Prenatal diagnosis of 22q11 microdeletion

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.     

Interleukin-6 and development of vasospasm after subarachnoid haemorrhage

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.     

Coagulative and fibrinolytic activation in cerebrospinal fluid and plasma after subarachnoid hemorrhage

OBJECTIVE: Intrathecal fibrinolytic therapy has been used as one of the anticerebral vasospasm (VS) preventative therapies in patients with subarachnoid hemorrhage (SAH). However, the changes in coagulation and fibrinolysis in the blood and cerebrospinal fluid (CSF) after SAH remain unknown. METHODS: Fifty patients with SAH caused by ruptured cerebral aneurysms were studied postoperatively to detect the serial changes of the thrombin-antithrombin III complex, active plasminogen activator inhibitor (PAI)-1, and tissue plasminogen activator (tPA)-PAI complex (tPA-PAI) activities in the plasma and CSF collected from cisternal drainage catheters. RESULTS: The CSF levels of all parameters and plasma PAI-1 levels were significantly higher in patients with severe SAH than in those with mild SAH. There was no relationship between the CSF and plasma levels of these parameters (except the CSF levels of tPA-PAI) and the initial neurological statuses. The CSF PAI-1 levels increased to greater than 20 ng/ml near the time of the occurrence of cerebral VS, whereas they remained below 20 ng/ml in patients without VS. The CSF tPA-PAI levels showed the highest peak near the time of VS remission. The CSF PAI-1 and tPA-PAI levels were significantly lower in patients with good outcomes than in those with poor outcomes. CONCLUSION: Both the coagulative and fibrinolytic systems were activated in the CSF and plasma after SAH in correlating to the amount of SAH clot. The intrathecal administration of fibrinolytic agents should be started early after surgery, before CSF PAI-1 levels increase, for patients with severe SAH. Patients with CSF PAI-1 levels greater than 20 ng/ml experienced high incidence of VS and poor outcomes.     

Folding rate dependence on the chain length of RNA-like heteropolymers

BACKGROUND: Economical studies on surgery of intracranial aneurysms have considered only the significant benefit of surgical approach on unruptured aneurysms and no studies have been performed comparing cost/benefit analysis of early vs delayed surgery. The present study was retrospectively performed in order to verify whether different treatment options in aneurysm surgery have a different cost/benefit ratio. METHODS: We have analysed a series of 137 patients which underwent surgery for intracranial aneurysms (21 unruptured aneurysms, 56 early surgery and 60 delayed surgery). In the analysis we assumed that each state of an operated patient has an assigned quality of life value and an associated medical cost. We expressed the outcome of each patient as the expected length of survival adjusted for quality, and referred to it as "quality-adjusted life years" (QALY). We considered for each patient the direct cost of Hospitalisation (obtained from DRG reimbursement), the Rehabilitation cost and the correction due to QALY adjusted for age and deficit. RESULTS: Significantly higher costs are reported in patients which present as major complication the hydrocephalus and which are treated with nimodipine; moreover, the costs for patients operated for unruptured aneurysms is significantly lower than that of patients which presented with SAH. Meanwhile, the average QALY adjusted for post-operative neurological deficit at three months follow-up is higher in patients operated for unruptured aneurysms than in patients operated after SAH. The cost-effectiveness of different treatment strategies did not significantly differ considering age and neurological deficit adjustment; thus, after SAH, the choice of early or delayed surgery may depend on clinical and logistic conditions related to the neurosurgical department and its organisation, because there is no significant economical advantage leading to recommend early versus delayed surgery. CONCLUSIONS: In conclusion the present data suggest that a decreased length of hospitalisation and a decreased cost for treatment of unruptured aneurysms should justify a more rigorous preventive screening with available non invasive neuroimaging techniques.     

