J Neurosurg 112:800–807, 2010
The effects of posterior fossa decompressive surgery in adult patients with Chiari malformation and sleep apnea Clinical article Ricardo Vieira Botelho, M.D., Ph.D.,1,2 Lia Rita Azeredo Bittencourt, M.D., Ph.D., 2 José Marcus Rotta, M.D.,1 and Sérgio Tufik, M.D., Ph.D. 2 1 Neurosurgical Service, Hospital do Servidor publico do Estado de São Paulo; and 2Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil
Object. One of the feared consequences of craniovertebral junction diseases is apnea. Although several cases of patients with central apnea have been described, obstructive sleep apnea has been identified as the most frequent manifestation of sleep respiratory disorder. Neuronal involvement may be responsible for both central and obstructive apneas. The objective of this work was to study the effect of posterior fossa decompressive surgery on respiratory parameters during sleep in patients with craniovertebral junction malformations and breathing-related sleep disorders. Methods. In this study, prospectively enrolled consecutive symptomatic adult patients were monitored with fullnight polysomnography before and after surgical decompression of the cranial posterior fossa. Results. Of the 25 patients who were evaluated, 68% received a diagnosis of sleep apnea. After surgery, the mean number of respiratory events decreased from 180.70 to 69.29 (p = 0.005); the mean number of obstructive events decreased from 107.37 to 60.58 (p = 0.01); and the mean number of central events decreased from 38.45 to 8.05 (p = 0.01). The mean preoperative apnea/hypopnea index decreased from 26.68 to 12.98 (p = 0.06), and the mean central apnea index decreased from 13.81 to 1.68 (p = 0.01). Conclusions. Decompressive surgery in patients with craniovertebral junction malformations resulted in decreased respiratory events during sleep, lowered sleep fragmentation, and enhanced the sleep apnea index in a significant number of patients. The effect was more pronounced in patients with central apnea. (DOI: 10.3171/2009.7.JNS09174)
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Key Words • Chiari malformation • basilar invagination • sleep apnea • surgery
dult CM with and without BI is a malformation with the potential to produce distortion and compression in the neural structures within the region of the craniocervical junction. Neural changes have been considered to be caused by crowding of brain structures as a result of the smaller volume in the posterior fossa.18 Additionally, there may be direct neural compression from an upward-directed odontoid process in the BI or by cerebellar tonsillar herniation in a narrowed space at the foramen magnum. One of the feared consequences of these diseases is apnea, a serious manifestation of respiratory dysfunction culminating in cessation of breathing, possibly even leading to death.28 Systematic studies with polysomnog-
Abbreviations used in this paper: AHI = apnea/hypopnea index; BI = basilar invagination; BMI = body mass index; CAI = central apnea index; CM = Chiari malformation; CVJM = craniovertebral junction malformation; EEG = electroencephalogram; EMG = electromyogram; EOG = electrooculogram.
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raphy in patients with CVJMs have revealed an increased prevalence of respiratory dysfunction during sleep. The localization of malformations in the craniocervical junction suggests neural involvement in the respiratory structures. Although severe cases of central apnea are the main manifestation in many patients, obstructive sleep apnea has been identified as the most frequent manifestation of the respiratory disorder.8,26 Obesity and craniofacial abnormalities that alter the oropharyngeal airways may be responsible for the pathophysiological changes behind obstructive apnea.29 However, neuronal involvement may be responsible for both central and obstructive apneas by altering the reflex control of airways during sleep.11 The effect of decompressive surgery on the posterior fossa in symptomatic patients who present with adult respiratory dysfunction may play a role in the alleviation of this clinical manifestation. In this study our objective was to assess the effects of posterior fossa decompressive surgery on respiratory parameters during sleep in patients with CVJMs and breathing-related sleep disorders. J Neurosurg / Volume 112 / April 2010
Surgery for sleep apnea in patients with Chiari malformations Methods
Age, sex, and BMI before and after surgery were measured.
tems, Inc.) was used for the polysomnographic recordings, including the following: EEG (C3/A2, C4/A1, O1/A2, and O2/A1); EOG; submental EMG; left and right anterior tibialis EMG; electrocardiogram; thoracoabdominal effort; oronasal airflow (thermistor- and nasal pressure– based flow measurement); SaO2 with pulse oximetry; and body position. Sleep stages were determined using standard EEG, EOG, and EMG criteria.8,21 Scoring of abnormal respiratory events was based on the American Academy of Sleep Medicine (formerly American Sleep Disorders Association) criteria.13 The EEG arousals were quantified according to the guidelines published by the American Sleep Disorders Association Task Force.2 The polysomnography recording was evaluated by a physician who was not aware of the nature of the study or whether the patient had undergone an operation. The sleep respiratory variables studied were as follows: obstructive and central apneas; hypopneas; total number of respiratory events; AHI; and CAI score (Table 1). The microarousal index was described as a measure of sleep fragmentation, which is related to the amount of respiratory disturbance during sleep.
