Jorge Iriarte

Coupling between Beta and High-Frequency Activity in the Human Subthalamic Nucleus May Be a Pathophysiological Mechanism in Parkinson's Disease

In Parkinsons disease (PD), the oscillatory activity recorded from the basal ganglia shows dopamine-dependent changes. In the “off” parkinsonian motor state, there is prominent activity in the beta band (12–30 Hz) that is mostly attenuated after dopaminergic therapy (“on” medication state). The on state is also characterized by activity in the gamma (60–80 Hz) and high-frequency (300 Hz) bands that is modulated by movement. We recorded local field potentials from a group of 15 PD patients (three females) treated with bilateral deep brain stimulation of the subthalamic nucleus, using a high sampling rate (2 kHz) and filters suitable to study high-frequency activity (0.3–1000 Hz). We observed high-frequency oscillations (HFOs) in both the off and on motor states. In the off state, the amplitude of the HFOs was coupled to the phase of the abnormal beta activity. The beta-coupled HFOs showed little or even negative movement-related changes in amplitude. Moreover, the degree of movement-related modulation of the HFOs correlated negatively with the rigidity/bradykinesia scores. In the on motor state, the HFOs were liberated from this beta coupling, and they displayed marked movement-related amplitude modulation. Cross-frequency interactions between the phase of slow activities and the amplitude of fast frequencies have been attributed an important role in information processing in cortical structures. Our findings suggest that nonlinear coupling between frequencies may not only be a physiological mechanism (as shown previously) but also that it may participate in the pathophysiology of parkinsonism.

Changes in the Heart Rate Variability in Patients with Obstructive Sleep Apnea and Its Response to Acute CPAP Treatment

Introduction Obstructive Sleep Apnea (OSA) is a major risk factor for cardiovascular disease. The goal of this study was to demonstrate whether the use of CPAP produces significant changes in the heart rate or in the heart rate variability of patients with OSA in the first night of treatment and whether gender and obesity play a role in these differences. Methods Single-center transversal study including patients with severe OSA corrected with CPAP. Only patients with total correction after CPAP were included. Patients underwent two sleep studies on consecutive nights: the first night a basal study, and the second with CPAP. We also analyzed the heart rate changes and their relationship with CPAP treatment, sleep stages, sex and body mass index. Twenty-minute segments of the ECG were selected from the sleep periods of REM, no-REM and awake. Heart rate (HR) and heart rate variability (HRV) were studied by comparing the R-R interval in the different conditions. We also compared samples from the basal study and CPAP nights. Results 39 patients (15 females, 24 males) were studied. The mean age was 50.67 years old, the mean AHI was 48.54, and mean body mass index was 33.41 kg/m2 (31.83 males, 35.95 females). Our results showed that HRV (SDNN) decreased after the use of CPAP during the first night of treatment, especially in non-REM sleep. Gender and obesity did not have any influence on our results. Conclusions These findings support that cardiac variability improves as an acute effect, independently of gender or weight, in the first night of CPAP use in severe OSA patients, supporting the idea of continuous use and emphasizing that noncompliance of CPAP treatment should be avoided even if it is just once.

Are we overusing the diagnosis of psychogenic non-epileptic events?

In order to determine how often results of video/EEG (V-EEG) studies may change the clinical diagnosis of paroxysmal events, we prospectively studied 100 consecutive patients (75 females, 25 males) admitted for diagnosis of recurrent paroxysmal spells. The presumed diagnosis of the referring physician was obtained. Episodes were classified as epileptic seizures (ES), psychogenic non-epileptic events (PNEE), or physiologic non-epileptic events (PhysNEE). Eighty-seven patients had diagnostic events. A final diagnosis of ES was made in 21 patients, PNEE in 39, PNEE + ES in 20, and PhysNEE in seven. All PhysNEE were unsuspected. ES were misdiagnosed as PNEE more frequently than the reverse (57% vs. 12%, P < 0.001). Among the 64 patients with recorded events who had been suspected of having PNEE, 14 (21.9%) were misdiagnosed: two had PhysNEE and 12 (18.75%) had ES. Among the 23 patients with recorded events who were thought to have ES, 12 (39.1%) were misdiagnosed: seven had PNEE, five PhysNEE. V-EEG changed the clinical diagnosis in 29.8% of the patients with recorded events. Our data suggests that clinicians have become more aware of PNEE since the advent of V-EEG and have little problem recognizing them. However, they may be more prone to make a false-positive diagnosis of PNEE in ES with some atypical features. At this point, efforts should be channeled to better training in the proper recognition of ES that mimic PNEE.

