This is a review article based on 10 important papers on laryngeal paralysis published during the period of 1880 to 1897. Of the 10 papers, three were written by Rosenbach, four by Semon, one by Krause, one by Wagner and one by Grossmann. These papers discussed some issues related to “the law of Semon and Rosenbach” The present author emphasizes the followings :
1 : Either of Rosenbach or Semon did not propose the so-called “law” which described 3 stages in the course of laryngeal paralysis. They only emphasized the existence of early and exclusive occurrence of “abductor paralysis” which was characterized by the paralysed vocal cord fixed in the median position in progressive organic recurrent nerve paralysis.
2 :A contracture of the adductor muscles (in stage II of the “law”) was proposed by Krause in opposition to the existence of “abductor paralysis.” This hypothesis was not accepted either by Rosenbach or Semon.
3 : The terminology related to the position of the vocal cord was not consistent between Semon and Grossmann.
4 : Apart from validity of their conclusions, all of these clinical and experimental works conducted approximately 100 years ago should be highly appreciated as great contributions to the development of modern neurolaryngology in its early stage.

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The localizations of the neurons for the motor, sensory and autonomic nerve fibers supplying the larynx of the cats were described based on a review of literature and our current investigations. The motoneurons for the cricothyroid muscle were located in the rostral half of the nucleus ambiguus. Those for the other intrinsic laryngeal muscles were situated in the caudal half of the same nucleus. Distinct localizations of the neurons for each muscle in the rostrocaudal direction and in the transverse plane were determined. Localizations of sensory neurons for each branch of the superior and inferior laryngeal nerves in the nodose ganglion were determined. In the nodose ganglion, the sensory neurons innervating the superior laryngeal nerve were localized in the rostral part and those supplying the inferior laryngeal nerve were present in the middle part. The larynx received postganglionic sympathetic nerve fibers mainly from the superior and middle cervical ganglia and partly from the stellate ganglion. The laryngeal sympathetic postganglionic neurons were located in the lateral part of the superior cervical ganglion, in the medial part of the middle cervical ganglion and in the middle part of the stellate ganglion. The localization of the laryngeal parasympathetic neurons has not clearly been determined yet.

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The autonomic innervation of the larynx has been studied by fluorescence histochemistry and immunohistochemistry. In the laryngeal sympathetic nervous system, many problems has been solved using fluorescence histochemistry (Falck-Hillarp method) and immunohistochemistry for tyrosine hydroxylase. There are still many problems to be studied for the laryngeal parasympathetic nervous system. Advantages and disadvantages of the morphological techniques that have been used in this research field including ours were discussed in detail. Sympathetic nerve fibers were identified in the intrinsic laryngeal muscles and mucosa. In the intrinsic muscles, sympathetic nerve fiber running along the muscle fiber was observed. This finding suggests the existence of the direct sympathetic innervation of the intrinsic muscles. Using 5-hydroxydopamine technique, sympathetic innervation of the laryngeal gland was electron-microscopically clarified. Laryngeal nerves were also clarified to contain many sympathetic nerve fibers and the existence of the perivascular sympathetic innervation of the larynx was considered to be negative. CGRP immunore-activity in the laryngeal autonomic nervous system was also discussed.

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The larynx performs fine adjustments as the eye balls do. Motions of the vocal folds are, therefore, supposed to be regulated by the afferent and efferent innervation more precisely than many other skeletal muscles. The purposes of this paper were to investigate morphological features of the laryngeal muscles, muscle spindles and sensory nerve endings in different species which might explain the ability of fine laryngeal adjustments. Histochemical studies of muscle fibers and morphometrical analyses of subneural apparatus at the neuromuscular junctions of the canine larynges showed that the intrinsic laryngeal muscles consisted of three types of muscle fibers : type 1, 2 A and 2 C. Each type had a specific subneural apparatus. The postnatal differentiation of the muscle fibers of the larynx of rats was completed prior to the development of the subneural apparatus. The muscle spindles in the intrinsic muscles of human larynges contained rich collagenous fibrils in a narrow periaxial space. The density of muscle spindles was low. The same morphological features of the muscle spindle were also observed in monkeys. The sensory nerve endings on the intrafusal fibers were not of the annulo-spiral type, which had been generally observed in mammalian muscle spindles, but of a varicose type. The sensory nerve endings on the laryngeal muscles were richer more multiform in human beings than in monkeys. It is considered that a few muscle spindles regulate laryngeal motions in cooperation with rich sensory nerve endings

