Diffusion-weighted MRI in patients with non-diagnostic CT in the post-acute phase of cerebral ischemia.

BACKGROUND: Unenhanced computed tomography (CT) is the imaging technique used in acute stroke. In some cases it is unable to detect damage even 24-48 h after symptom onset. The aim of our work was to evaluate the diagnostic value of diffusion-weighted imaging (DWI) in the post-acute phase of cerebral ischemia in patients in whom CT did not yield a definitive diagnosis. METHODS: We retrospectively evaluated DWI findings in 214 patients, out of a series of 1,680 patients admitted to our hospital following the acute onset of focal neurological symptoms, in whom non-contrast CT, performed within 30 h of symptom onset, was normal (123), incongruous, i.e. a marked hypodensity indicative of an old infarct or a slight hypodensity not consistent with the clinical findings (66), or leukoaraiotic, i.e. diffuse chronic hypodensities in the periventricular white matter (25). RESULTS: DWI showed signs of recent brain ischemia in 125/214 (58%) patients: 64/123 (52%) with a normal CT, 41/66 (62%) with an incongruous CT, and 20/25 (80%) with leukoaraiosis (p=0.027). Multiple lesions were detected in 16/125 (16%) patients, while single lesions were

Embolism to the brain during carotid stenting and surgery.

UNLABELLED: The aim of this study was to assess the prevalence and clinical relevance of microembolism in one hundred unselected patients submitted to 50 carotid endarterectomy (CEA) and 50 carotid stenting (CAS) procedures from January 2005 to January 2006 for hemodynamic lesions of the carotid bifurcation (> 70% stenosis). MATERIAL AND METHODS: High-resolution Colour-Flow Mapping (CFM), Transcranial Doppler (TCD), cerebral computed tomography (CT) or magnetic resonance (MR) and four psychometric tests (Mini mental state, Beck depression inventory, Zung anxiety inventory, SF-12) were carried out in the preoperative evaluation in all the patients. In the CEAs loco-regional anesthesia (100%), patch angioplasty (84%) and Pruitt- Inahara shunt (4%) were employed; in the CASs local anesthesia (100%), three different carotid stents (Precise-Cordis, Acculink-Guidant and Carotid Wallstent-Boston Scientific) and three temporary distal filter protection devices (Angioguard-Cordis, Accunet-Guidant, Filterwire-EZ- Boston Scientific), without pre-dilatation, were employed. TCD monitoring was used intra-operatively and 12 hours post-operatively to evaluate the presence and the number of microembolic events (ME's) and to investigate the efficiency of neuroprotective filter devices. The efficacy of the in situ opened filter was judged evaluating the decrease of mean blood velocity in ipsilateral middle cerebral artery and the reduction rate of microembolic events (number of microemboli detected during the entire procedure/number of microemboli detected during the filter positioning). Diffusion-weighted magnetic resonance imaging (DWI) of the brain was obtained within 24 to 48 hours after the procedures to detect new ischemic brain lesions. Psychometric tests were repeated at the discharge of the patient and after two months to evaluate cognitive faculties. RESULTS: During postoperative period (30 days) and follow-up, no procedure-related death and three regressive minor strokes occurred : 1 in CEA (2%) and 2 in CASs (4%) ; a cranial nerve lesion occurred in CEA (2%). TCD monitoring showed ME's (a mean of five events) in 37 CEAs (74%) and in 50 CASs (100%) (a mean of 60 ME's). In five patients submitted to CAS repeated microemboli occurred during one hour postoperative TCD control (10%). A 10-30% decrease of mean blood velocity basal value was recorded in the ipsilateral middle cerebral artery when the filter device was opened. A mean 70% reduction of ME's was obtained with a cerebral protection system deployed. Postoperative DWI detected new focal ischemic lesions in 24 patients [22 after CAS (44%) (a mean of 5 new ipsi and contra-lateral lesions) , and 2 after CEA (4%). Cognitive capability worsened in 20 patients [18 after CAS (36%) e 2 after CEA (4%)]. CONCLUSIONS: Mortality and morbidity rates of patients submitted to CAS are comparable to the results obtained by CEA. A great number of ME's are recorded by TCD during endovascular procedures, more than during open surgery. ME's due to CAS are reduced by filter protection devices, but the cognitive faculties in a great number of "asymptomatic" patients are decreased after CAS.

Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.

