Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

Plasma levels of tumor necrosis factor alpha and soluble tumor necrosis factor receptors in patients with narcolepsy.

BACKGROUND: Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Recent studies suggest that the immune system might play a pathogenic role pointing to a possible involvement of inflammatory cytokines. METHODS: We investigated a sample of 30 patients with narcolepsy in comparison with 120 sex- and age-matched and 101 sex-, body mass index (BMI)-, and age-matched randomly selected normal controls. In these groups, plasma concentrations of tumor necrosis factor alpha (TNF-alpha) and its soluble receptors p55 and p75 (soluble TNF receptor [sTNF-R] p55 and sTNF-R p75) were measured using commercial enzyme-linked immunosorbent assays. RESULTS: The narcoleptic patients showed a significantly higher BMI compared with controls of the same age. Soluble TNF-R p75 levels were consistently elevated in the narcoleptic patients compared with their sex- and age-matched (P = .001) as well as sex-, BMI-, and age-matched counterparts (P = .003). Female narcoleptic patients exhibited higher sTNF-R p55 levels compared with their sex- and age-matched controls (P = .01), but this difference disappeared when comparing patients with sex-, BMI-, and age-matched normal controls. Tumor necrosis factor alpha levels did not differ significantly between groups. CONCLUSION: Narcoleptic patients show increased plasma levels of sTNF-R p75, suggesting a functional alteration of the TNF-alpha cytokine system, further corroborating a possible pathogenic role of the immune system in this sleep disorder.

Increased body mass index (BMI) in male narcoleptic patients, but not in HLA-DR2-positive healthy male volunteers.

BACKGROUND: There is growing evidence that hypocretin deficiency plays a pivotal role in human narcolepsy. Based on the physiological role of hypocretins in the regulation of food intake, one might suspect that narcoleptic patients should display reduced energy intake and as a consequence a reduced body weight compared to healthy controls. METHODS: The body mass indices (BMIs) of 30 male narcoleptic patients were compared with large community-based reference samples. Because it is unclear whether increased BMI is an acquired consequence of the disease or a genetically determined premorbid feature of narcolepsy, we additionally examined the influence of the HLA-DR2 antigen, strongly associated with narcolepsy, on the BMI in a group of 117 healthy male volunteers. RESULTS: Narcoleptic patients displayed higher age- and gender-specific BMI percentiles compared to a community-based sample from the German (normal) population. Within the patient sample, BMI distribution did not significantly differ between subjects who had previously received pharmacological treatment compared to drug-naive patients, or between the HLA-DR2 positive and negative healthy subjects. CONCLUSIONS: The results of the present study suggest that an increased BMI in narcolepsy is neither associated with the HLA-DR2 antigen per se nor with medication, but is more likely to be a consequence of disease-associated neuroendocrine abnormalities.

Glucose tolerance in patients with narcolepsy.

STUDY OBJECTIVES: Obesity is a common feature of narcolepsy. In addition, an increased occurrence of non-insulin dependent diabetes has been reported. So far, it is not known whether glucose metabolism in narcolepsy is disturbed due to, or independently of obesity. DESIGN: Case-control study. SETTING: Sleep medicine clinic at a research institute. PATIENTS: We studied 17 patients with narcolepsy/cataplexy compared to 17 healthy controls matched for age, sex, and body mass index (BMI). INTERVENTIONS: A 75-g oral glucose tolerance test was performed. MEASUREMENTS: Glucose tolerance was determined by computing plasma glucose curve following oral glucose challenge for 240 minutes; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis. RESULTS: Standard outcome measures and indices of the oral glucose tolerance test did not differ between the patient group and the group of control subjects. CONCLUSIONS: In this study, no clinically relevant pathologic findings in the glucose metabolism of narcoleptic patients compared to weight matched controls were found. Thus, narcolepsy is unlikely to be a risk factor per se for impaired glucose tolerance or diabetes.

Impaired glucose tolerance in sleep disorders.

BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases.