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Sleep apnea and intracranial hypertension in men
Sleep Apnea and Intracranial Hypertension in Men Andrew G. Lee, MD,1,3,4 Karl Golnik, MD,2 Randy Kardon, MD, PhD,1 Michael Wall, MD,1,3 Eric Eggenberger, DO,5 Sunita Yedavally, DO5 Purpose: To investigate sleep apnea as an associated finding in idiopathic intracranial hypertension (IIH) in men. Design: Multicenter, retrospective, noncomparative interventional case series. Methods: Retrospective review of all men with the diagnosis of IIH seen within the last 5 years at three tertiary care academic ophthalmologic institutions. Cases with sleep apnea (SA) and IIH were identified and reviewed. Results: Thirty-two cases of IIH in men were reviewed. Six cases with SA met the modified Dandy criteria for the diagnosis of IIH. Of these six patients, one received acetazolamide alone, four received acetazolamide and continuous positive airway pressure (CPAP), and one was treated with CPAP alone. All patients had preserved central acuity (20/20 or better in both eyes), enlarged blind spots, and optic disc edema in both eyes. Five patients had normal visual fields after treatment, and one patient had residual visual field loss. Three patients had normal optic nerve examinations, with resolution of the optic disc edema at last follow-up. After resolution of the optic disc edema, these three patients were maintained on CPAP but discontinued acetazolamide. Two patients had persistent but improved papilledema and are under continued treatment with acetazolamide and CPAP. One patient had optic disc pallor in both eyes and is stable. Conclusions: SA was a common finding in men meeting the modified Dandy criteria for IIH in adults. Treatment of sleep apnea with nocturnal oxygenation may improve the signs and symptoms of IIH in affected men. Ophthalmology 2002;109:482– 485 © 2002 by the American Academy of Ophthalmology. Idiopathic intracranial hypertension (IIH) is a condition that affects predominantly young, obese, women. The modified Dandy criteria for the diagnosis of IIH are (1) signs and symptoms related solely to increased intracranial pressure (ICP), (2) normal neuroimaging results, (3) normal cerebrospinal fluid (CSF) analysis with an elevated ICP; and (4) no other cause for increased ICP present. We reviewed all of the cases of IIH in men since 1995 at three tertiary care institutions and identified a subgroup of patients with sleep apnea (SA). We report six cases and review the Englishlanguage literature on SA associated with optic disc edema in men.
Originally received: June 14, 2001. Accepted: July 31, 2001. Manuscript no. 210406. 1 Department of Ophthalmology, The University of Iowa Hospitals and Clinics. 2 Department of Ophthalmology, The University of Cincinnati, Cincinnati, Ohio. 3 Department of Neurology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. 4 Department of Neurosurgery, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. 5 Department of Neurology, Michigan State University, East Lansing, Michigan. Reprint requests to Andrew G. Lee, MD, 200 Hawkins Drive PFP, Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242.
482
© 2002 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Methods The charts of all men with the diagnosis of IIH seen within the last 5 years at the University of Iowa Department of Ophthalmology, the University of Cincinnati and the Cincinnati Eye Institute, and the Michigan State University Neuroophthalmology Unit were reviewed. Patient data included age, signs and symptoms at onset, medications, associated conditions, height and weight, visual acuity, visual field, and optic disc appearance. Information regarding medical therapy, surgical treatment if applicable, and visual acuity and visual field status at the patients’ last visit were recorded. We used the Metropolitan Life Insurance Company (New York) criteria to define obesity.1 Patients were excluded if they were younger than 18 years at the time of diagnosis, because the aim of the study was to examine adult men only. Patients were also excluded if they had inadequate follow-up or documentation or if they did not meet modified Dandy criteria for the diagnosis of IIH. SA in all patients was defined by sleep study. A subgroup of patients with SA was identified and reviewed.
