Narcolepsy type 1 patients have lower levels of effector memory CD4+ T cells compared to their siblings when controlling for H1N1-(Pandemrix™)-vaccination and HLA DQB1∗06:02 status

Maximum likelihood or restricted maximum likelihood (REML) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled REML criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or REML criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer. Journal of Statistical Software, 67 (1) ISSN:1548-7660

The development and use of a new scale, the Epworth sleepiness scale (ESS), is described. This is a simple, self-administered questionnaire which is shown to provide a measurement of the subject's general level of daytime sleepiness. One hundred and eighty adults answered the ESS, including 30 normal men and women as controls and 150 patients with a range of sleep disorders. They rated the chances that they would doze off or fall asleep when in eight different situations commonly encountered in daily life. Total ESS scores significantly distinguished normal subjects from patients in various diagnostic groups including obstructive sleep apnea syndrome, narcolepsy and idiopathic hypersomnia. ESS scores were significantly correlated with sleep latency measured during the multiple sleep latency test and during overnight polysomnography. In patients with obstructive sleep apnea syndrome ESS scores were significantly correlated with the respiratory disturbance index and the minimum SaO2 recorded overnight. ESS scores of patients who simply snored did not differ from controls.

We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.