Growth factors in ischemic stroke.

Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects.

Stenting for the treatment of high-grade intracranial stenoses.

To date, evidence to recommend endovascular treatment in patients with intracranial stenoses is lacking. Recently, the introduction of self-expanding stents (Wingspan Stent System) aroused considerable expectations in their employ for stroke prevention. We report a single-center experience of percutaneous transluminal angioplasty and stenting in a series of consecutive patients with intracranial stenoses and compare the safety and performance of balloon-mounted stents versus self-expanding stent systems (Wingspan). Thirty-four patients with 39 severe (>70%) intracranial stenoses were treated during a 6-year period. An independent stroke neurologist collected data about intra and periprocedural complications and short-term outcome. We considered as endpoint measures (1) any 30-day stroke or death (2) any major 30-day complication and (3) procedure technical success. Technical success was achieved in all patients. No vessel dissection or ruptures were observed. The 30-day stroke/death rate was 17.9%. Five ischemic strokes in the territory of treated vessels and two intracranial hemorrhages occurred respectively within 24 h and 5 days after endovascular treatment. Three (17.6%) patients of Wingspan treated group and four (18.2%) of the patients treated with different stent systems had unfavorable outcome. Our study confirms that endovascular treatment can be performed with a high technical success rate, even though the safety of these devices has still to be demonstrated.

Aphasia burden to hospitalised acute stroke patients: need for an early rehabilitation programme.

BACKGROUND/PURPOSE: The aim of our study is to evaluate the frequency of aphasia and to describe the characteristics of aphasics among a large sample of acute stroke patients in Italy. METHODS: Out of the 11 572 stroke patients hospitalised within 48 h from stroke onset, included in the PROSIT study, we selected 9594 alert cases for the estimation of aphasia frequency. The presence of aphasia was accepted when registered in the clinical records at the first neurological examination. All patients/caregivers underwent to a 2-year telephone follow-up evaluation. RESULTS: Twenty-eight per cent of alert acute stroke patients had aphasia, which was associated with arm and/or limb weakness in 74% of cases. In our series, aphasia was more frequent in females than males, in patients older than 75 years and was associated with more severe stroke. Aphasics, compared with nonaphasics, died more frequently. Aphasia was also significantly associated with residual poststroke disability. CONCLUSIONS: This is the first study considering the frequency of aphasia in a wide population of hospitalised acute stroke patients. The presence of aphasia is more common in patients with severe stroke and contributes to residual disability. Our findings should be considered for setting early specific rehabilitation programmes.

Transthyretin Asn90 variant: amyloidogenic or non-amyloidogenic role.

A number of mutations were described in the TTR gene. They were generally related to a variety of inherited syndromes named 'familial TTR-related amyloidoses'. Although TTR mutations were mostly associated with familial amyloid polyneuropathy (FAP), these molecular variants were also found in patients with recurrent stroke, subarachnoidal bleeding and radiological findings of cerebral, cerebellar, cortical-subcortical infarctions and hemosiderosis. We describe a 46 y.o. man with recurrent cerebral haemorrhages carrying Asn90His variant of TTR gene. This mutation has been reported both in FAP and asymptomatic subjects raising the doubt on the possible amyloidogenetic role of this variant. The absence of mutation in the patient's father, who had a history of unexplained cerebral haemorrhage and the lack of symptoms and sign of cerebral bleeding in the two patient's sisters, carrying the same mutation, seem to support the hypothesis that His90Asn TTR mutation do not have an impact in amyloid formation. It has still to be established whether other gene variants in our patient could act synergistically with His90Asn TTR mutation in increasing the risk of CNS haemorrhages.

Safety of carotid stenting for stroke prevention: need of an independent outcome assessor.

