Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study.

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper-connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper-connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep.

The culturally adapted Italian version of the Barthel Index (IcaBI): assessment of structural validity, inter-rater reliability and responsiveness to clinically relevant improvements in patients admitted to inpatient rehabilitation centers.

The Barthel Index (BI) is widely used to determine eligibility criteria for inpatient rehabilitation and to monitor patients' recovery, irrespective of the illnesses that affect them. The culturally adapted Italian version of the Barthel Index (IcaBI) was recently validated. This paper reports the structural validity and inter-rater reliability of the IcaBI and its responsiveness to the results of inpatient rehabilitation. The IcaBI was administered to a cohort of 264 patients hospitalized in two rehabilitation centers in Rome, Italy. Factor analysis using principal component analysis revealed a monofactorial structure for neurological patients and, after removal of item 1 "feeding", also for orthopedic patients. Substantial to optimal inter-rater reliability was found (0.74 > intraclass correlation coefficient < 0.96). The IcaBI was found to be accurate (area under the curve= 0.72) with a minimal clinically important change score of 35 points. This work confirms that IcaBI is a useful tool for measuring disability in health and social care settings along the continuum of care. Further studies are needed to assess its criterion validity, interpretability and responsiveness in other specific disease conditions.

Are stroke cases affected by sleep disordered breathings all the same?

Sleep disordered breathings (SDB) worsens the clinical prognosis of stroke patients. Continuous positive airway pressure (CPAP) is a promising effective treatment. Unfortunately, not all patients are compliant with CPAP, suggesting that it is not appropriate for all patients with obstructive sleep apnoea (OSA) after stroke. People with the highest likelihood of benefiting have to be identified. We present a classification of cases with stroke and SDB to be adopted in order to identify the best responders to CPAP treatment. We propose to classify patients in four subgroups: (1) patients who terminate the apnoea by arousing from sleep; these cases are those affected either by an anatomical or a functional obstruction of upper airways that may precede or are the consequence of stroke; (2) cases that alternate OSA to central sleep apnoea (CSA) cause of an altered loop gain; (3) cases in whom ischemic damages have altered the sleep microstructure (CAP); (4) cases that manifest a CSA as the direct consequence of stroke on the central neuronal drive to breath. So far, no study has investigated the consequences of stroke on sleep microstructure. In order to better elucidate these relationships, when reviewing the PSG tracings of stroke patients, the microstructure of sleep should be systematically analysed.

Post stroke sleep apnea hypopnea syndrome: a series of 12 consecutive stable stroke cases.

OBJECTIVES: Sleep Disordered Breathing (SDB) is a negative prognostic factor for stroke patients. In order to reveal: (1) the frequency of Sleep Apnea-Hypopnea Syndrome (SAHS) in the stable phase of the illness; (2) the type of SAHS, either obstructive (OSAHS) or central (CSAHS); (3) the possible association between SAHS and daily sleepiness, cardiac arrhythmias, stroke / TIA recurrence and location of the brain lesion, an observational study is on-going at Sapienza University of Rome. We report here the results of cases included in the feasibility study. PATIENTS AND METHODS: clinical evaluations, brain images and polisomnographic study were performed at discharge and after 4 and 9 months of stroke. RESULTS: Eleven out of the 12 patients included (91.6%) had an Apnea/Hypopnea Index-AHI >= 5. In 5 cases, the majority of total respiratory events were purely central in origin. In 3 of these 5 cases, a concomitant obstruction of the upper airways was revealed; the 2 remaining had risk factors for OSAHS (smoke, hypertension, BMI > 25). A significant association was found between central apnea/hypopnea events and cardiac arrhythmias (p value 0.017). CONCLUSIONS: These findings confirm the high prevalence of SDB, either obstructive or/and central, even in the stable phase of the illness, which in those patients who had accumulated risk factors for OSAHS result in Complex-sleep apnea/hypopnea syndrome (CompSAHS). As patients with CompSAHS are left with very disrupted breathing on continuous positive airway pressure, in order to select cases with stable stroke who benefit from continuos-positive airway pressure (C-PAP) treatment, further and more detailed clinical studies are needed to better distinguish CompSAHS from mixed SAHS.

