Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

Over 30 Years of DiI Use for Human Neuroanatomical Tract Tracing: A Scoping Review.

In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations.

Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

The lateral retrocanthal transorbital endoscopic approach to the middle fossa: cadaveric stepwise approach and review of quantitative cadaveric data.

OBJECTIVE: The lateral retrocanthal transorbital endoscopic approach (LRCTEA) facilitates trajectory to the middle fossa, preserving the lateral canthal tendon and thus avoiding postoperative complications such as eyelid malposition. Here, the authors sought to define the surgical anatomy and technique of LRCTEA using a stepwise approach in cadaveric heads and offer an in-depth examination of existing quantitative data from cadaveric studies. METHODS: The authors performed LRCTEA to the middle cranial fossa under neuronavigation in 7 cadaveric head specimens that underwent high-resolution (1-mm) CT scans preceding the dissections. RESULTS: The LRCTEA provided access to middle fossa regions including the cavernous sinus, Meckel's cave, and medial temporal lobe. The trajectories and endpoints of the approach were confirmed using electromagnetic neuronavigation. A stepwise approach was delineated and recorded. CONCLUSIONS: The authors' cadaveric study delineates the surgical anatomy and technique of the LRCTEA, providing a stepwise approach for its implementation. As these approaches continue to evolve, their development and refinement will play an important role in expanding the surgical options available to neurosurgeons, ultimately improving outcomes for patients with complex skull base pathologies. The LRCTEA presents a promising advancement in skull base surgery, particularly for accessing challenging middle fossa regions. However, surgeons must remain vigilant to potential complications, including transient diplopia, orbital hematoma, or damage to the optic apparatus.

Parcellating the vertical associative fiber network of the temporoparietal area: Evidence from focused anatomic fiber dissections.

Introduction: The connectivity of the temporoparietal (TP) region has been the subject of multiple anatomical and functional studies. Its role in high cognitive functions has been primarily correlated with long association fiber connections. As a major sensory integration hub, coactivation of areas within the TP requires a stream of short association fibers running between its subregions. The latter have been the subject of a small number of recent in vivo and cadaveric studies. This has resulted in limited understanding of this network and, in certain occasions, terminology ambiguity. Research question: To systematically study the vertical parietal and temporoparietal short association fibers. Material and methods: Thirteen normal, adult cadaveric hemispheres, were treated with the Klinger's freeze-thaw process and their subcortical anatomy was studied using the microdissection technique. Results: Two separate fiber layers were identified. Superficially, directly beneath the cortical u-fibers, the Stratum proprium intraparietalis (SP) was seen connecting Superior Parietal lobule and Precuneal cortical areas to inferior cortical regions of the Parietal lobe, running deep to the Intraparietal sulcus. At the same dissection level, the IPL-TP fibers were identified as a bundle connecting the Inferior Parietal lobule with posterior Temporal cortical areas. At a deeper level, parallel to the Arcuate fasciculus fibers, the SPL-TP fibers were seen connecting the Superior Parietal lobule to posterior Temporal cortical areas. Discussion and conclusion: To our knowledge this is the first cadaveric dissection study to comprehensively study and describe of the vertical association fibers of the temporoparietal region while proposing a universal terminology.

The Anatomical Variation of the Distal Anterior Cerebral Artery: An Angiographic Study in a Greek Population Sample.

Objective The current retrospective angiographic study establishes the rates of variants in the distal anterior cerebral artery (DACA) in a sample of the Greek population. Methods Data were collected from 456 patients who underwent two-dimensional (2D) or three-dimensional (3D) digital subtraction angiography (DSA) of the carotid and vertebral arteries bilaterally. The study focused on patients with good visualization of the anterior and posterior circulations and employed magnetic resonance (MR) or computed tomography (CT) angiography for 3D reconstruction. The anterior cerebral artery (ACA) was classified into one of its two basic configurations, that is, with or without the callosomarginal artery (CMA). The bihemispheric, median, and azygos ACA patterns were also identified. Results The majority (373/456, 81.8%) exhibited a typical DACA pattern. The bihemispheric, median, and azygos patterns were identified in 66/456 (14.5%), 10/456 (2.2%), and 7/456 (1.5%), respectively. The CMA was present in 824/912 (90.4%) of the hemispheres, with a trend toward male predominance for bilateral presence (males: 167/192, 86.98%; females: 210/264, 79.55%; p = 0.05). In particular, the CMA was present significantly more frequently (p = 0.002) in the left hemispheres of male patients. Gender differences in CMA presence persisted in the analysis of the patients with a typical DACA pattern. Conclusion This study provides insights into the variations of the DACA in the Greek population. The observed gender differences in CMA rates suggest potential morphological variations in cerebral vasculature between males and females and contribute to a better understanding of vascular anatomy for clinical and surgical applications.