BACKGROUND: 3,4-diaminopyridine (3,4-DAP), a potassium (K+) channel blocker, improves fatigue and motor function in multiple sclerosis (MS). Although it was thought to do so by restoring conduction to demyelinated axons, recent experimental data show that aminopyridines administered at clinical doses potentiate synaptic transmission. OBJECTIVE: To investigate motor cerebral activity with fMRI and transcranial magnetic stimulation (TMS) after a single oral dose of 3,4-DAP in patients with MS. METHODS: Twelve right-handed women (mean +/- SD age 40.9 +/- 9.3 years) underwent fMRI on two separate occasions (under 3,4-DAP and under placebo) during a simple motor task with the right hand. FMRI data were analyzed with SPM99. After fMRI, patients underwent single-pulse TMS to test motor threshold, amplitude, and latency of motor evoked potentials, central conduction time, and the cortical silent period; paired-pulse TMS to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF); and quantitative electromyography during maximal voluntary contraction. RESULTS: FMRI motor-evoked brain activation was greater under 3,4-DAP than under placebo in the ipsilateral sensorimotor cortex and supplementary motor area (p < 0.05). 3,4-DAP decreased ICI and increased ICF; central motor conduction time and muscular fatigability did not change. CONCLUSION: 3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation.

Transient mutism was observed in a liver transplant patient under immunosuppressant therapy with cyclosporine A and antifungal prophylaxis with amphotericin B. Fluid-attenuated inversion recovery and diffusion-weighted images revealed reversible bilateral symmetric hyperintensity located in the frontal motor cortex and corticospinal tracts. These MRI abnormalities may be caused by acute edema, possibly a combination of cytotoxic and vasogenic edema, which resolved with a prompt change in therapy.

Real-time MR artifacts filtering during continuous EEG/fMRI acquisition.

The purpose of this study was the development of a real-time filtering procedure of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI acquisition. The development of a combined EEG and fMRI technique has increased in the past few years. Preliminary "spike-triggered" applications have been possible because in this method, EEG knowledge was only necessary to identify a trigger signal to start a delayed fMRI acquisition. In this way, the two methods were used together but in an interleaved manner. In real simultaneous applications, like event-related fMRI study, artifacts induced by MRI events on EEG traces represent a substantial obstacle for a right analysis. Up until now, the methods proposed to solve this problem are mainly based on procedures to remove post-processing artifacts without the possibility to control electrophysiological behavior of the patient during fMRI scan. Moreover, these methods are not characterized by a strong "prior knowledge" of the artifact, which is an imperative condition to avoid any loss of information on the physiological signals recovered after filtering. In this work, we present a new method to perform simultaneous EEG/fMRI study with real-time artifacts filtering characterized by a procedure based on a preliminary analytical study of EPI sequence parameters-related EEG-artifact shapes. Standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes included: high-performance acquisition device; electrodes/cap/wires/cables materials and geometric design; shielding box for EEG signal receiver; optical fiber link; and software. The effects of the RF pulse and time-varying magnetic fields were minimized by using a correct head cap wires-locked environment montage and then removed during EEG/fMRI acquisition with a subtraction algorithm that takes in account the most significant EPI sequence parameters. The on-line method also allows a further post-processing utilization.

fMRI/EEG in paroxysmal activity elicited by elimination of central vision and fixation.

Using functional MRI (fMRI) with concurrent EEG monitoring the authors studied cortical activation associated with epileptiform discharges in three patients with fixation-off sensitivity. The EEG paroxysmal activity elicited by eliminating central vision correlated significantly with an increased blood oxygen level-dependent signal in the extrastriate cortex (Brodmann areas 19 and 37). fMRI provides a unique opportunity for localizing precisely the cortical areas generating paroxysmal activity in patients with fixation-off sensitivity.

Cerebral hemodynamics on MR perfusion images before and after bypass surgery in patients with giant intracranial aneurysms.

