The Technique for Transorbital Ventricular Puncture: An Anatomic Approach.

BACKGROUND AND OBJECTIVES: Transorbital ventricular puncture is a minimally invasive described procedure with poor landmarks and anatomic references. This approach can be easily performed to save patients with intracranial hypertension, especially when it is secondary to an acute decompensated hydrocephalus. This study aims to describe anatomic structures and landmarks to facilitate the execution of transorbital puncture in emergency cases. METHODS: We analyzed 120 head computed tomographies to show the best area to perform the procedure in the orbital roof. Two adult cadavers (4 sides) were punctured in the predetermined area. Angles, distances, landmarks, and anatomic structures were registered. This approach to the ventricular system may be performed at bedside to relieve intracranial hypertension only in specific cases. RESULTS: The perforation point is 2.5 cm (female) or 3.0 cm (male) lateral to the midline and immediately inferior to the superciliary arch. A vertical line, parallel to midline, was drawn on the outer edge of the patient's forehead, the needle was 45° inferiorly and 20° medially and then progressed 2.0 cm backwards to reach the bone perforation point. After that, it was advanced another 4.5cm approximately until it reached the anterior horn of the lateral ventricle. CONCLUSION: Based on statistical and experimental evidences, we were able to establish reliable anatomic reference points to access the anterior horn of the lateral ventricle through transorbital puncture.

Evolution of Globus Pallidus Targeting for Parkinson's and Dystonia Deep Brain Stimulation: A 15-Year Experience.

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting. Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies. Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (ß = 0.09, p < 0.0001), posteriorly [slope (ß) = 0.04, p < 0.05], and dorsally (ß = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (ß = 0.06, p = 0.053). Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.

Time for a New 3-D Image for Globus Pallidus Internus Deep Brain Stimulation Targeting and Programming.

Deep brain stimulation (DBS) is an effective neuromodulatory therapy for Parkinson's disease (PD). Early studies using globus pallidus internus (GPi) DBS for PD profiled the nucleus as having two functional zones. This concept disseminated throughout the neuromodulation community as the "GPi triangle". Although our understanding of the pallidum has greatly evolved over the past 20 years, we continue to reference the triangle in our clinical decision-making process. We propose a new direction, termed the spatial boundary hypothesis, to build upon the 2-dimensional outlook on GPi DBS. We believe an updated 3-D GPi model can produce more consistent, positive patient outcomes.

Desarrollo de técnicas microquirúrgicas usando tinción vascular con y sin silicona en placenta humana con modelos craneales 3D / Development of microsurgical techniques using vascular staining with and without silicone in human placenta with 3D cranial models

En las ultimas décadas, ha habido un cambio en la formación en las especialidades quirúrgicas, lo cual ha llevado a plantearse la necesidad de adquisición de habilidades por fuera del quirófano por medio de la simulación. El objetivo de este trabajo es demostrar que el uso de placentas humanas con modelo craneal tridimensional (3D), es un método de alta fidelidad y retroalimentación para el desarrollo de técnicas microquirúrgicas. Se realizó un estudio de evaluación técnica en el Laboratorio de Microcirugía Dr. Evandro de Oliveira del Hospital de la Beneficiencia de Portugal de São Paulo, utilizando 15 placentas con técnicas de coloración y preservación vascular con silicona para moldes; realizando ejercicio de anastomosis vasculares, ejercicios de disección parenquimatosa placentaria que remedan la disección aracnoidea y del valle silviano, además de simulación de resección de tumores. Cualitativamente la placenta humana es un método con alta fidelidad y retroalimentación, además, es de acceso universal para la adquisición de habilidades microquirúrgicas, que asociada a un modelo craneal 3D permite el perfeccionamiento de craneotomías, coordinación visomotriz, propiocepción y relación de profundidad que se requieren para abordajes neuroquirúrgicos.

