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Intraoperative diagnosis of primary ciliary dyskinesia
Intraoperative diagnosis of primary ciliary dyskinesia JOHN R BENTIII, MD, and RICHARDJ. H. SMITH,MD, Augusta, Georgia, and Iowa City, Iowa Primary ciliary dyskinesia refers to clinical disease attributable to congenitally abnormal or absent ciliary motility. Diagnosis typically requires electron microscopy to document aberrant axoneme ultrastructure. Electron microscopy, however, remains inaccurate and inconvenient as a screening test for symptomatic individuals. To avoid delays in diagnosis and to ensure a d e q u a c y of the tissue sample, we recommend a tracheal biopsy with an intraoperative histologic examination of ciliary motion. This study included patients evaluated at our institution for recurrent or chronic upper respiratory conditions characterized by chronic sinusitis, chronic mucoid otitis, and chronic bronchitis. A tracheal mucosa biopsy sample was obtained from each patient and was immediately examined in the operating room using light microscopy. If the magnified image demonstrated normal ciliary motility, primary ciliary dyskinesia was excluded and electron microscopy was not ordered. In the absence of normal ciliary motility, the specimen was placed in glutaraldehyde and ultrastructural axoneme morphology was evaluated. In the last 5 years, we have evaluated ciliary motility in 20 patients. Three patients had abnormal ciliary motility identified by light microscopy, and primary ciliary dyskinesia was confirmed histologically in each patient. In the remaining 17 patients, normal ciliary motility was observed, obviating the need for electron microscopy. We advocate intraoperative microscopic study of ciliary motility as a rapid, simple, accurate, and inexpensive technique to screen patients for primary ciliary dyskinesia. (Oto[aryngol Head Neck Surg 1997;I 16:64-7.)
r " r i m a r y ciliary dyskinesia (PCD) refers to a condition caused by congenitally dyskinetic cilia. Afflicted patients suffer from derangements of mucociliary clearance and experience chronic otitis media, sinusitis, and bronchiectasis. Male patients generally manifest infertility caused by immobile sperm flagella. The common pathologic defect responsible for these symptoms lies in the central element (axoneme) of cilia and sperm flagella. Numerous axoneme morphologic defects have been detected, including absent inner or outer dynein arms, radial spoke defects, absence of the central sheath, or transposition or rearrangements of microtubules. 1-3 Primary ciliary dyskinesia occurs in approx-
From the Division of Otolaryngology, the Medical College of Georgia (Dr. Bent), and the Department of Otolaryngology, University of Iowa Hospitals and Clinics (Dr. Smith). Presented at the Annual Meeting of the American Academy of Otolaryngology-Headand Neck Surgery, New Orleans, La., Sept. 17-20, 1995. Reprint requests: John E Bent III, MD, Division of Otolaryngology, BP-4154, The Medical College of Georgia, Augusta, GA 309124060. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/97/$5.00 + 0 23/1/72291 64
imately 1 out of 20,000 live births via autosomal recessive inheritance. 4 Evidence of PCD in the literature can be traced back for almost a century to Siewert's description of situs inversus coexisting with chronic upper and lower respiratory infections. 5 In 1932, Kartagener became the first author to classify the triad of situs inversus, nasal polyposis, and bronchiectasis as a unique clinical syndrome. 6 Four decades later, Camner et al. demonstrated that sperm immobility in patients with this syndrome was caused by abnormal dynein arms. It then became evident that a malfunctioning ciliated epithelium caused their respiratory symptoms.7 Shortly thereafter, several investigators used electron microscopy of immotile human spermatozoa to document abnormal axoneme ultrastructure as the underlying mechanical problem. On the basis of these reports, the disease became known as "immotile cilia syndrome."8 This term was replaced by "dyskinetic cilia syndrome'several years later when it became apparent that some patients had mobile cilia that moved asynchronously and ineffectively. 9 Most recently, the name has evolved to PCD to distinguish it from cases of acquired ciliary dysmotility. The lack of embryonic ciliary movement in
OtolaryngologyHead and Neck Surgery
BENT and SMITH 65
Volume 116 Number 1
Fig. 1. View of ciliated tracheal mucosa seen through the light microscope at 400x magnification. Arrow indicates ciliary surface. Material to the left of the ciliary border consists of blood and mucus mixed with saline solution.