Safety and efficacy of carotid artery stenting have still to be fully established. We propose a standardized registry of carotid artery stenting in use at our hospital to evaluate whether the presence of an independent neurologist performing basal, procedural and post-procedural observation increases the accuracy of outcome assessment. We collected a cohort of patients receiving carotid stenting. An external neurologist supervised the endovascular intervention and monitored the patient's clinical conditions during procedure and follow-up time (12 months). The procedure was carried out successfully in all cases. We registered two intra-procedural strokes and two strokes within 24 h. The risk of major complications in our study was 9.1% at 30 days. Our complication rate is higher than in previous studies. These findings could be partly explained by the unemployment of distal protection devices, but also by the presence of an independent observer that might have increased the accuracy of neurological evaluation.

Statins and stroke.

Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence atherogenesis not only by increasing atherosclerotic plaque stability but also by modulating endothelial function and inflammation and acting on platelet aggregation and thrombosis. Despite a strong association between increased levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) has been well proven, it not yet established whether serum LDL-C levels are related to stroke incidence. The major aim of this paper is to perform a comprehensive up-to-date review of research papers, meta-analyses and randomized controlled clinical trials reporting the effects of statins in primary and secondary stroke prevention strategies. In addition, our work provides an overview on statin chemical structure, mechanism of action and pharmacological properties, investigating also most common adverse effects and relationship between statin therapy and haemorrhagic stroke risk, in order to assess drugs safety. Although studies are heterogeneous, our analysis shows that statins reduce the risk of stroke occurrence in high risk patients and seem also to reduce stroke recurrence. Moreover, the low incidence and reversibility of adverse effects, and the unclear association with hemorrhagic events, support the safe use of these drugs.

Recovery after L-DOPA treatment in peginterferon and ribavirin induced parkinsonism.

BACKGROUND: Hepatitis C virus (HCV) chronically infects approximately 2% of the European population. Antiviral therapy with pegInterferon-alpha (PegIFN) and ribavirin (Rbv) is the standard of care, leading to HCV eradication in roughly 50% of patients. IFN-based therapy has been associated with high rates (20%) of central nervous system side effects, but only a few case reports exist on extrapyramidal side effects. RESULTS: We report a 64-year-old man developing parkinsonism during PegIFN alfa-2a and ribavirin therapy for chronic hepatitis C. No improvement was observed after treatment discontinuation. Therefore, on the basis of previous clinical and experimental reports, levodopa-benserazide treatment was started. After substantial improvement, symptoms relapsed following drug tapering. CONCLUSIONS: This is the first case of parkinsonism in a Caucasian patient receiving PegIFN/Rbv therapy. The rapid and significant improvement of symptoms obtained in our patient with levodopa-benserazide, suggests that this therapy could be considered as first line symptomatic treatment.

Genetic polymorphisms for the study of multifactorial stroke.

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.

Antidepressant drugs for narcolepsy.

BACKGROUND: Narcolepsy is a disorder of the central nervous system, the main symptoms of which are excessive daytime sleepiness (EDS) and cataplexy (an abrupt and reversible decrease in or loss of muscle tone, affecting the limbs or trunk or both, elicited by emotional stimuli). Narcolepsy has an adverse impact on people's quality of life. Together with stimulant drugs (used to control EDS), antidepressants are usually recommended to counteract cataplexy. In addition, some antidepressants are also reported to improve EDS. OBJECTIVES: To evaluate the effects of antidepressant drugs on EDS, cataplexy, quality of life, and their side effects in people with narcolepsy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2007), MEDLINE (1966 to 2007), EMBASE (1980 to 2007), PsycINFO (1872 to 2007), and CINAHL (1981 to 2007). Bibliographies of identified articles were reviewed to find additional references. Unpublished randomised trials were searched for by consulting governmental and non-governmental clinical trial registers, disease-specific websites, investigators and experts in the field, pharmaceutical companies/manufacturers. SELECTION CRITERIA: Parallel or cross-over randomised or quasi-randomised controlled trials testing the treatment of narcolepsy with any type of antidepressant drug versus no treatment, placebo, or another antidepressant drug. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Three cross-over and two parallel trials were included with a total of 246 participants. The methodological quality of all studies was unclear. As the trials tested different comparisons, or had a different design or dealt with different outcome measures, meta-analysis was not performed. In one cross-over trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS but significantly reduced cataplexy. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In a second cross-over trial (56 participants) viloxazine significantly reduced EDS and cataplexy. In a third cross-over trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug. Two more trials with parallel design tested ritanserin versus placebo without finding differences of effectiveness in reducing EDS or cataplexy. AUTHORS' CONCLUSIONS: There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.

