eMedicine Specialties > Plastic Surgery > Craniofacial

Craniofacial, Pharyngoplasty and Pharyngeal Flaps

Pravin K Patel, MD, Associate Professor of Surgery, Division of Plastic Surgery, Northwestern University School of Medicine; Chief of Plastic and Craniofacial Surgery, Shriners Hospitals for Children; Head of Craniofacial Surgery, Children's Memorial Hospital
Erin K McGraw, MA, CCC-SLP/L, Speech-Language Pathologist, Cleft Palate and Craniofacial Team, Shriners Hospital for Children-Chicago; Raja Ramaswamy, MS, The Chicago Medical School; Mary M O'Gara, MA, Director, Cleft Lip and Palate Institute, Inc; Associate Professor, Northwestern University Medical School; Mitchell F Grasseschi, MD, Assistant Professor, Department of Plastic Surgery, Feinberg School of Medicine, Northwestern University; Private Practice, Plastic and Reconstructive Surgery

Updated: Feb 23, 2009

Introduction

A competent and dynamically functional velopharyngeal sphincter is essential for normal eating, normal breathing, and intelligible speech. The sphincter is positioned between the oral and nasal cavities and coordinates appropriate airflow through each chamber to allow a voice that has quality, richness, and carrying power. Closure of the velopharyngeal port prevents nasal regurgitation during eating and allows pronunciation of consonants, while opening of the port allows for normal respirations and specific nasal articulations. Velopharyngeal dysfunction (VPD), velopharyngeal incompetence, velopharyngeal insufficiency (VPI), and velopharyngeal inadequacy are frequently used terms to denote an improperly functioning velopharynx. Several interventions are available for management of VPD, depending on differential diagnosis and etiology of pathology.

History of the Procedure

Surgery directed to correct velopharyngeal incompetence is not a novel topic. A documented awareness of the connection between cleft palate and poor speech may date back to Pierre Franco in 1561.¹ During the 19th century, surgical procedures were developed that are still being used in modified forms today. In 1865, after a detailed study of velopharyngeal physiology, Passavant was the first to tether the uvula to the pharynx in an attempt to restore a competent valvular mechanism during speech.² Since that time, in addition to the use of removable devices designed to obturate the velopharyngeal (VP) space, numerous surgical procedures have been devised to restore the physiologic closure of this sphincter-like mechanism. In 1875, Schoenborn, using the earlier concepts of Trendelenburg, devised an inferiorly-based pharyngeal flap,³ and Roselli later reported on the superiorly-based flap.⁴

More recently, Jackson and Silverton, Orticochea, and Moss et al have emphasized an anatomic reconstruction using adynamic sphincter pharyngoplasty.⁵ Over the years, numerous VP augmentation techniques have been suggested in lieu of pharyngeal flaps or pharyngoplasties. These procedures bring autogenous, allogeneic, or synthetic materials into the retropharynx but have fallen out of favor.

Problem

VPD includes any structural and/or neuromuscular disorder of the velum and/or pharyngeal walls at the level of the nasopharynx that results in interference of the normal sphincteric closure. VPD may result from anatomic, myoneural, behavioral, or a combination of disorders. Because this article details pharyngoplasty and pharyngeal flaps, the term velopharyngeal dysfunction specifically refers to speech and resonance symptoms related to a known structural deficit that has been determined by perceptual and instrumental differential diagnosis. VPD is diagnosed clinically by a constellation of symptoms that includes pathologically-incurred nasal resonance (hypernasality), compensatory misarticulations, escape of air through the nose (nasal emissions), and aberrant facial movements (grimacing).

Frequency

Approximately 20-38% of children who undergo cleft palate repair develop velopharyngeal insufficiency that requires active intervention, which comprises speech therapy, surgery, or both.

Etiology

The etiology of VPD can be divided into 2 categories: (1) structural deficiency of the palate or its related musculature (eg, cleft palate) and (2) neurologic deficiency (eg, myasthenia gravis, cerebrovascular accident, upper or lower motor neuron lesions, head trauma). Peterson-Falzone discusses noncleft causes of VPD, such as neuromuscular disorders, palatopharyngeal disproportion, and the effects of tonsils and adenoids.⁶ The degree to which each component contributes to VPD is difficult to determine.

