Abstract
A trigeminovagal complex, as described in some animals, could help to explain the effect of vagus nerve stimulation as a treatment for headache disorders. However, the existence of a trigeminovagal complex in humans remains unclear. This study, therefore investigated the existence of the trigeminovagal complex in humans. One post-mortem human brainstem was scanned at 11.7T to obtain structural (T1-weighted) and diffusion magnetic resonance images ((d)MR images). Post-processing of dMRI data provided track density imaging (TDI) maps to investigate white matter at a smaller resolution than the imaging resolution. To evaluate the reconstructed tracts, the MR-scanned brainstem and three additional brainstems were sectioned for polarized light imaging (PLI) microscopy. T1-weighted images showed hyperintense vagus medullar striae, coursing towards the dorsomedial aspect of the medulla. dMRI-, TDI- and PLI-images showed these striae to intersect the trigeminal spinal tract (sp5) in the lateral medulla. In addition, PLI images showed that a minority of vagus fibers separated from the vagus trajectory and joined the trigeminal spinal nucleus (Sp5) and the sp5. The course of the vagus tract in the rostral medulla was demonstrated in this study. This study shows that the trigeminal- and vagus systems interconnect anatomically at the level of the rostral medulla where the vagus fibers intersect with the Sp5 and sp5. Physiological and clinical utility of this newly identified interconnection is a topic for further research.
Highlights
Primary headache disorders are one of the most common disorders in neurology and cause substantial levels of disability globally[1,2]
In frogs, Kecskes et al discovered that axon collaterals from the spinal- and mesencephalic tract of the trigeminal nerve could be followed into the glossopharyngeal-vagal motor neurons, alongside the perikaryia and dendrites of the nucleus ambiguus (Amb)[20]
polarized light imaging (PLI) is a microscopy technique that quantifies fiber orientation based upon birefringence of the myelin sheath in histological brain sections and has been reported as a technique that is highly effective in validating MR findings[21]
Summary
Primary headache disorders are one of the most common disorders in neurology and cause substantial levels of disability globally[1,2]. Noxious stimulation of the meninges surrounding the brain and the dura mater in particular, or dural blood vessels (i.e. the superior sagittal sinus and the middle meningeal artery and other large cerebral arteries), can induce pain similar to that experienced when a person is suffering from a migraine or cluster headache attack[5,6,7]. Based on these mechanisms, modulation of the trigeminal nerve can be regarded as an experimental treatment option for both migraine and cluster headaches. The aim of this study was to combine post-mortem, 11.7T MRI, and PLI results in order to demonstrate the existence of the trigeminovagal complex in humans
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