Reversible widespread ischemia after early reperfusion detected by initial diffusion-weighted magnetic resonance imaging.

We herein report the time-related dynamic changes according to the diffusion-weighted image (DWI) findings after a cerebral ischemic attack in a 63-year-old woman. At 2 weeks after undergoing a lower limb amputation due to diabetic atherosclerosis, she experienced a sudden loss of consciousness and right hemiparesis. Magnetic resonance image revealed left frontal and parietal areas with an increased signal on the DWI, and magnetic resonance angiography (MRA) showed the left middle cerebral artery to be occluded at the superior M2 branch. However, on the next day the lesion on DWI, except for the gray matter, was observed to have almost completely resolved, and MRA showed complete recanalization of the left superior M2 branch with diminished clinical symptoms. Although a few cases of reversible DWI-identified lesions have been described in the literature, the occurrence of large, reversed DWI lesions in the middle cerebral artery territory with severe apparent diffusion coefficient decreases, as seen in our case, are exceedingly rare.

2D Thick-section MR digital subtraction angiography for the assessment of dural arteriovenous fistulas.

BACKGROUND AND PURPOSE: Although dynamic contrast-enhanced MR angiography studies for arteriovenous malformations (AVFs) and brain tumors have shown promising results, no formal attempt has yet been made to similarly evaluate dural AVFs. To assess the practical applicability of 2D thick-section contrast enhanced MR digital subtraction angiography (MRDSA) for the diagnosis and management of dural AVFs, MRDSA and intra-arterial digital subtraction angiography (IADSA) were comparatively evaluated. METHODS: We performed 80 consecutive MRDSA studies for 25 dural AVFs, including 11 cavenous sinuses, 9 sigmoid sinuses, 2 tentorial sinuses, one anterior condylar vein, one craniocervical junction, and one spine. MR images were continuously obtained following the initiation of a bolus injection of gadrinium chelates and subtraction images were constructed. We thereafter evaluated the imaging quality and hemodynamic information from all 46 MRDSA images performed in parallel with IADSA in either perioperative or follow-up studies. RESULTS: Most MRDSA images detected early venous filling, sinus occlusion, leptomeningeal venous drainage, and varices. It was difficult, however, to identify the feeding arteries because of both the partial volume effect and a low spatial resolution. Most important, MRDSA accurately detected aggressive lesions with leptomeningeal venous drainage and varices. CONCLUSION: Our MRDSA technique was found to have limited value for depicting all the anatomic details of dural AVFs, though it was able to identify important hemodynamic abnormalities related to the risk of hemorrhaging. MRDSA is therefore useful as a less invasive, dynamic angiographic tool, not only for perioperative studies but also for follow-up studies.

Surgical treatment of unruptured cerebral aneurysms in the elderly.

We retrospectively analyzed the prevalence and surgical outcomes of unruptured cerebral aneurysms in the elderly for the past five years. Between 1998 and 2002, we collected data from 575 subjects with unruptured aneurysms who had no history of subarachnoid hemorrhage (SAH). One hundred and eighty-two of these patients (31.7%) were aged > or = 70 years and they had 233 aneurysms. The proportion of older patients among all subjects increased significantly from 21.4% in 1998 to 40.3% in 2002. Unruptured aneurysms found in the elderly had a predominance of female, higher frequency of multiple aneurysms, and lower frequency of anterior communicating artery aneurysms when compared with those in the younger patients. The majority of intradural aneurysms detected in the elderly were less than 10 mm in diameter (84.8%). One hundred and eleven out of 224 intradural aneurysms in the elderly were treated (49.6%); most aneurysms were directly clipped, while only 13 aneurysms including six basilar artery aneurysms were coiled endovascularly. Among the 83 elderly subjects who underwent direct surgery, perioperative complication appeared in seven subjects (morbidity 8.4%, mortality 1.2%). No SAH occurred postoperatively and conservatively during 1-5 years of follow-up. Since the rupture rate of small unruptured aneurysms without SAH history is reported to be low, surgical indication should be considered with care particularly in the elderly.

Trends in subarachnoid haemorrhage in elderly persons from Nagasaki, Japan: analysis of the Nagasaki SAH Data Bank for cerebral aneurysm, 1989-1998.