In the last decades, there has been a change in training in surgical specialties, which has led to the need to acquire skills outside the operating room through simulation. The aim of this work is to demonstrate that the use of human placentas with a three-dimensional (3D) cranial model is a high fidelity and feedback method for the development of microsurgical techniques. A technical evaluation study was carried out in the Dr. Evandro de Oliveira Microsurgery Laboratory of the Hospital de la Beneficiencia de Portugal in São Paulo, using 15 placentas with coloration techniques and vascular preservation with silicone for molds; performing vascular anastomosis, placental parenchymal dissection exercises that mimic arachnoid and sylvian fissure dissection, in addition to simulating tumor resection. Qualitatively, the human placenta is a method with high fidelity and feedback, and it is also universally accessible for the acquisition of microsurgical skills, which, associated with a 3D cranial model, allows the refinement of the craniotomies, visomotor coordination, proprioception, and depth relationship required for neurosurgical approaches.

Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary.

INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

Navegando por la fisura silviana: anatomía microquirúrgica, neuroimágenes y técnica quirúrgica / Navigating the sylvian fissure: microsurgical anatomy, neuroimaging, and surgical technique

Objetivo: Describir la anatomía quirúrgica de la fisura silviana (FS) a través de disecciones cadavéricas y neuroimágenes; desarrollar su aplicación microquirúrgica. Materiales y métodos: Se estudiaron 10 hemisferios cadavéricos humanos fijados y un cráneo humano en seco, a través de la disección de fibras blancas y de la anatomía arterial y neural, utilizando un microscopio quirúrgico. Las arterias cerebrales fueron inyectadas con silicona coloreada. La anatomía quirúrgica fue correlacionada con la anatomía neuroimagenológica. Finalmente, se recolectó la experiencia microquirúrgica adquirida y, a su vez, la anatomía del Complejo Silviano, fue revisada. Resultados: La FS se extiende desde la cara basal a la lateral del cerebro. Cada superficie tiene una parte superficial (tronco silviano y sus ramos), intermedia (compartimientos anterior y opercular lateral) y profunda (compartimiento esfenoidal, hendidura insular anterior y lateral y la región retroinsular). En 7 de los 10 hemisferios, el surco central no se intersectó con la FS en la superficie lateral del cerebro. En el 80% de los hemisferios, la principal bifurcación de la arteria cerebral media se localizó en o proximal al limen insular. Debajo de la pars triangularis se localiza el punto más ancho de la superficie lateral de la FS. Los autores comienzan la disección de la misma en o proximalmente a este punto. Conclusiones: El conocimiento anatómico profundo y su aplicación a las neuroimágenes, son herramientas esenciales para el planeamiento prequirúrgico y son requisitos mandatorios para operar con seguridad a través y alrededor de la FS

Objective: The aim of this study is to describe the microsurgical anatomy of the sylvian fissure, through cadaveric dissections and neuroimaging and to elucidate its clinical application for microsurgery. Methods: One human skull and ten cadaveric human hemispheres were studied through white matter fiber dissections and arterial and neural anatomy of the sylvian fissure and insular dissections under the microscope. The cerebral arteries were perfused with colored latex. The surgical anatomy was correlated with neuroimaging anatomy. Finally, the microsurgical experienced gained applying this anatomical knowledge was gathered, and the literature about the anatomy of the sylvian complex was revised, as well. Results: The Sylvian fissure extends from the basal to the lateral surface of the brain. Each surface has a superficial (sylvian stem and its rami), intermediate (anterior and lateral opercular compartments) and deep parts (sphenoidal compartment, anterior and lateral insular clefts and retroinsular region). In 7 out of 10 hemispheres, the central sulcus did not intersect with the sylvian fissure on the lateral surface of the brain. In 80% of the hemispheres, the middle cerebral artery main bifurcation was localized at or proximal to the limen insulae. Beneath the pars triangularis, the widest point of the lateral surface of the sylvian fissure is located. The authors start dissecting the sylvian fissure at this point. Conclusion: The thorough anatomical knowledge with its clinical application in modern neuroimaging are essential tools for preoperative planning and are mandatory requisites to safely operate through and around the sylvian fissure anatomical complex.

Postmortem Dissections of the Papez Circuit and Nonmotor Targets for Functional Neurosurgery.

