Corticosteroids for acute ischaemic stroke

The Cochrane Database of Systematic Reviews The Cochrane Library, Copyright 2003, The Cochrane Collaboration

Volume (1)? ? ? ? ? ? ?2003? ? ? ? ? ? ?[no page #]

Corticosteroids for acute ischaemic stroke [Review]

Qizilbash, N; Lewington, SL; Lopez-Arrieta, JM

Date of Most Recent Update: 18-February-2002 Updated

Date of Most Recent Substantive Update: 13-August-2001

Cochrane Stroke Group. Dr. Nawab Qizilbash, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow,

Essex CM19 5AW, UK. E-mail: [email protected].

Outline

l Abstract l Internal sources of support to the review l External sources of support to the review l Date of last minor update l Date new studies sought but none found l Background l Objectives l Criteria for considering studies for this review

l Types of participants

l Types of intervention

l Types of outcome measures

l Types of studies

l Search strategy for identification of studies l Methods of the review l Description of the studies l Methodological qualities of included studies l Results l Discussion l Conclusions

l Implications for practice

l Implications for research

l Potential conflict of interest l Acknowledgements l Contribution of Reviewer(s) l Synopsis l Table of comparisons l Characteristics of included studies l Characteristics of excluded studies l Comment l References to studies included in this review l References to studies excluded in this review

页码，1/22Ovid: Qizilbash: The Cochrane Library, Volume (1).2003.

2003-04-05http://gateway1.ovid.com/ovidweb.cgi

l Additional references

Graphics

l 01.01.00 All deaths... l 01.02.00 Deaths with...

Abstract

Background: Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to cell membrane dysfunction. Early treatment with corticosteroids may help reduce the swelling and improve the outcomes after a stroke.

Objectives: The objective of this review was to assess the effect of corticosteroids in acute presumed ischaemic stroke.

Search strategy: We searched the Cochrane Stroke Group trials register (last searched: 10 April 2001) and contacted investigators in the field.

Selection criteria: Published randomised trials comparing corticosteroids with placebo or control in people with acute (presumed or definite) ischaemic stroke. Trials were included if treatment began within 48 hours of stroke onset and if clinical outcome was assessed.

Data collection and analysis: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data.

Main results: Seven trials involving 453 people were included. Details of trial quality that may relate to bias were not available from most trials. No difference was shown in the odds of death within one year (odds ratio 1.08, 95% confidence interval 0.68 to 1.72). Treatment did not appear to improve functional outcome in survivors. Six trials reported neurological impairment but pooling the data was impossible because no common scale or time interval was used. The results were inconsistent between individual trials. The only adverse effects reported were small numbers of gastrointestinal bleeds, infections and deterioration of hyperglycaemia across both groups. Results unchanged since last update.

Conclusions: There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke. Conclusions unchanged since last update.

Internal sources of support to the review * University of Oxford UK

External sources of support to the review * NHS Anglia and Oxford Region Research and Development Programme, England UK



Date of last minor update

15 February, 2002

Date new studies sought but none found

10 April, 2001

Background

Cerebral oedema is considered to be a major cause of death in acute ischaemic stroke, possibly by producing direct pressure and vascular occlusive effects as well as indirect effects through vasospasm and necrosis (Battistini 1981). Cerebral oedema may be classified into cytotoxic and vasogenic types. Cytotoxic oedema is related to cell membrane dysfunction. Vasogenic oedema is related to the breakdown of the function of the blood brain barrier. Vasogenic cerebral oedema associated with intracranial tumours often responds well to corticosteroids (Shapiro 1975), but much of the brain swelling in cerebral infarcts is due to cytotoxic oedema and it is not clear if corticosteroids have a role (Battistini 1981). Although studies of their use in acute stroke have been disappointing, and perhaps because no other effective treatment exists, many physicians continue to treat stroke with corticosteroids, clinging to the belief that early treatment may be beneficial in reducing mortality (Patten 1972). For example, some 20% of patients with acute ischaemic stroke in the United States in the 1980s involved in the Stroke Data Bank study were treated with corticosteroids (Faulkes 1988). In a recent survey in China, 19% of physicians reported that they used corticosteroids routinely and 61% said that they used them at times for certain patients (Chen 1997). However, there are potentially serious side-effects in the use of corticosteroids.