BACKGROUND AND PURPOSE: Preoperative assessment of the anatomy and dynamics of cerebral circulation for patients with giant intracranial aneurysm can improve both outcome prediction and therapeutic approach. The aim of our study was to use perfusion MR imaging to evaluate cerebral hemodynamics in such patients before and after extraintracranial high-flow bypass surgery. METHODS: Five patients with a giant aneurysm of the intracranial internal carotid artery underwent MR studies before, 1 week after, and 1 month after high-flow bypass surgery. We performed MR and digital subtraction angiography, and conventional and functional MR sequences (diffusion and perfusion). Surgery consisted of middle cerebral artery (MCA)-internal carotid artery bypass with saphenous vein grafts (n = 4) or MCA-external carotid artery bypass (n = 1). RESULTS: In four patients, MR perfusion study showed impaired hemodynamics in the vascular territory supplied by the MCA of the aneurysm side, characterized by significantly reduced mean cerebral blood flow (CBF), whereas mean transit time (MTT) and regional cerebral blood volume (rCBV) were either preserved, reduced, or increased. After surgery, angiography showed good canalization of the bypass graft. MR perfusion data obtained after surgery showed improved cerebral hemodynamics in all cases, with a return of CBF index (CBFi), MTT, and rCBV to nearly normal values. CONCLUSION: Increased MTT with increased or preserved rCBV can be interpreted as a compensatory vasodilatory response to reduced perfusion pressure, presumably from compression and disturbed flow in the giant aneurysmal sac. When maximal vasodilation has occurred, however, the brain can no longer compensate for diminished perfusion by vasodilation, and rCBV and CBFi diminish. Bypass surgery improves hemodynamics, increasing perfusion pressure and, thus, CBFi. Perfusion MR imaging can be used to evaluate cerebral hemodynamics in patients with intracranial giant aneurysm.

Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic?

BACKGROUND AND PURPOSE: The term symptomatic hemorrhage secondary to ischemic stroke implies a clear causal relationship between clinical deterioration and hemorrhagic transformation (HT) regardless of the type of HT. The aim of this study was to assess which type of HT independently affects clinical outcome. METHODS: We used the data set of the European Cooperative Acute Stroke Study (ECASS) II for a post hoc analysis. All patients had a control CT scan after 24 to 96 hours or earlier in case of rapid and severe clinical deterioration. HT was categorized according to radiological criteria: hemorrhagic infarction type 1 and type 2 and parenchymal hematoma type 1 and type 2. The clinical course was prospectively documented with the National Institutes of Health Stroke Scale and the modified Rankin Scale: The independent risk of each type of HT was calculated for clinical deterioration at 24 hours and disability and death at 3 months after stroke onset and adjusted for possible confounding factors such as age, severity of stroke syndrome at baseline, and extent of the ischemic lesion on the initial CT. RESULTS: Compared with absence of HT, only parenchymal hematoma type 2 was associated with an increased risk for deterioration at 24 hours after stroke onset (adjusted odds ratio, 18; 95% CI, 6 to 56) and for death at 3 months (adjusted odds ratio, 11; 95% CI, 3.7 to 36). All other types of HT did not independently increase the risk of late deterioration. CONCLUSIONS: Only parenchymal hematoma type 2 independently causes clinical deterioration and impairs prognosis. It has a distinct radiological feature: it is a dense homogeneous hematoma >30% of the ischemic lesion volume with significant space-occupying effect.

Early prediction of irreversible brain damage after ischemic stroke at CT.

PURPOSE: To assess the capability of computed tomography (CT) in the prediction of irreversible ischemic brain damage and its association with the clinical course within 6 hours of stroke onset. MATERIALS AND METHODS: Serial CT scans obtained within 6 hours of stroke onset, at 22-96 hours (median, 1 day), and at 2-36 days (median, 7 days) after symptom onset in 786 patients with ischemic stroke were prospectively studied, and follow-up CT scans were used as the reference. Clinical variables were assessed prospectively and independently of CT evaluation. RESULTS: The specificity and positive predictive value of ischemic edema at baseline CT for brain infarcts were 85% (95% CI: 77%, 91%) and 96% (95% CI: 94%, 98%), respectively. Sensitivity and negative predictive values were 64% (95% CI: 60%, 67%) and 27% (95% CI: 23%, 32%), respectively. Patients without early CT findings were less severely affected (P<.001), developed smaller infarcts (P<.001), had fewer intracranial bleeding events (P<.001), and had a better clinical outcome at 90 days (P<.001) compared with patients with hypoattenuating brain tissue at early CT. CONCLUSION: After ischemic stroke, x-ray hypoattenuation at CT is highly specific for irreversible ischemic brain damage if detection occurs within the first 6 hours. Patients without hypoattenuating brain tissue have a more favorable clinical course.

Relationship between vascular enhancement, cerebral hemodynamics, and MR angiography in cases of acute stroke.