Oxidative stress in the human brain after subarachnoid hemorrhage

OBJECT: The aim of this study was to verify the patterns of antioxidant enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the human brain after subarachnoid hemorrhage (SAH) to verify whether an "oxidative stress situation" characterizes the brain response to subarachnoid bleeding. METHODS: Forty samples of gyrus rectus or temporal operculum that were obtained during a surgical approach to anterior circulation aneurysms were used for this study. The activity of total SOD, GSH-Px, and the SOD/GSH/Px ratio (which expresses the balance between the production of hydrogen peroxides by dismutation of superoxide radicals and the scavenging potential) were calculated in each case. Twelve samples were obtained from patients who underwent surgery for unruptured aneurysms (control group); 13 samples were obtained during surgical procedures performed within 72 hours of SAH; and 15 samples were obtained during delayed surgical procedures (> 10 days post-SAH). Ten patients presented with clinical deterioration caused by arterial vasospasm. In both SAH groups, the mean total SOD activity was significantly higher than in the control group (p=0.029). The mean activity of GSH-Px did not differ significantly between the SAH and control groups (p=0.731). There was a significant increase in the SOD/GSH-Px ratio in both SAH groups, as compared with controls (p < 0.05). There was a significant correlation between the enzymatic activity and the clinical severity of the hemorrhage, with findings of lower values of SOD and, mainly, of the SOD/GSH-Px ratio in the poor-grade patients. The SOD/GSH-Px ratio was 2.14+/-0.44 in patients who presented with clinical vasospasm and 1.24+/-0.2 in cases without vasospasm. CONCLUSIONS: The results of this study show an imbalance of the antioxidant enzymatic activities in the human brain after SAH. which is linked to the severity of the initial bleeding and possibly modified by the development of arterial vasospasm.     

Correlation between blood parameters and symptomatic vasospasm in subarachnoid hemorrhage patients

Serial changes in platelet and white blood cell (WBC) counts and other blood parameters were analyzed in 103 patients with aneurysmal subarachnoid hemorrhage (SAH). The WBC counts during days 3-5, 6-8, 9-11, and 12-14 after the onset of SAH were significantly higher in patients with than in patients without symptomatic vasospasm. Platelet counts during days 0-2, 3-5, 6-8, 9-11, 12-14, 15-17, 18-21, and 22-28 after SAH were significantly higher in patients with than in patients without symptomatic vasospasm. Monitoring of platelet and WBC counts may provide an indicator of the occurrence of symptomatic vasospasm.     

Understanding the three national databases on collegiate alcohol and drug use

Early admission and medical treatment can improve prognosis in patients with subarachnoid hemorrhage (SAH). In our Centre in 10 years, 595 patients with SAH have been treated: 422 were admitted within 24 hours (71%) and 498 (84%) within 72 hours. 374 underwent surgical treatment: 283 within 48 hours and 91 underwent late surgery. Thirty-three patients underwent emergency surgery for intracranial hematomas, with a mortality rate of 30%. One hundred eighty-one patients in Hunt-Hess grade I-II underwent early surgery. Mortality rate was 7%. Mortality rate for rebleeding, when surgery was delayed was more than 10%. Patients in Hunt-Hess grade III underwent early surgery in the majority of cases (68 out of 111). Only in 52% of cases surgical result was good. Thirty-four out of 108 in grade IV-V underwent early surgery, with a mortality rate of 45%. The analysis of general results shows that early surgery improves prognosis in Hunt-Hess grade III patients. Also patients in Hunt-Hess grade III-IV-V can take advantage of early surgery. Old age, arterial hypertension and angiographical vasospasm do not worsen prognosis even in patients operated on early. Endovascular treatment even in acute phase has improved results especially in cases of certain aneurysms types such as posterior circulation aneurysms.     

Propagation of a signal coordinating force generation along an actin filament in actomyosin complexes

We reviewed the medium-term results of endovascular treatment of intracranial aneurysms and compared patient selection and results with those of open surgery. Between January 1992 and December 1995, a total of 248 consecutive patients were treated for 297 aneurysms (61 unruptured and 236 ruptured). 162 aneurysms in 142 patients (mean age, 48.5 years) were treated microsurgically and 134 aneurysms in 106 patients (mean age, 54.2 years) were treated by endovascular embolization with Guglielmi detachable coils (GDC). The mean follow-up was 2.6 years (range, 1.5 to 4.5 years). There was no significant difference in patient population and selection in terms of age, sex or location of aneurysms between both methods. Both modalities achieved excellent results (defined as no neurological deficit) in patients with unruptured aneurysms and with no or minor deficits after subarachnoid hemorrhage (SAH) between 71% and 88%. Patients with moderate deficits after SAH had excellent outcomes in 49% after open surgery, and 47% after embolization. Poor grade patients had, equally, as well an acceptable as a pour outcome, between 0% and 50%. There was no significant difference between the outcome of surgical or endovascular patients. We conclude that GDC embolization is not associated with a higher risk of morbidity and mortality than open surgery. This risk may even be lower for lesions in surgically unfavorable locations. The GDC technique is a less invasive, effective option to prevent re-bleeding in early stage, even in poor-grade patients. However, these encouraging medium-term results have to be confirmed by a longer observation period.     