Management of glioblastoma in elderly patients: A review of the literature.

High grade gliomas are the most common primary aggressive brain tumours with a very poor prognosis and a median survival of less than 2 years. The standard management protocol of newly diagnosed glioblastoma patients involves surgery followed by radiotherapy, chemotherapy in the form of temozolomide and further adjuvant temozolomide. The recent advances in molecular profiling of high-grade gliomas have further enhanced our understanding of the disease. Although the management of glioblastoma is standardised in newly diagnosed adult patients there is a lot of debate regarding the best treatment approach for the newly diagnosed elderly glioblastoma patients. In this review article we attempt to summarise the findings regarding surgery, radiotherapy, chemotherapy, and their combination in order to offer the best possible management modality for this group of patients. Elderly patients 65-70 with an excellent functional level could be considered as candidates for the standards treatment consisting of surgery, standard radiotherapy with concomitant and adjuvant temozolomide. Similarly, elderly patients above 70 with good functional status could receive the above with the exception of receiving a shorter course of radiotherapy instead of standard. In elderly GBM patients with poorer functional status and MGMT promoter methylation temozolomide chemotherapy can be considered. For elderly patients who cannot tolerate chemotherapy, hypofractionated radiotherapy is an option. In contrast to the younger adult patients, it seems that a careful individualised approach is a key element in deciding the best treatment options for this group of patients.

Development of End-to-End AI-Based MRI Image Analysis System for Predicting IDH Mutation Status of Patients with Gliomas: Multicentric Validation.

Radiogenomics has shown potential to predict genomic phenotypes from medical images. The development of models using standard-of-care pre-operative MRI images, as opposed to advanced MRI images, enables a broader reach of such models. In this work, a radiogenomics model for IDH mutation status prediction from standard-of-care MRIs in patients with glioma was developed and validated using multicentric data. A cohort of 142 (wild-type: 32.4%) patients with glioma retrieved from the TCIA/TCGA was used to train a logistic regression model to predict the IDH mutation status. The model was evaluated using retrospective data collected in two distinct hospitals, comprising 36 (wild-type: 63.9%) and 53 (wild-type: 75.5%) patients. Model development utilized ROC analysis. Model discrimination and calibration were used for validation. The model yielded an AUC of 0.741 vs. 0.716 vs. 0.938, a sensitivity of 0.784 vs. 0.739 vs. 0.875, and a specificity of 0.657 vs. 0.692 vs. 1.000 on the training, test cohort 1, and test cohort 2, respectively. The assessment of model fairness suggested an unbiased model for age and sex, and calibration tests showed a p < 0.05. These results indicate that the developed model allows the prediction of the IDH mutation status in gliomas using standard-of-care MRI images and does not appear to hold sex and age biases.

Anaplastic Lymphoma Kinase (ALK) in Posterior Cranial Fossa Tumors: A Scoping Review of Diagnostic, Prognostic, and Therapeutic Perspectives.

Anaplastic Lymphoma Kinase (ALK) has been implicated in several human cancers. This review aims at mapping the available literature on the involvement of ALK in non-glial tumors localized in the posterior cranial fossa and at identifying diagnostic, prognostic, and therapeutic considerations. Following the PRISMA-ScR guidelines, studies were included if they investigated ALK's role in primary CNS, non-glial tumors located in the posterior cranial fossa. A total of 210 manuscripts were selected for full-text review and 16 finally met the inclusion criteria. The review included 55 cases of primary, intracranial neoplasms with ALK genetic alterations and/or protein expression, located in the posterior fossa, comprising of medulloblastoma, anaplastic large-cell lymphoma, histiocytosis, inflammatory myofibroblastic tumors, and intracranial myxoid mesenchymal tumors. ALK pathology was investigated via immunohistochemistry or genetic analysis. Several studies provided evidence for potential diagnostic and prognostic value for ALK assessment as well as therapeutic efficacy in its targeting. The available findings on ALK in posterior fossa tumors are limited. Nevertheless, previous findings suggest that ALK assessment is of diagnostic and prognostic value in medulloblastoma (WNT-activated). Interestingly, a substantial proportion of ALK-positive/altered CNS histiocytoses thus far identified have been localized in the posterior fossa. The therapeutic potential of ALK inhibition in histiocytosis warrants further investigation.

