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Evaluación neurofuncional del tallo cerebral. Parte I : Reflejo del parpadeo
(2009-10) Leon Sarmiento, Fidias E.; Gutiérrez, Claudia; Bayona Prieto, Jaime
The blink reflex is the neural response elicited in the orbicular oculi muscle after single or paired supraorbital nerve stimulation, by either electrical, mechanical, acoustic, thermal, chemical or magnetic stimulation. It is made up of three responses called R1, R2 and R3. R1 is an early response that follows A beta fibers, and does not habituate. R2 is a middle-latency response that follows A beta and A delta fibers, tends to habituate and is modulated by sensorimotor suprasegmental structures. R3 is a long-latency response, generated by stimulation of a multisynaptic chain of neurons that involve type C fibers belonging to a complex pontothalamic-amigdalo-cerebellar pathway. It is also possible to record three silent periods if the blink reflex is obtained while the subject makes a voluntary facial muscle effort. The functional study of this reflex allows to define with certainty whether the lesion is in afferent or efferent pathways or if it involves an abnormal sensorimotor integration due to disorders of the central, autonomic or peripheral nervous systems. A correct execution of these studies, and their appropriate interpretation, based on the underlying mechanisms of neural plasticity, will guide toward better neurorehabilitation protocols.
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Tumor maligno de la vaina del nervio periférico (MPNST) glandular de la órbita : Primera descripción de la literatura de localización orbitaria en un paciente con neurofibromatosis tipo 1
(2010-02) Romero Rojas, Alfredo E.; Diaz Perez, Julio A.; Lozano Castillo, Alfonso
Introducción. El tumor maligno de la vaina del nervio periférico (MPNST, por sus siglas en ingles Malignant Peripheral Sheath Tumor), es una neoplasia maligna originada en las células de Schwann de la vaina de revestimiento de los nervios periféricos. Esta neoplasia puede presentar componentes heterólogos benignos o malignos, con diferenciación divergente, como la diferenciación glandular. Objetivo. Describir el primer caso en la literatura de MPNST glandular maligno localizado a nivel orbitario y realizar una revisión sobre esta neoplasia. Caso clínico. Niño de 9 años de edad, con diagnostico de NF1, quien presentó exoftalmos ocular, dolor retro-ocular, cefalea, asimetría facial y descenso del globo ocular derecho de 1 año de evolución; a quien se documento masa sólida orbitaria, delimitada, lobulada, que se proyecta al parénquima cerebral frontal y temporal en los estudios de tomografía computarizada y resonancia magnética. La lesión se abordó en forma fronto-orbito-cigomática con resección completa de la misma. Posteriormente, se hizo una plastia dural en base de cráneo y reconstrucción con malla de titanio. Actualmente el paciente se encuentra asintomático después de 6 meses de tratamiento. En el estudio anatomopatológico se observó una neoplasia maligna bifásica, reactiva en los elementos mesenquimales para S100, PGP 9.5, neurofilamentos y vimentina. El componente glandular fue positivo para AE1/AE3, EMA, CEA y focalmente para CD57. Se observó además reactividad para cromogranina, sinaptofisina, serotonina y somatostatina. Se realizo el diagnostico de MPNST glandular de la órbita. Conclusión. Se describe el primer caso de MPNST glandular localizado en la órbita, el cual se presentó en un niño con NF1. Esta neoplasia extremadamente infrecuente debe ser tenida en cuenta en el estudio de lesiones bifásicas malignas, ya que su diagnostico es de peculiar importancia debido al pésimo pronóstico de los pacientes afectados.
