Differential diagnosis of recurrent or bilateral peripheral facial palsy.

OBJECTIVE: To describe the differential diagnosis of recurrent or bilateral peripheral facial palsy. METHOD: Case report and literature review. RESULTS: Two patients with recurrent, alternating, peripheral facial palsy are described. In both patients, additional investigation was performed to search for a specific diagnosis. In the first patient, only a positive family history was found, indicating a possible familial susceptibility. In the other patient, diabetes mellitus and hypertension were identified as risk factors. CONCLUSION: There is an important and extensive differential diagnosis of recurrent or bilateral facial palsy. However, in a large proportion of patients the cause remains unknown.

Small-fibre neuropathy can be detected in patients with chronic idiopathic axonal polyneuropathy.

BACKGROUND: The main sensory presenting symptoms of chronic idiopathic axonal polyneuropathy (CIAP) are paraesthesias, numbness and burning pain in the feet. Although these symptoms indicate the involvement of small nerve fibres, clinical analysis or electrophysiological investigations have not yet been studied in detail. METHOD: Cardiovascular autonomic tests and cold and heat pain perception threshold tests were performed in 10 patients with CIAP, 10 patients with diabetes mellitus (DM) and 10 healthy volunteers. The results of the DM group were used to see whether the tests were able to detect small-fibre neuropathy in patients with diabetes and pain. RESULTS: Quantitative sensory threshold and autonomic tests showed more frequent abnormal test results in the patients compared to the healthy control group. The proportion of abnormal test results reached significance for the deep breathing tests in both patient groups and for the cold threshold and heat pain test in patients with CIAP. The spectral analysis of RR intervals showed a significant decrease in the high frequency in both patients with DM and CIAP. CONCLUSION: The results of this study demonstrated that small-fibre neuropathy can be detected in patients with CIAP.

[No role for oral anticoagulants (target INR: 2.0-3.0) after transient ischaemic attack or cerebral infarction of arterial origin; the 'European/Australasian stroke prevention in reversible ischaemia trial' (ESPRIT)]. / Geen plaats voor orale antistollingsbehandeling (streef-INR: 2.0-3.0) na een 'transient ischaemic attack' ofeen herseninfarct van arteriële oorsprong; de 'European/Australasian stroke prevention in reversible ischaemia trial' (ESPRIT).

OBJECTIVE: The 'European/Australasian stroke prevention in reversible ischaemia trial' (ESPRIT) aimed to determine whether oral anticoagulation of moderate intensity (target international normalised ratio (INR): 2.0-3.0) is more effective than acetylsalicylic acid in preventing future vascular events in patients with transient ischaemic attack (TIA) or minor stroke of arterial origin. DESIGN: International, multicentre randomised clinical trial. METHOD: Patients were randomised within 6 months of TIA or minor stroke of arterial origin to oral anticoagulants (target INR: 2.0-3.0; n = 536) or acetylsalicylic acid (30-325 mg daily; n = 532). The primary endpoint was a composite of vascular death, non-fatal stroke, non-fatal myocardial infarction or major bleeding complications. In a post hoc analysis, the efficacy of anticoagulants was compared with that of the combination of acetylsalicylic acid and dipyridamole (200 mg twice daily), a third arm of ESPRIT. Treatment was unblinded, but auditing of endpoints was blinded. Data were analysed on an intent-to-treat basis. RESULTS: The comparison of anticoagulants and acetylsalicylic acid was stopped prematurely because the combination of acetylsalicylic acid and dipyridamole was found to be more effective than acetylsalicylic acid alone. The mean duration of follow-up was 4.6 years (SD: 2.2). The mean INR was 2.57 (SD: 0.86; nearly 70% of the time within target range). The primary endpoint occurred in 99 patients (19%) in the anticoagulation group and 98 patients (18%) in the acetylsalicylic acid group (hazard ratio: 1.02; 95% CI: 0.77-1.35). The hazard ratio was 0.73 (95% CI: 0.52-1.01) for ischaemic events and 2.56 (95% CI: 1.48-4.43) for major bleeding complications. The hazard ratio for the primary outcome event comparing anticoagulants with the combination of acetylsalicylic acid and dipyridamole was 1.31 (95% CI: 0.98-1.75). CONCLUSION: Oral anticoagulants (target INR: 2.0-3.0) were not more effective than acetylsalicylic acid in the secondary prevention of vascular events following TIA or minor stroke of arterial origin.

