Background Piracetam has neuroprotective and antithrombotic effects which may help to reduce death and disability in people with acute stroke.Objectives The objective of this review was to assess the effects of piracetam in acute presumed ischaemic stroke.Search strategy We searched the Cochrane Stroke Group Trials Register (last searched 20 June 2005). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), and ISI Science Citation Index (1981 to April 2005). We also contacted the manufacturer of piracetam to identify further published and unpublished studies.Selection criteria Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within approximately 48 hours of stroke onset.Data collection and analysis Two authors extracted data and assessed trial quality and this was checked by the other two authors. Study authors were contacted for missing information.Main results Three trials involving 1002 people were included, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependency or proportion of patients dead or dependent. Adverse effects were not reported.Authors' conclusions There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependency.

The key elements for developing a clinical guideline are (a) guidelines are developed by multidisciplinary groups, (b) they are based on a systematic review of the scientific evidence, and (c) recommendations are explicitly linked to the supporting evidence and graded according to the strength of that evidence. Besides reporting the statistical strength of the randomised controlled trial results, it is necessary to consider the strength of the evidence, the methodological quality of the studies and the external validity by applying a "considered judgement" to the whole amount of the data. The Scottish Intercollegiate Guidelines Network (SIGN) process for developing guidelines is based on 4 steps: (a) methodological evaluation, (b) synthesis of evidence, (c) considered judgement and (d) grading system. The judgement on grading of recommendations is made on the basis of an (objective) assessment of the study design and quality, and a (perhaps more subjective) judgement of the consistency, clinical relevance and external validity of the evidence. The SPREAD group decided to adopt this methodology starting from the 3rd edition (2003); however, it was agreed to integrate the principles of the SIGN [4] with the statistical considerations on alpha and beta error size suggested by the Centre for Evidence-Based Medicine methodology [6], to give a more comprehensive evaluation of the available evidence. By being the product of a multidisciplinary approach, being explicit and providing information on the way agreement has been reached or on the reasons of disagreement, the SPREAD guidelines seem to fulfil the needs for shared guidelines, and to avoid the concerns related to pitfalls in the transparency of the process and in the reaching of a consensus.

BACKGROUND:Brain oedema is a major cause of early death after stroke. A 10% solution of glycerol is a hyperosmolar agent that is claimed to reduce brain oedema. OBJECTIVES:To determine whether I.V. glycerol treatment in acute stroke, either ischaemic or haemorrhagic, influences death rates and functional outcome in the short or long term and whether the treatment is safe. SEARCH STRATEGY:The Cochrane Stroke Group Trials Register was searched, conference proceedings were screened and some trialists were personally contacted. SELECTION CRITERIA:All completed, randomised and quasi-randomized, controlled, published and unpublished comparisons, evaluating clinical outcome in which intravenous (I.V.) glycerol treatment was initiated within the first days after stroke onset. DATA COLLECTION AND ANALYSIS:Two reviewers independently applied the inclusion criteria, assessed the trial quality and extracted data and this was checked with all co-reviewers. Death from all causes, functional outcome and adverse effects were analysed. MAIN RESULTS:Eleven completed, randomised trials comparing I.V. glycerol and control were considered. Analysis of death during the scheduled treatment period for acute ischaemic and/or haemorrhagic stroke was possible in ten trials where 482 glycerol treated patients were compared with 463 control patients. Glycerol was associated with a non-significant reduction in the odds of death within the scheduled treatment period (OR 0.78, 95% Confidence Intervals 0.58 - 1.06). Among patients with definite or probable ischaemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (odds ratio 0.65, 95% CI 0.44-0.97). However, at the end of the scheduled follow up period, there was no significant difference in the odds of death (odds ratio 0.98, 95% CI 0.73-1.31). Functional outcome was reported in only two studies but there were non-significantly more patients who had a good outcome at the end of scheduled follow up (odds ratio 0.73, 95% CI 0.37-1.42). Haemolysis seems to be the only relevant adverse effect of glycerol treatment. REVIEWER'S CONCLUSIONS:This systematic review suggests a favourable effect of glycerol treatment on short term survival in patients with probable or definite ischaemic stroke but the magnitude of the treatment effect may be minimal (as low as a 3% reduction in odds). Due to the relatively small number of patients and that the trials have been performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.

To the Editor: We read with interest the Controversies in Stroke on steroids,1 and appreciated both Dr Norris’ and Dr Poungvarin’s papers. We fully agree with the conclusion of Drs Davis and Donnan, in that when no commercial attraction exists for some treatment, then only high-quality, investigator-driven trials are possible. However, we wish to stress the fact that if someone is …

Data Source We evaluated the Cochrane systematic review of randomised controlled trials [1]. Trials were identified by searching Medline, Embase, Central Cochrane Library, Cochrane Dementia and Cognitive Improvement Group database, abstract from proceedings of the main Dementia Conferences, and by contacting the pharmaceutical company, Novartis, for unpublished and published trials. The search was updated to December 2000.

