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UNLABELLED: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site. SIGNIFICANCE STATEMENT: Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site.
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Núcleo Caudado/metabolismo , Dopamina/metabolismo , Estimulación Eléctrica , Putamen/metabolismo , Núcleo Subtalámico/fisiología , Animales , Mapeo Encefálico , Imagenología Tridimensional , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiología , Núcleo Subtalámico/diagnóstico por imagenRESUMEN
OBJECTIVE: Although external landmarks and trajectories for external ventricular drainage have been described for the freehand-guided method, no standard trajectory has been reported for deep-seated intracerebral hemorrhage (ICH). This article presents a freehand-guided catheter insertion technique for deep-seated spontaneous ICH using external landmarks. METHOD: Freehand-guided hematoma aspiration using Kocher's point and the external auditory canal as landmarks was performed in 32 patients with a diagnosis of spontaneous ICH in basal ganglia treated between May 2015 and July 2018 at the author's institute. RESULTS: In computed tomographic images, the mean actual to planned catheter tip distance was 16.1 ± 7.7 mm, the mean right-left deviation was 4.6 ± 5.2 mm, the mean anterior-posterior deviation was 11.1 ± 9.5 mm, and the mean superior-inferior deviation was 8.7 ± 4.4 mm. On largest hematoma slice, the mean distance from hematoma centers to inserted catheter was 9.8 ± 4.9 mm, and the mean horizontal and vertical distances were 4.0 ± 4.7 mm and 7.7 ± 4.8 mm, respectively. In 29 of the 32 patients, all the catheter holes contacted hematomas, whereas in the other 3 patients, 1 or more holes were in contact with brain parenchymal tissue. CONCLUSION: For patients with basal ganglia hemorrhage, freehand-guided catheter insertion and hematoma aspiration with subsequent fibrinolysis is a feasible procedure that shortens procedural times. The described technique could be used as an alternative method because it can be performed when the patient is in a critical state without additional equipment.
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Hemorragia Cerebral/cirugía , Procedimientos Neuroquirúrgicos/métodos , Paracentesis/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hematoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Cerebrospinal fluid (CSF) leak is a common complication of spinal and cranial surgery, and patients undergoing spinal tumor surgery are probably particularly predisposed due to the presence of an intradural tumor and many other factors. Furthermore, a meticulous dural closure technique does not always result in watertight closure. A number of adjunctive methods have been used to assist with dural closure. Synthetic, absorbable polyethylene glycol hydrogel dural sealants are widely used and have been approved for use as adjuncts for cranial applications requiring sutured dural closure. We report a case of thecal sac compression by DuraSeal® Dural Sealant used to repair the CSF leak after intentional durotomy during lumbar schwannoma extirpation.
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OBJECTIVE: Astrocyte dysfunctions are related to several central nervous system (CNS) pathologies. Transcriptomic profiling of human mRNAs to investigate astrocyte functions may provide the basic molecular-biological data pertaining to the cellular activities of astrocytes. METHODS: Human Primary astrocytes (HPAs) and human neural stem cell line (HB1.F3) were used for differential digital gene analysis. In this study, a massively parallel sequencing platform, next-generation sequencing (NGS), was used to obtain the digital gene expression (DGE) data from HPAs. A comparative analysis of the DGE from HPA and HB1.F3 cells was performed. Sequencing was performed using NGS platform, and subsequently, bioinformatic analyses were implemented to reveal the identity of the pathways, relatively up- or down-regulated in HPA cells. RESULTS: The top, novel canonical pathways up-regulated in HPA cells than in the HB1.F3 cells were "Cyclins and cell cycle regulation," "Integrin signaling," "Regulation of eIF4 and p70S6K signaling," "Wnt/ß-catenin signaling," "mTOR signaling," "Aryl hydrocarbon receptor signaling," "Hippo signaling," "RhoA signaling," "Signaling by Rho family GTPases," and "Glioma signaling" pathways. The down-regulated pathways were "Cell cycle: G1/S checkpoint regulation," "eIF2 signaling," "Cell cycle: G2/M DNA damage checkpoint regulation," "Telomerase signaling," "RhoGDI signaling," "NRF2-mediated oxidative stress response," "ERK/MAPK signaling," "ATM signaling," "Pancreatic adenocarcinoma signaling," "VEGF signaling," and "Role of CHK proteins in cell cycle checkpoint control" pathways. CONCLUSION: This study would be a good reference to understand astrocyte functions at the molecular level, and to develop a diagnostic test, based on the DGE pattern of astrocytes, as a powerful, new clinical tool in many CNS diseases.
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Chronic subdural hematoma (CSDH) can be easily treated by burr hole surgery. However, several complications including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and acute subdural hematoma are rare after evacuation of a CSDH. A 77-year-old man was admitted with right hemiparesis and dysarthria. A brain computed tomography (CT) scan revealed a bilateral CSDH with midline shifting toward the right side. The patient got the burr hole trephination with the catheters insertion in the both sides of parietal area under the local anesthesia. After burr hole surgery immediately, he developed left side weakness and decreased level of consciousness. Repeat CT scans detected a diffuse SAH and multiple small ICHs. He was treated conservatively and fully recovered at discharge after 1 month. To avoid these complications, slow and gradual drainage of the CSDH is needed. The authors report a rare case of SAH and multipunctate ICHs in both cerebral hemispheres after evacuation of a bilateral CSDH.