Pathophysiology

VPD also may be anatomically classified as one of the following:

Poor mobility of the soft palate secondary to various factors, including short palate, scarred/tightened palate, or dysfunction/malposition of the levator palatini muscle
Poor mobility of the posterior and lateral pharyngeal walls due to poor muscular mobility

The latter is more commonly caused by a neurologic deficit.

Presentation

VPD manifests with hypernasality (hyperresonant) and often, but not always, misarticulated speech. Hypernasality is a quality perceived by the listener due to inappropriate nasal coupling, which refers to the balance of air traveling through the oral and nasal airways during speech. Errors in articulation of vowels and consonants occur from an inability to produce appropriate high intraoral pressure consonants, specifically, the stops, fricatives, and affricates. Tests such as the modified Müller maneuver cannot help distinguish patients with hypernasality.

Stop plosives (ie, "p, b, t, d, k, g" as in "go") are brief, purposeful interruptions of the airstream resulting in intraoral pressure buildup, with explosive release of that pressure buildup. Fricatives refer to sounds ("s, z, sh, zh, f, v," both voiced and voiceless "th") produced by constricting the airstream through a narrow channel between the 2 speech articulators. Affricates ("ch" and "g" as in "George") are high intraoral pressure consonants that begin as stops, but are released as fricatives.

Indications

Patients with symptoms of velopharyngeal (VP) dysfunction (ie, hypernasality, nasal emission, facial grimacing, compensatory misarticulations) are referred to a multidisciplinary VP diagnostic center for video-recorded standard perceptual, nasoendoscopic, and fluoroscopic speech evaluations. The videos provide direct visualization of VP closure for review by the interdisciplinary VP dysfunction team, and a consensus is reached for recommended management. Candidates for surgery fulfill the criterion of VP dysfunction resulting from an anatomic, myoneural, or combined deficiency of the VP sphincter that is not expected to be managed by speech therapy alone.

Relevant Anatomy

The 3 muscles (levator veli palatini, tensor veli palatini, uvularis) of the palate work in concert with the palatopharyngeus, the palatoglossus, and the pharyngeal constrictor muscles to produce VP closure. The tensor veli palatini muscles arise from the membranous wall of the eustachian tube. Their tendons pass around the hamular processes of the medial pterygoid plate of the sphenoid and insert into the palatine aponeurosis. The levator veli palatini muscles also have their origin along the eustachian tube orifice. They meet in the midline in a sling-like fashion above and behind the aponeurosis. The uvularis is a small midline muscle sitting above and behind the levator sling.

An unimpaired velum moves posteriorly and superiorly, the posterior pharyngeal wall can move ventrally diffusely or as a well-defined shelf (known as the Passavant ridge), and the lateral pharyngeal walls move toward the midsagittal midline. The uvularis also contracts during speech, adding bulk to the area of convexity on the upper surface of the soft palate. The adenoids, residing in the posterior pharyngeal wall, and the pharyngeal tonsils, on the lateral pharyngeal walls, may augment or interfere with the function of those walls in velopharyngeal closure.⁷

As a person prepares to speak, the velum is partially raised and held at the ready position before speech begins; it then moves to the closed position as phonation starts. For nasal sounds (eg, "m, n"), the sphincter remains open. The ability of the sphincter to close is essential for compression of air behind the point of constriction so that consonants, especially plosives (eg, "f, s, th") can release with sufficient strength.

Contraindications

Patients with known obstructive sleep apnea or other upper airway compromise must be approached with caution with regard to performing posterior pharynx surgery. Because of the possibility of triggering apneic episodes, pharyngeal flaps can be dangerous if performed in these patients. Patients requiring surgical velopharyngeal (VP) management who have risk factors for upper airway obstruction are preferentially recommended for sphincter pharyngoplasty based on reports of its minimal effect on the airway.

To stimulate collapse of the pharyngeal walls in patients with obstructive sleep apnea, have the patient perform a modified Müller maneuver. Instruct the patient to breathe rapidly with the mouth closed and the nose partially closed. Surgery to decrease the velopharyngeal port is contraindicated in these patients.