Specific therapies for ischaemic stroke: rTPA and others.

In the last few years there have been several important advances in the understanding of cerebrovascular disorder pathophysiology that have impacted on stroke management. The development of timely and effective treatment strategies was and is still considered a high priority issue. Therapeutic options dramatically increased both in the prevention and overall in the treatment of acute ischaemic stroke (AIS). At present, whereas neuroprotection remains experimental, intravenous (i.v.) thrombolysis is the only specific therapy effective in reducing mortality and disability associated with stroke. The efficacy and safety of the antithrombotic therapy in AIS treatment are not well established, and few issues in clinical stroke management are more controversial. However, some studies have brought new light and new doubts on the roles of these traditional therapies.

Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke.

OBJECTIVES: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. METHODS: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) in-hospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure). RESULTS: cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10-0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint "in-hospital death or non-fatal cardiac event". Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. CONCLUSIONS: cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.

Implementation of a surveillance system for stroke based on administrative and clinical data in the Lazio region (Italy): methodological aspects.

Stroke is the third leading cause of death and the most important cause of long-term disability in Italy and other developed countries, heavily influencing quality of life and costs of health care. In spite of the widespread occurrence of the disease and its relevant impact in Italy, there is neither a national nor a regional surveillance system of cerebrovascular diseases. A regional surveillance system for stroke has two important aims: to help to interpret the geographical and temporal trends of the disease for health care planning and resource allocation and to allow close monitoring of the quality of stroke services. Age-standardized mortality rates for cerebrovascular diseases in the Lazio region (5,242,709 inhabitants) in the period 1998-99 were 69.4 for males and 59.4 for females per 100,000 inhabitants. In the year 2000, about 3% of all hospital discharges were for cerebrovascular diseases with a hospitalisation rate of 4.36 per 1000 inhabitants. The mean length of stay is 12 days (median of 9 days) and in-hospital death is 15.4%. The admission rate for cerebrovascular diseases to emergency departments is 3.40 per 1000 inhabitants. The goal of the Lazio Regional Health Authority is to implement a surveillance system for stroke based both on current data (mortality and discharge data) and on information collected in a registry for quality assessment of stroke care. The first step of the study is to develop a regional register of acute stroke using an 'ad hoc' data sheet integrated in the computer-based patient record system of clinical and administrative data (GIPSE) operating in all emergency departments in the region.

Acute stroke trials: the problems of local investigators?

During stroke trials local investigators have to face many practical problems and time consuming procedures (filling in huge case report forms, performing repeat blood sample drawings for pharmacokinetic studies etc.) which, however, simply require organizational structures which is understood to be necessary to be able to conduct such kind of studies. Other, and most worrisome problems, are indeed to be solved when a sponsored research may rise potential ethical issues, or when academic research proposals clash with the interest of pharmaceutical companies or find difficulties in being funded by public institutions. It is just a greater involvement of these latter, possibly free from bureaucratic laces, which might help a balance to be struck between academic and industrial aims.

Emergency and early carotid endarterectomy in patients with acute ischemic stroke selected with a predefined protocol. A prospective pilot study.