Dipyridamole for preventing stroke and other vascular events in patients with vascular disease.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. OBJECTIVES: To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (searched June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to May 2006) and EMBASE (1980 to May 2006). We contacted authors and pharmaceutical companies in the search for further data on published and unpublished studies. SELECTION CRITERIA: We selected randomised long-term secondary prevention trials with concealed treatment allocation, treatment for more than one month, starting within six months after presentation of an arterial vascular disease. Treatment consisted of dipyridamole with or without other antiplatelet drugs compared with no drug or an antiplatelet drug other than dipyridamole. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle. MAIN RESULTS: Twenty-nine trials were included, with 23019 participants, among whom 1503 vascular deaths and 3438 fatal and non-fatal vascular events occurred during follow up. Compared with control, dipyridamole had no clear effect on vascular death (relative risk (RR) 0.99, 95% confidence interval (CI) 0.87 to 1.12). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. Compared with control, dipyridamole appeared to reduce the risk of vascular events (RR 0.88, 95% CI 0.81 to 0.95). This effect was only statistically significant in patients presenting with cerebral ischaemia. AUTHORS' CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it reduces the risk of further vascular events. This benefit was found only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin.

Severity of cerebral white matter lesions and infarcts in patients with transient or moderately disabling cerebral ischaemia: reproducibility of grading by neurologists.

Diffuse or multifocal ischaemic white matter lesions increase the risk of intracranial haemorrhage in patients using oral anticoagulants for secondary prevention after cerebral ischaemia of arterial origin. We studied whether neurologists could reliably assess the presence of these white matter abnormalities. As part of the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), the severity of white matter lesions and presence of ischaemic lesions were twice assessed in a consensus meeting of three neurologists (from a pool of nine) as absent, moderate or severe, in a sample of 126 randomly selected CT or MRI scans. The neurologists were not aware of the duplicate grading. The degree of agreement between the first and second observation was calculated with kappa statistics. The kappa value for agreement between the first and second assessment of white matter lesions was 0.58 (95% CI 0.40-0.76). The kappa value for the presence of clinically relevant and/or irrelevant ischaemic lesions was 0.68 (95% CI 0.58-0.78). Clinicians can assess the presence of white matter lesions with sufficient reliability. Such assessment may prevent unnecessary risk with oral anticoagulation in secondary prevention after cerebral ischaemia of arterial origin, of which the efficacy is currently being assessed in ESPRIT.

Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin have an annual risk of major vascular events between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with oral anticoagulants is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy. OBJECTIVES: To compare the efficacy and safety of oral anticoagulants and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (searched 16 September 2004). Authors of published trials were contacted for further information and unpublished data. SELECTION CRITERIA: Randomised trials examining long-term secondary prevention after recent ischaemic stroke of presumed arterial origin were selected. The oral anticoagulant therapy had to be of specified intensity with warfarin, phenprocoumon or acenocoumarol versus antiplatelet therapy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Subgroup analyses with treatment International Normalized Ratio (INR) 1.4 to 2.8 (low intensity), INR 2.1 to 3.6 (medium intensity) and INR 3.0 to 4.5 (high intensity) were performed. MAIN RESULTS: Five trials, with 4076 patients were selected. The data do not allow a robust conclusion on whether anticoagulants are more or less efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation relative risk (RR) 0.96, 95% confidence intervals (CI) 0.38 to 2.42; high intensity anticoagulation RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low or medium intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents. The relative risk for major bleeding complications for low intensity anticoagulation was 1.27 (95% CI 0.79 to 2.03) and for medium intensity anticoagulation 1.19 (95% CI 0.59 to 2.41). However, it was clear that high intensity oral anticoagulants with INR 3.0 to 4.5 were not safe, because they yielded a higher risk of major bleeding complications (RR 9.0, 95% CI 3.9 to 21). AUTHORS' CONCLUSIONS: For secondary prevention of further vascular events after limited ischaemic stroke of arterial origin, there is insufficient evidence to justify the routine use of medium-intensity oral anticoagulants; such treatment should only be used as part of a clinical trial. More intense anticoagulation is not safe and should not be used in this setting. Low-intensity anticoagulation is not likely to be more or less efficacious than aspirin.