In addition, syndromic patients (ie, those with velocardiofacial syndrome) may have anomalous carotid artery anatomy, which places these structures within the operative field of posterior pharynx surgery.

Workup

Laboratory Studies

Patients with symptoms of velopharyngeal (VP) dysfunction (ie, hypernasality, nasal emission, facial grimacing, compensatory misarticulations) on perceptual speech screen are referred to a VP diagnostic center for video-recorded standard perceptual, nasoendoscopic, and fluoroscopic speech evaluations. The videos and patient records are reviewed by the interdisciplinary VP dysfunction team (ie, speech/language pathologist, otolaryngologist, prosthodontist, plastic surgeon), and a consensus is reached for recommended management.
Based initially on history and physical examination, appropriate tests and procedures should be performed to confirm or rule out concomitant abnormalities of syndromic etiology.

Imaging Studies

The videofluoroscopic technique involves the instillation of barium into the nasopharynx. Real-time imaging can be used for playback at normal speed or slow motion. The images can be obtained in 3 dimensions (lateral, frontal, and basal). A major advantage of videofluoroscopy is its ability to help evaluate patients who are uncooperative or noncompliant. The examination usually takes 2-3 minutes, with radiation exposure of less than 0.02 Gy.
Videoendoscopy or nasopharyngoscopy uses a fiberoptic nasopharyngoscope with a high-intensity light attached to an endoscopic video monitor. The procedure can be videotaped. The scope is highly flexible and well tolerated (tip size of 3 mm).
- Topical anesthesia and phenylephrine are sprayed into the nasopharynx to establish mucosal decongestion and to induce superficial vessel vasoconstriction. The nasopharyngoscope is placed through the nasal cavity superior to the VP port, and the movements of the velum, the lateral pharyngeal walls, and the posterior pharyngeal wall are observed while the patient repeats oral speech targets that he or she can correctly articulate. In addition, the depth and width of the pharynx and abnormal morphology and distortions in movements of the palate and pharyngeal walls are evaluated.
- The major advantage of videoendoscopy is the lack of ionizing radiation. This allows for a longer, more in-depth examination that can be repeated as often as necessary.
- Further, the ability of videoendoscopy to help assess all structures at the same time in relation to each other is superior to the 2-dimensional view obtained from videofluoroscopy.

Other Tests

Pre-VP management tonsillectomy and/or adenoidectomy are advised if the initial airway evaluation findings indicate that the lymphoid mass will compromise the operation or patency of the ports.
- These procedures are performed 3 months before VP surgery, as needed to facilitate technical execution of the subsequent procedure.
- Clinical manifestations of VP insufficiency may worsen after tonsillectomy and adenoidectomy. Repeating the evaluation 3 months after these procedures is a wise plan because of potential changes in closure patterns that may alter the treatment plan as a result of such surgery.
Preoperative consultations from appropriate subspecialists are recommended as needed by the VPI team.
Pulsations of the posterior wall should alert the surgeon to possible anomalous internal carotid arteries that are placed too medial in location. Angiography should be performed to help with visualization and avoid injury to the vasculature.
To minimize the risk of surgically-induced obstructive sleep apnea, a careful assessment of the upper airway, which may include formal sleep studies, is done before performing surgery.

Diagnostic Procedures

A video-recorded standard perceptual speech screen should be performed by a trained speech/language therapist.
A nasoendoscopic speech evaluation should be performed.
A fluoroscopic speech evaluation should be performed.
The video-recorded evaluations and patient records are reviewed by the interdisciplinary VP dysfunction team (ie, speech/language pathologist, otolaryngologist, prosthodontist, plastic surgeon), and a consensus is reached for recommended management.

Treatment

Medical Therapy

Acquisition of objective, quantitative, preoperative, and postoperative evaluation data allows for a rational informed decision regarding surgical and nonsurgical intervention. Determining the precise etiology of the velopharyngeal dysfunction (VPD) is paramount prior to embarking on treatment modalities.

