Matthias Gugger

Sleep-Disordered Breathing and Acute Ischemic Stroke: Diagnosis, Risk Factors, Treatment, Evolution, and Long-Term Clinical Outcome

Background and Purpose— Sleep-disordered breathing (SDB) is frequent in stroke patients. Risk factors, treatment response, short-term and long-term outcome of SDB in stroke patients are poorly known. Methods— We prospectively studied 152 patients (mean age 56±13 years) with acute ischemic stroke. Cardiovascular risk factors, Epworth sleepiness score (ESS), stroke severity/etiology, and time of stroke onset were assessed. The apnea-hypopnea index (AHI) was determined 3±2 days after stroke onset and 6 months later (subacute phase). Continuous positive airway pressure (CPAP) treatment was started acutely in patients with SDB (AHI ≥15 or AHI ≥10+ESS >10). CPAP compliance, incidence of vascular events, and stroke outcome were assessed 60±16 months later (chronic phase). Results— Initial AHI was 18±16 (≥10 in 58%, ≥30 in 17% of patients) and decreased in the subacute phase (P<0.001). Age, diabetes, and nighttime stroke onset were independent predictors of AHI (r2=0.34). In patients with AHI ≥30, age, male gender, body mass index, diabetes, hypertension, coronary heart disease, ESS, and macroangiopathic etiology of stroke were significantly higher/more common than in patients with AHI <10. Long-term incidence of vascular events and stroke outcome were similar in both groups. CPAP was started in 51% and continued chronically in 15% of SDB pts. Long-term stroke mortality was associated with initial AHI, age, hypertension, diabetes, and coronary heart disease. Conclusions— SDB is common particularly in elderly stroke male patients with diabetes, nighttime stroke onset, and macroangiopathy as cause of stroke; it improves after the acute phase, is associated with an increased poststroke mortality, and can be treated with CPAP in a small percentage of patients.

Restless Legs Syndrome: A Clinical Study of 55 Patients

Background: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. Objective: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. Methods: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 ± 16 years). Results: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and ‘internally’ (45%). Motor disturbances included ‘dyskinesias while awake’ (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with ‘growing pains’ (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. Conclusions: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.

In vivo Platelet Activation Is Increased during Sleep in Patients with Obstructive Sleep Apnea Syndrome

Background: Patients with obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular events including myocardial infarction and stroke. Objective: To determine whether in vivo platelet activation and the generation of procoagulant platelet-derived microparticles (PMP) are increased during sleep in patients with OSAS. Methods: In vivo platelet activation and PMP formation was determined using flow cytometry in 12 patients with untreated OSAS during and after sleep (4 and 7 a.m.). To study the effect of treatment with continuous positive airway pressure (CPAP), the measurements were repeated at the same time points after initiation of CPAP therapy. Healthy volunteers served as controls (n = 6). Results: Patients with OSAS had an increased percentage of platelets positive for the activation-dependent epitopes CD63 and CD62P during sleep (4 a.m.) compared to controls (4.8 ± 0.8 vs. 1.9 ± 0.4% for CD63, p < 0.01, and 2.0 ± 0.5 vs. 1.1 ± 0.3% for CD62P, p < 0.05). In OSAS patients, the amount of CD63- and CD62P-positive platelets was significantly elevated at 4 compared to 7 a.m. (4.8 ± 0.8 vs. 2.6 ± 0.4% for CD63 and 2.0 ± 0.5 vs. 1.1 ± 0.2% for CD62P, p < 0.05), but not in the control group. The levels of PMP were similar in patients with OSAS and controls at 4 and 7 a.m. After 1 night of CPAP therapy, there was a trend to reduced levels of CD63- and CD62P-positive platelets at 4 a.m. Conclusions: Patients with OSAS have increased in vivo platelet activation during sleep, which may contribute to the increased incidence of cardiovascular events in patients with OSAS.