Objectives

To determine whether the administration of intravenous corticosteroids in patients with acute presumed ischaemic stroke is a safe and effective treatment.

The main outcomes of interest were:

1. Death from all causes 2. Disability 3. Adverse effects

Criteria for considering studies for this review Types of participants

Patients with acute (presumed or definite) ischaemic stroke, where attempts were made to exclude intracerebral haemorrhage, were included in the review. Definite ischaemic stroke implies patients in whom a CT scan was performed before randomisation. Presumed ischaemic stroke means patients who did not have a CT scan and, therefore, where haemorrhage could



not be reliably excluded.

Types of intervention

Corticosteroid (intravenous, intra-muscular or oral) versus control.

Types of outcome measures

The main outcomes of interest were:

1. The number of patients who died from any cause during the scheduled follow-up period. 2. Functional outcome among survivors. 3. Adverse effects of treatment, where documented.

Wherever possible, results were analysed on an intention-to-treat basis

Types of studies

All attempts were made to identify all unconfounded, definitely or possibly truly randomised trials in which treatment with corticosteroid therapy was compared to control in patients following an acute (presumed) ischaemic stroke. Trials in which allocation to treatment or control group was not definitely truly random or in which treatment allocation was not concealed were excluded since prior knowledge of treatment allocation may have led to biased treatment allocation (Schulz 1995).

Search strategy for identification of studies

This review has drawn on the search strategy developed for the Stroke Group as a whole (please see Review Group information for details). Trials were identified in the Stroke Group Trials Register, which was last searched by the Review Group Co-ordinator on 10 April 2001.

For the original review, we contacted numerous researchers in an effort to identify unpublished and ongoing studies, and asked investigators of published trials to provide additional information on cause of death. We have not repeated this exercise for this update.

No new trials meeting the inclusion criteria have been identified for this update.

Methods of the review

Two reviewers (NQ, SL) independently selected the trials for inclusion in the review. Disagreements were resolved by discussion. The same two reviewers assessed the methodological quality of each trial. No scoring system was used to assess quality but the following details were noted: randomisation method, blinding, whether intention-to-treat (ITT) analyses were documented and possible from the published data, and the number of patients lost to follow-up. Data were independently extracted by the same



two reviewers and cross-checked. Any discrepancies were discussed. Data were sought on the number of patients with each outcome measure (where available) by allocated treatment group. To allow an ITT analysis, the data were sought irrespective of compliance, whether or not the patient was subsequently deemed ineligible, or otherwise excluded from treatment or follow-up. Data on whether or not CT scanning was performed prior to randomisation were sought. If any of the above data were not available in the publications, further information was requested through correspondence with the trialists. Where no further information was obtained, the results from the "on-treatment" analysis were used, based on the data extractable from the publication.

Due to the age of many of the studies, data regarding disability were difficult to obtain. Where data were not available about the type of stroke and cause of death, these were sought from the trialists.

Both proportional and absolute risk reductions were calculated for each outcome. A test for heterogeneity of treatment effect between the trials was made using a standard chi-squared statistic. The typical treatment effect across trials, the "typical odds ratio" (i.e. the odds of an unfavourable outcome amongst treatment-allocated patients to the corresponding odds amongst controls) was calculated using Peto's odds ratio method.

Description of the studies

See "Characteristics of Included Studies". Seven of the 22 trials fulfilled the entry criteria. No ongoing trial has been identified. All included trials used dexamethasone except two which used betamethasone. Four trials compared dexamethasone with unspecified placebo, one trial compared dexamethasone with placebo water, one trial compared betamethasone with vitamin C and one trial compared betamethasone with unspecified placebo.