Van Demark and Hardin discussed the effectiveness of exclusive articulation therapy in children with cleft palate and noted less improvement and slower improvement then expected.⁸ Perceptual speech evaluation by a qualified speech pathologist who has experience and expertise in cleft pathology is the mainstay of any evaluation and ongoing treatment, since the goal of therapy is the ability to communicate successfully using speech. In patients with cleft palate, residual articulation abnormalities associated with hypernasality should be corrected after palate closure but before secondary surgery for VPD. Ruscello reviewed nonsurgical palatal training procedures such as articulation therapy, sucking and blowing exercises, electrical and tactile stimulation, speech appliances, and biofeedback techniques.⁹ Learned compensatory misarticulations must be addressed and corrected through focused intervention with a trained speech pathologist.

The prosthetic speech bulb is most useful in patients with little or no VP motion. VP movement is essential to surgical success for the VP flap procedure or sphincteroplasty. Patients with little VP movement are good candidates for prosthetic management. A VP speech prosthesis can elevate the velum (lift), fill the residual velopharyngeal gap (obturator), or both (lift-orator).

A lift is usually effective in patients with a long supple velum and a normal ratio of velar length to nasopharyngeal depth with myoneural dysfunction. An obturator is usually necessary when the velum is short and scarred, and the ratio of velar length to nasopharyngeal depth is excessive, such as seen in some patients with repaired cleft palate. A combined prosthesis is useful when elevation of the velum alone is not sufficient to achieve closure. Such speech prostheses are fit under endoscopic control with an interdisciplinary team, which includes a prosthodontist, a speech/language pathologist, and an endoscopist.

One study that compared speech outcomes using prosthetic versus surgical management showed no difference for patients who complied with the prosthesis.¹⁰ However, because nearly 30% of patients referred for prosthesis did not comply, surgery was more efficacious overall.

Surgical Therapy

The goals of surgery are to eliminate the symptoms of hypernasality and eliminate audible nasal emissions without causing complete obstruction of the VP port, allowing for nasal breathing and nasal resonance. Multiple procedures have been described. Studies indicate that the success of repair depends on selecting the appropriate procedure based on the anatomy and the movement of the VP port.

Pharyngeal flap

The pharyngeal flap has been the most common method for secondary management of VPD for the past 3 decades. This procedure seems to benefit patients with satisfactory lateral pharyngeal wall motion with sagittal or circular closure patterns who have a residual velopharyngeal gap of moderate size. Tissue from the posterior pharyngeal wall is attached to the soft palate, creating a midline subtotal obstruction of the oral and nasal cavities with 2 small lateral openings, or ports, that ideally remain patent during respiration and nasal consonant production and close for oral consonants.

The soft palate is incised in the sagittal midline from the uvula toward the junction of the soft and hard palate. The superiorly based pharyngeal flap is elevated off the prevertebral fascia. The flap is inset to the soft palate and sutured to the nasal side of the soft palate with interrupted sutures. The donor site is partially closed with 3-0 Vicryl sutures. Nasopharyngeal airways are placed through each lateral pharyngeal port for sizing and postoperative airway support. With the flap inset and the nasal side closed, the soft palate musculature is further dissected and approximated as indicated. The oral side of the soft palate is then closed with interrupted sutures (see Image 2).

Through the years, several problems and complications have been identified with the pharyngeal flap procedure. As a result, it has undergone several modifications. The problems include construction of the appropriate width of flap, the use of a superiorly or inferiorly based flap, and whether the flap should be lined. A higher surgical success rate can probably be achieved by taking into account an individual patient's pattern of VPD. How to precisely tailor the flap to balance speech and airway is patient-dependent and objectively difficult to elucidate.

Sphincter pharyngoplasty

Patients with poor posterior pharyngeal wall movement and smaller VP ports tend to benefit more from this procedure. Sphincter pharyngoplasty involves reduction of the lateral and posterior aspects of the VP ports while maintaining the centric opening. The palatopharyngeus muscle is incised, and a flap is constructed from the posterior tonsillar pillar. These bilateral superiorly-based musculomucosal flaps are juxtaposed in the midline of the posterior pharyngeal wall (see Image 1). This procedure is advantageous in that it potentially recreates a functional sphincter, and the incidence of postoperative nasal obstruction is less than that with the pharyngeal flap.

