Paradigms in chronic subdural hematoma pathophysiology: Current treatments and new directions.

ABSTRACT: Chronic subdural hematomas (CSDHs) are an increasingly common pathology encountered in a neurosurgical trauma practice. Although the operative and nonoperative management of CSDH has been studied extensively, the recurrence rate of CSDH remains high, with no significant decrease in recent years. We undertook a detailed assessment of the known pathophysiological mechanisms by which CSDHs recur to improve our ability to treat patients with this disease successfully. In this review of the literature from the PubMed and Scopus databases, we used the search terms "(pathophysiology) AND chronic subdural hematoma [tiab]" to identify pertinent reviews and articles in English. The results demonstrated a complex inflammatory response to subdural blood, which begins with the formation of a collagen neomembrane around the clot itself. Proinflammatory mediators, such as vascular endothelial growth factor, interleukin-6, interleukin-8, tissue necrosis factor α, matrix metalloproteinases, and basic fibroblast growth factor, then contribute to chronic microbleeding by promoting the formation of fragile, leaky blood vessels, and widening of gap junctions of existing vessels. It is evident that the lack of improvement in recurrence rate is due to pathological factors that are not entirely alleviated by simple subdural evacuation. Targeted approaches, such as middle meningeal artery embolization and anti-inflammatory therapies, have become increasingly common and require further prospective analysis to aid in the determination of their efficacy.

DynaCT Enhancement of Subdural Membranes After Middle Meningeal Artery Embolization: Insights into Pathophysiology.

OBJECTIVE: Middle meningeal artery (MMA) embolization could be an effective method of inhibiting neovascularization of the subdural capsular membrane and preventing hematoma maintenance. We sought to better understand how the MMA might affect subdural hematoma physiology and how this process might be modified by embolization. METHODS: We performed a retrospective review of 27 patients with 29 subdural hematomas (SDHs) who had undergone MMA embolization from July 2018 to May 2019. Of the 27 patients, 8 had undergone postembolization DynaCT imaging studies and were included in the present study. RESULTS: The average patient age was 75 years. The baseline noncontrast-enhanced cranial computed tomography (CT) scans showed the presence of a hematoma membrane in all 8 patients. The postembolization DynaCT scans of all patients demonstrated enhancement of all 4 components (i.e., dura, capsular membrane, septations, and subdural hematoma fluid). All patients had a minimum of 60-day imaging and clinical follow-up data available. The average decrease in SDH volume at the last follow-up examination was 87% compared with that at baseline. A significant difference was found between the average baseline and average last follow-up SDH volume (P < 0.0001, paired t test) in all 8 patients. The average interval from the date of the procedure to the last follow-up scan was 89 days (range, 61-122 days). No patient experienced postembolization complications, subsequent SDH drainage, or mortality. CONCLUSIONS: Our data lend support to the theory of contiguous vascular networks between the MMA and SDH membranes. Targeting these leaky vascular networks might remove the source of hematoma accumulation. These data add to the pathophysiological understanding of the disease and suggests potential insights into the mechanism of action of MMA embolization.

CT-Based Quantitative Analysis for Pathological Features Associated With Postoperative Recurrence and Potential Application Upon Artificial Intelligence: A Narrative Review With a Focus on Chronic Subdural Hematomas.

Chronic subdural hematomas (CSDHs) frequently affect the elderly population. The postoperative recurrence rate of CSDHs is high, ranging from 3% to 20%. Both qualitative and quantitative analyses have been explored to investigate the mechanisms underlying postoperative recurrence. We surveyed the pathophysiology of CSDHs and analyzed the relative factors influencing postoperative recurrence. Here, we summarize various qualitative methods documented in the literature and present our unique computer-assisted quantitative method, published previously, to assess postoperative recurrence. Imaging features of CSDHs, based on qualitative analysis related to postoperative high recurrence rate, such as abundant vascularity, neomembrane formation, and patent subdural space, could be clearly observed using the proposed quantitative analysis methods in terms of mean hematoma density, brain re-expansion rate, hematoma volume, average distance of subdural space, and brain shifting. Finally, artificial intelligence (AI) device types and applications in current health care are briefly outlined. We conclude that the potential applications of AI techniques can be integrated to the proposed quantitative analysis method to accomplish speedy execution and accurate prediction for postoperative outcomes in the management of CSDHs.