The mean age of the patients in the trials, where it is quoted, ranged from 66 to 75 years. Approximately half the patients were male. Only one trial (Norris 1986) used CT scanning to exclude haemorrhage. The severity of stroke as judged by overall case fatality ranged from 7% to 79%, though this assessment is confounded with duration of follow up. Only two trials had follow up beyond one month; three months for McQueen et al (McQueen 1978) and twelve months for Mulley et al (Mulley 1978). The timing of treatment from onset of stroke was within 24 hours for three trials, 48 hours for three trials and not specified for one trial (McQueen 1978). Only one trial had a measure of functional disability (Mulley 1978), the remainder used neurological impairment scales.

Methodological qualities of included studies

Seven trials met our inclusion criteria and have been included in the analysis and are summarised in "Characteristics of included studies". The reasons for excluding the 15 trials from the analysis are summarised in "Characteristics of excluded studies". Information about trial quality (see



table of included studies) that may relate to bias was not available from many trials for:

(a) reporting of randomisation and concealment

(b) whether concealment was adequate

(c) whether blinding was adequate

(d) assessment of the success of blinding

(e) any important imbalances in the treatment groups

(f) number of patients excluded from analysis

Adverse events were reported in a systematic fashion in only one trial, so the adverse event data have not been pooled but merely described.

Results

The total number of individuals included in the seven trials was 453. There was no evidence of statistical heterogeneity. The seven trials showed a non-significant increase in the odds of death (within one year) of 1.08 (95% confidence interval 0.68 - 1.72). Only one small trial reported a marginal statistically significant hazard in the odds of death and all other trials were statistically non-significant. There was no evidence of early deaths occurring within one month (odds ratio 0.94; 95% confidence interval 0.59-1.52) being substantially different from overall deaths (within one year). The results of the trials that used betamethasone did not substantially differ from those using dexamethasone.

Analysis by cause of death could not be done since appropriate data were not received from trial investigators.

Six trials reported neurological impairment scales but pooling these data was impossible because no common scale nor time interval was used. Four trials reported no difference in neurological impairment, one reported a statistically significant benefit (Patten 1972) and one reported a statistically significant worsening (Norris 1976). The only trial to report functional disability found a non significant difference at 12 months - full independence in 10 survivors in the dexamethasone group and 8 in the placebo group; for severe disability the figures were 4 in the dexamethasone group and 3 in the placebo group.

Only one of the seven trials reported non-fatal adverse effects in a systematic manner (Norris 1986); there were generally few adverse events and were limited to gastro-intestinal bleeding, infection and hyperglycaemia. Diabetes or its worsening was reported to be more frequent in the treatment group in three trials (12 versus 0). Infection was more frequent in the treatment group in two trials (4 versus 0) but less frequent in one trial (0 versus 4). Gastro-intestinal bleeding was reported as being more frequent in the treatment group in three trials (7 versus 4) but less



frequent in one trial (0 versus 3). The trial of Norris (Norris 1986) reported withdrawals from adverse events as follows (treatment versus control): Gastro-intestinal bleeding (3 versus 2), infection (0 versus 4), worsening hyperglycaemia (4 versus 0).

Discussion

The results of this review do not support the hypothesis that intravenous or intramuscular corticosteroids reduce all-cause case fatality following stroke. However, the small number of patients and events in the trials mean that there is great imprecision and that this treatment could increase the odds of death by as much as 72%, or reduce it by as much as 32% (95% confidence interval). Few patients had the diagnosis of ischaemic stroke confirmed by CT-scan, and it is conceivable that the results were influenced by the inclusion of haemorrhagic strokes. It is possible that the relative treatment effects of corticosteroids may vary between patients with differing levels of absolute risk. Although the evidence is limited, the present review would be compatible with the notion that corticosteroids are beneficial in high risk patients with large infarcts and much vasogenic oedema (Mulley 1978), and either ineffective or harmful among low risk patients with smaller infarcts and less vasogenic oedema. The two trials with higher case-fatality rates in the control groups (Mulley 1978; Norris 1986) both reported trends (statistically non-significant) in favour of treatment. There was no significant heterogeneity of results from the different trials. Nor was there any evidence to suggest bias from selective reporting of trials based on the results. The point estimates of the odds ratios for the different trials were evenly spread around the pooled point estimate.

