Sean Higgins

Multiple system atrophy presenting as central sleep apnoea

A 61‐yr-old male presented with apparent idiopathic central sleep apnoea but after 4 yrs developed features of autonomic, cerebellar and extrapyramidal dysfunction consistent with a diagnosis of multiple system atrophy (MSA). Though central sleep apnoea can occur in multiple sleep apnoea, it is less frequent than obstructive sleep apnoea and occurs in the later stages of the disease. The pathogenesis of MSA involves gliosis and neuronal cell loss in specific areas of the central nervous system. Central sleep apnoea in MSA may be due to the depletion of cholinergic neurons in the arcuate nucleus of the medulla by apoptosis. This is the first description of multiple system atrophy presenting as central sleep apnoea. The current authors believe that multiple system atrophy should be considered in the differential diagnosis of late onset central sleep apnoea and progressive hypoventilation.

Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias

Background The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. Methods We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N−C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. Results All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N−C only 52% arose from NREM1. Within the N−C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). Conclusions These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Derived Arterial Stiffness is Increased in Patients with Obstructive Sleep Apnea and Periodic Limb Movements during Sleep.

STUDY OBJECTIVES Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) have been associated with increased risk of cardiovascular disease (CVD). OSA has also been linked to increased large arterial stiffness, which is considered an independent risk factor for CVD. We utilized a previously validated index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) to seek comparison in patients with PLMS and OSA. METHODS Forty-nine adult male subjects, without known comorbidities that could affect arterial stiffness or on vasoactive medication, were retrospectively identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17), and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index (PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h. SIDVP was derived from the raw data of photoplethysmography of the nocturnal polysomnography, averaged for 2 min prior to sleep study initiation (baseline), after completion in the morning, and every half hour after sleep onset. RESULTS The groups were age/body mass index-matched. Controls showed lower baseline, morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with PLMS (PLMI: 50.69 ± 9.7 events/h) and the OSA group (AHI: 29.7 ± 2 events/h) demonstrated similar overall SIDVP (6.78 ± 0.08 versus 6.94 ± 0.04, respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 ± 8, PLMI: 50.63 ± 7.2) group demonstrated the highest (7.40 ± 0.06, p < 0.001). CONCLUSIONS Based on an easily reproducible and applicable marker of large arterial stiffness, patients with significant PLMS had higher SIDVP when compared to controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had the highest SIDVP, implying a possible additive effect of OSA and PLMS on arterial stiffness.

Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice

Background Sodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments. Materials and methods This was a retrospective single centre study including patients with severe narcolepsy with cataplexy refractory to other treatments, who were initiated on sodium oxybate between 2009 and 2015. Patients were allowed to be on other stimulants or/and anti-cataplectic agents. Epworth sleepiness scale (ESS) and weekly cataplexy events were recorded. Side effects (SEs) were recorded at every follow-up visit. Results 90 patients were prescribed sodium oxybate, with a total of 3116 patient-months of drug exposure. ESS and weekly cataplexy events were significantly reduced by sodium oxybate for all patients (ΔESS = 4.3 ± 4.4 and Δcataplexy = 21.8 ± 18.5 events/week; p < 0.0001, respectively). The required maintenance dose could not be predicted based upon gender, body mass index, or clinical factors. 60% of patients were able to reduce or come off other medications. Half of the patients experienced at least one SE, and 26.6% had to stop treatment due to limiting SEs. Nausea, mood swings and enuresis were the most commonly reported SEs. SEs that led to drug discontinuation, particularly psychosis, were associated with increasing age and were observed early after the initiation of the drug. Conclusions Sodium oxybate provides a good clinical efficacy and acceptable safety profile in routine clinical practice for the treatment of patients suffering from narcolepsy with cataplexy. A quarter of patients experience SEs requiring withdrawal of the drug with older patients being more vulnerable to the more serious SEs.

NREM parasomnias: a treatment approach based upon a retrospective case series of 512 patients

Background Non-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients. Patients Five hundred and twelve patients with Non-REM parasomnia or parasomnia overlap disorder (POD), who had undergone a video polysomnography and were exposed to treatment, were retrospectively identified. Treatment outcome was assessed based on patients’ reports, and treatment approach on a locally accepted hierarchy of interventions. Results Forty percent of patients were diagnosed with sleepwalking, 23.8% with mixed-phenotype and 10% with POD. Ultimately, 97.2% reported adequate control of their symptoms. Moreover, 60.1% were treated with pharmacotherapy and 32.0% without, consistent across all phenotypes (p = 0.09). Benzodiazepines were the most common drugs prescribed (47.1%, p < 0.05). In the end, 37.7% of our patients were receiving a benzodiazepine as part of their successful treatment, 11.7% an antidepressant, 9.2% a z-drug, and 10.7% melatonin. Finally, 13.2%, 12.1%, and 5.8% of our patients reported good control of their symptoms with sleep hygiene, management of sleep-disordered breathing, and psychological interventions (cognitive behavioral therapy [CBT] or mindfulness-based stress reduction [MBSR]), as monotherapy, respectively. Conclusion The treatment approach to effective treatment of the patients with Non-REM parasomnias or POD offering first sleep hygiene advice, next treatment of concurrent sleep disorders and management of other priming factors like stress and anxiety, and lastly pharmacotherapy for Non-REM parasomnia is supported by our results. Non pharmacological interventions were effective in one third of our patients, and CBT/MBSR and melatonin appeared promising new treatments.

