Hypoxic tissue in ischaemic stroke: persistence and clinical consequences of spontaneous survival.

In ischaemic stroke, expansion of the infarct core occurs at the expense of surrounding hypoxic, metabolically compromised tissue over a period of 24 h or more in a considerable proportion of patients. It is uncertain whether hypoxic tissue observed at later times after stroke onset retains the potential for survival or whether such survival has an impact on functional outcome. These factors may determine the effectiveness of therapeutic strategies aimed at salvaging this tissue. We tested the hypotheses that metabolically compromised hypoxic tissue observed within 48 h after onset of ischaemic stroke retains the potential for spontaneous survival and that the impact of such survival on functional outcome is time dependent. Consecutive patients presenting within 48 h of ischaemic stroke were studied with [(18)F]fluoromisonidazole, a ligand binding to hypoxic but viable tissue, and PET. Subjects were grouped into two time epochs, 12 h, based on the interval from stroke onset to the time of tracer injection, and had infarct volumes measured on CT/MRI at 7 days (n = 60). The total ischaemic volume (TIV) and the proportion of the TIV that spontaneously survived (surviving hypoxic volume ratio, SHVR) were defined from the co-registered CT/MRI images. These volumetric measures were correlated with neurological outcome assessed at day 7-10 by percentage change in the National Institutes of Health Stroke Scale (DeltaNIHSS), and at 3 months by Barthel Index (BI) and modified Rankin Score (mRS). Of 66 patients investigated, hypoxic tissue occurred in 33 and outcome data was available in 27. Hypoxic tissue constituted >20% of the TIV in 60% of studies 12 h. The spontaneously surviving proportion of the TIV (median 6.9%) or hypoxic tissue (median 45.9%) was not significantly different in patient subgroups studied 12 h after stroke onset. Spontaneous survival of hypoxic tissue (surviving hypoxic volume ratio) was associated with improved neurological outcome in both time epochs: 12 h, DeltaNIHSS (r = 0.59, P < 0.01) and day 90 mRS (r = -0.46, P < 0.05). The finding that similar proportions of hypoxic tissue survived spontaneously within each time epoch suggests that its fate is not predetermined. The favourable neurological outcome associated with spontaneous survival of hypoxic tissue, even 12-48 h after stroke onset, suggests that the volume of hypoxic tissue that progressed to infarction may represent a valuable target for therapeutic intervention.

Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke.

BACKGROUND AND PURPOSE: We sought to characterize the spatial and temporal evolution of human cerebral infarction. Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18F-fluoromisonidazole (18F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke. METHODS: Patients with acute middle cerebral artery territory stroke were imaged with 18F-FMISO PET (n=19; <6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (P<0.05; >1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch. RESULTS: Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; P<0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; P<0.05). CONCLUSIONS: These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.

Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke.

Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.

Lacunar stroke: transoesophageal echocardiographic factors influencing long-term prognosis.

OBJECTIVE: Since little is known concerning factors which may influence long-term prognosis of patients presenting with lacunar stroke, we conducted a longitudinal study of this stroke subtype. Variables likely to affect outcome were assessed at baseline, including those from transoesophageal echocardiographic studies. METHODS: Consecutive patients presenting with first-ever lacunar stroke underwent diagnostic workup that included brain CT or MRI, carotid duplex, and transthoracic and transoesophageal echocardiography. An assessment of patients was planned at entry (baseline), and thereafter every 12 months (clinic visit or telephone call), drop-out, or endpoint. The primary endpoint was nonfatal or fatal stroke. Secondary endpoint was death due to any cause. RESULTS: Among 60 consecutive lacunar patients with the mean follow-up period of 3.9 years, 12 patients (20%) had stroke recurrence. The mean annual rate for stroke was 5.2%, and for death 2.8%. For multivariate Cox proportional hazards analysis, the following three variables with the values of p < 0.1 after univariate testing were chosen: age (p = 0.095); aortic atheroma (p = 0.066); and any source of embolism from heart (p = 0.007). Any source of embolism from heart was the only factor which significantly enhanced the risk of stroke recurrence (p = 0.015). Using Kaplan-Meier life table analysis, the curves of percent free of recurrent stroke were significantly different (log rank test p = 0.002). CONCLUSIONS: Until the mechanism of lacunar stroke is better understood, it is reasonable to suggest that its investigation and prevention should be directed at all potential causes of future strokes including cardioembolism.

Risk factors for lacunar stroke: a case-control transesophageal echocardiographic study.