GFAP and UCHL1 in Non-traumatic SAH: The Story thus Far. A Systematic Review of the Literature.

OBJECTIVE: Non-traumatic subarachnoid hemorrhage (SAH) is associated with a high percentage of misdiagnosis and poor prognosis. Biomarkers could be useful in the identification, treatment/management guidance, and outcome improvement of SAH patients. The current systematic review aims to investigate the potential role of biomarkers GFAP (Glial Fibrillary Acidic Protein) and UCH-L1 (Ubiquitin C-Terminal Hydrolase L1) in the diagnosis and prognosis of non-traumatic SAH. METHODS: A systematic search of PubMed, Scopus, and Web of Science databases was conducted from their inception through February 2023. RESULTS: 17 studies met the inclusion criteria and were included in this review. The vast majority of the included studies (82%) were on GFAP. Most studies used blood and/or CSF samples and incorporated multiple measurements through the initial hospitalization days. The majority of identified studies significantly reported higher levels of GFAP and UCHL1 in SAH patients with poor outcomes. There was notable variation in the specimen type and the timing of sampling. CONCLUSION: Quantification of GFAP and UCHL1 through the initial days of hospitalization shows promise in the prediction of SAH patient outcomes. Further research is nevertheless warranted to confirm these findings and further clarify the use of the two biomarkers in SAH diagnosis and the prediction of severity and secondary events.

Preoperative neurocognitive function as an independent survival prognostic marker in primary glioblastoma.

Background: Aim of the present study is to investigate whether preoperative neurocognitive status is prognostically associated with overall survival (OS) in newly diagnosed glioblastoma (GBM) patients. Methods: Ninety patients with dominant-hemisphere IDH-wild-type GBM were assessed by Mini Mental Status Exam (MMSE), Trail Making Test (TMT) A and B parts, and Control Word Association Test (COWAT) phonemic and semantic subtests. Demographics, Karnofsky Performance Scale, tumor parameters, type of surgery, and adjuvant therapy data were available for patients. Results: According to Cox proportional hazards model the neurocognitive variables of TMT B (P < .01), COWAT semantic subset (P < .05), and the MMSE (P < .01) were found significantly associated with survival prediction. From all other factors, only tumor volume and operation type (debulking vs biopsy) showed a statistical association (P < .05) with survival prediction. Kaplan Meier Long rank test showed statistical significance (P < .01) between unimpaired and impaired groups for TMT B, with median survival for the unimpaired group 26 months and 10 months for the impaired group, for COWAT semantic (P < .01) with median survival 23 months and 12 months, respectively and for MMSE (P < .01) with medial survival 19 and 12 months respectively. Conclusions: Our study demonstrates that neurocognitive status at baseline-prior to treatment-is an independent prognostic factor for OS in wild-type GBM patients, adding another prognostic tool to assist physicians in selecting the best treatment plan.

An Applied Anatomic Guide to Anterior Temporal Lobectomy and Amygdalohippocampectomy: Laboratory Cranial and White Matter Dissections to Inform Surgical Practice.

BACKGROUND AND OBJECTIVES: Anterior temporal lobectomy and amygdalohippocampectomy is a challenging procedure because of the deep surgical trajectory and complex regional neurovascular anatomy. A thorough knowledge of the involved anatomic structures is crucial for a safe and effective procedure. Our objective is to explore the white matter pathways in or around the operative corridor and to illuminate the 3-dimensional relationships of the pertinent operative parenchymal and skull base anatomy, aiming to inform and simplify surgical practice. METHODS: Four normal, adult, cadaveric, formalin-fixed cerebral hemispheres (2 left and 2 right) treated with the Klinger's technique and 2 formalin-fixed and colored-latex-injected cadaveric heads (4 sides) were used. Focused white matter and cadaveric dissections were used to study the relevant anatomy implicated during an anterior temporal lobectomy. Four illustrative cases were also included. Digital photographs from every dissection step were obtained. RESULTS: Major white matter pathways that are inevitably traversed during the approach are the inferior longitudinal fasciculus, uncinate fasciculus, and inferior arm of the cingulum. Tracts that can be potentially injured, should the dissection plane tilt inadvertently superiorly or posteriorly, are the inferior fronto-occipital fasciculus, Meyer's loop, superior longitudinal fasciculus/arcuate fasciculus complex, and basal ganglia. Consistent cranial and parenchymal landmarks that can act as a roadmap during the procedure are recorded and paired with their intraoperative equivalent to provide a thorough, yet simple, stepwise guide for the surgeon. CONCLUSION: White matter dissections, cadaveric cranial dissections, and intraoperative images are put together to provide a simplified stepwise surgical manual for anterior temporal lobectomy. Laboratory investigations that focus on the intricate 3-dimensional relationships of the pertinent operative anatomy from the surgeon's eye may enrich anatomic knowledge and push surgical boundaries, to minimize complication rates and ultimately improve patient outcomes.

