Analysis of ischemic cerebral lesions using 3.0-T diffusion-weighted imaging and magnetic resonance angiography after revascularization surgery for ischemic disease.

BACKGROUND: Cerebral revascularization surgery (CRS) is increasingly recognized as an important component in the treatment of complex cerebral vascular disease and tumors. CRS requires that the incidence of perioperative neurological complications should be minimized, because CRS for ischemic disease is often not the goal of treatment, but rather a prophylactic surgery. CRS carries the risk of focal postoperative neurological deficits. Little has been established concerning mechanisms of post-CRS ischemia. We used 3.0-T diffusion-weighted magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) to analyze the incidence and mechanism of ischemic lesions. METHODS: We studied the anterior circulation territory after 20 CRS procedures involving 33 vascular anastomosis procedures (13 double anastomoses and 7 single anastomoses) in 12 men and 8 women between June 2007 and October 2011. The operations included single or double superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis to treat internal carotid artery/MCA occlusions or severe MCA stenosis. A combined STA-MCA anastomosis and indirect bypass were performed for moyamoya disease. Postoperative DWI and MRA were obtained in all patients between 24 and 96 h after surgery to detect thromboembolism, hypoperfusion, or procedural ischemic complications and vasospasms of the donor STA. RESULTS: Follow-up DWI and MRA were carried out 1.8±0.6 days after CRS (range, 1-4 days). Temporary occlusion time for anastomoses averaged 18.9 min (range, 16-32 min). Asymptomatic new hyperintensities occurred in the ipsilateral hemisphere of 2 patients on postoperative DWI (10% patients/6.0% anastomoses), and 1 moyamoya patient (5.0% patients/3.0% anastomoses) developed a symptomatic hyperintensity in the ipsilateral occipital lobe in response to the operation. Two abnormal small (<5 mm) cortical DWI lesions were caused by sacrifices of a small branch of the recipient MCA. CONCLUSION: This study is the first postoperative 3.0-T DWI study of CRS and related clinical events. The incidence of symptomatic postoperative DWI abnormalities was restricted to 1 moyamoya patient representing 5.0% of total patients and 3.0% anastomoses. Although some postoperative DWI abnormalities occurred, CRS was found to be safe with a low risk of symptomatic ischemia.

Early computed tomography signs as early predictors of hemorrhagic transformation under heparinization in patients with cardiogenic embolism.

AIM: Early computed tomography (CT) signs are crucial to predict the onset of hemorrhagic transformation (HT) and are preventive to avoid a fatal hematoma after thrombolysis. In the present study, we retrospectively reviewed the clinical records of patients receiving heparinization to investigate the correlation between early CT signs and the frequency of HT. METHODS: We reviewed 96 patients with cardiogenic cerebral embolism. These patients were admitted within 24 h of the onset and were subsequently given 5000-15,000 units of heparin per day for 3 days. Owing to CT on admission, early CT changes were evaluated. Patient characteristics were also estimated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease and history of smoking. The probability of hemorrhagic transformation, or good outcome and independence was assessed by backward stepwise logistic regression analysis based on the maximum likelihood ratio. RESULTS: Higher baseline National Institutes of Health Stroke Scale (NIHSS) score, early CT signs and absence of hyperlipidemia diversely correlated with the occurrence of HT. Also, the presence or absence of early CT signs was significantly related to HT classification (χ(2)-test; P < 0.05). It was statistically significant that a higher baseline NIHSS score (OR 8.51; 95% CI 3.11-27.75) affected the outcome without showing a significant relationship to early CT signs. CONCLUSIONS: Presence of early CT signs correlated more strongly with HT than with the interval from symptom onset to hospital arrival. We might extend the therapeutic time for thrombolytic therapy, only if the early CT sign does not appear.

Early depressive symptoms after ischemic stroke are associated with a left lenticulocapsular area lesion.

BACKGROUND: Poststroke depression is one of the most frequent and important complications of stroke. Although many studies of depression after stroke have been reported, clinical association between the risk of depression after stroke and the lesion location remains unclear. The presence of depression after stroke reportedly confers a poor prognosis; however, early recognition of depressive symptoms may improve outcomes. We examined the relation between lesion location and presence of depressive symptoms 1 month after ischemic stroke, with a view toward early management of depressive symptoms. METHODS: In all, 134 consecutive patients with ischemic stroke were followed up to determine whether depression was present 1 month after stroke onset. Depressive symptoms were assessed by means of the Zung Self-rating Depression Scale. The lesion location was determined on magnetic resonance or computed tomography images. RESULTS: The incidence of depressive symptoms 1 month after stroke onset was 34.3%. Backward stepwise logistic regression analysis showed hypertension, education, and the presence of a left lenticulocapsular infarct, in particular, to be independent predictors of depressive symptoms. CONCLUSIONS: Patients with ischemic stroke, particularly in the left lenticulocapsular area, should be carefully evaluated for early detection and treatment of depressive symptoms, which may greatly influence outcome.

