Periodic limb movement in OSA patient & difficulty in sleep with HNS

Our research group is particularly interested in patient-centred research on the pathophysiology of OSA and its associated comorbidities. 

Although periodic limb movement disorder (PLMD) and obstructive sleep apnoea (OSA) are overlapping clinical syndromes with common risk factors a clear pathophysiological link between them could not yet be established. A common drawback of the respective clinical studies in OSA patients in the past has been that the respective studied OSA cohorts had comorbidities in addition to OSA acting as significant confounders. As a result, little is known about periodic limb movements (PLM) in otherwise healthy patients with suspected OSA. 

We performed a retrospective analysis of 112 very carefully selected patients with suspected OSA but without clinically significant comorbidities who underwent full-night polysomnography for the first time. We found that both the PLM index (PLMI) and the total number of periodic limb movements during sleep (PLMS), showed a significant increase in patients with severe OSA. In addition, AHI and apnoea index (AI) were significantly higher in patients with PLMI >15/h, with a similar trend for hypopnea index (HI). PLMI was significantly positively correlated with AHI, AI, and HI. While patients with PLMI >15/h were significantly older than those with PLMI < 15/h, we found no significant association between body mass index (BMI) and PLMI >15/h (Seifen et al. 2024). 

Of note, after performing a quite granular multimodal signal analysis of the EEG and lower limb EMG PSG signals we had previously found no evidence for a specific pattern of cortico-peripheral neuro-muscular motor dissociation in OSA patients. This was in strong contrast to the motor cortico-peripheral uncoupling regarding the respiratory muscles in the same patient cohort (Gouveris et al. 2020). 

We are curious about whether future prospective studies with larger collectives would verify the above-presented results and presented in our paper some potential mechanistic aspects to be assessed for a more detailed evaluation of such a connection. 

 Another area in which we have accumulated significant clinical experience during the last years and are continuously asking research questions is peripheral hypoglossal nerve stimulation (HGNS) for the treatment of sleep apnoea in patients not tolerating positive airway pressure (PAP) therapy. 

Over the years and through the everyday routine management of this particular group of individuals we recognised that insomnia played a significant role in the actual clinical response to HGNS. Based on this initial clinical impression and due to our long-term interest on the interactions between increased arousability and OSA in humans (Bahr et al. 2021, Malatantis-Ewert et al. 2022, Bahr-Hamm et al. 2022), we performed a targeted evaluation of the respective outcomes from our practice. By capturing insomnia using the Insomnia Severity Index (ISI), we could found that especially sleep-onset insomnia features are strongly associated with worse treatment outcomes among patients not tolerating PAP therapy at all and eventually being treated with HGNS neurostimulation (Pordzik et al. 2024).   

Interestingly, in a further quite recent report from our group we could show that the insomnia component of the overall sleep-related affection of this particular, although common, group of patients may better respond to HGNS therapy than to PAP-therapy (Pordzik et al. 2024). The same was true for patient-reported excessive daytime sleepiness, as captured by the Epworth sleepiness scale, in the same patient cohort. These effects resulted a much more significant reduction in AHI in the PAP therapy group compared to the HGNS group. These results emerged when two well-matched groups of OSA patients, one treated with auto-titrating PAP and one treated with HGNS, were compared. This evidence supports further the argument that AHI (and possibly other respiratory PSG-based metrics) may be significantly dissociated from behaviourally relevant end points and features, such as insomnia and sleepiness (and their related metrics) in OSA patients. 

We are conducting further research to better understand these clinical facts. Newer results on our study of predictors of clinical response to HGNS therapy and on the interactions between insomnia and sleepiness in OSA patients are going to be presented by our group during Sleep Europe in September later this year in Sevilla, Spain (”Insomnia-related symptoms are key predictors of daytime sleepiness in patients with obstructive sleep apnea” by Gouveris et al. Poster 936 and “Cortimuscular coherence during NREM3 sleep stage and response to hypoglossal nerve stimulation therapy in obstructive sleep apnoe” by Ludwig et al. Poster 5139).  

Wish you all a great Sleep Europe and looking very forward to seeing you in Sevilla!