PCD leaves organ rotation to chance, and as a result, half the patients will have situs inversus (Kartagener's syndrome). The diagnosis of PCD may be suspected if the patient has a history of lifelong chronic upper and lower respiratory infections. In the absence of dextrocardia, the diagnosis becomes especially challenging. Measurements of nasal or tracheobronchial clearance can be performed with various substances,10.I1 but are marred by subject-to-subject variability and poor reproducibility. More commonly, electron microscopy of a ciliated mucosal biopsy sample is used to reach a diagnosis. Nasal mucosa, a frequent source for biopsy samples, often lacks enough cilia for study. Cilia along the anterior-superior tracheal wall are abundant and beat with a higher frequency than cilia in other regions, 4 making it a well-suited biopsy location. Electron microscopy, however, also has several flaws. Tissue processing and pathologic examination delay diagnosis by at least several days. In some instances, the tissue specimen lacks sufficient cilia, necessitating a second biopsy, which in children requires another general anesthetic agent. Leading ultrastructural pathologists recently acknowledged "that current knowledge and technical capabilities are woefully inadequate for diagnostic questions" regarding ciliary dysfunction.12 One study reported that ciliary axoneme abnormalities were no more common in PCD than in other chronic respiratory conditions. 13 The fact that normal ciliary ultrastructure has been described in Kartagener's syndrome14 further complicates the diagnostic role of electron microscopy. Given these deficiencies, we have sought alternative diagnostic techniques. This report describes our experience with intra-
operative diagnosis of PCD, which we advocate as a simple, cost-effective addition to current means of diagnosis. METHODS
We reviewed the charts of 20 consecutive patients evaluated at the University of Iowa Hospitals and Clinics between 1990 and 1995 for suspected PCD. All patients had long histories of chronic upper and lower respiratory- infections. In the absence of dextrocardia, cystic fibrosis and immunodeficiencies were excluded before tracheal biopsies were performed. In preparation for the biopsy, patients required general anesthesia via mask ventilation. Neuromuscular relaxing agents do not affect ciliary motility and were used for this procedure. Without performing an endotracheal intubation, the endoscopist exposed the glottis with a laryngoscope. An assistant applied cricoid pressure to bring the anterior tracheal wall into view. The biopsy sample was taken from the anterior tracheal wall, immediately below the cricoid, using a 3 mm 45 degrees forceps. Bleeding was usually minimal. Immediately after the biopsy, the anesthesiologist resumed mask ventilation while the otolaryngotogist placed the biopsy sample in normal satine solution on a microscope slide. The mucosal surface was identified using the light microscope at 400x magnification (Fig. 1). After gaining experience in examining She specimen, the otolaryngologist can quickly locate the cilia. When ciliary motility was clearly present and synchronized, PCD cou!d be excluded without using electron microscopy. Lack of identifiable ciliated epithelium warranted an immediate second biopsy. If ciliary movement were either absent or irregular, the biopsy speci-
OtolaryngologyHead and Neck Surgery January 1997
66 BENTand SMITH
men was preserved in 2% gluteraldehyde and sent for electron microscopy studies to confirm the PCD diagnosis. RESULTS
All 20 patients underwent a tracheal biopsy using the aforementioned technique. Seventeen patients clearly had normal ciliary motility, permitting exclusion of PCD without further testing. Three patients, however, had abnormal ciliary motility. Electron microscopy studies confirmed PCD in all three cases. The following case histories summarize the clinical course of these 3 patients. Patient 1
An 18-year-old man presented with chronic upper and lower respiratory infections. His first set of myringotomy tubes were inserted when he was 4 months old, and subsequently 10 additional sets were placed. He also reported undergoing two sinus procedures and two mastoid procedures on each ear. The patient had no history of dextrocardia and no family history to suggest PCD. Evaluation of his immune system and a sweat test revealed no abnormalities. A chest radiograph suggested bronchiectasis of the left lower lobe, which was confirmed by a computed tomographic scan of his chest. A nasal biopsy sample obtained under local anesthesia showed squamous metaplasia with no ciliated cells. A tracheal biopsy performed under general anesthesia revealed immotile cilia. An ultrastructural examination showed that the outer dynein arms were present but the inner dynein arms were rarely present. Patient 2