BACKGROUND: Many industrialized countries are facing a volumetric growth of the senior population. We studied the trends in the incidence and outcome of subarachnoid haemorrhage (SAH) in patients aged >or=70 years. METHOD: We retrospectively reviewed the cases of 1030 patients registered in the Nagasaki SAH Data Bank from 1989 to 1993 and 1274 patients registered from 1994 to 1998. FINDINGS: The annual age-adjusted incidence of SAH per 100,000 increased only in women, from 15.4 in the 1989-1993 period to 19.7 in the 1994-1998 period. The average annual incidence of SAH per 100,000 women in the elderly aged >or=70 years increased significantly from 44.3 in the first period to 58.2 in the second period. In patients aged >or=70 years, the proportion of high-grade SAH (Hunt & Kosnik Grade IV and V) significantly increased from 27.2% in the first 5 years to 38.2% in the second 5 years. In patients aged<70 years, it increased slightly from 23.4% to 26.7%. The rate of favorable outcomes significantly fell from 43.9% (first period) to 30.9% (second period) in patients aged >or=70 years but was stable in patients aged<70 years. INTERPRETATION: Although the incidence of elderly patients with SAH in our study is compatible with or higher than that of other reports, we believe that elderly patients (especially women) with high-grade SAH may not have all been identified. When we discuss the management of ruptured and unruptured aneurysms in the elderly, we should bear these trends of SAH in mind.

N-acetylcysteine inhibited nuclear factor-kappaB expression and the intimal hyperplasia in rat carotid arterial injury.

Neointima formation associated with vascular restenosis is a complex local inflammatory process actively involving the vascular smooth muscle cell (SMC) proliferation. Nuclear factor-kappaB (NF-kappaB) is a transactivator of a diverse group of genes whose activation has been strongly associated with the cellular response to inflammation. Since anti-oxidant N-acetylcysteine (NAC) inhibit NF-kappaB activity in vascular SMC in vitro, we examined the in vivo effect of the NAC on balloon-induced neointimal formation in the carotid artery of rats. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. One group of these rats (n = 9) were treated with daily intraperitoneal injection of NAC (200 mg kg(-1)) for 14 consecutive days, whereas the control group (n = 9) was treated with saline. Fourteen days after the injury, the left carotid arteries were removed and analyzed under microscope. Several rats underwent the same treatment as above and were sacrificed three days after injury for immunohistochemistry and Western blot studies. A morphometric analysis revealed that there were significant differences in intima/media ratio between the two groups. Immunohistochemical and Western blotting studies demonstrated that NAC suppressed the injury-induced NF-kappaB activity in the medial SMC layer. Treatment with NAC suppresses vascular NF-kappaB activation and this inhibition reduced the pathological thickening of the arterial wall. The NF-kappaB pathway, therefore, represents an attractive therapeutic target for strategies to prevent vascular restenosis.

Differentiation between high-grade glioma and metastatic brain tumor using single-voxel proton MR spectroscopy.

The purpose of this study was to clarify the efficacy of single-voxel proton magnetic resonance spectroscopy (MRS) in differentiating high-grade glioma from metastasis. Thirty-one high-grade gliomas (11 anaplastic gliomas and 20 glioblastomas) and 25 metastases were studied. Proton MRS was performed using point-resolved spectroscopy with echo times (TEs) of both 136 and 30 ms. The peaks for lipid were evaluated at short TE, and those for N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were assessed at long TE. All the tumors exhibited a strong Cho peak at long TE. Twenty-one of 25 metastases showed no definite Cr peak. The remaining 4 metastases showed NAA and Cr peaks; however, the presence of NAA and relatively high NAA/Cr ratio (1.58+/-0.56) indicated normal brain contamination. All the gliomas, except for a single glioblastoma, showed a Cr peak with (n=16) or without (n=14) NAA. At short TE all metastases and glioblastomas showed definite lipid or lipid/lactate mixture, but anaplastic gliomas showed no definite lipid signal. Intratumoral Cr suggests glioma. Absence of Cr indicates metastasis. Definite lipid signal indicates cellular necrosis in glioblastoma and metastasis, and no lipid signal may exclude metastases.

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain.

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

Strategy for the treatment of inaccessible unruptured giant and large aneurysms of the internal carotid artery.

