Chronic Subdural Hematoma

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 20882

Special Issue Editors


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Guest Editor
Department of Neurosurgery, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece
Interests: neuro-oncology and skullbase; hydrocephalus; neurocritical care; neurotrauma; haemorrhagic stroke; neurosurgical anatomy; neuroepidemiology

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Guest Editor
Department of Neurosurgery, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece
Interests: neurological disease biomarkers (CNS tumors, hydrocephalus, chronic subdural hematoma, traumatic brain injury); neuroprotection and functional recovery following brain injury; circadian rhythms and sleep disorders; neuroepidemiology (stroke, CNS tumors, epilepsy, traumatic brain injury)
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Special Issue Information

Dear Colleagues,

The incidence of chronic subdural hematoma (CSDH), the common neurosurgical disorder typically associated with old age, is on the rise. While surgical evacuation remains the standard of care for symptomatic CSDH, additional treatment options such as embolization and adjuvant or stand-alone pharmacotherapies are under investigation. 

Previous preclinical and clinical research on CSDH has provided valuable insights into putative mechanisms of pathogenesis and progression, including cerebrospinal fluid leaks, neomembrane formation, inflammatory angiogenesis, as well as abnormal coagulation and fibrinolysis. This research has indicated therapeutic targets and highlighted potential imaging and molecular biomarkers of CSDH recurrence; the latter is a significant and not uncommon outcome consideration in these patients. Nevertheless, a theranostic or prognostic biomarker has yet to find its way into clinical practice.

The overarching goal of this Special Issue entitled “Chronic Subdural Hematoma” is to collect knowledge and provide further insights into several pertinent nosological aspects of CSDH, including but not limited to:

  1. Epidemiology, risk factors, and patient outcomes;
  2. Molecular and imaging biomarkers;
  3. Surgical therapy;
  4. Pharmacotherapy.

Original preclinical and clinical studies, theoretical research, and reviews on this topic will be considered.

Prof. Dr. George Stranjalis
Dr. Theodosis Kalamatianos
Guest Editors

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Keywords

  • chronic subdural hematoma
  • surgery
  • drug
  • trial
  • biomarker
  • theranostics
  • prognosis
  • risk factor
  • imaging
  • therapy
  • outcome

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Published Papers (7 papers)

