Upper-airway stimulation for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is associated with considerable health risks. Although continuous positive airway pressure (CPAP) can mitigate these risks, effectiveness can be reduced by inadequate adherence to treatment. We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea. METHODS: Using a multicenter, prospective, single-group, cohort design, we surgically implanted an upper-airway stimulation device in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea-hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ≥15 indicating moderate-to-severe apnea) and the oxygen desaturation index (ODI; the number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points from baseline). Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawal trial. RESULTS: The study included 126 participants; 83% were men. The mean age was 54.5 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68%, from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy-maintenance group (8.9 and 7.2 events per hour, respectively); the AHI score was significantly higher (indicating more severe apnea) among the 23 participants in the therapy-withdrawal group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure-related serious adverse events was less than 2%. CONCLUSIONS: In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea. (Funded by Inspire Medical Systems; STAR ClinicalTrials.gov number, NCT01161420.).

Finite-difference time-domain simulation of spacetime cloak.

In this work, we present a numerical method that remedies the instabilities of the conventional FDTD approach for solving Maxwell's equations in a space-time dependent magneto-electric medium with direct application to the simulation of the recently proposed spacetime cloak. We utilize a dual grid FDTD method overlapped in the time domain to provide a stable approach for the simulation of a magneto-electric medium with time and space varying permittivity, permeability and coupling coefficient. The developed method can be applied to explore other new physical possibilities offered by spacetime cloaking, metamaterials, and transformation optics.

Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Individuals with obstructive sleep apnea (OSA), characterized by frequent sleep disruptions from tongue muscle relaxation and airway blockage, are known to benefit from on-demand electrical stimulation of the hypoglossal nerve. Hypoglossal nerve stimulation (HNS) therapy, which activates the protrusor muscles of the tongue during inspiration, has been established in multiple clinical studies as safe and effective, but the mechanistic understanding for why some stimulation parameters work better than others has not been thoroughly investigated. METHODS: In this study, we developed a detailed biophysical model that can predict the spatial recruitment of hypoglossal nerve fascicles and axons within these fascicles during stimulation through nerve cuff electrodes. Using this model, three HNS programming scenarios were investigated including grouped cathode (---), single cathode (o-o), and guarded cathode bipolar (+-+) electrode configurations. RESULTS: Regardless of electrode configuration, nearly all hypoglossal nerve axons circumscribed by the nerve cuff were recruited for stimulation amplitudes <3 V. Within this range, monopolar configurations required lower stimulation amplitudes than the guarded bipolar configuration to elicit action potentials within hypoglossal nerve axons. Further, the spatial distribution of the activated axons was more uniform for monopolar versus guarded bipolar configurations. CONCLUSIONS: The computational models predicted that monopolar HNS provided the lowest threshold and the least sensitivity to rotational angle of the nerve cuff around the hypoglossal nerve; however, this setting also increased the likelihood for current leakage outside the nerve cuff, which could potentially activate axons in unintended branches of the hypoglossal nerve. CLINICAL TRIAL REGISTRATION: NCT01161420.

Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study.

STUDY OBJECTIVES: To determine the frequency of impulse control disorders (ICDs) with the use of dopaminergic agents in restless legs syndrome (RLS). DESIGN: Prospective case-control study using a screening questionnaire for ICDs, followed by phone interview to confirm diagnoses for those meeting preset scoring thresholds on the questionnaire. SETTING: Academic, comprehensive sleep medicine center. PATIENTS OR PARTICIPANTS: (1) One hundred patients with RLS treated with dopaminergic agents, (2) 275 patients with obstructive sleep apnea (OSA) without RLS or exposure to dopaminergic agents; and (3) 52 patients with RLS who were never treated with dopaminergic agents. Subjects with parkinsonism were excluded. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Based on the questionnaire, frequencies of ICDs for the RLS treatment group were 10% compulsive shopping, 7% pathologic gambling, 23% compulsive eating, 8% hypersexuality, and 10% punding. These values were statistically significant when compared with control subjects with OSA for compulsive shopping and pathologic gambling. With additional information from the phone interview, adjusted frequencies for the RLS treatment group were 9% compulsive shopping, 5% pathologic gambling, 11% compulsive eating, 3% hypersexuality, 7% punding, and 17% any ICD. These values were statistically significant when compared with those of control subjects with OSA for compulsive shopping, pathologic gambling, punding, and any ICD, as well as for compulsive shopping when compared with control subjects with RLS who were not treated with dopaminergic agents. In the RLS treatment group, a statistically significant dose effect was found for pramipexole in those subjects confirmed to have ICDs by both the questionnaire and phone interview. Mean duration of treatment at ICD onset was 9.5 months. CONCLUSIONS: ICDs are common with the use of dopaminergic agents for treatment of RLS. Given the potentially devastating psychosocial consequences of these behaviors, it is critical to actively screen for ICDs in this population.

