Takashi Minakawa

Multivariate Analysis of Predictors of Hematoma Enlargement in Spontaneous Intracerebral Hemorrhage

BACKGROUND AND PURPOSE We conducted this study to determine, through use of multivariate analyses, the independent predictors of hematoma enlargement occurring after hospital admission in patients with spontaneous intracerebral hemorrhage (i.c.h.). METHODS We reviewed 627 patients with ICH admitted within 24 hours of onset. The first CT was performed at admission and the second within 24 hours of admission, and a blood sample was taken for laboratory examinations. Univariate and multivariate analyses were performed to assess the relationships between hematoma enlargement and time from onset, consciousness level, CT findings, amount of alcohol consumption, systolic blood pressure at and after admission, clinical outcome, and hematologic parameters. RESULTS Eighty-eight patients (14.0%) showed enlarged hematomas after admission. Multivariate analyses revealed that the following five factors were independently associated with hematoma enlargement: the time from onset (odds ratio [OR], 0.26 for a 1-SD change; 4.9 hours; P < 0.001); the amount of alcohol consumption (OR, 1.50 for 1 SD; 46.3 g/d; P = 0.002); the sharp of hematoma (OR, 1.40 for 1 SD; 0.45 round; P = 0.006); the presence of consciousness disturbance (OR, 1.38 for 1 SD; 0.50 coma; P = 0.026); and the level of fibrinogen (OR, 0.74 for 1 SD; 87.1 mg/dL; P = 0.042). Hematoma enlargement was an independent factor increasing the mortality rate in the ICH patients (OR, 1.57; P < 0.001). CONCLUSIONS A particularly high likelihood of hematoma enlargement was observed in patients who (in order of importance) were admitted shortly after onset, who were heavy drinkers; who had an irregularly shaped hematoma, whose consciousness was disturbed, and who had a low level of fibrinogen.

Angiographic follow-up study of cerebral arteriovenous malformations with reference to their enlargement and regression.

Twenty patients with cerebral arteriovenous malformations (AVMs) were followed up by angiography. Of the 20 AVMs, 16 were nontreated and the remaining 4 were residual. The follow-up periods between the two examinations were from 5 to 28 years, with a median interval of 15 years. At follow-up, the size of the AVM had increased in 4 patients (20%), decreased in 4 (20%), totally regressed in 4 (20%), and was unchanged in 8 (40%). In cases of enlarged AVMs, the patients were all young: from 0 to 11 years old at first angiography and from 6 to 30 at second angiography. The decrease or total regression of the AVM occurred in older patients (over 30 years old at second angiography), and the AVMs were relatively small and fed by single or a few feeders. The patients age and the size of AVM should be considered when operative indications are discussed.

Liver dysfunction in spontaneous intracerebral hemorrhage.

The purpose of this study was to investigate the relationship between mild degrees of liver dysfunction and spontaneous intracerebral hemorrhage (ICH) from the hemostatic standpoint. A detailed study of hemostatic systems was made in 462 patients with ICH. To compare ICH with the other cerebrovascular diseases, data from 120 patients with subarachnoid hemorrhage and 114 others with cerebral infarction were reviewed. At admission, the medical histories of the patients, including information about previous alcohol consumption, was taken, and blood samples were collected to perform the following studies: platelet count, fibrinogen level, prothrombin time, activated partial thromboplastin time, antithrombin III, plasminogen and alpha 2-antiplasmin activity, platelet aggregability, and liver function tests. The incidence of liver dysfunction and alcohol consumption in patients with ICH was significantly (P < 0.05) higher than in patients with subarachnoid hemorrhage and in those with cerebral infarction. Hematoma volume, mortality rate, and past alcohol consumption in patients with ICH significantly increased with worsening severity of liver dysfunction. Although almost all hemostatic parameters became worse with increasing severity of liver dysfunction, they changed within the normal limits. Platelet aggregability and alpha 2-antiplasmin activity in patients with liver dysfunction were remarkably deteriorated beyond normal limits. In conclusion, liver dysfunction associated with alcohol consumption appears to be an important factor in the deterioration of the clinical status of patients with ICH and may be one of the causative factors in the development of ICH. Although mildly impaired hemostatic systems may be partially responsible for these adverse effects of liver dysfunction on ICH, it seems probable that nonhemostatic mechanisms are attributed to the effects.

