Background and Purpose - Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms.Methods - The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 x control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke.Results - A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9% versus 28.6%; P = 0.025). In addition, in the same group, there were fewer deaths (16.8% versus 21.9%; P = 0.189), more symptomatic brain hemorrhages (6.2% versus 1.4%; P = 0.008), and more major extracerebral bleedings (2.9% versus 1.4%; P = 0.491).Conclusions - Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.

Background and Purpose — Guidelines for medical practice in stroke have been proposed in different countries, but their impact on stroke outcome has not been verified to date. The aim of this study was to evaluate the impact of the American Heart Association guidelines for acute stroke and for transient ischemic attack on first-ever stroke patients. Methods — Three hundred eighty-six first-ever ischemic stroke patients were admitted to the study. Those observed within 6 hours from stroke onset were eligible for the acute clinical phase of the study, while all were admitted to the early clinical phase. The follow-up lasted 6 months. Primary end points were survival and the effectiveness of treatment on disability, measured as the proportion of potential improvement in the Barthel Index score achieved during treatment. A rating of noncompliance with the guideline recommendations was calculated for each patient, and its association with the end points was investigated. The Kaplan-Meier method and log-rank test were used to estimate and compare survival curves between groups; Cox proportional hazards model and logistic regression were used to identify risk factors for mortality; and correlation tests and regression analysis were used to evaluate the influence of guideline compliance on disability. Both univariate and multivariate statistical analyses were performed. Results — Survival and treatment effectiveness were directly correlated with guideline compliance. The relative risk of death for patients with a noncompliance rating ≥5 was 2.26 with respect to patients with a noncompliance rating <5 (95% CI, 1.51 to 4.67; P <0.0007). In this latter group, at 6 months we detected a 15% decrease in mortality (95% CI, 9.1% to 17.5%). Treatment effectiveness showed a Spearman’s rank correlation with the noncompliance rating of −0.3 ( P <0.001). At discharge we observed a 13% increase in treatment effectiveness, while no significant differences were detectable at 3 and 6 months. These associations were confirmed by the multivariate analysis, in which we included, together with the noncompliance rating, all the variables previously identified as independent predictors of mortality and disability. Conclusions — This study demonstrates an association between adherence to guidelines and stroke outcome, and it can be viewed as a study that prepares the way for a randomized controlled trial in this area. It also emphasizes the need to develop personnel and structures devoted to stroke care because an evidence-based clinical approach could significantly reduce the risk of death.

We describe the case of a large brain lesion whose computed tomography appearance and clinical evolution mimicked a herniating tumor. The patient progressed to coma within 6 days of hospitalization despite high-dose steroid treatment. Emergency excision of the lesion was carried out. Histological analysis showed massive demyelination, axon preservation and no tumor cells. No lesions recurrence was seen during a 55-month follow-up. Recognition of such lesions through magnetic resonance imaging or spectroscopy may spare unnecessary surgery or biopsy. However, our case shows that such lesions may still require resection in the face of a rapid clinical progression and poor response to medical treatment.

Background: There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of enlimomab after ischemic stroke. Methods: A total of 625 patients with ischemic stroke were randomized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival. Results: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die. Conclusions: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.

We prospectively verified whether an ad-hoc questionnaire administered by phone supports pre-hospital suspicion of stroke in the order to reduce the time before care is given. Form June 1996 to May 1997, physicians of the Emergency Medical Service in the area of Bergamo, Italy asked all people calling for a patient with symptoms and signs suggesting a cerebral vascular injury to immediately answer some questions on common symptoms and signs of stroke. The medical records of the patients hospitalized at Ospedali Riuniti of Bergamo were reviewed at the end of the study by a single neurologist, skilled in stroke management and blinded to the questionnaires. Sensitivity and specificity, in addition to positive and negative predictive values, of single questions versus final diagnosis were assessed. Logistic regression analysis was also performed to identify those questions useful to suspect strokes. We collected 143 valid questionnaires, related to 63 men and 80 women, aged 34–99 years (mean, 71.8 years). The question concerning headache had the lowest sensitivity and specificity, respectively 57.1% and 36.5%, and teh question concerning leg palsy had the highest sensitivity and specificity, respectively 82.0% and 52.4%. Multivariate analysis identified questions on facial and leg palsy as independent predictors of a final diagnosis of stroke. A few questions on motor deficits proposed by emergency medical service operators may be useful in the pre-hospital identification of stroke patients. Concordance of any questions versus final diagnosis of stroke was, however, far to be satisfying. Thus, our experience supports the need for an educational program to improve the efficiency of a pre-hospital diagnosis of stroke.