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Research

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12 pages, 2597 KiB  
Article
Immunometabolic Profiling of Chronic Subdural Hematoma through Untargeted Mass Spectrometry Analysis: Preliminary Findings of a Novel Approach
by Maria Kipele, Michael Buchfelder, R. Verena Taudte, Andreas Stadlbauer, Thomas Kinfe and Yavor Bozhkov
Diagnostics 2023, 13(21), 3345; https://doi.org/10.3390/diagnostics13213345 - 30 Oct 2023
Viewed by 1494
Abstract
Objective: Metabolomics has growing importance in the research of inflammatory processes. Chronic subdural hematoma (cSDH) is considered to be, at least in part, of inflammatory nature, but no metabolic analyses yet exist. Therefore, a mass spectrometry untargeted metabolic analysis was performed on [...] Read more.
Objective: Metabolomics has growing importance in the research of inflammatory processes. Chronic subdural hematoma (cSDH) is considered to be, at least in part, of inflammatory nature, but no metabolic analyses yet exist. Therefore, a mass spectrometry untargeted metabolic analysis was performed on hematoma samples from patients with cSDH. Methods: A prospective analytical cross-sectional study on the efficacy of subperiosteal drains in cSDH was performed. Newly diagnosed patients had the option of granting permission for the collection of a hematoma sample upon its removal. The samples were analyzed using liquid chromatography–mass spectrometry to obtain different types of metabolites from diverse biochemical classes. The statistical analysis included data cleaning, imputation, and log transformation, followed by PCA, PLS-DA, HCA, and ANOVA. The postoperative course of the disease was followed for 3 months. The metabolite concentrations in the hematoma fluid were compared based on whether a recurrence of the disease was recorded within this time frame. Results: Fifty-nine samples from patients who were operated on because of a cSDH were gathered. Among those, 8 samples were eliminated because of missing metabolites, and only 51 samples were analyzed further. Additionally, 39 samples were from patients who showed no recurrence over the course of a 3-month follow-up, and 12 samples were from a group with later recurrence. We recorded a noticeable drop (35%) in the concentration of acylcarnitines in the ”recurrence group“, where 10 of the 22 tested metabolites showed a significant reduction (p < 0.05). Furthermore, a noticeable reduction in different Acyl-CoA-dehydrogenases was detected (VLCAD-deficiency p < 0.05, MCAD-deficiency p = 0.07). No further changes were detected between both populations. Conclusions: The current study presents a new approach to the research of cSDH. The measurements presented us with new data, which, to date, are without any reference values. Therefore, it is difficult to interpret the information, and our conclusions should be considered to be only speculative. The results do, however, point in the direction of impaired fatty acid oxidation for cases with later recurrence. As fatty acid oxidation plays an important role in inflammatory energy metabolism, the results suggest that inflammatory processes could be aggravated in cases with recurrence. Because our findings are neither proven through further analyses nor offer an obvious therapy option, their implications would not change everyday practice in the management of cSDH. They do, however, present a further possibility of research that might, in the future, be relevant to the therapy. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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13 pages, 1054 KiB  
Article
The Role of Active or Passive Drainage after Evacuation of Chronic Subdural Hematoma: An Analysis of Two Randomized Controlled Trials (cSDH-Drain-Trial and TOSCAN Trial)
by Florian Ebel, Ladina Greuter, Katharina Lutz, Levin Häni, Javier Fandino, Raphael Guzman, Luigi Mariani, Jürgen Beck, Andreas Raabe, Werner J. Z’Graggen, Philippe Schucht and Jehuda Soleman
Diagnostics 2022, 12(12), 3045; https://doi.org/10.3390/diagnostics12123045 - 5 Dec 2022
Cited by 3 | Viewed by 1686
Abstract
The evacuation of a chronic subdural hematoma (cSDH) is one of the most common procedures in neurosurgery. The aim of this study was to assess the influence of drainage suction in the surgical treatment of cSDH on the recurrence rate. Post hoc analysis [...] Read more.
The evacuation of a chronic subdural hematoma (cSDH) is one of the most common procedures in neurosurgery. The aim of this study was to assess the influence of drainage suction in the surgical treatment of cSDH on the recurrence rate. Post hoc analysis was conducted on two randomized controlled trials (cSDH-Drain-Trial and TOSCAN trial) stratifying a total of 581 patients into active or passive drain type. Of the 581 patients, 359 (61.8%) and 220 (37.9%) were stratified into the active and passive drainage groups, respectively. The reoperation rate following postoperative recurrence was 23.1% and 14.1% in the active and passive drainage groups, respectively (p < 0.011). After propensity score matching, the differences in recurrence rate remained significant (26.6% versus 15.6%, p = 0.012). However, the functional outcome (mRS) at 6–12 months did not differ significantly (median [IQR]) between the 2 groups (passive drainage group 0.00 [0.00, 2.00], active drainage group 1.00 [0.00, 2.00], p = 0.431). Mortality was comparable between the groups (passive drainage group 12 (5.5%), active drainage group 20 (5.6%), p = 0.968). In the univariate analysis, active drainage, short (<48 h) duration of drainage, and early (<48 h) postoperative mobilization were significantly associated with a higher recurrence rate. However, the multivariate logistic regression model could not confirm that any of these parameters were significantly associated with recurrence. Our post hoc analysis proposes that using a passive instead of an active drain might be associated with a reduced recurrence rate after evacuation of a cSDH. We suggest gathering further evidence by means of a randomized controlled trial. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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10 pages, 1148 KiB  
Article
Investigation of Neutrophil Extracellular Traps as Potential Mediators in the Pathogenesis of Non-Acute Subdural Hematomas: A Pilot Study
by Michael T. Bounajem, Frederik Denorme, John L. Rustad, Robert A. Campbell and Ramesh Grandhi
Diagnostics 2022, 12(12), 2934; https://doi.org/10.3390/diagnostics12122934 - 24 Nov 2022
Viewed by 1400
Abstract
Non-acute subdural hematomas (NASHs) are a cause of significant morbidity and mortality, particularly with recurrences. Although recurrence is believed to involve a disordered neuroinflammatory cascade involving vascular endothelial growth factor (VEGF), this pathway has yet to be completely elucidated. Neutrophil extracellular traps (NETs) [...] Read more.
Non-acute subdural hematomas (NASHs) are a cause of significant morbidity and mortality, particularly with recurrences. Although recurrence is believed to involve a disordered neuroinflammatory cascade involving vascular endothelial growth factor (VEGF), this pathway has yet to be completely elucidated. Neutrophil extracellular traps (NETs) are key factors that promote inflammation/apoptosis and can be induced by VEGF. We investigated whether NETs are present in NASH membranes, quantified NET concentrations, and examined whether NET and VEGF levels are correlated in NASHs. Samples from patients undergoing NASH evacuation were collected during surgery and postoperatively at 24 and 48 h. Fluid samples and NASH membranes were analyzed for levels of VEGF, NETs, and platelet activation. NASH samples contained numerous neutrophils positive for NET formation. Myeloperoxidase-DNA complexes (a marker of NETs) remained elevated 48 h postoperatively (1.06 ± 0.22 day 0, 0.72 ± 0.23 day 1, and 0.83 ± 0.33 day 2). VEGF was also elevated in NASHs (7.08 ± 0.98 ng/mL day 0, 3.40 ± 0.68 ng/mL day 1, and 6.05 ± 1.8 ng/mL day 2). VEGF levels were significantly correlated with myeloperoxidase-DNA levels. These results show that NETs are increasing in NASH, a finding that was previously unknown. The strong correlation between NET and VEGF levels indicates that VEGF may be an important mediator of NET-related inflammation in NASH. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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12 pages, 1790 KiB  
Article
Homogeneous Chronic Subdural Hematoma with Diverse Recurrent Possibilities
by Woon-Man Kung, Yao-Chin Wang, Wei-Jung Chen and Muh-Shi Lin
Diagnostics 2022, 12(11), 2695; https://doi.org/10.3390/diagnostics12112695 - 4 Nov 2022
Viewed by 3354
Abstract
Background: Evidence suggests that hyperdense (HD) chronic subdural hematomas (CSDHs) have a higher recurrence than hypodense (LD) chronic subdural hematomas. The value of mean hematoma density (MHD) has been proven to be associated with postoperative recurrence. The MHD levels in homogeneous CSDHs likely [...] Read more.
Background: Evidence suggests that hyperdense (HD) chronic subdural hematomas (CSDHs) have a higher recurrence than hypodense (LD) chronic subdural hematomas. The value of mean hematoma density (MHD) has been proven to be associated with postoperative recurrence. The MHD levels in homogeneous CSDHs likely underestimate the risk of recurrence in HD homogeneous subtypes. Methods: This study investigated 42 consecutive CSDH cases between July 2010 and July 2014. The area of the hematoma was quantified to determine the MHD level using computer-based image analysis of preoperative brain CT scans. Results: In terms of the MHD distribution of the four types of CSDHs (homogeneous, laminar, separated, and trabecular), wide 95% CI (11.80–16.88) and high standard deviation (4.59) can be found in homogeneous types, reflecting a high variability in the MHD levels between cases (from low to high density). The categorization of homogeneous types into LD and HD (type five) displayed a minor standard deviation in the MHD levels for LD and HD subtypes (1.15, and 0.88, respectively). MHD values demonstrated concentrated distributions among the respective five types, compared to the four-type setting. Conclusions: In the current research, we provide a consideration that if LD and HD hematomas are separated from homogeneous CSDHs, the variability of the MHD quantification can potentially be reduced, thereby avoiding the possibility of undetected high-risk groups. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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Review