AIM: The appropriateness of early carotid endarterectomy (CEA) in patients with acute ischemic stroke is still unsettled. The aim of this study was to verify the safety and feasibility of early CEA in a consecutive series of patients with acute ischemic stroke observed in an emergency Department Stroke Unit. METHODS: During a 24-month study, out of 756 patients with acute ischemic stroke 33 (4.4%) were scheduled for early CEA. Endarterectomy procedures were distinguished according to the time between the onset of stroke and operation as emergency (within 8 hours), early CEA (1-18 days). Patients with impaired consciousness or an infarct larger than 2.5 cm on computed tomographic (CT) or magnetic resonance (MR) scans or both were excluded from surgery. All patients underwent spiral CT, echo-color-Doppler (ECD) sonography, transcranial Doppler (TCD) sonography and, when necessary, MR angiography within 6 hours of admission. No patient underwent conventional angiography. Most patients were operated on under cervical block (CB) anesthesia; general anesthesia (GA) was used only for those with an unstable neurological deficit. Selective shunting was used on the basis of intra-operative transcranial Doppler in patients under GA and the onset or worsening of neurological deficit under CB anesthesia. RESULTS: Of the 6 patients operated on within a median 6 hours after the onset of stroke, 1 (16.5%) had a fatal hemorrhagic transformation of the infarct, while the remaining 5 (83.5%) stopped fluctuating or progressing and had a favourable neurological outcome. Of the 16 patients operated on within a median 36 hours and of the 11 patients operated on within 7 days, none deteriorated after operation. CONCLUSION: Emergency CEA is feasible for acute ischaemic stroke provided that strict selection criteria are applied and the door-to-surgery interval is kept short (within 8 hours). Early CEA for secondary prevention is feasible and safe, confirming that a delayed operation is in most cases unwarranted. Large randomized trials are warranted before implementing emergent and early CEA in routine clinical practice.

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.

Dichotomized efficacy end points and global end-point analysis applied to the ECASS intention-to-treat data set: post hoc analysis of ECASS I.

BACKGROUND AND PURPOSE: It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial. METHODS: We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS. RESULTS: The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS (P=0.044; odds ratio [OR], 1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group. CONCLUSIONS: Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.

Early spontaneous improvement and deterioration of ischemic stroke patients. A serial study with transcranial Doppler ultrasonography.

BACKGROUND AND PURPOSE: The purpose of our study was to investigate whether emergency transcranial Doppler (TCD) findings and their modifications over the first 48 hours are related to early neurological changes in acute ischemic stroke patients. METHODS: Ninety-three patients underwent CT scan within 5 hours of a first-ever ischemic hemispheric stroke, and TCD serial examinations at 6, 24, and 48 hours after stroke onset. We classified TCD findings as follows: normal; middle cerebral artery (MCA) asymmetry (asymmetry index between affected and contralateral MCAs below -21%); and MCA no-flow (absence of flow signal from the affected MCA in the presence of ipsilateral anterior and posterior cerebral artery signals through the same acoustic window). We considered early deterioration and early improvement to be a decrease or an increase of 1 or more points, respectively, in the Canadian Neurological Scale score over the same period. RESULTS: At 6-hour TCD examination, MCA asymmetry and MCA no-flow were present in 6 (22%) and 2 (7%), respectively, of 27 improving patients; in 20 (43%) and 10 (22%) of 46 stable patients, and in 9 (45%) and 8 (40%) of 20 deteriorating patients. TCD findings were normal in the remaining patients (P = 0.001). At serial TCD, we detected early (within 24 hours) recanalization (from no-flow to asymmetry or normal and from asymmetry to normal) in 2 (25%) improving patients, in 7 (23%) stable patients, and in 5 (29%) deteriorating patients and late (between 24 and 48 hours) recanalization in 4 (50%) improving patients, in 6 (20%) stable patients, and in none of the deteriorating patients (P = 0.03, chi 2 for trend, improving versus nonimproving irrespective of the timing of recanalization). One deteriorating patient (5%) developed a non-flow from an initial MCA asymmetry. Logistic regression selected normal TCD (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.06 to 0.46) as an independent predictor of early improvement and abnormal TCD (asymmetry plus no-flow) (OR, 5.02; 95% CI, 1.31 to 19.3) as an independent predictor of early deterioration. CONCLUSIONS: TCD examination within 6 hours after stroke can help to predict both early deterioration and early improvement. Serial TCD shows that propagation of arterial occlusion is rarely related to early deterioration, whereas the fact that it can detect early recanalization (within 24 hours) in deteriorating patients and both early and late recanalization (after 24 hours) in improving patients suggests the existence of individual time frames for tissue recovery.

