Liancai Mu

Human Tongue Neuroanatomy: Nerve Supply and Motor Endplates

The human tongue has a critical role in speech, swallowing, and respiration, however, its motor control is poorly understood. Fundamental gaps include detailed information on the course of the hypoglossal (XII) nerve within the tongue, the branches of the XII nerve within each tongue muscle, and the type and arrangement of motor endplates (MEP) within each muscle. In this study, five adult human tongues were processed with Sihlers stain, a whole‐mount nerve staining technique, to map out the entire intra‐lingual course of the XII nerve and its branches. An additional five specimens were microdissected into individual muscles and stained with acetylcholinesterase and silver staining to study their MEP morphology and banding patterns. Using these techniques the course of the entire XII nerve was mapped from the main nerve to the smallest intramuscular branches. It was found that the human tongue innervation is extremely dense and complex. Although the basic mammalian pattern of XII is conserved in humans, there are notable differences. In addition, many muscle fibers contained multiple en grappe MEP, suggesting that they are some variant of the highly specialized slow tonic muscle fiber type. The transverse muscle group that comprises the core of the tongue appears to have the most complex innervation and has the highest percentage of en grappe MEP. In summary, the innervation of the human tongue has specializations not reported in other mammalian tongues, including nonhuman primates. These specializations appear to allow for fine motor control of tongue shape. Clin. Anat. 23:777–791, 2010.

Parkinson disease affects peripheral sensory nerves in the pharynx.

Dysphagia is very common in patients with Parkinson disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Current therapies are largely ineffective for dysphagia. Because pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD patients for Lewy pathology.Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined the glossopharyngeal nerve (cranial nerve IX), the pharyngeal sensory branch of the vagus nerve (PSB-X), and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was greater in PD patients with dysphagia versus those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in cranial nerve IX and PSB-X. These findings suggest that pharyngeal sensory nerves are directly affected by pathologic processes in PD. These abnormalities may decrease pharyngeal sensation, thereby impairing swallowing and airway protective reflexes and contributing to dysphagia and aspiration.

Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease.

Parkinson disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor manifestations and CNS pathology. Current drug therapies can often stabilize these cardinal motor symptoms, and attention has shifted to the other motor and nonmotor symptoms of PD that are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug-resistant symptom because it leads to aspiration and pneumonia, the leading cause of death. Here, we present direct evidence for degeneration of the pharyngeal motor nerves in PD. We examined the cervical vagal nerve (cranial nerve X), pharyngeal branch of nerve X, and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, that is, from 10 patients with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. Alpha-synuclein aggregates were revealed in nerve X and the pharyngeal branch of nerve X, and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all of the PD patients but in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathologic process of PD. Notably, PD patients who have had dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves than those without dysphagia. These findings indicate that motor involvement of the pharynx in PD is one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.

Altered pharyngeal muscles in Parkinson disease.

Abstract Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

A three-dimensional atlas of human tongue muscles.

The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongues anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a three‐dimensional (3D) computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue. Anat Rec, 296:1102–1114, 2013.

The Human Tongue Slows Down to Speak: Muscle Fibers of the Human Tongue

Little is known about the specializations of human tongue muscles. In this study, myofibrillar adenosine triphosphatase (mATPase) histochemical staining was used to study the percentage and distribution of slow twitch muscle fibers (slow MFs) within tongue muscles of four neurologically normal human adults and specimens from a 2‐year‐old human, a newborn human, an adult with idiopathic Parkinsons disease (IPD), and a macaque monkey. The average percentage of slow MFs in adult and the 2‐year‐old muscle specimens was 54%, the IPD was 45%, while the neonatal human (32%) and macaque monkey (28%) had markedly fewer slow MFs. In contrast, the tongue muscles of the rat and cat have been reported to have no slow MFs. There was a marked spatial gradient in the distribution of slow MFs with the highest percentages found medially and posteriorly. Normal adult tongue muscles were found to have a variety of uniquely specialized features including MF‐type grouping (usually found in neuromuscular disorders), large amounts of loose connective tissue, and short branching MFs. In summary, normal adult human tongue muscles have by far the highest proportion of slow MFs of any mammalian tongue studied to date. Moreover, adult human tongue muscles have multiple unique anatomic features. As the tongue shape changes that are seen during speech articulation are unique to humans, we hypothesize that the large proportion of slow MFs and the anatomical specializations observed in the adult human tongue have evolved to perform these movements. Anat Rec, 296:1615–1627, 2013.

