Central Apneas Due to the CLIFAHDD Syndrome Successfully Treated with Pyridostigmine

NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia, and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. We present a patient in whom congenital myasthenic syndrome (CMS) was suspected due to the occurrence of hypotonia and apnea episodes requiring resuscitation. For this reason, treatment with pyridostigmine was introduced. After starting the treatment, a significant improvement was observed in reducing the apnea episodes and slight psychomotor progress. In the course of further diagnostics, CMS was excluded, and CLIFAHDD syndrome was confirmed. Thus, we try to explain a possible mechanism of clinical improvement after the introduction of treatment with pyridostigmine in a patient with a mutation in the NALCN gene.

Passive longitudinal weight and cardiopulmonary monitoring in the home bed

Home health monitoring has the potential to improve outpatient management of chronic cardiopulmonary diseases such as heart failure. However, it is often limited by the need for adherence to self-measurement, charging and self-application of wearables, or usage of apps. Here, we describe a non-contact, adherence-independent sensor, that when placed beneath the legs of a patient’s home bed, longitudinally monitors total body weight, detailed respiratory signals, and ballistocardiograms for months, without requiring any active patient participation. Accompanying algorithms separate weight and respiratory signals when the bed is shared by a partner or a pet. Validation studies demonstrate quantitative equivalence to commercial sensors during overnight sleep studies. The feasibility of detecting obstructive and central apneas, cardiopulmonary coupling, and the hemodynamic consequences of non-sustained ventricular tachycardia is also established. Real-world durability is demonstrated by 3 months of in-home monitoring in an example patient with heart failure and ischemic cardiomyopathy as he recovers from coronary artery bypass grafting surgery. BedScales is the first sensor to measure adherence-independent total body weight as well as longitudinal cardiopulmonary physiology. As such, it has the potential to create a multidimensional picture of chronic disease, learn signatures of impending hospitalization, and enable optimization of care in the home.

Hypercapnia-Induced Vasodilation in the Cerebral Circulation is Reduced in Older Adults with Sleep Disordered Breathing

The prevalence of sleep disordered breathing (SDB) is higher in older adults compared to young individuals. The increased propensity for ventilatory control instability in older adults may contribute to the increased prevalence of central apneas. Reductions in the cerebral vascular response to CO2 may exacerbate ventilatory overshoots and undershoots during sleep. Thus, we hypothesized that hypercapnia-induced cerebral vasodilation (HCVD) will be reduced in older vs. young adults. In 11 older and 10 young adults with SDB, blood flow velocity in the middle cerebral artery (MCAV) was measured using Doppler transcranial ultrasonography, during multiple steady state hyperoxic hypercapnic breathing trials while awake, interspersed with room air breathing. Changes in ventilation, MCAV and mean arterial pressure (MAP) via finger plethysmography during the trials were compared with baseline eupneic values. For each hyperoxic hypercapnic trial, the change (Δ) in MCAV for a corresponding change in end-tidal CO2 and the HCVD or the change in cerebral vascular conductance (MCAV divided by MAP) for a corresponding change in end-tidal CO2 were determined. The hypercapnic ventilatory response was similar between the age groups, as was ΔMCAV/ΔPETCO2. However, compared with young, older adults had a significantly smaller HCVD (1.3 ± 0.7 vs. 2.1 ± 0.6 units/mmHg, p=0.004). Multivariable analyses demonstrated that age and nadir oxygen saturation during nocturnal polysomnography were significant predictors of HCVD. Thus, our data indicate that older age and SDB-related hypoxia are associated with diminished HCVD. We hypothesize that this impairment in vascular function may contribute to breathing instability during sleep in these individuals.

