Subdural haematomas drain into the extracranial lymphatic system through the meningeal lymphatic vessels.

Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.

Development of chronic encapsulated intracerebral hematoma after radiosurgery for a cerebral arteriovenous malformation.

BACKGROUND: We report a rare case of chronic encapsulated intracerebral hematoma (CEIH) after radiosurgery for a cerebral arteriovenous malformation (AVM). METHODS: Seven years after radiosurgery, magnetic resonance imaging revealed a high-intensity mass in the right basal ganglia with a peripheral low signal ring and fluid level on both T1- and T2-weighted images, which was compatible with CEIH. RESULTS: Stereotactic evacuation and placement of an Ommaya reservoir were performed. CONCLUSION: The concentration of vascular endothelial growth factor was high in the hematoma, suggesting that CEIH may be similar to chronic subdural hematoma.

Semiquantitative expression analysis of ephrine-receptor tyrosine kinase mRNA's in a rat model of traumatic brain injury.

The molecular mechanisms involved in recovery of function of the central nervous system (CNS) after injury to the brain are incompletely understood. Here the expression of ephrine (Eph) kinases following traumatic brain injury (subdural haematoma) was analysed in order to find out whether these developmentally regulated genes may be involved in tissue remodelling after brain damage. mRNA was isolated from ipsilateral cortices 7, 18, and 28 days after surgery and semiquantitative reverse transcription-polymerase chain reaction was performed. Most Eph kinases did not show significant regulation at gene expression level during the time course of recovery from acute brain injury but there is some evidence that mRNA of EphB1 might be slightly upregulated.

Effect of hypocapnea on CBF and extracellular intermediates of secondary brain injury.

We examined the metabolic response of the brain underlying subdural hematomas or surrounding contusions to hyperventilation and looked for evidence of ischemia. Twelve consecutive patients with severe traumatic brain injury (TBI) (GCS < 8) who required surgery for evacuation of subdural hematoma or hemorrhagic contusion were studied. At surgery, a microdialysis catheter was placed into the cortex in a gyrus adjacent to the contusion or underlying the subdural hematoma. A thermal diffusion flow probe was placed on the cortex directly above the dialysis catheter. On days 1 and 3 post injury, two trials of hyperventilation were performed which dropped the patients' pCO2 10 mm Hg for 30 minutes. Monitoring of CBF and collection of dialysis fluid continued throughout each hyperventilation trial. Data was analyzed for a three hour window surrounding each hyperventilation. Brief periods of hyperventilation did not cause a significant elevation of the extracellular lactate/pyruvate ratio or glutamate level in areas of the brain likely to be the most vulnerable to secondary injury. In spite of hyperventilation leading to a significant decline in local CBF in 20% of the trials, there was no evidence of ischemia or excitatory amino acid release associated with hyperventilation.

Cortical cholinergic dysfunction after human head injury.

Loss of cholinergic neurotransmission is implicated in memory impairment and cognitive dysfunction after head injury. The aim of the present study was to investigate presynaptic markers, particularly in relation to cholinergic neurotransmission in human postmortem brain from patients who died following a head injury and age-matched controls. Choline acetyltransferase activity and high-affinity nicotinic receptor binding sites were assayed in the inferior temporal gyrus, cingulate gyrus, and superior parietal cortex of 16 head-injured patients and 8 controls. Synaptophysin immunoreactivity was determined in the left cingulate gyrus from the same patient groups. In the head-injured group, choline acetyltransferase activity was consistently reduced in each cortical region compared to control subjects. The presence of a subdural haematoma and a prolonged survival period after head injury tended to be associated with lower choline acetyltransferase activity. In contrast to the marked reduction in choline acetyltransferase activity, nicotine receptor binding was unchanged in head-injured compared to control patients. Synaptophysin immunoreactivity in the cingulate gyrus was reduced by approximately 30% (p < 0.05) in the head-injured group compared to controls. Correlation of choline acetyltransferase activity with synaptophysin immunoreactivity indicated there is a deficit of cholinergic presynaptic terminals in postmortem human brain following head injury.

Inflammatory cytokines locally elevated in chronic subdural haematoma.