BACKGROUND: It has been known for decades that monoclonal IgM gammopathies are associated with peripheral neuropathies. However, available data are from ultraspecialized laboratories, while little is reported about their epidemiology. PATIENTS AND mETHODS: Since 1988 we have recorded a registry of the patients referred for a peripheral neuropathy. Database included clinical, electrophysiological, laboratory, immunological and pathological data. All the patients were followed‐up with clinical visits or at least phone interview every six months. In case of death we evaluated death certificates and contacted general practitioners. Results: In the period from 1988–1999 we saw and followed‐up 512 patients with clinical ascertained peripheral neuropathy. Of those patients, 35 (6.8%) had a MGUS: 18 IgG, 10 IgM, and 7 IgA. The patients with IgM paraprotein were all men, except 1 woman, aged 48 to 71 years at the onset of symptoms. Eight patients had a predominantly sensitive neuropathy and two patients a motor neuropathy. Of the 8 patients with sensitive neuropathy, 3 had a demyelinating disease and antiMAG antibodies, 4 an axonal disease and antisulphatide antibodies, and 1 an axonal neuropathy with both antiMAG and antisulphatide antibodies. The two patients with motor neuropathy had both an axonal disease and anti‐GM1 antibodies. The patients with sensory neuropathy were treated with periodic plasmaphoresis plus i.v. cyclophosphamide every 4–6 months. The patients with motor neuropathy were treated every month with i.v. immunoglobulins alternated with i.v. cyclophosphamide. Follow‐up of those patients lasted 12 to 108 months. Four patients died: 3 with antisulfatide antibodies because of a developing cancer (2 a primary hepatic cancer and 1 a bladder neoplasm) and 1 with anti‐GM1 antibodies for respiratory failure. The remaining patients showed a slowly progressive invalidating disease especially with the loss of hand ability. Conclusions: The patients with monoclonal IgM gammopathy are a minority among those observed because of a peripheral neuropathy in a General Hospital. Prognosis is severe either because of growing dependency or of life shortening (directly or for developing cancer). Aggressive therapies probably deserve multicentric studies.

OBJECTIVE:We have investigated recurrence of stroke in a consecutive series of young adults, aged 16 to 45 years, after a first cerebral infarction. METHODS:From January 1, 1988 to December 31, 1996 we submitted those patients to a diagnostic protocol including angiographic, cardiological, and haematological investigations. The patients were followed at 6 month intervals up to December 31, 1998. RESULTS:We have evaluated and followed-up 135 patients, 71 men and 64 women, who were 3.99% of all the admitted stroke patients. At 12 months after stroke, 83 patients had returned to work, 40 patients were mildly to moderately handicapped, 4 were using a wheel-chair, and 8 had died. Follow-up was 26 to 123 months (mean 68.8). Recurrence of stroke, always of ischaemic nature, was seen in 15 patients (11.1%), 3 to 76 months after the first stroke (mean 27.4), for an annual incidence of 2.26%. Recurrence was significantly associated with Partial Anterior Circulation Syndrome and Haematological subtype of first stroke (respectively, P = 0.0209 and P = 0.0135, chi2 test), but not with age (< or = or > 35 years) or risk factors. Repetition of stroke was never fatal, but it caused heavy disability in 13 patients, 8 of whom had completely or nearly completely recovered after the first event. CONCLUSIONS:Our data suggest that recurrence of stroke is a major clinical problem also for the patients aged less than 45 years and that it might be more frequent with specific clinical syndromes and etiologic subtypes of first stroke.

OBJECTIVE:To assess if Doppler microembolic signals (MES) associated with > or = 60% symptomatic extracranial carotid stenosis may predict ischemic recurrences before endarterectomy or angioplasty.METHODS:All patients with > or = 60% carotid stenosis with symptoms in the preceding 2 months were prospectively considered. MES were identified using current criteria. All patients were followed-up until endarterectomy or angioplasty.RESULTS:We studied 50 patients, at a median of 7 days from their last symptom. Twenty patients showed MES (40.0%); median embolus rate was 4/h. During a median follow-up of 19 days 7 patients had recurrences (transient monocular blindness = 2; TIAs=4; stroke=1); 6 of them had shown MES. The association between recurrences and MES was significant (P=0.012).CONCLUSIONS:MES may identify patients with symptomatic carotid stenosis who are likely to suffer an ischemic recurrence before endarterectomy. This information may affect medical treatment and referral to the vascular surgeon.