A 13-year-old boy presented with multiple complaints of respiratory infections, including more than 50 episodes of otitis media, a persistent cough since he was 5 years old, prolonged hospitalization as a neonate for recalcitrant rhinorrhea, and 2 episodes of pneumonia in the preceding year. The boy had no clinically significant family history, but a chest radiograph revealed dextrocardia. A tracheal biopsy sample revealed immotile cilia, and electron microscopy illustrated a generalized absence of inner and outer dynein arms. Patient 3
A 9-year-old boy presented with long-term coughing and rhinorrhea. His surgical history included bilateral modified radical mastoidectomies, intranasal ethmoidectomies, Caldwell-Luc procedures, and 10 sets of myringotomy tubes. An evaluation of the immune sys-
tern sweat testing, and family history of the patient were unremarkable. Dextrocardia was not present. Intraoperative light microscopy of a tracheal biopsy sample revealed diffusely immotile cilia with a small region of asynchronous ciliary movement. Electron microscopy showed absence of inner dynein arms and multiple microtubular transposition anomalies. DISCUSSION
The greatest disadvantage of intraoperative light microscopy is the requirement for general anesthesia. A nasal biopsy is preferable to a tracheal biopsy. In fact, some authors have reported success in observing in vitro ciliary motility in nasal biopsy samples or scrapings. 15 Chronic rhinosinusitis, however, denudes nasal mucosa of cilia. To investigate the viability of nasal mucosal biopsy samples, we microscopically examined nasal biopsy samples from healthy volunteers for cilia on two occasions. Overall, nasal biopsy samples of 12 of 36 (33%) volunteers had inadequate cilia for study, indicating that a nasal biopsy sample is an unreliable source of tissue. For this reason, tracheal biopsies were performed for examining ciliary motility. If the straightforward nasal scraping technique described by Rutland et al. 15 could be applied universally, it would be a significant advance in patient care. Magnified observation of ciliary motility is not a new concept. Jahrsdoerfer et al. 16viewed immotile middle ear cilia with the operating microscope, but conventional microscopes lack sufficient magnification for detailed ciliary observation. More complicated methods, such as microphoto-oscillography,iv involve technical sophistication that obviates widespread clinical application. Intraoperative light microscopy allows adequate magnification without requiring unnecessarily complex skills. One must be aware that ciliary movement does not automatically exclude PCD. Several different awkward patterns of ciliary movement have been described, including a "windshield wiper" motion18 and an "eggbeater rotation."9 In the operating room, the clinician should look for microscopic evidence of a slow, synchronous ciliary backstroke followed by a quick, efficient whipping motion. If the cilia are functioning properly, blood and other debris should be visible moving in a uniform direction along the ciliated surface. If any doubt about ciliary motility exists, the specimen should be preserved in gluteraldehyde and sent for electron microscopy studies. The diagnosis of PCD remains an unrefined art, about which many questions remain. The technique described in this report, however, used in combination
OtolaryngologyHead and Neck Surgery
BENT and SMITH 67
Volume !16 Number 1
with preexisting methods, significantly augments diagnostic accuracy. Not only does intraoperative light microscopy provide adequate tissue sampling, it also is a simple procedure that obviates the need for electron microscopy in m a n y instances, reducing costs and expediating results. Future prospective studies are needed to validate this technique. For instance, the sensitivity of intraoperative light microscopy could be compared with that of electron microscopy studies of apparently n o r m a l l y motile ciliary axonemes. Specificity w o u l d be reflected by the ability of a b l i n d e d investigator to detect a b n o r m a l in vitro ciliary motility in a patient with dextrocardia and clinically obvious PCD. B l i n d e d studies of adult male P C D patients c o m p a r i n g the results of ciliary biopsies, sperm samples, and a x o n e m e ultrastructure could possibly yield i n f o r m a t i o n on the true accuracy of each diagnostic method. These a n d other investigations should facilitate greater insight into the true pathophysiology of this condition.
REFERENCES 1. Smrgess JM, Thompson MW, Czegledy-Nagy E, Turner JAR Genetic aspects of immotile cilia syndrome. Am J Med Genet 1986;25:149-60. 2. Rott H-D. Genetics of Kartagener's syndrome. Eur J Respir Dis 1983;64(suppl 127):1-4. 3. Afzelius BA, Eliasson R. Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. Ultrastruct Res 1979;69:43-52. 4. Schidlow DV. Primary ciliary dyskinesia (the irmnaotilecilia syndrome). Ann Allergy 1994;73:457-68.