BACKGROUND AND PURPOSE: The use of MR angiography and contrast-enhanced T1-weighted MR imaging in cases of acute cerebral ischemia may be helpful in the evaluation of middle cerebral artery (MCA) occlusion and leptomeningeal collaterals, respectively. The aim of our work was to investigate the relationship between MCA occlusion, T1-weighted vascular contrast enhancement, hemodynamic alterations, and tissue damage in cases of acute ischemic stroke. METHODS: We studied the MCA territory in 15 patients with acute ischemic stroke within 8 hr of symptom onset. The first MR imaging study (<8 hr after onset) comprised diffusion-weighted imaging, MR angiography, perfusion-weighted imaging, and contrast-enhanced T1-weighted MR imaging sequences. Follow-up MR imaging, performed 1 week later, consisted of MR angiography and T2-weighted fluid-attenuated inversion recovery MR imaging. RESULTS: Early MR angiography showed MCA stem occlusion in nine of 15 patients. Patients with MCA occlusion had significantly larger areas of abnormality on early diffusion-weighted images, significantly larger areas of altered hemodynamics, larger final lesion volumes, and poorer clinical outcome. Among the nine patients with MCA stem occlusion, vascular enhancement was marked in seven and absent in two who had complete MCA infarcts and poor clinical outcome. Among patients with MCA patency, vascular enhancement was marked in only one, mild in four, and absent in one. Patients with marked vascular enhancement had significantly larger regions of altered hemodynamics and significantly higher asymmetries in both regional cerebral blood volume and mean transit time because of increased values in the affected hemisphere. CONCLUSION: Among patients with stroke with MCA occlusion, marked vascular enhancement and increased blood volume indicate efficient leptomeningeal collaterals and compensatory hemodynamic mechanisms.

Computed tomography findings in the first few hours of ischemic stroke: implications for the clinician.

In order to evaluate the clinical usefulness of emergency computed tomography (CT) in acute ischemic stroke, we assessed whether CT findings within the first few hours of stroke onset reliably predict type, site and size of the index infarction, and risk of death or disability. For this reason we reviewed clinical and CT findings in a cohort of unselected consecutive patients referred to the stroke unit of a large urban hospital because of a presumed ischemic stroke in the anterior circulation (AC), and submitted to CT within 5 h from onset. Out of 158 total patients, emergency CT revealed parenchymal changes compatible with AC focal ischemia in 77 (49%) and a hyperdense middle cerebral artery (MCA) in 41 (26%). Parenchymal changes and hyperdense MCA predicted an AC territorial infarction respectively in 97% of cases (95% C.I. 93% to 100%) and in 95% of cases (95% C.I. 88% to 100%). Site and size of early changes coincided with those of final lesions in 79% of patients with cortical changes and in 95% of patients with cortico-subcortical changes, but only in 37% of patients with initial subcortical changes, the remainder of whom developed a cortico-subcortical infarction. At logistic regression parenchymal changes were the only independent predictor of an AC territorial infarction. Negative predictive power, however, was only 40% (95% C. I. 29% to 51%) for parenchymal changes, and 35% for hyperdense MCA (95% C.I. 26% to 44%). The odds for death or disability at 1 month associated with parenchymal changes were thrice as high as with negative CT, even after adjustment for clinical severity on admission. These results indicate that CT scan adds significantly to the prediction of outcome made on clinical grounds. The frequent development of a territorial infarction in patients with initially negative CT and the subsequent recruitment of the cortex in those initially exhibiting only subcortical changes suggest that the transition from ischemia to infarction often occurs after the first five h following stroke.

Cortical motor reorganization in akinetic patients with Parkinson's disease: a functional MRI study.

Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's disease is restricted to the rostral part of the SMA and to the dorsolateral prefrontal cortex. These results also show that, apart from the lateral premotor and parietal cortices, increased fMRI signals can be found in other cortical motor areas of these patients, including the posterior SMA, the anterior cingulate cortex and the primary sensorimotor cortices, which are then likely to participate in the same putative attempt by the dopamine-denervated brain to recruit parallel motor circuits in order to overcome the functional deficit of the striatocortical motor loops.

Correlation between MRI findings and long-term outcome in patients with severe brain trauma.