OBJECTIVES:To evaluate the presence of microembolic signals (MES) in the middle cerebral artery distal to a stented carotid artery late after stent deployment. MES may be a signal of thrombus formation at the stent level.PATIENTS AND METHODS:Two patient groups were studied with transcranial Doppler at different intervals after deployment of Palmaz stents or Wallstents for stenosis of the internal or common carotid artery. Group 1: from 6 to 12 months after stent deployment; Group 2: > 12 months after stenting.RESULTS:One out of 19 patients in Group 1 showed MES (5.0%); however, this patient also had two mechanical heart valves. None out of 17 patients in Group 2 had MES.CONCLUSIONS:Carotid stents seem to have a very low emboligenic potential after the early post-deployment period. This is a reassuring message for present and future patients harboring such stents.

Objective: To determine the direct costs of hospital care of acute ischemic stroke in a large Italian hospital, and to identify the main components of such costs. Background: Cost containment in stroke care requires an up-to-date assessment of expenditures in the different areas of stroke management. However, costs may vary among countries because of different health system organizations. Methods: All patients with ischemic stroke admitted during 1996 were considered. Total cost was the sum of a daily component, reflecting personnel wages and general care, and an ancillary component, reflecting mostly investigations and treatments. The real costs were used, not fixed charges. Results: We included 245 patients, with a mean length of stay (LOS) of 13.1 +/- 7.0 days, and an in-hospital case fatality rate of 8.2%. The mean total cost per patient was 5,087,000 +/- 2,536,000 Italian Lira (LIT; $3,289 +/- $1,640), with a mean cost per day of 388,000 LIT ($251). Approximately 80% of total costs were due to the daily component and 20% to the ancillary component. A multiple linear regression model of length of stay, which determines the daily cost, showed that the Rankin score at entry, the clinical syndrome type, and the destination at discharge independently contributed to LOS. A second linear regression model showed that younger age and longer LOS significantly increased ancillary costs. Conclusions: The containment of hospital costs of ischemic stroke may be achieved mostly through measures that reduce LOS, such as effective treatments and a quicker deployment.

OBJECTIVE To investigate the frequency of cancer developing in patients with peripheral sensory neuropathy of unexplained cause. DESIGN Prospective study. SETTING A neurologic unit in a general hospital. METHODS Following the diagnosis of neuropathy, we searched for occult malignancy. This search was repeated together with neurologic evaluations every 6 months thereafter. Patient recruitment began January 1, 1988, and ended December 31, 1995. The end point of the study was December 31, 1996. RESULTS In the study period, we observed 363 patients with peripheral sensory neuropathy. Of these, 53 patients without any identified cause of neuropathy were invited to participate in the study. Of the 53, 2 patients refused. Thus, we examined and followed up 51 patients, 42 men and 9 women, with a mean age of 64.5 years (range, 19-80 years). The range between the onset of neurologic symptoms and the diagnosis of neuropathy was 2 to 72 months (mean, 13.9 months). The follow-up period ranged from 14 to 94 months (mean, 51.4 months). In 18 patients (35.3%) (16 men and 2 women) whose mean age at diagnosis of neuropathy was 66.5 years. malignant growths were found 3 to 72 months (mean, 27.4 months) after the onset of the neuropathy. The cancer was in the liver in 4 patients (all had a primary hepatoma), the bladder in 3, the lymph nodes in 3 (all with non-Hodgkin lymphoma), the prostate gland in 2, the lungs in 2 (small cell lung cancer in both), the breast in 1, the pancreas in 1, the sublingual gland in 1, and the bone in 1 (a metastatic sarcoma). CONCLUSIONS More than one third of the patients with peripheral sensory neuropathy of unexplained cause developed cancer without any predominating type of malignancy.

