Michael Hlavac

Sleep disordered breathing in patients with primary Sjögren’s syndrome: A group controlled study

OBJECTIVE Patients with primary Sjögrens syndrome (pSS) have higher fatigue levels and also suffer from excessive day time sleepiness. The underlying mechanisms for this are not fully understood. Knowing that these patients have higher salivary surface tension, we postulated that sleep disordered breathing (SDB) would be more common and would be a contributor to these symptoms amongst pSS patients. We investigated the prevalence of SDB in pSS patients and its relationship to their symptoms of fatigue and excessive daytime sleepiness. METHODS This was an observational study of 28 pSS patients (mean±SEM age, 58.7±1.9) and 18 healthy subjects (mean±SEM age, 55.8±3.4) matched for age, sex, and BMI. All the participants underwent an overnight polysomnography. The two groups were compared for fatigue, sleepiness, anxiety, and depression scores, and for the frequency of obstructive apneas and hypopneas during sleep. Correlation analyses were used to explore relationships between sleep study variables and excess sleepiness and fatigue. RESULTS Fatigue, sleepiness, anxiety and depression symptoms, and sleep onset latency were significantly greater in pSS patients than controls. pSS patients had twice the frequency of obstructive apneas and hypopneas compared with control subjects (median[IQR],18.6/h [10.4-40.1] vs. 9.9/h [6.5-23.4]; p=0.032) and OSA defined as an apnea-hypopnea index >15 events/h of sleep was more prevalent amongst pSS patients than controls (64% vs. 28%; p=0.033). While no significant correlations were found between parameters of sleep disordered breathing and sleepiness scores or fatigue scores in the pSS group, CPAP treatment in a small subset of the pSS who were more severely affected by OSA suggested significant symptomatic benefit. CONCLUSION OSA appears to be increased in pSS and may be a useful therapeutic target to improve the quality of life of these patients.

Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

STUDY OBJECTIVES To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. DESIGN Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. SETTING Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. PARTICIPANTS 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. CONCLUSIONS There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes.

Three families with Perry syndrome from distinct parts of the world

OBJECTIVES Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1. METHODS Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency. Dopaminergic therapy was initiated in probands from two families. RESULTS Besides the probands, 17 symptomatic relatives from all families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their fifth or sixth decade of life. Parkinsonism was moderate with a partial response to dopaminergic treatment. All affected persons but two died of respiratory insufficiency. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half-year follow-up examination has revealed that the diaphragmatic pacemaker is optimally functioning without any major complications. In the Colombian and US families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C mutations were identified. In functional assays, both mutations altered microtubule binding consistent with a pathogenic role. CONCLUSIONS Perry syndrome is a rare condition, but new cases are expected to be diagnosed worldwide. Early diagnosis prevents life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as an effective symptomatic treatment option.

Development and outcomes of a primary care-based sleep assessment service in Canterbury, New Zealand

Prior to 2007, increasing demand for sleep services, plus inability to adequately triage severity, led to long delays in sleep assessment and accessing continuous positive airway pressure. We established a community sleep assessment service carried out by trained general practices using a standardised tool and overnight oximetry. All cases were discussed at a multi-disciplinary meeting, with four outcomes: severe obstructive sleep apnoea treated with continuous positive airway pressure; investigation with more complex studies; sleep physician appointment; no or non-severe sleep disorder for general practitioner management. Assessment numbers increased steadily (~400 in 2007 vs. 1400 in 2015). Median time from referral to assessment and multi-disciplinary meeting was 28 and 48 days, respectively. After the first multi-disciplinary meeting, 23% of cases were assessed as having severe obstructive sleep apnoea. More complex studies (mostly flow based) were required in 49% of patients, identifying severe obstructive sleep apnoea in a further 13%. Thirty-seven percent of patients had obstructive sleep apnoea severe enough to qualify for funded treatment. Forty-eight percent of patients received a definitive answer from the first multi-disciplinary meeting. Median time from referral to continuous positive airway pressure for ‘at risk’ patients with severe obstructive sleep apnoea, e.g., commercial drivers, was 49 days, while patients with severe obstructive sleep apnoea but not ‘at risk’ waited 261 days for continuous positive airway pressure. Ten percent of patients required polysomnography, and 4% saw a sleep specialist. In conclusion, establishment of a community sleep assessment service and sleep multi-disciplinary meeting led to significantly more assessments, with short waiting times for treatment, especially in high-risk patients with severe obstructive sleep apnoea. Most patients can be assessed without more complex studies or face-to-face review by a sleep specialist.Sleep disorders: More assessments, shorter waits with community sleep serviceA community-based service for common sleep disorders can provide rapid and easily accessed sleep assessment and treatment. A team led by Michael Hlavac and Michael Epton from Christchurch Hospital describe the creation of a sleep assessment service within the Canterbury district of New Zealand, in which initial assessments are conducted throughout the community by general practice teams under guidance and advice from sleep specialists at the region’s largest hospital. Before the service, there were around 300 sleep assessments per year in all of Canterbury, a region with a population of around 510,000. Now, that number has more than tripled, with shorter waiting times for treatment, especially for people with severe sleep apnoea. The authors conclude that most patients can be assessed for a suspected sleep disorder without needing to visit a hospital’s sleep unit.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease

Rationale: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. Objectives: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. Methods: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow‐up, and the urinary albumin‐to‐creatinine ratio was measured at study exit. Measurements and Main Results: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were −1.64 (−3.45 to −0.740) in the CPAP group and −2.30 (−4.53 to −0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between‐group differences in end‐of‐study urinary albumin‐to‐creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. Conclusions: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).

The effects of long-term CPAP on weight change in patients with co-morbid OSA and cardiovascular disease: data from the SAVE trial

Background Although recent evidence suggests that OSA treatment may cause weight gain, the long‐term effects of CPAP on weight are not well established. Methods This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow‐up were included. Linear mixed models were used to examine sex‐specific temporal differences, and a sensitivity analysis compared high CPAP adherers (≥ 4 h per night) with propensity‐matched control participants. Results A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 ± 1.5 measures of weight available). After a mean follow‐up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between‐group difference, 0.07 kg [–0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between‐group difference, –0.14 kg [–0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP ≥ 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between‐group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects. Conclusions Long‐term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change. Trial Registry ClinicalTrials.gov; No.: NCT00738179; URL: www.clinicaltrials.gov.