Is there an interest in performing a systematic CT scan within the first two months after chronic subdural hematoma evacuation? A ten-year single-center retrospective study.

OBJECTIVES: The aims of the present study were to evaluate the frequency of late recurrence after chronic subdural hematoma (CSDH) evacuation and to examine the interest in the use of a systematic CT scan within the first two months after surgery. PATIENTS AND METHODS: We performed a retrospective study that included all patients who underwent CSDH evacuation between 2007 and 2017. We evaluated the rate of late recurrence, defined as the need to perform a new surgery after the first month of follow-up. All the patients underwent a clinical examination and a systematic CT scan between one and 2 months after the first surgery (delayed systematic CT scan). We evaluated the rate of clinical recurrence, defined as the association between clinical symptoms and radiological abnormalities, and of radiological recurrence, defined only on CT scan data. RESULTS: During the inclusion period, 696 patients underwent CSDH evacuation in our unit. Overall, 54 patients (7.7%) had recurrence, of whom 21 (39%) had recurrence after 4 weeks (late recurrence). Of the 21 patients with late recurrence, 7 (1%) had radiological recurrence, and 14 (2%) had clinical recurrence. There was no difference in the CT scan characteristics between patients with clinical and radiological recurrence. CONCLUSION: The use of a delayed systematic CT scan after CSDH surgery has a marginal impact on patient management, and the indication for reoperation without symptoms seems highly subjective. In patients without neurological symptoms, the use of a delayed cerebral CT scan may not be indicated.

Statistical analysis plan for the Dex-CSDH trial: a randomised, double-blind, placebo-controlled trial of a 2-week course of dexamethasone for adult patients with a symptomatic chronic subdural haematoma.

BACKGROUND: The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the 6-month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate. METHODS AND DESIGN: Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0-3) versus unfavourable (a score of 4-6). CONCLUSIONS: This paper and the accompanying additional material describe the statistical analysis plan for the trial. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015.

Kernohan-Woltman Notch Phenomenon ­ Case Report

The Kernohan-Woltman notch phenomenon is a paradoxical neurological manifestation consisting of a motor deficit ipsilateral to a primary brain injury. It has been observed in patients with brain tumors and with supratentorial hematomas. It is considered a false localizing neurological sign. Magnetic resonance imaging (MRI) scan has been the test of choice. The recognition of this phenomenon is important to prevent a surgical procedure on the opposite side of the lesion. The present case report describes a case of chronic subdural hematoma with a probable finding of the Kernohan-Woltman phenomenon, and it discusses its pathophysiology, imaging findings, treatment, and prognosis.

Subdural Tension on the Brain in Patients with Chronic Subdural Hematoma Is Related to Hemiparesis but Not to Headache or Recurrence.

BACKGROUND: Hemiparesis is a major symptom of chronic subdural hematoma (CSDH). Its severity does not always correlate with hematoma size. The authors analyzed hematoma thickness, pressure, and tension to clarify the mechanism of hemiparesis in CSDH patients. METHODS: A burr-hole surgery was performed on 124 CSDHs in 102 patients. Hematoma thickness and midline shift were measured by computed tomography, and hematoma pressure was measured in surgery. According to Laplace law, tension was calculated as follows: (half the hematoma thickness × hematoma pressure)/2. Student t test and Pearson correlation coefficient (r) were applied in statistical analysis of findings. RESULTS: Motor weakness was identified in 76.5% of our cases. Tension was strongly related to hemiparesis (r = -0.747, P < 0.01), whereas hematoma thickness (r = -0.458, P < 0.01) and pressure (r = -0.596, P < 0.01) were moderately correlated. Mean age of 14 patients (13.7%) with headache was much younger than those without headache (P < 0.01). Stronger midline shift (P < 0.01) and greater ratio of midline shift to hematoma thickness (P < 0.01) were statistically correlated with headache. Recurrence was recognized in 8 patients (7.8%), and stronger midline shift (P < 0.05) and greater ratio of midline shift to hematoma thickness (P < 0.05) were statistically associated with recurrence. CONCLUSIONS: Tension is the most influencing factor to hemiparesis in CSDH patients. This study also elucidates the mechanism for quick recovery from hemiparesis after surgery in that tension on the motor cortex is decreased immediately by drainage.

Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient. METHODS: We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH. RESULTS: After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH. CONCLUSIONS: Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient.

Evaluation of Cortical Brain Parenchyma by Diffusion and Perfusion MRI Before and After Chronic Subdural Hematoma Surgery.

AIM: To evaluate microcirculatory changes in neighboring parenchyma as a result of pressure due to chronic subdural hematoma (CSDH) in early and late periods after hematoma drainage. MATERIAL AND METHODS: The subject group consisted of 25 patients who underwent CSDH drainage. Brain diffusion and perfusion magnetic resonance images (MRIs) were obtained preoperatively, and at 48 hours (early period) and 2 months (late period) postoperatively. Measurements were performed on 1 cm2 regions of interest (ROI) in the neighboring parenchymal tissue. RESULTS: The early postoperative diffusion values showed improvement compared to the preoperative values. The late postoperative values showed improvement compared to the preoperative and early postoperative values. The early postoperative perfusion values showed slight decline compared to the preoperative values. However, the late postoperative values showed improvement compared to the preoperative and early postoperative values. CONCLUSION: The fact that there was an increase in diffusion values from early to late postoperative periods, compared with the preoperative period, indicates that the beneficial effects of surgery increase over time. Brain perfusion was found to be slightly decreased in early postoperative period. Following CSDH drainage, neurological deteriorations are observed in some patients in the early postoperative periods; a slight impairment in perfusion may account for this. However, during the late postoperative period, perfusion was seen to recover prominently.

Headache in patients with chronic subdural hematoma: analysis in 1080 patients.

Headache is a major symptom in chronic subdural hematoma (CSDH) patients. However, some CSDH patients do not complain headache although the hematoma is thick with definite midline shift. This clinical study was performed to identify the mechanism of headache in CSDH patients. We compiled clinical data of 1080 surgically treated CSDH patients (711 males and 369 females), and in 54 cases, the pressure of hematoma was measured during burr hole surgery using a glass-stick manometer. Headache was recognized in 22.6% of patients, while nausea or vomit suggesting increased intracranial pressure was detected in only 3.0%. Ophthalmological examination was performed in 238 patients, and papilledema was identified in only one patient (0.4%). The mean age of patients with headache (59.8 ± 16.9 years) was significantly younger than that of those without (75.7 ± 11.2 years) (P < 0.01). In 54 cases, the mean hematoma pressure was not significantly different between patients with (17.1 ± 6.2 mmH2O) and without (18.4 ± 7.2 mmH2O) headache (P > 0.10). Hematoma thickness was significantly greater in patients without headache (P < 0.01), but the ratio of midline shift to hematoma thickness was significantly greater in patients with headache (P < 0.01). In our results, the status of increased intracranial pressure was rare in CSDH patients, and high hematoma pressure was not a cause of headache. Midline shift was the most influenced factor for headache in our study, and based on the results, the authors consider that the potential cause of headache in CSDH might be stretching or twisting of the pain-sensitive meninges and meningeal arteries or veins.

Efficacy of Reinforced Restriction of Physical Activity on Chronic Subdural Hematoma: Prospective Pilot Study.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common entity in neurosurgical practice. However, as a result of the high rate in recurrence, morbidity, and mortality for surgical management, conservative management of CSDH is emerging as a new treatment strategy. Head trauma is a known risk factor of CSDH and plays as an initiator in the genesis of CSDH. We hypothesized that physical activity might also play an important role in the progression of an asymptomatic CSDH. METHODS: A prospective pilot study aiming to evaluate the efficacy of reinforced restriction of physical activity for the management of asymptomatic or mild symptomatic CSDH was conducted. Twenty-six patients were enrolled in this study. RESULTS: All 26 patients experienced complete resolution of the CSDH ranging from 32 to 182 days (73.1 ± 19.6 days) since the initiation of reinforced restriction of physical activity. Ages ranged from 43 to 84 years old (64.4 ± 9.6 years). No patient experienced recurrence of CSDH during the follow-up. CONCLUSIONS: According to our study, physical activity might play a role in the progression of CSDH. Further prospective randomized controlled study is warranted in stable patients without evident intracranial hypertension and impending cerebral herniation.

Subdural effusion protects the aging brain from harmful ventriculomegaly.