The Cochrane Collaboration is an international non-profit and independent organization, dedicated to making up-to-date, accurate information about the effects of healthcare readily available worldwide. It produces and disseminates systematic reviews of healthcare interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. The major product of the Collaboration is the Cochrane Database of Systematic Reviews which is published quarterly as part of The Cochrane Library. A systematic review, when well done, is a reliable summary of the body of knowledge at the time. Its result may mean that one has to temper one’s opinion of the value of a particular treatment but there is no place nowadays for ineffective or hazadous treatments. Systematic reviews should be looked upon as extremely useful sorting tools to get a better perspective of current status of knowledge, and looked to see what questions new trials should seek to answer in future. This is the case of the reviews on the treatment of Carpal Tunnel Syndrome (CTS). On October 26, 2002, in Corciano, the Cochrane Neurological Network organised its 2nd Multidisciplinarian Workshop to discuss Cochrane systematic reviews on the treatment of CTS. A variety of experts participated in the presentation, including neurologists and orthopaedic hand surgeons of different backgrounds. The main outcome of the meeting was to capture the current state of knowledge on CTS by looking back at evidence from sistemtic reviews and their single trials. Secondary outcome of the meeting was determined that it is necessary to favor controlled clinical studies on the disease correcting for the drawbacks highlighted in previous studies. Such corrections should include specific diagnostic criteria of the CTS; a larger sample size of the single trials; suitable follow up; subgroup division by age, sex, and clinically and instrumentally determined severity of the disease; duration of the disease; and degree of stressful activity.

Background and Purpose— We sought to assess the relationship between 2 simple questions on recovery (question 1: do you feel that you have made a complete recovery from your stroke?) and dependency (question 2: do you require help from another person for everyday activities?) and the Barthel Index (BI) and Oxford Handicap Scale (OHS), as well as the relationship between BI and OHS, in a large number of Italian stroke survivors who participated in the International Stroke Trial (IST). Methods— We used data from 2423 patients interviewed by telephone at 6 months after the event. The &kgr; statistic, sensitivity, and specificity were calculated for several comparisons. Internal consistency for BI was calculated. Results— The reliability of the dependency question compared with BI=20 (&kgr;=0.93) and the reliability of the recovery question compared with OHS=0 (&kgr;=0.89) were good. Sensitivity of the dependency question in predicting whether patients scored BI >18 was 0.98; sensitivity of the recovery question in predicting whether patients scored OHS=0 was 0.99. The reliability of BI=20 compared with OHS <3 was good (&kgr;=0.87). Internal consistency of BI was very high (Cronbach’s &agr;=0.96). Conclusions— The 2 simple questions are a good means of evaluating outcome from a patient’s view and of dichotomizing the stroke survivor in a time-effective and reliable way.

Background and purpose: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic.Patients and methods: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed.Results: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury.Conclusions: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

We studied whether the administration of piracetam in acute, presumed ischemic stroke affects case fatality and functional outcome. The Cochrane Stroke Group strategy was used to evaluate all randomized controlled trials of patients with presumed ischemic stroke examined within 48 h; death and (when available) functional outcome were used as end points. Three studies were included; the most recent one contributed more than 97% of the data. There were 501 patients treated with piracetam and 501 controls. Piracetam was associated with a nonsignificant 31% increase in the odds of death (95% CI –5% to 81%). This result was due almost completely to the effect of the larger trial, which, however, reported that the difference in case fatality rate between piracetam and control disappeared after correcting for the imbalance in stroke severity between the two groups. Data on functional outcome were available only for the largest study, and no difference was reported. Data obtained from the manufacturer suggested a nonsignificant trend (–10%) towards reduction in dependency with piracetam (CI –33% to 20%); the proportions of patients dead or dependent in the two groups were the same. Relevant adverse effects were not reported. The evidence from this review does not support routine administration of piracetam in patients with acute ischemic stroke; however, since a possible beneficial effect cannot completely be ruled out, further controlled trials are warranted.