BACKGROUND: The Papez circuit was first described as the anatomic basis of emotion. Subsequent studies consolidated recognition of its limbic activities but showed a more important role in memory. Anatomic dissections and advanced neuroimaging have deepened our understanding of the various interconnections and white matter tracts present in this circuit. The aim of our study is to describe the anatomy of the Papez circuit through cadaveric dissection with correlation to ultrahigh-field magnetic resonance imaging (MRI) and MRI tractography. METHODS: White fiber dissection was performed on 5 cadaveric human brain hemispheres. The Papez circuit was dissected mediolaterally to show its anatomy and relation to other nuclei and tracts. Open-source MRI tractography data from the Human Connectome Project is combined with ultrahigh resolution, 7T structural MRI, and 17.6T diffusion tractography to further show the anatomy. RESULTS: The network connecting the anterior and posterior cingulate, entorhinal cortex, hippocampus, fimbria, dentate gyrus, fornix, mammillary bodies, and anterior thalamus was described using white matter fiber dissection and compared with MRI tractography and ultrahigh-field structural and diffusion MRI. We showed for the first time (through portmortem dissection) fibers directly connecting the anterior thalamic nucleus and the subgenual cingulate via the septal area. CONCLUSIONS: The description of the anatomy of the Papez circuit through cadaveric dissection and comparisons with advanced neuroimaging studies allow a better understanding of its three-dimensional spatial layout, in addition to showing new areas of connectivity with adjacent structures and possibilities for surgical approaches or stimulation.

Comparison Between Transcortical and Interhemispheric Approaches to the Atrium of Lateral Ventricle Using Combined White Matter Fiber Dissections and Magnetic Resonance Tractography.

OBJECTIVE: The objective of this study was to compare transcortical and posterior interhemispheric approaches to the atrium using a combined approach of white matter fiber dissections and magnetic resonance (MR) tractography. METHODS: Ten cerebral hemispheres were examined and dissected from the lateral-to-medial surface and from the medial-to-lateral surface, with special attention to the white matter tracts related to the atrium. MR tractography was used to show the relationship of three-dimensional white matter fibers with the atrium of the lateral ventricle and to compare with cadaveric dissection results. RESULTS: The atrium was related laterally to the superior longitudinal fasciculus II and III, middle longitudinal fasciculus, arcuate fasciculus, vertical occipital fasciculus, and sagittal stratum. Medially, it is related to the superior longitudinal fasciculus I, cingulum, sledge runner, and forceps major. CONCLUSIONS: A combined approach of cadaveric white matter fiber dissections and MR tractography were used to describe the main white matter tracts related to the posterior interhemispheric approach and the transcortical approach, providing an in-depth understanding of the three-dimensional anatomy of white matter fibers and the atrium. In the present study, among approaches examined, the posterior interhemispheric parasplenial transprecuneus approach placed fewer eloquent tracts at risk; however, traversing the sledge runner and the forceps major is unavoidable by this approach.

Microsurgical Anatomy Review of Bifrontal Limited Transbasal Approach - Quantitative and Anatomy Study.

INTRODUCTION: The bifrontal transbasal approach is an anterior midline skull base approach to anterior skull base, sellae region and, if needed, to posterior skull base in the midline, often used for tumoral lesions but also useful for vascular or infectious pathologies. METHODS: Descriptive anatomic study, 5 formalin-fixed human cadaveric heads were used injected with colored silicone. The dissection was made step-by-step to describe every anatomic structure encountered. The working distance was obtained from the posterior wall of the frontal sinus with and without orbital rim to the pituitary stalk, the sellae, the pontomedullary sulcus, and the anterior margin of the foramen magnum. RESULTS: Stepwise anatomic dissection was performed dividing the surgical technique into 6 stages: soft-tissue stage, bone stage, sinus stage, clival stage, intradural, and measurements. The objective of making the supraorbital osteotomy was to improve the vision over the neural structures without brain retraction and limited to the midline supraorbital rim to avoid aggressive manipulation and injury to the orbit. The working distances measured with the orbital rim were on average: to the pituitary stalk, 70.5 mm; to the sellae, 81.3 mm; to the pontomedullary sulcus, 97 mm; and the foramen magnum, 99.5 mm. Without the orbital rim measures were: to the pituitary stalk, 57 mm; to the sellae, 62.5 mm; to the pontomedullary sulcus, 96 mm; and the foramen magnum, 98.5 mm. CONCLUSIONS: The addition of osteotomies including removing of the orbital rim improves the access to the central skull base with special benefits on the working distances to the sellae region.