Long-term monitoring of CSF lactate levels and lactate/pyruvate ratios following subarachnoid haemorrhage

Ventricular cerebrospinal fluid (CSF) lactate concentrations and lactate/pyruvate (L/P) ratios were measured daily in 20 patients from day 1 to day 12 after subarachnoid haemorrhage due to ruptured aneurysms. Patients without symptomatic vasospasm were classified in Group 1, patients with symptomatic vasospasm were classified in Group 2, and patients who were Hunt and Kosnik grade 4 on admission clinically were classified in Group 3. Patients in all three groups had high CSF lactate concentrations on day 1, and, especially in Group 3, the high lactate was accompanied by an increased L/P ratio and a decreased CSF bicarbonate. Lactate concentrations in Group 1 decreased throughout the observation period. Lactate concentrations in Group 2 also decreased but then began to increase again on days 5 to 7, correlating well with the onset of cerebral vasospasm. The delayed increase of CSF lactate in Group 2 was also accompanied by increases in the CSF pyruvate level and the CSF L/P ratio. Daily monitoring of CSF lactate may thus serve as a chemical marker for cerebral vasospasm.     

Net efflux of cysteine, glutathione and related metabolites from rat hippocampal slices during oxygen/glucose deprivation: dependence on gamma-glutamyl transpeptidase

BACKGROUND: Effect of clot removal and surgical manipulation on cerebral blood flow (CBF) and delayed vasospasm was studied in early aneurysm surgery for subarachnoid hemorrhage (SAH). METHODS: Thirty-two patients in this study fulfilled the following criteria: ruptured anterior communicating aneurysms, computed tomography (CT) within 2 days and unilateral pterional approach within 3 days after the ictus, bilaterally symmetrical clots without intracerebral hematoma, no postoperative complication, and CBF studies with single photon emission computed tomography (SPECT) with 123I-IMP. RESULTS: Postoperative regional hypoperfusion due to brain retraction was frequently recognized on 123I-IMP-SPECT without infarction. The regional CBF (rCBF) showed a continuous fall during the first 4 weeks after the ictus, followed by improvement. The rCBF in the vicinity of the surgical route was significantly lower, especially in the acute stage (Day 3-7). A significant association between decrease of cisternal blood after surgery and the degree of local vasospasm and local CBF values during spasm stage was observed in the interhemispheric cisterns, A2 and medial frontal cortex, but not in the sylvian fissure or insular cisterns, M1 or M2, and frontal watershed and temporal cortex. CONCLUSIONS: The present study provides evidence for the effectiveness of direct clot removal by early surgery for SAH on local vasospasm and CBF reduction. However, a potential improvement in local CBF with clot removal could be masked by brain retraction, which was demonstrated to affect rCBF adversely. Therefore, it is critical to perform brain retraction as gently as possible.     

CO2 reactivity in patients after subarachnoid haemorrhage

CO2 reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO2 measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO2 and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidental aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO2 reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO2 reactivity was normal at the time of investigation. Furthermore, normal CO2 reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH.     

Cerebrospinal fluid tissue factor and thrombin-antithrombin III complex as indicators of tissue injury after subarachnoid hemorrhage

BACKGROUND AND PURPOSE: No marker that reflects and predicts brain injury due to subarachnoid hemorrhage (SAH) and cerebral vasospasm has been reported. We hypothesized that membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) in the cerebrospinal fluid (CSF) of patients with SAH become markers indicating brain injury. To evaluate the hypothesis, we correlated levels of mTF and TAT in the CSF of patients with SAH with clinical severity, the degree of SAH, and outcome. METHODS: We assayed CSF mTF, TAT and myelin basic protein (MBP) in patients with SAH at intervals that included days 0 to 4 and days 5 to 9 after ictus. Classification of clinical severity of disease on admission was based on Hunt and Hess grade, degree of SAH on CT on Fisher's grading, and outcome 3 months after SAH on the Glasgow Outcome Scale. RESULTS: In the interval from days 0 to 4, mTF and TAT correlated with Hunt and Hess and Fisher grades, and occurrence of cerebral infarction due to vasospasm. Only mTF correlated significantly in this period with outcome. TAT, mTF, and MBP all correlated significantly with each other. From days 5 to 9, only mTF correlated with cerebral infarction, infarction volume, MBP levels, and outcome. CONCLUSIONS: Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.     

Heart transplantation in infants and children with situs inversus

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.     

Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations

BACKGROUND: This is the first report on the use of intra-arterial papaverine and percutaneous transluminal angioplasty in two patients with severe, symptomatic cerebral vasospasm who suffered ruptured arteriovenous malformations (AVMs). CASE DESCRIPTIONS: The source of hemorrhage was a venous aneurysm in the first case and a pedicular aneurysm of the distal posterior inferior cerebellar artery in the second case. In both cases, the AVMs were located in the superior vermis and there was minimal subarachnoid hemorrhage. The first patient underwent removal of the AVM before the period of cerebral vasospasm and the second patient underwent removal of the AVM after the cerebral vasospasm had resolved. The outcome was excellent in the first patient and poor in the second patient. CONCLUSION: Arteriovenous malformation with ruptured aneurysms may be at high risk for cerebral vasospasm even when there is minimal subarachnoid hemorrhage. We recommend early treatment of AVMs with ruptured pedicular, intranidal, or venous aneurysms to avoid rebleeding and to allow for aggressive treatment of cerebral vasospasm. The management of cerebral vasospasm after AVM rupture is discussed.     

Timing of surgery in patients with aneurysmal subarachnoid haemorrhage: rebleeding is still the major cause of poor outcome in neurosurgical units that aim at early surgery

OBJECTIVE: To investigate prospectively the proportion of patients actually operated on early in units that aim at surgery in the acute phase of aneurysmal subarachnoid haemorrhage (SAH) and what is the main current determinant of poor outcome. METHODS: A prospective analysis of all SAH patients admitted during a one year period at three neurosurgical units that aim at early surgery. The following clinical details were recorded: age, sex, date of SAH, date of admission to the neurosurgical centre, whether a patient was referred by a regional hospital or a general practitioner, Glasgow coma scale and grade of SAH (World Federation of Neurological Surgeons (WFNS) score) on admission at the neurosurgical unit, results of CT and CSF examination, the presence of an aneurysm on angiography, details of treatment with nimodipine or antifibrinolytic agents, and the date of surgery to clip the aneurysm. At follow up at three months, the patients' clinical outcome was determined with the Glasgow outcome scale and in cases of poor outcome the cause for this was recorded. RESULTS: The proportion of patients that was operated on early--that is, within three days after SAH--was 55%. Thirty seven of all 102 admitted patients had a poor outcome. Rebleeding and the initial bleeding were the main causes of this in 35% and 32% respectively of all patients with poor outcome. CONCLUSIONS: In neurosurgical units with what has been termed "modern management" including early surgery, about half of the patients are operated on early. Rebleeding is still the major cause of poor outcome.     

Amount of subarachnoid blood and vasospasm: current aspects. A transcranial Doppler study

Subsequent to admission after aneurysmal subarachnoid haemorrhage (SAH), 120 patients (74 women and 46 men) underwent microsurgical clipping of a total of 158 cerebral aneurysms within 96 hours after the bleed. Their mean age was 46 (20-91) years. Computed tomography (CT) findings were graded according to the modified Fisher scale and all patients had daily transcranial doppler (TCD) recordings of their basal cerebral arteries. In 19% of SAH was grade I on CT, in 44% grade II and in 37% grade III. The rate of patients who developed severe vasospasm as documented by TCD (mean blood flow velocities exceeding 160 cm/s on 2 or more consecutive days) was 39% for grade I patients, 26% for grade II patients and 34% for patients with SAH grade III on the initial CT. There was no difference in the rate of occurrence of severe vasospasm, when the patients were split into 2 groups according to the time of performance of the initial CT scan-within 24 hours, and 48-80 hours after SAH, respectively. It is concluded that the amount of subarachnoid blood on the initial CT scan should no longer be used as the indicator for occurrence and severity of the multifactorial entity vasospasm.     

Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis

BACKGROUND AND PURPOSE: Greater availability and improvement of neuroradiological techniques have resulted in more frequent detection of unruptured aneurysms. Because prognosis of subarachnoid hemorrhage is still poor, preventive surgery is increasingly considered as a therapeutic option. Elective surgery requires reliable data on its risks. Therefore, we performed a meta-analysis on the mortality and morbidity of surgery for unruptured intracranial aneurysms. METHODS: Through Medline and additional searches by hand, we retrieved studies on clipping of unruptured (additional, symptomatic, or incidental) aneurysms published from 1966 through June 1996. Two authors independently extracted data. We used weighted linear regression for data analysis. RESULTS: We included 61 studies that involved 2460 patients (57% female; mean age, 50 years) and at least 2568 unruptured aneurysms (27% >25 mm, 30% located in the posterior circulation). Mortality was 2.6% (95% confidence interval [CI], 2.0% to 3.3%). Permanent morbidity occurred in 10.9% (95% CI, 9.6% to 12.2%) of patients. Postoperative mortality was significantly lower in more recent years for nongiant aneurysms and aneurysms with an anterior location; the last 2 characteristics were also associated with a significantly lower morbidity. CONCLUSIONS: In studies published between 1966 and 1996 on clipping of unruptured aneurysms, mortality was 2.6% and morbidity was 10.9%. In calculating the pros and cons of preventive surgery, these proportions should be taken into account.     