Diagnosis of PLMD from increased pulse rate variability on overnight oximetry.

Study objective This study was undertaken in a group of patients with periodic limb movement disorder (PLMD) to assess whether the presence of increased pulse rate variability (PRV) without desaturation on overnight oximetry was suggestive of the occurrence of periodic limb movements (PLMs). Methods Seventy sleepy patients with a polysomnographic diagnosis of PLMD and 25 controls with obstructive sleep apnea were included in this retrospective study. All patients had undergone initial domiciliary oximetry and subsequent polysomnography (PSG). The oximetry tracings were independently interpreted by five sleep unit personnel for the presence of increased PRV. Further, the association between increased PRV and PLMs was evaluated in the summary graph of the PSG. Results Fifty seven (81.4%) patients had definite evidence of increased PRV without episodes of desaturation on initial oximetry, which was later confirmed to be due to PLMs on PSG. 13 (18.6%) patients had no PRV on oximetry and PSG but had PLMD. The inter-interpreter concurrence in suspecting a diagnosis of PLMD based on oximetry alone was more than 80% in 64 (91%) patients. Conclusion The presence of isolated increased PRV on overnight oximetry is a valuable tool in suspecting nonsleep apnea disorders like PLMD.

Catathrenia, a REM predominant disorder of arousal?

OBJECTIVES Catathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis, and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and polysomnographic characteristics, and their subsequent management. METHODS Consecutive patients with catathrenia who had undergone full polysomnography in our institution over a 5.5-year period were included. Catathrenia events (CEs) were examined in clusters, which formulated catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, electroencephalogram (EEG) arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients. RESULTS A total of 427 CPs were identified in 38 patients, 81% arising from rapid eye movement (REM) sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3 ± 56.8 vs. 32.2 ± 29.4 s, p < 0.001). Each CE had a characteristic airflow signal, with inspiration preceding a protracted expiration and a brief more rapid exhalation, followed by deep inspiration. Although the majority of patients were referred on the basis of bed partner complaints, 44.7% complained of daytime sleepiness. Continuous positive airway pressure therapy and sleep-consolidating pharmacotherapy led to subjective improvement, but were limited by poor long-term adherence. CONCLUSIONS In the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of CPs.

Video polysomnographic findings in non-rapid eye movement parasomnia

Although video polysomnography (vPSG) is not routinely recommended for the evaluation of typical cases of non‐rapid eye movement (NREM) parasomnias, it can aid diagnosis of unusual cases, other sleep disorders and complicated cases with REM behaviour disorder (RBD), and in differentiating parasomnias from epilepsy. In this study, we aimed to assess vPSG findings in consecutive patients with a clinical diagnosis of NREM‐parasomnia covering the whole phenotypic spectrum. Five hundred and twelve patients with a final diagnosis of NREM parasomnia who had undergone vPSG were retrospectively identified. vPSGs were analysed for features of NREM parasomnia and for the presence of other sleep disorders. Two hundred and six (40.0%) patients were clinically diagnosed with sleepwalking, 72 (14.1%) with sleep terrors, 39 (7.6%) with confusional arousals, 15 (2.9%) with sexsomnia, seven (1.4%) with sleep‐related eating disorder, 122 (23.8%) with mixed phenotype, and 51 (10.0%) with parasomnia overlap disorder (POD). The vPSG supported the diagnosis of NREM parasomnia in 64.4% of the patients and of POD in 98%. In 28.9% of the patients, obstructive sleep apnea (OSA) or/and periodic limb movements during sleep (PLMS) were identified, most commonly in older, male, sleepy and obese patients. vPSG has a high diagnostic yield in patients with NREM parasomnia and should be routinely performed when there is diagnostic doubt, or in patients where there is a suspicion of OSA and PLMS.

Catathrenia as a REM predominant disorder of arousal

Catathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and PSG characteristics, and their subsequent management. Consecutive patients with catathrenia who had undergone full PSG in our institution over a 5-and-half-year period were included. Catathrenia events (CEs) were examined in clusters, formulating catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, EEG arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients. A total of 427 CPs were identified in 38 patients, 81% arising from REM sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3±56.8 vs 32.2±29.4 sec, p In the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern, and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of catathrenia periods.