The human brain loses its volume and its function during aging. The solid part of the brain within the intracranial space, the brain parenchyma, decreases in volume with age; while the cerebrospinal fluid (CSF) volume increases. With progressive loss of brain parenchymal volume (BPV), CSF may shift from cerebral ventricles to the subdural space, forming subdural effusion (SDE), whose role in the brain aging process remains unclear. We hypothesize that damages associated with ventriculomegaly can be lessened after formation of SDE. As the BPV decreases, the enlarged ventricular surface area causes dysfunction of its lining ependymal cells, followed by damages to the periventricular tissue. The periventricular nerve fibers are stretched by the enlarged ventricles. We hypothesize that after the formation of SDE, ventriculomegaly can be stopped or even reversed. By allowing the atrophic brain to reside in a smaller fraction of the intracranial volume, damages associated with ventriculomegaly can be alleviated. If our hypothesis is correct, physicians should continue to maintain a conservative approach for uncomplicated SDE. For focal or global brain parenchymal loss caused by various pathologies, intracranial spacers can be employed to simulate the effect of SDE to protect the brain. For treatment of idiopathic normal pressure hydrocephalus, aggressive ventricular size reduction should be pursued. Finally, the protective effects of SDE have its limits. Extremely enlarged subdural volume can cause acute or chronic subdural hematoma, further damaging the brain.

Chronic Subdural Hematoma: A Perspective on Subdural Membranes and Dementia.

OBJECTIVE: To review the complex pathogenesis of the subdural membrane and the link between head trauma, dementia, and dural lymphatics. METHODS: A thorough literature search of published English-language articles was performed using PubMed, Ovid, and Cochrane databases. RESULTS: Chronic subdural hematoma (cSDH) is a common intracranial pathology and a leading cause of reversible dementia. cSDH is projected to affect at least 60,000 new individuals in the United States annually by 2030. This condition can result from mild to moderate head trauma that leads to hemorrhaging in the dura-arachnoid interface. The short-term and long-term effects of cSDH and the subdural membrane on the pathogenesis of dementia and the newly discovered dural lymphatics is a topic of increasing importance. CONCLUSIONS: Further research into the possible link between traumatic brain injury and cSDH in particular and dural lymphatics and intracranial fluid dynamics is warranted.

Chronic subdural haematoma presenting as freezing of gait.

In this report, we describe a case of freezing of gait (FOG) in a patient with chronic subdural haematoma (CSDH). An 81-year-old patient presented with progressive FOG about 6 weeks after a minor head trauma. MRI revealed CSDH in the left hemisphere, resulting in a marked compression of the hemisphere. His FOG disappeared after neurosurgical evacuation of the haematoma. It is suggested that the subdural haematoma in his left frontal cortices caused FOG. CSDH should be considered as a differential diagnosis when FOG develops after a head trauma in elderly patients, and prompt evaluations including neuroimaging and timely neurosurgical intervention are required.

Chronic Subdural Hematoma Spontaneous Resolution

Introduction Chronic subdural hematoma (CSH) is a hemorrhagic brain injury that persists for more than 21 days after its initial formation. The incidence is predominantly among the elderly population (> 65 years), and varies from 58 to 74/100,000 inhabitants. Spontaneous resolution is considered variable; in the literature series, it is < 1­20% of cases. Objectives To expose the CSH pathophysiological mechanisms of spontaneous resolution and some treatments that lead to hematoma volume reduction. Methods Literature review between 1971 to 2016, using the PubMed, Medline, Embase, Scielo, LILACS and Cochrane databases using key-words, with inclusion and exclusion criteria. Discussion Spontaneous resolution of the CSH pathophysiology is controversial; however, it can be attributed to four basic mechanisms: 1) outer capsule membrane maturation; 2) decreased fibrinolysis; 3) bidirectional flow of blood vessels; and 4) platelet plug. Some drugs, such as mannitol, corticosteroids, tranexamic acid and atorvastatin, contribute to CSH resolution, since they change the capsule membrane permeability, and inhibit the fibrinolytic and inflammatory systems. Conclusion Spontaneous resolution is unpredictable; in some cases, it has a large temporal evolution (of up to 6 years). It occurs in small or laminar collections, asymptomatic or with transient neurological symptoms, and the pathophysiology is still controversial to this day. Therefore, surgical treatment should remain the first option, even though the conservative management is adopted for some patients. Rigorous outpatient and radiological follow-up are recommended.

