Nuestros investigadores

Manuel Alegre Esteban

Departamento
Neurología y Neurocirugía
Facultad de Medicina. Universidad de Navarra
Neurofisiología
Clínica Universidad de Navarra. Clínica Universidad de Navarra
Líneas de investigación
Neurofisiología del control motor, Fisiopatología de la enfermedad de Parkinson
Índice H
22, (WoS, 10/05/2017)

Publicaciones científicas más recientes (desde 2010)

Autores: Guridi Legarra, Jorge; Alegre Esteban, Manuel
Revista: MOVEMENT DISORDERS
ISSN 0885-3185  Vol. 32  Nº 1  2017  págs. 64 - 69
Over the past 10 years, research into the neurophysiology of the basal ganglia has provided new insights into the pathophysiology of movement disorders. The presence of pathological oscillations at specific frequencies has been linked to different signs and symptoms in PD and dystonia, suggesting a new model to explain basal ganglia dysfunction. These advances occurred in parallel with improvements in imaging and neurosurgical techniques, both of which having facilitated the more widespread use of DBS to modulate dysfunctional circuits. High-frequency stimulation is thought to disrupt pathological activity in the motor cortex/ basal ganglia network; however, it is not easy to explain all of its effects based only on changes in network oscillations. In this viewpoint, we suggest that a return to (C) 2016 International Parkinson and Movement Disorder Society
Autores: Alegre Esteban, Manuel; Molero Santos, Patricio; Valencia Ustárroz, Miguel; et al.
Revista: PSYCHIATRY RESEARCH
ISSN 0165-1781  Vol. 247   2017  págs. 214 - 221
The symptoms of schizophrenia might be mediated by a cortical network disconnection which may disrupt the cortical oscillatory activity. Steady-state responses are an easy and consistent way to explore cortical oscillatory activity. A chirp-modulated tone (increasing the frequency of the modulation in a linear manner) allows a fast measure of the steady-state response to different modulation rates. With this approach, we studied the auditory steady-state responses in two groups of patients with schizophrenia (drug-naive and treated with atypical antipsychotic drugs), in order to assess the differences in their responses with respect to healthy subjects, and study any potential effect of medication. Drug-naive patients had reduced amplitude and inter-trial phase coherence of the response in the 30¿50 Hz range, and reduced amplitude of the response in the 90¿100 Hz range, when compared to controls. In the treated patients group, the response in the 30¿50 Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90¿100 Hz range remained as in the drug-naive group. These results suggest that gamma activity impairment in schizophrenia is a complex phenomenon that affects a wide band of frequencies and may be influenced by antipsychotic treatment.
Autores: Honorato Cía, María Cristina; Martínez Simón, Antonio; Guridi Legarra, Jorge; et al.
Revista: WORLD NEUROSURGERY
ISSN 1878-8750  Vol. 101  2017  págs. 114 - 121
BACKGROUND: The anesthetic management of patients requiring surgery for movement disorders needs to balance microrecording quality and patient cooperation with safety and comfort. Anesthetics can alter microrecording, although the effect on outcome is debatable. They also provide a rested and cooperative patient and minimize complications such as intracranial hemorrhage by providing better hemodynamic control. Most teams use local anesthesia with monitored anesthesia care or conscious sedation with propofol. Recently, dexmedetomidine has emerged as an alternative that, at low doses, does not affect microrecording, and that does not impair respiratory drive. METHODS: In the past 15 years, we have used in our institution local anesthesia, remifentanil, or dexmedetomidine sedation. We compared functional outcome and rate of complications in a group of 145 patients with similar characteristics. RESULTS: We found 5 (3.4%) intracranial hemorrhages. Two (1.4%) were symptomatic. The remifentanil group had the highest risk of having systolic blood pressure > 160 mm Hg during surgery (odds ratio [OR], 2.8; 95% confidence interval [CI], 0.9-9.9), whereas the dexmedetomidine group had the lowest (OR, 0.7; 95% CI, 0.2-1.8), compared with the local anesthesia group. Surgical time was shortest with dexmedetomidine (mean, 283 minutes) and longest with local anesthesia only (mean, 328 minutes). Functional outcome (Unified Parkinson's Disease Rating Scale, Part III motor component scale) was similar among groups. The dexmedetomidine group had a statistically significant lower risk of perioperative neurologic events compared with the local anesthesia group (OR, 0.09; 95% CI, 0.002-0.68). CONCLUSIONS: Sedation can be used safely without affecting outcome, and dexmedetomidine provides better hemodynamic management. Clinical significance remains unclear and larger studies need to be undertaken.