Video-Assisted Thoracoscopic Surgery for Fibrinopurulent Pleural Empyema in 67 Patients

BACKGROUND The roles of different drainage procedures in the management of empyema have to be redefined now that video-assisted thoracoscopic surgery (VATS) has been introduced. The debridement of fibrinopurulent stage II empyema with the use of VATS was assessed prospectively in regard to control of infection and restoration of pulmonary function. METHODS Between January 1992 and May 1996, all patients at our institution with fibrinopurulent empyema that did not respond to chest tube drainage and antibiotic therapy were treated by debridement with the use of VATS. The patients were followed up prospectively by clinical and radiologic assessments 3 and 6 months after the operation and by spirometry 6 months after the operation. RESULTS Video-assisted thoracoscopic surgery was initiated in 67 patients, but conversion to open decortication was required because of the finding of advanced disease in 19 patients (28%). Forty-eight patients underwent successful debridement with the use of VATS. The mean operative time was 82.1 minutes (range, 50 to 135 minutes), the mean duration of postoperative chest tube placement was 4.1 days (range, 2 to 8 days), and the mean duration of postoperative hospitalization was 12.3 days (range, 4 to 42 days). No wound infections were observed during the postoperative course. Both the 30-day mortality rate and the recurrence (ie, need for thoracotomy) rate were 4%. The mean predicted vital capacity was 84.8% +/- 14.9% and the mean predicted forced expiratory volume in 1 second was 88.6% +/- 19.2% 6 months after the operation. CONCLUSIONS Debridement with the use of VATS is safe and efficient for stage II empyema, but open decortication should be used for more advanced disease.

Pulmonary function testing after operative stabilisation of the chest wall for flail chest

OBJECTIVE This is a prospective evaluation of chest wall integrity and pulmonary function in patients with operative stabilisation for flail chest injuries. METHODS From 1990 to 1999, 66 patients (56 men, 10 women; mean age 52.6 years) with antero-lateral flail chest (> or =4 ribs fractured at > or =2 sites) underwent surgical stabilisation using reconstruction plates. Clinical assessment and pulmonary function testing were performed at 6 months following surgery. RESULTS Fifty-five (83%) patients had various combinations of injuries of the thorax, head, abdomen and extremities. Sixty-three (95.5%) patients underwent unilateral and 3 (4.5%) patients bilateral stabilisation with a median delay of 2.8 days (range 0-21 days) from admission. The 30-day mortality was 11% (seven of 66 patients). Immediate postoperative extubation was feasible in 31 of 66 patients (47%) and extubation within 7 days following stabilisation in 56 of 66 patients (85%). No plate dislocation was observed during the follow-up. The shoulder girdle function was intact in 51 of 57 patients (90%). Chest wall complaints were noted in 6 of 57 (11%) patients, requiring removal of implants in three cases. All patients returned to work within a mean period of 8 (range 3-16) weeks following discharge. Pulmonary function testing (n=50) at 6 months after the operation revealed a significant difference of predicted vs. recorded vital capacity (VC) and forced expiratory volume in 1s (FEV1) (P=0.04 and P=0.0001, respectively; Wilcoxon signed-rank test). The median ratio of the recorded and predicted total lung capacity (TLC) was shown to be significantly higher than 0.85 (P=0.0002; Wilcoxon signed-rank test), indicating prevention of pulmonary restriction. CONCLUSION Antero-lateral flail chest injuries accompanied by respiratory insufficiency can be effectively stabilised using reconstruction plates. Early restoration of the chest wall integrity and respiratory pump function may be cost effective through the prevention of prolonged mechanical ventilation and restriction-related working incapacity.

Functional assessment of chest wall integrity after methylmethacrylate reconstruction

BACKGROUND All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.

Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors

BACKGROUND To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.