Amino acid changes in the amino terminus of the Na,K-adenosine triphosphatase alpha-2 subunit associated to familial and sporadic hemiplegic migraine.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura inherited with an autosomal dominant pattern. Here, we report the genetic analysis of four families and one sporadic case with hemiplegic migraine (HM) in whom we searched for mutations in the three genes associated with the disease CACNA1A, ATP1A2 and SCN1A. Two novel amino acid changes p.Arg65Trp and p.Tyr9Asn, in the Na,K-adenosine triphosphatase (ATPase) alpha-2 subunit encoded by the ATP1A2 gene, were found in one FHM family and in the sporadic case, respectively. These mutations are peculiar for their location in the extreme N-terminus, an uncommon mutation target in this protein. Low frequency of migraine attacks in all our mutant patients with low complexity of the associated aura symptoms in the sporadic case is also observed. Besides the two novel mutations, the data here reported confirm the involvement of ATP1A2 gene in the sporadic form of HM, while the negative results on the other families tested for all genes known in HM strengthen the hypothesis of the existence of at least another locus involved in FHM.

Monogenic vessel diseases related to ischemic stroke: a clinical approach.

The identification of stroke cases caused by monogenic disorders is important both for therapeutic decisions and genetic counselling, although they represent less than 1% of all stroke patients. The purpose of this review is to summarize genetic, pathological, and clinical features of single-gene disorders related to ischemic stroke. The following monogenic disorders are considered: cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal-recessive arteriosclerosis with subcortical infarcts and leukoencephalopathy, hereditary endotheliopathy with retinopathy, nephropathy, and stroke, Fabry disease, pseudoxanthoma elasticum, Neurofibromatosis type 1, familial MoyaMoya disease, Ehlers-Danlos syndrome type IV, Marfan syndrome. For each monogenic disorder, mode of inheritance, pathophysiological aspects, clinical phenotype, and diagnostic tools are carefully described. Furthermore, the classification of monogenetic disorders is presented according to stroke mechanisms, which include small vessel diseases, large artery diseases, and arterial dissections. This review could be useful to identify specific diagnostic pathways for patients with a suspicion of monogenic disease.

Stroke Unit care in Italy. Results from PROSIT (Project on Stroke Services in Italy). A nationwide study.

The future challenge for improving stroke patients' outcome will be to implement new Stroke Units (SUs) worldwide. However the best SU model remains uncertain. The aim of this study was to evaluate the number of SUs and the quality characteristics of acute stroke care in Italy. We conducted a SU survey in Italy, interviewing the directors of the hospital wards that discharged at least 50 acute stroke patients a year. A SU was defined as an acute ward area with stroke-dedicated beds and staff. To compare the quality of care provided in SUs with that in general wards (GWs) we investigated the characteristics of five domains: hospital setting, unit setting, staffing, process of care and diagnostic investigations. We identified 68 SUs and 677 GWs. Multivariate logistic regression analyses demonstrated that SUs compared to GWs had higher quality scores in unit setting (ROC area=0.9721), staffing (ROC area=0.8760) and care organisation (ROC area=0.7984). The hospital setting (ROC area=0.7033) and the availability of rapid diagnostic investigations (ROC area=0.7164) had lower power in discriminating SU from GW. In Italy in 2003/04 only 9% of the hospital services had organised SU care. The study demonstrated that SUs admitted more than 100 patients per year, had more monitoring equipment and staffing time, and practised multidisciplinary meetings and early mobilisation. The utility of these structural and performance characteristics needs validation from outcome studies.

Stroke units in Italy.

