Truncal but Not Selective Vagotomy May Protect Against Parkinson's

Daniel M. Keller, PhD

June 28, 2016

BERLIN — Truncal vagotomy is associated with a reduced risk of developing Parkinson's disease (PD) at more than 5 years after the procedure, a study reports.

The finding supports the hypothesis that PD may begin as an α-synuclein pathology in the enteric nervous system that propagates via the vagus nerve into the central nervous system. Selective vagotomy showed no such association.

In a presentation here at the 20th International Congress of Parkinson's Disease and Movement Disorders, researchers led by PhD student Bojing Liu of the Department of Medical Epidemiology and Biostatistics at the Karolinska Institute in Stockholm drew upon the Swedish National Patient Register to conduct a matched cohort study comparing 9840 patients who underwent vagotomy between 1970 and 2010 with reference patients who did not have vagotomy (n = 378,840).

The reference patients were randomly selected on the basis of the date of surgery and matched by sex and year of birth. Patients were followed from the date of vagotomy to PD diagnosis, death, emigration, or the end of 2010, whichever occurred first.

At more than 5 years after vagotomy, truncal vagotomy was associated with a lower risk of developing PD, but selective vagotomy was not. At greater than 10 years, the association of truncal vagotomy and lower PD risk showed the same trend but was not significant.

Table. Vagotomy and Risk of Developing Parkinson's Disease

Follow-up Point Adjusted HR (95% CI) for Truncal Vagotomya Adjusted HR (95% CI) for Selective Vagotomya
Entire 0.77 (0.55 - 1.08) 1.11 (0.87 - 1.42)
>5 y 0.58 (0.37 - 0.91) 1.15 (0.89 - 1.49)
>10 y 0.58 (0.33 - 1.01) 1.11 (0.83 - 1.48)
>20 y 0.76 (0.31 - 1.87) 0.76 (0.44 - 1.32)

CI = confidence interval; HR = hazard ratio.

aAdjusted for chronic obstructive pulmonary disease (as a proxy for smoking), comorbidity index, and country of birth.

 

The authors concluded that an inverse association of truncal vagotomy and PD risk existed after 5 years but that larger samples should be used or pooled analyses should be done to verify these findings because only a limited number of vagotomies were included in this study.

They did not see a clear association of vagotomy and PD risk overall.

Per Borghammer, MD, PhD, DMSc, associate professor in the Department of Nuclear Medicine and the PET Center at Aarhus University Hospital in Denmark, has performed similar studies. "Basically, what we found is that a full truncal vagotomy protects you against Parkinson's disease and more or less decreases your risk by 50% whereas a more selective vagotomy only of the stomach has no benefit," he told Medscape Medical News. "It doesn't protect you at all."

He explained the different findings with full truncal vs selective vagotomy.

"When you do the selective vagotomy, only the stomach is denervated, but I guess perhaps 90% of the vagal fibers…to the rest of the intestine are still intact and could in principle be a highway for an ascending spread of pathology from the nerve terminals in the gut and to the central nervous system," he said, "whereas if you have a full truncal vagotomy the entire highway is cut so there is no pathway left."

Dr Borghammer emphasized that no one would do a vagotomy in hopes of preventing PD many years later. "These studies only provide evidence that ascending pathology from the nerve terminals in the gut to the brain could be carried partly by the vagal highway," he said.

According to the evidence so far, he says he thinks it is α-synuclein that aggregates in the peripheral nerve terminals and travels via the vagus nerve to the central nervous system to become Lewy bodies. What starts the aggregation — whether a toxin, something in the very long and highly branched axons of the vagus itself, or another process — is not known.

Because truncal vagotomy is only about 50% protective against PD, there may be other mechanisms or pathways for α-synuclein to accumulate in the central nervous system, or it may have already traveled up the vagus before vagotomy occurred. There is also recent evidence of a pathway through the olfactory nerve directly to the dopaminergic neurons of the substantia nigra.

There was no commercial funding for the study. Ms Liu has disclosed no relevant financial relationships.

20th International Congress of Parkinson's Disease and Movement Disorders: Abstract #476. Presented June 20, 2016.

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