Signs and Symptoms
Statistical Analysis
Patient Population
For this study we prospectively enrolled consecutive symptomatic adult patients between the ages of 15 and 70 years. The study was conducted between 1996 and 2008. The patients presented with CM (with or without BI and syringomyelia) and incapacitating or progressive symptoms with surgical indications. Exclusion criteria included previous operation for CM, incidental diagnosis, gross obesity, and oligosymptomatic patients. The patients were studied prospectively with full-night polysomnographic monitoring. Patients with a diagnosis of sleep apnea were studied with pre- and postoperative polysomnography, and respiratory parameters were evaluated. The study protocol was submitted to the Ethics in Research Committee of the Hospital do Servidor Publico Estadual de São Paulo, Brazil.
Demographic Data
The patient’s signs and symptoms were recorded using a standardized questionnaire created by Bindal et al.,3 which provided a quantitative score for comparisons between pre- and postoperative clinical changes (the Bindal scoring system has been described elsewhere).7,11 The scores were recorded by the surgical team members. Somnolence Score
Because drowsiness is the result of sleep fragmentation caused by respiratory disturbances, the Epworth somnolence scale score14 was collected pre- and postoperatively, before the sleep study. Operative Technique
All patients underwent surgical decompression of the posterior fossa, and the procedures were performed by the same surgeon. In all patients, the modified technique of Sahuquillo et al.22 (Fig. 1) was used. All patients except 1 (the first patient in this series5) underwent operations with the extraarachnoidal technique, which was performed by opening the dura mater and leaving intact the arachnoid and cerebellar tonsils, but without anchoring the dura. All patients except 3 underwent their operations in a semisitting position. Two patients with BI underwent cranial traction in an attempt to reduce the invagination and were treated with craniocervical fixation (Fig. 2). Control MR Imaging
The patients were studied with craniocervical MR imaging pre- and postoperatively. The postoperative MR images demonstrated adequate decompression of the posterior fossa in all patients, with the presence of a new cisterna magna and narrowing or disappearance of syringomyelia (Figs. 2 and 3).
Polysomnographic Data
A standard montage (EMBLA S7000, Embla Sys-
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Statistical analysis was performed using the STATISTICA 6.1 software. All values were summarized by descriptive statistics and are expressed as the mean ± SD and 95% CI. Preoperative and postoperative polysomnographic values were compared using the Wilcoxon test for paired samples, whereas the differences between patients with and without apnea were calculated using the Mann-Whitney U test. A value of p ≤ 0.05 was deemed statistically significant.
Results
Prospectively, 27 patients with a CM were evaluated using polysomnography and were treated with surgery. Of these 27 patients, 1 did not return for examination and was lost to follow-up, and another died immediately after an uncomplicated surgery. The postmortem examination in the latter patient revealed deep vein thrombosis and massive pulmonary embolism. Thus, 25 patients were included in the final analysis. The cases of CVJM were classified as follows: 6 patients had BI (of whom 5 had syringomyelia), 17 had CM and syringomyelia, and 2 had a CM. According to demographic data, the average age of the 25 patients was 43 ± 13 years (range 38–49 years). The preoperative BMI score was 25 ± 3.9 (range 23–26) and postoperatively it was the same. There were 11 male and 14 female patients. Seventeen patients (68%) had AHI scores of > 5 and were studied before and after surgery. Of these, 8 were male and 9 were female. The average age of patients in this subgroup was 43 ± 17 years (95% CI 37–48 years). There were no differences in patient weight and body mass indices before and after surgery. The average preoperative weight was 64 ± 13 kg (95% CI 59.12–70.39 kg) and the postoperative weight was 63 ± 12 kg (95% CI 58–68 kg) (p = 0.83, Wilcoxon test). The mean preopera801
R. V. Botelho et al.
Fig. 1. Intraoperative photograph showing extraarachnoidal decompression according to the modified Sahuquillo technique but without anchoring the dura mater.