When should induction protocols be used in the diagnostic evaluation of patients with paroxysmal events

Summary: Purpose: To determine the timing of spontaneous psychogenic nonepileptic events (PNEE) during video‐EEG telemetry (VEEG), and the need to use induction protocols (IP).

Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies

Sleep and circadian disorders in Alzheimer’s disease (AD) are more frequent than in the general population and appear early in the course of the disease. Quality of sleep and quality of life are parallel in these patients, and such disorders also represent a heavy burden for caregivers. Although alterations in melatonin and hypocretins (orexins) seem to play a key role in the origin of these disturbances, the etiology of these disorders is multifactorial, including many factors such as environment, behavior, treatments, and comorbidities, among others. A comprehensive evaluation of sleep in each patient is essential in the design of the treatment that includes nonpharmacological and pharmacological approaches. One particularly interesting point is the possibility of a role of sleep disorders in the pathogenesis of AD, raising the possibility that treating the sleep disorder may alter the course of the disease. In this review, we present an update on the role of sleep disorders in AD, the bidirectional influence of sleep problems and AD, and treatment options. Behavioral measures, bright light therapy (BLT), melatonin, and other drugs are likely well known and correctly managed by the physicians in charge of these patients. In spite of the multiple treatments used, evidence of efficacy is scarce and more randomized double-blind placebo-controlled studies are needed. Future directions for treatment are the establishment of BLT protocols and the development of drugs with new mechanisms of action, especially hypocretin receptor antagonists, melatonin receptor agonists, and molecules that modulate the circadian clock.

Increased Sympathetic and Decreased Parasympathetic Cardiac Tone in Patients with Sleep Related Alveolar Hypoventilation

OBJECTIVE To assess autonomic function by heart rate variability (HRV) during sleep in patients with sleep related alveolar hypoventilation (SRAH) and to compare it with that of patients with obstructive sleep apnea (OSA) and control patients. DESIGN Cross-sectional study. SETTING Sleep Unit, University Hospital of University of Navarra. PATIENTS Fifteen idiopathic and obesity related-SRAH patients were studied. For each patient with SRAH, a patient with OSA, matched in age, sex, body mass index (BMI), minimal oxygen saturation (SatO2), and mean SatO2 was selected. Control patients were also matched in age, sex, and BMI with patients with OSA and those with SRAH, and in apnea/hypopnea index (AHI) with patients with SRAH. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Time- and frequency-domain HRV measures (R-R, standard deviation of normal-to-normal RR interval [SDNN], very low frequency [VLF], low frequency [LF], high frequency [HF], LF/HF ratio) were calculated across all sleep stages as well as during wakefulness just before and after sleep during a 1-night polysomnography. In patients with SRAH and OSA, LF was increased during rapid eye movement (REM) when compared with control patients, whereas HF was decreased during REM and N1-N2 sleep stages. The LF/HF ratio was equally increased in patients with SRAH and OSA during REM and N1-N2. Correlation analysis showed that LF and HF values during REM sleep were correlated with minimal SatO2 and mean SatO2. CONCLUSIONS Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory events.

De novo psychogenic nonepileptic seizures after epilepsy surgery

Summary: Purpose: The occurrence of de novo nonepileptic seizures (NES) after epilepsy surgery have been reported only twice in the literature (one article and one abstract).