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13 pages, 1118 KiB  
Review
Subdural Lesions Linking Additional Intracranial Spaces and Chronic Subdural Hematomas: A Narrative Review with Mutual Correlation and Possible Mechanisms behind High Recurrence
by Muh-Shi Lin
Diagnostics 2023, 13(2), 235; https://doi.org/10.3390/diagnostics13020235 - 8 Jan 2023
Cited by 10 | Viewed by 2472
Abstract
The purpose of this study was two-fold. The first was to investigate the pathologic mechanisms underlying the formation of subdural fluid collection, an umbrella term referring to a condition commonly seen in the clinical setting. Accumulation of the cerebrospinal fluid (CSF) in the [...] Read more.
The purpose of this study was two-fold. The first was to investigate the pathologic mechanisms underlying the formation of subdural fluid collection, an umbrella term referring to a condition commonly seen in the clinical setting. Accumulation of the cerebrospinal fluid (CSF) in the subdural space can be referred to in this disease category, disregarding the underlying source of the subdural fluid. However, in these two clinical situations, especially after trauma or brain surgery, fluid collection from the subarachnoid space (subdural hygroma) or from the ventricle to the subarachnoid space and infusion into the subdural space (external hydrocephalus), surgical management of critical patients may adopt the strategies of burr-hole, subduroperitoneal shunt, or ventriculoperitoneal shunt, which present distinctly different thoughts. Crucially, the former can be further transformed into chronic subdural hematoma (CSDH). The second significant theme was the pathogenesis of CSDH. Once the potential dural border cell (DBC) layer is separated such as if a wound is formed, the physiological mechanisms that seem to promote wound healing will resume in the subdural space as follows: coagulation, inflammation, fibroblast proliferation, neovascularization, and fibrinolysis. These aptly correspond to several key characteristics of CSDH formation such as the presence of both coagulation and fibrinolysis signals within the clot, neomembrane formation, angiogenesis, and recurrent bleeding, which contribute to CSDH failing to coagulate and absorb easily. Such a complexity of genesis and the possibility of arising from multiple pathological patterns provide a reasonable explanation for the high recurrence rate, even after surgery. Among the various complex and clinically challenging subdural lesions, namely, CSDH (confined to the subdural space alone), subdural hygroma (linked in two spaces), and external hydrocephalus (linked in three spaces), the ability to fully understand the different pathological mechanisms of each, differentiate them clinically, and devote more interventional strategies (including anti-inflammatory, anti-angiogenic, and anti-fibrinolysis) will be important themes in the future. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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Other

