Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Intravenous thrombolysis for patients with reverse magnetic resonance angiography and diffusion-weighted imaging mismatch: SAMURAI and NCVC rt-PA Registries.

BACKGROUND AND PURPOSE: The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA). METHODS: Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of <7. RMM was defined as DWI-ASPECTS <7 without MAO. Clinical characteristics, symptomatic intracerebral hemorrhage (sICH) and favorable functional outcome (modified Rankin Scale score 0-2) at 90 days were compared amongst the four groups. RESULTS: Of the 486 patients enrolled (167 women, median age 74 years, median initial National Institutes of Health Stroke Scale score 13), reverse MRA-DWI mismatch was observed in 24 (5%). Of the clinical characteristics, cardioembolism was the only factor that was independently associated with RMM [odds ratio (OR) 5.49, 95% confidence interval (CI) 1.25-24.1]. Multivariable analyses revealed that patients with RMM more commonly had sICH than those with DWI-ASPECTS ≥ 7 irrespective of the presence (OR 5.44, 95% CI 1.13-26.1) or absence (13.1, 2.07-83.3) of MAO, and they had a more favorable functional outcome than those with DWI-ASPECTS < 7 plus MAO (7.45, 2.39-23.2). CONCLUSION: RMM was observed in 5% of patients treated with rt-PA and associated with cardioembolism. Patients with RMM may benefit from thrombolysis compared with those with EIC with MAO, although increment in the rate of sICH is a concern.

Run-up to participation in ATACH II in Japan.

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial.

Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt-PA Registry.

OBJECTIVE: To evaluate whether the pretreatment Alberta Stroke Programme Early CT Score (ASPECTS) assessed using diffusion-weighted imaging (DWI) predicts stroke outcomes at 3 months following IV recombinant tissue-type plasminogen activator (rt-PA) therapy. METHODS: Stroke patients treated with rt-PA (0.6 mg/kg alteplase) in 10 stroke centers in Japan were retrospectively studied. ASPECTS was assessed on DWI just prior to rt-PA injection. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 3 months. Secondary outcomes included death at 3 months and symptomatic intracerebral hemorrhage (sICH) within 36 hours. RESULTS: For the 477 patients (316 men, 71 +/- 11 years old) enrolled, the median NIH Stroke Scale score was 13 (interquartile range 7-18.5), the median ASPECTS on DWI was 8 (7-10), and sICH was identified in 15 patients (3.1%). At 3 months, 245 (51.4%) had an mRS score of 0-2, and 29 (6.1%) had died. Patients with an mRS score of 0-2 had higher median ASPECTS (9; interquartile range 8-10) than other patients (8; 6-9, p < 0.001). Using receiver operating characteristic curves, the optimal cutoff ASPECTS to predict an mRS score of 0-2 was > or =7. On multivariate regression analysis, ASPECTS > or =7 was related to an mRS score of 0-2 (odds ratio 1.85; 95% confidence interval 1.07-3.24), ASPECTS < or =4 was related to death (3.61; 1.23-9.91), and ASPECTS < or =5 was related to sICH (4.74; 1.54-13.64). CONCLUSION: ASPECTS on DWI was independently predictive of functional and vital outcomes at 3 months, as well as sICH within 36 hours, following rt-PA therapy for stroke patients.

Putaminal hyperperfusion in dystonic posturing on subtracted SPECT: a case report.

Dystonic posturing (DP) is one of the most reliable lateralizing symptoms for mesial temporal lobe epilepsy, although the mechanism remains unclear. We demonstrated a hyperperfusion area in the right putamen on subtracted postictal SPECT by using the automatic registration technique in one patient with ictal DP of the left hand. The putamen may play a key role in DP, similar to other diseases with dystonia.

[Paradoxical embolism with Chiari network, subsequently being accompanied by probable incomplete infarction: a case report].

We presented a patient of paradoxical embolism with Chiari network, subsequently being accompanied by probable incomplete infarction. This 21-year-old man suffered from consciousness disorder, aphasia and right hemiparesis, and hospitalized in November 6, 1999. Magnetic resonance imaging showed mixed intensity on T1 and T2-weighted images in part of the areas of the left anterior and middle cerebral arteries. Cerebral angiography revealed the early venous fillings and the capillary blushs. These findings implicated stroke in young adult. Still more transcranial color-flow imaging showed high intensity transient signals with "Chirp" sounds on the left middle cerebral artery. Transesophageal echocardiography detected Chiari network. Chiari network was thought the course of cerebral infarction. Over again 123I-IMP single-photon emission CT findings revealed the marked reduction of his cerebral blood flow comprehensively in the left hemispherium. It was suggested that the recanalization after the paradoxical cerebral embolism had caused incomplete infarction.

[Quantitative evaluation for scatter and attenuation correction in 99mTc SPECT--multicenter cooperation phantom study].

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).

Local fibrinolysis for middle cerebral artery embolism. Criteria for the indication by evaluation of residual cerebral blood flow and the results.

