ADAR regulates APOL1 via A-to-I RNA editing by inhibition of MDA5 activation in a paradoxical biological circuit.

APOL1 risk variants are associated with increased risk of kidney disease in patients of African ancestry, but not all individuals with the APOL1 high-risk genotype develop kidney disease. As APOL1 gene expression correlates closely with the degree of kidney cell injury in both cell and animal models, the mechanisms regulating APOL1 expression may be critical determinants of risk allele penetrance. The APOL1 messenger RNA includes Alu elements at the 3' untranslated region that can form a double-stranded RNA structure (Alu-dsRNA) susceptible to posttranscriptional adenosine deaminase acting on RNA (ADAR)-mediated adenosine-to-inosine (A-to-I) editing, potentially impacting gene expression. We studied the effects of ADAR expression and A-to-I editing on APOL1 levels in podocytes, human kidney tissue, and a transgenic APOL1 mouse model. In interferon-γ (IFN-γ)-stimulated human podocytes, ADAR down-regulates APOL1 by preventing melanoma differentiation-associated protein 5 (MDA5) recognition of dsRNA and the subsequent type I interferon (IFN-I) response. Knockdown experiments showed that recognition of APOL1 messenger RNA itself is an important contributor to the MDA5-driven IFN-I response. Mathematical modeling suggests that the IFN-ADAR-APOL1 network functions as an incoherent feed-forward loop, a biological circuit capable of generating fast, transient responses to stimuli. Glomeruli from human kidney biopsies exhibited widespread editing of APOL1 Alu-dsRNA, while the transgenic mouse model closely replicated the edited sites in humans. APOL1 expression in mice was inversely correlated with Adar1 expression under IFN-γ stimuli, supporting the idea that ADAR regulates APOL1 levels in vivo. ADAR-mediated A-to-I editing is an important regulator of APOL1 expression that could impact both penetrance and severity of APOL1-associated kidney disease.

DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants.

BACKGROUND: Two variants in the gene encoding apolipoprotein L1 (APOL1) that are highly associated with African ancestry are major contributors to the large racial disparity in rates of human kidney disease. We previously demonstrated that recruitment of APOL1 risk variants G1 and G2 from the endoplasmic reticulum to lipid droplets leads to reduced APOL1-mediated cytotoxicity in human podocytes. METHODS: We used CRISPR-Cas9 gene editing of induced pluripotent stem cells to develop human-derived APOL1G0/G0 and APOL1G2/G2 kidney organoids on an isogenic background, and performed bulk RNA sequencing of organoids before and after treatment with IFN-γ. We examined the number and distribution of lipid droplets in response to treatment with inhibitors of diacylglycerol O-acyltransferases 1 and 2 (DGAT1 and DGAT2) in kidney cells and organoids. RESULTS: APOL1 was highly upregulated in response to IFN-γ in human kidney organoids, with greater increases in organoids of high-risk G1 and G2 genotypes compared with wild-type (G0) organoids. RNA sequencing of organoids revealed that high-risk APOL1G2/G2 organoids exhibited downregulation of a number of genes involved in lipogenesis and lipid droplet biogenesis, as well as upregulation of genes involved in fatty acid oxidation. There were fewer lipid droplets in unstimulated high-risk APOL1G2/G2 kidney organoids than in wild-type APOL1G0/G0 organoids. Whereas DGAT1 inhibition reduced kidney organoid lipid droplet number, DGAT2 inhibition unexpectedly increased organoid lipid droplet number. DGAT2 inhibition promoted the recruitment of APOL1 to lipid droplets, with associated reduction in cytotoxicity. CONCLUSIONS: Lipogenesis and lipid droplet formation are important modulators of APOL1-associated cytotoxicity. Inhibition of DGAT2 may offer a potential therapeutic strategy to attenuate cytotoxic effects of APOL1 risk variants.

Alternative cost-effective method to record 3D intra-operative images: a technical note.

The educational value of stereoscopic imaging in neurosurgical training has increasingly been appreciated and its use increased during the last decade. We describe a technique that we developed to acquire and reproduce intra-operative stereoscopic images.

Safety and Efficacy of a Preemptive Mycophenolate Mofetil Dose Reduction Strategy in Kidney Transplant Recipients.

