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C. Carlos, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

Medical Instructor, University of Tennessee College of Medicine

A significant portion of posterior or extensive lesions may also be approached in this manner but may ultimately require an atticotomy or mastoidectomy. In contrast to acquired cholesteatoma, congenital lesions result in minimal inflammatory reactions or adhesions between the matrix and the middle ear mucosa. A clear plane can be easily developed between the cholesteatoma and the surrounding mucosa of the middle ear or ossicles, especially if prior surgeries have not been performed. Evidence of bony erosion in the mastoid on preoperative imaging studies are contraindications to attempted removal via an extended tympanotomy. A speech reception threshold worse than 30 dB has been defined as an indication for surgery. General Considerations Ossicular anomalies may be unilateral or bilateral and may be associated with anomalies of the external ear (atresia), the middle ear (facial nerve, stapedial muscle, tendon, or pyramidal eminence), or with a multiorgan syndrome (Treacher Collins or Goldenhar syndrome) (Table 48­1). Classification Historically, congenital malformations of the ear have been divided into major and minor types with the latter limited to the middle ear alone. Finally, multiple ossicular anomalies with subtle but significant variations have been described (Figure 48­2 and Table 48­3). Children with multisystem syndromes may be at a considerably higher anesthetic risk if there is involvement of the upper airway, heart, lungs, or kidneys. For children in overall good health, the indications, timing, and ideal method of surgical correction remain a source of controversy. The patient should be assessed for a delay in speech acquisition and the presence of cognitive and learning delays. Deferring surgery until at least the age of 5 is associated with a decreased incidence of otitis media, improved patient cooperation, and more sophisticated audiometric testing. Surgery for unilateral disease in the setting of a normal contralateral ear either can be performed at the age of 5 or delayed until the patient is able to participate fully in the decision-making progress. Delaying surgery remains a source of controversy since the beneficial effects of binaural hearing on speech and development are continually being discovered. Finally, amplification with hearing aids, as a transition or an alternative to surgery, should be offered to the patient and family. Approximately 1­2% of patients with congenital conductive hearing loss have isolated middle ear anomalies. In addition to this low incidence, other factors make accurate preoperative diagnosis difficult. With the exception of malleus-incus fusion, hypoplasia of the malleus, and middle ear aplasia, the otoscopic examination is unremarkable. Furthermore, audiometric evaluation demonstrates a similarly moderate-to-severe conductive hearing loss that is fixed over time with most anomalies. These factors mandate a high index of suspicion to ensure both an accurate diagnosis and appropriate management. A general examination of the patient is performed to evaluate the overall health and to search for any findings suggestive of a syndrome. Otoscopic examination of patients with anomalies of the malleus or combined ossicular anomalies may demonstrate loss of the tympanic membrane landmarks. Hypoplasia or aplasia of the malleus results from a failure of embryogenesis between weeks 7 and 25. Given the common pharyngeal arch origin, hypoplasia of the malleus is often associated with hypoplasia of the incus. An ossicular replacement prosthesis can be placed at the time of middle ear exploration in these cases. Fixation of the head of the malleus represents 80% of all isolated congenital anomalies of the malleus (Figure 48­3). Exploration of the temporal bone in these patients reveals bony bridges between the head of the malleus and the lateral epitympanum in 75­80% of cases. The term "malleus bar" has been used when this bridge connects to the posterior tympanic wall. Malleus fixation, in general, is presumed to result from failure of mesenchymal absorption and is correctable by either laser division of the connecting bridge or Table 48­1. This anomaly is thought to result from a failure of the resorption and remodeling that occurs during the final stages of stapes development and accounts for up to 20% of all ossicular anomalies.