Normal-tension glaucoma is associated with sleep apnea syndrome

Introduction: In normal-tension glaucoma, optic nerve damage occurs without elevated intraocular pressures, hence vascular and pathogenic mechanisms other than intraocular pressure effects have been postulated. However, the exact cause(s) remain unknown. We have looked for an association between normal-tension glaucoma and sleep apnea syndrome, a disease characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of late cardiovascular and neurological sequelae. Methods: We performed overnight polysomnography in 16 consecutive Caucasian patients with normal-tension glaucoma. The respiratory disturbance index (RDI) during night sleep was used to diagnose and grade obstructive sleep apnea. Patients with an RDI of 10 or more were diagnosed as having obstructive sleep apnea. Results: We observed the following prevalences of obstructive sleep apnea in normal-tension glaucoma patients: 0% (0 of 2) for the group of patients younger than 45 years, 50% (3 of 6) for the age group 45–64 years, and 63% (5 of 8) for the group older than 64 years. Prevalences in the middle and older age group were significantly higher than in a historic control group (p < 0.025 for both, binomial test). Conclusion: Normal-tension glaucoma patients constitute a high-risk population for sleep apnea syndrome. Therefore, they should be screened for sleep apnea syndrome, and, if necessary, be treated to avoid late cardiovascular and neurological sequelae.

Eyelid, conjunctival, and corneal findings in sleep apnea syndrome

OBJECTIVE To determine the prevalence of eyelid, conjunctival, and corneal findings in patients with sleep apnea syndrome (SAS). DESIGN Case series. PARTICIPANTS Seventy-two white patients referred for evaluation of suspected SAS. INTERVENTION Complete examination of eyelids, conjunctiva, and cornea, including videokeratography. MAIN OUTCOME MEASURES Spearman rank correlations were determined between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and grade SAS, and tear film break-up time, eyelid distraction distance, presence or absence of ocular irritation symptoms, blepharoptosis, floppy eyelids, lacrimal gland prolapse, keratoconus, and endothelial dystrophy. Each correlation was controlled for age and body mass index. RESULTS According to the RDI, 44 (61 %) of the 72 patients had SAS. The RDI correlated positively with the eyelid distraction distance (P = 0.05), presence or absence of floppy eyelids (P = 0.01), and lacrimal gland prolapse (P = 0.01), and correlated negatively with tear film break-up time (P = 0.02). None of our patients with floppy eyelids had corneal abnormalities. One patient with SAS had bilateral keratoconus; another had bilateral Fuch endothelial dystrophy. CONCLUSIONS Sleep apnea syndrome was significantly associated with reduced tear film break-up time, floppy eyelids, and lacrimal gland prolapse. However, ocular irritation symptoms and corneal involvement were rare among patients with SAS. These findings do not confirm previous studies that reported a high prevalence of corneal involvement in floppy eyelid syndrome.

Epilepsy and Obstructive Sleep Apnea

A few publications documented the coexistence of epilepsy and obstructive sleep apnea (OSA). The extent, nature, and clinical relevance of this association remain poorly understood. We retrospectively reviewed the database of our sleep center to identify patients with both sleep apnea and epilepsy. Characteristics of epilepsy, sleep history, presence of excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)] and polysomnographic data were assessed. The effect of continuous positive airway pressure (CPAP) on seizure reduction was prospectively analyzed after a median interval of 26 months (range: 2–116 months) from the diagnosis of OSA. OSA was found in 29 epilepsy patients (25 men and 4 women) with a median age of 56 years (range: 37–79). The median apnea hypopnea index was 33 (range: 10–85), the oxygen desaturation index was 12 (range 0–92), and 52% of the patients had an ESS score >10. In 27 patients, epilepsy appeared 1 month to 44 years prior to the diagnosis of OSA. In 21 patients, the appearance of OSA symptoms coincided with a clear increase in seizure frequency or the first appearance of a status epilepticus. Treatment with CPAP was continued with good compliance in 12 patients and led to a significant reduction of both ESS scores and seizure frequency in 4 patients. Our data suggest the importance of considering diagnosis and treatment of OSA in epilepsy patients with poor seizure control and/or reappearance of seizures after a seizure-free interval.