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The distributions of the sensory nerve fibers in the larynx of cats was investigated with the use of the wheat germ agglutinin-horseradish peroxidase (WGA-HRP) technique (44 cats) and the immunoreactive histochemistry technique for calcitonine gene-related peptide (CGRP) (10 cats). In addition, WGA-HRP labeled fibers and CGRP positive fibers were identified alternately in serial sections of eight larynges. The results were as follows (1) WGA-HRP labeled fibers innervated the ipsilateral supraglottic region and the bilateral subglottic areas. (2) They were much more abundant in the laryngeal aspect of the epiglottis, the aryepiglottic fold and the arytenoid eminence than in the other parts of the larynx. (3) CGRP positive fibers were observed in the entire laryngeal mucosa except for that of the vocal fold. They were identified also around the blood vessels and glands and in the motor end plates of the muscles. (4) Their density was greater at the laryngeal aspect of the epiglottis, aryepiglottic fold, arytenoid eminence and posterior glottis than at the other portions of the larynx. (5) WGA-HRP labeled fibers and CGRP positive fibers were the same fibers in the aryepiglottic fold, arytenoid eminence and posterior glottis, indicating that they were sensory fibers.

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Morphological changes of the neuromuscular junctions were studied ultrastructurally in the denervated and reinnervated posterior cricoarytenoid (PCA) muscle of the cat. Acetylcholinesterase (AchE) activity and acetylcholine receptors (AchR) were also investigated histochemically. The left recurrent laryngeal nerve was transected at the level of the second tracheal ring and neurorraphy was done immediately after the transection. AchE activity was demonstrated by Karnovsky and Lewis method whereas AchRs were identified by snake neurotoxin (α-bungarotoxin or erabutoxin b) which had a curare-like action. Two days after denervation nerve terminals at the neuromuscular junctions almost disapeared. Three to six weeks after denervation some primary synaptic clefts were narrowed and others were flattened while the secondary synaptic clefts were relatively preserved. The intensity of AchE activity at the neuromuscular junctions was almost same as that of the nonaffected side six weeks after denervation. Fourteen weeks after denervation AchE activity decreased. The regenerating axons appeared at the neuromuscular junctions three weeks after neurorrhaphy. An evoked electromyogram was observed at this stage. Nerve terminals were small and the secondary synaptic clefts were distorted until 22 weeks after neurorrhaphy. AchRs were detected at the neuromuscular junctions of the normal PCA muscle by snake neurotoxins. Ultrastructurally AchRs were localized at the postsynaptic membrane of the neuromuscular junctions. We were also able to demonstrate ultrastructurally calcitonin gene-related peptid (CGRP) immunoreactivity in the nerve terminals of the PCA muscle. These results strongly suggest that CGRP is involved in the regulation of the contractile function of the intrinsic laryngal muscle. The motor nerve innervation of the larynx and the neuromuscular junctions in the intrinsic laryngeal muscles

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Nerve terminals of unknown origin at the chronically denervated neuromuscular junctions of the cat intrinsic laryngeal muscles were studied. Light-microscopically, TH (tyrosine hydroxylase) fibers approached the acetylcholinestelase-stained sites 5 weeks after denervation. Electron-microscopically, nerve varicosities labeled by 5-OHDA (5-hydroxydopamine) were observed in the Schwann tubes (the Böngner's bands). Nine to 30 weeks after denervation nerve terminals were found at the original neuromuscular junctions in all nine experimental animals. A cat in which the recurrent laryngeal nerve was sectioned 20 weeks before and the ipsilateral vagus nerve was transected three weeks before demonstrated nerve terminals at the neuromuscular junction. This implied that the regenerated nerve terminals were not from the recurrent laryngeal nerve.
Electromyographically, fibrillation-like activities were recognized in seven of ten animals. The results indicated that autonomic nerve fibers around the blood vessels entered the Schwann tubes and ultimately made synaptic contact with the neuromuscular junctions.