Autores: Rodríguez Díez, María Cristina; Alegre Esteban, Manuel; Díez Goñi, María de las Nieves; et al.
Revista: BMC MEDICAL EDUCATION
ISSN 1472-6920  Vol. 16  Nº 1  2016  págs. 47
The formal quality of the MIR exam items has improved over the last five years with regard to testwiseness. A more detailed revision of the items submitted, checking systematically for the presence of technical flaws, could improve the validity and discriminatory power of the exam, without increasing its difficulty.
Autores: García García, David; Guridi Legarra, Jorge; Toledo Atucha, Juan Bautista; et al.
Revista: JOURNAL OF NEUROSURGERY
ISSN 0022-3085  Vol. 125  Nº 5  2016  págs. 1068 - 1079
OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used in patients with Parkinson's disease (PD). However, which target area of this region results in the highest antiparkinsonian efficacy is still a matter of debate. The aim of this study was to develop a more accurate methodology to locate the electrodes and the contacts used for chronic stimulation (active contacts) in the subthalamic region, and to determine the position at which stimulation conveys the greatest clinical benefit. METHODS The study group comprised 40 patients with PD in whom bilateral DBS electrodes had been implanted in the STN. Based on the Morel atlas, the authors created an adaptable 3D atlas that takes into account individual anatomical variability and divides the STN into functional territories. The locations of the electrodes and active contacts were obtained from an accurate volumetric assessment of the artifact using preoperative and postoperative MR images. Active contacts were positioned in the 3D atlas using stereotactic coordinates and a new volumetric method based on an ellipsoid representation created from all voxels that belong to a set of contacts. The antiparkinsonian benefit of the stimulation was evaluated by the reduction in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score and in the levodopa equivalent daily dose (LEDD) at 6 months. A homogeneous group classification for contact position and the respective clinical improvement was applied using a hierarchical clustering method. RESULTS Subthalamic stimulation induced a significant reduction of 58.0% ± 16.5% in the UPDRS-III score (p < 0.001) and 64.9% ± 21.0% in the LEDD (p < 0.001). The greatest reductions in the total and contralateral UPDRS-III scores (64% and 76%, respectively) and in the LEDD (73%) were obtained when the active contacts were placed approximately 12 mm lateral to the midline, with no influence of the position being observed in the anteroposterior and dorsoventral axes. In contrast, contacts located about 10 mm from the midline only reduced the global and contralateral UPDRS-III scores by 47% and 41%, respectively, and the LEDD by 33%. Using the ellipsoid method of location, active contacts with the highest benefit were positioned in the rostral and most lateral portion of the STN and at the interface between this subthalamic region, the zona incerta, and the thalamic fasciculus. Contacts placed in the most medial regions of the motor STN area provided the lowest clinical efficacy. CONCLUSIONS The authors report an accurate new methodology to assess the position of electrodes and contacts used for chronic subthalamic stimulation. Using this approach, the highest antiparkinsonian benefit is achieved when active contacts are located within the rostral and the most lateral parts of the motor region of the STN and at the interface of this region and adjacent areas (zona incerta and thalamic fasciculus).
Autores: Rodríguez Díez, María Cristina; Tejedor, J. , ; Alegre Esteban, Manuel; et al.
Revista: ATENCION PRIMARIA
ISSN 0212-6567  Vol. 48  Nº 7  2016  págs. 501 - 502
Autores: Iriarte Franco, Jorge; Campo Ezquibela, Aránzazu; Alegre Esteban, Manuel; et al.
