LAUSR

IgLON5 antibodies were recently identified in patients with a complex syndrome of rapid-eye-movement and non-rapideye-movement parasomnias, insomnia, sleep apnea, excessive daytime sleepiness, bulbar symptoms and movement disorders. The prognosis appears to be unfavorable as a considerable number of reported patients died from sudden death during sleep or by respiratory failure [1,2]. Moreover, most patients were unresponsive to immunotherapy [3]. Recent studies, however, may have investigated a higher number of patients in more advanced disease stages where immunosuppressive therapy may have been insufficient due to advanced neuroinflammation and subsequent taurelated neurodegeneration [1,4]. Although the syndrome is typically characterized by a combination of several neurological signs, monosymptomatic or oligosymptomatic disease courses may exist at least in early stages [5]. Moreover, the phenotype of IgLON5 disease may be even broader than previously thought [6]. Thus, screening for IgLON5 antibodies in patients with more uniform phenotypes is warranted. In this regard, a recent screening of 33 patients with tauopathies remained negative [7]. Here the aim was to assess the frequency of IgLON5 antibodies in a sample of patients with obstructive sleep apnea (OSA) as a cardinal sign of IgLON5 disease. Among 70 screened OSA patients (26 female, age 54.8 16.1 years, range 19– 85), sleep disturbances and daytime sleepiness were the main complaints. Eleven patients had a history of stroke (n = 2), Parkinson’s disease (n = 1), restless legs syndrome (n = 1), brain surgery (n = 1), depression (n = 4), borderline personality disorder (n = 2) and restless legs syndrome (n = 1). All patients were diagnosed with obstructive mild to severe sleep apnea (OSA) and apnea hypopnea indices (AHI) between 10.5 and 57.3/h. Fifty-nine patients were diagnosed using a home sleep test with 22 exhibiting moderate or severe OSA. Continuous positive airway pressure therapy was initiated in them during an in-laboratory titration (group 1, Table 1). The remaining 37/59 patients were initially diagnosed with mild OSA with mild severity using a home sleep test. An additional polysomnography was thus initiated due to suspicious clinical symptoms (group 2, Table 1): fourteen patients finally suffered from mild OSA (AHI ≥ 5 and <15/h), 31 from moderate OSA (AHI ≤ 15 and <30/h) and 14 from severe OSA (AHI ≤ 30/h). In the remaining 11/70 patients, OSA was already diagnosed previously (group 3, Table 1). The antibody screening for IgLON5 was negative in all cases included. In summary, no IgLON5 antibodies were found in this patient sample which indicates that this antibody may be rather specific for a combination of more complex sleep-related disorders and additional neurological signs. Taken together, anti-IgLON5 disease is a multi-faceted condition that is characterized by a combination of sleeprelated problems and neurological signs. Isolated OSA appears not to be part of the clinical spectrum, so a screening based on isolated OSA as a potential oligo/monosymptomatic disease at an early stage appears to be of limited use. Screening of IgLON5 antibodies, however, should be performed in patients with other characteristic IgLON5-related manifestations such as isolated dysphagia of unknown cause or isolated parasomnias. The identification of patients in earlier rather than late disease stages with advanced tauassociated neurodegeneration may open