease, indicating mild symptoms and unaffected mobility. The remaining eight (44.4%) had Coutinho stage 2 disease, with moderate symptoms requiring walking assistance.

All had sensorimotor polyneuropathy, and nearly all — 17 patients or 94.4% of group — had autonomic neuropathy. Sensorimotor polyneuropathy is a condition in which nerves responsible for relaying sensory messages or controlling body movements become damaged.

Half of the patients had early-onset disease, with symptoms starting before the age of 50 and lasting for a median three years, and the other half had late-onset disease, with symptoms after age 50 and lasting a median of 1.5 years. Patients with early-stage disease were a mean 14.8 years younger than those with late-stage disease.

However, “autonomic dysfunction was not significantly different between early- and late-onset disease groups,” the researchers wrote.

As controls, 17 healthy age- and gender-matched individuals (13 men and four women; mean age of 47.6) were also enrolled.

On ultrasound scans, researchers looked at the cross-sectional area of the vagus nerve, or the area obtained when its image is sliced perpendicular to its sides.

The cross-sectional area of both the left and right vagus nerve was greater in patients than in controls, results showed. It was also greater in patients with Coutinho stage 2 disease than in those with milder, stage 1 disease.

Researchers next set out to identify a cutoff value that could be used to distinguish patients from controls. They found that value to be 1.5 square millimeters (mm2) for the left vagus nerve and 2.5 mm2 for the right vagus nerve.

A relationship between clinical measures and the cross-sectional area of the vagus nerve was also established. Researchers found that the wider the vagus nerve, the longer the disease course (excluding from the analysis one patient with the longest disease course but a smaller nerve area) and the higher the score on the COMPASS 31 questionnaire. COMPASS 31, short for Composite Autonomic Symptom Score 31, is a self-rating tool that assesses several aspects of autonomic function; higher scores indicate more severe symptoms.

The vagus nerve seemed to increase in size as the disease progresses from its early stages, before decreasing in size in later stage.

“However, because of the limited number of cases, we could not reach a definitive conclusion” regarding this change, the researchers wrote.

A correlation was also seen between vagus nerve dimensions and heart measures, namely interventricular septum thickness — a measure of the thickness of the wall separating the lower chambers of the heart — and left ventricular posterior wall thickness (wall thickness of the left lower heart chamber).

Based on these findings, the researchers concluded vagus nerve enlargement is common in FAP patients, and ultrasound “may be an important clinical tool for assessing the severity of autonomic dysfunction” in FAP.