Results Thirty-two cases of IIH in men were identified. Of these 32 cases, 8 were excluded because of age less than 18 years, and 4 were excluded because of the presence of venous sinus thrombosis or possible medication-induced IIH. The medications in these patients included tetracycline, cyclosporine, and corticosteroid withdrawal. Two patients were excluded because of normal or unavailable opening pressure measurements. Of the remaining 18 patients, 6 adult cases met the modified Dandy criteria for the diagnosis of IIH and had SA syndrome. ISSN 0161-6420/02/$–see front matter PII S0161-6420(01)00987-3
Lee et al 䡠 Sleep Apnea Table 1. Sleep Apnea in Men with Intracranial Hypertension Patient (Age) Height/Weight
Treatment
Visual Acuity
1 (33) 2 (50) 3 (55)
5⬘8⬙/390# 6⬘1⬙/255# 5⬘9⬙/335#
CPAP Acetazolamide; CPAP Acetazolamide; CPAP
20/15 OU 20/15 OU 20/25 OU
4 (40) 5 (42)
6⬘7⬙/450# 6⬘1⬙/306#
Acetazolamide Acetazolamide; CPAP
20/15 OU 20/20 OU
6 (44)
5⬘4⬙/190#
Acetazolamide; CPAP
20/20 OU
Visual Field
At Last Exam: Optic Nerve
Enlarged BS, then normal OU Normal Enlarged BS, then normal OU Normal INS/PCS OD Optic atrophy OU INS/IAD OS Normal OU Normal Enlarged BS OU Papilledema improved with treatment Enlarged BS Papilledema improved with treatment
Sleep Study Apneic/Hyponeic Episodes per Hour (Minimum Oxygen Saturation) 135 (62%) 88 (70%) 45 (78%) 15 (81%) 46 (75%) 21 (70%)
BS ⫽ blind spot; CPAP ⫽ continuous positive airway pressure; IAD ⫽ inferior arcuate defect; INS ⫽ inferior nasal step; OD ⫽ right eye; OS ⫽ left eye; OU ⫽ both eyes; PCS ⫽ paracentral scotoma.
Table 1 lists the clinical features of the six patients. All patients were overweight as defined by the published large frame weight for height standards of the statistical bureau of the Metropolitan Life Insurance Company.1 All patients had preserved central acuity (20/20 or better in both eyes), enlarged blind spots on visual field testing, and optic disc edema in both eyes at presentation. All patients were treated; one received acetazolamide alone, four received acetazolamide and continuous positive airway pressure (CPAP), and one patient was treated with only CPAP. All six patients had resolution or improvement in optic disc edema. Five patients had normal visual fields after treatment, and one patient has residual visual field loss. Three patients had normal optic disc examinations at last follow-up. After resolution of the optic disc edema, these three patients were maintained on CPAP and discontinued acetazolamide. Two patients had persistent but improved papilledema and are under continued treatment with acetazolamide and CPAP. One patient had optic disc pallor develop in both eyes and is stable.
Discussion SA syndrome is a relatively common nocturnal breathing disorder that typically affects middle-aged obese men. The true prevalence of SA is unknown, but estimates range from 0.4% to 5.9% of men.2 In our study, six (33%) patients with SA were identified from a group of 18 patients with IIH. This figure is higher than the reported prevalence of SA in the general male population. Unfortunately, our study was retrospective, the sample size was small, our patients were selected from tertiary referral centers, and not all of our IIH patients had sleep studies. These limitations make it difficult to establish a valid prevalence number for SA in IIH in men. SA is characterized by recurrent complete or partial upper airway obstruction during sleep.3–5 The patients have excessive daytime somnolence (e.g., fatigue, sleep attacks), loud snoring, and periodic apnea with interruption of air flow, nocturnal hypoxia, hypercarbia, hypertension, and arterial oxygen desaturation. These apneic episodes may last from seconds to minutes, may occur hundreds of times per night, and are terminated by arousal from sleep. Systemic hypertension and cardiac arrhythmia may result from repetitive nocturnal sympathetic activation. The incidence of hypertension and cardiovascular disease among men with
SA is 30% to 40%.2 SA is associated with pulmonary arterial hypertension, cor pulmonale, polycythemia, ischemic heart disease, myocardial infarction, stroke, and death.3–5 The diagnosis is confirmed by overnight polysomnography. The treatments include weight loss, nocturnal oxygen therapy, nasal CPAP during sleep, and upper airway/oropharyngeal surgery.
Signs and Symptoms of Increased Intracranial Pressure in SA SA has been associated with headache and with optic disc edema.6 –19 Bucci and Krohel 6 reported a 46-year-old man with SA and bilateral optic disc edema. CSF contents were normal, and the opening pressure was 170 mm H2O. He subsequently underwent sequential rhinoplasty, uvulopalatopharyngoplasty, and permanent tracheostomy with resolution of his optic disc edema. Mojon et al,7 reported nine patients with SA who underwent complete eye examinations. Visual field defects caused by an underlying presumed optic neuropathy were noted. Mojon et al19 also reported in a separate article of 69 patients with SA that glaucoma was more prevalent in SA (7.2%) than in controls.19 In addition, Hayreh12 has reported a high prevalence of SA in patients with anterior ischemic optic neuropathy. Purvin et al18 studied four patients with bilateral optic disc edema and SA. Daytime ICP measurements were normal, but nocturnal monitoring in one patient demonstrated marked elevations of ICP associated with apnea and arterial oxygen desaturation. These authors concluded that intermittent elevation of ICP could produce papilledema. Patients with SA may complain of headaches that are worse in the morning. In addition, increased ICP and papilledema have been reported in SA. Sugita et al14 reported high CSF pressure during sleep in three patients. During the daytime these awake patients had CSF pressures that were relatively normal (mean, 260 mm H2O). During sleep, the CSF pressure showed marked, frequent, and episodic elevation, with CSF pressure waves from 50 to 750 mm H2O. Each nocturnal CSF pressure wave and elevation was preceded or accompanied by an episode of SA or hypopnea and decreased to normal within a few seconds of respiration.