It is well known that stroke is associated with high morbidity and mortality. Previous studies and metaanalysis provide evidence favouring care of stroke patients in Stroke Units (SU). We published data on SU coverage for seven Italian regions during 2000-2001. The aim of this study is to conduct a new recent survey of SUs in the entire national territory and to evaluate changes in number of SUs and in organisation of in-hospital care in the seven Italian regions evaluated in our previous survey. Hospital services were identified through the diagnosis-related groups (DRG 14) from national hospital discharge registers. We selected services recording at least 50 acute stroke discharges per year. The characteristics of hospital services were obtained from a structured questionnaire submitted by phone by trained researchers to the doctors in charge of services. A SU was defined as a ward that admits acute stroke patients cared for in dedicated beds and by dedicated staff. Out of 676 hospital services evaluated during 2003-2004, 68 were SUs. The national coverage for SU services was 10%, ranging from 0% to 50% in different regions. In 2003-2004 SUs admitted 10% of the total national acute stroke cases. SUs have a more facilitated access to diagnostic evaluations and also seem to be better organised than general wards. Between 2000 and 2004 the number of SUs increased from 7% to 11% in the seven regions evaluated in our first survey. Notwithstanding we found an increase of 30% in the number of SUs, at least in the regions previously evaluated, there is still a shortage of SU beds and high regional heterogeneity.

Stroke units and general wards in seven Italian regions: the PROSIT study.

PROSIT (research PROject on Stroke services in ITaly) is a study performed to evaluate number and work organisation of acute in-hospital services (stroke units, SU) and general wards (GW), in seven Italian regions (Liguria, Lombardia, Lazio, Veneto, Friuli-Venezia-Giulia, Emilia Romagna, Toscana), which have a population of 29,169,811 inhabitants and a relative ratio of 225/100,000 hospitalisations for acute stroke. The registers of hospital discharges from January to December 1999 were looked at identify to services recording at least 50 acute stroke discharges (DRG14) per year. A structured questionnaire investigating stroke service characteristics was submitted to the doctors in charge of the identified units and completed in the presence of an external observer between October 2000 and February 2001. SUs were identified as units with dedicated beds (at least 80%) and team (at least 1 physician and 1 nurse) for acute stroke patients. SUs are still uncommon in many Italian regions because only, as 7% of the wards evaluated were found to be a SU and less than 10% of acute stroke patients resulted to be admitted to a SU. Great heterogeneity was found between the different regions surveyed. The most striking differences between SUs and GW were related to the staffing and care organisation, with higher number/patients ratio in SUs as far as physicians and nurses, speech therapists and social workers were concerned.

Antidepressant drugs for narcolepsy.

BACKGROUND: Narcolepsy is a disorder of the central nervous system, the main symptoms of which are excessive daytime sleepiness (EDS) and cataplexy (an abrupt and reversible decrease in or loss of muscle tone, affecting the limbs and/or trunk, elicited by emotional stimuli). Narcolepsy has an adverse impact on people's quality of life. Together with stimulant drugs (used to control EDS), antidepressants are usually recommended to counteract cataplexy. In addition, some antidepressants are also reported to improve EDS. OBJECTIVES: To evaluate the effects of antidepressant drugs on EDS, cataplexy, quality of life, and their side effects in people with narcolepsy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), PsycINFO (1872 to 2003), and CINAHL (1981 to 2003). Bibliographies of identified articles were reviewed to find additional references. Unpublished randomised trials were searched for by consulting governmental and non-governmental clinical trial registers, disease-specific websites, investigators and experts in the field, pharmaceutical companies/manufacturers. SELECTION CRITERIA: Parallel or cross-over randomised or quasi-randomised controlled trials testing the treatment of narcolepsy with any type of antidepressant drug versus no treatment, placebo, or another antidepressant drug. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. Outcomes were: (a) elimination of EDS; (b) mean reduction of EDS; (c) elimination of cataplexy; (d) 50% or greater reduction in cataplexy frequency; (e) mean reduction of cataplexy; (f) mean improvement in quality of life; (g) adverse events; (h) withdrawal from treatment. MAIN RESULTS: Two cross-over trials were included. The methodological quality of both studies was unclear and so the influence of common biases was impossible to define. As the trials tested two different comparisons (one femoxetine versus placebo, the other fluvoxamine versus clomipramine) meta-analysis was not performed. In the first trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS; a significant reduction of cataplexy was in favour of femoxetine. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In the second trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug. AUTHORS' CONCLUSIONS: There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.