Our goal was to clarify the optimum management of the inaccessible unruptured giant and large aneurysms of the internal carotid artery (ICA). Since 1981, we have treated 18 patients with unclippable unruptured giant or large aneurysms of the ICA. Aneurysms were classified as either intracavernous or intradural. We performed proximal carotid occlusion in 12 patients and conservatively treated six patients. We retrospectively analyzed long-term outcomes in these patients. Four of seven patients with intradural aneurysm underwent proximal carotid occlusion, with good long-term outcomes. The three patients with intradural aneurysm, who were treated conservatively, died of subarachnoid hemorrhage. Eight of 11 patients with intracavernous aneurysm underwent proximal carotid occlusion, one dying of massive nasal bleeding 25 months after the procedure. In this case, the aneurysm was partially thrombosed, and residual lumen growth was revealed 22 months after proximal carotid occlusion. Cranial nerve paresis improved in five of the eight patients (63%), and two patients had a minor ischemic attack. Neurological problems failed to occur in the three patients with intracavernous aneurysm who were treated conservatively. The risk of rupture is relatively high in intradural giant and large aneurysms. Proximal carotid occlusion can effectively prevent bleeding from intradural aneurysms. Aggressive management is justified for intradural aneurysms with poor collateral circulation. Operative procedures in the management of an intracavernous aneurysm require careful consideration.

[A case of cerebral arteriovenous malformation complicated with intracerebral hemorrhage after endovascular embolization].

We reported a case of cerebral arteriovenous malformation (AVM), complicated with intracerebral hemorrhage (ICH), after endovascular embolization. A 51-year-old male suffered from intraventricular hemorrhage due to a rupture of an intranidal aneurysm on October 4, 1999. The first embolization procedure for the aneurysm and a part of the nidus was performed with 2-hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) and Liquid coil on day 21 after admission. On day 28, a second embolization was carried out for the residual nidus. Although most of the nidus was obliterated, the patient became comatose 10 hours after the second embolization. Computed tomography revealed a massive ICH in the right parietal lobe, and he underwent emergency evacuation of the hematoma. During the surgery, HEMA-MMA was seen in a draining vein. This caused venous stasis. Although the patient gradually improved postoperatively, he became comatose again because of a recurrence of ICH on day 36. Evacuation of the hematoma and removal of the nidus were performed again. The operative specimen showed AVM embolized by HEMA-MMA with non-specific inflammation and partial inflammatory degeneration of the vascular wall. Hemodynamic change such as venous stasis or elevated pressure of the feeding artery seemed to be the cause of the hemorrhage. Multi-staged embolization with longer intervals and intraoperative flow control were regarded as crucial for avoiding delayed hemorrhage.

[A case of spinal dural AVF treated by endovascular embolization].

Here we report a case of spinal dural arteriovenous fistula(AVF) treated by endovascular embolization. A 58-year-old female presented with progressive intermittent claudication and numbness of the lower extremities. MRI showed swelling of the spinal cord with intramedullary high signal intensity on T2-weighted image and intramedullary enhancement, suggested spinal cord myelopathy. Myelography demonstrated the dilated serpentine vessels in the subarachnoid space and focal filling defect. Angiography showed spinal dural AVF fed by bilateral lateral sacral artery. The draining vein was posterior spinal vein. Endovascular embolization using liquid material was performed under general anesthesia. The injection of glue included the distal feeding artery, the shunt itself and the initial part of draining vein. A complete cure was achieved, with a normal postoperative angiogram. MRI returned to normal with complete disappearance of T2 high signal, cord enlargement and enhancement by contrast medium. It was suggested that venous congestion induced the transient spinal ischemia, manifested as intermittent claudication. Endovascular embolization using liquid material was safe and quite effective for spinal dural AVF.

Computerized Assessment of Carotid Plaque Echogenicity before Stenting.

SUMMARY: To assess the ability of transcutaneous ultrasound (US) to identify carotid atherosclerotic plaques at high risk for development of procedural strokes, the authors retrospectively analyzed the plaque echomorphology by means of gray-scale value (GSV). Both transcutaneous and intravascular US demonstrated a similar ability to characterize the atherosclerotic plaques. A case with embolic complication was proven to have had the lowest GSV in the studied cases. With computerized assessment of plaque echogenicity, pre-procedural transcutaneous US may be used to predict plaques that are associated with a high risk of distal embolization.