483
Ophthalmology Volume 109, Number 3, March 2002 Doyle and Tami17 reported a 29-year-old obese man with SA, with acute papilledema, markedly elevated ICP (460 mm H2O), and severe visual loss who required a lumboperitoneal shunt. Meyer et al13 had reported elevated ICP and papilledema in a Pickwickian patient.
Possible Mechanisms of Increased ICP Mojon et al7 postulated several potential mechanisms of optic neuropathy in SA including (1) impaired optic nerve head blood flow autoregulation secondary to apneic episodes; (2) failure of optic nerve autoregulation because of arterial hypertension and arteriosclerosis induced by SA; (3) prolonged hypoxic damage to the optic nerve; and (4) imbalance between vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin). Sugita et al,14 proposed three possible mechanisms for increased CSF pressure in SA: (1) increased central venous pressure and secondary increased cerebrovascular volume; (2) increased systemic arterial blood pressure with secondary increased cerebral perfusion pressure; and (3) hypoxic and hypercapneic cerebral vasodilation and secondary increased intracranial blood volume. Chronic pulmonary insufficiency can cause optic disc edema.9 The Pickwickian syndrome (i.e., the sleep apnea, obesity, and hypoventilation syndrome) has been associated with optic disc edema. Jennum et al15 reported increased ICP and obstructive SA. Hypercapnia produces cerebral vasodilation, decreases vascular resistance, and increases cerebral blood flow.14 Breathing high carbon dioxide air increases ICP and intracranial blood volume. Kirkpatrick et al16 reported a morbidly obese woman with normal daytime ICP, but transient episodes of increased ICP were documented by invasive continuous ICP monitoring during sleep. These episodes were accompanied by hypoxia and hypercapnia and hemodynamic changes consistent with cerebral vasodilation. Wolin and Brannon8 reported an obese 46-year-old African American woman with SA, papilledema, and an elevated opening pressure (500 mm H2O). This patient was treated with bi PAP, home oxygen therapy, acetazolamide, and weight reduction with dramatic improvement of papilledema over 2 months. Digre and Corbett20 reviewed the literature on IIH in men in 1988. They reviewed 84 cases of IIH in men from the literature and documented the following associated conditions in these patients: head trauma, medication or toxin exposure (e.g., steroids, Kepone, lindane, vitamin A, tetracycline, amiodarone, phenytoin), infection (e.g., syphilis, otitis media), systemic diseases (e.g., thyroid disease, pseudohypoparathyroidism, Behc¸ et’s disease, paroxysmal nocturnal hemoglobinuria, systemic lupus erythematosus, microadenoma with adrenocorticotrophin hormone production, and neuroimaging abnormalities (e.g., empty sella, sagittal sinus thrombosis). They described 29 men with IIH. The average age was 33.7 years. Nineteen (66%) of 29 patients were obese, and 42% had hypertension. Eighteen (62%) of 29 patients improved, and 16 (55%) had normal visual outcome. These men were compared with agematched women with IIH. Men required surgical proce-
484
dures (34%) more frequently than women with IIH and tended to have more severe visual loss. The men were compared with age-matched male controls without IIH and were significantly more obese (66%) and more likely to have hypertension. Digre and Corbett20 in their large study of IIH in men concluded: (1) IIH occurs in men less frequently than women, (2) IIH occurs in men in the same age distribution as women, (3) the signs and symptoms of IIH were similar for both genders, (4) men required surgical therapy more often, (5) African American men seemed to have a higher risk of visual loss, and (6) men with IIH are often obese and require weight loss counseling.20 Kesler et al21 compared 18 men with IIH with 116 women. The clinical features were identical in the two groups, although the men in this study