Biomedical subjects

Matthias Gugger

Publications and source records attributed to Matthias Gugger.

14 recordsLinked to original sources

PubMed2006

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.

Adult↗

PubMed2006

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 > or =15 or AHI > or =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 (> or =10 in 58%, > or =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 > or =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.

Acute Disease↗

PubMed2006

Effects of sleep fragmentation on the arousability to resistive loading in NREM and REM sleep in normal men.

STUDY OBJECTIVE: In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. DESIGN: Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. PARTICIPANTS: Sixteen healthy men aged 20 to 29 years. INTERVENTIONS: In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. MEASUREMENTS AND RESULTS: During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. CONCLUSIONS: Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.

Adult↗

PubMed2005

Synergistic effect of low dose cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation.

OBJECTIVE: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. METHODS: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4 x 20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 microg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. RESULTS: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233+/-123 mmHg, vs 44+/-8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II-IIIA). hIL-10 serum levels on day 5 were 14+/-7 pg/ml in group B vs. 0 in group A. CONCLUSIONS: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.

Acute Disease↗

PubMed2004

Restless legs syndrome: clinical experience with long-term treatment.

BACKGROUND AND PURPOSE: There are limited data on long-term treatment efficacy, and almost none on predictors of treatment response in patients with restless legs syndrome (RLS). To assess: (1) long-term efficacy of RLS treatment in a clinical setting, (2) predictors of a good treatment response, and (3) the value of the RLS-severity score according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). PATIENTS AND METHODS: Over three years 70 patients (36 men, 34 women; mean age: 59 years; range: 29-79) with RLS were prospectively assessed. Diagnosis of RLS was made according to international criteria Severity of RLS symptoms was were assessed at the outset by the IRLSSG rating scale. Treatment was chosen individually according to clinical judgement. After a mean follow-up time of 16 months (range: 1-106 months) evolution of symptoms was assessed by both overall clinical impression and IRLSSG rating scale. Clinical characteristics and treatment effect were compared between patients never treated for RLS before this study ('naïve'=N-pts) and those with previous treatment ('treated'=T-pts). Predictors of treatment response were sought for comparing patients with good treatment response (good, better or much better on follow-up) and those with bad (B-pts) treatment response. RESULTS: There were 40 N-pts and 30 T-pts. The mean IRLSSG score (hereinafter, IRLSSG) at baseline was 26 (range 12-38). No significant differences were found between N-and T-pts in age, gender, etiology and duration of RLS, positive family history, presenting sleep complaint, IRLSSG, or percentage of patients with periodic limb movements in sleep (PLMS) on polysomnography (PSG). At final follow-up 30 (76%) of 40 N-pts and 23 (77%) of 30 T-pts had a good (G-pts) treatment response. The mean IRLSSG at follow-up was 19 (range:1-36). There was a significant correlation between improvement of overall clinical impression (better or much better on final follow-up) and reduction of IRLSSG (P<0.0001). PLMS were more common in B- than G-pts (100 vs 58% of patients, P=0.02). In all other variables considered the two groups were similar. CONCLUSION: (1) A good long-term treatment response can be obtained and maintained in a clinical setting in about 80% of RLS patients. (2) Patients with RLS and without PLMS may have a better long-term treatment response, and (3) the IRLSSG is a useful tool for assessment of evolution of RLS symptoms over time in individual patients.

Adult↗

PubMed2004

Grading airway stenosis down to the segmental level using virtual bronchoscopy.

OBJECTIVE: To assess the sensitivity of noninvasive virtual bronchoscopy based on multirow detector CT scanning in detecting and grading central and segmental airway stenosis using flexible bronchoscopic findings as the reference standard. MATERIALS AND METHODS: In a blinded controlled trial, multirow detector CT virtual bronchoscopy and flexible bronchoscopy were used to search for and grade airway stenosis in 20 patients. CT scan data were obtained with a multirow detector CT scanner using 4 x 1 mm collimation. Flexible bronchoscopy findings were graded by a pulmonologist and served as the reference standard for 176 central airway regions (ie, trachea, main bronchi, and lobar bronchi) and 302 segmental airway regions. The extent of airway narrowing was categorized as grade 0 (no narrowing), grade 1 (< 50%), or grade 2 (> or =50%). RESULTS: Flexible bronchoscopy revealed 30 stenoses in the central airways and 10 in the segmental airways. Virtual bronchoscopy detected 32 stenoses in the central airways (sensitivity, 90.0%; specificity, 96.6%; accuracy, 95.5%) and 22 in the segmental airways (sensitivity, 90.0%; specificity, 95.6%; accuracy, 95.5%). The number of false-positive findings was higher in the segmental airways (13 false-positive findings) than in the central airways (5 false-positive findings), which caused a lower positive predictive value for the segmental airways (40.9%) than for the central airways (84.4%). Flexible and virtual bronchoscopic gradings correlated better for central airway stenosis (r = 0.87) than for segmental airway stenosis (r = 0.61). CONCLUSION: Although a high sensitivity was found for the detection of both central and segmental airway stenosis, the number of false-positive findings was higher for segmental airways. However, noninvasive multirow detector CT virtual bronchoscopy enables high-resolution endoluminal imaging of the airways down to the segmental bronchi.

