Revistas
Revista:
HANDBOOK OF CLINICAL NEUROLOGY
ISSN:
0072-9752
Año:
2022
Vol.:
184
Págs.:
259 - 271
Brain oscillations have been associated with Parkinson's disease (PD) for a long time mainly due to the fundamental oscillatory nature of parkinsonian rest tremor. Over the years, this association has been extended to frequencies well above that of tremor, largely owing to the opportunities offered by deep brain stimulation (DBS) to record electrical activity directly from the patients' basal ganglia. This chapter reviews the results of research on brain oscillations in PD focusing on theta (4-7Hz), beta (13-35Hz), gamma (70-80Hz) and high-frequency oscillations (200-400Hz). For each of these oscillations, we describe localization and interaction with brain structures and between frequencies, changes due to dopamine intake, task-related modulation, and clinical relevance. The study of brain oscillations will also help to dissect the mechanisms of action of DBS. Overall, the chapter tentatively depicts PD in terms of "oscillopathy."
Revista:
INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD AND NECK SURGERY
ISSN:
2231-3796
Año:
2022
Vol.:
74
N°:
2
Págs.:
158 - 165
Obstructive sleep apnea (OSA) is the most common respiratory disease in the developed world and is commonly treated with positive airway pressure therapy (PAP). Recently, hypoglossal nerve (HNS) has been introduced as alternative treatment for OSA patients with PAP intolerance. We report the initial results with HNS treatment from Spain. Patients with OSA and PAP intolerance were screened for HNS treatment with the Inspire (TM) system. After implantation and activation, efficacy was evaluated with polysomnography and indication-specific questionnaires. Adherence data was recorded from the stimulation system. 18 patients (51.83 +/- 11.64 years, 94% male, mean Body Mass Index 27.94 +/- 3.20) received an Inspire (TM) UAS system and were included for analysis. Mean procedure time was 202.83 +/- 64.87 min. and average hospital stay 26.67 +/- 7.54 h. Mean Apnea-Hypopnea-Index was reduced by 63.44% (p <= 0.0001), while daytime sleepiness improved to a mean ESS score of 6.60 +/- 1.25 (p <= 0.0001 Therapy response (AHI reduction > 50% and final AHI < 20), was reached in 64.70 and normalization of daytime sleepiness (final ESS score < 10) in 100% of patients. Therapy adherence was 6.32 +/- 1.71 h per night. HNS is a safe and leads to effective OSA control and symptom normalization in selected OSA patients with PAP intolerance. Stimulation therapy is well accepted, as demonstrated by high adherence. Implementation of HNS therapy into an OSA program in Spain is feasible with acceptable learning curve and moderate resource utilization.
Revista:
LIFE
ISSN:
2075-1729
Año:
2022
Vol.:
12
N°:
11
Págs.:
1737
Patients with obstructive sleep apnea (OSA) that do not tolerate/accept continuous positive airway pressure (CPAP) are candidates for surgical alternatives. Hypoglossal nerve stimulation (HNS) through the implantation of the Inspire (R) device constitutes a minimally invasive operative option. The main objective of this study is to estimate, under real-world clinical practice conditions, the 3-month impact on the quality of life (IQoL) of the HNS in patients with moderate/severe OSA who do not tolerate or accept CPAP, compared to patients who did not receive HNS. As a baseline, the unadjusted EuroQol utility index was 0.764 (SD:0.190) in the intervention group (IGr) and 0.733 (SD:0.205) in the control group (CGr); three months later, the indexes were 0.935 (SD: 0.101) and 0.727 (SD:0.200), respectively. The positive impact on quality of life was estimated to be +0.177 (95% CI: 0.044-0.310; p = 0.010). All dimensions in the IGr improved compared to CGr, especially for usual activities (p < 0.001) and anxiety/depression (p > 0.001). At the end of the follow-up, there was no significant difference in the quality of life between the general Spanish population and the IGr (difference: 0.012; CI95%: -0.03 to -0.057; p = 0.0578) for the same age range; however, there was a difference concerning the CGr (difference: -0.196; CI95%: -0.257 to -0.135; p < 0.001). In conclusion, patients with moderate/severe OSA implanted with the Inspire (R) device showed a positive IQoL.