Following the clot in spectacular shrinking deficit.

A subset of patients with major cerebral hemispheric ischemia due to distal internal carotid artery or proximal middle cerebral artery occlusion has rapid spontaneous improvement of neurologic deficits. This phenomenon has been designated the "spectacular shrinking deficit." A 79-year-old woman had the sudden onset of neurologic deficits consistent with a large right middle cerebral artery territory infarct. Serial multimodality imaging studies documented distal propagation and fragmentation of a proximal middle cerebral artery thrombus coinciding with rapid clinical improvement. Spectacular shrinking deficit provides a unique insight into the underlying characteristics of a patient population not treated with thrombolytics with impressive recovery from major hemispheric ischemia.

Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months.

OBJECTIVE: To determine the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. DESIGN: Prospective multicenter single group trial with participants serving as their own controls. SETTING: Twenty-two community and academic sleep medicine and otolaryngology practices. MEASUREMENTS: Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level for each participant was collected at three predefined thresholds during awake testing. Procedure- and/or device-related adverse events were reviewed and coded by the Clinical Events Committee. RESULTS: The median AHI was reduced by 67.4% from the baseline of 29.3 to 9.7/h at 18 mo. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 mo. The FOSQ and ESS improved significantly at 18 mo compared to baseline values. The functional threshold was unchanged from baseline at 18 mo. Two participants experienced a serious device-related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness reported at 18 mo. CONCLUSION: Upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 mo of follow-up.

Sleep manifestations of voltage-gated potassium channel complex autoimmunity.

OBJECTIVE: To identify the spectrum of sleep disorders associated with autoantibodies reactive with voltage-gated potassium channel (VGKC) complexes. DESIGN: Case series of all patients with neurologic disorders of VGKC autoimmunity evaluated in the Mayo Clinic Center for Sleep Medicine (Rochester, Minnesota) between January 1, 1994, and February 1, 2010. SETTING: Academic referral center. PATIENTS: Fifteen consecutive patients were identified with limbic encephalitis (n = 5), Morvan syndrome (n = 4), and overlapping features (n = 6). INTERVENTION: Ten patients received immunotherapy (corticosteroids, cyclophosphamide, or mycophenolate mofetil). MAIN OUTCOME MEASURE: Response to immunotherapy. RESULTS: The median VGKC autoantibody value at presentation was 1.51 nmol/L (range, 0.09-4.86 nmol/L). Neoplasms were discovered in 5 patients (33%) (thymoma [n = 2], prostate adenocarcinoma, colon adenocarcinoma, and melanoma). In 14 patients (93%), serious sleep disturbances were identified (insomnia, dream enactment behavior, suspected nocturnal epilepsy, and hypersomnia). Severe insomnia occurred in 9 patients (60%), regardless of neurologic presentation. Polysomnography at presentation (7 patients) revealed a mean sleep efficiency of 19% (4 patients had complete absence of sleep). Dream enactment behavior occurred in 8 patients (53%), including 3 of 5 with limbic encephalitis and all 4 with Morvan syndrome. Two of 7 polysomnograms demonstrated loss of rapid eye movement sleep muscle atonia; absent or minimal rapid eye movement sleep precluded interpretation in 4 patients. Sleep disorders resolved completely or almost completely in 8 of 10 patients who received immunotherapy. CONCLUSIONS: Sleep disorders are cardinal manifestations of VGKC complex autoimmunity in association with a spectrum of neurologic presentations. They may respond favorably to immunotherapy.

Visual symptoms in the Heidenhain variant of Creutzfeldt-Jakob Disease.

BACKGROUND AND PURPOSE: The distinguishing feature in Heidenhain variant Creutzfeldt-Jakob Disease (HvCJD) is the presence of visual symptoms preceding the appearance of other clinical manifestations. The purpose of this report is to describe the broad range of visual symptomatology in a patient with HvCJD. METHODS: The authors describe the clinical, neuroimaging, and EEG features of a 51-year-old man with progressive visual symptoms that were most likely due to HvCJD. Migraine and epilepsy were initial diagnostic considerations. RESULTS: Our patient presented with progressive visual decline and superimposed spells of visual dysfunction that had complex characteristics. Evolution of an abnormal signal in the parieto-occipital cortex on diffusion weighted MRI, changes on EEG, and clinical course were consistent with HvCJD. CONCLUSIONS: HvCJD should be considered in all patients who present with unexplained visual phenomena. A remarkable spectrum of visual disturbances can be seen. Close follow-up as well as serial MRI and EEG can help clarify the underlying disease process. Diffusion-weighted and FLAIR sequences should be included in the MRI protocol.