were less likely to be overweight. SA was not specifically commented on in these studies. Marcus et al22 reported 14 patients of 37 with IIH with symptoms of sleep disturbance. Of these 14 (2 men and 12 women), 6 had SA and 7 had upper airway resistance syndrome. The two men in this study were also the only two men in the authors’ population with IIH. In our study, all patients had preserved central acuity (20/20 or better in both eyes). All patients had enlarged blind spots caused by optic disc edema in both eyes at presentation. Four patients had normal visual fields after treatment, and one patient has residual visual field loss. This latter patient may have had a superimposed anterior ischemic optic neuropathy related to underlying papilledema and SA or visual field loss related to chronic optic disc edema. Three patients had normal optic discs at last follow-up and are continuing on CPAP treatment alone. One patient had persistent but improved papilledema and is under continued treatment with both CPAP and acetazolamide. The average number of apneic/hyponeic events in our patients was 58 per hour (range, 15–135/hour). The average minimum oxygen saturation was 73% (range, 62%– 81%). It is possible that patients with papilledema may have more severe SA. All of our patients were overweight, with an average height of 5 feet 11 inches and an average weight of 321 pounds. We recognize the limitations of our study. First, there are problems inherent in any retrospective review including referral bias, ascertainment bias, and selection bias. We did not prospectively evaluate all patients with polysomnography or standardized weight and height measurements. Second, the sample size is limited, because IIH is uncommon in men. In addition, SA may be a comorbid condition with IIH in men without a causal association, because both conditions are related to obesity. Third, we excluded patients without documented daytime intracranial hypertension. Despite these limitations, we believe that SA should be considered as an association with optic disc edema in men. The diagnosis of SA should be considered even without documented increased daytime ICP, because nocturnal elevation of ICP caused by hypoxia and hypercapnia may be the cause of optic disc edema in these patients. Treatment of SA has well-documented general medical benefits and theoretic merit in reducing ICP. It is possible that reducing nocturnal hypoxia and hypercarbia (e.g., CPAP, surgery) could reduce the risk of papilledema and visual loss in some
Lee et al 䡠 Sleep Apnea patients. Further work is necessary to establish the role of SA in the pathogenesis of IIH in men.
References 1. Metropolitan Life Insurance Company. New weight standards for men and women. Stat Bull Metropol Life Insur Co 1959; 40:1– 4. 2. Palomaki H, Partinen M, Erkinjuntti T, Kaste M. Snoring, sleep apnea, and stroke. Neurology 1992;42:75– 81; discussion 82. 3. Koskenvuo M, Kaprio J, Telakivi T, et al. Snoring as a risk factor for ischaemic heart disease and stroke in men. Br Med J (Clin Res Ed) 1987;294;16 –9. 4. Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients. Mortality. Chest 1988;94:1200 – 4. 5. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261– 4. 6. Bucci FA Jr, Krohel GB. Optic nerve swelling secondary to obstructive sleep apnea syndrome. Am J Ophthalmol 1988; 105:428 –30. 7. Mojon DS, Mathis J, Zulauf M, et al. Optic neuropathy associated with sleep apnea syndrome. Ophthalmology 1998;105: 874 –7. 8. Wolin MJ, Brannon WL. Disk edema in an overweight woman. Surv Ophthalmol 1995;39:307–14. 9. Spalter HF, Bruce GM. Ocular changes in pulmonary insufficiency. Trans Am Acad Ophthalmol Otolaryngol 1964;68: 661–76. 10. Jennum P, Borgensen SE. Intracranial pressure and obstructive sleep apnea. Chest 1989;95:279 – 83. 11. McNamara ME. Idiopathic intracranial hypertension without papilledema: related to sleep apnea? [letter]. Arch Neurol 1992;49:14.