Dipyridamole for preventing stroke and other vascular events in patients with vascular disease.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk-reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. OBJECTIVES: To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (searched November 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to November 2005) and EMBASE (1980 to November 2005). SELECTION CRITERIA: Randomised long-term secondary prevention trials with concealed treatment allocation, treatment for more than one month, starting within six months after presentation of an arterial vascular disease were selected. Treatment consisted of dipyridamole with or without other antiplatelet drugs compared with no drug or an antiplatelet drug other than dipyridamole. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle. MAIN RESULTS: Twenty-seven trials were included, with 20242 patients, among whom 1399 vascular deaths and 3090 fatal and non-fatal vascular events occurred during follow up. Compared with control, dipyridamole had no clear effect on vascular death (relative risk (RR) 1.02, 95% confidence internal (CI) 0.90 to 1.17). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. In the presence of aspirin, dipyridamole appeared to reduce the risk of vascular events compared with control (RR 0.90, 95% CI 0.82 to 0.97), due to a single large trial in patients presenting with cerebral ischaemia. AUTHORS' CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it may reduce the risk of further vascular events. However, this benefit was found in only one single large trial and only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole with aspirin versus aspirin alone are justified.

Type of stroke after transient monocular blindness or retinal infarction of presumed arterial origin.

BACKGROUND: Retinal infarction and transient monocular blindness (TMB) are associated with an increased risk of future ischaemic stroke. Little information is available on the type of subsequent ischaemic strokes that may occur (anterior or posterior circulation and small vessel or large vessel). AIM: To analyse the type of stroke after TMB. METHODS: Patients with transient or permanent retinal ischaemia were selected from three prospective studies: the Dutch TIA Trial, the Dutch Amaurosis Fugax Study and the European/Australian Stroke Prevention in Reversible Ischaemia Trial. On follow-up the type of stroke was classified according to the supply territory and the type of vessel involved. RESULTS: 654 patients were included. During a mean follow-up of 5.2 years, 42 patients were found to have had a cerebral or retinal infarct, of which 27 occurred in the carotid territory ipsilateral to the symptomatic eye, 9 in the territory of the contralateral carotid artery and 6 were infratentorial strokes. Thirty patients had a large-vessel infarct, four had a small-vessel infarct and eight had a retinal infarct. Characteristics associated with a notable increased risk for subsequent stroke or retinal infarction were age > or = 65 years, a history of stroke, a history of intermittent claudication, diabetes mellitus, Rankin score > or = 3, more than three attacks of retinal ischaemia and any degree of ipsilateral carotid stenosis on duplex ultrasonography observation. CONCLUSION: Ischaemic strokes after TMB or retinal infarction were found to be mainly large-vessel infarcts in the territory of the ipsilateral carotid artery. TMB and retinal infarction are probably manifestations of large-vessel disease.

Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke.