In general, neither neurological nor functional outcome was any better in those patients who survived. Treating severe disability and death as one endpoint (from the one trial that measured functional outcome) made no difference to the conclusion.

Adverse effects of treatment were few (approximately 10%; 22/210). They were generally more frequent in the treatment group, for infection, worsening hyperglycaemia and gastro-intestinal bleeding, as would be expected from the mode of action of corticosteroids. Given the unsystematic manner of reporting adverse events in these trials, there may have been underreporting as trials of dexamethasone using similar doses in cerebral haemorrhage report much higher adverse event rates in the treatment group (Poungvarin 1987).

Conclusions Implications for practice

Trials of corticosteroids do not provide evidence of a beneficial effect on death following acute (presumed) ischaemic stroke. Nor do the data on neurological impairment or functional outcome suggest any benefit.

Corticosteroids should not currently be used in the routine management of acute ischaemic stroke.



Implications for research

Given the adverse effects of corticosteroids, the benefits on both case fatality and functional outcome would need to be substantial for this treatment to be recommended. We do not feel that the present data hold enough promise of clinically worthwhile benefits to advocate a large scale trial. Factoring in corticosteroid treatment as an additional arm of a large trial of some more promising treatment might be sensible and cost effective.

Given the likely mode of action of corticosteroids in acute ischaemic stroke, patients with large infarcts and much cerebral oedema might be considered the ones likely to benefit, if this treatment were shown to be effective. Perhaps newer ways of administration such as the use of mega-doses of corticosteroids (eg methylprednisolone 500 - 1000 mg/day) may be more effective on the vasogenic component of the oedema of large infarcts

Potential conflict of interest

None

Acknowledgements

We should like to thank those trialists who provided additional data: G Mulley, JW Norris, BM Patten

Thanks to M Murphy for helping in the correspondence with the trialists.

ONGOING TRIALS

We are not aware of any ongoing trials of corticosteroids but would be grateful for any information about any other relevant trials not included in this review.

Contribution of Reviewer(s)

Nawab Qizilbash: formulated the question, conducted the searches, selected the articles, abstracted the data, conducted the analysis and wrote the review.

Jesus Lopez Arrieta: selected the articles, co-wrote the review.

Sarah Lewington: Abstracted and analysed the data.

Synopsis

No evidence of benefit from corticosteroids for acute ischaemic stroke

Stroke from blockage of an artery to a part of the brain causes swelling of that part of the brain. The swelling produces pressure effects, may



cause additional brain cells to die or delay the recovery of damaged but recoverable brain cells. Reduction of this swelling may relieve pressure on adjacent parts of the brain, reduce the number of brain cells that are killed and allow better recovery of damaged brain cells. Corticosteroids have been used to reduce this brain swelling to help limit damage and speed recovery. However, from the small and inadequate amount of evidence available, this review found no benefit of corticosteroids on reducing death or improving functional outcome in survivors.

Table of comparisons

Fig 01 corticosteroids vs. placebo

01.01.00 All deaths

01.02.00 Deaths within 1 month

Characteristics of included studies

Study: Bauer 1973

Methods: Double-blind, placebo controlled.

Randomisation: method not stated, but assumed computer generated by Merck, Sharp & Dohme.



Allocation concealment: Blind until last patient assessed.

