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• Laryngomalacia has been described in the medical literature for over 100 years. During this time many different names have been used for the same condition. There have been numerous discussions of symptoms, cause, pathogenesis, relationships to other conditions, hereditary factors, and treatment. The purpose of this study is to historically review the literature, clarify terminology, and describe the clinical aspects of the disease. We also summarize and make conclusions regarding cause, pathogenesis, genetic and disease relationships, prognosis, and treatment. Finally, we present a case report of severe laryngomalacia and describe a surgical technique used to treat it.(Arch Otolaryngol 1984;110:546-551)

The larynges of 33 premature and term neonates who were intubated for the management of respiratory difficulties were studied. In addition to the changes commonly associated with endotracheal intubation (epithelial erosion, ulceration, squamous metaplasia, edema, inflammation, and perichondritis), the intrinsic laryngeal muscles were damaged in 26 of the 33 cases and, in 4 cases, oriented striated skeletal muscle regeneration was found. The active synthetic nature of the myotube formations in the latter cases was confirmed by the demonstration of concentrated vimentin intermediate-filament immunoreactivity. In view of the frequency of neonatal intubation, the probability of muscle damage, and the generally infrequent critical sequelae of this procedure, regeneration of the intrinsic muscles may help to explain the excellent functional recovery of the neonatal larynx. This phenomenon also occurs in the postintubated adult larynx and is therefore not limited to the neonatal period. In addition, these findings support the fact that skeletal muscle regeneration occurs in nonmyopathic human skeletal muscles following injury, as has been shown in experimental animal models.

The notochordal-basichondrocranium relationships have been investigated in cranioschisis occulta with encephalocoele (CSO-EN) and in cranioschisis aperta with exencephaly (CSA-EX) which represent, respectively, a minimal and a severe form of experimentally induced axial skeletal (dysraphic) disorders. Although apparently different, these two malformations are considered to represent different degrees of the same basic abnormality (mesodermal insufficiency) which affects the paraxial mesoderm early in embryonic development. Three different experimental models (vitamin A, sodium arsenate and clofibrate) have been used to induce these disorders. The administration of a single dose of each of these three agents during the primitive streak stage of embryonic development in the golden hamster resulted in a variety of axial skeletal (dysraphic) disorders, including the two mentioned above. Regardless of the teratogen used, the basichondrocranium in both CSOEN and in CSA-EX is shorter than normal and slightly lordotic to the vertebral axis. Theshortness of the basichondrocranium in these two disorders is caused mainly by the shortness of the basioccipital. Both the shortness of the base of the skull and its lordotic or elevated position in relation to the vertebral axis are more pronounced in CSA-EX than in CSO-EN. The intracranial course of the notochord in these two axial disorders is considered to be within normal limits. However, the notochord itself is shorter than normal and depicts terminal folds which are considered to be the result of crowding. Both the shortness of the notochord and its terminal folding are also more pronounced in CSA-EXthan in CSO-EN. The sole difference encountered betwesn the abnormal basichondrocraniumsof these two disorders is in the severity of their common malformations (quantitative differences), but not in their type or quality. These findings give further support to the idea that these two principal developmental variations encountered are those pertaining to: (o) the overall intracranial course of the notochord; (b) the specific relationships of the notochord to the basioccipital and the basisphenoid; and (c) the notochordal relationship (or the lack of it) to the pharyngeal epithelium, and hence, its close association with the development of the bursa pharyngea in some mammals (e.g. man). The segmental nature of the notochordal enlargements of the basioccipital, found in the human and hamster embryos studied here, as well as their relation to the somitic origin of thisbone, have been analyzed and discussed. The present study has also emphasized the need to understand the developmental variations of the notochordal-basichondrocranium relationships among mammalian embryos for the study and interpretation of both clinically, as well as experimentally, induced malformations of the base of the skull. axial skeletal disorders are not different types of malformations, but different degrees of the same basic abnormality. The CNS involvement (encephalocoele or exencephaly) is also considered to be secondary to the paraxial mesodermal insufficiency. It is believed, and supported by the present findings, that the normal development of the paraxial mesoderm is needed for the normal process of formation and subsequent elevation and closure of the neural folds. A primary paraxial insufficiency could result in the partial (encephalocoele) or the complete (exencephaly) failure of closure of the neural folds which characterizes this type of axial skeletal (dysraphic) disorder. In addition, the normal notochordal-basichondrocranium relationships have been investigated in a group of mammalian embryos including man, hamster, mouse, and several others gathered from the literature. The significant developmental variations of the intracranial course of the notochord, and of its relationships to the components of the basichondrocranium, found among different mammals have been emphasized and illustrated. The principal developmental variations encountered are those pertaining to: (a) the overall intracranial course of the notochord; (b) the specific relationships of the notochord to thebasioccipital and the basisphenoid; and (c) the notochordal relationship (or the lack ofit) to the pharyngeal epithelium, and hence, its close association with the development of the bursa pharyngea in some mammals (e.g. man). The segmental nature of the notochordal enlargements of the basioccipital, found in the human and hamster embryos studied here, as well as their relation to the somitic origin of this bone, have been analyzed anddiscussed. The present study has also emphasized the need to understand the developmental variations of thenotochordal-basichondrocranium relationships among mammalian embryos for the study and interpretation of both clinically, as well as experimentally, induced malformations of the base of the skull.

