Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

Arterial occlusion sites on magnetic resonance angiography influence the efficacy of intravenous low-dose (0.6 mg/kg) alteplase therapy for ischaemic stroke.

AIMS: To determine the predictors of efficacy, including magnetic resonance imaging information, for low-dose intravenous alteplase therapy for stroke patients. METHODS: Seventy-eight patients were prospectively enrolled in a single Stroke Unit (SU) receiving alteplase at a dose of 0.6 mg/kg during the initial 27 months after its approval in Japan. Ischaemic changes and vascular lesions were identified using computed tomography, diffusion-weighted magnetic resonance imaging, and magnetic resonance angiography. Early ischaemic signs were assessed using the Alberta Stroke Program Early CT Score. RESULTS: The median baseline National Institutes of Health Stroke Scale score of 78 patients was 12. In 19 patients (24%), the National Institutes of Health Stroke Scale score improved by >or=8 points at 24 h. After multivariate adjustment, occlusion at the internal carotid artery (odds ratio 11.82, 95% confidence interval 1.73-142.74), Alberta Stroke Program Early CT Score on diffusion-weighted imaging

Baseline NIH Stroke Scale Score predicting outcome in anterior and posterior circulation strokes.

OBJECTIVE: The NIH Stroke Scale (NIHSS) may not appropriately assess the spectrum of posterior circulation (PC)-related neurologic deficits. We determined the cutoff baseline NIHSS score that predicts independent daily life activity during the chronic stage in anterior circulation (AC) vs PC ischemic strokes. METHODS: A total of 310 consecutive patients hospitalized within 3 days after the onset of an ischemic stroke were prospectively enrolled in the study. Patients on thrombolytic therapy were excluded. In all patients, infarcts and vascular lesions were identified primarily using magnetic resonance techniques. A favorable outcome was defined as a modified Rankin Scale score of < or =2 at 3 months poststroke. RESULTS: In 101 patients with PC stroke, the total baseline NIHSS score was lower (p < 0.001), and the subscores of ataxia (p < 0.001) and visual fields (p = 0.043) were higher than in 209 patients with AC stroke. Multivariate-adjusted OR for the favorable outcome in patients with PC vs AC stroke was 2.339 (95% CI 1.331-4.109, p = 0.003). A low baseline NIHSS score was independently predictive of a favorable outcome in both patients with PC (OR 1.547, 95% CI 1.232-1.941) and AC (1.279, 1.188-1.376) stroke. The optimal cutoff scores of the baseline NIHSS for the favorable outcome were < or =5 for patients with PC stroke (sensitivity, 84%; specificity, 81%) and < or =8 for patients with AC stroke (sensitivity, 80%; specificity, 82%). CONCLUSIONS: The cutoff score of the baseline NIH Stroke Scale (NIHSS) for a favorable chronic outcome was relatively low in patients with PC stroke compared to patients with AC stroke. The NIHSS appears to have limitations with respect to its use when comparing the neurologic severity of PC and AC stroke.

Eccentric stenosis of the carotid artery associated with ipsilateral cerebrovascular events.

BACKGROUND AND PURPOSE: Eccentric stenosis of the coronary artery is associated with plaque disruption and acute coronary syndrome. The purpose of the present study was to determine whether eccentric stenosis of the carotid artery contributes to cerebrovascular events. MATERIALS AND METHODS: Of 6859 patients with vascular diseases who underwent duplex carotid ultrasonography, we studied 512 internal carotid arteries in 441 patients who had a maximum area stenosis at or more than 70%, which corresponds with approximately 50% or more by the NASCET method. The maximal (A) and minimal wall thicknesses (B) were measured on cross-sectional sonography images, and an eccentricity index was calculated using the following formula: (A - B)/A. Arteries in the lowest quartile of the eccentricity index (<0.69) were defined as having a concentric stenosis, whereas the others were defined as having eccentric stenosis. The underlying clinical characteristics and plaque morphologies, as well as the occurrence of ipsilateral ischemic stroke or transient ischemic attack in the preceding year, were compared between patients with eccentric and concentric stenosis. RESULTS: Patient characteristics and plaque morphology were similar between the 2 groups. Cerebrovascular events occurred more frequently ipsilaterally to the artery with eccentric stenosis (13.5%) than to the artery with concentric stenosis (5.5%; P = .013); the difference was more evident when cerebrovascular events of presumed carotid arterial origin were assessed (P = .005). After adjusting for risk factors and plaque morphology, eccentric stenosis was independently related to the presence of recent cerebrovascular events (odds ratio = 2.76; 95% confidence interval = 1.19-6.40). CONCLUSIONS: In patients with an area carotid stenosis of 70% or more, eccentric plaque was associated with a significantly increased incidence of ipsilateral cerebrovascular events compared with patients with concentric stenosis.