12. Hayreh SS. Acute ischemic disorders of the optic nerve: pathogenesis, clinical manifestations, and management. Ophthalmol Clin North Am 1996;9:407– 42. 13. Meyer JS, Gotham J, Tazaki Y, Gotoh F. Cardiorespiratory syndrome of extreme obesity with papilledema. Report of a fatal case with electroencephalographic, metabolic, and necropsy studies. Neurology (Minneap) 1961;11:950 – 8. 14. Sugita Y, Iijima S, Teshima Y, et al. Marked episodic elevation of cerebrospinal fluid pressure during nocturnal sleep in patients with sleep apena hypersomnia syndrome. Electroencephalogr Clin Neurophysiol 1985;60:214 –9. 15. Jennum P, Hein HO, Suadicani P, Gyntelberg F. Headache and cognitive dysfunction in snorers. A cross-sectional study of 3323 men aged 54 to 74 years: the Copenhagen Male Study. Arch Neurol 1994;51:937– 42. 16. Kirkpatrick PJ, Meyer T, Sarkies N, et al. Papilloedema and visual failure in a patient with nocturnal hypoventilation [letter]. J Neurol Neurosurg Psychiatry 1994;57:1546 –7. 17. Doyle KJ, Tami TA. Increased intracranial pressure and blindness associated with obstructive sleep apnea. Otolaryngol Head Neck Surg 1991;105:613– 6. 18. Purvin VA, Kawasaki A, Yee RD. Papilledema and obstructive sleep apnea syndrome. Arch Ophthalmol 2000;118:1626 – 30. 19. Mojon DS, Hess CW, Goldblum D, et al. High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology 1999;106:1009 –12. 20. Digre KB, Corbett JJ. Pseudotumor cerebri in men [published erratum appears in Arch Neurol 1989;46:72]. Arch Neurol 1988;45:866 –72. 21. Kesler A, Goldhammer Y, Gadoth N. Do men with pseudotumor cerebri share the same characteristics as women? A retrospective review of 141 cases. J Neuroophthalmol 2001; 2:15–7. 22. Marcus DM, Lynn J, Miller JJ, et al. Sleep disorders: a risk factor for pseudotumor cerebri? J Neuroophthalmol 2001;21: 121–3.
485
Originally received: June 14, 2001. Accepted: July 31, 2001. Manuscript no. 210406. 1 Department of Ophthalmology, The University of Iowa Hospitals and Clinics. 2 Department of Ophthalmology, The University of Cincinnati, Cincinnati, Ohio. 3 Department of Neurology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. 4 Department of Neurosurgery, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. 5 Department of Neurology, Michigan State University, East Lansing, Michigan. Reprint requests to Andrew G. Lee, MD, 200 Hawkins Drive PFP, Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242.
482
© 2002 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Methods The charts of all men with the diagnosis of IIH seen within the last 5 years at the University of Iowa Department of Ophthalmology, the University of Cincinnati and the Cincinnati Eye Institute, and the Michigan State University Neuroophthalmology Unit were reviewed. Patient data included age, signs and symptoms at onset, medications, associated conditions, height and weight, visual acuity, visual field, and optic disc appearance. Information regarding medical therapy, surgical treatment if applicable, and visual acuity and visual field status at the patients’ last visit were recorded. We used the Metropolitan Life Insurance Company (New York) criteria to define obesity.1 Patients were excluded if they were younger than 18 years at the time of diagnosis, because the aim of the study was to examine adult men only. Patients were also excluded if they had inadequate follow-up or documentation or if they did not meet modified Dandy criteria for the diagnosis of IIH. SA in all patients was defined by sleep study. A subgroup of patients with SA was identified and reviewed.
Results Thirty-two cases of IIH in men were identified. Of these 32 cases, 8 were excluded because of age less than 18 years, and 4 were excluded because of the presence of venous sinus thrombosis or possible medication-induced IIH. The medications in these patients included tetracycline, cyclosporine, and corticosteroid withdrawal. Two patients were excluded because of normal or unavailable opening pressure measurements. Of the remaining 18 patients, 6 adult cases met the modified Dandy criteria for the diagnosis of IIH and had SA syndrome. ISSN 0161-6420/02/$–see front matter PII S0161-6420(01)00987-3
Lee et al 䡠 Sleep Apnea Table 1. Sleep Apnea in Men with Intracranial Hypertension Patient (Age) Height/Weight
Treatment
Visual Acuity
1 (33) 2 (50) 3 (55)
5⬘8⬙/390# 6⬘1⬙/255# 5⬘9⬙/335#
CPAP Acetazolamide; CPAP Acetazolamide; CPAP
20/15 OU 20/15 OU 20/25 OU
4 (40) 5 (42)
6⬘7⬙/450# 6⬘1⬙/306#
Acetazolamide Acetazolamide; CPAP
20/15 OU 20/20 OU
6 (44)
5⬘4⬙/190#
Acetazolamide; CPAP
20/20 OU
Visual Field
At Last Exam: Optic Nerve
Enlarged BS, then normal OU Normal Enlarged BS, then normal OU Normal INS/PCS OD Optic atrophy OU INS/IAD OS Normal OU Normal Enlarged BS OU Papilledema improved with treatment Enlarged BS Papilledema improved with treatment
Sleep Study Apneic/Hyponeic Episodes per Hour (Minimum Oxygen Saturation) 135 (62%) 88 (70%) 45 (78%) 15 (81%) 46 (75%) 21 (70%)
BS ⫽ blind spot; CPAP ⫽ continuous positive airway pressure; IAD ⫽ inferior arcuate defect; INS ⫽ inferior nasal step; OD ⫽ right eye; OS ⫽ left eye; OU ⫽ both eyes; PCS ⫽ paracentral scotoma.