To reassess the independent risk factors for lacunar stroke and to clarify the role of potential embolic sources, we conducted a case-control study using transesophageal echocardiography and duplex ultrasonography. Among 62 consecutive patients with their first lacunar stroke and 202 normal controls, we found that hypertension (p < 0.001), smoking (p = 0.001), and aortic arch atheroma (p = 0.006) were independently associated with an increased risk of lacunar stroke. Whether proximal aortic arch atheroma is mechanistically associated with lacunar stroke or merely coexistent is uncertain.

[Homolateral ataxia and crural paresis following anterior cerebral artery territory infarction].

Homolateral ataxia and crural paresis (HACP) is defined as predominantly crural paresis with ipsilateral ataxia, a variant of ataxic hemiparesis (AH), by Fisher and his colleagues. HACP usually resulted from lacunar infarction in the basis pontis at the junction of the upper one-third and inferior two-third of the pons, or in the posterior limb of the internal capsule. We reported a patient with HACP which was caused by an infarct in the paracentral gyrus irrigated by the anterior cerebral artery (ACA). He had had no cerebellar signs before the onset of HACP, although he had old small infarcts in the right pons, right thalamus and left cerebellar hemisphere. Neuroimaging and other clinical studies suggested that the mechanism of the present infarction was the most-likely embolic, but not lacunar. As far as we know, there has been only one abstract presentation of a patient with HACP due to ACA territory infarction in Japan, although five such cases were recently reported by Bogousslavsky and others.

Presymptomatic brain lesions on MRI in a patient with intravascular malignant lymphomatosis.

A 58-year-old man with a intravascular malignant lymphomatosis initially developed myeloradiculopathy without cerebral symptoms. His MRI, however, demonstrated solid, wedge-shaped, and well-demarcated lesions in the deep white matter and a string-shaped lesion along with nerve fibers in the splenium of corpus callosum. A variety of cerebral symptoms manifested a month afterward. The possibility of this disease should be considered in cases of undiagnosed myeloradiculopathy with such silent brain lesions.

Predisposing factors to enlargement of spontaneous intracerebral hematoma.

BACKGROUND AND PURPOSE: Enlargement of intracerebral hemorrhage is a major cause of clinical deterioration. Identification of factors that predispose to hematoma enlargement is important in managing patients. METHODS: We selected 186 patients (71 women and 115 men; mean age, 64.8 +/- 12.5 years) with spontaneous intracerebral hemorrhage who had undergone an initial CT within 24 hours and a second scan within 120 hours of symptom onset. We compared patients with (n = 41) and without (n = 145) hematoma enlargement according to clinical characteristics and laboratory data. RESULTS: By multiple logistic regression analysis (n = 139), interaction of long interval (> 6 hours) from onset to first CT and small hematoma (< 25 cm3) strongly reduced risk of enlargement. The analysis also demonstrated that the following factors independently predisposed to enlargement: history of brain infarction; liver disease; interaction of fasting plasma glucose > or = 141 mg/dL and systolic blood pressure on admission > or = 200 mm Hg; and interaction of glycosylated hemoglobin A1c > or = 5.1% and systolic blood pressure on admission > or = 200 mm Hg. CONCLUSIONS: A patient examined > 6 hours after ictus who has a hematoma volume < 25 cm3 is unlikely to experience further hematoma growth. Prevention of brain infarction and premorbid management of liver disease may serve to lower the risk of hematoma enlargement. Although it remains controversial whether antihypertensive drugs should be used in the acute phase of intracerebral hemorrhage, poorly controlled diabetics with high systolic blood pressure (> or = 200 mm Hg) on admission also were at high risk of hematoma enlargement.

[A case of multiple cerebral arterial thrombosis due to congenital protein C deficiency].

We report a 49-year-old man who had right hemiparesis and motor aphasia. A computed tomography revealed hypodense areas in the left frontal subcortex. A cerebral angiography demonstrated occlusion of the left distal internal carotid artery and both anterior cerebral arteries, as well as stenosis of the left internal carotid artery at the cervical portion. The second angiogram obtained a month later showed no changes. The diagnosis of atherothrombotic cerebral infarction was established on the basis of clinical profile and angiographic findings. Protein C activity and antigen levels were reduced to approximately one half of the normal level in the patient and his brother. The patient had no other risk factors for stroke. Protein C deficiency has been considered one of the risk factors for thrombotic diseases. Venous thrombosis is the most common clinical manifestation, whereas arterial thrombosis is relatively rare. It is generally believed that arterial ischemic stroke associated with protein C deficiency occurs with embolic mechanism, and atherothrombotic infarction is extremely rare. This is the first report suggesting the possibility that protein C deficiency can cause cerebral thrombosis.

Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course.

BACKGROUND AND PURPOSE: Standard radiographic criteria for hematoma enlargement have not been established. We undertook this investigation to assess the incidence and time course of hematoma growth using objective cutoff values. METHODS: We reviewed the clinical records of 204 patients with spontaneous intracerebral hemorrhage treated nonsurgically who underwent initial computed tomography (CT) within 48 hours and repeat CT within 120 hours of the onset of symptoms. The consensus of five observers reading the CT films was considered the "gold standard" for hematoma enlargement. The discriminant values of the difference (V2-V1) or the ratio (V2/V1) of the hematoma volume on the initial (V1) and second (V2) CT scans were determined by use of receiver operating characteristic curves. We chose the cutpoint that had the highest sensitivity and specificity for identifying hematoma expansion. RESULTS: The cutpoint for hematoma enlargement was determined as V2-V1 = 12.5 cm3 or V2/V1 = 1.4 (sensitivity = 94.4%, specificity = 95.8%). Forty-one patients (20%) had changes that exceeded these criteria. Frequency of hematoma expansion was greatest among those who underwent the initial CT scan early (27 [36%] of 74 patients at < or = 3 hours) and progressively declined as the time to initial scan was prolonged (7 [16%] of 45 patients at 3 to 6 hours; 5 [15%] of 33 patients at 6 to 12 hours; 2 [6%] of 34 patients at 12 to 24 hours; and 0 [0%] of 18 patients at 24 to 48 hours). CONCLUSIONS: The enlargement of hematoma was defined radiographically as the increase of its volume by > or = 12.5 cm3 or by > or = 1.4 times. Although expansion of intracerebral hemorrhage on CT scan was common in the hyperacute stage, 17% of hematoma expansion occurred even after 6 hours of onset. Enlargement after 24 hours of onset seems extremely rare. Early CT scanning appears to increase the rate of detection of enlarging hematomas.

Very early demonstration of secondary pyramidal tract degeneration by computed tomography.

BACKGROUND: While magnetic resonance imaging has revealed progressive changes in the pyramidal tract in accordance with histopathologic stages of wallerian degeneration secondary to a supratentorial lesion, computed tomography (CT) has only demonstrated a shrinkage of the pyramidal tract in the midbrain or pons during the chronic stage. We present a patient with frontoparietal subcortical hemorrhage in whom serial CT scans clearly demonstrated wallerian degeneration along the axis of the pyramidal tract early in the acute stage. CASE DESCRIPTION: A 63-year-old man with a history of hypertension suddenly developed a deterioration of consciousness, transcortical mixed aphasia, and dense hemiplegia on the right side. CT scans revealed a massive intracerebral hematoma in the frontoparietal subcortices of the left hemisphere. Although initial CT did not detect any hypodense areas along the left pyramidal tract below the hematoma, ill-defined areas of decreased density appeared in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and pontine base of the left side on day 13 after the stroke. These areas became well demarcated on day 22 and persisted thereafter. CONCLUSIONS: An extensive hematoma can interrupt the pyramidal tract fibers that arise not only from the motor cortex and caudal premotor cortex but also from the somatosensory and parietal cortices, allowing very early CT demonstration of wallerian degeneration of the pyramidal tract.

Accelerated brain infarction in hypertension complicated by hereditary heterozygous protein C deficiency.

BACKGROUND: Protein C deficiency leads to reduced inhibition of coagulation and an increased likelihood of thrombosis. It is widely accepted that the most common syndromes associated with protein C deficiency are venous thrombosis and pulmonary thromboembolism, whereas arterial thrombosis is rare. Here we describe two patients with hypertension and hereditary heterozygous protein C deficiency who developed multiple lacunar infarcts. CASE DESCRIPTIONS: Patient 1 was a 46-year-old man with a history of hypertension who developed a right upper quadrantanopia and gradually progressive intellectual and behavioral deterioration. Patient 2 was a 61-year-old man with history of hypertension and two episodes of right-sided motor weakness who developed left sixth and seventh cranial-nerve palsies and reduced pinprick sensation in the right extremities. In both patients, magnetic resonance imaging revealed multiple small lesions in the pons as well as the bilateral basal ganglia, thalamus, corona radiata, and other subcortical structures, which are consistent with lacunar infarcts. Protein C activity and antigen levels were reduced to approximately one half of normal in these two patients, as well as in some of their family members who had no other serological or coagulation abnormalities. A diagnosis of heterozygous protein C deficiency type 1 was thus established. CONCLUSIONS: Although it remains uncertain whether protein C deficiency itself increases the risk of cerebral artery thrombosis, it may predispose a patient to develop multiple brain infarctions in association with hypertension.