Revista:
SCIENCE TRANSLATIONAL MEDICINE
ISSN:
1946-6234
Año:
2022
Vol.:
14
N°:
627
Págs.:
eabc0700
Correction of enzymatic deficits in hepatocytes by systemic administration of a recombinant protein is a desired therapeutic goal for hepatic enzymopenic disorders such as acute intermittent porphyria ( AIP), an inherited porphobilinogen deaminase (PBGD) deficiency. Apolipoprotein A-I (ApoAI) is internalized into hepatocytes during the centripetal transport of cholesterol. Here, we generated a recombinant protein formed by linking ApoAI to the amino terminus of human PBGD (rhApoAI-PBGD) in an attempt to transfer PBGD into liver cells. In vivo experiments showed that, after intravenous injection, rhApoAI-PBGD circulates in blood incorporated into high-density lipoprotein (HDL), penetrates into hepatocytes, and crosses the blood-brain barrier, increasing PBGD activity in both the liver and brain. Consistently, the intravenous administration of rhApoAI-PBGD or the hyperfunctional rApoAI-PBGD-I129M/N340S (rApoAI-PBGDms) variant efficiently prevented and abrogated phenobarbital-induced acute attacks in a mouse model of AIP. One month after a single intravenous dose of rApoAI-PBGDms, the protein was still detectable in the liver, and hepatic PBGD activity remained increased above control values. A long-lasting therapeutic effect of rApoAI-PBGDms was observed after either intravenous or subcutaneous administration. These data describe a method to deliver PBGD to hepatocytes with resulting enhanced hepatic enzymatic activity and protection against AIP attacks in rodent models, suggesting that the approach might be an effective therapy for AIP.
Revista:
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
ISSN:
1661-7827
Año:
2022
Vol.:
19
N°:
11
Págs.:
6934
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure-Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.
Revista:
NEUROREPORT
ISSN:
0959-4965
Año:
2022
Vol.:
33
N°:
11
Págs.:
487 - 494
There is a growing interest about the effects of static transcranial magnetic stimulation (tSMS) over different cortical areas, being the motor cortex the most widely studied region. Previous experiments have shown that noninvasive magnetic static stimulation of the human brain may change its excitability in a reversible way for a period that outlasts the time of application of the magnetic field. However, evidence about the effects over the auditory cortex are poor and this is the purpose of the present study. Twelve voluntary subjects were studied in two different sessions, immediately before and 20 min after the placement of a magnet or a sham over the left primary auditory cortex, for 30 min. No significant effects of the magnet were observed on auditory responses, including onset and offset potentials and oscillatory responses to stimulus frequency modulation. A reduction in the amplitude of the cortical onset and offset potentials was observed after the two sessions, both with the magnet and with the false magnet (sham). No effects of unilateral static magnetic stimulation on cortical auditory responses have been observed. However, we probe the feasibility and tolerability of the protocol performed and suggest the use of different stimulation protocols.
Revista:
BRITISH JOURNAL OF ANAESTHESIA
ISSN:
0007-0912
Año:
2021
Vol.:
127
N°:
2
Págs.:
245 - 253
Background: Dexmedetomidine is frequently used for sedation during deep brain stimulator implantation in patients with Parkinson's disease, but its effect on subthalamic nucleus activity is not well known. The aim of this study was to quantify the effect of increasing doses of dexmedetomidine in this population. Methods: Controlled clinical trial assessing changes in subthalamic activity with increasing doses of dexmedetomidine (from 0.2 to 0.6 mg kg(-1) h(-1)) in a non-operating theatre setting. We recorded local field potentials in 12 patients with Parkinson's disease with bilateral deep brain stimulators (24 nuclei) and compared basal activity in the nuclei of each patient and activity recorded with different doses. Plasma levels of dexmedetomidine were obtained and correlated with the dose administered. Results: With dexmedetomidine infusion, patients became clinically sedated, and at higher doses (0.5-0.6 mg kg(-1) h(-1)) a significant decrease in the characteristic Parkinsonian subthalamic activity was observed (P<0.05 in beta activity). All subjects awoke to external stimulus over a median of 1 (range: 0-9) min, showing full restoration of subthalamic activity. Dexmedetomidine dose administered and plasma levels showed a positive correlation (repeated measures correlation coefficient=0.504; P<0.001). Conclusions: Patients needing some degree of sedation throughout subthalamic deep brain stimulator implantation for Parkinson's disease can probably receive dexmedetomidine up to 0.6 mg kg(-1) h(-1) without significant alteration of their characteristic subthalamic activity. If patients achieve a 'sedated' state, subthalamic activity decreases, but they can be easily awakened with a non-pharmacological external stimulus and recover baseline subthalamic activity patterns in less than 10 min.