tive BMI was 27 ± 15 kg/m2 (95% CI 21–34 kg/m2), and the mean postoperative BMI was 24 ± 3.9 kg/m2 (95% CI 22–26 kg/m2) (p = 0.92, Wilcoxon test). The BMI of the 17 patients with apnea was 24 ± 3.5 kg/m2 (95% CI 22–26 kg/m2), and this was not significantly different from the BMI in the 8 without apnea, which was 25 ± 4.6 kg/m2 (95% CI 21–30 kg/m2) (p = 0.55, Mann-Whitney U test). The signs and symptoms were quantified for the entire sample of 25 patients by using the Bindal score. Before surgery, the patients had Bindal score of 80 ± 32 (95% CI 67–94), and after surgery the score was 56 ± 32 (95% CI 42–70) (p = 0.0009, Wilcoxon test). The 17 patients with a diagnosis of sleep apnea had an average Bindal score of 88 ± 34, whereas the 8 patients without a diagnosis of sleep apnea had an average score of 62 (p = 0.34, Mann-Whitney U test). Both groups (with and without sleep apnea) had significantly improved (reduced) Bindal scores after surgery (p = 0.00029 and 0.00065, respectively; Wilcoxon test). The Mean Interval Until the Polysomnographic Follow-Up Study
The last polysomnographic study was performed almost 2 years after the preoperative examination for the majority of patients, and 90% of those in the sample were studied > 1 year after the initial examination. The mean time between the pre- and postoperative studies was 20 ± 17.44 months (95% CI 13.21–27.61 months). There was no difference between the sleep anatomical variables before and after surgery among patients with and without sleep apnea. The microarousal index of the group with apnea decreased from 24 ± 14 to 17 ± 11 after surgery (p = 0.04), and became similar (without significant difference) to the group without sleep apnea (p = 0.56).
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Fig. 2. Preoperative (left) and postoperative (right) MR images demonstrating the reappearance of the cisterna magna, narrowing of syringomyelia cavity, and the presence of CSF in the craniocervical junction.
Analysis of Patients With Polysomnographic Diagnosis of Sleep Apnea
The isolated and grouped pre- and postsurgery data are displayed and compared in Table 2, as well as in Fig. 4. Of 25 patients, 17 (68%) had AHI values of > 5, along with a diagnosis of sleep apnea. The mean number of respiratory events decreased from 181 ± 191 (95% CI 82–279) to 69 ± 55 (95% CI 41–97, p = 0.005). The mean number of obstructive events presurgery decreased from 107 ± 63 (95% CI 74–141) to 61 ± 54 (95% CI 32–88, p = 0.013). The mean number of central events decreased from 38 ± 48 (95% CI 13–63) to 8 ± 16 (95% CI −0.43 to 16, p = 0.012). The mean preoperative AHI score in patients with sleep apnea was 26 ± 30 (95% CI 11–42), and the postoperative AHI score was 13 ± 9 (95% CI 8–17, p = 0.061). The mean CAI score decreased from 14 ± 32 (95% CI −2.7 to 30) to 1.6 ± 3 (95% CI −0.07 to 3.4, p = 0.012). The minimum saturation of oxyhemoglobin in patients with sleep apnea was 79 ± 11% (95% CI 73–84%) preoperatively, and the minimum oxygen saturation of the same patients was 81 ± 10% (95% CI 75–86%) postoperatively (p = 0.28).
Patients With Central Apnea (CAI Score > 5)
Seven (41%) of 17 patients had CAI values > 5 (central apnea). All patients had syringomyelia. Figure 5 displays the MR images of patients with central apnea. The mean preoperative CAI value in this sample was 32 ± 45 (95% CI −9.4 to 74), and the mean postoperative value was 3 ± 5 (95% CI −0.9 to 7.7, p = 0.017). After surgery, in 5 (71.4%) of 7 patients, the CAI value was lowered significantly, and in 4 patients it reached 0 or almost 0 (0.5). One patient had associated palatine tonsillar hypertrophy, J Neurosurg / Volume 112 / April 2010
Surgery for sleep apnea in patients with Chiari malformations
Fig. 3. Preoperative (A, C, E, and G) and postoperative (B, D, F, and H) pairs of MR images obtained in 4 patients. In these cases, the new cisterna magna formation and narrowing of the syringomyelia cavity may be seen. The patients whose MR images are displayed in the upper left (A and B) and lower left (E and F) pairs of panels were treated with cranial traction and craniocervical fixation to reduce the BI.
