Ira Sanders

Quantifying the spread of botulinum toxin through muscle fascia

Botulinum toxin was recently approved for treating several head and neck dystonias. Paralysis of neighboring muscles is the major complication of its use. Spread of toxin from the injected muscle has been suggested as an etiology. This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis.

Neuromuscular organization of the canine tongue

The tongue manipulates food while chewing and swallowing, dilates the airway during inspiration, and shapes the sounds of speech in humans. While performing these functions the tongue morphs through many complex shapes. At present it is not known how the muscles of the tongue perform these complex shape changes. The difficulty in understanding tongue biomechanics is partly due to gaps in our knowledge regarding the complex neuromuscular anatomy of the tongue. In this study the motor and sensory nerve anatomy of four canine tongues was studied with Sihlers stain, a technique that renders most of the tongue tissue translucent while counterstaining nerves. An additional tongue specimen was serially sectioned to provide a reference for the muscle structure of the tongue.

Reanimation of the Paralyzed Human Larynx With an Implantable Electrical Stimulation Device

Objectives/Hypothesis Electrical stimulation of the posterior cricoarytenoid muscle, when paced with inspiration, offers a physiological approach to restore ventilation in bilateral laryngeal paralysis without any of the disadvantages associated with conventional treatment.

Sensory nerve supply of the human oro- and laryngopharynx: a preliminary study.

To date, the details of human sensory innervation to the pharynx and upper airway have not been demonstrated. In this study, a single human oro‐ and laryngopharynx obtained from autopsy was processed with a whole‐mount nerve staining technique, Sihlers stain, to determine its entire sensory nerve supply. The Sihlers stain rendered all mucosa and soft tissue translucent while counterstaining nerves. The stained specimen was then dissected and the nerves were traced from their origins to the terminal branches. It was found that the sensory innervation of the human pharynx is organized into discrete primary branches that innervate specific areas, although these areas are often connected by small neural anastomoses. The density of innervation varied, with some areas receiving almost no identifiable nerve supply (e.g., posterior wall of the hypopharynx) and certain areas contained much higher density of sensory nerves: the posterior tonsillar pillars; the laryngeal surface of the epiglottis; and the postcricoid and arytenoid regions. The posterior tonsillar pillar was innervated by a dense plexus formed by the pharyngeal branches of the IX and X nerves. The epiglottis was densely innervated by the internal superior laryngeal nerve (ISLN) and IX nerve. Finally, the arytenoid and postcricoid regions were innervated by the ISLN. The postcricoid region had higher density of innervation than the arytenoid area. The use of the Sihlers stain allowed the entire sensory nerve supply of the pharyngeal areas in a human to be demonstrated for the first time. The areas of dense sensory innervation are the same areas that are known to be the most sensitive for triggering reflex swallowing or glottic protection. The data would be useful for further understanding swallowing reflex and guiding sensory reinnervation of the pharynx to treat neurogenic dysphagia and aspiration disorders. Anat Rec 258:406–420, 2000.

Anatomy of the human internal superior laryngeal nerve.

The mucosa of the larynx contains one of the most dense concentrations of sensory receptors in the human body. This sensitivity is used for reflexes that protect the lungs, and even momentary loss of this function is followed rapidly by life‐threatening pneumonia. The internal superior laryngeal nerve (ISLN) supplies the innervation to this area, and, to date, the distribution and branching pattern of this nerve is unknown.

The innervation of the human posterior cricoarytenoid muscle: Evidence for at least two neuromuscular compartments

Recent work has demonstrated that the dog posterior cricoarytenoid (PCA) muscle is composed of three neuromuscular compartments: a vertical, an oblique, and a horizontal. In this study, the human PCA muscle was examined for evidence of neural compartments. Fifteen human PCA muscles were processed by Sihlers stain, which renders the muscle translucent while counterstaining the nerve supply. The results clearly show that in all specimens the nerve supply of the human PCA muscle is separated into at least two main branches: one supplies the horizontal compartment and a second further subdivides to innervate both the vertical and oblique compartments. In 10 of the specimens, these nerve branches arose as separate branches from the recurrent laryngeal nerve. In all specimens, the nerve branch to the horizontal compartment was either combined or connected with the nerve branch to the interarytenoid muscle. The results suggest that the different compartments of the PCA muscle have distinct functions. In addition, the strong connections with the interarytenoid nerve complicate reinnervation procedures to reanimate a paralyzed or transplanted larynx.

The innervation of the human upper esophageal sphincter

The neuroanatomy and physiology of the human upper esophageal sphincter (UES) has long been controversial. As a result, there has been little progress in diagnosing and treating dysphagias involving this area. In this study, three specimens of the UES obtained from human autopsies were examined by Sihlers stain. This stain clears soft tissue while counterstaining the nerves, thereby allowing nerve supply to each muscle of the UES to be demonstrated. It was found that the nerve supply to each component of the UES is substantially different. The inferior pharyngeal constrictor (IPC) is supplied by a dense linear plexus which is about 1.0–1.5 cm wide and 10 cm long and located about 1.5 cm lateral to the attachment of the IPC on the thyroid lamina. The cricopharyngeal (CP) muscle receives its innervation from below via the recurrent laryngeal nerve (RLN) and from above via the pharyngeal plexus. Neural connections between the RLN and the pharyngeal plexus were observed. Finally, the upper esophagus (UE) is innervated by the RLN. The innervation pattern of each component of the UES suggests functional differences between these muscles. These observations help clarify the innervation of the UES. Accurate knowledge of the neuroanatomy of the UES is necessary for advances in diagnosis and treatment of pharyngeal dysphagia.