BACKGROUND: The effectiveness of medication is influenced by treatment adherence. After TIA or minor disabling stroke patients usually are advised to take antithrombotic medication. Stroke patients are an interesting group of patients with respect to adherence, since cardiovascular risk factors and stroke may (indirectly) negatively influence brain function, which can affect adherence. We investigated determinants of non-adherence in patients who used aspirin or oral anticoagulation after cerebral ischaemia of arterial origin. METHODS: Data of patients prospectively followed in two clinical trials (the Dutch TIA Trial and the Stroke Prevention In Reversible Ischaemia Trial) were analysed with Cox proportional hazards modelling. RESULTS: In the two trials 3796 patients were treated with aspirin. During a mean follow-up of 2.1 years, 689 patients (18%) prematurely stopped treatment, 305 (8 %) did so without a clear medical reason (non-adherence). Age >or= 65 years and the use of 300 instead of 30 mg of aspirin were independently associated with non-adherence. Diastolic blood pressure of >or= 90 mmHg and dizziness were associated with better adherence. Of 651 patients on oral anticoagulation, 143 patients (22 %) stopped after a mean follow-up of 1.0 year, 66 (10 %) did so because of nonadherence. No statistically significant determinants for non-adherence were identified. CONCLUSION: As found in the literature on nonadherence in general, age of >or= 65 years and a higher dose of aspirin (300 mg versus 30 mg) were independently associated with non-adherence with aspirin treatment that was prescribed for secondary prevention after cerebral ischaemia of arterial origin. Older patients may require extra encouragement to continue antithrombotic treatment. Lower doses of aspirin may improve treatment adherence.

Dipyridamole in stroke prevention: effect of dipyridamole on blood pressure.

BACKGROUND AND PURPOSE: Trial data suggest that dipyridamole, with or without aspirin, is more efficacious in the secondary prevention of stroke than of coronary events. This selective effect might be attributed to blood pressure lowering by dipyridamole. Therefore, we aimed to assess the effect on blood pressure in the setting of a randomized clinical trial in patients with cerebral ischemia of presumed arterial origin. METHODS: In this study, 591 patients with recent cerebral ischemia of arterial origin were randomly allocated to treatment with aspirin 30 to 325 mg/d or with the combination of aspirin and dipyridamole 400 mg/d in the European/Australian Stroke Prevention in Reversible Ischemia Trial. In an on-treatment analysis, the change in blood pressure measurements from baseline to values after at least 6 months of follow up was assessed with linear regression analysis. RESULTS: After an average period of 15 months, systolic blood pressure dropped 6.2 mm Hg in the aspirin plus dipyridamole group (n=273) and 6.2 mm Hg in the aspirin group (n=318), for a difference of 0.0 mm Hg (95% confidence interval, -3.8 to 3.7). Diastolic blood pressure dropped 3.6 mm Hg in the aspirin plus dipyridamole group compared with 2.7 mm Hg in the aspirin group, for a difference of 0.9 mm Hg (95% confidence interval, -1.0 to 2.9). CONCLUSIONS: It is unlikely that dipyridamole leads to a permanent reduction in blood pressure and that this would explain why this drug might prevent strokes rather than coronary events.

Cochrane review: dipyridamole for preventing major vascular events in patients with vascular disease.

BACKGROUND: Patients enrolled in clinical trials after nondisabling cerebral ischemia have an annual risk of vascular events (death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction) of 4% to 11%. Aspirin reduces the incidence by 13%. Many trials in patients presenting with vascular disease investigated the efficacy of (addition of) dipyridamole in secondary prevention. We systematically compared the efficacy and safety of dipyridamole versus control in the presence and absence of other antiplatelet drugs in clinical trials on the secondary prevention of vascular events in patients with vascular disease. SUMMARY OF REVIEW: Randomized trials with concealed treatment allocation in patients with a nonembolic arterial vascular disease were selected. Therapy consisted of dipyridamole in the presence or absence of other antiplatelet drugs compared with no drug or an antiplatelet drug(s) other than dipyridamole. Twenty-six trials were included, with a total of 19 842 patients. Dipyridamole was not more efficacious in the prevention of vascular death (relative risk [RR], 1.02; 95% CI, 0.90 to 1.17). It appeared more efficacious in the prevention of vascular events (RR, 0.90; 95% CI, 0.83 to 0.98), but this result only reached statistical significance because of 1 large trial in patients presenting with cerebral ischemia. Combination treatment of dipyridamole and aspirin compared with aspirin had an RR of 1.03 (95% CI, 0.87 to 1.22) for vascular death and an RR of 0.90 (95% CI, 0.80 to 1.00) for vascular events. CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug (chiefly aspirin), reduced the risk of vascular death, although it may reduce the risk of further vascular events. However, this benefit was found only in a single large trial and only in patients presenting after cerebral ischemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole plus aspirin with aspirin alone are justified.