Gangliosides for acute ischaemic stroke.

BACKGROUND: Gangliosides may have a protective effect on the central and peripheral nervous systems. OBJECTIVES: The objective of this review was to assess the effect of exogenous gangliosides in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: May 2001) and contacted drug companies and main investigators of included trials. SELECTION CRITERIA: Randomised trials of gangliosides compared with placebo or standard treatment in people with definite or presumed ischaemic stroke. Trials were included if people were randomised within 15 days of symptom onset and if mortality data were available. DATA COLLECTION AND ANALYSIS: One reviewer applied the inclusion criteria. Two reviewers independently extracted the data. Trial quality was assessed. MAIN RESULTS: Twelve trials involving 2265 people were included. All the trials tested purified monosialoganglioside GM1. Only three trials described the randomisation procedure. Follow-up was between 15 to 180 days. Death at the end of follow-up showed no significant difference (odds ratio 0.91, 95% confidence interval 0.73 to 1.13). There was no difference shown between early (within 48 hours) and delayed treatment. For disability, three trials did not show any improvement in Barthel index score with gangliosides (weighted mean difference 2.1; 95% confidence interval -4.8 to 8.9). In two trials, eight patients experienced adverse effects that led to discontinuation of ganglioside treatment, seven had skin reactions and one developed Guillain-Barré syndrome. REVIEWER'S CONCLUSIONS: There is not enough evidence to conclude that gangliosides are beneficial in acute stroke. Caution is warranted because of reports of sporadic cases of Guillain-Barré syndrome after ganglioside therapy.

The Cochrane collaboration in neurology: acquisitions, research, and new initiatives.

The Cochrane Collaboration (CC) is an international organization involving 16 national centers around the world, set up in response to the need for collecting all randomized controlled trials on health care interventions, with the aim of facilitating and coordinating the preparation, maintenance and dissemination of periodic systematic reviews of these trials. These are prepared by Collaborative Review Groups (CRGs) working together in an area of common interest under the guidance of an editorial team, supported by national Cochrane centers. Nine CRGs are involved in each neurological field, with more than 300 reviewers and members of editorial teams. For a review to be called a 'Cochrane review', it must be structured in the format outlined in the Cochrane Handbook. It is then published and disseminated through the Cochrane Database of Systematic Reviews (CDSR) in the Cochrane Library (CL). Each Cochrane review is prepared using the Review Manager software distributed to CRGs by CC. The editorial team is responsible for assembling an edited module of reviews prepared by CRGs for incorporation and dissemination using electronic media through the CDSR located in the CL. The CL contains information about the CC and 4 other databases: the Database of Abstracts of Reviews of Effectiveness, the Cochrane Controlled Trials Register, the Cochrane Review Methodology Database and the NHS Economic Evaluation Database. The authors use an example of Cochrane reviews about cerebrovascular disorders to illustrate that the CL is a powerful source of evidence for answering clinical questions and providing information as a basis for therapeutic decisions, for the improvement of neurological practice. A new initiative, the Cochrane Neurological Network, has recently been set up with the aim of improving communication among neurological CRGs, and between them and health care professionals interested in neurological diseases so as to update neurologists on the activity of the CC.

Corticosteroids or ACTH for acute exacerbations in multiple sclerosis.