Background: There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of allograft rejection with that of infections and malignancy. At our center, KTRs are managed with either a "preemptive" dose reduction strategy, where the MMF dose is reduced after the first year before the development of adverse events, or with a "reactive" dosing strategy, where they are maintained on the same MMF dose and only reduced if they develop an adverse event. We hypothesized that a preemptive MMF dosing strategy after the first year of transplantation is associated with decreased infections without increasing alloimmune complications. Methods: We conducted a retrospective cohort study of all KTRs receiving MMF from January 1, 2015, to December 31, 2020. The primary outcome was the incidence of infections requiring hospitalization. Results: One hundred forty-two KTRs met the inclusion criteria, of whom 44 (31%) were in the preemptive group and 98 (69%) were in the reactive group. The median follow-up was 4 y (interquartile range, 3.8-4.0). Multivariable analysis showed that a preemptive MMF dose reduction strategy was associated with a lower risk of infections requiring hospitalization (adjusted hazard ratio = 0.39; 95% confidence interval, 0.16-0.92). There was no difference in graft loss, rejection, or estimated glomerular filtration rate slope. Conclusions: Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection. Randomized clinical trials are needed to confirm these findings.

Inhibitory innate receptors and their potential role in transplantation.

The regulatory arm of the immune system plays a crucial role in maintaining immune tolerance and preventing excessive immune responses. Immune regulation comprises various regulatory cells and molecules that work together to suppress or regulate immune responses. The programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) are examples of inhibitory receptors that counteract activating signals and fine-tune immune responses. While most of the discoveries of immune regulation have been related to T cells and the adaptive immune system, the innate arm of the immune system also has a range of inhibitory receptors that can counteract activating signals and suppress the effector immune responses. Targeting these innate inhibitory receptors may provide a complementary therapeutic approach in several immune-related conditions, including transplantation. In this review, we will explore the potential role of innate inhibitory receptors in controlling alloimmunity during solid organ transplantation.

Transanterior Limiting Sulcus of the Insula Approach: Novel Surgical Approach to the Ventral Striatum Region.

BACKGROUND: Lesions in the ventral striatum region (above the anterior perforated substance) are a challenge for neurosurgeons due to their direct relationship with the lenticulostriate arteries, which difficult the surgical access. The standard approaches for this region include the following: 1) transfrontal approach, 2) transanterior perforating substance approach, 3) transcallosal transventricular approach, and 4) pterional transsylvian-transinsular route. In this study, we aimed to describe a novel anatomical approach through the anterior limiting sulcus of the insula in order to access the ventral striatum. METHODS: We reviewed the literature and performed a detailed dissection of this region by using Klingler's technique with brain specimens injected with silicone, paying special attention to the white fibers and lenticulostriate arteries, and provided a description of an illustrative case of a cavernous malformation. RESULTS: Neuroanatomical dissections showed that the lenticulostriate arteries had an inverted C-shaped anterior concavity, leaving less significant vascular relationships in the depth of the anterior limiting sulcus of the insula. In the case we described, the cavernous malformation was completely resected and the patient was discharged without any neurological deficits. CONCLUSIONS: The transanterior limiting sulcus of the insula approach to the ventral striatum offers a safe access route for selected cases and can be performed on the basis of anatomical references. Three-dimensional understanding of the intrinsic brain architecture and its relationships with vascular structures in this specific area is important and can be acquired mainly through laboratory training.

The value of pre-transplant coronary angiography findings in kidney transplant candidates at high risk for cardiovascular disease.

Introduction: Cardiovascular disease is a significant cause of mortality after kidney transplantation. Whether pre-transplant screening for coronary artery disease (CAD) in asymptomatic kidney transplant candidates (KTCs) is beneficial is unclear. Methods: We conducted a retrospective cohort study evaluating post-transplant cardiovascular events in 192 high-risk KTCs who underwent pre-transplant CAD evaluation. The study aimed to identify risk factors associated with finding severe CAD on pre-transplant angiography, and to assess the relationship between screening strategies and post-transplant cardiovascular events. Results: At five years post-transplant, cardiovascular events occurred in 23.9% of subjects. Prior CAD history and left ventricular ejection fraction (LVEF) < 50% were associated with higher odds of finding severe CAD on pre-transplant angiography. Severe CAD on angiography was associated with a higher risk of early cardiovascular events within six months of transplantation. However, coronary intervention in KTCs with severe CAD was not associated with lower rates of post-transplant cardiovascular events. Conclusion: Pre-transplant coronary angiography to identify severe CAD is of highest yield in KTCs with a history of CAD or an LVEF < 50%. Our findings indicate that the identification of severe CAD in KTCs has prognostic significance for the early post-transplant period. Optimization of medical therapy in these high-risk KTCs may improve post-transplant cardiovascular outcomes.