Correlation between insulin resistance and white matter lesions among non-diabetic patients with ischemic stroke.

OBJECTIVE: We investigated whether a correlation exists between insulin resistance and the severity of cerebral white matter lesions among non-diabetic patients with ischemic stroke. METHODS: The subjects were 105 consecutive patients without diabetes who were hospitalized due to non-cardioembolic stroke. The insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMA-IR). The degrees of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) were evaluated by the brain MRI. The HOMA-IR values >or=2.5 were indicative of the insulin resistance. RESULTS: The presence of PVH and DSWMH were 86.7 and 83.8%, respectively. The ratio of insulin resistance increased with higher grades of PVH and DSWMH. The HOMA-IR level in grade 3 PVH was significantly higher than those in grades 0 and 1. The HOMA-IR level in grade 3 DSWMH was significantly higher than those in grades 0-2. Multiple linear regression analysis showed that HOMA-IR was significantly associated with PVH or DSWMH. CONCLUSION: It was found that insulin resistance correlated with white matter lesions among non-diabetic patients with non-cardiogenic ischemic stroke.

Thrombosis in Japanese patients with Fabry disease.

Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme alpha-galactosidase (alpha-Gal) A. It has been postulated that the accumulation of globotriaosylceramide in the endothelial cells of blood vessels may lead to thrombosis of the brain and other tissues. Recently, enzyme replacement therapy (ERT) for Fabry disease is available. A high incidence of thrombotic accidents in Fabry disease has been postulated. However, a systemic study on thrombosis in cases of Fabry disease has not been undertaken. To clarify the incidence of thrombosis in Fabry disease, we screened 65 patients with Fabry disease (49 hemizygotes and 16 heterozygotes) from 39 unrelated Japanese families. We found that ten patients with Fabry disease (7 hemizygous males and 3 heterozygous females) had experienced thrombotic accidents, under 45-years-old in 8 cases. These 10 patients showed the gene mutations of classical Fabry disease. Nine of these thrombotic patients developed brain infarctions, one man who had the complication of recurrent thrombophlebitis, and the remaining woman showed central retinal artery occlusion and thrombophlebitis. We demonstrated a high incidence of thrombosis in Fabry disease (15%). ERT should be performed in patients not only in hemizygous males but also in heterozygous females and started at their early ages.

Administration of free radical scavenger edaravone associated with higher frequency of hemorrhagic transformation in patients with cardiogenic embolism.

Free radicals are known to activate coagulation and inhibit fibrinolysis. Edaravone, a free radical scavenger, protects vascular endothelial cells and neurons during acute brain ischemia in in vitro models. Hemorrhagic transformation and treatment outcomes were retrospectively examined in 76 patients with acute cardiogenic embolism treated with edaravone in addition to routine treatment within 24 hours of the onset of symptoms. Hemorrhagic transformation was categorized according to European Cooperative Acute Stroke Study-II. Patient characteristics were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, history of smoking, National Institutes of Health Stroke Scale on arrival, and modified Rankin scale at 3 months post-onset. Edaravone administration was one of the factors that contributed to increased frequency of hemorrhagic transformation, but had showed no significant relationship with the outcome. The present study showed that edaravone administration increased the frequency of hemorrhagic transformation with heparin in patients with cardiogenic embolism. Free radical scavenging may have promoted the coagulating conditions. Edaravone administration may allow reduction of the dose of heparin and tissue plasminogen activator in patients with acute ischemic stroke.

Effects of selective LDL apheresis on plasma concentrations of ICAM-1, VCAM-1 and P-selectin in diabetic patients with arteriosclerosis obliterans and receiving maintenance hemodialysis.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a serious complication in patients with end-stage renal disease (ESRD) caused by diabetic nephropathy. Adsorption of low-density lipoprotein (LDL) has been performed to treat ASO. While efficacy of this treatment has been reported in limb ischemia, the mechanism underlying the benefit remains unclear. We investigated how LDL adsorption affected soluble adhesion molecules; P-selectin, an endothelial and platelet activation marker; inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tissue necrosis factor (TNF)-alpha; and lipids in serum. METHODS: Selective LDL adsorption by dextran sulfate columns (LDL apheresis) was performed weekly for 10 weeks to treat eight hemodialysis patients with ASO, ESRD, and type 2 diabetes mellitus. Serum was sampled before and immediately after apheresis. RESULTS: LDL apheresis was performed safely. After LDL apheresis lipid concentrations were significantly reduced and clinical findings, such as Fontaine's classification and ankle brachial pressure index values, were improved. Pretreatment concentrations of soluble intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1) and also P-selectin were higher in patients than healthy controls. After apheresis these decreased, especially P-selectin. IL-1beta, IL-6, and TNF-alpha concentrations before apheresis were similar to those in controls and were unaffected by treatment. CONCLUSION: Effectiveness of LDL apheresis against ASO may involve decreased endothelial cell and platelet activation.