Embolization of cerebral aneurysms using Guglielmi detachable coils--problems and treatment plans in the acute stage after subarachnoid hemorrhage and long-term efficiency

This study investigated the problems in treating ruptured aneurysms using Guglielmi detachable coils (GDCs) in the acute stage and evaluated the long-term efficacy in a series of 25 patients with 29 aneurysms. Eight patients with ruptured aneurysm treated within 2 weeks of the onset of subarachnoid hemorrhage (SAH) suffered no mortality or morbidity related to the procedure. Five patients achieved good outcomes despite severe SAH and returned to their previous lives. Three patients had poor clinical outcomes, two related to vasospasm and one related to pulmonary complication. More than 9 months follow-up was completed in 14 patients with 16 aneurysms. All six small aneurysms with small necks were completely obliterated and no recanalization was seen, and two of the eight large or giant aneurysms were completely obliterated. Recanalization was seen in four large or giant aneurysms and one small aneurysm due to coil compaction within 13 months. One patient died of rupture of a large aneurysm 18 months after complete obliteration of the aneurysm. Embolization using GDCs in the acute stage after SAH can prevent rerupture of cerebral aneurysms. However, recanalization due to coil compaction was the major problem in the chronic stage. Intensive follow-up and additional embolization, if necessary, is important.     

Surgical outcome of anterior communicating artery aneurysms

During a 6-year period, 65 consecutive patients who had undergone anterior communicating artery aneurysmal surgery were reviewed at a follow-up examination from 6 to 78 months (mean 35 months) after operation. On admission 69% of cases had a good Hunt and Hess scale (grades I to II) and 31% a poor grade (grades III to V). The degree of subarachnoid hemorrhage (SAH) was determined by Fisher's grade. Sixteen (25%) patients were classified in grades I and II. Forty-six percent of cases had pre-existing hypertension. Early surgery (within the first three days after the bleeding) was performed in 17% of cases. Intraoperative rupture of aneurysm occurred in six (9.2%) patients. Symptomatic cerebral vasospasm was diagnosed in 14 (22%) cases, but only 8 (12%) had evidence of low density on the computerized tomographic scan. Hydrocephalus developed in 16 (25%) cases and 10 needed ventriculoperitoneal shunting. The outcome was determined using the activity of daily life. Sixty-five percent of the patients made a good recovery and 13.8% died. The significant poor prognostic factors included a poor pre-operative grade of the Hunt and Hess scale, the presence of symptomatic cerebral vasospasm, and the Fisher's SAH grade of greater than II. Other factors which apparently were not related to the outcome included age, sex, timing of surgery, history of hypertension, intraoperative rupture, and the development of hydrocephalus.     

Combination of serine protease inhibitor FUT-175 and thromboxane synthetase inhibitor OKY-046 decreases cerebral vasospasm in patients with subarachnoid hemorrhage

The preventive effect of the serine protease inhibitor FUT-175 (nafamostat mesilate), a potent inhibitor of the complement system, against vasospasm was evaluated in 34 high risk patients with thick and diffuse subarachnoid hemorrhage (SAH) demonstrated by computed tomography corresponding to Fisher group 3. All patients underwent surgery within 96 hours following SAH and received the thromboxane A2 synthetase inhibitor, OKY-046, as part of standard care. FUT-175 (40-160 mg/day) was administered during the initial 4 days following surgery. 455 patients treated without FUT-175 in the Nagasaki SAH Data Bank (non-FUT group) formed the control group. FUT-175 significantly decreased the incidence of symptomatic vasospasm in patients with severe neurological grade (Hunt and Hess grade 3, p < 0.02; Hunt and Hess grade 4, p < 0.02). The incidence of favorable outcome was 76.5% in the FUT group and 60.4% in the non-FUT group, but not statistically different. However, when patients of Hunt and Hess grade 5 were excluded, the FUT group had a significantly improved outcome (p < 0.05). This study suggests that FUT-175 has an additive effect to OKY-046 in preventing vasospasm in high risk patients with severe SAH.