Revista:
MOLECULAR THERAPY - NUCLEIC ACIDS
ISSN:
2162-2531
Año:
2021
Vol.:
25
Págs.:
207 - 219
Variegate porphyria (VP) results from haploinsufficiency of pro-toporphyrinogen oxidase (PPDX), the seventh enzyme in the heme synthesis pathway. There is no VP model that recapitulates the clinical manifestations of acute attacks. Combined administrations of 2-allyl-2-isopropylacetamide and rifampicin in rabbits halved hepatic PP OX activity, resulting in increased accumulation of a potentially neurotoxic heme precursor, lipid peroxidation, inflammation, and hepatocyte cytoplasmic stress. Rabbits also showed hypertension, motor impairment, reduced activity of critical mitochondrial hemoprotein functions, and altered glucose homeostasis. Hemin treatment only resulted in a slight drop in heme precursor accumulation but further increased hepatic heme catabolism, inflammation, and cytoplasmic stress. Hemin replenishment did protect against hypertension, but it failed to restore action potentials in the sciatic nerve or glucose homeostasis. Systemic porphobilinogen deaminase (PBGD) mRNA administration increased hepatic PBGD activity, the third enzyme of the pathway, and rapidly normalized serum and urine porphyrin precursor levels. All features studied were improved, including those related to critical hemoprotein functions. In conclusion, the VP model recapitulates the biochemical characteristics and some clinical manifestations associated with severe acute attacks in humans.
Revista:
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
ISSN:
1090-3798
Año:
2020
Vol.:
24
Págs.:
134 - 141
Objective: To evaluate the capability of children with Dravet syndrome to generate brain gamma-oscillatory activity in response to auditory steady-state stimulation. Methods: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. Results: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) gamma-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. Conclusions: The ability to generate brain gamma-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. Significance: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Revista:
HUMAN MOLECULAR GENETICS
ISSN:
0964-6906
Año:
2020
Vol.:
29
N°:
19
Págs.:
3211 - 3223
Revista:
ACTA OTORRINOLARINGOLOGICA ESPAÑOLA
ISSN:
0001-6519
Año:
2020
Vol.:
71
N°:
4
Págs.:
225 - 234
Introduction: Cochlear implants have been able to treat some types of hearing loss, but those related to cochlear nerve impairment made it necessary to find new ways to manage these deficits; leading to auditory brainstem implants (ABI).
Aim: Our objective is to present the clinical profile of patients treated through an ABI and the results obtained from 1997 to 2017.
Material and methods: On the one hand, patients with statoacoustic nerve tumours (VIIIcranial nerve) were selected, and on the other hand, patients withoutVIII tumours with congenital malformations of the inner ear. Before and after the placement of the ABI, hearing was assessed through tonal audiometry, from which the PTA (Pure Tone Average) and the CAP (Categories of Auditory Performance) scale were obtained.
Results: A total of 20 patients undergoing ABI surgery were included. Eight were of tumour cause (40%) and 12 non-tumour (60%). In 15 subjects (75%) a suboccipital approach was performed and in 5 (25%) translabyrinthine. The mean of active electrodes before the implantation of Cochlear® (Nucleus ABI24) was 13/21 (61.90%) versus 8.5/12 (70.83%) of the Med-el® (ABI Med-el). An improvement in the mean PTA of 118.49dB was found against 46.55dB at 2years. On the CAP scale, values of1 were obtained in the preimplantation and of 2.57 (1-5) in the 2-year revision.
Conclusion: The ABI is a safe option, and with good hearing results when the indication is made correctly.