[Early detection of ischemic lesions in the super-acute phase of ischemic cerebrovascular diseases by imaging].

A thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), was recently approved in Japan for use on patients within 3 hrs of the onset of cerebral infarction. In order to salvage cerebral tissue after an ischemic insult, it is crucial to detect the ischemic lesion before it becomes irreversible and to detect the core and penumbra areas of the lesion for guidance in selecting the suitable therapy. In this symposium we discuss the detection of ischemic lesions using plain CT, perfusion CT, and MRI. In the section on plain CT, we present a typical case with early CT signs. In the section on perfusion CT, we report on the feasibility and limitation of the technique for the diagnosis of acute cerebral infarction. In the section on MRI, we study the usefulness of DWI for the early and highly reliable detection of ischemic stroke.

Enzyme replacement therapy for Fabry disease: morphologic and histochemical changes in the urinary sediments.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme alpha-galacotsidase A. Accumulation of glycosphingolipids, especially globotriaosylceramide, leads to renal damage in Fabry disease. In patients with Fabry disease, the urinary sediment contains excreted glycosphingolipids. With enzyme replacement therapy for Fabry disease now currently available, we examined whether the urinary sediment could be used to noninvasively monitor effectiveness of enzyme replacement therapy. METHODS: Four male patients with hemizygous classical Fabry disease received recombinant alpha-galactsidase A biweekly, and urinary sediments were assessed at 3-month intervals. RESULTS: The morphologic and immunohistochemical changes in urinary sediment at 6 and 18 months suggested that accumulations of glycosphingolipids in renal tissues were cleared by enzyme replacement. CONCLUSION: Examination of urinary sediments could serve as noninvasive monitoring of the effect of therapy in patients with Fabry disease.

Efficacy of edaravone, a free radical scavenger, for the treatment of acute lacunar infarction.

The effect of edaravone as an inhibitor of ischemic brain damage in addition to routine treatment was retrospectively examined in 70 patients with lacunar infarction who were admitted within 24 hours of symptom onset. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS). The modified Rankin Scale (MRS) was used to assess clinical outcomes at 3 months after onset, with a good outcome defined as MRS score < or =2. Risk factors were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, and a history of smoking longer than 2 months. The probability of a good outcome and independence at 3 months was assessed by backward stepwise logistic regression analysis based on the maximum likelihood ratio. Administration of edaravone yielded an odds ratio with multivariate adjustment of 6.49 (95% confidence interval, 1.35 to 50.32; p < 0.05) for a good outcome at 3 months. Higher baseline NIHSS score and higher age also adversely affected the outcome at 3 months (p < 0.005). Administration of edaravone improves the outcome of patients with lacunar infarction.

Aneurysmal subarachnoid hemorrhage in a patient with Wegener's granulomatosis.

A 34-year-old Japanese man admitted to hospital with pneumonia had previously undergone surgery for paranasal sinusitis and also for the clipping of an aneurysm at the origin of the anterior choroidal artery after subarachnoid hemorrhage. Laboratory tests performed at the present admission showed renal insufficiency and serological findings of raised proteinase 3 antineutrophil cytoplasmic antibody level. A renal biopsy was performed that showed diffuse necrotizing glomerulonephritis with fibrocellular crescents. The diagnosis of Wegener's granulomatosis(WG) was confirmed on the basis of the clinical picture, laboratory findings, and biopsies of renal tissues. The disease responded to prednisolone and cyclophosphamide. The association of WG with a ruptured intracranial aneurysm is rare and has not previously been confirmed.