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Primary gliosarcoma of the brain : Radiologic and histopathologic features
(2013) Romero Rojas, Alfredo E.; Diaz Perez, Julio A.; Ariza Serrano, Lina María; Amaro, Deirdre E.; Lozano Castillo, Alfonso
Gliosarcoma is a rare central nervous system (CNS) neoplasm with biphasic glial and non-glial malignant components. Here we describe the radiologic and histopathologic features observed in five cases of primary gliosarcoma. The mean age at diagnosis in the studied patients was 54.2 years; these patients were predominantly males (male: female ratio = 4:1). At diagnosis all patients had several clinical deterioration. The most common symptoms of presentation were: headache (5/5 cases), seizures (4/5 cases) and hemiparesis (1/5 cases). All the tumors were large (mean major diameter= 4.12±1.64 cm) at diagnosis as evidenced in computer tomography (CT) scans and magnetic resonance images (MRIs), with preferential involvement of the temporal lobe and frequent associated deviation of the midline structures. Other common characteristics identified on CT scans and MRIs were partial contrast medium uptake with annular pattern (5/5 cases), peripheral edema (5/5 cases), and central calcification (3/5 cases). In additional a peak of dye uptake was observed (4/5 cases) on MRI spectrometry. In the histopathology, the glial component showed malignant astrocytes, with high Ki67 (>60%) and p53 positivity; the sarcomatous components displayed pleomorphic spindle cells similarly with p53 positivity and high Ki67 (75-90%) in all cases. Dedifferentiation to pleomorphic sarcoma (two cases), fibrosarcoma (one case), leiomyosarcoma (one case) and MPNST (one case) were documented. All patients received radiotherapy/chemotherapy and had a median overall survival of ten months. The study of radiologic and histopathologic features in primary gliosarcomas of the brain is a priority to achieve early diagnosis that can be translated to better outcomes. Here we describe the radiologic and histopathologic features observed in a group of gliosarcoma patients with variable histopathologic dedifferentiation.
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Dysfunctional chemosensation in myasthenia gravis : A systematic review
(2013-09) Leon Sarmiento, Fidias E.; Leon Ariza, Daniel S.; Doty, Richard L.
Myasthenia gravis has traditionally been viewed as a disorder that solely affects the neuromuscular junction within the peripheral nervous system. However, there is now evidence that the cholinergic dysfunction of this disorder may be more widespread than previously believed. This article provides a systematic review of the studies that examined smell and taste function in myasthenia gravis. Methods: We analyzed studies that reported chemosensory function alterations in patients with myasthenia gravis. PubMed, MEDLINE, Web of Science, EMBASE, and SciELO, searched to identify articles published from January 1950 through December 2012, were supplemented by relevant articles. The following information was identified from each article: the number of patients, number of controls (if any), clinical stage of patients, neurological involvement, serological state, taste or smell involvement, chemosensory test used, and country of publication. Results: Ten studies reporting smell and taste function and dysfunction in patients with myasthenia gravis were identified, most of which were case reports commenting on apparent abnormalities in the taste system. The sole empirical study that investigated taste function, however, was negative, suggesting that some reports of taste loss may reflect olfactory loss. One study clearly documented olfactory dysfunction in patients with myasthenia gravis, dysfunction most likely attributable to altered central nervous system cholinergic function. Conclusions: Chemosensory dysfunction has been reported in a number of patients with myasthenia gravis. Given the close association between complaints of taste dysfunction and loss of flavor sensations secondary to olfactory system damage, quantitative testing should be used to accurately assess the nature and degree of the dysfunction present in this debilitating disorder.
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Histopathological and immunohistochemical profile in anaplastic gangliogliomas
(2013-11) Romero Rojas, Alfredo E.; Diaz Perez, Julio A.; Chinchilla Olaya, Sandra I.; Amaro, Deirdre E.; Lozano Castillo, Alfonso; Restrepo Escobar, Ligia I.
The anaplastic ganglioglioma (AG) is the high-grade counterpart of ganglioglioma, a rare mixed tumor composed of neuronal/ganglion and glial cells. Materials and methods We describe the histopathology and immunohistochemistry in 7 cases of AG and correlate them with the clinical and radiological features. Results Our AG patients correspond to 2.5% of the central nervous system tumor patients evaluated in our institution. The mean age at presentation was 25.7 years, with a male predominance. The most common clinical presentation was generalized tonic–clonic seizures (3/7 cases), in correlation with frequent cortical/subcortical location (6/7 cases). Histopathologically, all our cases showed high-grade features in glial (glial fibrillary acid protein-positive) and neuron-ganglion cells (synaptophysin, PGP-9.5, neurofilament, NSE and CD56-positive), as well as moderate cellularity, frequent mitotic figures and a Ki-67 labeling index >5%. All our patients had poor survival. Conclusion We found that a typical histopathological and immunohistochemical profile is constant and can be useful in early diagnosis of these aggressive neoplasms.