Gods and monsters: Greek mythology and Christian references in the neurosurgical lexicon.

BACKGROUND: Myths and religion are belief systems centered around supernatural entities that attempt to explain the observed world and are of high importance to certain communities. The former is a collection of stories that belong to a cultural tradition and the latter are organized faiths that determine codes of ethics, rituals and philosophy. Deities or monstrous creatures in particular act as archetypes instructing an individual's conduct. References to them in Greek mythology and Christianity are frequently manifested in the modern neurosurgical vernacular. METHODS: A review of the medical literature was performed using the PubMed and MEDLINE bibliographic databases. Publications from 1875 to 2021 related to neurosurgery or neuroanatomy with the medical subject headings (MeSH) terms mythology, religion, Christianity and Catholicism were reviewed. References pertaining to supernatural beings were classified to either a deity or a monstrosity according to their conventional cultural context. RESULTS: Twelve narratives associated with neurosurgery were identified, nine relating to Greek mythology and three associated with the Christian-Catholic faith. Eight accounts concerned deities and the remaining with monstrous creatures. CONCLUSION: This article explores the etymology of commonly utilized terms in daily neurosurgical practice in the context of mythology and religion. They reveal the ingenuity and creativity of early pioneers who strived to understand the brain.

Microbiome and oral squamous cell carcinoma: a possible interplay on iron metabolism and its impact on tumor microenvironment.

There is increasing evidence showing positive association between changes in oral microbiome and the occurrence of oral squamous cell carcinoma (OSCC). Alcohol- and nicotine-related products can induce microbial changes but are still unknown if these changes are related to cancerous lesion sites. In an attempt to understand how these changes can influence the OSCC development and maintenance, the aim of this study was to investigate the oral microbiome linked with OSCC as well as to identify functional signatures and associate them with healthy or precancerous and cancerous sites. Our group used data of oral microbiomes available in public repositories. The analysis included data of oral microbiomes from electronic cigarette users, alcohol consumers, and precancerous and OSCC samples. An R-based pipeline was used for taxonomic and functional prediction analysis. The Streptococcus spp. genus was the main class identified in the healthy group. Haemophilus spp. predominated in precancerous lesions. OSCC samples revealed a higher relative abundance compared with the other groups, represented by an increased proportion of Fusobacterium spp., Prevotella spp., Haemophilus spp., and Campylobacter spp. Venn diagram analysis showed 52 genera exclusive of OSCC samples. Both precancerous and OSCC samples seemed to present a specific associated functional pattern. They were menaquinone-dependent protoporphyrinogen oxidase pattern enhanced in the former and both 3',5'-cyclic-nucleotide phosphodiesterase (purine metabolism) and iron(III) transport system ATP-binding protein enhanced in the latter. We conclude that although precancerous and OSCC samples present some differences on microbial profile, both microbiomes act as "iron chelators-like" potentially contributing to tumor growth.

The cerebral sulci and gyri.

The aim of this study was to describe in detail the microanatomy of the cerebral sulci and gyri, clarifying the nomenclature for microneurosurgical purposes. An extensive review of the literature regarding the historical, evolutionary, embryological, and anatomical aspects pertinent to human cerebral sulci and gyri was conducted, with a special focus on microneuroanatomy issues in the field of neurosurgery. An intimate knowledge of the cerebral sulci and gyri is needed to understand neuroimaging studies, as well as to plan and execute current microneurosurgical procedures.

Understanding Anatomy of the Petrous Pyramid-A New Compartmental Approach.

BACKGROUND: Learning surgical anatomy of the petrous pyramid can be a challenge, especially in the beginning of the training process. Providing an easier, holistic approach can be of help to everyone with interest in learning and teaching skull base anatomy. We present the complex organization of petrous pyramid anatomy using a new compartmental approach that is simple to understand and remember. METHODS: The surfaces of the petrous pyramid of two temporal bones were examined; and the contents of the petrous pyramid of 8 temporal bones were exposed through progressive drilling of the superior surface. RESULTS: The petrous pyramid is made up of a bony container, and its contents were grouped into 4 compartments (mucosal, cutaneous, neural, and vascular). Two reference lines were identified (mucosal and external-internal auditory canal lines) intersecting at the level of the middle ear. The localization of contents relative to these reference lines was then described, and 2 methods of segmentation (the X method and the V method) were then proposed. This description was then used to describe middle ear relationships, facial nerve anatomy, and air cell distribution. CONCLUSIONS: This new compartmental approach allows a comprehensive understanding of the distribution of petrous pyramid contents. Dividing it into anatomic compartments, and then navigating this mental map along specific reference points, lines, spaces, and segments, could create a useful tool to teach or learn its complex tridimensional anatomy.