Local thrombolysis for acute ischemic stroke based on findings of diffusion and perfusion MRI.

SUMMARY: Cerebral per fusion and cerebral tissue integrity were studied in 13 patients with acute embolic stroke in the territory of the internal carotid artery by diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) within six hours after onset. PWI/DWI mismatch lesion was depicted in six patients. MCA was occluded in five of six patients, who underwent local thrombolytic therapy. In three cases, complete restoration of the cerebral circulation was obtained and enlargement of irreversible brain damage compared to initial DWI lesion was prevented. Seven patients without PWI/DWI mismatch did not undergo thrombolytic therapy. Spontaneous reopening of occluded MCA was verified with subsequent cerebral angiography in one of seven patients. CT depicted symptomatic intracerebral hemorrhage in this patient. It is concluded that DWI and PWI in combination are useful in selection of patients for thrombolytic therapy.

[Penetrating head injury caused by an icepick].

The patient was a 39-year-old man, with a three year history of schizophrenia, who attempted suicide by piercing his head with an icepick. Spinal cord injuries and shock caused by falling from the fifth floor of the building following this penetrating injury were also noted on admission. The CT scan revealed that the icepick had deeply penetrated the posterior fossa from the forehead. No new neurological deficits or cerebrospinal fluid leakage appeared after admission. The icepick was removed completely without difficulty. In penetrating head injuries, early assessment with cerebral angiography to determine the extent of vascular injury is useful for deciding if surgery should be performed.

Local distribution into brain tumor and pharmacokinetics of 4-pyridoxate diammine hydroxy platinum, a novel cisplatin derivative, after intracarotid administration in rats with 9L malignant glioma: simultaneous brain microdialysis study.

Local distribution into brain tumor and the pharmacokinetics of 4-pyridoxate diammine hydroxy platinum (PyPt), a novel cisplatin derivative, were examined using rats implanted with 9L glioma and compared with cisplatin. PyPt (5.0 mg/kg) and cisplatin (3.5 mg/kg) were administered as selective intracarotid infusions for 30 min to the rats. Dialysates from extracellular fluid (ECF) in tumor and non-tumor brain tissues were collected by simultaneous microdialysis. The amount of platinum was determined by atomic absorption spectrophotometry, as representative of the drug administered. Plasma concentration of total and protein unbound platinum, and urinary excretion amount and tissue distribution of total platinum were also determined. Unbound platinum was accumulated preferentially in the brain tumor tissue ECF after drug administration, while there was little distribution into normal tissue ECF of the brain. In the brain tumor, the values of the unbound platinum AUC and MRT, where AUC is the area under the concentration-time curve and MRT is the mean residence time, for PyPt were 1.7 and 1.3 times larger than with cisplatin, respectively. The brain tumor distribution coefficient (the ratio of brain tumor ECF platinum AUC to plasma protein unbound platinum AUC) for PyPt (0.85) was higher than that for cisplatin (0.69), indicating that the local amount of platinum distributed into the glioma is enhanced by PyPt rather than by cisplatin. The binding to plasma proteins of PyPt (23%) was lower than that of cisplatin (65%). The total platinum concentration in tissues after administration of PyPt was significantly lower than that of cisplatin in the kidney, liver and spleen. In addition, the urinary excretion amount of total platinum after the administration of PyPt was significantly larger than that of cisplatin. These results suggested that PyPt is easily eliminated by rapid urinary excretion because of its reduced interaction with plasma proteins and poor distribution to the kidney or reticuloendothelial tissues such as the liver and spleen. It is concluded that PyPt is an effective cisplatin derivative for the treatment of gliomas with the added advantage of enhancing local distribution of drug into the brain tumor and reducing its accumulation in the kidney, which has previously caused severe nephrotoxicity.

Mild hypothermia on anoxic depolarization and subsequent cortical injury following transient ischemia.