Table 1 lists the clinical features of the six patients. All patients were overweight as defined by the published large frame weight for height standards of the statistical bureau of the Metropolitan Life Insurance Company.1 All patients had preserved central acuity (20/20 or better in both eyes), enlarged blind spots on visual field testing, and optic disc edema in both eyes at presentation. All patients were treated; one received acetazolamide alone, four received acetazolamide and continuous positive airway pressure (CPAP), and one patient was treated with only CPAP. All six patients had resolution or improvement in optic disc edema. Five patients had normal visual fields after treatment, and one patient has residual visual field loss. Three patients had normal optic disc examinations at last follow-up. After resolution of the optic disc edema, these three patients were maintained on CPAP and discontinued acetazolamide. Two patients had persistent but improved papilledema and are under continued treatment with acetazolamide and CPAP. One patient had optic disc pallor develop in both eyes and is stable.
Discussion SA syndrome is a relatively common nocturnal breathing disorder that typically affects middle-aged obese men. The true prevalence of SA is unknown, but estimates range from 0.4% to 5.9% of men.2 In our study, six (33%) patients with SA were identified from a group of 18 patients with IIH. This figure is higher than the reported prevalence of SA in the general male population. Unfortunately, our study was retrospective, the sample size was small, our patients were selected from tertiary referral centers, and not all of our IIH patients had sleep studies. These limitations make it difficult to establish a valid prevalence number for SA in IIH in men. SA is characterized by recurrent complete or partial upper airway obstruction during sleep.3–5 The patients have excessive daytime somnolence (e.g., fatigue, sleep attacks), loud snoring, and periodic apnea with interruption of air flow, nocturnal hypoxia, hypercarbia, hypertension, and arterial oxygen desaturation. These apneic episodes may last from seconds to minutes, may occur hundreds of times per night, and are terminated by arousal from sleep. Systemic hypertension and cardiac arrhythmia may result from repetitive nocturnal sympathetic activation. The incidence of hypertension and cardiovascular disease among men with
SA is 30% to 40%.2 SA is associated with pulmonary arterial hypertension, cor pulmonale, polycythemia, ischemic heart disease, myocardial infarction, stroke, and death.3–5 The diagnosis is confirmed by overnight polysomnography. The treatments include weight loss, nocturnal oxygen therapy, nasal CPAP during sleep, and upper airway/oropharyngeal surgery.
Signs and Symptoms of Increased Intracranial Pressure in SA SA has been associated with headache and with optic disc edema.6 –19 Bucci and Krohel 6 reported a 46-year-old man with SA and bilateral optic disc edema. CSF contents were normal, and the opening pressure was 170 mm H2O. He subsequently underwent sequential rhinoplasty, uvulopalatopharyngoplasty, and permanent tracheostomy with resolution of his optic disc edema. Mojon et al,7 reported nine patients with SA who underwent complete eye examinations. Visual field defects caused by an underlying presumed optic neuropathy were noted. Mojon et al19 also reported in a separate article of 69 patients with SA that glaucoma was more prevalent in SA (7.2%) than in controls.19 In addition, Hayreh12 has reported a high prevalence of SA in patients with anterior ischemic optic neuropathy. Purvin et al18 studied four patients with bilateral optic disc edema and SA. Daytime ICP measurements were normal, but nocturnal monitoring in one patient demonstrated marked elevations of ICP associated with apnea and arterial oxygen desaturation. These authors concluded that intermittent elevation of ICP could produce papilledema. Patients with SA may complain of headaches that are worse in the morning. In addition, increased ICP and papilledema have been reported in SA. Sugita et al14 reported high CSF pressure during sleep in three patients. During the daytime these awake patients had CSF pressures that were relatively normal (mean, 260 mm H2O). During sleep, the CSF pressure showed marked, frequent, and episodic elevation, with CSF pressure waves from 50 to 750 mm H2O. Each nocturnal CSF pressure wave and elevation was preceded or accompanied by an episode of SA or hypopnea and decreased to normal within a few seconds of respiration.
483
Ophthalmology Volume 109, Number 3, March 2002 Doyle and Tami17 reported a 29-year-old obese man with SA, with acute papilledema, markedly elevated ICP (460 mm H2O), and severe visual loss who required a lumboperitoneal shunt. Meyer et al13 had reported elevated ICP and papilledema in a Pickwickian patient.