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Desmoplastic infantile ganglioglioma with late presentation : A clinical, radiological and histopathological analysis
(2013-12) Romero Rojas, Alfredo E.; Diaz Perez, Julio A.; Lozano Castillo, Alfonso
Desmoplastic infantile ganglioglioma (DIG) is a rare supratentorial tumor in the central nervous system. Definitive diagnosis of this neoplasm is based on histopathologic analysis evaluating distinctive findings such as the fibroblastic differentiation. Here we present a clinical case of DIG with a long follow-up in an eight-year-old boy with a six-month history of recurrent emesis, psychomotor hyperactivity and generalized tonic-clonic seizures. Computed tomography scan and magnetic resonance imaging (MRI) showed a cystic, heterogeneous, mass on the right temporal uncus. A histopathological diagnosis of late presentation DIG was made. We documented the immunohistochemical expression of a molecular soft tissue / muscle differentiation marker (h-CaD) in addition to a low proliferative index (Ki-67) in this case. After surgical intervention, a control MRI showed changes of right frontal-temporal craniotomy and a persistent mass in the anterior and medial temporal lobe with basal extension. Further surgical intervention was performed, completely removing the tumor, which had the same characteristics. The patient is asymptomatic while receiving anticonvulsant therapy (phenytoin) with no evidence of tumor recurrence on MRI after a follow-up of five years. The low grade and soft tissue appearance in images are correlated with the histopathologic and immunohistochemical profile of this tumor, but the rarity of this tumor makes a presumptive diagnosis by images a challenge. The above-mentioned molecular markers or new ones could be used as molecular targets for molecular imaging studies to increase the probability of a pre-operative diagnosis based on molecular features through images.
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Fisiopatología y tratamiento del dolor de miembro fantasma
(2013-12-12) Malavera Angarita, Mayra Alejandra; Carrillo Villa, Sandra; Gomezese Ribero, Omar Fernando; García, Ronald G.; Silva Sieger, Federico Arturo
Introduction: Phantom limb pain may be present in up to 80% of patients subjected to amputation because oftrauma or peripheral vascular disease. Severalfactors have been associated with its occurrence, including pre-amputation pain, the etiology, and the amputation level. Objective: To review the current status of the pathophysiological mechanisms, treatment options and their efficacy for the management of phantom limb pain. Method: Non-systematic review ofthe literature in PubMed and Cochrane, of articles describing the pathophysiology and treatment of phantom limb pain. Results and conclusions: The proposed pathophysiological mechanisms are still in research and include peripheral, central and psychologicalfactors. Treatment options are still limited, and less than 10% of patients report long-term improvement.
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Neuroradiology and histopathology in two cases of adult medulloblastoma
(2014) Romero Rojas, Alfredo E.; Diaz Perez, Julio A.; Raju, Sharat; Lozano Castillo, Alfonso
Medulloblastoma (MB) is the most common central nervous system neoplasm in children and only rarely presents in the adult population. Recent molecular biology findings have characterized MB as a heterogeneous neoplasm distinguished by well-defined tumour subsets each with specific histologic and molecular features. Available immunohistochemical stains can now be used to differentiate the distinct molecular types of MB. This report analyzed the histopathologic and neuroradiologic features of two new cases of adult MB. Imaging studies in these patients revealed the morphological appearance of high-grade, well-circumscribed heterogeneous tumours with necrosis, located laterally within the posterior cranial fossa. Histopathology of resected samples demonstrated high-grade tumours (WHO grade IV) containing sheets of undifferentiated neural cells with high mitotic activity and evidence of necrosis. The histopathologic and molecular characteristics of these cases of MB are reviewed for potential applications in new molecular methods of imaging.
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Fundamentos y aplicaciones clínicas de la estimulación magnética transcraneal en neuropsiquiatría
(2014) Malavera Angarita, Mayra Alejandra; Silva Sieger, Federico Arturo; García, Ronald G.; Rueda, Ligia C.; Carrillo Villa, Sandra
Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice.
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Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks
(2015-03-04) Kim, Hyungjun; Kim, Jieun; Loggia, Marco L.; Cahalan, Christine M.; García, Ronald G.; Vangel, Mark G.; Wasan, Ajay D.; Edwards, Robert R.; Napadow, Vitaly
Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N=42) and age- and sex-matched pain-free adults (N=63).We investigated network topology using spectral partitioning,which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number ofwhitematter fibers between specific submodule regionswas also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients.