Our aim was to relate MRI findings in patients with severe traumatic brain injury (TBI) to clinical severity and long-term outcome. We studied 37 patients with severe TBI, who were submitted to clinical assessment for disability and cognition and to MRI 60-90 days after trauma. Clinical assessment was also performed 3, 6 and 12 months later. The number and volume of lesions in various cerebral structures were calculated semiautomatically from FLAIR and fast field-echo images. Possible correlations between total and regional lesion volume and clinical deficits were then investigated. The frontal and temporal lobes were most frequently involved. Total lesion volume on FLAIR images correlated significantly with clinical outcome, whereas that on FFE images did not. Regional analysis showed that FLAIR lesion volume in the corpus callosum correlated significantly with scores on disability and cognition scales at the first clinical assessment. FLAIR lesion volume in the frontal lobes correlated significantly with clinical scores 1 year later.

Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

BACKGROUND AND PURPOSE: The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. METHODS: We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. RESULTS: Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. CONCLUSIONS: Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.

[Usefulness of selective partial inversion recover (SPIR) sequences in optic nerve diseases]. / Utilità delle sequenze "Selective Partial Inversion Recover" (SPIR) nelle malattie del nervo ottico.

PURPOSE: To evaluate the yield of SPIR sequences with fat suppression in the diagnosis of optic nerve lesions. MATERIAL AND METHODS: Ten patients with suspected optic nerve involvement on the basis of clinical data and abnormalities of visual evoked potentials were examined. MRI was performed with a 1.5 T unit (Philips NT 15) using T1 weighted conventional spin-echo and T1- and T2 weighted SPIR sequences with fat suppression. Axial images were obtained along the optic nerve course, while coronal images throughout the optic nerve axis; slices were 3 mm thick. Axial T2 weighted SPIR sequences were also performed with the volumetric technique (1.5 mm thickness); coronal and parasagittal reconstructions along the nerve axis were obtained too. After paramagnetic contrast medium injection, conventional T1 weighted and SPIR sequences were performed on axial and coronal planes. RESULTS: Optic nerve lesions consistent with the diagnosis of neuritis were demonstrated with T2 weighted images in 4 of 10 patients. No abnormalities and/or nerve enlargement were found on T1 weighted images. An enhancement area was seen after contrast medium injection in only one case. MRI showed a pilocytic astrocytoma in one patient and selective atrophy of the right optic nerve in another. MRI showed normal findings in 4 patients. CONCLUSIONS: T1 and T2 weighted fat-suppressed SPIR imaging of the optic nerve improves anatomical definition, lesion detection and characterization in optic nerve conditions.

Association of hyperdense middle cerebral artery sign with clinical outcome in patients treated with tissue plasminogen activator.

BACKGROUND AND PURPOSE: The hyperdense middle cerebral artery sign (HMCAS) is a marker of thrombus in the middle cerebral artery. The aim of our study was to find out the frequency of the HMCAS, its association with initial neurological severity and early parenchymal ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous recombinant tissue plasminogen activator (rtPA) in patients with the HMCAS. METHODS: Secondary analysis of the data from 620 patients who received either rtPA or placebo in the European Cooperative Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial. The baseline CT scans were obtained within 6 hours from the onset of symptoms. Functional and neurological outcomes were assessed using the modified Rankin Scale and the Scandinavian Stroke Scale at day 90. RESULTS: We found an HMCAS in 107 patients(17.7%). The initial neurological deficit was more severe in patients with the HMCAS than in those lacking this sign (P<0.0001). Early cerebral edema and mass effect were also more common in patients with the HMCAS (P<0.0001). The HMCAS was related to the risk of poor functional outcome (grade of 3 to 6 on the modified Rankin Scale) on univariate analysis: 90 patients (84%) with the HMCAS and 310 patients (62%) lacking this sign were dependent or dead at day 90 (P<0.0001). However, this association was no longer significant in a logistic model accounting for the effect of age, sex, treatment with rtPA, initial severity of neurological deficit and early parenchymal ischemic changes on CT. Patients with the HMCAS who were given rtPA had better neurological recovery than those who received placebo (P=0.0297). CONCLUSIONS: The HMCAS is associated with severe brain ischemia and poor functional outcome. However, it has no significant independent prognostic value when accounting for the effect of initial severity of neurological deficit and of early parenchymal ischemic changes on CT. Patients with the HMCAS may benefit from intravenous rtPA.

Delayed increase in infarct volume after cerebral ischemia: correlations with thrombolytic treatment and clinical outcome.

BACKGROUND AND PURPOSE: Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome. METHODS: Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS: Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups. CONCLUSIONS: In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.