which may also have resulted in an underestimation of the final improvement rate. The Epworth Scale is used to assess the consequences of sleep respiratory disorders and daytime sleepiness. In our study, this scale was applied at the time of polysomnography. It was available in only 12 of 17 patients with sleep apnea. The Epworth Scale values evolved from 10 ± 5 (95% CI −3 to 18) to 8 ± 5 (95% CI −4 to 21) during the pre- and postsurgery periods (p = 0.10). Two patients had no improvement in their AHI score after surgery (24.3 before to 18.7 after surgery in one, and 9 before to 15.8 after surgery in the other). These 2 patients and another individual who was not described (who did not undergo an operation) had received a diagnosis of palatine tonsillar hypertrophy. Their tonsils were removed, and their AHI values decreased significantly. Tonsillar hypertrophy is a rare situation in adults, but this finding, along with other oropharyngeal factors,12 may be important in patients who experience no benefit from the surgery and should be studied in candidates for decompressive surgery. J Neurosurg / Volume 112 / April 2010
Discussion
Adult CM and BI are the main CVJMs that occur in adults. Syringomyelia, in which there is a block of CSF flow mainly in the foramen magnum region, accompanies most of these malformations. Syringomyelia occurs in at least 60% of cases and may worsen the clinical picture. There is some evidence that these malformations are at least part of a continuum.18 The distortion and compression of the neural craniovertebral structures varies according to the nature of the malformation. In BI, the posterior cranial fossa is generally smaller than that in CMs without BI, and the ventral compression of the brainstem and spinal cord is more evident. Patients with craniovertebral junction abnormalities may harbor other mesodermal alterations in such structures as the mouth, face, and neck.15 Experimental models of CM have demonstrated that animals that present with small oral cavities and relative hyperglossia have fewer facial airway spaces. Studies comparing the compliance of head and neck structures between patients with and 803
R. V. Botelho et al. TABLE 1: Definitions of polysomnographic parameters Event central apnea
obstructive apnea
hypopnea
respiratory events AHI CAI
TABLE 2: Preoperative and postoperative respiratory sleep variables of the 17 patients in the CM group with sleep apnea*
Definition event characterized by complete cessation of airway flow w/o respiratory effort; event lasts ≥10 sec event characterized by complete cessation of airway flow w/ respiratory effort persistence; event lasts ≥10 sec ≥50% reduction in airflow for >10 sec or dis cernible reduction in airflow for 10 sec, w/ 3% desaturation, or termination w/ arousal total no. of apnea & hypopnea events total no. of apnea & hypopnea events ÷ total sleep time (normal value: 5 (Fig. 4 right). Of these, 5 patients had normalized CAI values after decompressive surgery. One had palatine tonsillar hypertrophy that required surgery to improve his clinical situation. Only 1 of these 7 patients maintained her original CAI score. The mechanisms of apneas are partly shared by both types of this disorder (central and obstructive).20 There is evidence that, due to secondary alterations in the local reflex control of breathing in patients with obstructive apnea, central apnea occurs as a result of the oropharynx hyperexcitability reflex, thereby inhibiting the inspiratory drive. However, some patients have predominantly (but not exclusively) central events. The main issue addressed in this work is the improvement in respiratory dysfunction obtained by surgery. This effect was observed for all respiratory events. In particular, the change in AHI score revealed borderline results, with a level of significance close to 0.05 (p = 0.06). HowJ Neurosurg / Volume 112 / April 2010
