Increased incidence rates of narcolepsy type 1 (NT1) after the 2009-2010 H1N1 influenza pandemic (pH1N1) have been reported world-wide. While some European countries found an association between the NT1 increase and H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus rather than Pandemrix to be linked with the increase of new NT1 cases. We analyzed the number of de-novo NT1 cases in the last two decades until 2016 using the European Narcolepsy Network (EU-NN) database. Using robust data-driven modelling approaches we confirmed the peak of NT1 incidence in 2009-2010 pH1N1 and identified a new peak in 2013 that is age-specific for children/adolescents. Most of these de-novo cases showed a subacute disease onset consistent with an immune-mediated type of narcolepsy, which is most likely not related to Pandemrix vaccination that was used in 2009-2010, but may have been triggered by some new epidemiological event in Europe. Our finding of an unexpected peak in de-novo children narcolepsy in 2013 provides a unique opportunity to develop new hypotheses, such as considering other (influenza) viruses to further investigate the pathophysiology of immune-mediated narcolepsy.

Super-refractory status epilepticus has a high mortality, and its treatment remains a challenge for clinical epileptologists. Deep brain stimulation (DBS) is successfully used in pharmacotherapy-resistant epilepsy and larger studies showed significant seizure reduction by high frequency stimulation in the anterior nucleus of the thalamus (ANT) [1]. Furthermore, several case reports indicate that DBS is also effective in the management of status epilepticus. In a recent, very comprehensive publication, Lehtimäki et al.

Narcolepsy type 1 is a neurological disorder characterized by a unique syndrome, including the pathognomonic symptom of cataplexy. The diagnosis can be confirmed by objective measures, such as typical findings in the multiple sleep latency test, reduced or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, and linkage to a specific HLA haplotype. Nevertheless, the mean time that elapses from symptom onset to the correct diagnosis ranges between 10 and 20 years, and the causes and correlates of this delay are poorly understood. Diagnostic delay was assessed on 52 well-defined patients with narcolepsy type 1, evaluating clinical, electrophysiological and neurochemical parameters and the results of a 41-item questionnaire developed to obtain the patients' perspective on various aspects of the diagnostic process. The mean time gap between disease onset and first medical consultation was 3.2 +/- 5.1 years; the mean diagnostic delay was 8.9 +/- 11.0 years. Prior to correct diagnosis, patients received a wide variety of misdiagnoses. The self-ratings of the patients revealed that the undiagnosed symptoms caused high levels of anxiety and unjustified criticism by family, friends and employers. Multiple regression analysis identified higher cerebrospinal fluid orexin levels (beta = 0.311, P = 0.01), and a longer interval between the onset of excessive daytime sleepiness and cataplexy (beta = 0.368, P = 0.002) as independent associates of longer diagnostic delay. The diagnostic delay decreased over the last decades (beta = -0.672, P < 0.001). In conclusion, delayed diagnosis of narcolepsy type 1 is very common, associated with many adverse consequences, and requires educational efforts to improve awareness on narcolepsy among healthcare providers and the general population.

The modulating effect of subthalamic beta oscillations on motor control in patients with Parkinson’s disease (PD) is a well-established observation: beta oscillations are enhanced in PD, and are reduced by voluntary movements, dopaminergic treatment or deep brain stimulation (DBS). PD patients with REM sleep behavior disorder (RBD) reveal mostly unimpaired motor behavior during REM sleep, despite lack of dopaminergic treatment during the night. However, it is unknown whether normalized neuronal signaling in the subthalamic nucleus during REM sleep is linked to this phenomenon which contrasts strongly to coexistent nocturnal bradykinesia in PD. We aim at investigating the dynamic electrophysiological properties of basal ganglia motor networks during nocturnal movements in PD patients by measuring event related potentials of limb movements in both REM and non-REM sleep. Specifically, we set out to determine whether phenotypically normal REM sleep-related movements are mirrored by reduced subthalamic beta oscillations. After implantation of deep brain stimulation (DBS) electrodes, we recorded local field potentials in the subthalamic nucleus (STN) and scalp EEG (modified 10/20 montage) during sleep in 5 PD patients with clinically manifest REM sleep behavioral disorder (12 h recording, 8 pm–8 am). Nocturnal movements were assessed by video-EEG monitoring and EMG recordings. Time-locked event-related beta band oscillations were then calculated to assess the relative and absolute beta (de-)synchronization during movements in REM (206 events) and non-REM sleep (112 events). Spectral analysis of local field potentials in the STN revealed elevated beta band power during REM sleep as compared to NREM sleep and tonic beta activity in REM sleep reached levels similar as in the waking state. Despite the continuously elevated beta band activity, event related analysis showed no significant beta desynchronization prior to or during movements in REM sleep. In other words, we observed unimpaired movements in REM sleep and recorded continuously elevated beta activity in the STN. Beta band power in NREM sleep was limited to the lower beta band (13–20 Hz), whereas in REM sleep beta power was more prominent in the high beta range (20–35 Hz). In contrast to voluntary motor control in wakefulness, subthalamic beta oscillations are poorly modulated during movements in REM and NREM sleep, indicating that nocturnal movements are not processed by the same cortico-basal ganglia networks as in the waking state. In this line, we propose that motor performance during REM sleep in PD patients with RBD is significantly improved because alternative motor networks for movement initiation might be activated. By this mechanism, the pathological movement-inhibiting basal ganglia networks in PD patients could be bypassed during REM sleep.