□ CASE REPORT □ Obstructive Sleep Apnea Syndrome (OSAS) Presenting as Cerebral Venous Thrombosis Naohide Kondo 1, Yasuhiro Ito 2, Makoto Kawai 3, Junichiro Suzuki 2, Hirotake Tsuji 2, Suguru Nishida 2, Takeshi Yasuda 2 and Gen Sobue 1 Abstract There are many reports that obstructive sleep apnea syndrome (OSAS) is a risk factor for ischemic stroke of arterial origin, however, the relationship between OSAS and cerebral venous thrombosis (CVT) remains unknown. We report the case of a 44-year-old man who had episodic headaches, unconsciousness attacks and seizures. Cerebral angiography showed CVT. He was obese and had severe OSAS. Noninvasive continuous positive airway pressure (CPAP) therapy prevented the recurrence of CVT as well as of headache. OSAS may be one of the multiple risk factors of CVT as well as arterial ischemic stroke. Key words: obstructive sleep apnea syndrome, cerebral venous thrombosis, dehydration, erythrocytosis, noninvasive continuous positive airway pressure therapy (Inter Med 48: 1837-1840, 2009) (DOI: 10.2169/internalmedicine.48.2037) Introduction Obstructive sleep apnea syndrome (OSAS) has been recognized as a common but treatable form of disordered breathing in which the upper airway closes repeatedly during sleep (1). The syndrome is associated with vascular risk factors and substantial cardiovascular morbidity and mortality. OSAS is also a risk factor for ischemic stroke of arterial origin (2). However, the relationship between OSAS and cerebral venous thrombosis (CVT) is not known. Here, we describe a case of CVT with OSAS. We successfully treated the patient with noninvasive continuous positive airway pressure (CPAP) therapy. Case Report A 44-year-old man was admitted to our hospital with the sudden onset of a transient loss of consciousness and seizure. The duration of the unconsciousness attack was a few minutes and he bit his tongue. On the day of admission, he had worked about 2 hours in hot weather and experienced severe dehydration. He noticed only nausea before the onset of unconsciousness attack. His medical history showed hypertension with no medication and episodic headaches in his entire head. He had often had headaches for several years and his wife noticed his strong snoring for the same term but no previous seizure attack was confirmed. He was neither a smoker nor a drinker. On admission, he was very obese, 169.0 cm in height and 90.0 kg in body weight. His body mass index (BMI) was 31.4 kg/cm2. His body weight had not changed for about 10 years. He was afebrile. His blood pressure was 211/104 mmHg with a regular pulse of 119/min. There was no other significant abnormality in general physical examinations. He had no clinical symptoms and physical findings indicating heart failure. And there was no symptom indicating Behçet’s disease or ulcerative colitis. He was alert and showed no significant neurological deficit. Results of laboratory investigations were normal in electrolyte, blood sugar and liver enzyme levels, but abnormal in red blood cell count, hemoglobin and hematocrit levels (RBC 510×104/μL, Hb 18.9 g/dL, Ht 51.2%). He was considered to be in a state of dehydration because of a large quantity of sweat, but serum BUN level and Cr level were normal (BUN 13 mg/dL, Cr 1.0 mg/dL). And the platelet count was normal (20.5×104/μL). Antinuclear antibody and 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, 2Department of Neurology, TOYOTA Memorial Hospital, Toyota and 3Department of Integrated Medicine, TOYOTA Memorial Hospital, Toyota Received for publication January 10, 2009; Accepted for publication June 30, 2009 Correspondence to Dr. Naohide Kondo, naohidek@med.nagoya-u.ac.jp 1837 Inter Med 48: 1837-1840, 2009 DOI: 10.2169/internalmedicine.48.2037 A B Fi g ur e1 . Ma g ne t i cr e s o na nc ei ma g ei ndi c a t i ngal o wi nt e ns i t ya r e ao nt her i g htt e mpo r a ll o be ( A)( a r r o w)a ndahi g hi nt e ns i t ya r e ao nt hepa r i e t a ll o be( B)( a r r o whe a d)i nt heFLAI Ri ma g e . A B Fi g ur e2 . Ce r e br a la ng i o g r a phys ho we dno r ma ls upe r i o rs a g i t t a ls i nus( A)a ndat hr o mbuso n t hel e f tc o r t i c a lv e i ni nt hel a t epha s e( B)( a r r o w) . rheumatoid factor were negative. Protein C, protein S and antithrombin III levels were normal. D-dimer level was 0.5 μg/mL. A chest X-ray film indicated the increase in cardiothoracic ratio by about 62%. Electrocardiogram was normal. There was no data about serum BNP level or cardiac echo before CPAP therapy. Cerebrospinal fluid analysis including cell count, glucose, protein, and cultures was normal. An electroencephalogram (EEG) was normal. A computed tomography of the head was normal. Magnetic resonance imaging performed three hours after the onset of unconsciousness attack showed a low-intensity area on the right temporal lobe in the FLAIR and T2* images. A highintensity area in the FLAIR image on both sides of the parietal lobe resembles a vessel (Fig. 1). Magnetic resonance venography and CT venography indicated defects in the cortical veins. Cerebral angiography showed a thrombus on the parietal cortical veins in the late phase, however, the superior sagittal, transverse and straight sinuses were patent (Fig. 2). The venous thrombus in cerebral angiography was on the left parietal lobe, which was contrary to the lesion of