Revista: SLEEP MEDICINE
ISSN 1389-9457  Vol. 16  Nº 7  2015  págs. 827 - 830
Background The International Classification of Sleep Disorders ¿ Third Edition (ICSD-3) classifies catathrenia among the respiratory disorders and not as a parasomnia as in ICSD-2. Few patients have been reported during these years, and the clinical description of the sound is different from group to group. In fact, there is no full agreement about its nature, origin, meaning, and treatment. Methods and results In this paper we review the literature on catathrenia focusing on the characteristics of the sound, demographics of the patients, aetiology, response to treatment, etc., in order to support its classification as a respiratory disorder or a parasomnia. We also discuss the possibility of Catathrenia being not one disorder but two variants or two different disorders.
Autores: Jahanshahi, M. , ; Obeso, I. , ; Baunez, C. , ; et al.
Revista: MOVEMENT DISORDERS
ISSN 0885-3185  Vol. 30  Nº 2  2015  págs. 128 - 140
Although Parkinson's disease (PD) is primarily considered a disorder of initiation of actions, patients also have deficits in inhibitory control, both in the motor and cognitive domains. Impulse control disorders, which can develop in association with dopaminergic medication in a small proportion of patients with PD, are the symptoms most commonly considered as representing inhibitory deficits. However, there is now also a body of evidence suggesting a role for the subthalamic nucleus (STN), which is ordinarily hyperactive in PD, in inhibitory control. Here, we review evidence from animal studies, imaging studies, and investigations recording STN activity intra- or perioperatively in patients with PD having surgery for DBS of the STN (STN-DBS). We also highlight relevant hypotheses about the role of the STN and consider evidence from studies that have examined the effect of STN-DBS in patients with PD on performance of experimental tasks requiring inhibition of prepotent or habitual responses or decision making under conflict, as well as the psychiatric side effects of STN-DBS. Though the results are not always consistent, nevertheless, this body of evidence supports the role of the STN in inhibitory and executive control.
Autores: Palma Carazo, José Alberto; Iriarte Franco, Jorge; Fernández González, Secundino; et al.
Revista: CLINICAL AUTONOMIC RESEARCH
ISSN 0959-9851  Vol. 25  Nº 4  2015  págs. 225 - 232
BACKGROUND: Cardiac autonomic tone after long-term continuous positive airway pressure therapy in patients with obstructive sleep apnea remains unexplored. METHODS: Thirty patients with obstructive sleep apnea (14 with moderate and 16 with severe obstructive sleep apnea) were studied during a baseline polysomnographic study, after a full night of acute continuous positive airway pressure treatment, and after long-term (~2 years) chronic continuous positive airway pressure therapy. Twenty age- and gender-matched controls with baseline sleep study were selected for comparison purposes. Cross-spectral analysis and the low-frequency (LF) and high-frequency (HF) components of the heart rate variability were computed separately over 10-min ECG epochs during rapid eye movement sleep, non-rapid eye movement sleep, and wakefulness. RESULTS: During the baseline study, obstructive sleep apnea patients exhibited increased LF, decreased HF, and increased LF/HF ratio during sleep when compared to controls. In a multiple regression model, the mean oxygen saturation explained the increased LF during rapid and non-rapid eye movement sleep in obstructive sleep apnea patients. Acute continuous positive airway pressure therapy decreased the LF modulations and the LF/HF ratio and increased the HF modulations during sleep in patients with severe obstructive sleep apnea. Long-term continuous positive airway pressure therapy decreased LF modulations and LF/HF ratio with increased HF modulations during sleep in patients with moderate and severe obstructive sleep apnea. CONCLUSIONS: Long-term continuous positive airway pressure reduces the sympathovagal imbalance in patients with moderate and severe obstructive sleep apnea, both during rapid and non-rapid eye movement sleep. Continuous positive airway pressure seems to exert its changes in cardiac autonomic modulation by decreasing the burden of nocturnal hypoxia.
Autores: Honorato Cía, María Cristina; Martínez Simón, Antonio; Alegre Esteban, Manuel; et al.
Revista: STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
ISSN 1011-6125  Vol. 93  Nº 6  2015  págs. 393-399
Dexmedetomidine provides adequate sedation during surgery for PD, but it might affect motor signs making intraoperative testing difficult or even impossible. Dosage appears not to be the determining factor in motor changes, whose cause remains unclear.
Autores: Cordón Medrano, Iván; Nicolás Apesteguía, María Jesús; Arrieta Eguren, Sandra; et al.
