A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

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.

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.

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.

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.

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.

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.

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.

Anatomic Investigation of the Trajectory for Stereotactic Laser Amygdalohippocampectomy.

BACKGROUND: Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) has emerged as a promising treatment for mesial temporal lobe epilepsy. Surgeons must understand the relevant anatomy that is traversed by the catheter and affected by ablation. OBJECTIVE: To study the anatomic structures crossed by the LITT catheter until it reaches the amygdala. METHODS: Three human cadaveric heads were implanted with catheters using a frameless stereotactic technique. The Visualase® system (Medtronic, Dublin, Ireland) was utilized to ablate along the trajectory. Coronal and oblique axial slices were created. Fiber tract dissections were performed in a lateral-medial and inferior-superior scheme. Magnetic resonance tractography was acquired to illustrate the tracts dissected. RESULTS: Entry points occurred within 4 cm of the transverse and sagittal sinus, inferior to the lambdoid suture. The cortex of the inferior occipital gyrus was crossed in the region of the transverse occipital sulcus. The vertical occipital fasciculus was crossed en route to passing through the optic radiations. The catheter crossed through or inferior to the optic radiations before piercing the parahippocampal gyrus at about 4 cm from the skull. The catheter entered the hippocampus as it pierced the superior margin of the parahippocampus at 6 cm. The catheter entered the head of the hippocampus to lie inferolateral to the amygdala in the last centimeter of the trajectory. CONCLUSION: Understanding the anatomic principles of LITT catheter trajectories will improve the ability to perform this procedure. The current study is the first to examine the anatomy of this trajectory and will serve as the basis for future studies.

Microsurgical anatomy of the subthalamic nucleus: correlating fiber dissection results with 3-T magnetic resonance imaging using neuronavigation.

OBJECTIVE: Despite the extensive use of the subthalamic nucleus (STN) as a deep brain stimulation (DBS) target, unveiling the extensive functional connectivity of the nucleus, relating its structural connectivity to the stimulation-induced adverse effects, and thus optimizing the STN targeting still remain challenging. Mastering the 3D anatomy of the STN region should be the fundamental goal to achieve ideal surgical results, due to the deep-seated and obscure position of the nucleus, variable shape and relatively small size, oblique orientation, and extensive structural connectivity. In the present study, the authors aimed to delineate the 3D anatomy of the STN and unveil the complex relationship between the anatomical structures within the STN region using fiber dissection technique, 3D reconstructions of high-resolution MRI, and fiber tracking using diffusion tractography utilizing a generalized q-sampling imaging (GQI) model. METHODS: Fiber dissection was performed in 20 hemispheres and 3 cadaveric heads using the Klingler method. Fiber dissections of the brain were performed from all orientations in a stepwise manner to reveal the 3D anatomy of the STN. In addition, 3 brains were cut into 5-mm coronal, axial, and sagittal slices to show the sectional anatomy. GQI data were also used to elucidate the connections among hubs within the STN region. RESULTS: The study correlated the results of STN fiber dissection with those of 3D MRI reconstruction and tractography using neuronavigation. A 3D terrain model of the subthalamic area encircling the STN was built to clarify its anatomical relations with the putamen, globus pallidus internus, globus pallidus externus, internal capsule, caudate nucleus laterally, substantia nigra inferiorly, zona incerta superiorly, and red nucleus medially. The authors also describe the relationship of the medial lemniscus, oculomotor nerve fibers, and the medial forebrain bundle with the STN using tractography with a 3D STN model. CONCLUSIONS: This study examines the complex 3D anatomy of the STN and peri-subthalamic area. In comparison with previous clinical data on STN targeting, the results of this study promise further understanding of the structural connections of the STN, the exact location of the fiber compositions within the region, and clinical applications such as stimulation-induced adverse effects during DBS targeting.

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.

VIM thalamotomy in the treatment of Holmes' tremor secondary to HIV-associated midbrain lesion: a case report.

Holmes' tremor (rubral tremor, cerebellar outflow tremor) is characterized by rest, intention and postural tremor, often localized to one upper extremity, associated with ipsilateral dysmetria and dysdiadochokinesia. We describe a case of successful treatment of Holmes' tremor with unilateral nucleus ventralis intermedius (VIM) thalamotomy. The subject is a 43-year-old woman with unremarkable previous medical history. She presented with complete left hemiparesis in the context of human immunodeficiency syndrome and the magnetic resonance image disclosed a contrast-enhancing lesion in right brain peduncle, in topography of red nucleus. She developed a progressive rest, intention and postural tremor in left upper limb. She was submitted to a stereotactic biopsy and the tremor became worse. She performed awake right VIM thalamotomy, with immediate complete resolution of tremor. There were no complications after procedure, and the result is stable after six months. We highlight the role of thalamotomy in cases like ours, once patient recovered well and, due to HIV, will need further neuroimage studies to evaluate neurologic complications of HIV. Deep brain stimulation in such cases may interfere with coming neuroimage quality and may act like a foreign body.

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.

Assessment of Cerebral Blood Flow with Micro-Doppler Vascular Reduces the Risk of Ischemic Stroke During the Clipping of Intracranial Aneurysms.

OBJECTIVE: To analyze the impact of the introduction of Micro-Doppler vascular (MDV) as a method of cerebral blood flow analysis during microsurgical clipping of intracranial aneurysms to check the partial occlusion of the aneurysm and the occurrence of stenosis by comparing these results with those provided by the postoperative digital subtraction angiography (DSA) scan as well as the occurrence of ischemic infarction on the postoperative computed tomography (CT) images. PATIENTS AND METHODS: We reviewed retrospectively the last 50 patients operated on before the introduction of the MDV (group 1) compared with the first 50 patients operated on using this technique (group 2). RESULTS: Nine (18%) of the 50 patients evaluated in the group 1 showed a new hypodensity in the postoperative CT images, whereas only 2 (4%) patients showed infarction in the group 2 (P = 0.02). In addition, in the group 1, 10 (20%) patients presented unexpected findings on DSA images (residual aneurysms, stenosis, and arterial occlusion), whereas in the group 2, those unexpected DSA findings were observed in only 3 (6%) patients (P = 0.023). CONCLUSION: MDV is an excellent method for cerebral blood flow assessment during the microsurgical clipping of intracranial aneurysms, reducing the unexpected angiographic results (residual aneurysms, stenosis, and arterial occlusion), as well as reducing the incidence of ischemic infarction on postoperative CT images, evidence of the positive impact of this method in the microsurgical treatment of intracranial aneurysms.