Palatal lengthening

The primary goals of this procedure are to lengthen the palate, occlude a small gap in the VP port, and retrodisplace the palate in a more physiologically normal place. The most commonly used procedure for palatal lengthening is known as the V-Y pushback procedure (Veau-Wardill-Kilner operation). It is designed to displace the palatal mucoperiosteum and velar musculature after a primary palatoplasty has been performed. Because this procedure does not obstruct the nasal airway, VP valving may be achieved without the troublesome adverse effects of complete nasal obstruction (eg, chronic mouth breathing, sleep apnea). However, numerous problems are reported in association with the use of lengthening procedures. The extensive mucoperiosteal stripping the technique requires may have a deleterious effect on long-term facial growth. High rates of fistulization have been reported, and the ultimate length gain with this surgical maneuver is unpredictable.

During the last 20 years, the Furlow double-opposing Z-plasty palatoplasty has become accepted as a means of gaining palatal length and restoring the velar musculature anatomically.¹¹ It provides for closure of the hard and soft palates in one procedure without pushback or lateral relaxing incisions. Modifications of this procedure from the Children's Hospital of Philadelphia include lateral relaxing incisions. The unique repair of the soft palate is achieved with mirror-image musculo-mucosal Z-plasties to retroposition and overlap the soft palate muscles to recreate the palatal muscular sling. The Z-plasties provide length to the velum without borrowing tissue from the hard palate.

Intraoperative Details

The detailed operative techniques for each procedure have been described by Witt in the eMedicine article Craniofacial, Postpalatoplasty Speech Dysfunction.

Postoperative Details

Patients are routinely hospitalized for 24 hours postoperatively for airway observation. The diet is advanced initially from liquids for the first 24-48 hours, followed by mechanically soft foods for approximately 2 weeks after the procedure. Perioperative intravenous antibiotics are continued for 24 hours, followed by an oral equivalent elixir for a total of 5 days. Patients are instructed to sleep with their heads elevated on several pillows for 2 weeks. Oral hygiene is encouraged.

Follow-up

Postsurgical VP assessment is performed at 3 and 12 months postoperatively and consists of the same perceptual, nasoendoscopic, fluoroscopic, and airway evaluations performed preoperatively. Follow-up with a speech pathologist is essential to continue reinforcement of correct speech and to help prevent residual articulation errors.

Complications

Acute obstructive sleep apnea occurs in approximately 15% of patients with pharyngeal flaps and in slightly less with sphincter pharyngoplasty. A history of perinatal respiratory dysfunction, early age at sphincter pharyngoplasty, upper respiratory tract infections, and microretrognathia are risk factors. The severity of this complication diminishes with time, partially because of a reduction in edema and postoperative inflammation.

Dehiscence correlates inversely with surgical experience and directly with a previous history of tonsillectomy or adenoidectomy. Either of these procedures may result in compromised blood flow to the palatopharyngeal flaps during performance of a sphincter pharyngoplasty.

Persistent hypernasality usually results from a port size that is too large. Hyponasality is caused by constriction of the port, overtightening of the port, or closure from contracture or scar formation.

Outcome and Prognosis

Studies have shown success rates for pharyngeal flap surgery of 80-90%. The classification of failure or success depends on the investigator. Certain studies classify patients with hyponasality as a successful outcome. Other studies classify postsurgical hyponasality of greater than 4 years a failure. In those studies, the success rate is somewhat lower.

Sphincter pharyngoplasty has been associated with lower success rates of 40-60%. More recent studies show that the success rate can reach approximately 80% with appropriate patient selection based on velopharyngeal (VP) port anatomy.

The effectiveness of the Furlow procedure in properly selected patients is reported to be greater than 90% in most series. Ongoing debate in the literature surrounds patient selection for the Furlow procedure.

Future and Controversies

Sufficient prospective and randomized studies have not been performed on the various procedures for repairing a velopharyngeal (VP) port. A coordinated multicenter study that correlates the outcomes for the types of procedures based on VP anatomy is necessary. Such a study must be designed to produce data that can be appropriately interpreted, generalized, and applied by surgeons in making definitive conclusions on the optimal procedure for each patient.