Revista: EUROPEAN NEUROPSYCHOPHARMACOLOGY
ISSN 0924-977X  Vol. 25  Nº 8  2015  págs. 1375 - 1387
Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals¿ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.
Autores: Rodríguez Díez, María Cristina; Díez Goñi, María de las Nieves; Alegre Esteban, Manuel; et al.
Revista: ATENCION PRIMARIA
ISSN 0212-6567  Vol. 48  Nº 3  2015  págs. 210 - 212
Autores: Palma Carazo, José Alberto; Iriarte Franco, Jorge; Fernández González, Secundino; et al.
Revista: CLINICAL NEUROPHYSIOLOGY
ISSN 1388-2457  Vol. 125  Nº 9  2014  págs. 1783 - 1791
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.
Autores: Palma Carazo, José Alberto; Alegre Esteban, Manuel; Valencia Ustárroz, Miguel; et al.
Revista: JOURNAL OF NEURAL TRANSMISSION
ISSN 1435-1463  Vol. 121  Nº 4  2014  págs. 385-390
The relationship between the autonomic nervous system and periodic leg movements during sleep (PLMS) is not completely understood. We aimed to determine whether patients with PLMS exhibit any changes in their basal heart rate variability (HRV), excluding episodes of leg movements and arousals. To investigate this, we conducted a cross-sectional study including 13 patients with PLMS (PLMS ¿ 20) and 13 matched controls, free of cardiovascular diseases and medications. Time-and frequency-domain HRV measures [mean R-R interval, low frequency (LF), high frequency (HF), LF/HF] were calculated across all sleep stages as well during wakefulness just before and after sleep during one-night polysomnography. We only took ECG segments of sleep without arousals and excluded periods of 30 s before and after the leg movements. No statistical differences between PLMS and control subjects were found in any of the time- or frequency-domain HRV measures across sleep stages. Basal cardiac autonomic modulation in patients with PLMS is similar to that of control subjects. Our results argue against a role for a basal disturbance of the cardiac autonomic nervous system in the pathogenesis of PLMS
Autores: Toledo Atucha, Juan Bautista; López Azcárate, Jon; García García, David; et al.
Revista: NEUROBIOLOGY OF DISEASE
ISSN 0969-9961  Vol. 64  2014  págs. 60-65
p-FOG patients showed higher power in the high-beta band (F=11.6, p=0.002) that was significantly reduced after l-dopa administration along with suppression of FOG (F=4.6, p=0.042). High-beta cortico-STN coherence was maximal for midline cortical EEG electrodes, whereas the low-beta band was maximal for lateral electrodes (¿(2)=20.60, p<0.0001). CONCLUSIONS: The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.
Autores: Palma Carazo, José Alberto; Iriarte Franco, Jorge; Alegre Esteban, Manuel; et al.
Revista: CLINICAL NEUROPHYSIOLOGY
ISSN 1388-2457  Vol. 125  Nº 1  2014  págs. 208 - 210
Autores: Palma Carazo, José Alberto; Iriarte Franco, Jorge; Alegre Esteban, Manuel; et al.
Revista: CLINICAL NEUROPHYSIOLOGY
ISSN 1388-2457  Vol. 125  Nº 1  2014  págs. 208-210
Autores: Alegre Esteban, Manuel; Valencia Ustárroz, Miguel
Revista: EXPERIMENTAL NEUROLOGY
ISSN 0014-4886  Vol. 248  2013  págs. 183 - 186
The implantation of deep brain stimulators in different structures of the basal ganglia to treat neurological and psychiatric diseases has allowed the recording of local field potential activity in these structures. The analysis of these signals has helped our understanding of basal ganglia physiology in health and disease. However, there remain some major challenges and questions for the future. In a recent work, Tan et al. (Tan, H., Pogosyan, A., Anam, A., Foltynie, T., Limousin, P., Zrinzo, L., et al. 2013. Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease. Exp. Neurol. 240,122-129) take profit of these recordings to study the changes in subthalamic oscillatory activity during the hold and release phases of a grasping paradigm, and correlate the changes in different frequency bands with performance parameters. They found that beta activity was related to the release phase, while force maintenance related most to theta and gamma/HFO activity. There was no significant effect of the motor state of the patient on this latter association. These findings suggest that the alterations in the oscillatory activity of the basal ganglia in Parkinson's disease are not limited to the beta band, and they involve aspects different from movement preparation and initiation. Additionally, these results highlight the usefulness of the combination of well-designed paradigms with recordings in off and on motor states (in Parkinson's disease), or in different pathologies, in order to understand not only the pathophysiology of the diseases affecting the patients, but also the normal physiology of the basal ganglia.