Callosal apraxia without agraphia.

We describe a patient with left unilateral ideomotor apraxia without left-sided agraphia caused by a callosal lesion that was demonstrated by magnetic resonance imaging. The clinical features, together with data in the literature, suggest that the callosal fibers for writing are concentrated in the posterior corpus callosum, while those for praxis cross in the more rostral part of the posterior half of the callosum.

Angiographic evaluation of brain infarction limited to the anterior cerebral artery territory.

BACKGROUND AND PURPOSE: Brain infarction localized in the anterior cerebral artery territory is rather uncommon, and its etiology has not yet been fully elucidated. METHODS: Based on computed tomographic findings, 17 patients with solitary anterior cerebral artery territory infarction were selected from among 3,619 patients admitted consecutively to our institute. Patients without angiographic examinations were excluded. The angiographic findings and clinical category of stroke were analyzed in each patient. RESULTS: Angiographic abnormalities were revealed in all patients. These consisted of occlusive changes (n = 10) or reversible segmental dilatation (n = 3) of the anterior cerebral artery, A1 hypoplasia (n = 5), and occlusive changes of the carotid artery (n = 3). In one patient with anterior cerebral artery occlusion, the occluded artery was reopened and subsequently became reoccluded. The clinical category of stroke was classified as atherothrombotic in 10 patients, cardioembolic in three, and undetermined in the remaining four. In eight of the 10 patients with atherothrombotic infarction, the anterior cerebral artery was narrowed or occluded. In all patients with cardioembolic infarction, the A1 segment contralateral to the infarction was hypoplastic. CONCLUSIONS: In our series, solitary anterior cerebral artery territory infarction was attributable most commonly to local atherothrombosis and occasionally to cardiogenic embolism. A hypoplastic A1 segment may facilitate the occurrence of embolism in the anterior cerebral artery. Reversible dilatatory and occlusive changes of this artery may be another important cause of infarction.

Transformation of Broca's aphasia into conduction aphasia: a case report.

We describe a patient with a cerebral infarction localized mainly in the left posterior frontal and anterior parietal subcortices who experienced a Broca's aphasia which evolved into a conduction aphasia. Such a rare recovery pattern of aphasia appeared to result from amelioration of the damage to the left precentral gyrus.

Sequential gadolinium-DTPA enhanced MRI studies in neuro-Behçet's disease.

Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behçet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images hich were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behçet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behçet's disease and for evaluating the efficacy of treatment.

Subcortical auditory agnosia.

A case of generalized auditory agnosia without aphasia secondary to cardiogenic cerebral embolism is reported. The infarcts in this patient were localized within the bitemporal subcortices as confirmed by computerized axial tomography and magnetic resonance imaging. The findings suggested that interruption of both auditory radiations by bilateral subcortical lesions may play an important role in the occurrence of "cerebral auditory disorders."

Estimation of vertebral arterial asymmetry by computed tomography.

In 80 patients with no stenotic lesions in the vertebrobasilar arterial system, a study was made of the relationship between the deviation of the basilar artery (BA) from the midline on computed tomography (CT) and the right-to-left vertebral arterial caliber difference on angiograms. In 66 patients (83%), the BA was visible on plain CT films, and 55 of them showed deviation of the BA to either side. In 44 of these patients (80%), the vertebral artery (VA) contralateral to the side of BA deviation had a larger caliber compared with the ipsilateral one on angiograms. In 6 patients whose unilateral VA terminated in the posterior inferior cerebellar artery (PICA) and showed an extremely small caliber compared to the contralateral one, the BA was always deviated to the side of the smaller VA. Our data suggest that the deviation of the BA on plain CT films may represent a good indicator for estimating the right-to-left VA caliber difference. At the time of vertebral angiography, injection of contrast medium should preferably be made from the larger VA in order to avoid laminar flow in the BA and to shorten the procedure. Prior estimation of the right-to-left VA caliber difference by CT may be of great benefit to the angiographic procedure.