Characteristics of Tetanic Force Produced by the Sternomastoid Muscle of the Rat

The sternomastoid (SM) muscle plays an important role in supporting breathing. It also has unique anatomical advantages that allow its wide use in head and neck tissue reconstruction and muscle reinnervation. However, little is known about its contractile properties. The experiments were run on rats and designed to determine in vivo the relationship between muscle force (active muscle contraction to electrical stimulation) with passive tension (passive force changing muscle length) and two parameters (intensity and frequency) of electrical stimulation. The threshold current for initiating noticeable muscle contraction was 0.03 mA. Maximal muscle force (0.94 N) was produced by using moderate muscle length/tension (28 mm/0.08 N), 0.2 mA stimulation current, and 150 Hz stimulation frequency. These data are important not only to better understand the contractile properties of the rat SM muscle, but also to provide normative values which are critical to reliably assess the extent of functional recovery following muscle reinnervation.

Force Characteristics of the Rat Sternomastoid Muscle Reinnervated with End-to-End Nerve Repair

The goal of this study was to establish force data for the rat sternomastoid (SM) muscle after reinnervation with nerve end-to-end anastomosis (EEA), which could be used as a baseline for evaluating the efficacy of new reinnervation techniques. The SM muscle on one side was paralyzed by transecting its nerve and then EEA was performed at different time points: immediate EEA, 1-month and 3-month delay EEA. At the end of 3-month recovery period, the magnitude of functional recovery of the reinnervated SM muscle was evaluated by measuring muscle force and comparing with the force of the contralateral control muscle. Our results demonstrated that the immediately reinnervated SM produced approximately 60% of the maximal tetanic force of the control. The SM with delayed nerve repair yielded approximately 40% of the maximal force. Suboptimal recovery of muscle force after EEA demonstrates the importance of developing alternative surgical techniques to treat muscle paralysis.

Nerve-muscle-endplate band grafting: a new technique for muscle reinnervation..

BACKGROUND Because currently existing reinnervation methods result in poor functional recovery, there is a great need to develop new treatment strategies. OBJECTIVE To investigate the efficacy of our recently developed nerve-muscle-endplate band grafting (NMEG) technique for muscle reinnervation. METHODS Twenty-five adult rats were used. Sternohyoid (SH) and sternomastoid (SM) muscles served as donor and recipient muscle, respectively. Neural organization of the SH and SM muscles and surgical feasibility of the NMEG technique were determined. An NMEG contained a muscle block, a nerve branch with nerve terminals, and a motor endplate band with numerous neuromuscular junctions. After a 3-month recovery period, the degree of functional recovery was evaluated with a maximal tetanic force measurement. Retrograde horseradish peroxidase tracing was used to track the origin of the motor innervation of the reinnervated muscles. The reinnervated muscles were examined morphohistologically and immunohistochemically to assess the extent of axonal regeneration. RESULTS Nerve supply patterns and locations of the motor endplate bands in the SH and SM muscles were documented. The results demonstrated that the reinnervated SM muscles gained motor control from the SH motoneurons. The NMEG technique yielded extensive axonal regeneration and significant recovery of SM muscle force-generating capacity (67% of control). The mean wet weight of the NMEG-reinnervated muscles (87% of control) was greater than that of the denervated SM muscles (36% of control). CONCLUSION The NMEG technique resulted in successful muscle reinnervation and functional recovery. This technique holds promise in the treatment of muscle paralysis.

Locations of the Motor Endplate Band and Motoneurons Innervating the Sternomastoid Muscle in the Rat

Sternocleidomastoid (SCM) is a long muscle with two bellies, sternomastoid (SM) and cleidomastoid (CM) in the lateral side of the neck. It has been widely used as muscle and myocutaneous flap for reconstruction of oral cavity and facial defects and as a candidate for reinnervation studies. Therefore, exact neuroanatomy of the SCM is critical for guiding reinnervation procedures. In this study, SM in rats were investigated to document banding pattern of motor endplates (MEPs) using whole‐mount acetylcholinesterase (AChE) staining and to determine locations of the motoneurons innervating the muscle using retrograde horseradish peroxidase (HRP) tracing technique. The results showed that the MEPs in the SM and CM were organized into a single band which was located in the middle portion of the muscle. After HRP injections into the MEP band of the SM, ipsilaterally labeled motoneurons were identified in the caudal medulla oblongata (MO), C1, and C2. The SM motoneurons were found to form a single column in lower MO and dorsomedial (DM) nucleus in C1. In contrast, the labeled SM motoneurons in C2 formed either one (DM nucleus), two [DM and ventrolateral (VL) nuclei], or three [DM, VL, and ventromedial (VM)] columns. These findings are important not only for understanding the neural control of the muscle but also for evaluating the success rate of a given reinnervation procedure when the SM is chosen as a target muscle. Anat Rec, 2011.