Advances on Liquid Biopsy Analysis for Glioma Diagnosis.

Gliomas comprise the most frequent primary central nervous system (CNS) tumors, characterized by remarkable genetic and epigenetic heterogeneity, difficulty in monitoring, and increased relapse and mortality rates. Tissue biopsy is an established method of tumor cell collection and analysis that enables diagnosis, classification of different tumor types, and prediction of prognosis upon confirmation of tumor's location for surgical removal. However, it is an invasive and often challenging procedure that cannot be used for frequent patient screening, detection of mutations, disease monitoring, or resistance to therapy. To this end, the minimally invasive procedure of liquid biopsy has emerged, allowing effortless tumor sampling and enabling continuous monitoring. It is considered a novel preferable way to obtain faster data on potential tumor risk, personalized diagnosis, prognosis, and recurrence evaluation. The purpose of this review is to describe the advances on liquid biopsy for glioma diagnosis and management, indicating several biomarkers that can be utilized to analyze tumor characteristics, such as cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating proteins, circulating tumor cells (CTCs), and exosomes. It further addresses the benefit of combining liquid biopsy with radiogenomics to facilitate early and accurate diagnoses, enable precise prognostic assessments, and facilitate real-time disease monitoring, aiming towards more optimal treatment decisions.

Biofluid Biomarkers in the Prognosis of Chronic Subdural Hematoma: A Systematic Scoping Review.

The present systematic scoping review aimed at mapping and analyzing the available literature on biological fluid (biofluid) biomarkers showing promise in the prediction of chronic subdural hematoma (cSDH) recurrence and the prognosis of neurological/functional patient outcome. Twenty-three studies published between 2003 and 2023 investigating a diverse range of biomarkers in hematoma fluid and/or the circulation in 3749 patients were included. Immune cell populations and inflammatory/anti-inflammatory cytokines comprised the most studied category of biomarkers displaying significant findings. A notable time trend in biomarker studies was a recent shift in research focus towards the analysis of circulating biomarkers. Several biomarkers were indicated as independent predictors of cSDH recurrence and/or functional/neurological outcome, including circulating fibrinogen degradation products (FDP), brain natriuretic peptide (BNP-1) and high-density lipoprotein (HDL), as well as blood urea nitrogen (BUN) and the ratios of blood neutrophil to lymphocyte (NLR) or red blood cell distribution width to platelet count (RPR). While studies on cSDH prognostic biomarkers have gained, in recent years, momentum, additional multicenter prospective studies are warranted to confirm and extend their findings. The identification of prognostic biofluid biomarkers in cSDH is an active field of research that may provide future tools, guiding clinical decisions and allowing for the design of treatments based on risk stratification.

Medial Pulvinar Stimulation in Temporal Lobe Epilepsy: A Literature Review and a Hypothesis Based on Neuroanatomical Findings.

While bilateral stimulation of the anterior thalamic nuclei remains the only approved deep brain stimulation (DBS) option for focal epilepsy, two additional thalamic targets have been proposed. Earlier work indicated the potential of centromedian thalamic nucleus stimulation with recent findings highlighting the medial pulvinar nucleus. The latter has been shown to exhibit electrophysiological and imaging alterations in patients with partial status epilepticus and temporal lobe epilepsy. On this basis, recent studies have begun assessing the feasibility and efficacy of pulvinar stimulation, with encouraging results on the reduction of seizure frequency and severity. Building on existing neuroanatomical knowledge, indicating that the medial pulvinar is connected to the temporal lobe via the temporopulvinar bundle of Arnold, we hypothesize that this is one of the routes through which medial pulvinar stimulation affects temporal lobe structures. We suggest that further anatomic, imaging, and electrophysiologic studies are warranted to deepen our understanding of the subject and guide future clinical applications.

The effectiveness of mental imagery on motor, cognitive and emotional status of older people with early-stage dementia: A study protocol.