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Two handred and eighty two cases of laryngeal carcinoma treated for the past 15 years in the University of Tokyo were reviewed. During the first five years a combination of repeated mass-reduction surgeries and small-dose radiotherapy was employed. The 5-year survival rate was 53% and the 5-year local no-recurrence rate of Tla glottic carcinomas was 59%. During the following four years a radical radiotherapy (50 Gy in total) was applied for all cases. Salvage operation was conducted for failures. The 5-year survival rate was 58% and the 5-year local no-recurrence rate of Tla glottic carcinoma was 50%. During the latest six years a radical radiotherapy (60 Gy or more in total) was indicated to early cases and radical surgical therapy was conducted for advanced cases. The 5-year survival rate was 85% and the 5-year local no-recurrence rate of Tla glottic carcinomas treated with radiotherapy was 83 %. When the radical radiotherapy was combined with a pre-radiation mass-reduction procedure, 95% of Tla glottic carcinoma was controlled. Laser in useful to the mass reduction procedure.

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It is commonly accepted that radiotherapy is a first choice for treatment of T1 glottic cancer. However, side effects caused by irradiation are sometimes troublesome to a patient and to a physician. Among side effects, oncogenic problem and late radiation change are most undesirable and may become fatal. Hence, we avoid radiation therapy especially for younger aged patients. We prefer surgical therapy to radiotherapy for such a case. In our clinic, laser therapy has been employed. A laser beam is introduced through an operation microscope and a lesion can be microscopically vaporized. In this study, a survey of 40 patients with T1 glottic cancer submitted to laser surgery was reviewed. From those patients 25 were T1a and 15 were T1b. From our experience, laser vaporization is recomendable for T1 glottic cancer in younger aged patients. However, in order to obtain cure rate comparable to radiation therapy, the indication must be correctly designated.

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Of the 850 patients who visited our division with previously untreated carcinoma of the larynx between 1962 and 1988, 68 received partial laryngectomy as the first treament. Of these 68 cases, 50 patients with more than five-year follow-up were studied relative to the local control, cervical metastases, and survival. These patients consisted of 34 cases who underwent vertical partial laryngectomy for glottic carcinoma and 16 cases who received horizontal partial laryngectomy for supraglottic carcinoma. In the vertical partial laryngectomy group, four patients developed local recurrence between three to 36 months after the first surgery. All these cases were salvaged with total laryngectomy. Cervical metastases were observed in four cases between two to 11 months after laryngectomy and were successfully treated with neck dissection in all cases. The five-year crude survival rate was 88.2% (30/34). All deaths resulted from causes other than laryngeal carcinoma. For the 16 patients with horizontal partial laryngectomy, the five-year crude survival rate was 81% (13/16). No local recurrece was observed in this group. Three cases developed cervical metastases between two and ten months after laryngectomy.

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For the past ten years, the choice of treatment modalities for laryngeal carcinoma has depended not only on the T-stage but also on the cancer characteristics including the growing type, anatomical location and extension, and depth of invasion. A total or an extended total laryngectomy has been indicated for the following lesions; 1) glottic T2 invading the subglottic region (especially that of anterior type), T3 and T4, 2) supraglottic T2 invading the ventricle, the vocal cord and/or the anterior commissure, T3 and T4, 3) transglottic carcinomas and 4) subglottic carcinomas. To prevent local recurrence in case of (extended) total laryngectomy, it is important to understand the feature of tumor extension outside of the larynx and confirm the extent of the lesion directly by opening the larynx at the midline of the cricoid lamina.
A total of 735 patients were treated at our hospital between 1979 and 1988. Forty-six percent of the patients received radiation (60-70 Gy) whereas the remaining patients underwent laryngectomy (partial laryngectomy in 4%, total laryngectomy in 50%). Only two local recurrences were observed in the totally laryngectomized patients. The overall 5-year cumulative survival rate was 72.4 % (cause specific 87.3%, minimum follow up interval : 5 years, n=319). The cumulative survival rates for stage III and IV lesions were 62.6%, and 55.6% for glottic, 62.5% and 51.2% for supraglottic, and 65.5% and 35.9% for transglottic lesions, respectively.