825 Central Sleep Apnea and Sinus Bradycardia

Introduction Central sleep apnea (CSA) is characterized by a lack of respiratory drive during sleep resulting in repetitive periods of apneas. There are multiple manifestations of CSA as defined by the ICSD3. CSA with Cheyne-Stokes Breathing (CSB) is characterized by a series of crescendo-decrescendo pattern of ventilation followed by central apnea and is often associated with heart failure. Bradyarrythmias have been associated with obstructive sleep apnea (OSA), but an association with central sleep apnea is less clear. Report of case(s) A 76 y/o male with no significant past medical history but with multiple instances of sinus bradycardia on previous EKGs, was referred to sleep medicine for evaluation of snoring, witnessed apneas, and daytime sleepiness. He had no history of CVA, CHF, atrial fibrillation, renal disease, or opioid use. PSG was completed for suspected OSA, and revealed moderate CSA (AHI 10.9 using hypopnea type 1B criteria, CAI 6.1). Central apneas at the latter portion of the study were consistent with a CSA-CSB. Awake heart rate at time of study was 44 bpm. During sleep, his heart rate ranged from 39–89 with a mean of 57 bpm. Due to this unexpected central apnea finding, cardiac evaluation was recommended and echocardiogram revealed a LVEF of 51%, a dilated left atrium, normal left ventricle chamber size, no wall motion abnormalities, and an inability to assess left sided filling pressures. EKG was consistent with sinus bradycardia without AV blocks. Holter monitor revealed sinus rhythm with moderate burden of ectopy. He underwent CPAP titration which revealed an effective CPAP pressure to control obstructive events, but central apneas persisted without CSB pattern. Conclusion In this patient, CSA/CSA-CSB was found in the absence of known risk factors for CSA. Although potentially an early sign of HFpEF related to his longstanding sinus bradycardia, this case raises the question as to whether sinus bradycardia in isolation could decrease cardiac output enough to destabilize ventilation and promote this finding of CSA/CSA-CSB. Support (if any):

802 Seizure-Associated Central Respiratory Events: What’s Sleep Go To Do With It?

Introduction Seizure-related respiratory dysfunction has been reported in patients with epilepsy(PWE) on scalp EEG. We assessed this in Stereo-EEG(SEEG) recordings in patients with pharmacoresistant focal epilepsy. Methods PWE undergoing SEEG wore temperature/pressure-based airflow,RIP belts, SpO2, and EtCO2/TcpCO2. Interpretable recordings required SpO2 and at least one airflow and effort channel. Respiratory events including apneas, hypopneas(3%) and central pauses (5 to<10sec). Respiratory events, respiratory rate(RR), SpO2 nadir, total desaturation time, Peak EtCO2/TcpCO2, and hypercapnia duration were analyzed surrounding seizures. Frequency and duration of central events were compared in sleep-onset and awake seizures. Linear mixed-effects models evaluated relationships between respiratory variables and the frequency and duration of central events associated with seizures and compared respiratory variables between seizures with and without events. Results 44 seizures were recorded in 23 patients. Seizures were focal-onset in 79.5%(n=35), GTC in 20.5%(9). Respiratory events accompanied 61.4%(27) of the seizures with median duration/seizure duration of 0.40(IQR: 0.27, 0.61). Of the 47 respiratory events, 42 were central events, and 66.6%(28) were central apneas. Respiratory events occurred during the seizure in 73.8%, postictal in 26.2%; median SpO2 nadir was 90%(77.0, 93.0), total desaturation duration 104.3(50.3, 195.0)sec, peak TcpCO2 41.3(38.7, 44.8) mmHg, hypercapnia duration 157.6(51.0, 367.9) sec, and ictal-postictal RR change 3.3 ± 4.0bpm. For every 1 sec duration increase in central event duration, there was a significant increase in peak TcpCO2 0.35(95%CI [0.09,0.62],p=0.015) and TcpCO2 change 0.25(95%CI [0.02,0.49],p=0.037). Presence of central events were associated with increased peak TcpCO2(9.82[3.77,15.9], p=0.006). Seizures with central events trended greater changes in RR, SpO2, and EtCO2/TcpCO2, desaturation and hypercapnia time, with negative changes in SpO2 nadir. No significant difference on central event frequency was found between sleep-onset and awake seizures. Conclusion Central events including apneas and pauses are common in focal seizures arising from sleep and wake and are associated with hypercapnia. In addition to the significant association between TcpCO2 and the frequency and duration of central events, there is a positive trend of association of other respiratory dysfunction parameters. These findings suggest that central events may lead to a cascade of respiratory disturbance that may participate in the pathophysiology of sudden unexplained death in epilepsy. Support (if any):