Multimedia

Media file 1: Sphincter pharyngoplasty. The palatopharyngeus muscles are incised bilaterally, and 2 flaps are constructed from the posterior tonsillar pillars. These superiorly based musculomucosal flaps are approximated on the midline of the posterior pharyngeal wall.

Media file 2: Pharyngeal flap. A mucosal flap from the posterior pharyngeal wall is attached to the soft palate, creating a midline subtotal obstruction of the oral and nasal cavities with 2 small lateral openings, or ports, that ideally remain patent during respiration and nasal consonant production and close for oral consonants.

References

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Keywords

velopharyngeal dysfunction, VPD, velopharyngeal insufficiency, velopharyngeal inadequacy, velopharyngeal incompetence, VPI, VP inadequacy, VP incompetence, VP insufficiency, VP augmentation, velopharyngeal augmentation, cranio-facial surgery, cranio-facial pharyngoplasty, craniofacial pharyngoplasty, pharyngeal flap, speech disorder, resonance disorder, hypernasality, misarticulation, escape of air through the nose, nasal emissions, aberrant facial movements, grimacing, cleft palate repair, cleft palate, structural palate deficiency, myasthenia gravis, cerebrovascular accident, upper motor neuron lesion, lower motor neuron lesion, head trauma, short palate, scarred palate, tightened palate, levator palatini dysfunction, levator palatini malposition, poor pharyngeal wall mobility, misarticulated speech, palatal prosthesis, velar lift, VP obturator, velopharyngeal obturator

Contributor Information and Disclosures

Author

Coauthor(s)

Erin K McGraw, MA, CCC-SLP/L, Speech-Language Pathologist, Cleft Palate and Craniofacial Team, Shriners Hospital for Children-Chicago
Erin K McGraw, MA, CCC-SLP/L is a member of the following medical societies: American Cleft Palate/Craniofacial Association and American Speech-Language-Hearing Association
Disclosure: Nothing to disclose.

Raja Ramaswamy, MS, The Chicago Medical School
Raja Ramaswamy, MS is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.

Mary M O'Gara, MA, Director, Cleft Lip and Palate Institute, Inc; Associate Professor, Northwestern University Medical School
Disclosure: Nothing to disclose.

Mitchell F Grasseschi, MD, Assistant Professor, Department of Plastic Surgery, Feinberg School of Medicine, Northwestern University; Private Practice, Plastic and Reconstructive Surgery
Disclosure: Nothing to disclose.

Medical Editor

Larry Hollier, Jr, MD, Assistant Professor, Department of Plastic Surgery, Baylor University College of Medicine
Larry Hollier, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American Cleft Palate/Craniofacial Association, American College of Surgeons, American Medical Association, American Society of Maxillofacial Surgeons, AO Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

S Anthony Wolfe, MD, Chief, Division of Plastic Surgery, Miami Children's Hospital; Voluntary Professor, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Miami School of Medicine
S Anthony Wolfe, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Plastic Surgeons, American Cleft Palate/Craniofacial Association, American College of Surgeons, American Society for Aesthetic Plastic Surgery, American Society of Maxillofacial Surgeons, American Society of Plastic and Reconstructive Surgery, Florida Medical Association, and Southeastern Society of Plastic and Reconstructive Surgeons
Disclosure: Nothing to disclose.

CME Editor

Nicolas (Nick) G Slenkovich, MD, Director, Colorado Plastic Surgery Center
Nicolas (Nick) G Slenkovich, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, American Society of Aesthetic Plastic Surgery, American Society of Plastic Surgeons, and Colorado Medical Society
Disclosure: Nothing to disclose.

Chief Editor

Jorge I de la Torre, MD, FACS, Professor of Surgery and Physical Medicine and Rehabilitation, Residency Program Director, Division of Plastic Surgery, University of Alabama at Birmingham; Director, Center for Advanced Surgical Aesthetics
Jorge I de la Torre, MD, FACS is a member of the following medical societies: American Association of Plastic Surgeons, American Burn Association, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Society for Reconstructive Microsurgery, American Society of Maxillofacial Surgeons, American Society of Plastic Surgeons, Association for Academic Surgery, and Medical Association of the State of Alabama
Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Alexander Margulis, MD, and Glenn Herrmann, MD, to the development and writing of this article.

Further Reading