ever, this difference probably reflected the small sample size, and the result should not be ignored. Significant improvements were seen in all other respiratory values. A clinically beneficial improvement in polysomnographic values (cutoff for clinical improvement) is considered achieved if there is a 50% decrease in the initial values. Forty-seven percent of the 17 patients with apnea obtained this amount of improvement. Sleep apnea is a syndrome with defined clinical signs, symptoms, and polysomnographic findings. Typical symptoms of sleep apnea include snoring, restless sleep, excessive daytime somnolence, nocturnal enuresis, irritability, depression, memory deficits, inability to concentrate, and decreased alertness. The clinically relevant outcomes of these symptoms include impairment in work efficiency, increased automobile accident index, and decreases in the quality of life. Due to the prevalence of sleep apnea in patients with CMs, many of the symptoms of these 2 entities (CM and sleep apnea) may present together. We based our study on polysomnographic data only, due to the known variability in CM symptoms. Moreover, we did not use any specific questionnaire to evaluate sleep apnea symptoms. It is interesting to note that the patients 805
R. V. Botelho et al. with sleep apnea had a higher Bindal score than patients without apnea. Several isolated case reports of severe respiratory dysfunctions that were improved by surgery have been described.5,6,28 To our knowledge, only 1 other paper has described the results of a more systematic study regarding the effects of surgery on sleep respiratory dysfunction in patients with CVJMs.12 This study evaluated 16 patients and found sleep apnea in 12 of them, with 48% of cases being central apneas. Eight patients were surgically treated, and 6 underwent postoperative polysomnography, which indicated decreases in the patients’ apnea index from 23.5 ± 7.9 to 9.8 ± 6.6 (p = 0.1) and decreases in their CAI scores from 14.9 ± 5.5 to 1.3 ± 0.6 (p = 0.03). Although a smaller number of patients was studied in this paper, the results from previous studies were similar to our results. Sleep apnea disorder must be treated. Sleep apnea may produce sleepiness, mood disturbances, impairments in neurocognition, and reductions in quality of life. Cardiac and vascular morbidity in sleep apnea may include systemic hypertension, cardiac arrhythmias, pulmonary hypertension, cor pulmonale, left ventricular dysfunction, stroke, and sudden death. Treatment may reduce the condition’s consequences.25
Conclusions
Decompressive surgery in patients with CVJMs decreased respiratory events during sleep, improved sleep fragmentation, and enhanced the sleep apnea index in a significant number of patients. The effect was more pronounced in patients with central apnea. The oropharyngeal airway evaluation found other causes of respiratory dysfunction in 2 patients; thus, these evaluations should be performed in patients with CVJMs who suffer from sleep apnea. Disclaimer The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Acknowledgments The authors thank Dr. Marcia Pradella-Hallinan for her contribution in polysomnographic data analysis and Dr. Egmond Silva Santos for his assistance with images. References 1. Alvarez D, Requena I, Arias M, Valdés L, Pereiro I, De la Torre R: Acute respiratory failure as the first sign of Arnold– Chiari malformation associated with syringomyelia. Eur Respir J 8:661–663, 1995 2. Anonymous: EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 15:173– 184, 1992 3. Bindal AK, Dunsker SB, Tew JM Jr: Chiari I malformation: classification and management. Neurosurgery 37:1069–1074, 1995 4. Bokinsky GE, Hudson LD, Weil JV: Impaired peripheral
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chemosensitivity and acute respiratory failure in Arnold– Chiari malformation and syringomyelia. N Engl J Med 288:947–948, 1973 5. Botelho RV, Bittencourt LR, Rotta JM, Nery LE, Tufik S: Apnéia do sono central em paciente com malformaçäo de Chiari tipo I e siringomielia: tratamento com cirurgia descompressiva. Relato de caso. J Bras Neurocir 9:111–114, 1998 6. Botelho RV, Bittencourt LR, Rotta JM, Tufik S: Adult Chiari malformation and sleep apnoea. Neurosurg Rev 28:169–176, 2005 7. Botelho RV, Bittencourt LR, Rotta JM, Tufik S: Prospective controlled study of sleep respiratory events in patients with craniovertebral junction malformation. J Neurosurg 99:1004–1009, 2003 8. Dauvilliers Y, Stal V, Abril B, Coubes P, Bobin S, Touchon J, et al: Chiari malformation and sleep related breathing disorders. J Neurol Neurosurg