Anoxic depolarization (AD) is one of the major physiological characteristics in the ischemic core. The effect of mild hypothermia on the appearance of AD and subsequent brain injury following profound ischemia is studied to evaluate the protective mechanism of hypothermia against severe ischemia. Sprague-Dawley rats were subjected to transient ischemia by hypotension (50-20 mmHg) and bilateral carotid artery occlusion (BCA-O) for 20 min in normothermia and 30 min in hypothermia. The temperature of body and temporal muscles was maintained at 37.5 degrees C and 36.5 degrees C in normothermia and 33.0 degrees C and 31.0 degrees C in hypothermia, respectively. Recording of the DC potential shift and electrocorticogram and monitoring of the cortical blood flow (CoBF) with a laser Doppler flowmeter were done epidurally on the right parietal cortex. The right parietal cortex pathology was examined 24 h after ischemia in normothermia and after 30 days in hypothermia. AD appeared in all seven normothermic rats with a fall in the CoBF to 9%-10% of the control flow. However, in spite of CoBF reduction to 8%-9% of the control flow, it did not appear in five hypothermic rats. Intra-ischemic CoBF was not statistically different between these two groups. AD appeared with the CoBF decreasing to 4%-5% of the control flow in seven hypothermic rats. Intra-ischemic CoBF in hypothermic rats exhibiting AD was significantly lower than the other two groups. The interval between BCA-O and the appearance of AD in hypothermic rats was 5.1 +/- 0.3 min (mean +/- SE), which was significantly longer than the 2.2 +/- 0.5 min observed in normothermia (p < 0.0005). Of seven normothermic rats exhibiting AD, two died within 24 h and four revealed massive neuronal injury. Of seven hypothermic rats with AD, four died between day 2 and day 13, and one revealed diffuse cerebral infarction. However, no severe ischemic injury or ischemic death was observed in all five hypothermic rats without AD. The incidence of severe neuronal injury or ischemic death was significantly lower in hypothermic rats without AD compared with normothermic rats with AD (p < 0.02) or hypothermic rats with AD (p < 0.05). Although mild hypothermia delays AD, it is suggested that raising the cerebral blood flow threshold for AD appearance has a key role in the hypothermic protection of a severely ischemic area such as the ischemic core.

[Presurgical mapping with functional MRI: comparative study with transcranial magnetic stimulation and intraoperative mapping].

PURPOSE: The accuracy of preoperative mappings in patients with brain tumors near the central sulcus using functional magnetic resonance imaging (fMRI) or transcranical magnetic stimulation (TCS) was evaluated by comparative reference to intraoperative mapping. METHODS: The thumb movement was evoked by TCS for the mapping of the motor cortex. After the placement of the marker determined by TCS on the scalp, fMRI under motor tasks consisting of repetitive grasping was performed. For motor cortex activation, an axial oblique plane to maximize gray matter sampling in the rolandic cortex was employed in order to compare these different mapping techniques more precisely. Sixteen patients with brain tumors were included in this study. RESULTS: In nine patients, fMRI disclosed activation in one restricted gyrus or in the localized area around one restricted sulcus. Of these nine patients, preoperative TCS mapping corresponded closely with fMRI in six, while in the remaining three, the TCS marker fell between 1 and 2 cm apart from the fMRI-activated area. However, in these three patients, intraoperative electrocortical stimulation corresponded with the preoperative mapping with fMRI. In six patients, contigucus two gyri were activated by motor tasks. The TCS marker was disclosed on one of the two activated gyri. Of these six patients, the position of the TCS marker and fMRI-activated site corresponded with each other in four cases. They were found on the same gyrus but there was 1.0-2.0 cm distance between them in two cases. Intraoperative somatosensory evoked potential was monitored in two of these six cases. They corresponded well with the mapping by fMRI and TCS together. In only one patient, no significant activation area was obtained by fMRI because of excessive head motion during motor tasks. The TCS marker in this patient was identical with intraoperative electro-cortical stimulation mapping. CONCLUSION: For presurgical planning in patients with brain tumor near the central sulcus, comparative evaluation with fMRI and TCS is applicable and provides accurate functional mapping.

Characteristics of symptomatic chronic subdural haematomas on high-field MRI.