A disulfide bond contributes to the stability of the three-dimensional shape of the protein molecule and prevents it from becoming denatured in the extracellular environment. For example, many disulfide bonds are found in proteins such as immunoglobulins that are secreted by cells. Hydrophobic interactions: Amino acids with nonpolar side chains tend to be located in the interior of the polypeptide molecule, where they associate with other hydrophobic amino acids (Figure 2. In contrast, amino acids with polar or charged side chains tend to be located on the surface of the molecule in contact with the polar solvent. Hydrogen bonds: Amino acid side chains containing oxygen- or nitrogen-bound hydrogen, such as in the alcohol groups of serine and threonine, can form hydrogen bonds with electron-rich atoms, such as the oxygen of a carboxyl group or carbonyl group of a peptide bond (Figure 2. Formation of hydrogen bonds between polar groups on the surface of proteins and the aqueous solvent enhances the solubility of the protein. Protein folding Interactions between the side chains of amino acids determine how a long polypeptide chain folds into the intricate three-dimensional shape of the functional protein. Protein folding, which occurs within the cell in seconds to minutes, involves nonrandom, ordered pathways. As a peptide folds, secondary structures form driven by the hydrophobic effect (that is, hydrophobic groups come together as water is released). Additional events stabilize secondary structure and initiate formation of tertiary structure. In the last stage, the peptide achieves its fully folded, native (functional) form characterized by a lowenergy state (Figure 2. Denaturing agents include heat, organic solvents, strong acids or bases, detergents, and ions of heavy metals such as lead. Denaturation may, under ideal conditions, be reversible, such that the protein refolds into its original native structure when the denaturing agent is removed. Role of chaperones in protein folding the information needed for correct protein folding is contained in the primary structure of the polypeptide. However, most proteins when denatured do not resume their native conformations even under favorable environmental conditions. This is because, for many proteins, folding is a facilitated process that requires a specialized group of proteins, referred to as "molecular chaperones," and adenosine triphosphate hydrolysis. The chaperones, also known as "heat shock proteins" (Hsp), interact with a polypeptide at various stages during the folding process. Some chaperones bind hydrophobic regions of an extended polypeptide and are important in keeping the protein unfolded until its synthesis is completed (for example, Hsp70). The partially folded protein enters the cage, binds the central cavity through hydrophobic interactions, folds, and is released (for example, mitochondrial Hsp60). However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. The arrangement of these polypeptide subunits is called the quaternary structure of the protein. Subunits are held together primarily by noncovalent interactions (for example, hydrogen bonds, ionic bonds, and hydrophobic interactions). Subunits may either function independently of each other or may work cooperatively, as in hemoglobin, in which the binding of oxygen to one subunit of the tetramer increases the affinity of the other subunits for oxygen (see p. Isoforms are proteins that perform the same function but have different primary structures. They can arise from different genes or from tissue-specific processing of the product of a single gene. However, this quality control system is not perfect, and intracellular or extracellular aggregates of misfolded proteins can accumulate, particularly as individuals age. Amyloid diseases Misfolding of proteins may occur spontaneously or be caused by a mutation in a particular gene, which then produces an altered protein. In addition, some apparently normal proteins can, after abnormal proteolytic cleavage, take on a unique conformational state that leads to the formation of long, fibrillar protein assemblies consisting of -pleated sheets.

The uvula is also described as normal, long (> 1 cm), thick (> 1 cm), or embedded in the soft palate. The tonsils should be described as being surgically absent or by their size (1, 2, 3, or 4+, respectively, indicating a 0­ 25%, 25­50%, 50­75%, or > 75% lateral narrowing of the oropharynx). Hypopharynx-The hypopharynx can be evaluated by means of nasopharyngoscopy to assess the base of tongue and the lingual tonsils and to look for masses obstructing the supraglottic, glottic, or subglottic larynx. Any abnormalities in appearance, symmetry, and movement of the vocal cords should be noted. Many perform the Mьller maneuver to assess collapse of the retropalatal and retroglossal areas during inspiration against a closed nose and mouth. Images obtained with both modalities can be used to recreate three-dimensional models of the upper airway and have been used to evaluate apneic airway dynamics during respiration. Both modalities, however, are significantly more expensive than the previously mentioned modalities and have a number of contraindications. Subjective tests-Subjective tests permit the patient to evaluate his or her drive to sleep. Multiple sleep latency testing-The multiple sleep latency test is an objective test that evaluates sleep drive and consists of a series of naps occurring at 2-hour intervals repeated every 2 hours. Patients are encouraged to sleep while their physiologic parameters are monitored. Normal sleep latency is 10­20 minutes; however, patients with excessive daytime sleepiness often have sleep latencies of 5 minutes or less. Axial magnetic resonance images acquired at the retropalatal levels in a normal patient (left) and an apneic patient (right) demonstrating (1) increased lateral pharyngeal wall dimensions, (2) decreased retropalatal airway area, and (3) increased lateral pharyngeal fat pads in a representative apneic patient. Despite immediate objective and subjective improvements, no definitive studies establish the duration of regular use necessary to reduce or eliminate long-term sequelae. The more thoroughly tested of the oral appliances are the titratable mandibular repositioning devices. Legal standards and obligations