5. Siewert AK. Uber einen Fal von bronchiectasien bei einem Patienten mit situs inversus viscerum. Berl Klin Wochensehr 1904;41:139-41. 6. Kartagener M. Zur pathogenese der bronchiectasien. I Mitteilung: Bronchiectasien bei situs viscerum inversus. Betr Klin Tuberk 1933;83:498-50I. 7. Camner R Mossberg B, Afzelius BA. Evidence for congenitally non-functioning cilia in the ~acheobronchial tree in two subjects. Am Rev Respir Dis 1975;112:807-9. 8. Eliasson R, Mossberg B, Canmer R Afzetius BA. The immotile cilia syndrome: a congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med 1977;196:1-6. 9. Rossman CM, Forrest JB, Lee RMKW, Newhouse MT. The dyskinetic cilia syndrome. Chest 1980;78:580-2. 10. Anderson 1, Proctor DE Measurement of nasal mucociliary clearance. Eur J Respir Dis 1983;64(suppl 127):37-40. 11. Pavia D, Sutton PP, Agnew JE, et al. Measurement of bronchial mucociliary clearance. Eur J Respir Dis 1983;64(suppl 127):4156. 12. Mierau GW, Agostini R, Beals TF, et al. The role of electron microscopy in evaluating ciliary dysfunction: report of a workshop. Ultrastruct Pathol !992;16:245-54. 13. Lurie M, Rennert G, Goldenberg S, et al. Ciliary ultrasmlcture in primary ciliary dyskinesia and other chronic respiratory conditions: the relevance of microtubular abnormalities. Ultrastxuct Pathol 1992;16:547-53. 14. Herzon FS, Murphy S. Normal ciliary motility in children with Kartagener's syndrome. Ann Otol Rhino! Laryngol 1980;89:8i-3. 15. Rutland J, Dewer A, Cox T, Cole R Nasal brushing for the study of ciliary ultrastructure. J Clin Pathol 1982;37:357-9. I6. Jahrsderfer R, Feldman PS, Rubel EW, et al. Otitis media and the immotile cilia syndrome. Laryngoscope i979;89:769-77. 17. Pederson M. Specific types of abnormal ciliary motility in Kartagener's syndrome and analogous respiratory disorders. Eur J Respir Dis 1983;64(suppl 127):78-90. I8. Rut!and J, Cole E Ciliary dyskinesia. Lancet 1980;2(8199):859.
Neuroradiology Update 1997 This 5-day course is designed to present in a practical manner the principles of the standard and recently advanced MR imaging techniques and their applications in the evaluation of the brain, spine, head and neck, and vascular regions. It is sponsored by the University of Pennsylvania Medical Center and will be held March 24-28, 1997. Credits include 25 category I hours. For further information, contact Janice Ford, Hospital of the University of Pennsylvania, 3400 Spruce St., 1 Silverstein Bldg., Philadelphia, PA 19 t 04; phone, (215) 662-6904; Fax, (215) 349-5925.
r " r i m a r y ciliary dyskinesia (PCD) refers to a condition caused by congenitally dyskinetic cilia. Afflicted patients suffer from derangements of mucociliary clearance and experience chronic otitis media, sinusitis, and bronchiectasis. Male patients generally manifest infertility caused by immobile sperm flagella. The common pathologic defect responsible for these symptoms lies in the central element (axoneme) of cilia and sperm flagella. Numerous axoneme morphologic defects have been detected, including absent inner or outer dynein arms, radial spoke defects, absence of the central sheath, or transposition or rearrangements of microtubules. 1-3 Primary ciliary dyskinesia occurs in approx-
From the Division of Otolaryngology, the Medical College of Georgia (Dr. Bent), and the Department of Otolaryngology, University of Iowa Hospitals and Clinics (Dr. Smith). Presented at the Annual Meeting of the American Academy of Otolaryngology-Headand Neck Surgery, New Orleans, La., Sept. 17-20, 1995. Reprint requests: John E Bent III, MD, Division of Otolaryngology, BP-4154, The Medical College of Georgia, Augusta, GA 309124060. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/97/$5.00 + 0 23/1/72291 64
imately 1 out of 20,000 live births via autosomal recessive inheritance. 4 Evidence of PCD in the literature can be traced back for almost a century to Siewert's description of situs inversus coexisting with chronic upper and lower respiratory infections. 5 In 1932, Kartagener became the first author to classify the triad of situs inversus, nasal polyposis, and bronchiectasis as a unique clinical syndrome. 6 Four decades later, Camner et al. demonstrated that sperm immobility in patients with this syndrome was caused by abnormal dynein arms. It then became evident that a malfunctioning ciliated epithelium caused their respiratory symptoms.7 Shortly thereafter, several investigators used electron microscopy of immotile human spermatozoa to document abnormal axoneme ultrastructure as the underlying mechanical problem. On the basis of these reports, the disease became known as "immotile cilia syndrome."8 This term was replaced by "dyskinetic cilia syndrome'several years later when it became apparent that some patients had mobile cilia that moved asynchronously and ineffectively. 9 Most recently, the name has evolved to PCD to distinguish it from cases of acquired ciliary dysmotility. The lack of embryonic ciliary movement in
OtolaryngologyHead and Neck Surgery
BENT and SMITH 65
Volume 116 Number 1
Fig. 1. View of ciliated tracheal mucosa seen through the light microscope at 400x magnification. Arrow indicates ciliary surface. Material to the left of the ciliary border consists of blood and mucus mixed with saline solution.
