Chronic subdural hematoma
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
Chronic subdural hematoma (CSDH) is an encapsulated collection of old blood, mostly or totally liquefied and located between the dura mater and the arachnoid mater.
They are arbitrarily defined as those hematomas presenting 21 days or more after injury. These numbers are not absolute, and a more accurate classification of a subdural hematoma usually is based on imaging characteristics.
COVID-19 in chronic subdural hematoma
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cSDHs have a tendency to persist and gradually increase in volume over time. The disease is thought to be related to a cycle of chronic inflammation and angiogenesis. An original hemorrhage forms and fibrinolysis ensues with the liquefaction of the initial clot. The subsequent blood breakdown products stimulate inflammation and thickening of the inner dural layer (ie, ‘dural border cells). This process incites angiogenesis with the ingrowth of immature capillaries, which chronically leak blood. These microhemorrhages result in the progressive enlargement of the collection with increased fibrinolytic activity, inflammation, and further angiogenesis, membrane formation, and vessel proliferation. The rate of accumulation of blood products outpaces physiological reabsorption and the collection gradually enlarges. Thus the entire basis for the pathology is the formation of leaky vascular membranes, which incite a positive feedback cycle of continued hemorrhage, inflammation, and angiogenesis 1) 2)
Chronic subdural hematoma (CSDH) is characterized by an “old” encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura).
It is delimited by an outer and inner membrane. In between are blood, plasma, cerebrospinal fluid, membranes, and a mixture of inflammatory angiogenic fibrinolytic and coagulation factors. These factors maintain a self-perpetuating cycle of bleeding, lysis, and growing of neo-membranes and neo-capillaries 3).
The association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods.
Pripp et al. explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data, but lasso regression revealed an association with inflammatory and angiogenic biomarkers in hematoma fluid. They suggest that lasso regression should be a recommended statistical method in research on biological processes in CSDH patients 4).
Chronic subdural hematoma (CSDH) is a disease of the meninges and is to be distinguished from hygroma and subdural empyema.
Subdural effusion in the setting of dural metastases is very rare and may be difficult to be distinguished from chronic subdural hematoma. Such lesions could be missed and could be the cause of recurrence in CSDH. A contrast-enhanced brain CT scan is recommended to diagnose dural metastases.
Rosai–Dorfman disease may be mistaken for a CSDH on imaging. This disease is an uncommon, benign systemic histioproliferative disease characterized by massive lymphadenopathy, particularly in the head and neck region, and is often associated with extranodal involvement. CSDH can also develop in multifocal fibrosclerosis (MFS) which is a rare disorder of unknown etiology, characterized by chronic inflammation with dense fibrosis and lymphoplasmacytic infiltration into the connective tissue of various organs. The mechanism of the formation of CSDH is presumed to involve reactive granular membrane together with subdural collection. On the other hand, the extramedullary erythropoiesis within CSDH can be confused with metastatic malignant tumors, such as lymphoma, carcinoma, and malignant melanoma 5).
A 44-year old woman with gastric adenocarcinoma was presented with headache and a hypodense subdural collection in right fronto-parietal in brain CT. Burr-hole irrigation was performed with the impression of chronic subdural hematoma, but nonhemorrhagic xantochromic fluid was evacuated without malignant cell. Brain CT on the 11th day depicted fluid re-accumulation and noticeable midline shift, necessitating craniotomy and removing the affected dura.
Because the affected dura can be supposed as the main source of subdural effusion, resection of the involved dura is obligatory for the appropriate palliative management of such patients 6).
The progression of CSDH is an angiogenic process, involving inflammatory mediators that affect vascular permeability, microvascular leakage, and hematoma thickness.
A bibliometrics retrieved 1424 CSDH-related articles published since the beginning of the twenty-first century. There was a general increase in both the number of published articles and the mean number of citations. The authors, institutions, and journals that contributed the most to the field of CSDH were Jianning Zhang, Tianjin Medical University General Hospital, and world neurosurgery, respectively. The reference co-citation network identified 13 clusters with significant modularity Q scores and silhouette scores (Q = 0.7124, S = 0.8536). The major research categories were (1) the evolution of the therapeutic method and (2) the etiology and pathology of CSDH. Keyword analysis revealed that ‘middle meningeal artery embolization‘ was the latest burst keyword.
This study identified the most influential countries, authors, institutions, and journals contributing to CSDH research and discussed the hotspots and the latest subjects of CSDH research 7)
Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description.
D’Abbondanza et al. did not find a report of a reproducible, well-described animal model of human CSDH 8).
Zhuang Y, Jiang M, Zhou J, Liu J, Fang Z, Chen Z. Surgical Treatment of Bilateral Chronic Subdural Hematoma. Comput Intell Neurosci. 2022 Jun 27;2022:2823314. doi: 10.1155/2022/2823314. Retraction in: Comput Intell Neurosci. 2022 Dec 25;2022:9806807. PMID: 35795746; PMCID: PMC9252673.