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Nonlinear digital signal processing in mental health : Characterization of major depression using instantaneous entropy measures of heartbeat dynamics
(2015-03-13) Valenza, Gaetano; García, Ronald G.; Citi, Luca; Scilingo, Enzo P.; Tomaz, Carlos A.; Barbieri, Riccardo
Nonlinear digital signal processing methods that address system complexity have provided useful computational tools for helping in the diagnosis and treatment of a wide range of pathologies. More speciﬁcally, nonlinear measures have been successful this study, we propose the use of instantaneous measures of entropy, namely the inhomogeneous point-process approximate entropy (ipApEn) and the inhomogeneous point-process sample entropy (ipSampEn), to describe a novel characterization of MD patients undergoing affective elicitation. Because these measures are built within a nonlinear point-process model, they allow for the assessment of complexity in cardiovascular dynamics at each moment in time. Heartbeat dynamics were characterized from 48 healthy controls and 48 patients with MD while emotionally elicited through either neutral or arousing audiovisual stimuli. Experimental results coming from the arousing tasks show that ipApEn measures are able to instantaneously track heartbeat complexity as well as discern between healthy subjects and MD patients. Conversely, standard heart rate variability (HRV) analysis performed in both time and frequency domains did not show any statistical signiﬁcance. We conclude that measures of entropy based on non linear point-process models might contribute to devising useful computational tools for care in mental health
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The somatosensory link : S1 functional connectivity is altered by sustained pain and associated with clinical/autonomic dysfunction in fibromyalgia
(2015-05) Kim, Jieun; Loggia, Marco L.; Cahalan, Christine M.; Harris, Richard E.; Beissner, Florian; García, Ronald G.; Kim, Hyungjun; Wasan, Ajay D.; Edwards, Robert R.; Napadow, Vitaly
Objective—Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have found altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system, and its role in both somatic and non-somatic FM symptomatology. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity, and explore how sustained, evoked deep-tissue pain modulates this connectivity.Methods—We acquired fMRI and electrocardiography data from FM patients and healthy controls (HC) during rest (REST) and sustained mechanical pressure pain (PAIN) over the lower leg. Functional connectivity associated with different S1 subregions was calculated, while S1leg (leg representation) connectivity was contrast between REST and PAIN, and correlated with clinically-relevant measures in FM. Results—At REST, FM showed decreased connectivity between multiple ipsilateral and cross-hemispheric S1 subregions, which was correlated with clinical pain severity. PAIN, compared to REST, produced increased S1legconnectivity to bilateral anterior insula in FM, but not in HC. Moreover, in FM, sustained pain-altered S1legconnectivity to anterior insula was correlated with clinical/behavioral pain measures and autonomic responses. Conclusion—Our study demonstrates that both somatic and non-somatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are all closely linked with the degree to which evoked deep-tissue pain alters S1 connectivity to salience/affective pain processing regions. Additionally, diminished connectivity between S1 subregions at REST in FM may result from ongoing widespread clinical pain.
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Neuropéptidos en el encéfalo humano
(2015-08) Duque Díaz, Ewing Rafael; Rita Gáfaro, Claudia G.; Bermúdez Echeverry, Marcela
Los estudios en el encéfalo humano se han realizado con el fin de responder a varias preguntas de carácter científico relacionados con la neuroanatomía, neurofisiología, neurofarmacología, la neurología y la conducta. El encéfalo es el órgano en el que se encuentra la regulación de los reflejos y los mecanismos inconscientes como la transmisión del dolor, los cardiovasculares, los respiratorios, entre otros. Estos mecanismos están mediados por sustancias químicas tales como los neuropéptidos, que son cadenas cortas de aminoácidos que se han encontrado ampliamente distribuidos en el sistema nervioso central y periférico, además de ejercer acciones fisiológicas actuando como neurotransmisores, neuromoduladores (acciones paracrinas y autocrinas) y neurohormonas. En los últimos treinta años se ha incrementado el conocimiento sobre la distribución y función de los neuropéptidos en el sistema nervioso central de mamíferos (ratas, gatos, perros, alpacas, primates y humanos). Así, el objetivo de esta revisión se dirige a describir los datos más relevantes disponibles sobre los neuropéptidos en el encéfalo humano. Para ello se revisan aspectos importantes de los neuropéptidos en el encéfalo humano como: a) La distribución, b) Las relaciones anatómicas, c) Las funciones fisiológicas, d) La coexistencia, y e) Las investigaciones futuras a realizar.