Participants: ?Country

54 total. 30 female 24 male. Mean age 66 years

Enrolment within 48 hours of onset

Method of diagnosis: Lumbar puncture 100%

28 Dexamethasone

26 placebo

Interventions: Dexamethasone vs. placebo

Interventions

Rx: Dexamethasone 12mg i.v. stat

4mg i.m. 6 hourly for 3 days




Total dose: 120mg dexamethasone

Control

Placebo: unspecified

All patients: prophylactic ulcer diet and antacid (30cc maalox) four times a day where oral intake possible

Duration: 10 days

Outcomes: All assessments at 14 days

Death

Neurological impairment in the level of consciousness, the motor system and of mentation.

Notes: Exclusions: more than 300 red blood cells per cc in the cerebrospinal fluid; history of gastro-intestinal bleeding or symptomatic duodenal ulcer.

Follow-up: 14 days



Allocation concealment: B

Study: Gupta 1978

Methods: Double-blind, placebo controlled

Randomisation: method not specified

Number of patients excluded after randomisation: not stated

Number of losses to follow up: not stated

Participants: India

30 patients - 13 on treatment, 17 on placebo

Mean age: not stated

Sex: not stated

Time from onset of stroke to enrolment: less than 24 hours

Method of diagnosis: Clinical. Lumbar puncture to exclude haemorrhage (100%)

Interventions: Betamethasone versus placebo

Intervention group:

day 1: 10mg/day in divided doses





day 6,7,8: 6mg/day in divided doses

day 9,10,11: 4mg/day

day 12-21: 2mg/day

Control: placebo unspecified

Duration of treatment: 21 days

Outcomes: Death at 3 weeks

Neurological status (self-made method) at 1,2 and 3 days, and at 1,2,3



weeks.

Cerebrospinal fluid pressures

Adverse events not reported

Notes: Exclusions: not stated

Follow up: 3 weeks


Study: McQueen 1978


Randomisation: method not known but probably prepared by outsider to study.

Allocation concealment: Numbered, coded vials.

Participants: New Zealand

48.

Age: not provided

Sex: not provided.

Timing of enrolment from stroke onset: not stated

Method of diagnosis: Clinical diagnosis of cerebral thrombosis. Lumbar puncture ?%

24 betamethasone.

24 placebo.

Interventions: Betamethasone vs. placebo (vitamin C).

Interventions: Betamethasone

12mg i.m. stat dose

4mg i.m. 8 hourly for 1 day

4mg i.m. 8 hourly for days 2-10





Total dose: 272mg Betamethasone

Control: placebo (vitamin C)

Outcomes: Death: at 12 weeks

Death from gastrointestinal bleeding reported separately.

Other deaths stated to be related to the stroke

Neurological

scores: (not available) at 14-15th day and week 12

Notes: Exclusions: subarachnoid haemorrhage; severe diabetes; pre-existing steroid treatment; known peptic ulceration.

Follow-up: 12 weeks


Study: Mulley 1978

Methods: Allocation by code.

Treatment contained in sealed envelopes (unknown whether opaque) to be opened after allocation.

On-treatment analysis. 134 randomised and 18 withdrawn, only 4 of whom treatment allocation can be determined.

16 exclusions after randomisation (treatment group unknown)

Participants: United Kingdom

134 total. No breakdown by sex.

Mean age 70 years.

Enrolment within 48 hours of onset.

Method of diagnosis: Lumbar puncture ?%

63 dexamethasone.

59 placebo.

Interventions: Dexamethasone vs. placebo.

Interventions: Dexamethasone

4.2mg i.m. 6 hourly for days 1-10



4.2mg i.m. 8 hourly for day 11

4.2mg i.m. 12 hourly for days 12-13

4.2mg i.m. once for day 14

Total dose: 201.6mg Dexamethasone

Control: placebo of water

Duration: 14 days

Outcomes: Death at day 10 and at 3 and 12 months. Analysis used death at 12 months and at 10 days.

Functional disability (Adams method) at 12 months

Adverse effects of treatment

Quality of life

Duration of hospital stay

Notes: Exclusions: previous stroke; considered to have intracranial tumour, injury or subarachnoid haemorrhage; diabete mellitus; peptic ulcer; already receiving steroids.