Diffuse large B-cell lymphoma of the central nervous system presenting as "lymphomatosis cerebri" and dementia in elderly man: Case report and review of the literature.

RATIONALE: Lymphomatosis cerebri is a rare form of PCNSL, characterized by diffuse infiltration of lymphoma cells in cerebral parenchyma, without mass-formation and mild or no contrast enhancement on magnetic resonance (MR) imaging. There are less than 50 cases described in the literature under the term Lymphomatosis cerebri. PATIENT CONCERNS: A 74-year-old man presented to our service with progressive dementia for 12 months and accelerated cognitive decline within the last two months. Brain magnetic resonance imaging showed areas of hyperintensity involving predominantly the white matter of frontal lobes and knee of the corpus callosum, along with areas of blood-brain barrier disruption and areas of restricted diffusion. Stereotaxy brain surgery was indicated into contrasting areas and histologically there was heterogeneous foci of discreet infiltration of rare medium-large lymphoid cells intermingled with inflammatory cells and these atypical lymphoid cells were placed on breakdown neuropil and did not form tumor mass or sheets of cells, but occasionally displayed perivascular distribution. Immunohistochemically, these atypical lymphoid cells expressed CD20, Bcl2, Bcl6 and, heterogeneously, IRF4/MUM1. DIAGNOSIS: The diagnosis of a primary CNS diffuse large B-cell lymphoma manifested as lymphomatosis cerebri was performed. INTERVENTIONS: The treatment of choice was: temozolomide 100 mg/m (D1 to D5), methotrexate 3 g/m (D1, D10, and D20) and rituximab 375 mg/m. OUTCOMES: The patient evolved with progressive neurological deterioration, regardless of the improvement on neuroimaging. LESSONS: We described the diagnostic dilemma we faced with an elderly man with rapid cognitive impairment and a myriad of differential diagnoses, diagnosed with primary CNS diffuse large B-cell lymphoma with a lymphomatosis cerebri-like pattern.

Endoscopic anatomy of the pterygopalatine fossa and the transpterygoid approach: development of a surgical instruction model.

INTRODUCTION: The pterygopalatine fossa (PPF) is a narrow space located between the posterior wall of the antrum and the pterygoid plates. Surgical access to the PPF is difficult because of its protected position and its complex neurovascular anatomy. Endonasal approaches using rod lens endoscopes, however, provide better visualization of this area and are associated with less morbidity than external approaches. Our aim was to develop a simple anatomical model using cadaveric specimens injected with intravascular colored silicone to demonstrate the endoscopic anatomy of the PPF. This model could be used for surgical instruction of the transpterygoid approach. METHODS: We dissected six PPF in three cadaveric specimens prepared with intravascular injection of colored material using two different injection techniques. An endoscopic endonasal approach, including a wide nasoantral window and removal of the posterior antrum wall, provided access to the PPF. RESULTS: We produced our best anatomical model injecting colored silicone via the common carotid artery. We found that, using an endoscopic approach, a retrograde dissection of the sphenopalatine artery helped to identify the internal maxillary artery (IMA) and its branches. Neural structures were identified deeper to the vascular elements. Notable anatomical landmarks for the endoscopic surgeon are the vidian nerve and its canal that leads to the petrous portion of the internal carotid artery (ICA), and the foramen rotundum, and V2 that leads to Meckel's cave in the middle cranial fossa. These two nerves, vidian and V2, are separated by a pyramidal shaped bone and its apex marks the ICA. CONCLUSION: Our anatomical model provides the means to learn the endoscopic anatomy of the PPF and may be used for the simulation of surgical techniques. An endoscopic endonasal approach provides adequate exposure to all anatomical structures within the PPF. These structures may be used as landmarks to identify and control deeper neurovascular structures. The significance is that an anatomical model facilitates learning the surgical anatomy and the acquisition of surgical skills. A dissection superficial to the vascular structures preserves the neural elements. These nerves and their bony foramina, such as the vidian nerve and V2, are critical anatomical landmarks to identify and control the ICA at the skull base.

Microsurgical anatomy of the central core of the brain.