of the physician vary from state to state with regard to the issue of reporting patients at risk or with a history of sleep-related accidents. Patients wearing oral appliances may complain of jaw or temporomandibular joint pain (both of which seem to be lessened by the titratable oral appliances), headaches, and excessive salivation. Weight loss-Overweight patients should be encouraged to lose weight because moderate reductions in weight have been demonstrated to increase upper airway size and improve upper airway function. Coordination of weight loss with a dietitian may improve outcome and in many cases is necessary (eg, in diabetics and the morbidly obese). Lifestyle modifications-Patients should also be informed to avoid sedatives, alcohol, nicotine, and caffeine in the evening because these substances can influence upper airway muscle tone and central mechanisms. Patients are instructed to sleep in the lateral decubitus position rather than the supine position, and a host of techniques have been used to prevent reversion to the supine, such as sewing tennis balls to the backs of shirts and rearranging pillows. Genioglossal advancement can be achieved by performing a limited osteotomy (Figure 40­ 4A) or by creating a rectangular window and sliding the geniohyoid complex anteriorly (Figure 40­4B). The latter procedure may by performed using various sagittal or circular osteotomy devices with custom or prefabricated plating systems. Suspension of the hyoid bone from the mandible has been largely supplanted by approximating the hyoid bone and the thyroid cartilage (Figure 40­5). However, the overall success rate, which includes those dropping out of the protocol, is 77% (observed over an average of 9 months of follow-up). Risks of radiofrequency ablation include pain, bleeding, velopharyngeal insufficiency, palatal fistula, and infection. However, it is not 100% effective in eliminating symptoms and sequelae in all patients, and it is associated with complications such as dysphagia, plugging, tracheal stenosis, and granuloma formation. Decannulation and reversal of tracheostomy usually are uncomplicated and result in the return of symptoms. Complications such as implant extrusion and worsening of symptoms have been reported. More clinical studies need to be performed to draw conclusions regarding the efficacy of palatal implants. Continued postoperative follow-up permits the evaluation of subjective and objective improvement as well as the opportunity to address additional sites of obstruction as necessary. Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement. Modified myotomy in which the hyoid bone is advanced anteriorly and inferiorly and approximated to the thyroid cartilage.

If decompression of the sigmoid sinus is needed for exposure, a mastoidectomy may also be performed. The bone dust created is carefully confined and removed to prevent meningeal irritation. The endolymphatic duct and sac serve as landmarks to the proximity of the posterior semicircular canal and allow preservation of the inner ear and hearing. The facial nerve is normally anterior to the tumor or its position is ascertained with facial nerve monitoring. The primary advantage of the retrosigmoidal approach relative to the translabyrinthine approach is the ability for hearing preservation in properly selected tumors. The combination of intradural drilling leading to meningeal irritation by bone dust and dissection of suboccipital musculature causes nearly 10% of patients to have a persistent, severe, postoperative headache. The extent of cerebellar retraction is minimal in small tumors, but the amount of retraction increases with larger tumors. The surgical control of the facial nerve is adequate in the retrosigmoidal approach, but the exposure of the facial nerve is superior in the translabyrinthine approach. Middle fossa approach-The middle fossa approach provides a hearing-preserving approach to intracanalicular tumors with a < 1. The surgical technique involves an inverted U-shaped incision centered over the ear. The temporal muscle is reflected inferiorly to expose the squamous portion of the temporal bone. A 5 Ч 5 cm temporal craniotomy is performed and is centered over the zygomatic root. The tumor is dissected free of the facial nerve and removed in a medial to lateral direction. Any air cells are sealed and the dural defect is covered with a fat or muscle plug. This exposure allows for the removal of intracanalicular tumors while maintaining hearing preservation. The relative merits of the procedure with increased temporal lobe retraction and limited access to the posterior fossa in the event of bleeding relative to a retrosigmoidal approach continues to be defined. The disadvantages of the middle fossa approach include temporal lobe retraction and a possible poor surgical position of the facial nerve relative to the tumor. Temporal lobe retraction may cause transient speech and memory disturbances and auditory hallucinations. The facial nerve, especially if the tumor originates from the inferior vestibular nerve, will be between the surgeon and the tumor. The increased manipulation of the facial nerve during tumor removal increases the risk of transient facial paresis. The patient should understand that initial conservative management, rather than immediate surgical intervention, may necessitate a resection of a larger tumor that is less amenable to hearing preservation or stereotactic radiation (or both) if intervention becomes necessary in the future. This goal directly differs from the goal of complete tumor removal in microsurgical therapy. The mechanism of stereotactic radiation relies on delivering radiation to a specific intracranial target by using several precisely collimated beams of ionizing radiation. The beams take various pathways to the target tissue, therefore creating a sharp dose gradient between the target tissue and the surrounding tissue. The ionizing radiation causes necrosis and vascular fibrosis, and the time course of the effect is over 1­2 years. The ionizing radiation is most commonly delivered using a 201-source cobalt-60 gamma knife system. The standard linear accelerator can also be adapted to deliver stereotactic radiation. The success of stereotactic radiation in arresting tumor growth depends on the dose of radiation delivered.