Follow-up: 12 months

Allocation concealment: A

Study: Norris 1976


Randomisation: correspondence with author suggests random number tables.

Allocation concealment: not explicitly stated.

Participants: Canada

53 total. 24 female, 29 male.

Mean age 72 years.

Treatment within 24 hours.

Method of diagnosis: Lumbar puncture 100%

Brain scan 100%

Angiography ?%



26 dexamethasone.

27 placebo.

Interventions: Dexamethasone vs. placebo.

Interventions: dexamethasone 8mg stat bolus

4mg 6 hourly gradually decreased over 12 days to achieve a total dose of 140 mg

Control: unspecified placebo

Duration: 12 days

Outcomes: Death: at day 29

Cause of death at day 29

Neurological status (self-made scale) at days 1,8,15,22 and 29


Notes: Exclusions: recent peptic ulcer; concurrent infection, psychiatric disturbances.

Follow-up 29 days


Study: Norris 1986


Randomisation: Random number tables.

Allocation concealment: Not explicitly stated.

Participants: Canada.

113 total.

61 female, 52 male.

Mean age 75 years.

Treatment within 48 hours.

Method of diagnosis: CT used in (not stated but implied) 100%?

54 dexamethasone.



59 placebo.


Interventions

Treatment: dexamethasone, oral or parenteral to a total dose of 480mg, starting with 24mg four times a day, with progressive reduction of dose until day 12.

Control: unspecified placebo

Duration: 12 days

Outcomes: All: Death at day 21

Cause specific death at day 21

Neurological impairment (Toronto stroke method) at days 6,12,21


Notes: Exclusions: Cerebral haemorrhage by CT, mild stroke, massive previous stroke, terminal stroke, dementia, diabetes mellitus, concurrent sepsis, gastrointestinal haemmorrhage, or cardiac embolic source.

Follow-up: 21 days


Study: Patten 1972


Randomisation: Random number tables.

Allocation concealment: Identical vials with study number only for identification.

Participants: USA

31 total. 15 female, 16 male.

Mean age 69 years.

Enrolment within 24 hours of stroke onset

Method of diagnosis: Lumbar puncture: ?%

Isotope brain scan: ?%

Angiography: ?%



14 dexamethasone.

17 placebo.


Interventions: Dexamethasone

10mg i.v. stat dose

4 mg i.m. 6 hourly for 10 days

Dose gradually decreased to zero over 7 days

Total dose?

Control: placebo solution

All patients: oral antacid

Duration: 17 days

Outcomes: Death at day 17

Motor function (self made scoring) at days 3,6,10 and 17

Mental function (self made scoring) at days 3,6,10 and 17


Notes: Exclusions: subarachnoid haemorrhage

Follow-up: 17 days

Allocation concealment: A

Characteristics of excluded studies

Study: Albizzati 1979

Reason for exclusion: Glycerol treatment compared to dexamethasone and not placebo

Study: Barolin 1976

Reason for exclusion: Not randomised - alternate alloaction

Study: Dyken 1956

Reason for exclusion: Alternate allocation

Study: Freeman 1978



Reason for exclusion: No data on deaths in each treatment group given. Contained haemorrhagic stroke. Dexamethasone plus mannitol versus placebo

Study: Gahlot 1982

Reason for exclusion: Glycerol compared to dexamethasone and not placebo

Study: Gilsanz 1975

Reason for exclusion: Glycerol treatment compared to dexamethasone and not to placebo

Study: Hasan 1989

Reason for exclusion: Subarachnoid haemorrhage only - to be done by another reviewer.

Study: Hetzel 1957

Reason for exclusion: No information on randomisation procedure or blinding.

Study: Kaste 1976

Reason for exclusion: Dexamethasone plus dextran versus placebo

Study: Kumar 1989

Reason for exclusion: Uneven allocation between treatment (n=25) and control

(n=15) and confounded by the administration of antacids to

only the treatment group.