BACKGROUND: Corticosteroids are often used to improve the rate of recovery from acute exacerbation in multiple sclerosis (MS) patients. However, it is still unclear just how relatively effective these agents are and the type of drug, optimal dose, frequency, duration of treatment and route of administration are unknown. OBJECTIVES: The object of this review was to determine the efficacy and safety of corticosteroids or ACTH in reducing the short and long term morbidity from MS. Moreover, we wished to examine from indirect comparisons if the effect of corticosteroids is different according to different doses and drugs, routes of administration, length of treatment. SEARCH STRATEGY: A search strategy developed for the Cochrane MS Group (last searched: June 1999) completed with handsearching and personal contacts with trialists and pharmaceutical companies was used. SELECTION CRITERIA: All randomised, double-blind, unconfounded trials comparing corticosteroids or ACTH to placebo in patients with MS, treated for acute exacerbations, without any age or severity restrictions, were evaluated. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles for inclusion, assessed trials' quality and extracted the data. A third reviewer cross-checked them and disagreements were resolved by a joint discussion. MAIN RESULTS: Six trials contributed to this review; a total of 377 participants (199 treatment, 178 placebo) were randomised. The drugs analysed were methylprednisolone (MP) (four trials, 140 patients) and ACTH (two trials, 237 patients). Overall, MP or ACTH showed a protective effect against the disease getting worse or stable within the first five weeks of treatment (odds ratio[OR]=0.37, 95% confidence interval [CI] 0.24-0.57) with some but non significant greater effect for MP and intravenous administration. Short (five days) or long (15 days) duration of treatment with MP did not show any significant difference. Only one study (with 51 patients) reported data after one year of follow-up: no difference between oral MP and placebo in the prevention of new exacerbations or improvement in long term disability was detected. No data are available beyond one year of follow-up to indicate whether steroids or ACTH have any effect on long-term progression. One study reported that a short term treatment with high dose intravenous MP was not attended by adverse events. On the contrary, gastrointestinal symptoms and psychic disorders were significantly more common in the oral, high-dose MP than in the placebo group. Weight gain and edema were significantly more frequent in the ACTH group than in controls. REVIEWER'S CONCLUSIONS: We found evidence favouring the corticosteroid MP for acute exacerbation in MS patients. Data are insufficient to reliably estimate effect of corticosteroids on prevention of new exacerbations and reduction of long-term disability. Studies assessing long term risk/benefit and adverse effects of corticosteroids in MS patients are urgently needed.

Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials.

We conducted a meta-analysis of randomized controlled clinical trials on steroid treatment for multiple sclerosis and optic neuritis. Of the 25 trials comparing steroids and controls without steroid treatment that we identified 12 were selected for this review. A meta-analysis was conducted to calculate the overall odds ratio across the studies for the numbers of patients without functional improvement and with new relapses. The trials included a total of 1714 patients: 998 with multiple sclerosis and 716 with optic neuritis. Any type of corticosteroids or adrenocorticotropic hormone (ACTH) treatment was considered, as was any dosage, route of administration, and length of treatment. Main outcome measures were: (a) number of multiple sclerosis patients who did not improve by at least one point on the EDSS or equivalent scale, or number of optic neuritis patients without complete recovery of visual acuity at 8 or 30 days and at longer follow-up; (b) number of multiple sclerosis patients with at least one new relapse, or number of optic neuritis patients in whom definite multiple sclerosis was diagnosed at longer follow-up. We found that corticosteroids or ACTH produced a significant improvement in disability or visual acuity at 30 days (odds ratio 0.49; 95% CI 0.37-0.64). The improvement was not statistically significant at longer follow-up (0.85; 95% CI 0.67-1.09). The treatment did not significantly reduce the number of patients with relapses (0.74; 95% CI 0.54-1.01). Both low and high doses were effective for 30-day improvement, but only high-dose and short-term therapy were factors that identified subgroups with some reduction in the risk of new relapse. However, the power of the statistical analysis to detect a reliable difference in the subgroups was low. Steroid treatment is therefore effective in accelerating short-term recovery in patients with multiple sclerosis or optic neuritis. Whether steroids are also effective in reducing the risk of relapse, and the optimal dose and length of treatment must still be determined.