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OBJECT: Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury. METHODS: The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 µm in diameter, with a 30- to 60-µm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue. RESULTS: The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences between movements evoked by either of the 2 targeting techniques were revealed. However, frame-based targeting required fewer electrode penetrations to evoke target movements. CONCLUSIONS: Clinical restoration of functional movement via ISMS remains a distant goal. However, the technology presented herein represents the first step toward restoring functional independence for individuals with chronic spinal cord injury.
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Estimulación Eléctrica/métodos , Parálisis/terapia , Traumatismos de la Médula Espinal/terapia , Médula Espinal/fisiopatología , Tecnología Inalámbrica , Animales , Potenciales Evocados Motores/fisiología , Femenino , Microelectrodos , Modelos Animales , Movimiento/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Parálisis/fisiopatología , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Functional magnetic resonance imaging (fMRI) is a powerful method for identifying in vivo network activation evoked by deep brain stimulation (DBS). OBJECTIVE: Identify the global neural circuitry effect of subthalamic nucleus (STN) DBS in nonhuman primates (NHP). METHOD: An in-house developed MR image-guided stereotactic targeting system delivered a mini-DBS stimulating electrode, and blood oxygenation level-dependent (BOLD) activation during STN DBS in healthy NHP was measured by combining fMRI with a normalized functional activation map and general linear modeling. RESULTS: STN DBS significantly increased BOLD activation in the sensorimotor cortex, supplementary motor area, caudate nucleus, pedunculopontine nucleus, cingulate, insular cortex, and cerebellum (FDR < 0.001). CONCLUSION: Our results demonstrate that STN DBS evokes neural network grouping within the motor network and the basal ganglia. Taken together, these data highlight the importance and specificity of neural circuitry activation patterns and functional connectivity.
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Estimulación Encefálica Profunda , Imagen por Resonancia Magnética/métodos , Corteza Motora/fisiología , Vías Nerviosas , Oxígeno/sangre , Técnicas Estereotáxicas , Núcleo Subtalámico/fisiología , Animales , Ganglios Basales/fisiología , Núcleo Caudado/fisiología , Cerebelo/fisiología , Giro del Cíngulo/fisiología , Macaca mulatta , Masculino , Núcleo Tegmental Pedunculopontino/fisiología , Corteza Sensoriomotora/fisiologíaRESUMEN
Restoration of movement following spinal cord injury (SCI) has been achieved using electrical stimulation of peripheral nerves and skeletal muscles. However, practical limitations such as the rapid onset of muscle fatigue hinder clinical application of these technologies. Recently, direct stimulation of alpha motor neurons has shown promise for evoking graded, controlled, and sustained muscle contractions in rodent and feline animal models while overcoming some of these limitations. However, small animal models are not optimal for the development of clinical spinal stimulation techniques for functional restoration of movement. Furthermore, variance in surgical procedure, targeting, and electrode implantation techniques can compromise therapeutic outcomes and impede comparison of results across studies. Herein, we present a protocol and large animal model that allow standardized development, testing, and optimization of novel clinical strategies for restoring motor function following spinal cord injury. We tested this protocol using both epidural and intraspinal stimulation in a porcine model of spinal cord injury, but the protocol is suitable for the development of other novel therapeutic strategies. This protocol will help characterize spinal circuits vital for selective activation of motor neuron pools. In turn, this will expedite the development and validation of high-precision therapeutic targeting strategies and stimulation technologies for optimal restoration of motor function in humans.
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Terapia por Estimulación Eléctrica/métodos , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Médula Espinal/fisiopatología , Animales , Interfaces Cerebro-Computador , Modelos Animales de Enfermedad , Espacio Epidural , Femenino , Calidad de Vida , PorcinosRESUMEN
OBJECTIVE: To evaluate the efficacy of scalene injection in patients with thoracic outlet syndrome. METHODS: We selected 142 patients diagnosed with thoracic outlet syndrome between January 2005 and October 2009. We performed a series of scalene injection with conservative treatment in all cases. Patients rated their pain degrees using a visual analogue scale. We also evaluated the time to return to everyday life and work, and patients' functional capacity. RESULTS: There were no complications or instances of inadvertent somatic or sympathetic ganglionic blockade after scalene injection. Overall, 111 patients (76.5%) experienced improved symptoms after the first set of scalene injection and 128 patients (88.2%) improved after scalene injection followed by conservative treatment. Of the 68 patients who returned to work during the study period, 54 returned within 1 week, and 62 within 2 weeks. Of those who returned to work, 61 reported nearly full functional capacity. We found that scalene injection was more effective in cases of thoracic outlet syndrome related to trauma than in those related to work-related repetitive stress. CONCLUSION: In patients with thoracic outlet syndrome, scalene injection effectively reduces pain. We recommend scalene injection as an adjunct to conservative treatment.