PCD leaves organ rotation to chance, and as a result, half the patients will have situs inversus (Kartagener's syndrome). The diagnosis of PCD may be suspected if the patient has a history of lifelong chronic upper and lower respiratory infections. In the absence of dextrocardia, the diagnosis becomes especially challenging. Measurements of nasal or tracheobronchial clearance can be performed with various substances,10.I1 but are marred by subject-to-subject variability and poor reproducibility. More commonly, electron microscopy of a ciliated mucosal biopsy sample is used to reach a diagnosis. Nasal mucosa, a frequent source for biopsy samples, often lacks enough cilia for study. Cilia along the anterior-superior tracheal wall are abundant and beat with a higher frequency than cilia in other regions, 4 making it a well-suited biopsy location. Electron microscopy, however, also has several flaws. Tissue processing and pathologic examination delay diagnosis by at least several days. In some instances, the tissue specimen lacks sufficient cilia, necessitating a second biopsy, which in children requires another general anesthetic agent. Leading ultrastructural pathologists recently acknowledged "that current knowledge and technical capabilities are woefully inadequate for diagnostic questions" regarding ciliary dysfunction.12 One study reported that ciliary axoneme abnormalities were no more common in PCD than in other chronic respiratory conditions. 13 The fact that normal ciliary ultrastructure has been described in Kartagener's syndrome14 further complicates the diagnostic role of electron microscopy. Given these deficiencies, we have sought alternative diagnostic techniques. This report describes our experience with intra-
operative diagnosis of PCD, which we advocate as a simple, cost-effective addition to current means of diagnosis. METHODS
We reviewed the charts of 20 consecutive patients evaluated at the University of Iowa Hospitals and Clinics between 1990 and 1995 for suspected PCD. All patients had long histories of chronic upper and lower respiratory- infections. In the absence of dextrocardia, cystic fibrosis and immunodeficiencies were excluded before tracheal biopsies were performed. In preparation for the biopsy, patients required general anesthesia via mask ventilation. Neuromuscular relaxing agents do not affect ciliary motility and were used for this procedure. Without performing an endotracheal intubation, the endoscopist exposed the glottis with a laryngoscope. An assistant applied cricoid pressure to bring the anterior tracheal wall into view. The biopsy sample was taken from the anterior tracheal wall, immediately below the cricoid, using a 3 mm 45 degrees forceps. Bleeding was usually minimal. Immediately after the biopsy, the anesthesiologist resumed mask ventilation while the otolaryngotogist placed the biopsy sample in normal satine solution on a microscope slide. The mucosal surface was identified using the light microscope at 400x magnification (Fig. 1). After gaining experience in examining She specimen, the otolaryngologist can quickly locate the cilia. When ciliary motility was clearly present and synchronized, PCD cou!d be excluded without using electron microscopy. Lack of identifiable ciliated epithelium warranted an immediate second biopsy. If ciliary movement were either absent or irregular, the biopsy speci-
OtolaryngologyHead and Neck Surgery January 1997
66 BENTand SMITH
men was preserved in 2% gluteraldehyde and sent for electron microscopy studies to confirm the PCD diagnosis. RESULTS
All 20 patients underwent a tracheal biopsy using the aforementioned technique. Seventeen patients clearly had normal ciliary motility, permitting exclusion of PCD without further testing. Three patients, however, had abnormal ciliary motility. Electron microscopy studies confirmed PCD in all three cases. The following case histories summarize the clinical course of these 3 patients. Patient 1
An 18-year-old man presented with chronic upper and lower respiratory infections. His first set of myringotomy tubes were inserted when he was 4 months old, and subsequently 10 additional sets were placed. He also reported undergoing two sinus procedures and two mastoid procedures on each ear. The patient had no history of dextrocardia and no family history to suggest PCD. Evaluation of his immune system and a sweat test revealed no abnormalities. A chest radiograph suggested bronchiectasis of the left lower lobe, which was confirmed by a computed tomographic scan of his chest. A nasal biopsy sample obtained under local anesthesia showed squamous metaplasia with no ciliated cells. A tracheal biopsy performed under general anesthesia revealed immotile cilia. An ultrastructural examination showed that the outer dynein arms were present but the inner dynein arms were rarely present. Patient 2