Introdução O hematoma subdural crônico (HSDC) é uma lesão cerebral hemorrágica que persiste por mais de 21 dias após o começo de sua formação. A sua incidência é predominantemente na população idosa (> 65 anos), e varia de 58­74 /100.000 habitantes, e sua resolução espontânea é considerada rara e variável nas séries da literatura em < 1­20% dos casos. Objetivos Expor os mecanismos fisiopatológicos que favorecem a resolução espontânea do HSDC e alguns tratamentos que favorecem a redução do volume do hematoma. Métodos Revisão bibliográfica entre 1971 e 2016, utilizando as bases de dados PubMed, Medline, Embase, Scielo, LILACS e Cochrane, por meio de palavras-chave, com critérios de inclusão e exclusão. Discussão A fisiopatologia da resolução espontânea dos HSDCs é controversa, porém pode ser atribuída a quatro mecanismos: 1) maturação da membrana externa da cápsula; 2) diminuição da fibrinólise; 3) fluxo bidireccional de vasos sanguíneos; e 4) tampão plaquetário. Alguns medicamentos, tais como manitol, corticoesteroides, ácido tranexâmico e atorvastatina, também podem favorecer a resolução dos HSDCs, uma vez que alteram a permeabilidade da membrana da cápsula e inibem os sistemas fibrinolítico e inflamatório. Conclusão A resolução espontânea é imprevisível; em alguns casos, tem ampla evolução temporal em até 6 anos. Ocorre em coleções pequenas ou laminares, assintomáticas ou com sintomas neurológicos transitórios, e sua fisiopatologia ainda hoje é controversa. Portanto, o tratamento cirúrgico deve continuar sendo a primeira opção, embora se adote uma conduta conservadora para alguns pacientes. O seguimento ambulatorial e radiológico rigoroso é recomendado.

Prolonged Cerebral Hyperperfusion and Subcortical Low Intensity on Fluid-Attenuated Inversion Recovery Images: Unusual Manifestation After Removal of Organized Chronic Subdural Hematoma.

BACKGROUND: Cerebral hyperperfusion sometimes occurs after removal of chronic subdural hematoma (CSH) and usually resolves within a few days without any symptoms. Subcortical low intensity (SCLI) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance images is rare and has been reported in some diseases other than CSH. A case of organized CSH who suffered prolonged neurologic deterioration, SCLI, and cerebral hyperperfusion postoperatively is described. CASE DESCRIPTION: An 81-year-old man, presenting with left hemiparesis, underwent craniotomy for right organized CSH after 2 burr-hole surgeries. After the craniotomy, the symptoms improved, but on postoperative day 2, left hemiparesis, hemispatial neglect, and hemiasomatognosia developed. Magnetic resonance imaging revealed SCLI on FLAIR images, and single-photon emission computed tomography with N-isopropyl-p-[123I]-iodoamphetamine revealed cerebral hyperperfusion in the right hemispheric cortex. Antihypertensive treatment improved the symptoms gradually, which resolved completely 1 month postsurgery. CONCLUSIONS: A case of organized CSH, which showed postoperative neurologic deterioration associated with prolonged cerebral hyperperfusion and SCLI on FLAIR images, is reported. Prolonged cerebral hyperperfusion could be a cause of postoperative neurologic deterioration in organized CSH.

Spontaneous resolution of post-traumatic chronic subdural hematoma: a case report.

Chronic subdural hematomas often occurs in late middle and old age following trivial head trauma. Surgical intervention is the first treatment option in chronic subdural hematomas which compressed the cerebral parenchym. Hematoma may be calcified or ossified in untreated patients. Spontaneous resolution of post-traumatic chronic subdural hematoma is a rare event. Spontaneous resolution is rarer if the subdural hematoma is bilateral. In the literature, this condition is reported mostly in patients with idiopathic thrombocytopenic purpura. Here, we present a case of spontaneously resolved post-traumatic bilateral chronic subdural hematoma within a period of one month in a 55-year-old male and we discuss the probable mechanisms of pathophysiology in the spontaneous resolution of chronic subdural hematoma.