Revista:
ACTA OPHTHALMOLOGICA
ISSN:
1755-375X
Año:
2020
Vol.:
98
N°:
3
Págs.:
e397 - e399
Revista:
HUMAN GENE THERAPY
ISSN:
1043-0342
Porphobilinogen deaminase (PBGD) gene therapy represents a promising therapeutic option for acute intermittent porphyria (AIP) patients suffering recurrent acute attacks. A first-in-human Phase I clinical trial confirmed the safety and tolerability of adeno-associated virus (AAV)-AAT-PBGD gene therapy, but higher doses and/or more efficient vectors are needed to achieve therapeutic expression of the transgene. This study assayed the insertion into the promoter of a short enhancer element able to induce transgene expression during exposure to endogenous and exogenous stimuli related to the pathology of the disease. The inclusion in tandem of two elements of the minimal functional sequence of human -aminolevulinic acid synthase drug-responsive enhancing sequence (ADRES) positioned upstream of the promoter strongly induced transgene expression in the presence of estrogens, starvation, and certain drugs known to trigger attacks in porphyria patients. The inclusion of two ADRES motives in an AAV vector improved therapeutic efficacy, reducing 10-fold the effective dose in AIP mice. In conclusion, the inclusion of specific enhancer elements in the promoter of gene therapy vectors for AIP was able to overexpress the therapeutic transgene when it is most needed, at the time when porphyrinogenic factors increase the demand for hepatic heme and precipitate acute porphyria attacks.
Revista:
ACTA OTORRINOLARINGOLOGICA ESPAÑOLA
ISSN:
0001-6519
Año:
2018
Vol.:
69
N°:
1
Págs.:
42 - 47
The objective of this communication is to describe our preliminary results in upper airway stimulation surgery via hypoglossal nerve stimulation implantation for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery were analysed using the Epworth scale, apnoea-hypopnoea index, minimal 02 Sat, average 02 Sat and snoring intensity. In all cases a significant reduction in Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The minimum and average oxygen saturation had better values after the surgery, however, there was no statistically significant difference. The snoring severity measured subjectively changed from "intense" to "absent", in all cases. The preliminary results obtained with the upper airway stimulation surgery via hypoglossal nerve stimulation showed objective and subjective improvement after the implant activation. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Otorrinolaringologia y Cirugia de Cabeza y Cuello. All rights reserved.
Revista:
ACTA OTORRINOLARINGOLOGICA ESPAÑOLA
ISSN:
0001-6519
Año:
2018
Vol.:
69
N°:
1
Págs.:
42 - 47
The objective of this communication is to describe our preliminary results in upper airway stimulation surgery via hypoglossal nerve stimulation implantation for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery were analysed using the Epworth scale, apnoea-hypopnoea index, minimal O2 Sat, average O2 Sat and snoring intensity. In all cases a significant reduction in Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The minimum and average oxygen saturation had better values after the surgery, however, there was no statistically significant difference. The snoring severity measured subjectively changed from «intense» to «absent» in all cases. The preliminary results obtained with the upper airway stimulation surgery via hypoglossal nerve stimulation showed objective and subjective improvement after the implant activation.
Revista:
M.L.T.J. MUSCLES, LIGAMENTS AND TENDONS JOURNAL
ISSN:
2240-4554
Año:
2018
Vol.:
8
N°:
2
Págs.:
261-275
Conclusion: Animal models for muscular degeneration after rotator cuff tears have been well established and described. The next challenge is the achievement of a therapeutic target that could be transferred to the clinical setting.
Revista:
NATURE MEDICINE
ISSN:
1078-8956
Año:
2018
Vol.:
24
N°:
12
Págs.:
1899 - 1909
Acute intermittent porphyria (AIP) results from haploinsufficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis pathway. Patients with AIP have neurovisceral attacks associated with increased hepatic heme demand. Phenobarbital-challenged mice with AIP recapitulate the biochemical and clinical characteristics of patients with AIP, including hepatic overproduction of the potentially neurotoxic porphyrin precursors. Here we show that intravenous administration of human PBGD (hPBGD) mRNA (encoded by the gene HMBS) encapsulated in lipid nanoparticles induces dose-dependent protein expression in mouse hepatocytes, rapidly normalizing urine porphyrin precursor excretion in ongoing attacks. Furthermore, hPBGD mRNA protected against mitochondrial dysfunction, hypertension, pain and motor impairment. Repeat dosing in AIP mice showed sustained efficacy and therapeutic improvement without evidence of hepatotoxicity. Finally, multiple administrations to nonhuman primates confirmed safety and translatability. These data provide proof-of-concept for systemic hPBGD mRNA as a potential therapy for AIP.