OBJECTIVE The purpose of this study was to describe in detail the cortical and subcortical anatomy of the central core of the brain, defining its limits, with particular attention to the topography and relationships of the thalamus, basal ganglia, and related white matter pathways and vessels. METHODS The authors studied 19 cerebral hemispheres. The vascular systems of all of the specimens were injected with colored silicone, and the specimens were then frozen for at least 1 month to facilitate identification of individual fiber tracts. The dissections were performed in a stepwise manner, locating each gray matter nucleus and white matter pathway at different depths inside the central core. The course of fiber pathways was also noted in relation to the insular limiting sulci. RESULTS The insular surface is the most superficial aspect of the central core and is divided by a central sulcus into an anterior portion, usually containing 3 short gyri, and a posterior portion, with 2 long gyri. It is bounded by the anterior limiting sulcus, the superior limiting sulcus, and the inferior limiting sulcus. The extreme capsule is directly underneath the insular surface and is composed of short association fibers that extend toward all the opercula. The claustrum lies deep to the extreme capsule, and the external capsule is found medial to it. Three fiber pathways contribute to form both the extreme and external capsules, and they lie in a sequential anteroposterior disposition: the uncinate fascicle, the inferior fronto-occipital fascicle, and claustrocortical fibers. The putamen and the globus pallidus are between the external capsule, laterally, and the internal capsule, medially. The internal capsule is present medial to almost all insular limiting sulci and most of the insular surface, but not to their most anteroinferior portions. This anteroinferior portion of the central core has a more complex anatomy and is distinguished in this paper as the "anterior perforated substance region." The caudate nucleus and thalamus lie medial to the internal capsule, as the most medial structures of the central core. While the anterior half of the central core is related to the head of the caudate nucleus, the posterior half is related to the thalamus, and hence to each associated portion of the internal capsule between these structures and the insular surface. The central core stands on top of the brainstem. The brainstem and central core are connected by several white matter pathways and are not separated from each other by any natural division. The authors propose a subdivision of the central core into quadrants and describe each in detail. The functional importance of each structure is highlighted, and surgical approaches are suggested for each quadrant of the central core. CONCLUSIONS As a general rule, the internal capsule and its vascularization should be seen as a parasagittal barrier with great functional importance. This is of particular importance in choosing surgical approaches within this region.

The suprapetrosal craniotomy.

OBJECTIVE: The primary aim of this study was to establish standard sites for bur holes that maintain constant anatomical relationships with the skull base and neural structures and can serve as the basal aspect of supratentorial temporooccipital craniotomies. METHODS: To determine cranial-cerebral relationships, the authors created bur holes in 16 adult cadaveric skulls. Three bur holes were made on each side of the skulls (32 cerebral hemispheres). The authors then introduced plastic catheters through the bur holes to evaluate pertinent cranial and neural landmarks. The first bur hole, located anterior to the auricle of the ear, appeared to have a particular anatomical relationship with the anterior aspect of the petrous portion of the temporal bone and the most anterior aspect of the midbrain. The second bur hole, whose base was located 1 cm above the interface of the parietomastoid and squamous sutures, had a particular relationship with the posterior border of the petrous portion of the temporal bone and with the posterior aspect of the midbrain. The third bur hole, whose base was located 1 cm above the asterion, was mostly supratentorial and particularly related to the preoccipital notch. CONCLUSIONS: The preauricular bur hole and the bur hole whose base was located 1 cm above the interface of the parietomastoid and squamous sutures delimit anteriorly and posteriorly the external projection of the petrous bone and the midbrain. The middle fossa floor is located anterior to the site of the preauricular bur hole, and the superior surface of the tentorium is posterior to the bur hole located above the parietomastoid-squamous suture interface. Together with the bur hole whose base is located above the asterion, these bur holes can be considered standards for temporooccipital craniotomies.

[The insula and the central core concept]. / A ínsula e o conceito de bloco cerebral central.

The characterization of well defined and circumscribed brain regions is particularly useful for the neurosurgical practice once it enhances the tridimensional understanding of its structures and related lesions, and because it induces the development and the utilization of more standard microneurosurgical approaches. In this direction, it is noteworthy that each cerebral hemisphere harbors an evident central core constituted externally by the insula, internally by the basal ganglia and the thalamus, and with the internal capsule within. With a biconvex configuration when seen from above, and located between the sylvian cistern and the supratentorial ventricular cavities, morphologically this central core resembles a head of each brainstem half top, covered by the neocortical mantle of its hemisphere. The central core is attached to the rest of the cerebral hemisphere by isthmi constituted by the different internal capsule fibers. Anteriorly and under the anterior limiting sulcus of the insula there are fibers of the internal capsule anterior limb, superiorly and under the superior limiting sulcus there are the rest of the anterior limb fibers, and the knee and posterior limb fibers that harbors the corticonuclear and the corticospinal tracts, and inferiorly and under the insular inferior limiting sulcus there are the sub- and the retrolentiform internal capsule fibers that enclose the auditory and the optic radiations. Laterally the central core is composed by the insular surface that resembles a shield of the main cerebral subcortical structures. The options of microneurosurgical approaches to the central core related lesions should consider particularly their relationships with the thalamus and with the internal capsule fibers.