Postmortem Dissections of Common Targets for Lesion and Deep Brain Stimulation Surgeries.

BACKGROUND: The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects. OBJECTIVE: To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways. METHODS: A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography. RESULTS: The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly. CONCLUSION: This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.

Parkinson's disease and wearable devices, new perspectives for a public health issue: an integrative literature review.

Parkinson's disease is the second most common neurodegenerative disease, with an estimated prevalence of 41/100,000 individuals affected aged between 40 and 49 years old and 1,900/100,000 aged 80 and over. Based on the essentiality of ascertaining which wearable devices have clinical literary evidence and with the purpose of analyzing the information revealed by such technologies, we conducted this scientific article of integrative review. It is an integrative review, whose main objective is to carry out a summary of the state of the art of wearable devices used in patients with Parkinson's disease. After the review, we retrieved 8 papers. Of the selected articles, only 3 were not systematic reviews; one was a series of cases and two prospective longitudinal studies. These technologies have a very rich field of application; however, research is still necessary to make such evaluations reliable and crucial to the well-being of these patients.

Parkinson's disease and wearable devices, new perspectives for a public health issue: an integrative literature review

SUMMARY Parkinson's disease is the second most common neurodegenerative disease, with an estimated prevalence of 41/100,000 individuals affected aged between 40 and 49 years old and 1,900/100,000 aged 80 and over. Based on the essentiality of ascertaining which wearable devices have clinical literary evidence and with the purpose of analyzing the information revealed by such technologies, we conducted this scientific article of integrative review. It is an integrative review, whose main objective is to carry out a summary of the state of the art of wearable devices used in patients with Parkinson's disease. After the review, we retrieved 8 papers. Of the selected articles, only 3 were not systematic reviews; one was a series of cases and two prospective longitudinal studies. These technologies have a very rich field of application; however, research is still necessary to make such evaluations reliable and crucial to the well-being of these patients.

RESUMO A doença de Parkinson figura como a segunda doença neurodegenerativa mais comum. Sua prevalência é estimada de 41 por 100.000 pessoas entre 40 e 49 anos a 1.900 por 100.000 pessoas com 80 anos ou mais. Baseando-se na essencialidade de averiguar os dispositivos vestíveis que possuem evidências clínicas literárias e com o objetivo de analisar as informações reveladas por tais tecnologias, temos a construção deste artigo científico de revisão integrativa. Trata-se de uma revisão integrativa que tem como principal objetivo realizar um sumário do estado da arte de dispositivos vestíveis utilizados em pacientes com doença de Parkinson. Após realizada a revisão, obtiveram-se oito artigos. Pode-se observar que dos artigos selecionados, apenas três não eram revisões sistemáticas, sendo um deles uma série de casos e outros dois, estudos longitudinais prospectivos. A utilização dessas tecnologias possui um campo muito rico para atuar, contudo ainda são necessárias pesquisas para que tais avaliações sejam fidedignas e cruciais para o bem-estar desses pacientes.

White Matter Relationships Examined by Transillumination Technique Using a Lateral Transcortical Parietal Approach to the Atrium: Three-Dimensional Images and Surgical Considerations.