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

Background and purpose-To test the design and feasibility of a very large randomised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke. Design-Randomised controlled multicentre open study, with a 3 x 2 factorial design, allocating patients to: medium dose subcutaneous heparin (12 500 units twice per day), versus low dose subcutaneous heparin (5000 units twice per day) versus no heparin; and aspirin (300 mg daily) versus no aspirin. Treatment was given for two weeks or until discharge from hospital if sooner.Results-984 patients were randomised. CT was performed in 924 (94%) (before randomisation in 622/984 (63%)). Within 14 days: 97 patients had died (10%), 30 (3.0%) had a fatal or non-fatal recurrent ischaemic stroke, nine (0.9%) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage, and eight (0.8%) had a fatal or non-fatal pulmonary embolus. At six months, vital status was known for 975 patients (99%), of whom treatments. 210 (22%) were dead, 373 (38%) were alive but dependent, and 225 (23%) were independent but not fully recovered.Conclusions-The trial procedures ELIGIBILITY proved practicable and a wide variety of patients were recruited. Sample size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20000 patients. Recruitment rates in the pilot study indicated that if about 200 hospitals participated, recruitment could be completed by 1997.

In the case of a patient with sudden-onset focal neurological deficit, clinicians must answer three fundamental questions: is it a stroke? is it ischemia or hemorrhage? and what kind of ischemic stroke is it? Clinical information (i.e., history and examination) is available in any situation, and its role in answering these questions is extremely important, even though certainty can only be achieved from instrumental diagnostic tools. In fact, when diagnosis is based on properly designed clinical criteria, the percentage of mistakes is quite low. Clinical methods are still the best way to orient topographic and etiologic diagnosis, as well as estimate prognosis. In addition, time might be saved if randomization in clinical trials were performed using clinical methods before initiating complex investigations.

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.

Objective-To compare two available clinical scores for the differential diagnosis of cerebral ischaemia and haemorrhage in acute stroke patients.Design-Prospective, multicentre study of acute stroke patients evaluated with computed tomography and Allen and Siriraj scores; the scores were tested for comparability (kappa statistic) and validity (sensitivity, specificity, positive and negative predictive values, diagnostic gain). The effect of a policy of using Allen and Siriraj scores to determine pathological type of stroke before computed tomography was calculated.Setting-Three hospitals in Italy, all participating in the international stroke trial, with different access facilities to computed tomography.Subjects-231 consecutive patients who were screened in the three hospitals for possible inclusion in the international stroke trial from 1 November 1991 to 31 May 1993.Results-The prevalence of haemorrhage (diagnosed with computed tomography) was 14.7% (95% confidence interval 10.1% to 19.3%). Allen scores were ''uncertain'' in 44 cases and Siriraj scores in 38 cases; in the 164 cases with both the scores in the range of ''certainty'' kappa was 0.72. Sensitivity, specificity, positive and negative predictive values, and diagnostic gain for haemorrhage were 0.38, 0.98, 0.71, 0.91, and 0.58 for Allen scores and 0.61, 0.94, 0.63, 0.93, and 0.48 for Siriraj scores; positive predictive values for infarction were 91% for Allen scores and 93% for Siriraj scores. According to these data, of 1000 patients with acute stroke, 680 would be correctly and 70 wrongly diagnosed as ''ischaemic'' with the Alien score; the figures would be 671 and 48 with Siriraj score.Conclusion-When computed tomography is not immediately available and the clinician wishes to start antithrombotic treatment (or randomise patients in a clinical trial), the Siriraj score (and possibly the Alien score) can be useful to identify patients at low risk of intracerebral haemorrhage.

Clinicians faced with a patient having a sudden-onset, focal neurological deficit must answer three fundamental questions: is it a stroke?, is it ischemia or hemorrhage? and what kind of ischemic stroke is it? Clinical information (that is, history and examination) is immediately available to every physician, and its role in answering these questions is extremely important, even though a 100% certainty can only be obtained with instrumental diagnostic tools. In fact, when diagnosis is based on properly designed clinical criteria, the percentage of diagnostic mistakes is quite low. Clinical methods are still the best way of orientating topographic and etiologic diagnosis, as well as prognosis. In addition, time might be saved if randomization in clinical trials could be done using clinical methods before complex investigations are applied.