Psychiatry 78:1344–1348, 2007 9. Di X, Luciano MG, Benzel EC: Acute respiratory arrest following partial suboccipital cranioplasty for cerebellar ptosis from Chiari malformation decompression. Report of 2 cases. Neurosurg Focus 25(6):E12, 2008 10. Doherty MJ, Spence DP, Young C, Calverley PM: Obstructive sleep apnoea with Arnold–Chiari malformation. Thorax 50:690–691, 1995 11. Ely EW, McCall WV, Haponik EF: Multifactorial obstructive sleep apnea in a patient with Chiari malformation. J Neurol Sci 126:232–236, 1994 12. Flemons WW, Tsai W: Quality of life consequences of sleepdisordered breathing. J Allergy Clin Immunol 99:S750– S756, 1997 13. Gagnadoux F, Meslier N, Svab I, Menei P, Racineux JL: Sleepdisordered breathing in patients with Chiari malformation: improvement after surgery. Neurology 66:136–138, 2006 14. Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 14:540–545, 1991 15. Marin-Padilla M, Marin-Padilla TM: Morphogenesis of experimentally induced Arnold-Chiari malformation. J Neurol Sci 50:29–55, 1981 16. Melendres MC, Lutz JM, Rubin ED, Marcus CL: Daytime sleepiness and hyperactivity in children with suspected sleepdisordered breathing. Pediatrics 114:768–775, 2004 17. Miralbés Terraza S, García Oguiza A, López Pisón J, Sáenz Moreno I, Jiménez Escobar V, Peña Segura JL, et al: [Central sleep apnea syndrome as the first sign of type I Chiari malformation.] An Pediatr (Barc) 68:277–281, 2008 (Span) 18. Nishikawa M, Sakamoto H, Hakuba A, Nakanishi N, Inoue Y: Pathogenesis of Chiari malformation: a morphometric study of the posterior cranial fossa. J Neurosurg 86:40–47, 1997 19. Omer S, al-Kawi MZ, Bohlega S, Bouchama A, Mclean D: Respiratory arrest: a complication of Arnold–Chiari malformation in adults. Eur Neurol 36:36–38, 1996 20. Rabec C, Laurent G, Baudouin N, Merati M, Massin F, Foucher P, et al: Central sleep apnoea in Arnold–Chiari malformation: evidence of pathophysiological heterogeneity. Eur Respir J 12:1482–1485, 1998 21. Rechtschaffen A, Kales A: A Manual of Standardized Terminology and Scoring System for Sleep Stages of Human Subjects. Bethesda, MD: National Institute of Neurological Diseases and Blindness, 1968 22. Sahuquillo J, Rubio E, Poca MA, Rovira A, Rodriguez-Baeza A, Cervera C: Posterior fossa reconstruction: a surgical technique for the treatment of Chiari I malformation and Chiari I/syringomyelia complex—preliminary results and magnetic resonance imaging quantitative assessment of hindbrain migration. Neurosurgery 35:874–884, 1994 23 Stephany JD, Garavaglia JC, Pearl GS: Sudden death in a 27-year-old man with Chiari I malformation. Am J Forensic Med Pathol 29:249–250, 2008 24. Tsara V, Serasli E, Kimiskidis V, Papagianopoulos S, Kat-
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Surgery for sleep apnea in patients with Chiari malformations saridis V, Fylaktakis M, et al: Acute respiratory failure and sleep-disordered breathing in Arnold–Chiari malformation. Clin Neurol Neurosurg 107:521–524, 2005 25. Wiegand L, Zwillich CW: Obstructive sleep apnea. Dis Mon 40:197–252, 1994 26. Yglesias A, Narbona J, Vanaclocha V, Artieda J: Chiari type I malformation, glossopharyngeal neuralgia and central sleep apnoea in a child. Dev Med Child Neurol 38:1126–1130, 1996 27. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S: The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235, 1993 28. Zolty P, Sanders MH, Pollack IF: Chiari malformation and sleep-disordered breathing: a review of diagnostic and management issues. Sleep 23:637–643, 2000
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29. Zonato AI, Martinho FL, Bittencourt RA, de Oliveira Camponês Brasil O, Gregório LC, Tufik S: Head and neck physical examination: comparison between nonapneic and obstructive sleep apnea patients. Laryngoscope 115:1030–1034, 2005 Manuscript submitted February 5, 2009. Accepted July 1, 2009. Please include this information when citing this paper: published online August 7, 2009; DOI: 10.3171/2009.7.JNS09174. Address correspondence to: Ricardo Vieira Botelho, M.D., Ph.D., Department of Neurosurgery, Hospital do Servidor Publico de Estado, Haberbeck Brandão 68-92, Indianópolis-São Paulo, Brazil 04026040. email:
[email protected].
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