BACKGROUND: Numerous lesions are found in the ventricular atrium (VA). Access is gained through many white matter tracts with great relevance and specific neurologic functions. It is important to understand the configuration of the most relevant structures surrounding this zone and, thus, select the safest entry zone on the lateral cerebral surface. OBJECTIVE: We studied the white matter layers traversed in the lateral transcortical parietal approach through the intraparietal sulcus (IPS), adding a transillumination technique. With this knowledge, we selected the safest highway to improve this particular approach. METHODS: An in-depth study of the white matter tracts was performed on 24 cerebral hemispheres (12 human whole brains). The Klingler technique and microsurgical dissection techniques were used under ×6 to ×40 magnification. The transillumination technique (torch illuminating the ventricular cavity) was used to expose the layers surrounding the VA and, thus, guide the dissection. RESULTS: Taking the IPS on the cerebral surface as a reference, we identified the following white matter layers ordered from the surface to the ependyma: U fibers, superior longitudinal fascicle, arcuate fascicle, vertical occipital fascicle, sagittal stratum with the optic radiations, and tapetum fibers. The transillumination technique allowed for the easier identification of the white matter deep periventricular layers. CONCLUSIONS: Knowledge of the main fascicles in the path and neighborhood of the VA allowed us to understand how certain neurologic functions can be affected by lesions at this level and to select the most appropriate way to avoid damaging relevant fascicles.

Microneuroanatomy of the Anterior Frontal Laser Trajectory to the Insula.

BACKGROUND: Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an emerging minimally invasive procedure for the treatment of deep intracranial lesions. Insular lesions are challenging to treat because of the risk of damaging important surrounding structures. The precise knowledge of the neural structures that are at risk along the trajectory and during the ablation is essential to reduce associated complications. This study aims to describe the relevant anatomy of the anterior frontal LITT trajectory to the insular region by using sectional anatomy and fiber dissection technique. METHODS: Three silicone-injected cadaveric heads were used to implant laser catheters bilaterally to the insular region by using a frameless stereotactic technique from a frontal approach. Sections were cut in both the oblique axial plane parallel to the trajectory and in the coronal plane. White matter fiber dissections were used to establish the tracts related to the laser trajectory from lateral to medial and medial to lateral. RESULTS: Supraorbital regions were selected as entry points. After crossing the frontal bone, the track intersected the inferior frontal lobe. The catheter was illustrated reaching the insular region medial to the inferior fronto-occipital fasciculus and insular cortex, and superior to the uncinate fasciculus. The uncinate fasciculus, extreme capsule, claustrum, external capsule, and putamen were traversed, preserving the major vascular structures. CONCLUSIONS: Independent of the insular area treated, an understanding of the neuroanatomy related to the anterior frontal laser trajectory is essential to improve the ability to perform LITT of this challenging region.

Microsurgical Anatomy of the Insular Region and Operculoinsular Association Fibers and its Neurosurgical Application.

OBJECTIVE: To analyze the three-dimensional relationships of the operculoinsular compartments, using standard hemispheric and white matter fiber dissection and review the anatomy of association fibers related to the operculoinsular compartments of the Sylvian fissure and the main white matter tracts located deep into the insula. The secondary aim of this study was to improve the knowledge on this complex region to safely address tumor, vascular, and epilepsy lesions with an integrated perspective of the topographic and white matter fiber anatomy using 2D and 3D photographs. METHODS: Six cadaveric hemispheres were dissected. Two were fixed with formalin and the arteries were injected with red latex dye; the remaining four were prepared using the Kingler method and white fiber dissections were performed. RESULTS: The insula is located entirely inside the Sylvian fissure. The topographic hemispheric anatomy, Sylvian fissure, opercula, surrounding sulci and gyri, as well as the M2, M3, and M4 segments were identified. The anatomy of the insula, with the sulci and gyri and the limiting sulci, were also identified and described. The main white matter fiber tracts of the operculoinsular compartments of the Sylvian fissure as well as the main association and commissural fibers located deep in the insula were dissected and demonstrated. CONCLUSIONS: Complementing topographic anatomy with detailed study of white matter fibers and their integration can help the neurosurgeon to safely approach lesions in the insular region, improving postoperative results in the microsurgical treatment of aneurysmal lesions, insular tumors, or epilepsy surgery.