Dementia involves the loss of cognitive abilities and represents a decline from the prior level of function which impairs functional abilities in day-to-day life. No previous experimental research has been done to assess mental imagery (MI) effectiveness in the motor, cognitive and emotional status of individuals with early-stage dementia. One hundred and forty older individuals with early-stage dementia from the Day Care Centre of the Alzheimer Association in Athens will take part in this study. The sample will be randomly divided into three groups: MI and physical exercise (intervention group), only physical exercise (1st control group), and neither MI nor physical exercise (2nd control group). Assessment will be obtained one week prior to the program, in the middle of the program (6th week of the intervention program) and after the end of the program (13th week of the intervention program). Participants of the intervention group will perform a 30-minute MI programme after the end of every physiotherapy session. Reliable and valid instruments will be used to assess the primary outcomes, i.e., balance and functional status as well as the secondary outcomes i.e., cognitive ability, emotional state and quality of life. The two-way Mixed ANOVA with factors 'intervention' (between groups) and 'time' (within group) will be used as a statistical analysis. Approvals of clinical trial protocol: a) UNIWA Research Committee study protocol approval: 93292 - 26/10/2021. b) ClinicalTrials.gov: ID NCT05232526.

Association between preoperative neurocognitive status and IDH1 mutation status in high-grade gliomas.

Background: High-grade glioma (HGG) patients present with variable impairment in neurocognitive function (NCF). Based on that, isocitrate dehydrogenase 1 (IDH1) wild-type HGGs are more aggressive than IDH1 mutant-type ones, we hypothesized that patients with IDH1 wild-type HGG would exhibit more severe NCF deficits than their IDH1 mutant counterparts. Methods: NCF was assessed by Mini Mental Status Exam (MMSE), Trail Making Test (TMT), Digit Span (DS), and Controlled Word Association Test (COWAT) tests in 147 HGG patients preoperatively. Results: Analyses between IDH1 groups revealed a significant difference on MMSE concentration component (p ≤ .01), DS (p ≤ .01), TMTB (p ≤ .01), and COWAT (p ≤ .01) scores, with the IDH1 wild group performing worse than the IDH1 mutant one. Age and tumor volume were inversely correlated with MMSE concentration component (r = -4.78, p < .01), and with MMSE concentration (r = -.401, p < .01), TMTB (r = -.328, p < .01), and COWAT phonemic scores (r = -.599, p < .01), respectively, but only for the IDH1 wild-type group. Analyses between age-matched subsamples of IDH1 groups revealed no age effect on NCF. Tumor grade showed nonsignificance on NCF (p > .05) between the 2 IDH1 mutation subgroups of grade IV tumor patients. On the contrary, grade III group showed a significant difference in TMTB (p < .01) and DS backwards (p < .01) between IDH1 subgroups, with the mutant one outperforming the IDH1 wild one. Conclusions: Our findings indicate that IDH1 wild-type HGG patients present greater NCF impairment, in executive functions particularly, compared to IDH1 mutant ones, suggesting that tumor growth kinetics may play a more profound role than other tumor and demographic parameters in clinical NCF of HGG patients.

Autotaxin Activity in Chronic Subdural Hematoma: A Prospective Clinical Study.

Autotaxin (ATX) is the ectoenzyme producing the bulk of lysophosphatidic acid (LPA) in circulation. ATX and LPA-mediated signaling (the ATX-LPA axis) play critical roles in the vascular and nervous system development. In adults, this axis contributes to diverse processes, including coagulation, inflammation, fibroproliferation and angiogenesis under physiological and/or pathophysiological conditions. Given evidence implicating several of these processes in chronic subdural hematoma (CSDH) pathogenesis and development, we assessed ATX activity in CSDH patients. Twenty-eight patients were recruited. Blood and hematoma fluid were collected. Enzymatic assays were used to establish serum and hematoma ATX activity. Enzyme-linked immunosorbent assays were used to establish hematoma beta trace (BT) levels, a cerebrospinal fluid (CSF) marker, in a hematoma. ATX activity was nearly three folds higher in hematoma compared to serum (P < 0.001). There was no significant correlation between BT levels and ATX activity in a hematoma. The present results show, for the first time, that ATX is catalytically active in the hematoma fluid of CSDH patients. Moreover, our findings of significantly elevated ATX activity in hematoma compared to serum, implicate the ATX-LPA axis in CSDH pathophysiology. The CSF origin of ATX could not be inferred with the present results. Additional research is warranted to establish the significance of the ATX-LPA axis in CSDH and its potential as a biomarker and/or therapeutic target.