ABSTRACTParkinson 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.
ABSTRACTDysphagia 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.
Objectives:
At present it is believed that the pharyngeal constrictor (PC) muscles are innervated by the vagus (X) nerve and are homogeneous in muscle fiber content. This study tested the hypothesis ...that adult human PCs are divided into 2 distinct and specialized layers: A slow inner layer (SIL), innervated by the glossopharyngeal (IX) nerve, and a fast outer layer (FOL), innervated by nerve X.
Methods:
Eight normal adult human pharynges (16 sides) obtained from autopsies were studied to determine 1) their gross motor innervation by use of Sihler's stain; 2) their terminal axonal branching by use of acetylcholinesterase (AChE) and silver stain; and 3) their myosin heavy chain (MHC) expression in PC muscle fibers by use of immunocytochemical and immunoblotting techniques. In addition, the specialized nature of the 2 PC layers was also studied in developmental (newborn, neonate, and senescent humans), pathological (adult humans with idiopathic Parkinson's disease IPD), and comparative (nonhuman primate adult macaque monkey) specimens.
Results:
When nerves IX and X were traced from their cranial roots to their intramuscular termination in Sihler's-stained specimens, it was seen that nerve IX supplied the SIL, whereas branches of nerve X innervated the FOL in the adult human PCs. Use of AChE and silver stain confirmed that nerve IX branches supplying the SIL contained motor axons and innervated motor end plates. In addition to distinct motor innervation, the SIL contained muscle fibers expressing slow-tonic and α-cardiac MHC isoforms, whereas the FOL contained muscle fibers expressing developmental MHC isoforms. In contrast, the FOL became obscured in the elderly and in the adult humans with IPD because of an increased proportion of slow muscle fibers. Notably, distinct muscle fiber layers were not found in the human newborn and nonhuman primate (monkey), but were identified in the 2-year-old human.
Conclusions:
Human PCs appear to be organized into functional fiber layers, as indicated by distinct motor innervation and specialized muscle fibers. The SIL appears to be a specialized layer unique to normal humans. The presence of the highly specialized slow-tonic and α-cardiac MHC isoforms, together with their absence in human newborns and nonhuman primates, suggests that the specialization of the SIL may be related to speech and respiration. This specialization may reflect the sustained contraction needed in humans to maintain stiffness of the pharyngeal walls during respiration and to shape the walls for speech articulation. In contrast, the FOL is adapted for rapid movement as seen during swallowing. Senescent humans and patients with IPD are known to be susceptible to dysphagia, and this susceptibility may be related to the observed shift in muscle fiber content.
Bilateral vocal fold paralysis (BVCP) is a life threatening condition and appears to be a good candidate for therapy using functional electrical stimulation (FES). Developing a working FES system has ...been technically difficult due to the inaccessible location and small size of the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle. A naturally-occurring disease in horses shares many functional and etiological features with BVCP. In this study, the feasibility of FES for equine vocal fold paralysis was explored by testing arytenoid abduction evoked by electrical stimulation of the PCA muscle. Rheobase and chronaxie were determined for innervated PCA muscle. We then tested the hypothesis that direct muscle stimulation can maintain airway patency during strenuous exercise in horses with induced transient conduction block of the laryngeal motor nerve. Six adult horses were instrumented with a single bipolar intra-muscular electrode in the left PCA muscle. Rheobase and chronaxie were within the normal range for innervated muscle at 0.55±0.38 v and 0.38±0.19 ms respectively. Intramuscular stimulation of the PCA muscle significantly improved arytenoid abduction at all levels of exercise intensity and there was no significant difference between the level of abduction achieved with stimulation and control values under moderate loads. The equine larynx may provide a useful model for the study of bilateral fold paralysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cricopharyngeus (CP) muscle is a major component of the upper sphincter of the esophagus. Its physiology is complex; a variety of reflexes maintain CP sustained contraction except during ...swallowing, when it relaxes to allow a food bolus to pass into the esophagus. In order to understand CP function, we previously studied the normal adult human CP and found that it has an unusual layered structure, with a slow inner and fast outer layer. In addition, a majority of its muscle fibers express unusual myosin heavy chain (MHC) isoforms (slow‐tonic, α‐cardiac, neonatal, and embryonic) as well as the major MHC isoforms (types I, IIa, and IIx). In this study, autopsied adult human CP muscles were studied with immunocytochemical techniques to determine the patterns of MHC coexpression in CP muscle fibers. The results show that CP fibers were hybrids expressing from two to six MHC isoforms. Ten different combinations of MHC isoforms were identified in CP fibers, with the most common (54%) containing three MHC isoforms. The variety of hybrid CP fiber types suggests that the CP is capable of a wide range of contraction characteristics. Determination of MHC expression patterns of the CP muscle fibers is critical for evaluating the contractile properties of the sphincter. Muscle Nerve, 2007
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