Aged↗

PubMed2003

Progressive genomic alterations in intraductal papillary mucinous tumours of the pancreas and morphologically similar lesions of the pancreatic ducts.

Intraductal papillary mucinous tumours (IPMTs) of the pancreas are rare neoplasms characterized by a prominent intraductal component, and by malignant potential. Little data exists concerning numerical chromosome aberrations in IPMTs. The biological significance of mucinous epithelial changes (mucinous hyperplasia) in small branching ducts adjacent to IPMTs also remains unclear. From a series of 12 IPMTs, we investigated by interphase cytogenetics 22 foci with mucinous hyperplasia, 27 foci with borderline lesions, and 11 samples with either intraductal (CIS) or invasive carcinoma. Chromosome 6 loss was detected in areas with mucinous hyperplasia (36.3%), borderline lesions (96.3%), and CIS/invasive carcinoma (100%). Similar losses, indicating clonal progression, were found for chromosome 17 (18.2%, 81.5%, and 100%), and for chromosome 18 (0%, 18.5%, and 100%). Quantitative analysis showed a significant intraductal expansion of cell clones harbouring these numerical aberrations within the spectrum of IPMTs. Mucinous epithelial changes in 11 resection samples with chronic pancreatitis showed monosomy 6 (36%) and monosomy 17 (27%). Conversely, areas with low-grade pancreatic intraepithelial neoplasia (PanIN-1), obtained from eight surgical specimens with ductal adenocarcinoma, showed monosomies for chromosome 6, 17, and 18 (100%, 87%, and 50%, respectively). We conclude that monosomies, as defined by FISH analysis, are frequent in both IPMTs and mucinous hyperplasia of pancreatic ducts adjacent to IPMTs. Monosomy 6 may represent an early event in the stepwise accumulation of genomic mutations necessary for the neoplastic transformation of pancreatic duct epithelia, whereas loss of chromosome 18 may be implicated in the progression of borderline to malignant IPMT. The detection of complex chromosomal aberrations in mucinous epithelial changes, and the quantitative expansion of monosomic cell clones in pancreatic ducts, provide evidence for a continuum between hyperplastic and dysplastic epithelial changes.

Adenocarcinoma, Mucinous↗

PubMed2003

Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation.

OBJECTIVES: 1,25-Dihydroxycholecalciferol (calcitriol, vitamin D3) has immunosuppressive properties. This study evaluates the effect of calcitriol in combination with either cyclosporine A or tacrolimus on acute lung allograft rejection in a rat model of unilateral left lung allotransplantation. METHODS: Unilateral left lung transplantation was performed in male rats (Brown-Norway to Fischer F344, 200-250 g body weight). For immunosuppression, the following subtherapeutic doses were used: calcitriol 0.5 microg/kg/day, cyclosporine A 2.5 mg/kg/day i.p., and tacrolimus 40 microg/kg i.m. Five groups (n = 5) were analyzed: cyclosporine A; cyclosporine A and calcitriol; calcitriol; tacrolimus and calcitriol; and tacrolimus. The injections were performed for 5 days starting from the day of transplantation. Recipients were sacrificed on day 5 post-transplant. The contralateral right main bronchus and pulmonary artery were occluded for 5 min and blood was drawn for blood gas analysis. The grafts were excised, fixed in formaline and embedded in paraffin. Histological evaluation was done in blinded fashion (ISHLT 1999/rank scale). The mean and standard error of the mean (PaO2) or the median and range (rejection grading) are given. ANOVA followed by planned comparison for the PaO2 and Kruskal-Wallis ANOVA for rejection grading were applied, p < 0.05 considered significant. RESULTS: Arterial PaO2 on day 5 was very low in animals treated with subtherapeutic dosages of either cyclosporine A (48 +/- 10 mmHg), calcitriol (51 +/- 3) or tacrolimus (86 +/- 22). Combined treatment with cyclosporine A and calcitriol revealed a significant improvement (248 +/- 78; p < 0.05 vs. other groups), whereas the combination of tacrolimus with calcitriol did not reveal any benefit (65 +/- 9). Rejection grading with these subtherapeutic doses did not show any significant difference between groups. CONCLUSIONS: Our data indicate that cyclosporine A, but not tacrolimus, has a strong additive effect with calcitriol on acute rat lung allograft rejection.

Animals↗

PubMed2003

The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A).