Hemostasis in spontaneous subarachnoid hemorrhage.

To comprehensively examine changes in the hemostatic systems early after spontaneous subarachnoid hemorrhage (SAH) and to assess the relationships between those changes and neurological findings, computed tomographic findings, and clinical outcomes, we reviewed 167 patients who were admitted within 24 hours of the onset of SAH. Blood was taken from all of the patients at admission for detailed examinations of the hemostatic systems. The following results were obtained: 1) the levels of the thrombin-antithrombin complex (elevation indicating the activation fo the blood coagulation system), plasmin-antiplasmin complex, and D-dimer (elevation indicating the activation of the fibrinolytic system) significantly increased with the neurological severity, amount of subarachnoid clot, and severity of clinical outcome; 2) the levels of the thrombin-antithrombin complexes and plasmin-antiplasmin complexes were significantly higher in patients with intracerebral or intraventricular hematomas than in patients without those hematomas; 3) in each of almost all the neurological and computed tomographic grades, the levels of the thrombin-antithrombin complexes were significantly higher in the patients with poor outcomes than in those with good outcomes; 4) the poor outcome rate significantly increased with neurological severity and the amount of subarachnoid clot. These data suggest that the activation of the blood coagulation system as well as of the fibrinolytic system occurred early in the course of SAH and that these systems were activated to a greater extent with the severity of neurological grades, computed tomographic findings, and clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Long term results of ruptured aneurysms treated by coating

We report the long term results of the treatment of 23 intracranial ruptured aneurysms by coating. Twenty-three patients treated by coating were followed for a mean period of 11.2 years. The mean interval between the last hemorrhage and the operation was 22.4 days. Ten aneurysms underwent total coating, 9 with Biobond and 1 with Aron Alpha. Thirteen aneurysms underwent partial coating, 11 with Biobond and 2 with Aron Alpha. Six aneurysms were reinforced partially by other materials, but no aneurysm was wrapped totally with these materials. Rebleeding occurred in 6 patients, of whom 5 died. The mean interval between coating and rebleeding was 4 years. All patients suffering rebleeding had been treated with Biobond, and 3 patients had undergone total coating of aneurysms. The risk of recurrent hemorrhage after total coating with Biobond was 33%. One rebleeding patient underwent a second operation 10.5 years after total coating of the aneurysm. Biobond was found only at the tip of the aneurysmal sac. From these results, reinforcement of ruptured aneurysms with Biobond seems to be of little value, and a more reliable method must be developed for aneurysms that cannot be clipped.

Aneurysms associated with fenestrated anterior cerebral arteries. Report of four cases and review of the literature

Four cases of aneurysms associated with a fenestrated anterior cerebral artery are presented. The combination of aneurysms and fenestration of the anterior cerebral artery is rare, and nine cases including ours have been reported. In all cases fenestrations were found within the distal two-thirds of the horizontal portion of the anterior cerebral artery. It may be presumed that fenestration of the anterior cerebral artery is the remnant of the plexiform anastomosis in the fetal stage, especially between the anterior cerebral artery and the primitive olfactory artery.