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Seventy-eight cases of laryngeal carcinoma with regional lymphnode metastasis treated during the period from 1973 to 1984 in the Cancer Institute Hospital were reviewed.
Of the 78, 59 were supraglottic and 19 were glottic carcinomas. In 51 of the 59 supraglottic cases, radiotherapy was first employed for the metastatic lymphnodes. A complete remission of the node metastasis was obtained only in 17 cases. The primary tumors located in the suprahyoid epiglottis and the aryepiglottic fold were relatively radiosensitive whereas those situated in the infrahyoid epiglottis were radio-resistant. All cases of glottic carcinoma having positive regional nodes resisted radiotherapy. The results indicate that surgery is the most reliable treatment modality for laryngeal carcinoma with regional lymphnode metastasis.

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Seventy-nine patients with carcinoma of the larynx were studied for staging of the disease. Three procedures were employed for staging : physical examinations, laryngography and CT scan. Of the 79, 57 patients underwent an operation and their excised specimens were histologically studied. The histological findings were compared with the preoperative staging. The accuracy of T staging based on physical examinations was 51.6%, that by means of laryngograms was 57.7%, and that by CT was 89.5%. CT was particularly useful to accurately diagnose T 4 lesions. Fixation of the vocal cord is a criterian for the diagnosis of T 3 stage. For the staging by CT, obliteration of the paraglottic space and dislocation of the arytenoid cartilage were employed as criteria for T 3 lesions. Fifty-five percent of the patients showed the both CT findings. In the cases of glottic and subglottic carcinoma, vocal cord fixation was diagnosed on the basis of obliteration of the paraglottic space alone, while, in the cases of supraglottic and epilaryngeal carcinoma, fixation was diagnosed on the basis of dislocation of the arytenoid cartilage alone. Preepiglottic space invasions seen on CT were classified into ulcer type and infiltration type. They were correctly diagnosed by CT. CT was also useful for diagnosis of extralaryngeal involvements including oropharyngeal and hypopharyngeal involvements. Only 9.1 % of cases of cartilage destruction were detected by palpation, while 90.9% of cartilage involvements were diagnosed by CT.

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The purpose of this study is to compare mucosal blood flow with mucosal blood volume in human larynx. Subjects were two men who had vocal fold polyps. In laryngomicrosurgery under general anesthesia we measured hemoglobin concentration (IHb) by using spectrophotometric analyzer and measured mucosal blood flow (BF) by using laser speckle flow meter. In normal mucosa of the vocal fold, the mean value of IHb was 25.5 and the mean value of BF was 4.6, whereas in that of the ventricular fold, the mean value of IHb was 72.3 and the mean value of BF was 2.4. The IHb value was lower in the vocal fold than in the ventricular fold, while BF was higher in the vocal fold than in the ventricular fold. In the region of telangiectatic polyp of the vocal fold, IHb was 88 and BF was 4.1. IHb was 17 and BF was 2.0 in the region of gelatinous polyp. Both IHb and BF had higher value in the telangiectatic polyp than in the gelatinous polyp. It was considered reasonable for vocal fold vibration that blood flow was high and blood volume was low.

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The intrinsic laryngeal muscles (ILMs) play an important role in hightly specialized laryngeal functions. Morphological analysis was made to investigate histochemical properties compared with non-laryngeal skeletal muscles and to see if whether there were any reflections of physiological specialization in the structure of ILMs.
Forty-five ILMs from ten middle-aged male cadavers were removed and examined by using en-zyme histochemical methods. According to enzyme reactivities (mainly myosin ATPase), ILM fibers were classified into two types (type 1 and type 2 fibers in the skeletal muscle classification). Type 2 c fibers were identified, but type 2 fibers' subdivisions were not clear. In muscle fiber type composition, the thyroarytenoid muscle had the highest proportion of type 2 fibers, the posterior cricoarytenoid muscle had the highest proportion of type 1 fibers, and the other muscles had intermediate values. ILM fibers had more variability in size than skeletal muscles. ILM fiber size had difference among subjects, but not in the individual.
.These findings correspond to the development and speciality of physiological activity in human larynges.

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