Revista:
BRAIN STIMULATION
ISSN:
1935-861X
Año:
2018
Vol.:
11
N°:
1
Págs.:
231 - 238
Background: High-frequency deep brain stimulation (DBS) has become a widespread therapy used in the treatment of Parkinson's Disease (PD) and other diseases. Although it has proved beneficial, much recent attention has been centered around the potential of new closed-loop DBS implementations. Objective: Here we present a new closed-loop DBS scheme based on the phase of the theta activity recorded from the motor cortex. By testing the implementation on freely moving 6-OHDA lesioned and control rats, we assessed the behavioral and neurophysiologic effects of this implementation and compared it against the classical high-frequency DBS. Results: Results show that both stimulation modalities produce significant and opposite changes on the movement and neurophysiological activity. Close-loop stimulation, far from improving the animals' behavior, exert contrary effects to those of high-frequency DBS which reverts the parkinsonian symptoms. Motor improvement during open-loop, high-frequency DBS was accompanied by a reduction in the amount of cortical beta oscillations while akinetic and disturbed behavior during close-loop stimulation coincided with an increase in the amplitude of beta activity. Conclusion: Cortical-phase-dependent close-loop stimulation of the STN exerts significant behavioral and oscillatory changes in the rat model of PD. Open-loop and close-loop stimulation outcomes differed dramatically, thus suggesting that the scheme of stimulation determines the output of the modulation even if the target structure is maintained. The current framework could be extended in future studies to identify the correct parameters that would provide a suitable control signal to the system. It may well be that with other stimulation parameters, this sort of DBS could be beneficial. (C) 2017 Elsevier Inc. All rights reserved.
Revista:
PSYCHIATRY RESEARCH
ISSN:
0165-1781
Año:
2017
Vol.:
247
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 30-50Hz range, and reduced amplitude of the response in the 90-100Hz range, when compared to controls. In the treated patients group, the response in the 30-50Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90-100Hz 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.
Revista:
ANESTHESIOLOGY
ISSN:
0003-3022
Año:
2017
Vol.:
126
N°:
6
Págs.:
1033 - 1042
Background: Deep brain stimulation electrodes can record oscillatory activity from deep brain structures, known as local field potentials. The authors' objective was to evaluate and quantify the effects of dexmedetomidine (0.2 mu g.kg(-1).h(-1)) on local field potentials in patients with Parkinson disease undergoing deep brain stimulation surgery compared with control recording (primary outcome), as well as the effect of propofol at different estimated peak effect site concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 mu g/ml) from control recording.
Methods: A nonrandomized, nonblinded controlled clinical trial was carried out to assess the change in local field potentials activity over time in 10 patients with Parkinson disease who underwent deep brain stimulation placement surgery (18 subthalamic nuclei). The relationship was assessed between the activity in nuclei in the same patient at a given time and repeated measures from the same nucleus over time.
Results: No significant difference was observed between the relative beta power of local field potentials in dexmedetomidine and control recordings (- 7.7; 95% CI, - 18.9 to 7.6). By contrast, there was a significant decline of 12.7% (95% CI, - 21.3 to - 4.7) in the relative beta power of the local field potentials for each increment in the estimated peak propofol concentrations at the effect site relative to the control recordings.
Conclusions: Dexmedetomidine (0.2 mu g.kg(-1).h(-1)) did not show effect on local field potentials compared with control recording. A significant deep brain activity decline from control recording was observed with incremental doses of propofol.
Revista:
MOVEMENT DISORDERS
ISSN:
0885-3185
Año:
2017
Vol.:
32
N°:
1
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
Revista:
WORLD NEUROSURGERY
ISSN:
1878-8750
Año:
2017
Vol.:
101
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.
Revista:
WORLD NEUROSURGERY
ISSN:
1878-8750
Año:
2017
Vol.:
101
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.