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23 pages, 1018 KiB  
Systematic Review
Controversies in the Surgical Treatment of Chronic Subdural Hematoma: A Systematic Scoping Review
by Mary Solou, Ioannis Ydreos, Maria Gavra, Evangelos K. Papadopoulos, Stamatis Banos, Efstathios J. Boviatsis, Georgios Savvanis and Lampis C. Stavrinou
Diagnostics 2022, 12(9), 2060; https://doi.org/10.3390/diagnostics12092060 - 25 Aug 2022
Cited by 20 | Viewed by 6458
Abstract
Chronic subdural hematoma (cSDH) is one of the most common neurosurgical entities, especially in the elderly population. Diagnosis is usually established via a head computed tomography, while an increasing number of studies are investigating biomarkers to predict the natural history of cSDH, including [...] Read more.
Chronic subdural hematoma (cSDH) is one of the most common neurosurgical entities, especially in the elderly population. Diagnosis is usually established via a head computed tomography, while an increasing number of studies are investigating biomarkers to predict the natural history of cSDH, including progression and recurrence. Surgical evacuation remains the mainstay of treatment in the overwhelming majority of cases. Nevertheless, many controversies are associated with the nuances of surgical treatment. We performed a systematic review of the literature between 2010 and 2022, aiming to identify and address the issues in cSDH surgical management where consensus is lacking. The results show ambiguous data in regard to indication, the timing and type of surgery, the duration of drainage, concomitant membranectomy and the need for embolization of the middle meningeal artery. Other aspects of surgical treatment—such as the use of drainage and its location and number of burr holes—seem to have been adequately clarified: the drainage of hematoma is strongly recommended and the outcome is considered as independent of drainage location or the number of burr holes. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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8 pages, 408 KiB  
Brief Report
Autotaxin Activity in Chronic Subdural Hematoma: A Prospective Clinical Study
by Theodosis Kalamatianos, Evangelos Drosos, Christiana Magkrioti, Ioanna Nikitopoulou, Christos Koutsarnakis, Anastasia Kotanidou, George P. Paraskevas, Vassilis Aidinis and George Stranjalis
Diagnostics 2022, 12(8), 1865; https://doi.org/10.3390/diagnostics12081865 - 2 Aug 2022
Viewed by 1751
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Subdural Hematoma)
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