The involvement of inflammation in the development and propagation of chronic subdural haematoma (CSH) was investigated by measuring the levels of inflammatory cytokines (tumour necrosis factor [TNF] alpha, interleukin [IL]-1 beta, IL-6, and IL-8). Peripheral venous blood and subdural fluid were obtained at the time of burr hole surgery from 34 patients with CSH and from 9 with subdural effusion. The levels of the inflammatory cytokines were analysed by enzyme-linked immunosorbent assay. The blood levels of TNF alpha, IL-1 beta, IL-6, and IL-8 in both CSH and subdural effusion groups were almost within the range of normal subjects, and no differences were observed between the two groups. IL-6 and IL-8 in the subdural fluid were much higher than in the blood of both groups, and the levels in CSH patients were significantly higher (10 times) than in subdural effusion patients. Local elevation of inflammatory cytokines in the subdural space of both CSH and subdural effusion without systemic change suggests the presence of local inflammation in the two diseases. The same behavioural patterns of cytokines for these and higher levels of cytokines in the CSH also suggest that inflammatory cytokines may be involved in the continuous development from subdural effusion to CSH and propagation of CSH.

Effect of the novel high-affinity glycine-site N-methyl-D-aspartate antagonist ACEA-1021 on 125I-MK-801 binding after subdural hematoma in the rat: an in vivo autoradiographic study.

Acute subdural hematoma (SDH) complicates 20% of severe human head injuries and causes death or severe disability in 60% of these cases, due to brain swelling and high intracranial pressure. Although the mechanisms for these phenomena are unknown, previous studies have implicated excitatory amino acid-mediated mechanisms in both humans and animal models. The authors therefore performed in vivo autoradiography using 125I-MK-801, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, as a tracer to evaluate NMDA ion channel activation spatially and temporally as a factor causing cytotoxic swelling. Acute SDH was induced in 16 anesthetized rats using 0.4 ml autologous venous blood. Fifty microcuries of 125I-MK-801 was injected via an aortic arch cannula 30 minutes after onset of SDH. The effect of a new putatively neuroprotective drug, ACEA-1021, a glycine-specific binding site NMDA antagonist, on 125I-MK-801 binding was tested on five animals "Nonspecific" 125I-MK-801 binding in the rat brain was assessed by pretreatment with "cold" (nonradiolabeled) MK-801 in five more animals. Four hours later the animals were sacrificed and brain sections were apposed to radiation-detecting high-sensitivity photographic film with precalibrated plastic standards for 4 weeks. A striking and highly significant 1.7- to 4.8-fold increase in 125I-MK-801 binding was seen in the penumbra of viable tissue surrounding the ischemic zone beneath the acute SDH, when compared to contralateral hemisphere binding (p < 0.001). The MK-801 pretreatment markedly reduced 125I-MK-801 uptake in this penumbral zone (4.73 +/- 0.36 nCi/mg control vs. 2.85 +/- 0.08 nCi/mg cold MK-801; p < 0.0001), indicating that the increased binding in the penumbra of the lesion was due to NMDA ion channel activation. Pretreatment with ACEA-1021 reduced 125I-MK-801 uptake by 28% (3.41 +/- 0.26 nCi/mg vs. 4.73 +/- 0.36 nCi/mg; p < 0.05), indicating that this agent prevents opening of the NMDA ion channel and, thus, exposure of its receptor for MK-801 binding. These studies show intense foci of penumbral NMDA receptor-mediated ion channel activation after onset of SDH, which is markedly reduced by an NMDA antagonist. Such agents are thus likely to reduce cell swelling after SDH occurs.

Ultrastructure of collagen fibers in the outer membrane of recurrent chronic subdural hematoma.

The three-dimensional structure of the collagen fibers in the outer membrane of recurrent chronic subdural hematoma was studied by scanning electron microscopy (SEM). Specimens obtained at surgery were treated with NaOH at room temperature to digest away all cellular components and expose the collagen fibers. SEM observation of the dural side of the outer membrane showed the collagen fibers were woven into a compact feltwork with a dense arrangement. The fiber bundles had a honeycomb structure framed by the collagen fibers. Observation of the hematoma side found the collagen bundles had a sparse wavy appearance. The arrangement of the collagen fibers on the dural side is different from that on the hematoma side. The thick outer membrane may be formed by granulation resulting from inflammatory reaction. Collagen fibrillar networks are not fragile, and may reinforce the outer membrane of the recurrent hematoma.