SUMMARY: We summarize our clinical experience of the local fibrinolysis for the middle cerebral artery (MCA) embolism.We added residual CBF factors of the ischemic territories to the usual criteria for the indication of fibrinolysis by Xe-SPECT CBF measurement. Forty-nine cases of local fibrinolysis for MCA embolism were reviewed and the results were compared with the conservative medical treatment cases. Angiographical improvements were achieved in 38 cases (76%, full reopening 17/49, partial reopening 21/49) and favorable outcomes (good recovery at GOS) were obtained in 32 cases (65%) at three months follow-up outcome. In comparison with the conservative medical treatment, fibrinolysis was superior at good recovery rate, severe disability rate and the resulted large infarction rate with statistical significance. We concluded that the local fibrinolysis with evaluation of the residual CBF of the ischemic territories achieved good results and outcomes and superior to the conservative medical treatment at some points. To keep the therapeutic time window, it is necessary to include the CBF factor to the criteria for the indication of this treatment.

[A case of clear cell meningioma originating from the cerebellar tentorium].

We report herein on a case of clear cell meningioma originating from the cerebellar tentorium, surgically treated by occipital transtentorial approach (OTT). A 67-year-old woman was admitted to our hospital in September, 1996, complaining of gait disturbance. MRI revealed an isointense mass on T1 and T2 WI, clearly enhanced with gadolinium in the right upper cerebellum originating from the tentorium. A left vertebral angiogram showed tumor stain from the right superior cerebellar artery. The tumor was subtotally removed by OTT on September 24, 1996. Gamma knife radiosurgery was performed for regrowing tumor 6 months after surgery. Histological examination revealed that the tumors were composed of sheets of clear, glycogen-rich cells and lobulated by thin connective tissues. There were no malignant findings, but some tumor cells had infiltrated into the cerebellar cortex. Immunohistochemistry showed that tumor cells were positive for EMA and vimentin, but negative for keratin. MIB-1 staining index was 7.02%. From these findings, this case was diagnosed as a typical clear cell meningioma originating from the cerebellar tentorium. From a review of the literature including our case, clear cell meningioma may be clinicopathologically malignant, so careful follow-up will be necessary.

Thrombolytic therapy for cerebral embolism.

SUMMARY: We summarized our clinical experience of thrombolytic therapy for cerebral embolism to evaluate the relation between the prognosis and the occlusion site, and the role of pre-treatment CBF measurement for supratentorial cerebral embolism. 56 cases of thrombolysis were analyzed and results were compaired with conservative medical therapy group. For ICA embolism, we stopped thrombolysis in the early period because of its poor collateral circulation. MCA embolism seemed to be a good candidate for this treatment and results were significantly better than the conservative medical therapy group in good recovery rate, severe disablity rate and large size infarction rate. In basilar artery embolism, thrombolysis seemed to be the most effective treatment in spite of the high mortality rate. Pre-treatment CBF measurement was important and useful to estimate the severity of ischemia, and it could make it possible to avoid severe hemorrhagic complications.

Quantification of regional cerebral blood flow and vascular reserve in childhood moyamoya disease using [123I]IMP-ARG method.

Both regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) in ten childhood Moyamoya disease were quantified pre- and post-operatively by autoradiographic processing using single photon emission computed tomography (SPECT) and N-isopropyl-rho-iodoamphetamine (IMP) (IMP-ARG method) to estimate hemodynamic effectiveness of surgical revascularization. Before surgery, in two patients, rCBF was reduced in the whole territories and loss of rVR in the anterior circulation was observed; +4.3% in the anterior cerebral artery (ACA), -3.0% in the middle cerebral artery (MCA) and +17.5% in posterior cerebral artery (PCA) territories. After surgery, in eight patients without transient ischemic attack (TIA) episodes, rCBF at rest was maintained around subnormal level in the whole territories, and mean rVR was up to +11.9, +17.3 and +28.3% in ACA, MCA and PCA territories, respectively. However, rVR in the anterior circulation was significantly reduced in comparison with rVR in the posterior circulation. Quantification of both resting rCBF and rVR using IMP-ARG method could provide reliable information concerning on surgical indication and its effectiveness in childhood Moyamoya disease.

Early effects of gamma knife radiosurgery on brain metastases: assessment by 201TlCl SPECT and 99mTc-DTPA-human serum albumin SPECT.