Autores: Palma Carazo, José Alberto; Urrestarazu Bolumburu, Elena; López Azcárate, Jon; et al.
Revista: SLEEP
ISSN 0161-8105  Vol. 36  Nº 6  2013  págs. 933 - 940
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.
Autores: Palma Carazo, José Alberto; Urrestarazu Bolumburu, Elena; Alegre Esteban, Manuel; et al.
Revista: CLINICAL NEUROPHYSIOLOGY
ISSN 1388-2457  Vol. 124  Nº 6  2013  págs. 1163 - 1168
OBJECTIVE: Cardiac physiology during sleep in Parkinson's disease (PD) remains poorly explored. We studied heart rate variability (HRV) across sleep stages in PD patients and correlated the results with clinical features. METHODS: Cross-sectional study comprising 33 patients with PD and 29 controls matched for age, gender, and number of apneas/hypopneas per hour. HRV measures, (mean R-R interval, SDNN, ULF, VLF, LF, HF and LF/HF) were calculated separately for all sleep stages as well as wakefulness just before and after sleep during one-night polysomnography. Correlation analysis was performed between HRV values and PD patients' characteristics. RESULTS: The mean R-R interval was lower in all sleep stages in PD patients when compared with controls. VLF and LF were lower during REM sleep in PD patients. HF during N1-N2 stage was higher in PD. We found inverse correlations between VLF and LF during REM sleep and UPDRS-ON and UPDRS-OFF. CONCLUSION: VLF and LF during REM sleep might constitute surrogate markers of disease severity. SIGNIFICANCE: These findings provide additional clinical evidence of the autonomic impairment commonly observed in PD, and prove that cardiac autonomic dysfunction during REM sleep is correlated with disease severity.
Autores: Iriarte Franco, Jorge; Palma Carazo, José Alberto; Fernández González, Secundino; et al.
Revista: SLEEP MEDICINE
ISSN 1389-9457  Vol. 14  Nº 2  2013  págs. 217 - 219
Objectives This is a video case report of a 58-year-old male patient with severe obstructive sleep apnea (OSA) who underwent a pharyngo-laryngoscopy during non-drug-induced sleep. Methods The pharyngo-laryngoscopy was performed transnasally during a 30-minute nap, in the afternoon, with a flexible endoscope in supine position. During the procedure, the patient was monitored with polysomnography. Results The patient slept for 20 minutes in supine position, reaching N2 sleep stage. During the sleep, 15 respiratory events (apneas or hypopneas) were recorded. The video-recording showed that, during apneas, the obstruction at the pharyngeal level was never complete, although the nasal sensor showed a total stop in the nasal airflow. Conclusions This case highlights that OSA could not be as obstructive as generally thought, at least during N2 sleep; moreover, it suggests that apneic episodes are not a totally passive and monomorphic phenomenon, but a rather complex event.
Autores: Alegre Esteban, Manuel; López Azcárate, Jon; Obeso Martin, I., ; et al.