Oxytalan fibres in meningiomas and meningeal neomembranes.

The incidence of oxytalan fibres was studied in 202 meningiomas and 30 neomembranes. Oxytalan fibres were present in all samples of neomembranes and in the majority of meningiomas; 81% of the fibroblastic meningiomas contained oxytalan fibres. Their frequency was lowest in malignant meningiomas.

Plasmin-alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor in chronic subdural hematoma.

Levels of the plasmin-alpha 2-plasmin inhibitor complex (PLN-A2PI complex) and alpha 2-plasmin inhibitor (A2PI) were determined by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies in 59 patients with 66 chronic subdural hematomas (SDH's). Normal concentrations of the PLN-A2PI complex and A2PI in plasma are below 0.8 microgram/ml and 60.5 +/- 16.1 micrograms/ml, respectively (mean +/- 2 standard deviations). The hematoma fluid contained high concentrations of the PLN-A2PI complex (4.58 +/- 2.60 micrograms/ml) and low concentrations of A2PI (10.32 +/- 4.81 micrograms/ml), while both values in the plasma of 12 patients with chronic SDH's were within the normal range. This represents local hyperfibrinolytic activity in the hematoma. Stuporous or comatose patients had higher PLN-A2PI complex levels than did the alert and the drowsy or disoriented patients. The layering type of hematoma as seen on computerized tomography scans showed the highest PLN-A2PI complex levels among five types of hematoma. In the fluid drained postoperatively from the subdural cavities of chronic SDH's, both the PLN-A2PI complex and A2PI levels decreased gradually in healing cases. In two patients with hematoma reaccumulation after surgery, both levels increased. The postoperative increase of the PLN-A2PI complex represents the recurrence of intermittent cycles of fibrinolysis, bleeding, coagulation, and hemostasis in the subdural space.

Chronic subdural hematomas. Time-density curve and iodine concentration in enhanced CT.

Surgery was undertaken on 32 chronic subdural hematomas in a series of 28 patients who had preoperatively undergone delayed contrast-enhanced computed tomography (DCECT). Time-density curves on DCECT and iodine concentrations of subdural specimens revealed that chronic subdural hematomas, regardless of density, were significantly enhanced by the entrance of intravascular contrast medium into the interior of hematomas. The ingress of intravascular contrast medium into the interior of the hematomas was chemically proven and might result from a complex transcapillary shift.

Steroid receptors in the pathogenesis of chronic subdural hematoma.

Chronic subdural hematoma (CSDH), located between the dura mater and the arachnoid and usually characterized by a well-vascularized external capsule (HEM), has a higher incidence in male patients with elevated urinary estrogens than in female patients. In an attempt to increase our understanding of the physiopathogenesis of CSDH, total estrogen receptor (ER) was measured in HEM specimens from four male patients by a sodium thiocyanate exchange assay and cytosol progesterone receptor (PRc) in three specimens by a dextran-coated charcoal adsorption assay. Although no nuclear ER could be detected, ERc and PRc were found in all three specimens examined. The presence of ER in a mesenchymal tissue like HEM could suggest that, in addition to inducing vascular changes, estrogens might act directly on HEM through a receptor-mediated mechanism more pronounced in men than in women, whose vascular network is adapted to high estrogen values.

[Permanent registration of the energy transformation in patients with skull-brain injuries and brain tumors]. / Dauerregistrierung des Leistungsumsatzes bei Patienten mit Schädel-Hirn-Trauma und Hirntumoren

By means of a measuring device based on the principles of indirect calorimetry, long-term recording of energy transformation in patients with cerebral tumours and cerebral traumas is performed. Contrary to the conception that the catabolic state in the postoperative/posttraumatic period corresponds to a negative balance between requirement and enteral/parenteral supply, it appears that, as a rule, the energy requirement is only 1 to 1 1/2 times higher than under normal conditions. During long-term measurement, clinical phenomena that are characterized by increased muscular activity (seizures, extension automatisms, extreme psychomotor excitations) show a daily requirement of maximal 3,500 kcal. Considering the clearly lower requirement, the change of the catabolic state by a high-caloric intake (5,000 and 6,000 calories/day) can only be due to an effect on the regulation of the metabolic processes.