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.
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
Altered Pharyngeal Muscles in Parkinson Disease Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming ...
Journal of neuropathology and experimental neurology,
2012-June, 2012-Jun, 20120601, Letnik:
71, Številka:
6
Journal Article
Recenzirano
ABSTRACTDysphagia (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.
Because currently existing reinnervation methods result in poor functional recovery, there is a great need to develop new treatment strategies.
To investigate the efficacy of our recently developed ...nerve-muscle-endplate band grafting (NMEG) technique for muscle reinnervation.
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.
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).
The NMEG technique resulted in successful muscle reinnervation and functional recovery. This technique holds promise in the treatment of muscle paralysis.
The functional upper esophageal sphincter (UES) is composed of the cricopharyngeus muscle (CP), the most inferior part of the inferior pharyngeal constrictor (iIPC), and the upper esophagus (UE). ...This sphincter is collapsed and exhibits sustained muscle activity in the resting state; it only relaxes and opens during swallowing, vomiting, and belching. The tonic contractile properties of the UES suggest that the skeletal muscle fibers in this sphincter differ from those in the limb and trunk muscles. In this study, myosin heavy chain (MHC) composition in the adult human UES muscles obtained from autopsies was investigated using immunocytochemical and immunoblotting techniques. Results showed that the adult human UES muscle fibers expressed unusual MHC isoforms such as slow-tonic (MHC-ton), α-cardiac (MHC-α), neonatal (MHC-neo), and embryonic (MHC-emb), which coexisted with the major MHCs (i.e., MHCI, IIa, and IIx). MHC-ton and MHC-α were coexpressed predominantly with slow-type I MHC isoform, whereas MHC-neo and MHC-emb coexisted mainly with fast-type IIa MHC. A slow inner layer (SIL) and a fast outer layer (FOL) in the iIPC and CP were identified immunocytochemically. MHC-ton- and MHC-α-containing fibers were concentrated mainly in the SIL, whereas MHC-neo- and MHC-emb-containing fibers were distributed primarily to the FOL. Identification of the specialized muscle fibers and their distribution patterns in the adult human UES is valuable for a better understanding of the physiological and pathophysiological behaviors of the sphincter.
Parkinson’s disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor symptoms and central nervous system pathology. As current drug therapies can often stabilize these ...cardinal motor symptoms attention has shifted to the other motor and non-motor symptoms of PD which are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug resistant symptom as 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. In this study, we examined the cervical vagal (X) nerve, pharyngeal branch of the X nerve (Ph-X), and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, 10 subjects with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. α-Synuclein aggregates were revealed in the X nerve and Ph-X and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all the PD subjects and in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathological process of PD. Notably, PD subjects with dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves as compared with those without dysphagia. Motor involvement of the pharynx in PD appears to be one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.
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