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Introduction This study was designed to investigate the effect of Sodium Oxybate (SXB) treatment on vigilance in narcoleptics, by in-laboratory measurements as well as measurements in daily life with portable task equipment. Materials and methods This two-centre observational study comprised a nine-day protocol, in which two days of in-laboratory vigilance measurements were followed by seven days of portable digital assistant (PDA) task battery administrations. Narcoleptic patients followed this procedure before and three months after stable treatment with the normal therapeutic dose of SXB (4.5–9.0 g/day). In-laboratory measurements included the Maintenance of Wakefulness Test (MWT) and the Oxford Sleep Resistance (OSLER) test, a behavioural MWT. The MWT and OSLER test consisted both of four 40-min sessions in a quiet and dimly lit room. During the OSLER test, subjects were instructed to keep their finger in contact with a button which was placed in their lap, and to remove the finger for 1 s when a red light-emitting diode (LED) flashed four feet away at eye level in the frontal visual field. The OSLER test was terminated when sleep-onset occurred or after 40 min of being awake. Outcome measures of the OSLER were average sleep latency, the total omission error count (number of times the finger was not removed upon a flash) and the omission error count per minute duration of the test (OSLEROMIS/MIN). In-field testing comprised a 15-minute task battery consisting of a session of the Sustained Attention to Response Task (SART) and a session of the Psychomotor Vigilance Test (PVT) in random order, as well as the administration of the Stanford Sleepiness Scale. The task battery was administered on a pocket-size personal digital assistant (PDA) computer and had to be performed three times per day during 1-hour-intervals around 10:00 h, 14:00 h and 20:00 h for seven days. The SART error count and PVT reciprocal average reaction time (1/RT) were considered the main outcome measures. Since the PVT and OSLER test had not yet been described in narcoleptics, and the use of a portable device in this study population was also new, a control group was included to compare baseline measurements of vigilance and sleep resistance with, in order to assess feasibility and validity of these measures. Data were analyzed by means of linear mixed effect models (LMMs) adjusted for age, time of day and centre. Results In total, data from 26 narcoleptics (14 had post-treatment data available) and 16 controls were available for analysis. Data are presented as geometrical means with P values originating from the LMM analyses described above. Narcoleptics had a higher SART error count compared to controls (17.5 versus 10.4 errors), lower PVT 1/RT (0.32 versus 0.38 ms-1), higher OSLEROMIS/MIN (4.9 versus 0.7 errors/minute), lower OSLER sleep latency (9.4 versus 36.4 min), and lower MWT sleep latency (6.1 versus 33.4 min), all P 0.01. Treatment with SXB was associated with a longer MWT sleep latency (9.2 versus 6.1 min, P 0.01), lower OSLEROMIS/MIN (4.2 versus 4.9 errors/minute, P = 0.01), and a slightly lower SART error count (17.1 versus 17.5 errors, P = 0.02) in narcoleptics, but not with absolute changes in OSLER sleep latency or PVT reciprocal reaction time. Performance tended to decrease during the day for SART error count and OSLEROMIS/MIN after SXB treatment. Conclusion PDA vigilance measurements are feasible and consistent with in-laboratory OSLER and MWT measurements in narcoleptics and controls. Sodium Oxybate was associated with a better resistance to sleep, measured by the OSLER and the MWT, and with a slight but significant improved vigilance, measured by the SART. This was mainly manifested in the morning. Acknowledgements We thank our subjects for participating in this study; the sleep technologists from the University Hospital Zurich and the Leiden University Medical Centre for their help in data acquisition; and UCB for the financial support of this study.

We would like to thank Baumann et al . for their interest in our paper (Fronczek et al. , 2007). The questions raised are all relevant and mainly entail the relationship between the partial hypocretin loss in PD (Fronczek et al. , 2007; Thannickal et al. , 2007) and actual sleep disturbances. Furthermore, the selectivity of the hypocretin cell loss in PD is questioned. We fully agree with these remarks and therefore prominently discussed them in our original paper (Fronczek et al. , 2007). However, two of the issues warrant …