A 13-year-old boy presented with multiple complaints of respiratory infections, including more than 50 episodes of otitis media, a persistent cough since he was 5 years old, prolonged hospitalization as a neonate for recalcitrant rhinorrhea, and 2 episodes of pneumonia in the preceding year. The boy had no clinically significant family history, but a chest radiograph revealed dextrocardia. A tracheal biopsy sample revealed immotile cilia, and electron microscopy illustrated a generalized absence of inner and outer dynein arms. Patient 3
A 9-year-old boy presented with long-term coughing and rhinorrhea. His surgical history included bilateral modified radical mastoidectomies, intranasal ethmoidectomies, Caldwell-Luc procedures, and 10 sets of myringotomy tubes. An evaluation of the immune sys-
tern sweat testing, and family history of the patient were unremarkable. Dextrocardia was not present. Intraoperative light microscopy of a tracheal biopsy sample revealed diffusely immotile cilia with a small region of asynchronous ciliary movement. Electron microscopy showed absence of inner dynein arms and multiple microtubular transposition anomalies. DISCUSSION
The greatest disadvantage of intraoperative light microscopy is the requirement for general anesthesia. A nasal biopsy is preferable to a tracheal biopsy. In fact, some authors have reported success in observing in vitro ciliary motility in nasal biopsy samples or scrapings. 15 Chronic rhinosinusitis, however, denudes nasal mucosa of cilia. To investigate the viability of nasal mucosal biopsy samples, we microscopically examined nasal biopsy samples from healthy volunteers for cilia on two occasions. Overall, nasal biopsy samples of 12 of 36 (33%) volunteers had inadequate cilia for study, indicating that a nasal biopsy sample is an unreliable source of tissue. For this reason, tracheal biopsies were performed for examining ciliary motility. If the straightforward nasal scraping technique described by Rutland et al. 15 could be applied universally, it would be a significant advance in patient care. Magnified observation of ciliary motility is not a new concept. Jahrsdoerfer et al. 16viewed immotile middle ear cilia with the operating microscope, but conventional microscopes lack sufficient magnification for detailed ciliary observation. More complicated methods, such as microphoto-oscillography,iv involve technical sophistication that obviates widespread clinical application. Intraoperative light microscopy allows adequate magnification without requiring unnecessarily complex skills. One must be aware that ciliary movement does not automatically exclude PCD. Several different awkward patterns of ciliary movement have been described, including a "windshield wiper" motion18 and an "eggbeater rotation."9 In the operating room, the clinician should look for microscopic evidence of a slow, synchronous ciliary backstroke followed by a quick, efficient whipping motion. If the cilia are functioning properly, blood and other debris should be visible moving in a uniform direction along the ciliated surface. If any doubt about ciliary motility exists, the specimen should be preserved in gluteraldehyde and sent for electron microscopy studies. The diagnosis of PCD remains an unrefined art, about which many questions remain. The technique described in this report, however, used in combination
OtolaryngologyHead and Neck Surgery
BENT and SMITH 67
Volume !16 Number 1
with preexisting methods, significantly augments diagnostic accuracy. Not only does intraoperative light microscopy provide adequate tissue sampling, it also is a simple procedure that obviates the need for electron microscopy in m a n y instances, reducing costs and expediating results. Future prospective studies are needed to validate this technique. For instance, the sensitivity of intraoperative light microscopy could be compared with that of electron microscopy studies of apparently n o r m a l l y motile ciliary axonemes. Specificity w o u l d be reflected by the ability of a b l i n d e d investigator to detect a b n o r m a l in vitro ciliary motility in a patient with dextrocardia and clinically obvious PCD. B l i n d e d studies of adult male P C D patients c o m p a r i n g the results of ciliary biopsies, sperm samples, and a x o n e m e ultrastructure could possibly yield i n f o r m a t i o n on the true accuracy of each diagnostic method. These a n d other investigations should facilitate greater insight into the true pathophysiology of this condition.