Revista: EXPERIMENTAL NEUROLOGY
ISSN 0014-4886  Vol. 239  2013  págs. 1 - 12
Normal actions and behaviors often require inhibition of unwanted and inadequate movements. Motor inhibition has been studied using the stop signal task, in which participants are instructed to respond to a go signal. Sporadically, a stop signal is also delivered after a short interval following the go signal, prompting participants to inhibit their already started response to the go signal. Functional MRI studies using this paradigm have implicated the activation of the subthalamic nucleus in motor inhibition. We directly recorded subthalamic nucleus activity from bilaterally implanted deep brain stimulation electrodes in a group of 10 patients with Parkinson's disease, during performance of the stop signal task. Response inhibition was associated with specific changes in subthalamic activity in three different frequency bands. Response preparation was associated with a decrease in power and cortico-subthalamic coherence in the beta band (12-30 Hz), which was smaller and shorter when the response was successfully inhibited. In the theta band, we observed an increase in frontal cortico-subthalamic coherence related to the presence of the stop signal, which was highest when response inhibition was unsuccessful. Finally, a specific differential pattern of gamma activity was observed in the "on" motor state. Performance of the response was associated with a significant increase in power and cortico-subthalamic coherence, while successful inhibition of the response was associated with a bilateral decrease in subthalamic power and cortico-subthalamic coherence. Importantly, this inhibition-related decrease in gamma activity was absent in the four patients with dopamine-agonist related impulse-control disorders. Our results provide direct support for the involvement of the subthalamic nucleus in response inhibition and suggest that this function may be mediated by a specific reduction in gamma oscillations in the cortico-subthalamic connection.
Autores: Kufoy, E., ; Palma Carazo, José Alberto; López Azcárate, Jon; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 3  2012  págs. e33769
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/m(2) (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.
Autores: Alegre Esteban, Manuel; López Azcárate, Jon; Alonso-Frech, F., ; et al.
Revista: MOVEMENT DISORDERS
ISSN 0885-3185  Vol. 27  Nº 9  2012  págs. 1178-1981
From a neurophysiological viewpoint, patients exhibited oscillatory activity typical of the "on" medication state during diphasic dyskinesias. The minimal presence of gamma activity during diphasic dyskinesias, however, suggests that this "on" state might be incomplete or limited to dopaminergic mechanisms affecting the lower limbs
Autores: Guridi Legarra, Jorge; Rodríguez Oroz, María Cruz; Alegre Esteban, Manuel; et al.
Revista: PARKINSONISM AND RELATED DISORDERS
ISSN 1353-8020  Vol. 18  Nº 6  2012  págs. 765-769
It is important to identify this hardware problem in view of the growing number of patients receiving this therapy. A protocol for patients with loss of stimulation efficacy and electrode impedance increment needs to be created in clinical visits in order to detect the failed stimulation mechanism.
Autores: Rodríguez Oroz, María Cruz; López Azcárate, Jon; García García, David; et al.
Revista: BRAIN
ISSN 0006-8950  Vol. 134  Nº 1  2011  págs. 36-49
Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson's disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson's disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4-10 Hz) activity (mean peak: 6.71 Hz) that was generated 2-8 mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0-2 mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4-7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5-10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson's disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with l-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson's disease, specifically engaging different anatomo-functional territories
Autores: Iriarte Franco, Jorge; Fernández González, Secundino; Fernández-Arrechea, Natalia; et al.
Revista: SLEEP AND BREATHING
ISSN 1520-9512  Vol. 15  Nº 2  2011  págs. 229 - 235
Purpose: Catathrenia (nocturnal groaning) is a rare and relatively little-understood parasomnia. The characteristics of the sound and the recordings are not similar in all the relevant research papers. Indeed, there is currently some discussion regarding whether or not this is a single entity. For some authors, catathrenia is a particular form of parasomnia; for others, it may be a variant of snoring or a respiratory problem. The goal is to establish whether or not catathrenia may be regarded as an expiratory vocal sound. An attempt was made to classify the origin of this sound according to its sound structure. Methods: We present the sound analysis of two patients, a man and a woman, with clinically diagnosed catathrenia and we compared them with the analysis of snoring. We use the spectrogram and the oscillogram. We classified the sounds according to the Yanagihara criteria. Results: The vocal nature of the sound was confirmed, and several significant differences to some snoring sounds were discovered. The analysis of the catathrenia samples demonstrated that these signals are type II according to Yanagihara classification; these signals had a very short jitter, and had formants and harmonics. However, snoring is a type III, very irregular and had formants but not harmonics. Conclusions: The oscillogram and the spectrogram in these patients show that the origins of the sounds are clearly different: catathrenia is laryngeal, while snoring is guttural. Catathrenia cannot be considered as expiratory snoring.
Autores: Nicolás Apesteguía, María Jesús; López Azcárate, Jon; Valencia Ustárroz, Miguel; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 6  Nº 7  2011  págs. e21814-
Autores: Rodríguez Oroz, María Cruz; López Azcárate, Jon; García García, David; et al.