Characterizing the phenotypes of obstructive sleep apnea: Clinical, sleep, and autonomic features of obstructive sleep apnea with and without hypoxia

OBJECTIVE The pathophysiological basis of obstructive sleep apnea (OSA) is not completely understood and likely varies among patients. In this regard, some patients with OSA do not exhibit hypoxemia. We aimed to analyze the clinical, sleep, and autonomic features of a group of patients with severe OSA without hypoxia (OSA-h) and compare to OSA patients with hypoxia (OSA+h) and controls. METHODS Fifty-six patients with OSA-h, 64 patients with OSA+h, and 44 control subjects were studied. Clinical and sleep features were analyzed. Besides, time- and frequency-domain heart rate variability (HRV) measures comprising the mean R-R interval, the standard deviation of the RR intervals (SDNN), the low frequency (LF) oscillations, the high frequency (HF) oscillations, and the LF/HF ratio, were calculated across sleep stages during a one-night polysomnography. RESULTS OSA-h patients had a lower body mass index, a lower waist circumference, lower apnea duration, and a higher frequency of previous naso-pharyngeal surgery when compared to OSA+h patients. In terms of heart rate variability, OSA+h had increased LF oscillations (i.e., baroreflex function) during N1-N2 and rapid eye movement (REM) sleep when compared to OSA-h and controls. Both OSA+h and OSA-h groups had decreased HF oscillations (i.e., vagal inputs) during N1-N2, N3 and REM sleep when compared to controls. The LF/HF ratio was increased during N1-N2 and REM sleep, only in patients with OSA+h. CONCLUSIONS Patients with OSA-h exhibit distinctive clinical, sleep, and autonomic features when compared to OSA with hypoxia. SIGNIFICANCE OSA is a heterogeneous entity. These differences must be taken into account in future studies when analyzing therapeutic approaches for sleep apnea patients.

Sleep structure in patients with periodic limb movements and obstructive sleep apnea syndrome.

Abstract: Periodic limb movements (PLM) and obstructive sleep apnea syndrome (OSAS) are two frequent sleep disorders which often occur in the same patient. The goal of this study was to know the influence of the presence of PLM in the sleep architecture in patients with and without OSAS. Two hundred twenty consecutive patients (69 women and 151 men) participated in this transversal study. They were patients with clinical suspicion of dysomnia, including snoring, OSAS, and PLM. All of them underwent a full polysomnography and were interviewed using questionnaires about the sleep quality. The sleep parameters (percentage of sleep stages, rapid eye movement latency, sleep efficiency, awakenings, PLM presence, apnea-hypopnea index) were calculated and compared between groups. Descriptive statistics and nonparametric distribution techniques were used for the analysis. Patients with PLM when compared with patients with OSAS had lower sleep efficiency and less rapid eye movement percentage. The presence of PLM in patients with sleep apnea was less relevant being responsible only for an increase in the rapid eye movement latency and a decrease in the duration of the three to four sleep stages. However, the presence of OSAS was related to a better sleep efficiency (patients with PLM plus OSAS had a better sleep efficiency than patients with only PLM). PLM alters the structure of sleep. In patients with sleep apnea, the presence of PLM is less relevant.

Independent component analysis in the study of focal seizures.

Independent component analysis (ICA) is a novel technique that can separate statistically independent elements from complex signals. It has demonstrated its utility in separating artifacts and analyzing interictal discharges in EEG. ICA has been used recently in ictal recordings, showing the possibility of isolating the ictal activity. The goal of our study was to analyze focal seizures with ICA, decomposing the elements of the seizures to understand their genesis and propagation, and to differentiate between various types of focal seizures. We studied 26 focal seizures of temporal, frontal, or parietal origin. Only seizures with suspected focal onset were included in the study. The EEG recordings were acquired by using standard video-EEG equipment, with scalp electrodes. All the off-line analysis was carried out on a PC by means of specific software developed in the Matlab environment. ICA components were calculated with the use of the JADE (Joint Approximate Diagonalization of Eigen-matrices) algorithm. The decomposition of the seizures varied according to the EEG seizure pattern. In the seizures with focal rhythmic theta slow or sharp waves, the rhythmic activity was separated into one to five components, having an initial component with a clear concordance with the focus, whereas the others had an onset a few milliseconds later and corresponded to neighboring areas. In the 6 frontal seizures with regional rhythmic low voltage fast activity, 4 to 10 components were found, practically with a simultaneous timing, having a frontal distribution. In the three frontal seizures with a diffuse attenuation of the EEG signal, it was not possible to differentiate components of cerebral origin from the components of muscle artifact. ICA is an interesting tool to study the nature of focal seizures. The results depend on the EEG pattern. In the seizures with a clear EEG focal pattern, ICA may be useful to separate components of the ictal onset from the propagated activity.