We studied the frequency of various features of the appearances on high-field MRI in symptomatic patients with chronic subdural haematomas (CSDH). The ability to predict recurrence after treatment with one burr-hole procedure using MRI was evaluated. A total of 40 patients with symptomatic CSDH underwent MRI at 1.5 T. All haematomas were evacuated within a few days of the MRI examination. Symptomatic CSDH were divided into five groups according to the MRI findings: group A (11 cases), isointense or low signal on T1- and low signal on T2-weighted images; group B (18 cases), high signal on T1- and low signal on T2-weighted images; group C (5 cases), high signal on both T1- and T2-weighting; group D (1 case), low signal on T1- and high signal on T2-weighted images; group E (5 cases), heterogeneous intensity on T1- and T2-weighting throughout the haematoma cavity. The mean interval between onset of symptoms and MRI for group A was 5.0 +/- 4.1 days, which was significantly shorter than that for group B (9.4 +/- 4.4 days, P < 0.02), group C (27.8 +/- 20 days, P < 0.005) or group E (17.8 +/- 12.2 days, P < 0.01). Recurrence was seen in three haematomas of group A and one of group B. Reoperation was most closely correlated with diffuse low signal on T2-weighted images but not with a multiloculated appearance. Low signal on T2 weighting was surprisingly high (72.5%) and the age of the haematomas as estimated on the MRI correlated well with the interval between the onset of symptoms and MRI. Our findings support the causative role of recurrent bleeding in the enlargement of CSDH.

An additional monitoring of regional cerebral oxygen saturation to HMPAO SPECT study during balloon test occlusion.

BACKGROUND AND PURPOSE: To increase the reliability of 99mTc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) study in the evaluation of hemodynamic change with balloon test occlusion (BTO) of the internal carotid artery, we attempted to clarify the usefulness of additional monitoring of regional oxygen saturation of the brain (rSO2). METHODS: During BTO, rSO2 monitoring with transcranial near infrared spectroscopy was performed 17 times on 16 patients. Asymmetrical distribution of the tracer was classified visually as follows: group 1, little or no asymmetry, and group 2, moderate or severe asymmetry. Seven regions of interest (ROI) were defined in the middle cerebral artery area of each hemisphere, and the asymmetry index (AI)=200x(Cnon-Coccl)/(Cnon+Coccl)), where Cnon=mean counts on the nonoccluded side, and Coccl=mean counts on the occluded side were also calculated. Then, mean AI (MAI) was obtained from AI of 7 ROIs for each study. RESULTS: Of the 17 procedures, 10 BTOs were in group 1 and 5 BTOs were in group 2. Two patients did not undergo SPECT study because of the immediate appearance of a neurological deficit with BTO; they were defined as group 3. The MAI in group 1 was 2. 6+/-3.3%, which was significantly smaller than the MAI in group 2 (25.6+/-5.0%, P<0.02). The DeltarSO2 (baseline rSO2-rSO2 during ICA occlusion) with BTO in group 1 was 1.5+/-1.4% (n=10), which was statistically smaller than that in group 2 (5.5+/-1.3%, n=4, P<0.05). The DeltarSO2 in group 3 was 9.0+/-0.0% (n=2). In group 1, however, rSO2 began to decline when the stump pressure fell to 45 mm Hg and always declined when the stump pressure fell below 40 mm Hg. Furthermore, in group 1, a significant correlation was observed between the DeltarSO2 and stump pressure (r=0.85, P<0.0001). CONCLUSIONS: This preliminary study reveals that an obvious asymmetrical SPECT pattern always accompanies a profound decrease in rSO2 and that rSO2 parallels a severe reduction in stump pressure in cases exhibiting a symmetrical SPECT pattern. Thus, the cerebral oximetry sensitively reflects the cerebral oxygenation, and simultaneous measurements of rSO2 and stump pressure with 99mTc-HMPAO SPECT study apparently are useful in evaluating hemodynamic integrity with BTO.

Anoxic depolarization determines ischemic brain injury.

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shifts, electrocorticogram, and cortical blood flow (CoBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of 28 animals. Circulation was reinitiated 15 min after AD onset in 11 rats (group A) and 10 min after onset in 10 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 12 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 14 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of 5 rats from group A. Ischemic neuronal changes were absent or minimal in only 1/5 of group A animals, a much lower fraction than in group B (4/4, p < 0.05) or in group C (5/5, p < 0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 15 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37 degrees C.

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.