[The pterional craniotomy: step by step]. / A craniotomia pterional: descrição passo a passo.

This article intends to describe in a didactical and practical manner the frontotemporosphenoidal craniotomy, that is usually known as pterional craniotomy and that constitute the cranial approach mostly utilized in the modern neurosurgery. This is then basically a descriptive text, divided according to the main stages involved in this procedure, and that describes with details how the authors currently perform this craniotomy.

[Neuroanatomical basis of behavior: history and recent contributions]. / As bases neuroanatômicas do comportamento: histórico e contribuições recentes.

Considering the most recent contributions, the limbic cortical areas, originally known as the greater limbic lobe, besides the cingulated and the parahippocampal gyri also includes the insula and the posterior orbital cortex. In contrast to the nonlimbic cortical areas that project to the basal ganglia (particularly over the dorsal aspects of the striatum, constituted by the caudate nucleus and by the putamen), the limbic cortical areas are characterized by projecting to the hypothalamus and also to the ventral striatum (particularly to the nucleus accumbens). Once all the striatum projects to the globus pallidus which projects to the thalamus and then to the cortex, generating cortical-subcortical reentrant circuits, while the dorsal striatum and pallidum related cortico-subcortical loops are involved with motor activities, the ventral cortical-striatal-pallidal system is particularly related with behavior functions. The extended amygdala (central medial amygdala, stria terminalis or dorsal component, ventral component, and bed nucleus of stria terminalis) receives inputs primarily from the limbic cortical areas, is particularly modulated by the prefrontal cortex, and receives also direct connections from the thalamus that enables the amygdala to generate nonspecific and quick responses through its projections to the hypothalamus and to the brainstem. The ventral striatal-pallidal and the extended amygdala are then two basal forebrain macro-anatomical systems, that together with the basal nucleus of Meynert and with the septal-diagonal band system, constitute the main structures that are particularly connected with the limbic cortical areas, and that altogether project to the hypothalamus and to the brainstem which give rise to the autonomic, endocrine and somatosensory components of the emotional experiences, and that regulate the basic activities of drinking, eating, and related to the sexual behavior.

Surgical Approaches to the Temporal Horn: An Anatomic Analysis of White Matter Tract Interruption.

BACKGROUND: Surgical access to the temporal horn is necessary to treat tumors and vascular lesions, but is used mainly in patients with mediobasal temporal epilepsy. The surgical approaches to this cavity fall into 3 primary categories: lateral, inferior, and transsylvian. The current neurosurgical literature has underestimated the interruption of involved fiber bundles and the correlated clinical manifestations. OBJECTIVE: To delineate the interruption of fiber bundles during the different approaches to the temporal horn. METHODS: We simulated the lateral (trans-middle temporal gyrus), inferior (transparahippocampal gyrus), and transsylvian approaches in 20 previously frozen, formalin-fixed human brains (40 hemispheres). Fiber dissection was then done along the lateral and inferior aspects under the operating microscope. Each stage of dissection and its respective fiber tract interruption were defined. RESULTS: The lateral (trans-middle temporal gyrus) approach interrupted "U" fibers, the superior longitudinal fasciculus (inferior arm), occipitofrontal fasciculus (ventral segment), uncinate fasciculus (dorsolateral segment), anterior commissure (posterior segment), temporopontine, inferior thalamic peduncle (posterior fibers), posterior thalamic peduncle (anterior portion), and tapetum fibers. The inferior (transparahippocampal gyrus) approach interrupted "U" fibers, the cingulum (inferior arm), and fimbria, and transected the hippocampal formation. The transsylvian approach interrupted "U" fibers (anterobasal region of the extreme capsule), the uncinate fasciculus (ventromedial segment), and anterior commissure (anterior segment), and transected the anterosuperior aspect of the amygdala. CONCLUSION: White matter dissection improves our knowledge of the complex anatomy surrounding the temporal horn. Identifying the fiber bundles at risk during each surgical approach adds important information for choosing the appropriate surgical strategy.