Dipyridamole for preventing stroke and other vascular events in patients with vascular disease.

BACKGROUND: Patients with transient ischaemic attacks (TIA) and minor ischaemic strokes are at risk of serious vascular events (death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction). Their risk of vascular events lies between 4 and 11 percent per year. Aspirin only, in a daily dose of 30 mg or more, offers only modest protection in such patients: it reduces the incidence of major vascular events by 13 percent. In a single trial, adding dipyridamole (an alternative antiplatelet agent) to aspirin was associated with a 22 percent reduction in the risk of major vascular events compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. We therefore sought to assess the effects of dipyridamole in more detail. OBJECTIVES: 1) To assess the efficacy of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease in the presence and absence of other antiplatelet drugs. 2) To assess the safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease in the presence and absence of other antiplatelet drugs. SEARCH STRATEGY: The Cochrane Stroke Group Trials Register was searched and other relevant Cochrane Groups were contacted to search their specialised registers (last search 29 April 2002). In addition the Cochrane Controlled Trials Register, MEDLINE and EMBASE were searched and Dutch manufacturers of dipyridamole were contacted to identify further published and unpublished studies. SELECTION CRITERIA: Randomised long term secondary prevention trials with concealed treatment allocation, treatment for > 1 month, starting within 6 months after presentation of a arterial vascular disease were selected (coronary artery disease, myocardial infarction, angina pectoris, retinopathy, nephropathy, peripheral arterial disease, stroke, TIA, amaurosis fugax). Therapy consisted of dipyridamole in any dose in the presence or absence of other antiplatelet drugs compared with no drug or an antiplatelet drug(s) other than dipyridamole (control group). DATA COLLECTION AND ANALYSIS: Two reviewers selected trials which met the inclusion criteria and extracted details of randomisation methods, blinding of treatments and assessments, whether intention-to-treat analysis was possible from the published data, whether treatment groups were comparable with regard to major prognostic factors, the number of patients who were excluded or lost to follow-up, definition of outcome events, and entry and exclusion criteria. The methodological quality of each trial was assessed by the two reviewers on the basis of these extracted data. In addition, dose and type of antiplatelet treatments, duration of follow-up and the numbers of defined outcome events were recorded. Data published by the Antithrombotic Trialists' Collaboration were used. The remaining data were independently extracted by the same two reviewers and cross checked. Data were analysed according to the intention-to-treat principle. Relative and absolute risk reductions were calculated by means of the statistical software provided by the Cochrane Collaboration (RevMan). MAIN RESULTS: Twenty-six trials were included, with a total of 19842 patients, among whom 1399 vascular deaths and 3085 fatal and non-fatal vascular events occurred during follow-up. Compared with control, dipyridamole had no clear effect on vascular death (RR 1.02, 95% CI 0.90 to 1.17). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. Compared with control, dipyridamole appeared to reduce the risk of vascular events (RR 0.90, 95% CI 0.83 to 0.98), but this effect was only statistically significant due to a single large trial in patients presenting with cerebral ischaemia (6602 patients). Comparing dipyridamole plus aspirin with aspirin alone: there was no clear difference in vascular death, the RR was 1.03 (95% CI 0.87 to 1.22); the combination was associated with fewer vascular events with an RR of 0.90 (95% CI 0.80 to 1.00). Combination treatment of dipyridamole and aspirin compared with placebo had an RR of 0.89 (95% CI 0.79 to 1.01) for vascular death and an RR of 0.74 (95% CI 0.68 to 0.80) for vascular events. REVIEWER'S CONCLUSIONS: This review found that, for patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of an other antiplatelet drug (chiefly aspirin) reduced the risk of vascular death, though it may reduce the risk of further vascular events. However, this benefit was found in only a single large trial and only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole with aspirin with aspirin alone are justified.