Acute ischemic strokes improving during the first 48 hours of onset: predictability, outcome, and possible mechanisms. A comparison with early deteriorating strokes.

BACKGROUND AND PURPOSE: Our aims were to identify predictors of early neurological improvement in acute ischemic stroke patients, to evaluate its impact on clinical outcome, and to investigate possible mechanisms. METHODS: A consecutive series of 152 first-ever ischemic hemispheric stroke patients hospitalized within 5 hours of onset underwent a first CT scan within 1 hour of hospitalization, and the initial subset of 80 patients also underwent angiography. During the first 48 hours of hospital stay, an increase or a decrease of 1 or more points in the admission Canadian Neurological Scale (CNS) score was defined as early improvement or early deterioration, respectively. Repeated CT scan or autopsy was performed 5 to 9 days after stroke. RESULTS: Thirty-four patients (22%) improved, 84 (56%) remained stable, and 34 (22%) deteriorated. Logistic regression, which took into account vascular risk factors, baseline clinical and CT data, and therapies administered, selected younger age, lower admission CNS score, and absence of early hypodensity at first CT as independent predictors of early improvement. Among the patients who underwent angiography, logistic regression selected arterial patency and presence of collateral blood supply as independent predictors of early improvement. At the repeated CT scan or autopsy, improving patients presented the highest frequency of small infarcts. Thirty-day case-fatality rate and disability were lower in improving patients. Variables independently associated with outcome at logistic regression were admission CNS score, early deterioration, and early improvement. CONCLUSIONS: Early improvement can be predicted by the absence of early CT hypodensity and is highly predictive of good outcome. Presence of collateral blood supply and presumably early spontaneous recanalization are likely to be the mechanisms underlying early improvement.

Posterior circulation infarcts simulating anterior circulation stroke. Perspective of the acute phase.

BACKGROUND AND PURPOSE: Ischemic stroke patients whose initial clinical presentation suggests an involvement of the anterior circulation (AC) are sometimes found to have a posterior circulation (PC) infarct, a fact that may generate erroneous decisions in clinical management. We investigated the prevalence of this misdiagnosis in the first few hours after stroke onset. METHODS: We performed a cohort study of 158 patients hospitalized within 5 hours of onset of a presumed AC ischemic stroke, as diagnosed on clinical grounds. RESULTS: Final CT or pathology diagnosis was AC infarct in 128 patients (81%), a repeatedly negative CT in 14 (9%), PC infarct (5 pons, 1 midbrain and cerebellum, 6 supratentorial territory of the posterior cerebral artery) in 12 (8%), and other or undiagnosed lesions in 4 (3%). AC and PC stroke patients did not differ in terms of age, vascular risk factors, and initial severity, but the latter were more frequently men (83% versus 53%; P = .04), were hospitalized later (mean +/- SD, 168 +/- 86 versus 109 +/- 55 minutes; P = .001), and presented a pure motor hemiparesis or a sensorimotor stroke (50% versus 33%) more often than their counterparts. At baseline CT, PC stroke patients never exhibited an early parenchymal hypodensity in the carotid territory or a hyperdense middle cerebral artery, which were instead found in 59% (P = .0003) and 31% (P = .02) of AC stroke patients, respectively. Early neurological deterioration, 1 month case-fatality rate, and disablement in survivors were comparable in the two groups. CONCLUSIONS: Shortly after onset the clinical discrimination between AC and nontypical PC infarcts is not reliable, which explains the frequent occurrence of this misdiagnosis. Emergency CT scan helps in the differential diagnosis only when it demonstrates an early focal hypodensity within the carotid territory.

Hemorrhagic transformation of brain infarct: predictability in the first 5 hours from stroke onset and influence on clinical outcome.