The Mechanistic Basis for Photobiomodulation Therapy of Neuropathic Pain by Near Infrared Laser Light

Background and Objective Various irradiances have been reported to be beneficial for the treatment of neuropathic pain with near infrared light. However, the mechanistic basis for the beneficial outcomes may vary based on the level of irradiance or fluence rate used. Using in vivo and in vitro experimentalmodels, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance. Study Design/Materials and Methods ln vitro experiments: Cultured, rat DRG were randomly assigned to control or laser treatment (L T) groups with different irradiation times (2, 5, 30, 60 or 120s). The laser parameters were: output power » 960 mW, irradiance » 300mW/cm2, 808 nm wavelength and spot size » 3cm diameter/ area » 7.07cm2, with different fluences according to irradiation times. Mitochondrial metabolic activity was measured with the MTS assay. The DRG neurons were immunostained using a primary antibody to ß-Tubulin III. ln vivo experiments: spared nerve injury surgery (SNI), an animal model of persistent peripheral neuropathic pain, was used. The injured rats were randomly divided into three groups (n » 5). 1) Control: SNI without LT, 2) Short term: SNI with LT on day 7 and euthanized on day 7, 3) Long term: SNI with LT on day 7 and euthanized on day 22. An 808 nm wavelength laser was used for all treatment groups. Treatment was performed once on Day 7 post-surgery. The transcutaneous treatment parameters were: output power: 10 W, fluence rate: 270 mW/cm2, treatment time: 120s. The laser probe was moved along the course of the sciatic/sural nerve during the treatment. Within 1 hour of irradiation, behavior tests were performed to assess its immediate effect on sensory allodynia and hyperalgesia caused by SNI. Results ln vitro experiments: Mitochondrial metabolism was significantly lower compared with controls for all LT groups. Varicosities and undulations formed in neurites of DRG neurons with a cell body diameter 30µm or less. ln neurites of DRG neurons with a cell body diameter of greater than 30µm, varicosities formed only in the 120s group. ln vivo experiments: For heat hyperalgesia, there was a statistically significant reduction in sensitivity to the heat stimulus compared with the measurements done on day 7 prior to LT. A decrease in the sensitivity to the heat stimulus was found in the LT groups compared with the control group on day 15 and 21. For cold allodynia and mechanical hyperalgesia, a significant decrease in sensitivity to cold and pin prick was found within 1 hour after L T. Sensitivity to these stimuli returned to the control levels after 5 days post-L T. No significant difference was found in mechanical allodynia between control and L T groups for all time points examined. Conclusion These in vitro and in vivo studies indicate that treatment with an irradiance/fluence rate at 270 m W/cm2 or higher at the level of the nerve can rapidly block pain transmission. A combination therapy is proposed to treat neuropathic pain with initial high irradiance/fluence rates for fast pain relief, followed by low irradiance/ fluence rates for prolonged pain relief by altering chronic inflammation.

Structural connectivity-based segmentation of the thalamus and prediction of tremor improvement following thalamic deep brain stimulation of the ventral intermediate nucleus.

OBJECTIVES: Traditional targeting methods for thalamic deep brain stimulation (DBS) performed to address tremor have predominantly relied on indirect atlas-based methods that focus on the ventral intermediate nucleus despite known variability in thalamic functional anatomy. Improvements in preoperative targeting may help maximize outcomes and reduce thalamic DBS-related complications. In this study, we evaluated the ability of thalamic parcellation with structural connectivity-based segmentation (SCBS) to predict tremor improvement following thalamic DBS. METHODS: In this retrospective analysis of 40 patients with essential tremor, hard segmentation of the thalamus was performed by using probabilistic tractography to assess structural connectivity to 7 cortical targets. The volume of tissue activated (VTA) was modeled in each patient on the basis of the DBS settings. The volume of overlap between the VTA and the 7 thalamic segments was determined and correlated with changes in preoperative and postoperative Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores by using multivariable linear regression models. RESULTS: A significant association was observed between greater VTA in the supplementary motor area (SMA) and premotor cortex (PMC) thalamic segment and greater improvement in TRS score when considering both the raw change (P = .001) and percentage change (P = .011). In contrast, no association was observed between change in TRS score and VTA in the primary motor cortex thalamic segment (P ≥ .19). CONCLUSIONS: Our data suggest that greater VTA in the thalamic SMA/PMC segment during thalamic DBS was associated with significant improvement in TRS score in patients with tremor. These findings support the potential role of thalamic SCBS as an independent predictor of tremor improvement in patients who receive thalamic DBS.