Thallium-201 chloride (201TlCl) single photon emission computed tomography (SPECT) was used to determine tumor viability, and the early and delayed images of technetium-99m-diethylenetriaminepenta-acetic acid-human serum albumin (99mTc-HSA-D) SPECT were used to assess tumor vascularity and permeability, respectively, in 17 patients with 18 brain metastases. SPECT was performed before, 1 week after, and 1 month after radiosurgery. The ratios of 201Tl and 99mTc-HSA-D uptake in a tumor were expressed as a ratio to uptake in the corresponding normal contralateral areas (uptake index). Magnetic resonance imaging with gadolinium was used to determine tumor volume. 201Tl index decreased significantly 1 week (p < 0.05) and 1 month (p < 0.005) after radiosurgery. In contrast, 99mTc-HSA-D indices of early and delayed images obtained at 1 week after radiosurgery were not significantly different from the pretreatment values. However, both were significantly low (p < 0.05) 1 month after radiosurgery. No change in tumor volume was detected 1 week following radiosurgery, but there was a significant decrease (p < 0.005) after 1 month. The reduction in tumor viability that occurs before the appearance of evidence of tumor shrinkage represents the early effect of radiosurgery on brain metastases. Reduction in tumor size, vascularity, and permeability occur subsequently.

Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil.

BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). CONCLUSIONS: The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.

Multiple segmental agenesis of the cerebral arteries: case report.

A case of multiple segmental agenesis of the cerebral arteries is presented. Cerebral angiography demonstrated bilateral so-called carotid rete mirabile, a similar "rete" of the right vertebral artery and intradural duplication of the left vertebral artery. These abnormalities are thought to be caused by multiple segmental agenesis of the cerebral arteries as they penetrate the dura mater. The embryological and anatomical significance of these findings is discussed.

Ischemic stroke and incomplete infarction.

BACKGROUND: The concept of selective vulnerability or selective loss o f individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke. SUMMARY OF REVIEW: A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute states of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in gamma-aminobutyric acid-ergic receptor sites at places where many neurons have been lethally injured. CONCLUSIONS: We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL x 100 g-1 x min-1).

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 1)--report on clinical usefulness in diagnosis of various brain diseases].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. The safety and clinical effectiveness of 123I-IMZ SPECT in the diagnosis of brain diseases were evaluated in 655 patients with various brain diseases, such as epilepsy, cerebrovascular diseases, degenerative diseases and mental disorders relating to BZR. This was a Phase 3 study conducted as a multicenter trial at 52 collaborating institutions. There was no significant adverse reactions in the clinical symptoms or abnormal laboratory test values. The investigators judged 123I-IMZ SPECT to be effective in 95% of 638 analyzed cases. The injected dose did not correlate with the image quality or the clinical effectiveness of 123I-IMZ SPECT, suggesting that these items depend largely on the characteristics of the apparatus used, the disease or pathology of the patients, rather than the dose. We conclude that 123I-IMZ imaging is safe and provides effective information based on BZR binding which is useful in the diagnosis of various brain diseases.

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 2)--Report on clinical usefulness in diagnosis of degenerative neurological diseases and mental disorders].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. A multi-center Phase 3 clinical study was performed to evaluate the clinical usefulness of 123I-IMZ-SPECT in the diagnosis of brain disorders in 169 patients with degenerative neurological diseases and 37 patients with mental disorders such as neurotic, stress-related and somatoform disorders. In dementia, the decrease in activity in late images, obtained three hours after administration of 123I-IMZ, correlated negatively with the dementia score. In Parkinson's disease and spinocerebellar degeneration. 123I-IMZ showed a more profound decrease in uptake in late images than seen in the cerebral blood flow (CBF) images, and this decrease was in proportion to the duration and severity of the illness. In mental disorders, the ratio of the late to early image counts showed a negative correlation with Hamilton's anxiety scale in all regions in the brain cortices. In panic disorders, the ratio of the cerebral count to the cerebellar count in the late images correlated negatively with the severity of the attack in the frontal, temporal and parietal cortices. These results suggest that 123I-IMZ-SPECT enables us to evaluate the neuronal damage in degenerative diseases and the decrease in the BZR binding potential in mental disorders.

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 3)--Report on clinical usefulness in epilepsy].

A Phase 3 clinical trial of 123I-Iomazenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors (BZR), was performed, and the clinical usefulness of IMZ was evaluated in 121 patients with epilepsy (106 cases with partial epilepsy and 15 cases with generalized epilepsy). A regional abnormality in the BZR distribution was detected in late IMZ images in 20 of 24 cases without abnormal MRI and/or X-ray CT findings. Moreover, only 16 of these 20 cases showed abnormal findings in the cerebral blood flow (CBF) images. In partial epilepsy, abnormal regions in late IMZ images agreed or partially agreed with epileptic foci estimated from the clinical symptoms of epileptic seizures, interictal EEG, and MRI and/or X-ray CT findings in 76%, 70% and 96% of the cases detected. These regions also agreed or partially agreed with the estimated epileptic foci in 92% of the cases with foci estimated by combination of those three methods and in 72% of those estimated by ictal EEG. The agreement or partial agreement rates of late IMZ images with each of the other methods were higher than those of CBF images, although the differences were not significant. For surgically-proven epileptic foci without any abnormality in the CBF image, abnormal regions were detected in late IMZ images. These findings suggest that IMZ SPECT is a useful new tool for detecting epileptic foci based on the distribution of BZR in the brain.