HomeStrokeVol. 25, No. 11Silent infarctions in first-ever stroke patients. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBSilent infarctions in first-ever stroke patients. S Ricci, M G Celani, E Righetti, N Caputo, F La Rosa and E Duca S RicciS Ricci , M G CelaniM G Celani , E RighettiE Righetti , N CaputoN Caputo , F La RosaF La Rosa and E DucaE Duca Originally published1 Nov 1994https://doi.org/10.1161/01.STR.25.11.2293Stroke. 1994;25:2293–2294"Silent infarctions in first-ever stroke patients.." Stroke, 25(11), pp. 2293–2294 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Kobayashi A, Karlinski M, Litwin T and Czlonkowska A (2012) Do silent infarcts modify the effect of thrombolysis for stroke?, Acta Neurologica Scandinavica, 10.1111/j.1600-0404.2012.01699.x, 127:4, (227-232), Online publication date: 1-Apr-2013. Cleary P, Shorvon S and Tallis R (2004) Late-onset seizures as a predictor of subsequent stroke, The Lancet, 10.1016/S0140-6736(04)15946-1, 363:9416, (1184-1186), Online publication date: 1-Apr-2004. Olsen T (2001) Post-stroke epilepsy, Current Atherosclerosis Reports, 10.1007/s11883-001-0029-4, 3:4, (340-344), Online publication date: 1-Jul-2001. Jørgensen H (1996) The Copenhagen Stroke Study experience, Journal of Stroke and Cerebrovascular Diseases, 10.1016/S1052-3057(96)80020-6, 6:1, (5-16), Online publication date: 1-Sep-1996. November 1994Vol 25, Issue 11 Advertisement Article InformationMetrics Copyright © 1994 by American Heart Associationhttps://doi.org/10.1161/01.STR.25.11.2293 Originally publishedNovember 1, 1994 PDF download Advertisement

The great technological progress in the Neurosciences area, which has appeared in the last few years, can cause, beside obvious scientific and practical advantages, an important risk: in fact, efficiency might be preferred at the expense of efficacy. In this paper we try and outline a sort of "efficacy route in Neurology", based on well known general principles of Clinical Epidemiology, both for diagnosis and treatment. We stress the fact that clinical evaluation is still an essential instrument in the diagnostic process, and that the result of any therapeutic procedure must be evaluated by means of hard end points, strictly related to the real problems of the neurological patient.

The incidence of somatosensory, visual half-field and motor deficits contralateral to a hemispheric lesion in a continuous series of 154 left brain damaged and 144 right brain damaged stroke patients were investigated. These contralateral disorders were more frequent after lesions of the right hemisphere. This difference cannot be attributed to a bias in patients' selection. It is suggested that left spatial neglect is the factor underlying this hemispheric difference.

Background and Purpose. The relative frequency of computed tomographic evidence of old cerebral infarctions without prior history of stroke, and their effect on short- and long-term outcome of patients with first-ever ischemic stroke, are currently unknown. Silent infarctions may relate to specific risk factors and may influence the rate of survival free of handicap.Methods: We studied the prevalence of such lesions in patients registered with SEPIVAC, a community-based survey of stroke incidence and outcome in the Sixth Local Health Unit of Umbria, Italy. Of 375 first-ever strokes, 209 patients with cerebral infarction (computed tomogram done within 30 days after the stroke) were included in this study. Computed tomograms were reviewed blindly, and cases were classified as having a single lesion or multiple lesions; in the latter case, it was assumed that at least one silent brain infarction was present. The two groups were compared in terms of risk factors and outcome. To avoid a selection bias, these patients were also compared with 68 patients who were not submitted to computed tomography but were judged on clinical grounds to have a >90% probability of having suffered a cerebral infarction.Results: Risk factors and outcome did not differ between patients without and with a computed tomogram. In the latter group, 80 patients (38.3%; 95% confidence interval, 31.7%-44.9%) had silent brain infarction. Male sex (odds ratio, 1.84; 95% confidence interval, 1-3.4), ischemic changes on an electrocardiogram (odds ratio, 2.5; 95% confidence interval, 1.3-4.9), and - in the multivariate analysis - hypertension (odds ratio, 1.46; 95% confidence interval, 1.1-2) were significantly more frequent in these patients. Outcome at 1, 6, and 12 months was not influenced by the presence of silent infarctions.Conclusions: This community-based study shows that silent brain infarctions in patients with first-ever stroke are not significantly related to risk factors commonly described in hospital-based series (atrial fibrillation, transient ischemic attack, etc.); rather, silent infarctions seem to be a marker of widespread vascular disease.

Recently published data show that stroke incidence is no longer declining, while case fatality rates has had a less pronunced fall in recent years than in the past. Projections of the increasing number of elderly people, combined with the greater risk of stroke in old age, suggest that in the forthcoming decades we will be faced with an increased request of health resources for patients with stroke. We have therefore used data from a community-based study on stroke incidence and outcome to project the number of first ever strokes, death from stroke and handicap from stroke in Italy, up to the year 2016. Results show that incidence will increase by 22.2%, and death at 6 months from first ever stroke by 29%. However, since patients already handicapped for other reasons are more likely to die from their stroke, the net number of newly handicapped persons will only increased by 5%. These results suggest that in the next decades the major increase in request of health care resources will result from the acute event and the immediate post-ictal phase, and not from the management of chronic handicap after a stroke.