Possible Mechanisms of Increased ICP Mojon et al7 postulated several potential mechanisms of optic neuropathy in SA including (1) impaired optic nerve head blood flow autoregulation secondary to apneic episodes; (2) failure of optic nerve autoregulation because of arterial hypertension and arteriosclerosis induced by SA; (3) prolonged hypoxic damage to the optic nerve; and (4) imbalance between vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin). Sugita et al,14 proposed three possible mechanisms for increased CSF pressure in SA: (1) increased central venous pressure and secondary increased cerebrovascular volume; (2) increased systemic arterial blood pressure with secondary increased cerebral perfusion pressure; and (3) hypoxic and hypercapneic cerebral vasodilation and secondary increased intracranial blood volume. Chronic pulmonary insufficiency can cause optic disc edema.9 The Pickwickian syndrome (i.e., the sleep apnea, obesity, and hypoventilation syndrome) has been associated with optic disc edema. Jennum et al15 reported increased ICP and obstructive SA. Hypercapnia produces cerebral vasodilation, decreases vascular resistance, and increases cerebral blood flow.14 Breathing high carbon dioxide air increases ICP and intracranial blood volume. Kirkpatrick et al16 reported a morbidly obese woman with normal daytime ICP, but transient episodes of increased ICP were documented by invasive continuous ICP monitoring during sleep. These episodes were accompanied by hypoxia and hypercapnia and hemodynamic changes consistent with cerebral vasodilation. Wolin and Brannon8 reported an obese 46-year-old African American woman with SA, papilledema, and an elevated opening pressure (500 mm H2O). This patient was treated with bi PAP, home oxygen therapy, acetazolamide, and weight reduction with dramatic improvement of papilledema over 2 months. Digre and Corbett20 reviewed the literature on IIH in men in 1988. They reviewed 84 cases of IIH in men from the literature and documented the following associated conditions in these patients: head trauma, medication or toxin exposure (e.g., steroids, Kepone, lindane, vitamin A, tetracycline, amiodarone, phenytoin), infection (e.g., syphilis, otitis media), systemic diseases (e.g., thyroid disease, pseudohypoparathyroidism, Behc¸ et’s disease, paroxysmal nocturnal hemoglobinuria, systemic lupus erythematosus, microadenoma with adrenocorticotrophin hormone production, and neuroimaging abnormalities (e.g., empty sella, sagittal sinus thrombosis). They described 29 men with IIH. The average age was 33.7 years. Nineteen (66%) of 29 patients were obese, and 42% had hypertension. Eighteen (62%) of 29 patients improved, and 16 (55%) had normal visual outcome. These men were compared with agematched women with IIH. Men required surgical proce-
484
dures (34%) more frequently than women with IIH and tended to have more severe visual loss. The men were compared with age-matched male controls without IIH and were significantly more obese (66%) and more likely to have hypertension. Digre and Corbett20 in their large study of IIH in men concluded: (1) IIH occurs in men less frequently than women, (2) IIH occurs in men in the same age distribution as women, (3) the signs and symptoms of IIH were similar for both genders, (4) men required surgical therapy more often, (5) African American men seemed to have a higher risk of visual loss, and (6) men with IIH are often obese and require weight loss counseling.20 Kesler et al21 compared 18 men with IIH with 116 women. The clinical features were identical in the two groups, although the men in this study were less likely to be overweight. SA was not specifically commented on in these studies. Marcus et al22 reported 14 patients of 37 with IIH with symptoms of sleep disturbance. Of these 14 (2 men and 12 women), 6 had SA and 7 had upper airway resistance syndrome. The two men in this study were also the only two men in the authors’ population with IIH. In our study, all patients had preserved central acuity (20/20 or better in both eyes). All patients had enlarged blind spots caused by optic disc edema in both eyes at presentation. Four patients had normal visual fields after treatment, and one patient has residual visual field loss. This latter patient may have had a superimposed anterior ischemic optic neuropathy related to underlying papilledema and SA or visual field loss related to chronic optic disc edema. Three patients had normal optic discs at last follow-up and are continuing on CPAP treatment alone. One patient had persistent but improved papilledema and is under continued treatment with both CPAP and acetazolamide. The average number of apneic/hyponeic events in our patients was 58 per hour (range, 15–135/hour). The average minimum oxygen saturation was 73% (range, 62%– 81%). It is possible that patients with papilledema may have more severe SA. All of our patients were overweight, with an average height of 5 feet 11 inches and an average weight of 321 pounds. We recognize the limitations of our study. First, there are problems inherent in any retrospective review including referral bias, ascertainment bias, and selection bias. We did not prospectively evaluate all patients with polysomnography or standardized weight and height measurements. Second, the sample size is limited, because IIH is uncommon in men. In addition, SA may be a comorbid condition with IIH in men without a causal association, because both conditions are related to obesity. Third, we excluded patients without documented daytime intracranial hypertension. Despite these limitations, we believe that SA should be considered as an association with optic disc edema in men. The diagnosis of SA should be considered even without documented increased daytime ICP, because nocturnal elevation of ICP caused by hypoxia and hypercapnia may be the cause of optic disc edema in these patients. Treatment of SA has well-documented general medical benefits and theoretic merit in reducing ICP. It is possible that reducing nocturnal hypoxia and hypercarbia (e.g., CPAP, surgery) could reduce the risk of papilledema and visual loss in some
Lee et al 䡠 Sleep Apnea patients. Further work is necessary to establish the role of SA in the pathogenesis of IIH in men.