Revista: BRAIN
ISSN 0006-8950  Vol. 134  Nº Pt.1  2011  págs. 36-49
Autores: Alegre Esteban, Manuel; Guridi Legarra, Jorge; Artieda González-Granda, Julio
Revista: Journal of the Neurological Sciences
ISSN 0022-510X  Vol. 310  Nº 1-2  2011  págs. 194 - 196
Autores: Alegre Esteban, Manuel; Urrestarazu Bolumburu, Elena
Revista: J CLIN NEUROPHYSIOL
ISSN 0736-0258  Vol. 122  Nº 8  2011  págs.  1480 - 1481
Autores: Arrondo Ostiz, Gonzalo; Alegre Esteban, Manuel; Villoslada Díaz, Pablo
Revista: THE EUROPEAN NEUROLOGICAL JOURNAL
ISSN 2041-8000  Vol. 1  2010  págs. 1 - 8
Memantine, an uncompetitive, low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, is an approved compound for use inmoderate to severe Alzheimer¿s disease. Its pharmacological features allow it to block excessive neuronal activation produced by glutamate,while permitting normal activation of the NMDA receptor channel. A review of the trials that have evaluated the use of the compound invascular dementia, Alzheimer¿s disease, or both shows that it is well tolerated and has mild but statistically significant positive effects oncognition and other domains of patients with advanced Alzheimer¿s disease. Recently, a double-blind, placebo-controlled trial in patients withmultiple sclerosis reported neurological worsening in several patients similar to the typical pseudoexacerbations of this disease. Also, the useof memantine in patients with Lewy body disease produces adverse effects. Although the mechanisms of such side-effects are unknown, wesuggest that they could be due to the impairment of synaptic transmission in the demyelinated pathways.
Autores: Alegre Esteban, Manuel; Rodríguez Oroz, María Cruz; Valencia Ustárroz, Miguel; et al.
Revista: Clinical Neurophysiology
ISSN 1388-2457  Vol. 121  Nº 3  2010  págs. 414 - 425
Autores: López Azcárate, Jon; Tainta, M; Rodríguez Oroz, María Cruz; et al.
Revista: JOURNAL OF NEUROSCIENCE
ISSN 0270-6474  Vol. 30  Nº 19  2010  págs. 6667 - 6677
Autores: Unzu Ezquerro, Carmen María; Sampedro Pascual, Ana; Mauleon Mayora, Miren Itsaso; et al.
Revista: Molecular Therapy
ISSN 1525-0016  Vol. 19  Nº 2  2010  págs. 243 - 250
Acute intermittent porphyria (AIP) is characterized by a hereditary deficiency of hepatic porphobilinogen deaminase (PBGD) activity. Clinical features are acute neurovisceral attacks accompanied by overproduction of porphyrin precursors in the liver. Recurrent life-threatening attacks can be cured only by liver transplantation. We developed recombinant adeno-associated virus (rAAV) vectors expressing human PBGD protein driven by a liver-specific promoter to provide sustained protection against induced attacks in a predictive model for AIP. Phenobarbital injections in AIP mice induced porphyrin precursor accumulation, functional block of nerve conduction, and progressive loss of large-caliber axons in the sciatic nerve. Hepatocyte transduction showed no gender variation after rAAV2/8 injection, while rAAV2/5 showed lower transduction efficiency in females than males. Full protection against induced phenobarbital-attacks was achieved in animals showing over 10% of hepatocytes expressing high amounts of PBGD. More importantly, sustained hepatic expression of hPBGD protected against loss of large-caliber axons in the sciatic nerve and disturbances in nerve conduction velocity as induced by recurrent phenobarbital administrations. These data show for the first time that porphyrin precursors generated in the liver interfere with motor function. rAAV2/5-hPBGD vector can be produced in sufficient quantity for an intended gene therapy trial in patients with recurrent life-threatening porphyria attacks.
Autores: Pérez Alcázar, Marta; Nicolás Apesteguía, María Jesús; Valencia Ustárroz, Miguel; et al.
Revista: Brain Research
ISSN 0006-8993  Vol. 1310  2010  págs. 58 - 67