REFERENCES 1. Smrgess JM, Thompson MW, Czegledy-Nagy E, Turner JAR Genetic aspects of immotile cilia syndrome. Am J Med Genet 1986;25:149-60. 2. Rott H-D. Genetics of Kartagener's syndrome. Eur J Respir Dis 1983;64(suppl 127):1-4. 3. Afzelius BA, Eliasson R. Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. Ultrastruct Res 1979;69:43-52. 4. Schidlow DV. Primary ciliary dyskinesia (the irmnaotilecilia syndrome). Ann Allergy 1994;73:457-68.
5. Siewert AK. Uber einen Fal von bronchiectasien bei einem Patienten mit situs inversus viscerum. Berl Klin Wochensehr 1904;41:139-41. 6. Kartagener M. Zur pathogenese der bronchiectasien. I Mitteilung: Bronchiectasien bei situs viscerum inversus. Betr Klin Tuberk 1933;83:498-50I. 7. Camner R Mossberg B, Afzelius BA. Evidence for congenitally non-functioning cilia in the ~acheobronchial tree in two subjects. Am Rev Respir Dis 1975;112:807-9. 8. Eliasson R, Mossberg B, Canmer R Afzetius BA. The immotile cilia syndrome: a congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med 1977;196:1-6. 9. Rossman CM, Forrest JB, Lee RMKW, Newhouse MT. The dyskinetic cilia syndrome. Chest 1980;78:580-2. 10. Anderson 1, Proctor DE Measurement of nasal mucociliary clearance. Eur J Respir Dis 1983;64(suppl 127):37-40. 11. Pavia D, Sutton PP, Agnew JE, et al. Measurement of bronchial mucociliary clearance. Eur J Respir Dis 1983;64(suppl 127):4156. 12. Mierau GW, Agostini R, Beals TF, et al. The role of electron microscopy in evaluating ciliary dysfunction: report of a workshop. Ultrastruct Pathol !992;16:245-54. 13. Lurie M, Rennert G, Goldenberg S, et al. Ciliary ultrasmlcture in primary ciliary dyskinesia and other chronic respiratory conditions: the relevance of microtubular abnormalities. Ultrastxuct Pathol 1992;16:547-53. 14. Herzon FS, Murphy S. Normal ciliary motility in children with Kartagener's syndrome. Ann Otol Rhino! Laryngol 1980;89:8i-3. 15. Rutland J, Dewer A, Cox T, Cole R Nasal brushing for the study of ciliary ultrastructure. J Clin Pathol 1982;37:357-9. I6. Jahrsderfer R, Feldman PS, Rubel EW, et al. Otitis media and the immotile cilia syndrome. Laryngoscope i979;89:769-77. 17. Pederson M. Specific types of abnormal ciliary motility in Kartagener's syndrome and analogous respiratory disorders. Eur J Respir Dis 1983;64(suppl 127):78-90. I8. Rut!and J, Cole E Ciliary dyskinesia. Lancet 1980;2(8199):859.
Neuroradiology Update 1997 This 5-day course is designed to present in a practical manner the principles of the standard and recently advanced MR imaging techniques and their applications in the evaluation of the brain, spine, head and neck, and vascular regions. It is sponsored by the University of Pennsylvania Medical Center and will be held March 24-28, 1997. Credits include 25 category I hours. For further information, contact Janice Ford, Hospital of the University of Pennsylvania, 3400 Spruce St., 1 Silverstein Bldg., Philadelphia, PA 19 t 04; phone, (215) 662-6904; Fax, (215) 349-5925.