Authors response to “Deficits of attention and cognition in narcoleptic patients – is it hypocretin dependent?”

Abstract

To the Editor: We read with interest the letter by Iatallese et al. regarding our recent article [1]. The authors suggest that cognitive deficits in narcolepsy–cataplexy may be related to medial prefrontal cortex (mPFC) dysfunction, which is likely driven by hypocretin deficiency, and that inter-individual cognitive differences in narcolepsy may depend on hypocretin levels. In our study, we observed in 51 patients with narcolepsy (44 with cataplexy, 7 without cataplexy) slight attention and executivefunction deficits on an objective cognitive assessment. The patients’ subjective ratings of attention deficits did not correlate with the objectively measured performance, but ratings were predicted by momentary sleepiness and depression. Results did not change when patients without cataplexy were excluded from analysis. Due to the small sample size, a comparison between subgroups (with vs. without cataplexy) was not possible. The idea that cognitive deficits may be related to hypocretin levels is interesting and has not been tested so far either in our study or in a previous study on subjective cognitive deficits in patients with narcolepsy [2]. Hypocretin levels in cerebrospinal fluid (CSF) are not routinely measured in our patients as their determination is not needed for diagnosis of narcolepsy with cataplexy [3,4], and absent or reduced hypocretin levels are very likely in these patients. In patients without cataplexy, hypocretin levels are neither sensitive nor specific for diagnosis [3,4]. Although it seems plausible to expect more pronounced cognitive deficits in association with greater mPFC dysfunction, predictions about the association between hypocretin levels, mood, and its impact on the patients’ subjective cognitive complaints are speculative. Measurement of hypocretin levels in CSF cannot substitute a comprehensive neuropsychological assessment, which takes not only objective cognitive measures into consideration but also mood and individual impressions. Contrary to Iatallese et al., we believe that neuropsychological assessment is irreplaceable in the evaluation of the patients’ objective cognitive performance, subjective complaints, and mood.