Revista:
ATENCION PRIMARIA
ISSN:
0212-6567
Año:
2016
Vol.:
48
N°:
7
Págs.:
501 - 502
Revista:
JOURNAL OF NEUROSURGERY
ISSN:
0022-3085
Año:
2016
Vol.:
125
N°:
5
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).
Revista:
BMC MEDICAL EDUCATION
ISSN:
1472-6920
Año:
2016
Vol.:
16
N°:
1
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.
Revista:
EUROPEAN NEUROPSYCHOPHARMACOLOGY
ISSN:
0924-977X
Año:
2015
Vol.:
25
N°:
8
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.
Revista:
ATENCION PRIMARIA
ISSN:
0212-6567
Año:
2015
Vol.:
48
N°:
3
Págs.:
210 - 212
Revista:
STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
ISSN:
1011-6125
Año:
2015
Vol.:
93
N°:
6
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.
Revista:
CLINICAL AUTONOMIC RESEARCH
ISSN:
0959-9851
Año:
2015
Vol.:
25
N°:
4
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.
Revista:
JOURNAL OF NEURAL TRANSMISSION
Año:
2014
Vol.:
121
N°:
4
Págs.:
385 - 390
Revista:
CLINICAL NEUROPHYSIOLOGY: OFFICIAL JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL NEUROPHYSIOLOGY
ISSN:
1872-8952
Año:
2014
Vol.:
125
N°:
1
Págs.:
208 - 210
Revista:
CLINICAL NEUROPHYSIOLOGY
ISSN:
1388-2457
Año:
2014
Vol.:
125
N°:
9
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.
Revista:
NEUROBIOLOGY OF DISEASE
Año:
2014
Vol.:
64
Págs.:
60 - 65
Revista:
CLINICAL NEUROPHYSIOLOGY
ISSN:
1388-2457
Año:
2013
Vol.:
124
N°:
6
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:
López, Jon; Nicolas, Maria Jesus; Cordón, Iván; et al.
Revista:
FRONTIERS IN NEURAL CIRCUITS
ISSN:
1662-5110
Año:
2013
Vol.:
7
Págs.:
155
Revista:
SLEEP
ISSN:
0161-8105
Año:
2013
Vol.:
36
N°:
6
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.
Revista:
EXPERIMENTAL NEUROLOGY
ISSN:
00144886
Año:
2013
Vol.:
248
Págs.:
183 - 186
Revista:
SLEEP MEDICINE
ISSN:
1389-9457
Año:
2013
Vol.:
14
N°:
2
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.
Revista:
EXPERIMENTAL NEUROLOGY
ISSN:
0014-4886
Año:
2013
Vol.:
239
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.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2012
Vol.:
7
N°:
3
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.
Revista:
CHAOS, SOLITONS & FRACTALS
Año:
2012
Vol.:
45
N°:
5
Págs.:
619 - 628
Revista:
PARKINSONISM AND RELATED DISORDERS
ISSN:
1353-8020
Año:
2012
Vol.:
18
N°:
6
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.
Revista:
MOVEMENT DISORDERS
ISSN:
0885-3185
Año:
2012
Vol.:
27
N°:
9
Págs.:
1176 - 1179
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.
Revista:
BRAIN
ISSN:
0006-8950
Año:
2011
Vol.:
134
N°:
1
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
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2011
Vol.:
6
N°:
7
Págs.:
e21814-
Revista:
J CLIN NEUROPHYSIOL
ISSN:
0736-0258
Año:
2011
Vol.:
122
N°:
8
Págs.:
1480 - 1481
Revista:
SLEEP AND BREATHING
ISSN:
1520-9512
Año:
2011
Vol.:
15
N°:
2
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.
Revista:
Journal of the Neurological Sciences
ISSN:
0022-510X
Año:
2011
Vol.:
310
N°:
1-2
Págs.:
194 - 196
Revista:
BRAIN RESEARCH
ISSN:
1872-6240
Año:
2010
Vol.:
1310
Págs.:
58 - 67
Revista:
THE JOURNAL OF NEUROSCIENCE
ISSN:
1529-2401
Año:
2010
Vol.:
30
N°:
19
Págs.:
6667 - 6677
Revista:
Molecular Therapy
ISSN:
1525-0016
Año:
2010
Vol.:
19
N°:
2
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.