Serial Changes in Hemostasis after Intracranial Surgery

We performed hemostatic studies on eight patients undergoing clipping of unruptured cerebral aneurysms to assess the influence of intracranial surgery itself on hemostasis. Blood samples were collected from each patient 10 times: before and after the induction of anesthesia and 6, 12, and 24 hours and 2, 3, 5, and 7 days immediately after surgery. The changes and our interpretation of them include the following: 1) the elevation of thrombin antithrombin III complex levels (activation of blood coagulation) was transient and monophasic; 2) the elevation of plasmin alpha 2-antiplasmin complex and D-dimer levels (activation of fibrinolysis) was biphasic, despite the monophasic elevation of tissue plasminogen activator or plasminogen activator inhibitor-1 levels; 3) the elevation of beta-thromboglobulin and platelet-factor-4 levels (activation of platelet) was also biphasic; 4) fibrinogen level and alpha 2-antiplasmin activity increased in the acute phase of the postoperative course (acute phase reaction); 5) the changes in hematocrit appeared to parallel those in various other parameters, especially platelet count, antithrombin III, and plasminogen levels for 1 or 2 days after surgery; 6) fibronectin appeared to be consumed in the acute phase of postoperative course; and 7) general anesthesia did not significantly affect hemostasis. These serial changes seem to be related to the activation of hemostatic systems after intracranial surgery and the subsequent acute phase reaction.

Surgical experience with massive lobar haemorrhage caused by cerebral amyloid angiopathy

SummaryNineteen patients with massive lobar haemorrhage without angiographic lesions received direct or stereotactic surgery, and biopsy specimens were examined histologically. Ten patients (53%) were found to have vessels positive for Congo-red staining, and demonstrating amyloid angiopathy. In the patients with amyloid angiopathy, CT scan and surgical findings were investigated. Subarachnoid haemorrhage (9/10), irregularly shaped haematoma (9/10) and fluid-blood density level in the haematoma cavity (7/10) were frequently found on CT scan. The characteristic surgical findings in patients treated by direct surgery were subarachnoid haemorrhage adjacent to intracerebral haematoma (8/8) and the existence of a tangle of vessels in the haematoma cavity (4/8). Evacuation of haematomas was relatively easy, and difficulty of haemostasis was not encountered during surgery.

Blood Pressure Monitoring in Feeding Arteries of Cerebral Arteriovenous Malformations during Embolization: A Preventive Role in Hemodynamic Complications

To study the hemodynamics of arteriovenous malformations and to avoid hemodynamic complications during and after artificial embolization, we measured arterial blood pressures in 21 feeders in 14 patients through a microcatheter system. Before embolization, the pressures were significantly low in feeders with branches terminating in the malformation (terminal divided branches) and comparatively low in arteriovenous malformations with rapid blood flow through the malformation. The pressures in feeders with brain-nutrifying branches distal to the nidus (transient branches) were significantly high. Therefore, transient branches might be distinguishable from terminal divided branches with the use of feeder pressure monitoring. A hemorrhagic complication occurred in one patient. The feeder pressure in this patient was low before embolization and showed the maximum change among the patients after embolization. It seems that the lower the feeder pressure, the more likely complications are to occur, owing to remarkable hemodynamic alterations. Feeder pressure monitoring may be useful for preventing hemodynamic complications, especially when angiographic findings show feeding arteries giving off terminal divided or transient branches or rapid blood flow through the malformation.

Effects of Cytokines on Cultured Microvascular Endothelial Cells Derived from Gerbil Brain

Microvascular endothelial cells were isolated from gerbil brain and cultured. These cells retained an endothelial-specific marker, FVIII-related antigen. Alkaline phosphatase activity was also present in early passage. Two weeks after plating, these cells were attached to the culture dishes and had become like cobblestones in appearance. Then, the addition of tumor necrosis factor at a concentration of 1000 U/ml or more suppressed the DNA synthesis activity of endothelial cells by about 70% and induced morphological changes in the cells, which developed a spindle-like form and showed overlapping of cells, indicating loss of contact inhibition. The administration of interferon-tau induced no change. When a similar experiment was performed using culture supernatants of human glioma cells that had been cultured for a few days, DNA synthesis activity was suppressed by approximately 50% or more in 6 of 12 samples. The suppression of activity, however, was abolished by the addition of anti-tumor necrosis factor antibody in these 6 cases, suggesting the presence of activity resembling that of the tumor necrosis factor in the culture supernatants.