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Neuroimaging brainstem circuitry supporting cardiovagal response to pain : A combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study
(2016-01) García, Ronald G.; Sclocco, Roberta; Beissner, Florian; Desbordes, Gaelle; Polimeni, Jonathan R.; Wald, Lawrence L.; Kettner, Norman W.; Kim, Jieun; Renvall, Ville; Bianchi, Anna M.; Cerutti, Sergio; Napadow, Vitaly; Barbieri, Riccardo
Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain.
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Relationship between cardiac vagal activity and mood congruent memory bias in major depression
(2016-01) García, Ronald G.; Valenza, Gaetano; Tomaz, Carlos A.; Barbieri, Riccardo
Background Previous studies suggest that autonomic reactivity during encoding of emotional information could modulate the neural processes mediating mood-congruent memory. In this study, we use a point-process model to determine dynamic autonomic tone in response to negative emotions and its influence on long-term memory of major depressed subjects. Methods Forty-eight patients with major depression and 48 healthy controls were randomly assigned to either neutral or emotionally arousing audiovisual stimuli. An adaptive point-process algorithm was applied to compute instantaneous estimates of the spectral components of heart rate variability [Low frequency (LF), 0.04–0.15 Hz; High frequency (HF), 0.15–0.4 Hz]. Three days later subjects were submitted to a recall test. Results A significant increase in HF power was observed in depressed subjects in response to the emotionally arousing stimulus (p=0.03). The results of a multivariate analysis revealed that the HF power during the emotional segment of the stimulus was independently associated with the score of the recall test in depressed subjects, after adjusting for age, gender and educational level (Coef. 0.003, 95%CI, 0.0009–0.005, p=0.008). Limitations These results could only be interpreted as responses to elicitation of specific negative emotions, the relationship between HF changes and encoding/recall of positive stimuli should be further examined. Conclusions Alterations on parasympathetic response to emotion are involved in the mood-congruent cognitive bias observed in major depression. These findings are clinically relevant because it could constitute the mechanism by which depressed patients maintain maladaptive patterns of negative information processing that trigger and sustain depressed mood.
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Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea
(2016-02) García, Ronald G.; Kim, Jieun; Sheehan, James D.; Beissner, Florian; Bianchi, Anna M.; Cerutti, Sergio; Kuo, Braden; Barbieri, Riccardo; Napadow, Vitaly; Sclocco, Roberta
While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept-based (windows set by subjects’ ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti-correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anticorrelated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target.
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Repetitive transcranial magnetic stimulation for phantom limb pain in land mine victims : A double-blinded, randomized, sham-controlled trial
(2016-08) Malavera Angarita, Mayra Alejandra; Silva Sieger, Federico Arturo; Fregni, Felipe; Carrillo Villa, Sandra; García, Ronald G.
We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (−53.38 ± 53.12% vs −22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30–60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. Perspective High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.
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Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control
(2017-02-20) García, Ronald G.; Citi, Luca; NoggleTaylor, Jessica; Toschi, Nicola; Barbieri, Riccardo; Valenza, Gaetano
The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.
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Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem
(2017-03) Duque Díaz, Ewing Rafael; Díaz-Cabiale, Zaida; Narváez, José Angel; Coveñas, Rafael
An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.
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Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) effects on autonomic outflow in hypertension
(2017-09-05) Sclocco, Roberta; Garcia, Ronald G.; Gabriel, Aileen; Kettner, Norman W.; Napadow, Vitaly; Barbieri, Riccardo
Transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN) has been proposed as a non-invasive alternative to vagus nerve stimulation (VNS). However, its cardiovagal effects are inconsistent across studies, likely due to inhomogeneity in the stimulation parameters. Here, we evaluate respiratory-gated ABVN stimulation (Respiratory-gated Auricular Vagal Afferent Nerve Stimulation, RAVANS), where the stimuli are delivered in 1 s bursts during the exhalation phase of respiration, thus mimicking the breathing-induced modulation of cardiac vagal activity. In this study, we present preliminary results from an ongoing single-arm, open label trial investigating the effects of different intensities of RAVANS in hypertensive subjects. We found that a mid-intensity RAVANS stimulation (rated as a 5 on a 0-10 scale) increases the cardiovagal tone and reduces the sympathetic tone during a paced breathing task. The present results could contribute to optimize RAVANS as a non-invasive, low-cost therapeutic intervention for hypertension.

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