OBJECTIVES:To test the hypothesis that transoesophageal echocardiography (TOE) carried out within three days of a first stroke or transient ischaemic attack of cryptogenic or lacunar type may disclose more thrombi or spontaneous echo contrast (SEC) than previously reported. This finding may help early treatment decisions.METHODS:Patients aged between 40 and 80 years, admitted for transient ischaemic attack or ischaemic stroke during a 40 month period, were prospectively considered. TOE was carried out within 72 hours of symptom onset with a 5 MHz biplanar transducer. Subjects with recurring events, very severe strokes, large artery obstructions, or obvious cardiac sources of embolism were excluded.RESULTS:Sixty five patients were studied, 43 with a cryptogenic stroke or transient ischaemic attack (66.2%), and 22 with a lacunar stroke (33.8%). The mean (SD) interval between symptom onset and TOE was 43.4 (17.2) hours for cryptogenic, and 48.5 (19.5) hours for lacunar patients. Atrial thrombi were found in one patient with a cryptogenic stroke (2.32% of cryptogenic events; 95% confidence interval 0.06-12.29), whereas SEC was found in five patients (7.7% overall), two with a lacunar and three with a cryptogenic stroke.CONCLUSIONS:An early TOE does not seem to increase substantially the detection of atrial thrombi or SEC in patients with a first stroke or transient ischaemic attack of cryptogenic or lacunar nature. Therefore, this examination can be carried out when the patients' conditions are stable, and without overloading the cardiovascular laboratory daily schedule.

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Background and Purpose Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke. Methods All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded. Results Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes ( P =.029), atrial fibrillation ( P =.032), aphasia at entry ( P <.001), large middle cerebral artery infarctions ( P <.001), and a more severe neurological deficit at entry ( P =.003) and at 3 months ( P <.001). At CT scan, demented patients had a larger mean volume of the recent lesion ( P <.001) and more lesions in the frontal lobe ( P =.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR, 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia. Conclusions Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.

OBJECTIVES:To report experience of intra-arterial thrombolysis for acute stroke, performed with a microcatheter navigated into the intracranial circulation to impale the clot.METHODS:Patients were selected on the following criteria: (1) clinical examination suggesting a large vessel occlusion in stroke patients between 18 and 75 years; (2) no radiographic signs of large actual ischaemia on CT at admission; (3) angiographically documented occlusion of the middle cerebral artery (MCA) stem or of the basilar artery (BA), without occlusion of the ipsilateral extracranial internal carotid artery or of both the vertebral arteries; (4) end of the entire procedure within six hours of stroke. 12 patients with acute stroke were recruited, eight of whom had occlusion of the MCA stem and four of the BA. Urokinase was used as the thrombolytic agent.RESULTS:Complete recanalisation in six MCA stem and in two BA occurred, and partial recanalisation in two MCA stem and one BA. There was no recanalisation in one BA. A clinically silent haemorrhage occurred in two patients, and a parenchymal haematoma in one patient, all in MCA occlusions. At four months five patients achieved self sufficiency (four with MCA and one with BA occlusion). Six patients were dependent (three totally), and one died.CONCLUSIONS:The strict criteria of eligibility allowing the enrollment of very few patients and the procedure itself, requiring particular neuroradiological expertise, make this procedure not routine. Nevertheless, the approach can be considered a possible option for patients with acute ischaemic stroke.

In order to evaluate whether the results of ultrasound examination may be associated with 30-day outcome, 76 consecutive patients (43 men and 33 women; mean age 68.1+/-8.9 years) underwent duplex scanning of the carotid bifurcations and transcranial doppler investigation of the basal skull arteries within the first few hours of the onset of an acute carotid stroke. Forty-three patients (56.6%) had appropriate arterial occlusion at ultrasounds examination. On day 30, 22 patients (28.9%) were self-sufficient, 41 (53.9%) were disabled and 13 (17.1%) were dead. The chi-squared test showed that the ultrasound results were significantly related to 30-day outcome (p=.0003).After logistic regression analysis, the ultrasound results remained independent predictors of 30-days outcome (p=.0129), together with neurological impairment 24 hours after stroke onset and lesion size at control computed tomography.Our study suggests that the results of ultrasound examination may be useful in the management of acute carotid stroke as an early indicator of patients with a worse prognosis.

We report a series of nine patients younger than 45 years with angiographically-documented cerebral venous thrombosis, consecutively referred to our Stroke Unit from 1988 to 1994. Two of them were men and seven women. Eight patients initially complained of headache, often associated with other symptoms of increased intracranial pressure. Seven patients had focal motor deficits and four suffered from epileptic seizures. None of the patients died. Only one patient remained severely disabled, whereas the others recovered self-sufficiency within two months. The use of oral contraceptives was closely associated with the occurrence of venous thrombosis in the women.

In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2x2 factorial design to (i) a 1-hour intravenous infusion of 1 . 5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued.Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2 . 7; 95% confidence interval 1 . 7-4 . 3; 2p<0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3 . 5; 95% CI 1 . 9-6 . 5; 2p<0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0 . 9 (95% CI 0 . 7-1 . 3) and odds ratio for aspirin 0 . 9 (95% CI 0 . 6-1 . 3).The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.