Slow Tonic Muscle Fibers in the Thyroarytenoid Muscles of Human Vocal Folds; A Possible Specialization for Speech

Most of the sounds of human speech are produced by vibration of the vocal folds, yet the biomechanics and control of these vibrations are poorly understood. In this study the muscle within the vocal fold, the thyroarytenoid muscle (TA), was examined for the presence and distribution of slow tonic muscle fibers (STF), a rare muscle fiber type with unique contraction properties. Nine human TAs were frozen and serially sectioned in the frontal plane. The presence and distribution pattern of STF in each TA were examined by immunofluorescence microscopy using the monoclonal antibodies (mAb) ALD‐19 and ALD‐58 which react with the slow tonic myosin heavy chain (MyHC) isoform. In addition, TA muscle samples from adjacent frozen sections were also examined for slow tonic MyHC isoform by electrophoretic immunoblotting. STF were detected in all nine TAs and the presence of slow tonic MyHC isoform was confirmed in the immunoblots. The STF were distributed predominantly in the medial aspect of the TA, a distinct muscle compartment called the vocalis which is the vibrating part of the vocal fold. STF do not contract with a twitch like most muscle fibers, instead, their contractions are prolonged, stable, precisely controlled, and fatigue resistant. The human voice is characterized by a stable sound with a wide frequency spectrum that can be precisely modulated and the STF may contribute to this ability. At present, the evidence suggests that STF are not presented in the vocal folds of other mammals (including other primates), therefore STF may be a unique human specialization for speech. Anat Rec 256:146–157, 1999.

Neuromuscular specializations of the pharyngeal dilator muscles: II. Compartmentalization of the canine genioglossus muscle.

The genioglossus (GG) muscle is divided into horizontal and oblique compartments that are the main protrusor and depressor muscles of the tongue, respectively. In humans the GG plays an important role in speech articulation, swallowing, and inspiratory dilation of the pharynx. At present, little is known about the neuromuscular specializations of the GG in any mammal. This study examined the specializations of these compartments in the canine tongue using a variety of anatomical and histochemical techniques. Six canine GG muscles were sectioned and stained for myofibrillar ATPase to study muscle fiber types; five whole‐mount GG muscles were stained for acetylcholinesterase (AChE) to study the distribution of motor endplates; and eight whole mount GG muscles were processed with Sihlers stain to study the entire nerve supply pattern. In addition, the arrangement of muscle fibers of the GG within the tongue was also determined (N = 3). The most notable difference between the compartments of the GG was their proportions of fast and slow twitch muscle fibers: the horizontal compartment contained 64% slow twitch muscle fibers compared to 41% in the oblique compartment. In addition, although the oblique compartment appeared to be grossly homogeneous, it could be divided into thirds by significant differences in the percentages of slow twitch fibers: posterior (23%), middle (15%), and anterior (56%; P < 0.05). The muscle fibers of the oblique GG within the tongue were found to be divided into medial and lateral layers that run vertically and transversely, respectively. The nerve supply to each third of the oblique GG formed a plexus with the anterior third being the densest. The innervation pattern of the oblique GG was also notable as terminal nerve branches coursing parallel to the muscle fascicles gave off perpendicular secondary branches along each motor endplate band. These secondary nerve branches connected the primary nerves and formed a regularly spaced grid throughout the compartment. Evidently, the two compartments of the GG exhibited different anatomical specializations. The horizontal had a slow muscle fiber profile and simple innervation pattern; these qualities are possibly related to its single force vector and respiratory related activity. The oblique compartment had a relatively fast muscle fiber profile with evidence for three separate functional subdivisions. The most anterior part was noticeably different, and was presumably specialized for fine motor control of the tip of the tongue. The vertically oriented fibers of the oblique GG within the tongue body may function as a midline depressor of the tongue, whereas its transversely oriented fibers could play a role in narrowing the tongue during other motor tasks. Anat Rec 260:308–325, 2000.

The intramuscular innervation of the human interarytenoid muscle

The nerve supply of the human interarytenoid (IA) muscle has been controversial for more than a century. In this study the contribution of the recurrent and superior laryngeal nerves to the IA was investigated in 10 adult human larynges. The larynges were obtained from autopsies and processed with the modified Sihlers technique which clears soft tissue while staining nerve. The IA muscles were dissected off the specimens and transilluminated to demonstrate their nerve supply. The results demonstrated that all 10 IA muscles were bilaterally innervated by both recurrent laryngeal nerves (RLNs) as well as branches of both superior laryngeal nerves (SLNs). These nerves combined within the IA muscles to form a dense anastomotic plexus which was highly variable between specimens. The exact nature of the internal SLN neurons, whether motor or sensory, their innervation targets, or their function, were not discernible. Additional anatomic findings were the presence of large neural communications directly between the SLN and RLN, and smaller neural connections from side to side. All of these results disagree with currently accepted descriptions of laryngeal neuroanatomy.