Study: Poungvarin 1987

Reason for exclusion: Haemorrhagic stroke only - to be done by another reviewer

Study: Rompel 1980

Reason for exclusion: No data available.

Study: Rubinstein 1965

Reason for exclusion: Not randomised - unequal allocation between treatment (n=21) and placebo (n=6)

Study: Russek 1955

Reason for exclusion: Open, uncontrolled study.



Study: Santambrogio 1978

Reason for exclusion: No data provided on number of deaths

Study: Tellez 1973

Reason for exclusion: Haemorraghic stroke only - to be done by another reviewer

Study: Wright 1974

Reason for exclusion: No randomised allocation

Comment

Is it possible to compare outcomes between included and certain excluded trials where the latter were excluded on the grounds that they were confounded?

Since non-randomised studies may be biased towards a positive treatment

effect (Schulz et al, 1994), it would introduce a systematic bias into the

analysis by comparing outcomes between included studies and those excluded

trials which were confounded. Larger scale randomised evidence is required

if it is still considered appropriate to further test these drugs.

Walid Matat

References to studies included in this review

Bauer 1973

Bauer RB, Tellez H, Dexamethasone as treatment in cerebrovascular disease. 2. A controlled study in acute cerebral infarction. Stroke, 1973, 4, 547-555.

Gupta 1978

Gupta RC, Bhatnagar HN, Gambhir MS, Shah DR, Betamethasone therapy in acute cerebrovascular accidents. J Assoc Physicians India, 1978, 26, 589-594.

McQueen 1978

McQueen EG, Betamethasone in stroke (letter). NZ Med J, 1978, 87, 103-104. [Context Link]

Mulley 1978

Mulley G, Wilcox RG, Mitchell JR, Dexamethasone in acute stroke. BMJ, 1978, 2, 994-996.



[Context Link]

Norris 1976

Norris JW, Steroid therapy in acute cerebral infarction. Arch Neurol, 1976, 33, 69-71. [Context Link]

Norris 1986

Norris JW, Hachinski VC, High dose steroid treatment in cerebral infarction. BMJ, 1986, 292, 21-23. [Context Link]

Patten 1972

Patten BM, Mendell J, Bruun B, Curtin W, Carter S, Double-blind study of the effects of dexamethasone on acute stroke. Neurology, 1972, 22, 377-383. [Context Link]

References to studies excluded in this review

Albizzati 1979

Albizzati MG, Candelise L, Capitani E, Colombo A, Spinnler H, Association of stroke to dexamethasone in treatment of stroke patients. Acta Neurol Scand, 1979, 60, 77-84.

Barolin 1976

Barolin GS, Scholz H, Widhalm K, Hemmer W, Cortisone in non-haemorrgagic stroke. An anterospective comparative study. Munch Med Wochenschr, 1976, 118, 36, 1117-20.

Dyken 1956

Dyken M, White PT, Evaluation of cortisone in the treatment of cerebral infarction. JAMA, 1956, 162, 1531-1535.

Freeman 1978

Freeman J, Tappin J, Karat AB, Meecham J, Dexamethasone in acute stroke (letter). BMJ, 1978, 2, 1500.

Gahlot 1982

Gahlot SR, Goyal RK, Swaroop AK Mathur RN, Intravenous Glycerol versus dexamethasone therapy in the management of acute cerebral oedema in patients with acute cerebral infarction. JAPI, 1982, 30, 575-578.

Gilsanz 1975

Gilsanz v, Rebollar JL, Buencuerpo J, Chantres MT, Controlled trial of glycerol versus dexamethazone in the treatment of cerebral oedema in acute cerebral infarction. Lancet, 1975, 1, 7915, 1049-51.

Hasan 1989

Hasan D, Lindsay KW, Wijdicks EFM, Murray GD, Brouwers PJAM, Bakker WH, van Gijn J, Vermeulen M, Effect of fludrocortisone acetate in patients with subarachnoid haemorrhage. Stroke, 1989, 20, 1156-1161.