Association between signal hyperintensity on T1-weighted MR imaging of carotid plaques and ipsilateral ischemic events.

BACKGROUND AND PURPOSE: To investigate associations between cerebral ischemic events and signal hyperintensity in T1-weighted MR imaging (T1WI) of carotid plaque according to stenosis severity and to estimate persistence of T1WI signal hyperintensity. METHODS: A total of 222 patients (392 atherosclerotic carotid arteries) underwent plaque imaging using 3D inversion-recovery-based T1WI (magnetization-prepared rapid acquisition with gradient-echo [MPRAGE]). Carotid plaque with intensity on MPRAGE of >200% that of adjacent muscle was categorized as "high signal intensity" and correlated with ipsilateral ischemic events within the previous 6 months. A total of 58 arteries (35 patients) underwent repeat MR imaging a total of 70 times at a median interval of 279 days (range, 10-1037 days). RESULTS: Ipsilateral ischemic events were more frequent in patients with MPRAGE high signals than in patients with low signals in the 0%-29%, 30%-69%, and 70%-99% stenosis groups: Relative risk (95% confidence interval) was 2.50 (0.96-6.51), 7.55 (1.84-31.04), and 1.98 (1.01-3.90), respectively. In the 70 cases of repeat MR imaging, 29 of 30 cases with high signals on the preceding MR imaging maintained high signals. Of the 58 arteries that underwent repeat MR imaging, 4 of 22 carotid arteries with high signals developed ipsilateral subsequent ischemic events within 1 year, whereas none with low signals developed subsequent events. CONCLUSIONS: Carotid plaque signal hyperintensity on T1WI is strongly associated with previous ipsilateral ischemic events, persisting over a period of months, and may indicate risk of subsequent events. Larger clinical trials are warranted to clarify associations between signal hyperintensity and risk of subsequent cerebral ischemic events.

How to improve repetition ability in patients with Wernicke's aphasia: the effect of a disguised task.

Dissociation "automatico-voluntaire" is a symptom observed in aphasic patients. We elucidated the difference between voluntary and involuntary speech output in a quantitative manner using the same task materials in nine patients with Wernicke's aphasia. All the patients exhibited better ability and less paraphasias in a repetition task elicited in a disguised condition than in an ordinary repetition condition. This result indicates that the output difficulty in Wernicke's aphasia might be a disability of volitional control over the language system.

Losartan, an angiotensin II (AT1) receptor antagonist, preserves cerebral blood flow in hypertensive patients with a history of stroke.

In patients with severe hypertension, chronic heart failure or a history of stroke, the lower limit of autoregulation of cerebral blood flow (CBF) is shifted to higher levels of blood pressure (BP) than those observed in healthy subjects. The aim of pharmacotherapy for hypertensive patients with an impaired autoregulation of CBF should be to reduce BP while preserving an appropriate CBF. In the present study, 16 hypertensive patients who had had an episode of stroke more than 4 weeks previously were administered the angiotensin II (AT1) receptor antagonist losartan at daily doses of 25-100 mg for 4 weeks. Systolic and diastolic blood pressures were recorded for 24 h using an ambulatory BP monitoring system. CBF in both hemispheres of the cerebrum and cerebellum was quantified using single photon emission tomography with N-isopropyl-p-[123I]iodoamphetamine. At baseline, CBF was 29.7 +/- 6.7 ml/min/100 g in the cerebrum and 31.5 +/- 7.5 ml/min/100 g in the cerebellum. At the end of treatment, BP was lower, while CBF increased by 7.7% in the cerebrum, and remained at the baseline level in the cerebellum. Thus, CBF was preserved despite the reduction in BP. We consider the use of losartan is advantageous for hypertensive patients with a history of stroke in whom autoregulation of CBF is potentially impaired.

Predictor of cognitive deterioration in elderly subjects by auditory-evoked magnetic signal using magnetoencephalography.

Recent development of auditory-evoked magnetoencephalography (A-MEG) made it possible to measure interhemispheric neural conduction time (INCT) of auditory impulses. We estimated INCT with A-MEG and cognitive function with mini-mental state examination (MMSE) in 85 elderly patients with chronic dizziness (CD) and found that INCT was negatively correlated with MMSE scores (p<0.001). In 11 of 85 patients whose MMSE scores were within the normal range, A-MEG and MMSE were repeated for the subsequent 4 years to find longitudinal changes in INCT and cognitive function. The 11 patients were divided into two groups according to the baseline INCT values, such as Group A with normal INCT (n=7) and Group B with abnormally prolonged INCT (n=4). In Group A, INCT and MMSE scores remained within the normal range throughout the 4-year period. In Group B, INCT showed the tendency towards progressive prolongation during the follow-up period, and MMSE scores decreased to abnormally low levels at the third or fourth follow-up year in all the patients. The present results suggest that rapid neural interaction of both cerebral hemispheres is needed to maintain normal cognitive function. Abnormal INCT prolongation in elderly subjects suggests subclinical cortical network dysfunction and may predict the future development of cognitive deterioration.

Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose.

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value <3.0), but prothrombin fragment 1+2 increased minimally 10 min after administration (from 0.4 to 1.1 nmol/ml and from 0.4 to 0.7 nmol/ml, respectively, normal value 0.4-1.4 nmol/ml). Plasma levels of D-dimer remained unchanged. The massive subcutaneous hemorrhage in the former patient improved in 14 days. Anticoagulation was restarted in the latter patient after 14 days of PCC administration. There were no embolic episodes during the month after PCC administration. In conclusion, a small amount of PCC may be effective in immediately correcting increased INR levels with increased plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa and may partially activate the coagulation system without any effects on plasma levels of D-dimer.

Visualisation method of spatial interictal discharges in temporal epilepsy patients using magneto-encephalogram.

The aim of the study was to develop a method for investigating how interictal epileptic discharges in temporal epilepsy patients are activated spatially. The activity was measured using magneto-encephalography (MEG). The MEG data were used to produce a current-arrow map that reflected the topographic distribution of the electrical current for each peak epileptic waveform. A large current distribution was obtained that appeared to be contained in the limbic structure, in each temporal lobe. The large current orientation indicated two opposite directions. Furthermore, the decrease in the maximum strength of the current-arrow, depending on the medication (e.g. the decrease from 11 to 6 pT m-1 in the left temporal lobe (contralateral stimuli)), suggested that the discharge distributions could be used to verify the efficacy of medication. Thus the topographical visualisation method could be a new strategy for diagnosis in temporal epilepsy patients.

Homonymous defect of macular vision in ischemic stroke.

It is generally believed that a homonymous defect of macular vision (HMV) is caused by a small lesion restricted to the occipital lobe tip and rarely results from ischemic stroke. The incidence of HMV was studied retrospectively in 54 patients with infarction of the posterior cerebral artery territory who underwent Goldmann's visual field test. HMV was found in 6 patients (11%). In all of them, HMV was first dismissed due to a confrontation test of visual fields at the bedside and later detected by Goldmann's visual field test. All had a relatively large infarction extending from the occipital lobe tip to the posterior part of the calcarine cortex and/or the neighboring subcortical regions. Stroke-induced HMV can be caused by a large lesion involving the occipital pole and may not be so rare as generally considered.

Microembolic signals and diffusion-weighted MR imaging abnormalities in acute ischemic stroke.

BACKGROUND AND PURPOSE: The clinical significance of microembolic signals (MESs) detected by transcranial Doppler sonography (TCD) in acute ischemic stroke remains unclear. The purpose of the present study was to assess the findings of diffusion-weighted MR imaging (DWI) and other clinical characteristics in patients with acute ischemic stroke and MESs. METHODS: We performed TCD and DWI within 48 hours and 7 days, respectively, after stroke onset in 28 patients with acute brain infarction. The relationship between the number of MESs and DWI findings, risk factors for stroke, National Institutes of Health Stroke Scale (NIHSS) score on admission, and arterial disease was examined. RESULTS: Ten patients had MESs detected by TCD (MES group) and 18 had no MESs (control group). The frequency of hypertension, diabetes mellitus, hyperlipidemia, and smoking; NIHSS score; blood-coagulation parameters; and interval between stroke onset and DWI study did not differ between the two groups. However, arterial disease was more frequent in the MES group than in the control group. Small, multifocal ischemic lesions (<10 mm in diameter) on DWI were more frequent in the MES group than in the control group. Conventional CT and MR imaging often failed to show these lesions. CONCLUSION: Small, often asymptomatic DWI abnormalities were more frequent in patients with MESs detected by TCD and with large-vessel occlusive diseases than in stroke patients without MESs. TCD and DWI may provide early clues to the mechanism of stroke in the acute phase.

[Neuroprotective therapy for the treatment of acute ischemic stroke].

Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells. Ischemic insult causes damages of vascular wall including the endothelium which play an important role in the development of hemorrhagic changes or cerebral edema. Vascular protection is considered as important as neuroprotection in treatment of clinical stroke. Mild hypothermia has neuroprotective and vascular protective actions and hence may be more effective than neuroprotective drugs for the treatment of stroke. The prevention of fever, which often occurs in severe stroke, may exert the similar effect as hypothermia in neuroprotection. Neuroprotective therapy in the future should proceed toward the simultaneous protections of neurons and vessels using combination of multiple drugs.

Definition of the anterior choroidal artery territory in rats using intraluminal occluding technique.