OBJECTIVE: To identify, in the first 5 hours of acute brain infarct, clinical and radiologic predictors of subsequent hemorrhagic transformation (HT), and to evaluate its influence on the clinical course. BACKGROUND: The identification of early predictors of HT might be important to plan antithrombotic or thrombolytic treatments. PATIENTS: One hundred fifty consecutive patients with cerebral anterior circulation infarct systematically underwent a first CT within 5 hours of onset. During the first week after stroke, we performed a repeat CT or autopsy to look for HT. Outcome measures were early neurologic deterioration within the first week of onset and 30-day case fatality rate and disability. RESULTS: HT was observed in 65 patients (43%): 58 (89%) had a petechial HT and seven (11%) a hematoma. Among initial clinical an CT findings, the only independent predictor of HT was early focal hypodensity. Its presence was associated with subsequent HT in 77% of cases (95% CI, 68 to 86%), whereas its absence predicted the absence of subsequent HT in 94% of cases (95% CI, 89 to 99%). No baseline clinical or CT characteristic differentiated patients with petechial HT from those with hematoma. Antithrombotic and antiplatelet agents did not influence the occurrence of either type of HT. The frequency of early neurologic deterioration and of 30-day death or disability in HT patients was twice as high as in those without HT. However, a large-sized infarct and the presence of mass effect at the repeat CT or autopsy were the only factors independently linked to both the outcome events, irrespective of the development of HT. Clinical evolution of HT patients given antithrombotics was comparable with that of HT patients not receiving these drugs. CONCLUSIONS: HT of a brain infarct is a common event that occurs independently of anticoagulation and can be reliably predicted as early as 5 hours from stroke onset by the presence of focal hypodensity at CT. Apart from the infrequent cases of massive hematoma, HT does not influence prognosis, whereas a poor outcome in HT patients is correlated with a higher frequency of large edematous infarcts in this subgroup. The clinical course and final outcome of HT in anticoagulated patients does not differ from that of non-anticoagulated HT patients.

Thrombolysis acute ischemic stroke.

Thrombolysis is an attractive but potentially dangerous they for cerebral ischemia: it is capable of dissolving an arterial thrombus, but can also transform a pale infarct into a hematoma and/or may cause severe oedema and herniation. The safety and efficacy of the treatment critically depend on the timing of intervention ad on patient selection. In recent studies on ischemic stroke, spontaneous hemorrhagic transformation of an infarct seems to be related to the size of the lesion, and can be reliably predicted as early as five hours from stroke onset by the presence of focal hypodensity in the CT scan. That is why in the European Co-operative Acute Stroke (ECASS), a randomised, double blind trial on intravenous rt-PA in hemispheric stroke, patients showing, on the admission CT scan, extended early hypodensity, involving more than one third of the territory of the middle cerebral artery, were excluded from the day. Other ongoing trials on thrombolytic agents are expected to provide further indications on how to identify those patients most likely to benefit and least likely to experience adverse effects from this treatment.

Clinical and prognostic correlates of stroke subtype misdiagnosis within 12 hours from onset.