The administration of a single dose (20000 u) of vitamin A by gavage to the pregnant hamster is followed almost immediately by changes in the mesoderm of the embryos. These changes appear 6 h after the administration and after 10 h they have reached their maximum severity. The alterations appear first in the cephalic mesoderm, later in the axial non-segmented mesoderm of the body of the embryo and finally in the somitic mesoderm. They consist of shrinkage of the cell cytoplasm, enlargement of the intercellular spaces (fluid accumulation) and reduction of the mitotic rate of mesodermal cells. These alterations precede the cellular necrosis which appeared later in the somites and is considered a secondary change. An analysis of the embryogenesis of the vitamin A induced skeletal malformation based on the changes described is discussed.

An injury to the myocardium of armadillo embryos induced by thalidomide when administered to their mothers is reported. The injury consists of focal myocardial necrosis of both atria and ventricles. Myocardial necrosis is more severe and extensive in the youngest embryos (CR 3 mm.). The myocardial damage induced by thalidomide can cause fetal death. Cardiac rupture through an area of artrial necrosis and hemopericardium is reported in one embryo. Also, fetal death can occur from heart failure manifested by cardiomegaly, hepatomegaly and visceral congestion. The significance of myocardial necrosis as a possible cause of later congenital cardiac deformities is discussed.

A simple method for the induction of developmental malformation in the golden hamster is presented. The teratogenic agent used consists of a single dose of vitamin A. Correlations between the day of gestation at which the vitamin A is administered and the type and percentage of malformations induced are reported. Young embryos obtained from treated mothers on the 8th day of gestation show somite necrosis within 12 hr. of the administration of vitamin A, reaching its maximum at 24 hr. The somite necrosis is considered to be a basic alteration resulting in an abnormal axial mesoderm which then fails to fulfil its function of lodging and protecting the neural tube. The unprotected and exposed neural tissue secondarily degenerates. Somite necrosis is considered to be the primary defect induced by vitamin A causing developmental malformations such as cranioschisis and sacral rachischisis. When somite necrosis occurs before neural tube closure extensive degeneration of the neural tube follows (e.g. cranioschisis). Somite necrosis occurring after closure of neural tube results in only minimal change in the neural tube (e.g. occult sacral rachischisis). Notochordal alterations (hypertrophy and necrosis) are also found in the young hamster embryo after administration of vitamin A to their mother on the 8th day of gestation.