This manuscript delineates the territory of the anterior choroidal artery (AChA) in rats, as defined by the induction of an AChA infarction. By advancing a 0.24-mm surgical suture up the internal carotid artery (ICA) to a point 0.5-2 mm proximal to the middle cerebral artery (MCA) origin, the AChA could be occluded and a reliable AChA distribution infarction was produced in 62% (23/37) of animals. The infarct volume, as defined by TTC staining, was 55+/-7 mm(3). Maps of the infarction, generated by measuring the entire area of overlapping coronal slices, demonstrated that the internal capsule was always damaged. Other areas that might be affected included the hippocampus, thalamus, amygdaloid complex, piriform cortex, dorsal caudatoputamen, and lateral ventricular wall. Positioning the coated suture proximal to the AChA produced a much smaller infarct involving the medial and lateral hypothalamus, preoptic region, optic chiasm, and marginal region of the internal capsule near to the lateral hypothalamus exempt from AChA territory damage. A causative relationship between AChA occlusion and a deep cerebral infarct centered on the internal capsule was further established by: (1) identifying the AChA on the non-ischemic side with colored silicone perfusion, and subsequent similar delineation on the ischemic side, and (2) delineating infarction in the silicone perfused AChA region using hematoxylin and eosin staining and the TUNEL method. The AChA usually originated from the ICA (91% of cases), 1.75+/-0.12 mm proximal to the MCA bifurcation. Approximately 27% of the AChAs had periamygdaloid branch(es) on its initial segment.

Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase.

BACKGROUND: Cerebral saccular aneurysm is a major cause of subarachnoid hemorrhage, one of the cerebrovascular diseases with the highest mortality. The mechanisms underlying the development of aneurysms, however, still remain unclear. We have made a series of reports on an animal model of experimentally induced cerebral aneurysms that resemble human cerebral aneurysms in their location and morphology, suggesting that the arterial wall degeneration associated with aneurysm formation develops near the apex of arterial bifurcation as a result of an increase in wall shear stress. Using the animal model and human specimens, we examined the role of nitric oxide (NO) in the degenerative changes and cerebral aneurysm formation. METHODS AND RESULTS: Inducible NO synthase (iNOS) was immunohistochemically located at the orifice of human and rat aneurysms. Nitrotyrosine distribution was also seen in the human aneurysm. Although no iNOS immunostaining was found in normal arteries, iNOS immunoreactivity was observed in parallel with the development of early aneurysmal changes in rats. In contrast, during the early development of aneurysm, endothelial NOS immunostaining in the endothelium was weakened compared with that in the control arteries. An NOS inhibitor, aminoguanidine, attenuated both early aneurysmal changes and the incidence of induced aneurysms. A defibrinogenic agent, batroxobin, which may diminish shear stress by reduction of blood viscosity, prevented iNOS induction as well as early aneurysmal changes. CONCLUSIONS: The evidence suggests that NO, particularly that derived from iNOS, is a key requirement for the development of cerebral aneurysm. The iNOS induction may be caused by an increase in shear stress near the apex.

[An autopsy case of dementia with Lewy bodies who showed the typical parkinsonism in the initial five years].

A 76-year-old man with parkinsonism and dementia was reported. He developed resting tremor at age 69 followed by hypokinesia, rigidity and small step gait. L-dopa ameliorated his symptoms with no hallucinations for the initial 5 years. His mental level did not decrease during that period. He was admitted to our hospital because of dehydration and fever at age 74. Subsequently, his cognitive function deteriorated, with visual hallucination. Serial brain CT studies displayed a progressive cerebral cortical atrophy without focal lesions. He died of respiratory distress syndrome and disseminated coagulopathy resulting from pneumonia, dehydration and syndrome malin. Postmortem examination revealed a marked bilateral loss of melanin-containing neurons with Lewy bodies in the substantia nigra and locus ceruleus. Lewy bodies were also in the basal nucleus of Meynert, with moderate neuronal cell loss. The distribution of Lewy bodies was widespread in the cerebral cortical areas, corresponding to the neocortical subtype according to the consensus guideline for the pathologic diagnosis of dementia with Lewy bodies. According to the criteria of the Consortium to Establish a Registry for Alzheimer's Disease, the age-related plaque score in the present case suggested Alzheimer's disease, although cortical neurofibrillary changes corresponded to stage II by the criteria of Braak and Braak. These pathological findings established the diagnosis of dementia with Lewy bodies from the quantitative and distributional viewpoints. Based on recent neuropathological evidence, a spectral theory, which presents idiopathic Alzheimer's disease and Parkinson's disease as the two extremes of a spectrum of neurodegeneration, has been proposed. Dementia with Lewy bodies is located in the middle of this spectrum. Pathological evaluation based on quantitative consensus guidelines is important to establish the diagnosis in patients with parkinsonism and dementia, since neuropathological changes of Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies are often observed in a mixed manner in these patients.