BACKGROUND AND PURPOSE: Pure motor hemiparesis and sensorimotor stroke syndromes are not accurate predictors of lacunar infarct when described in the first 12 hours of stroke onset. We evaluate here whether this inaccuracy of clinical diagnosis might have influenced the planning of patient management either in routine practice or in therapeutic trials. METHODS: A consecutive hospital series of 517 first-ever ischemic hemispheric stroke patients presented lacunar or nonlacunar syndromes at the first examination within 12 hours of the event. A distinction was subsequently made, by means of a CT scan or autopsy performed within 15 +/- 2 days of stroke, between patients affected by lacunar or nonlacunar infarcts. We compared stroke risk factors, considered to be indicative of potential pathogenetic mechanisms, and the clinical outcome of lacunar infarct versus nonlacunar infarct patients and those of lacunar syndrome versus nonlacunar syndrome patients. RESULTS: Two hundred nineteen patients (42%) presented a lacunar syndrome and 298 (58%) a nonlacunar syndrome, while 170 (33%) had lacunar infarcts and 347 (67%) nonlacunar infarcts. Lacunar infarct patients were more frequently associated with hypertension and a previous transient ischemic attack and less frequently with atrial fibrillation when compared with their nonlacunar infarct counterparts, whereas no differences were apparent between lacunar syndrome and nonlacunar syndrome patients. Logistic regression analysis showed that hypertension and a previous transient ischemic attack on the one hand and atrial fibrillation on the other were strongly correlated with the diagnosis of lacunar infarct and nonlacunar infarct, respectively, while no risk factor was correlated with the diagnosis of lacunar syndrome. Twenty-two percent of lacunar infarct patients and 68% of nonlacunar infarct subjects had a poor outcome (death plus disability of survivors) as opposed to 40% of lacunar syndrome and 63% of nonlacunar syndrome patients. Logistic regression selected age, severity of neurological deficit at entry, cardiopathies, diabetes, and lacunar infarct, but not lacunar syndrome, as predictors of outcome. CONCLUSIONS: The inaccurate clinical diagnosis of lacunar infarct made in the first 12 hours of stroke might lead to no distinction being made between stroke subgroups with potentially different pathogenetic mechanisms and prognostic estimates, thus negatively influencing the planning of patient management.

Progressing neurological deficit secondary to acute ischemic stroke. A study on predictability, pathogenesis, and prognosis.

OBJECTIVES: To identify predictors and possible pathogenetic mechanisms of early neurological deterioration in patients with acute ischemic strokes and to evaluate their impact on clinical outcome. DESIGN: Case series. SETTING: University hospital's stroke unit. PATIENTS: A continuous series of 152 patients with first-ever ischemic hemispheric strokes were hospitalized within 5 hours of onset, evaluated with the Canadian Neurological Scale, and underwent a computed tomographic (CT) scan. The initial subset of 80 patients also underwent angiography. A repeated CT scan or autopsy was performed within 5 to 9 days of a patient's stroke. Progressing neurological deficit was defined as a decrease of one point or more in the global neurological scale score during hospitalization, when compared with that at entry. RESULTS: The conditions of 39 patients (26%) deteriorated during the initial 4 days; 20 patients (51%) had an impaired level of consciousness, and 19 patients (49%) had impaired limb strength and/or speech. They had been hospitalized earlier and had higher serum glucose levels at admission; the baseline CT scans of these patients showed an early focal hypodensity and initial mass effect more frequently. On the repeated CT scan (144 patients) or at autopsy (eight patients), patients with a progressing course more frequently had large infarcts, severe mass effect, and hemorrhagic infarction. We found no differences with regard to demographic data, medical history, and treatments that were given; only subcutaneous heparin calcium was more frequently administered to patients with a progressing course. Twenty-two (27%) of the 80 patients who underwent angiography had a progressing course, of whom 20 (91%) had an intracranial and/or extracranial arterial occlusion, with collateral blood supply in seven patients (35%). Logistic regression analysis showed that the independent predictors of progression were the serum glucose levels at admission and the early focal hypodensity with cortical and corticosubcortical locations, with the positive predictive values of the latter being 34% (95% confidence interval [CI], 26% to 42%) and 57% (95% CI, 47% to 67%), respectively. Among patients who underwent angiography, logistic regression analysis showed a significant correlation between carotid siphon occlusion and a progressing course. The 30-day case-fatality ratio and disability (Barthel index, < 60) were higher in patients with a progressing course (36% and 54% vs 12% and 35%, respectively). CONCLUSIONS: Early stroke deterioration is still an event that is difficult to predict; it is largely determined by cerebral edema following an arterial occlusion, as indicated by an early focal hypodensity and initial mass effect on the baseline CT scan. Since early deterioration anticipates a bad outcome in 90% of patients, it might be used as an early surrogate end point in therapeutic trials.