Hetzel 1957

Hetzel BS, Lander H, Robson HN, Immediate treatment of Apoplexy. BMJ, 1957, 1, 1122.

Kaste 1976

Kaste M, Fogelholm R, Waltimo O, Combined dexamethasone and low-molecular-weight dextran in acute brain infarction: double-blind study. BMJ, 1976, 2, 1409-1410.

Kumar 1989

Kumar N, Jain S, Maheshwari MC, Role of dexamethasone in the outcome from acute stroke. JAPI, 1989, 3, 315-317.

Poungvarin 1987

Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasari P, Sukondhabhant S, Hensley MJ, Strom BL, Effects of dexamethasone in primary supratentorial intracerebral haemorrhage. N Engl J Med, 1987, 316, 1229-1233. [Context Link]

Rompel 1980

Rompel C, Kramer W, Umlauf B, Ulm K, Hellhake T, Effect of dexamethasone phosphate in cerebral infarction compared with current standard therapy. Controlled double-blind method. Med Welt, 1980, 31, 1370-1372.

Rubinstein 1965

Rubinstein MK, The influence of adrenocortical steroids on severe cerebrovascular accidents. J. J Nervous and Mental Disorders, 1965, 141, 291-299.

Russek 1955

Russek HI, Russek AS, Zohman BL, Cortisone in immediate theray of apoplectic stroke. JAMA, 1955, 2, 102-105.

Santambrogio 1978

Santambrogio S, Martinotti R, Sardello F, Porro F, Randazzo A, Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients. Stroke, 1978, 9, 130-132.

Tellez 1973

Tellez H, Rauer B, Dexamethasone as treatment in cerebrovascular disease.1. A controlled study in intracerebral haemorrhage. Stroke, 1973, 4, 541-554.

Wright 1974

Wright WB, High-dosage dexamethasone in treatment of strokes in the elderly. Geront Clin, 1974, 16, 88-91.

Additional references

Battistini 1981



Battistini N, Studies in Cerebrovascular Disease, 1981, Mason Italia Editori, Milano, 181-194, Loeb C. [Context Link]

Chen 1997

Chen ZM, Sandercock P, Xie JX, Peto R, Collins R, Liu LS, Hospital management of acute ischaemic stroke in China. Journal of Stroke and Cerebrovascular Diseases, 1997, 6, 361-367. [Context Link]

Faulkes 1988

Faulkes MA, Wolf PA, Price TR, Mohr JP Hier DB, The Stroke Data Bank: design, methods and baseline characteristics. Stroke, 1988, 19, 547-54. [Context Link]

Schulz 1995

Schulz KF, Chalmers I, Hayes RJ, Altman DG, Failure to conceal treatment allocation schedules in controlled trials influences estimates of treatment effects: an analysis of 250 trials in 33 meta-analyses. Atlanta: Center for Disease control and prevention. JAMA, 1995, 273, 408-412. [Context Link]

Shapiro 1975

Shapiro HM, Intracranial hypertension: therapeutic and anaesthetic considerations. Anaesthesia, 1975, 43, 445-71. [Context Link]

Medical Subject Headings (MeSH): Human; *Anti-Inflammatory Agents, Steroidal/tu (therapeutic use); *Brain Edema/dt (drug therapy); *Brain Edema/et (etiology); *Brain Ischemia/cp (complications); *Brain Ischemia/dt (drug therapy); *Cerebrovascular Accident/cp (complications); *Cerebrovascular Accident/dt (drug therapy); *Glucocorticoids, Synthetic/tu (therapeutic use); *Randomized Controlled Trials

Accession Number: 00075320-100000000-00953

Copyright (c) 2000-2003 Ovid Technologies, Inc. Version: rel6.0.0, SourceID 1.7240.1.49



Corticosteroids for acute ischaemic stroke

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