References 1. Metropolitan Life Insurance Company. New weight standards for men and women. Stat Bull Metropol Life Insur Co 1959; 40:1– 4. 2. Palomaki H, Partinen M, Erkinjuntti T, Kaste M. Snoring, sleep apnea, and stroke. Neurology 1992;42:75– 81; discussion 82. 3. Koskenvuo M, Kaprio J, Telakivi T, et al. Snoring as a risk factor for ischaemic heart disease and stroke in men. Br Med J (Clin Res Ed) 1987;294;16 –9. 4. Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients. Mortality. Chest 1988;94:1200 – 4. 5. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261– 4. 6. Bucci FA Jr, Krohel GB. Optic nerve swelling secondary to obstructive sleep apnea syndrome. Am J Ophthalmol 1988; 105:428 –30. 7. Mojon DS, Mathis J, Zulauf M, et al. Optic neuropathy associated with sleep apnea syndrome. Ophthalmology 1998;105: 874 –7. 8. Wolin MJ, Brannon WL. Disk edema in an overweight woman. Surv Ophthalmol 1995;39:307–14. 9. Spalter HF, Bruce GM. Ocular changes in pulmonary insufficiency. Trans Am Acad Ophthalmol Otolaryngol 1964;68: 661–76. 10. Jennum P, Borgensen SE. Intracranial pressure and obstructive sleep apnea. Chest 1989;95:279 – 83. 11. McNamara ME. Idiopathic intracranial hypertension without papilledema: related to sleep apnea? [letter]. Arch Neurol 1992;49:14.
12. Hayreh SS. Acute ischemic disorders of the optic nerve: pathogenesis, clinical manifestations, and management. Ophthalmol Clin North Am 1996;9:407– 42. 13. Meyer JS, Gotham J, Tazaki Y, Gotoh F. Cardiorespiratory syndrome of extreme obesity with papilledema. Report of a fatal case with electroencephalographic, metabolic, and necropsy studies. Neurology (Minneap) 1961;11:950 – 8. 14. Sugita Y, Iijima S, Teshima Y, et al. Marked episodic elevation of cerebrospinal fluid pressure during nocturnal sleep in patients with sleep apena hypersomnia syndrome. Electroencephalogr Clin Neurophysiol 1985;60:214 –9. 15. Jennum P, Hein HO, Suadicani P, Gyntelberg F. Headache and cognitive dysfunction in snorers. A cross-sectional study of 3323 men aged 54 to 74 years: the Copenhagen Male Study. Arch Neurol 1994;51:937– 42. 16. Kirkpatrick PJ, Meyer T, Sarkies N, et al. Papilloedema and visual failure in a patient with nocturnal hypoventilation [letter]. J Neurol Neurosurg Psychiatry 1994;57:1546 –7. 17. Doyle KJ, Tami TA. Increased intracranial pressure and blindness associated with obstructive sleep apnea. Otolaryngol Head Neck Surg 1991;105:613– 6. 18. Purvin VA, Kawasaki A, Yee RD. Papilledema and obstructive sleep apnea syndrome. Arch Ophthalmol 2000;118:1626 – 30. 19. Mojon DS, Hess CW, Goldblum D, et al. High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology 1999;106:1009 –12. 20. Digre KB, Corbett JJ. Pseudotumor cerebri in men [published erratum appears in Arch Neurol 1989;46:72]. Arch Neurol 1988;45:866 –72. 21. Kesler A, Goldhammer Y, Gadoth N. Do men with pseudotumor cerebri share the same characteristics as women? A retrospective review of 141 cases. J Neuroophthalmol 2001; 2:15–7. 22. Marcus DM, Lynn J, Miller JJ, et al. Sleep disorders: a risk factor for pseudotumor cerebri? J Neuroophthalmol 2001;21: 121–3.
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