OBJECTIVES: Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin. The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were assessed in a consecutive series of 27 patients with hypersomnia of (mainly) neurological origin. METHODS: Diagnoses included classical narcolepsy (n=3), symptomatic narcolepsy (n=1), narcolepsy without cataplexy (n=4), idiopathic hypersomnia (n=5), hypersomnia associated with psychiatric disorders (n=5), and hypersomnia secondary to neurological disorders or of undetermined origin (n=9). Clinical assessment included BMI, Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), and history of REM-symptoms (sleep paralysis, hallucinations). HLA-typing, electrophysiological studies (conventional polysomnography, MSLT, 1-week actigraphy), and measurements of CSF levels of hypocretin and leptin were also performed. RESULTS: Hypocretin-1 was undetectable in three patients with classic narcolepsy and detectable in the remaining 24 patients. Other narcoleptic markers also frequently found in patients without narcolepsy included ESS>14 (78% of 27 patients), UNS>14 (75%), REM symptoms (30%), sleep latencies on MSLT<5 min (41%), >/=2 SOREM (30%), DQB1*0602 positivity (52%), BMI>25 (52%), and increased CSF leptin (48%). Hypersomnia was documented by an increased time 'asleep' in 41% of patients. Overlapping clinical and electrophysiological findings were seen mostly in patients with narcolepsy without cataplexy, idiopathic hypersomnia, and psychiatric hypersomnia. CONCLUSIONS: (1) Hypocretin dysfunction is not the 'final common pathway' in the pathophysiology of most hypersomnolent syndromes that fall on the borderline for a diagnosis of narcolepsy. (2) The observed overlap among these hypersomnolent syndromes implies that current diagnostic categories are not entirely unambiguous. (3) A common hypothalamic, hypocretin-independent dysfunction may be present in some of these syndromes.

Adolescent↗

PubMed2002

Sleep disordered breathing in neurologic disorders.

Wakefulness, NREM sleep, and REM sleep are accompanied by specific changes in breathing control, which arise from the interaction of automatic (metabolic, involuntary) and behavioural (voluntary and involuntary control systems. Considering the complexity in the neuroanatomy and neurophysiology of breathing control, it is not surprising that neurologic disorders are frequently accompanied by sleep disordered breathing. An introduction on pathophysiology, clinical features, diagnosis, and treatment of sleep disordered breathing in such diseases as stroke, epilepsy, dementia, spinal cord disease, polyneuropathies, and myopathies is presented.

Aged↗

PubMed2002

Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To determine if patients with nonarteritic ischemic optic neuropathy (NAION) have sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption. METHODS: We recruited 17 patients with NAION and 17 age- and sex-matched controls from patients referred for treatment because of suspected restless legs syndrome. We performed overnight polysomnography and determined the respiratory disturbance index during night sleep, a value used to diagnose and grade SAS. We compared the proportions of patients with SAS among patients with NAION and matched controls using the chi(2) test. Additionally, we compared the proportions of patients with SAS among patients with NAION and a large SAS prevalence study using the binomial test. RESULTS: Twelve (71%) of 17 patients with NAION had SAS. According to the respiratory disturbance index, 4 patients (24%) had mild, 4 patients (24%) had moderate, and 4 patients (24%) had severe SAS. Only 3 (18%) of 17 controls had SAS (P =.005). In the 45- to 64-year age group, 4 (50%) of 8 patients with NAION had SAS; 51 (11.9%) of 430 of the random sample in the prevalence study had SAS (P =.005). In the group older than 64 years, 8 (89%) of 9 patients with NAION had SAS; 18 (24%) of 75 of the random sample in the prevalence study had SAS (P<.001). CONCLUSIONS: We found a high prevalence of SAS in patients with NAION, which supports previous case reports suggesting that such an association exists. This association may explain why approximately 75% of all patients with NAION discover visual loss on first awakening or when they first use vision critically after sleeping. Our findings indicate that SAS may play an important role in the pathogenesis of NAION.

Aged↗

PubMed2002

Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome.

The occurrence of irresistible sleep episodes ('sleep attacks') has been noted in patients with Parkinson's syndrome treated with dopa-agonists. This is the first report of 'sleep attacks' in a patient with restless legs syndrome in whom treatment with pergolide was reduced from 2 to less than 1 mg/day. 'Sleep attacks' were accompanied by a reduced mean sleep latency of 5 min and 20 s (without sleep onset REM periods) on a multiple sleep latency test. 'Sleep attacks' disappeared when pergolide was tapered off and substituted with pramipexol. The appearance of 'sleep attacks' as a 'withdrawal' effect of pergolide is consistent with a wakefulness-promoting action of postsynaptic dopaminergic receptors at higher doses of dopamine agonists.

Journal Article↗

PubMed2002

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.

Aged↗

PubMedDate not supplied

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.

Adult↗