thrombus at the right temporal lobe found in the magnetic resonance. The right side lesion was thought to be an old venous thrombus. Thus, the headache was suspected to be a symptom of cerebral venous thrombosis. First, we started antidehydration and anticoagulation therapy with heparin and warfarin. After admission, he was noted to have severe snoring and sleep apnea. Polysomnography revealed that the apnea-hypopnea index (AHI), which is the number of apnea episodes per hour, was 54.0, the maximum apnea term was 84 seconds and the minimum O2 saturation was 43%. We diagnosed him as having severe obstructive sleep apnea syndrome (OSAS) according to the diagnostic criteria. Despite his recovery from dehydration, his polycythemia persisted (Hb 17.2 g/dL), suggesting that in addition to chronic polycythemia due to OSAS, his severe dehydration due to working under a hot weather induced cerebral venous thrombosis. The introduction of noninvasive CPAP treatment was very effective in controlling hypertension and chronic headache. The clinical course was very good and he was discharged on the 8th hospital day with no complications. Two months later, reexamination by magnetic resonance imaging revealed the same findings of abnormal lesions on the right temporal lobe and on both parietal lobes, but no re- 1838 Inter Med 48: 1837-1840, 2009 DOI: 10.2169/internalmedicine.48.2037 currence was noted. We stopped the anticoagulation therapy 3 months after the onset according to the guideline for cerebral venous thrombosis (3), and then we successfully prevented cerebral venous thrombosis recurrence and ameliorated the headache for more than one year by only noninvasive CPAP treatment. The follow-up data of hemoglobin level was 15.1 g/dL and blood pressure normalized without medication. Discussion There are many reports on the causes of cerebral venous thrombosis (CVT). Genetic prothrombotic conditions, acquired prothrombotic states, infections, inflammatory diseases, hematologic conditions, drugs, mechanical factors, trauma, and miscellaneous factors are well-known causes of CVT (3). However, no clear causes or risk factors are identified in about 10-40% of patients with CVT (3). In the present case, we could diagnose CVT soon by the symptoms and the findings of MRI. As for the serum D-dimer level, it was normal in this case. It is known that a negative D-dimer assay does not completely rule out CVT, particularly in the setting of recent isolated headache (4). He had no apparent risk factor for CVT except for dehydration and polycythemia. Dehydration is regarded as a cause of CVT in children or a specific condition (5). Polycythemia is also reported to be a cause of CVT (6), however the precise mechanism and etiology of polycythemia remains unknown. Thus far, there has been no report on CVT associated with OSAS. There is a possibility that OSAS has been ignored as a cause of CVT. We diagnosed our patient as having severe OSAS (7). OSAS causes catecholamine release and sleep disturbance stress, and nocturnal-hypoxia leads to stimulation of erythropoietin production and ultimately erythrocytosis (8). This status is associated with chronic polycythemia and hypertension (2). OSAS also leads to platelet activation (9). Polycythemia and platelet activation are significant risk factors of cerebral venous thrombosis. We suspect that acute dehydration under polycythemia and platelet activation due to OSAS triggered CVT (Fig. 3). OSAS with polycythemia and platelet activation is a Fi g ur e3 . Me c ha ni s mo fc e r e br a lv e no ust hr o mbo s i so c c ur r e nc ewi t ho bs t r uc t i v es l e e pa pne as y ndr o me .OSASc a us e s c a t e c ho l a mi ne r e l e a s ea nd s l e e p di s t ur ba nc es t r e s s ,a nd no c t ur na l hy po x i al e a dst os t i mul a t i o no fe r y t hr o po i e t i npr o duc t i o na ndul t i ma t e l ye r y t hr o c y t o s i s .Thi ss t a t usi sa s s o c i a t e dwi t hc hr o ni cpo l y c y t he mi aa ndhy pe r t e ns i o n.OSASa l s o l e a dst opl a t e l e ta c t i v a t i o n.Po l y c y t he mi aa ndpl a t e l e ta c t i v a t i o n a r e s i g ni f i c a nt r i s k f a c t o r so fc e r e br a lv e no us t hr o mbo s i s .I nt hi sc a s ei ti ss us pe c t e dt ha ta c ut ede hy dr a t i o n unde rpo l y c y t he mi aa ndpl a t e l e ta c t i v a t i o nduet oOSASt r i g g e r e dCVT. cause of CVT as well as arterial ischemic stroke. The most important observations suggesting that CVT is related to OSAS were the successful prevention of recurrence in CVT and the amelioration of headache by the treatments of OSAS; these include weight control, noninvasive CPAP therapy, orthostatic operation, and the use of a mouthpiece (10-12). It has been demonstrated that airway pressurization, the main medical therapy for the syndrome, can reverse hypercoagulability and hemodynamic change and can even reduce the risk of cardiovascular events (13, 14). In the present case, we successfully prevented the recurrence of CVT by noninvasive CPAP therapy. The introduction of noninvasive CPAP therapy for OSAS patients should be strongly recommended to prevent the occurrence of cerebral venous thrombosis as well as arterial infarction. References 1. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165: 1217-1239, 2002. 2. 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