Crossed cerebellar diaschisis in patients with cortical infarction: logistic regression analysis to control for confounding effects.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis (CCD) refers to reduced metabolism and blood flow in the cerebellar hemisphere contralateral to a cerebral lesion. Many cortical areas have been reported to cause CCD without consideration of confounding factors. We performed single-photon emission computed tomography (SPECT) in patients with cortical infarction to identify regions independently related to CCD, controlling for possible confounding effects. METHODS: Patients with unilateral cortical infarction (n=113; 75 male, 38 female; mean+/-SD age, 66+/-13 years) underwent SPECT of the brain with N-isopropyl-p-[(123)I]iodoamphetamine ((123)I-IMP). Regional cerebral blood flow was measured autoradiographically. Asymmetry indices (AIs) were calculated on the basis of ratios representing symmetrical regional cerebral blood flow in the cerebellum and 16 cerebral regions. CCD was defined as AI for cerebellum >0.1. AIs for 16 cortical regions were considered for both dichotomous and continuous variables for analysis of CCD occurrence by means of backward logistic regression. RESULTS: For dichotomized variables, hypoperfusion of postcentral (odds ratio [OR]=7.607; 95% CI, 2.299 to 25.174) and supramarginal (OR=3.916; 95% CI, 1.394 to 11.003) regions independently influenced CCD. For continuous variables, hypoperfusion of postcentral (OR=1.044; 95% CI, 1.019 to 1.068) and supramarginal (OR=1.021; 95% CI, 1.001 to 1.041) regions (and, as a negative factor, medial occipital regions; OR=0.942; 95% CI, 0.895 to 0.991) independently influenced CCD. CONCLUSIONS: Many cortical areas apparently do not contribute to CCD. Correspondence of CCD between dichotomized and continuous analyses suggests that location of a lesion, not severity, is the main determinant of CCD.

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Decreased cerebral blood flow in renal transplant recipients.

OBJECTIVE: We performed single-photon emission computed tomography (SPECT) to investigate the influence of renal transplantation on cerebral blood flow (CBF). PATIENTS AND METHODS: Fifteen renal transplant recipients and twelve normal subjects underwent cerebral SPECT with N-isopropyl-p -[123I] iodoamphetamine (123I-IMP). All transplant recipients received prednisolone and cyclosporine (CyA). Regional CBF (rCBF) was measured by defining regions of interest in the cerebral cortex, deep white matter, striatum, thalamus, and cerebellum. In transplant recipients, correlations to the mean overall cortical CBF were assessed using the interval from transplantation to measurement of SPECT, as well as the serum creatinine concentration. Moreover, to investigate the influence of CyA on CBF, the correlation between mean overall cortical CBF and CyA trough concentrations was assessed. RESULTS: In all regions, CBF in renal transplant recipients was significantly lower than in normal subjects. No significant correlation was seen between serum creatinine, interval from transplantation, or CyA trough concentrations and mean overall cortical CBF. CONCLUSION: Renal transplant recipients demonstrated a decrease in CBF, that can have an associated secondary pathology. Therefore, renal transplant recipients may benefit from post-operative MRI or CT.

Plasma immunoadsorption therapy for Guillain-Barré syndrome: critical day for initiation.

Immunoadsorption plasmapheresis (IAPP) is a method of removing circulating immune factors that is used to treat Guillain-Barré syndrome (GBS). We retrospectively analyzed the data on our GBS patients. In 21 patients treated with IAPP, linear regression analysis showed that the time from the onset of symptoms to the initiation of IAPP was correlated with the time required for improvement by one Hughes functional grade. We investigated the critical day for initiating treatment, which we defined as the day when initiation of IAPP was significantly more likely to improve function by at least one Hughes grade when compared with the outcome in patients receiving supportive therapy (non-IAPP group). The critical day was found to be day 6 after the onset of GBS.

Optimal hematocrit based on regional cerebral blood flow in hemodialysis patients with diabetic nephropathy.

BACKGROUND: The optimal hematocrit (Hctopt) in hemodialysis (HD) patients has yet to be determined based on the etiology and complications of their endstage renal disease (ESRD). To investigate this problem, we compared regional cerebral oxygen supply (rCOS) in diabetic (DM group) and non-diabetic HD patients (non-DM group) with data from subjects without renal disease or DM (control group) METHODS: Regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography (SPECT) by the N-isopropyl-p-[(123)I]-iodoamphetamine ((123)I-IMP)-autoradiographic (ARG) method, and both the O2 content (O2CT) of arterial blood and hematocrit (Hct) were evaluated. Using the regression lines of rCBF vs Hct and O2CT vs Hct, we established a convex curve between rCOS and Hct. The peak of the curve indicates the maximum rCOS (rCOSmax) and Hctopt for rCOSmax RESULTS: The rCBF in both the DM and non-DM groups was lower than that of the control group at the same Hct level, and the DM group had the lowest values. The rCOSmax values in the DM and non-DM groups were nearly equal, but both were lower than in controls. The Hctopt in the DM group was lower than that in the non-DM group by 6.3%±3.3% CONCLUSIONS: Although the difference in Hctopt values in the DM and non-DM groups was 6.3%, the rCOSmax values in both groups were nearly equal. This suggests that differences in the Hctopt may depend on complications or causes of ESRD. The optimal Hct in the DM group was 22.6%±1.9%, and that for the non-DM group was 29.0%±1.8%