A slightly oblique plane of the pelvis in color Doppler demonstrates the two umbilical arteries surrounding the urinary bladder with an intact abdominal wall. Note the presence of fluid-filled stomachs (asterisks) in the upper left abdomen in A and B. Note the presence of an intact anterior abdominal wall (arrow) and the fetal bowel appearing slightly more hyperechoic than surrounding tissue. Sagittal Planes In the sagittal and coronal planes of the fetus, the chest, abdomen, and pelvic organs are seen and are differentiated by their echogenicity. The lung and bowel are hyperechoic, the liver is hypoechoic, and the stomach and bladder are anechoic. As in the second trimester, the parasagittal views do not exclude a diaphragmatic hernia. In the midsagittal view of the abdomen, the anterior abdominal wall with the umbilical cord insertion can be demonstrated. In the corresponding 3D ultrasound in surface mode (C), the midgut herniation is shown as a bulge at the site of cord insertion into the abdomen (arrow). This view is best visualized with color Doppler (B), which can also confirm the intact abdominal wall (arrow). Coronal Planes A coronal view is rarely necessary in the first trimester, but it has been our experience that the coronal view is best suited to evaluate the position of the stomach when the diagnosis of diaphragmatic hernia is suspected (see Chapter 10). Transvaginal ultrasound examination of the abdomen in the first trimester provides high-resolution display of organs, which is helpful when abnormalities are suspected. It is important to note, however, that the fetal bowel appears more echogenic on transvaginal imaging, and differentiating normal bowel from hyperechogenic bowel because of pathologic conditions is difficult in early gestation. Fetus A is presenting in a dorso-posterior position and fetus B in a dorso-anterior position. Note the hyperechoic lungs and bowel, the hypoechoic liver, and anechoic stomach and bladder (not shown). Three-Dimensional Ultrasound of the Fetal Abdomen Similar to the use of 3D ultrasound in surface mode in the second and third trimester of pregnancy, 3D ultrasound in the first trimester provides additional information to the 2D ultrasound views. For the assessment of the intraabdominal organs, 3D ultrasound can also be used in multiplanar display, with reconstruction of planes for the specific evaluation of target anatomic regions displayed in tomographic view of axial. For more details on the use of 3D ultrasound in the first trimester, refer to Chapter 3 in this book and a recent book on the clinical use of 3D in prenatal medicine. In our experience, multiplanar mode can be of help especially in the transvaginal approach where transducer manipulation is limited. Note the normal insertion of the umbilical cord in the abdomen in A and B (arrows). Note the presence of the stomach (asterisk) and liver in the upper abdomen, kidneys (Kid. Bladder exstrophy and cloacal exstrophy are often listed as abdominal wall defects, but are discussed in Chapter 13 as part of the urogenital anomalies. Omphalocele Definition Omphalocele, also known as exomphalos, is a congenital defect of the anterior midline abdominal wall with herniation of abdominal viscera, such as bowel and/or liver into the base of the umbilical cord. Embryologically, omphalocele results from failure of fusion of the lateral folds of the primitive gut. The typical location of an omphalocele is in the middle of the abdominal wall at the level of the umbilical cord attachment, and the umbilical cord typically inserts on the dome of the herniated sac. When this occurs, differentiating an omphalocele from gastroschisis on prenatal ultrasound is difficult. The size of the omphalocele differs based upon its content, which may include bowel alone or bowel with liver and other organs. Omphaloceles are commonly associated with fetal genetic and structural abnormalities. In this view, the diaphragm, liver, stomach (asterisk), bowel, kidneys, and urinary bladder can be seen. Content can be small with bowel, but can also be large including bowel, liver, stomach, and other organs Paraumbilical defect typically to the right of the umbilical cord Omphalocele Gastroschisis insertion with evisceration of bowel. No covering membrane Five features: Abdominal defect similar to omphalocele but higher on abdomen (1), anterior defect of diaphragm (2), distal Pentalogy of Cantrell sternal defect (3), pericardial defect (4), cardiac abnormalities with partial or complete ectopia cordis (5) Ectopia cordis Sternal defect with the heart partly or completely exteriorized, with or without cardiac abnormalities Complex large anterior wall defect with the fetus fixed to the Body stalk anomaly placenta because of a short or absent umbilical cord. Body stalk anomaly can also result complex) from an amniotic band syndrome with a normal umbilical cord.