Sotirios Giannopoulos

Statin Therapy and Outcome After Ischemic Stroke Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials

Background and Purpose— Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods— The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (⩽72 hours after stroke), and (2) thrombolysis-treated patients. Results— The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients). Conclusion— In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

Is Vertebral Artery Hypoplasia a Predisposing Factor for Posterior Circulation Cerebral Ischemic Events? A Comprehensive Review

Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.

Recurrent Stroke and Patent Foramen Ovale A Systematic Review and Meta-Analysis

Background and Purpose— Recurrent cerebrovascular events are frequent in medically treated patients with patent foramen ovale (PFO), but it still remains unclear whether PFO is a causal or an incidental finding. Further uncertainty exists on whether the size of functional shunting could represent a potential risk factor. The aim of the present study was to evaluate if the presence of PFO is associated with an increased risk of recurrent stroke or transient ischemic attack and to investigate further if this relationship is related to the shunt size. Methods— We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of all available prospective studies reporting recurrent cerebrovascular events defined as cryptogenic stroke and transient ischemic attacks in medically treated patients with PFO diagnosed by echocardiography or transcranial sonography. Results— We identified 14 eligible studies including a total of 4251 patients. Patients with stroke with PFO did not have a higher risk of the combined outcome of recurrent stroke/transient ischemic attack (risk ratio=1.18; 95% confidence interval=0.78–1.79; P=0.43) or in the incidence of recurrent strokes (risk ratio =0.85; 95% confidence interval=0.59–1.22; P=0.37) in comparison with stroke patients without PFO. In addition, PFO size was not associated with the risk of recurrent stroke or transient ischemic attack. We also documented no evidence of heterogeneity across the included studies. Conclusions— Our findings indicate that medically treated patients with PFO do not have a higher risk for recurrent cryptogenic cerebrovascular events, compared with those without PFO. No relation between the degree of PFO and the risk of future cerebrovascular events was identified.

Complex Atheromatous Plaques in the Descending Aorta and the Risk of Stroke: A Systematic Review and Meta-Analysis

Background and Purpose— Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. Methods— We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. Results— We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6–40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4–10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5–26.9%) and unclassified (28.3%; 95% confidence interval, 23.9–33.1%) cerebral infarction. Conclusions— Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism.

Statin therapy after first stroke reduces 10-year stroke recurrence and improves survival

Objective: To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke. Methods: This was a retrospective observational study involving linked hospitalization and death records. The cohort comprised a series of 794 consecutive, first-ever acute ischemic stroke patients from the Athenian Stroke Registry, admitted to the acute stroke unit and the general medicine and neurology ward of our institutions since January 1997 for whom there was available information covering a 10-year follow-up period. Cox proportional hazards model was used to identify risk factors for stroke recurrence and death. Results: The recurrence rate was 16.3% among stroke patients not receiving a statin after hospital discharge compared with 7.5% among those who received statin therapy (p = 0.002). Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio [HR], 0.65, 95% confidence interval [CI] 0.39 to 0.97, p < 0.01). Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event (adjusted HR, 0.43; 95% CI 0.29 to 0.61, p < 0.01). Conclusions: Prescribing statin therapy upon hospital discharge to patients with first-ever acute stroke lowers the risk of 10-year stroke recurrence and improves survival.

Lateral medullary ischaemic events in young adults with hypoplastic vertebral artery

Objective: To present three cases of young adults with lateral medullary ischaemic events associated with a hypoplastic vertebral artery (VA). All three patients had two additional atherosclerotic or non-atherosclerotic risk factors for stroke. Patients and methods: One female, aged 40 years, and two males, aged 38 and 37 years, each with two risk factors for stroke, presented to the emergency department with acute onset of symptoms and findings consistent with lateral medullary syndrome. All three patients underwent emergency CT scan of the brain followed by MRI and magnetic resonance angiography (MRA). Results: The CT scans were negative in all patients. MRI revealed a lateral medullary lesion in only one patient. All three patients had a hypoplastic VA ipsilateral to the clinical ischaemic event on MRA. Conclusions: Hypoplasia of VA is not considered a risk factor for stroke as it is a common variant in up to 75% of the general population. However, in our patients, hypoplastic VA coexisted with two risk factors and resulted in stroke. Thus although a hypoplastic VA may not be an uncommon asymptomatic finding, it may contribute to stroke if additional risk factors are present.

Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies.

Real-time Validation of Transcranial Doppler Criteria in Assessing Recanalization During Intra-arterial Procedures for Acute Ischemic Stroke An International, Multicenter Study

Background and Purpose— We sought to evaluate the diagnostic accuracy of ultrasound criteria for recanalization during real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures in acute ischemic stroke patients in an international, multicenter study. Methods— Consecutive acute ischemic stroke patients with proximal intracranial occlusions underwent intra-arterial reperfusion procedures with simultaneous real-time transcranial Doppler monitoring at 3 tertiary-care stroke centers. Residual flow signals at the site of angiographically confirmed occlusions were monitored at a constant transtemporal insonation angle using a standard head-frame. Recanalization was assessed simultaneously by digital subtraction angiography and ultrasound using thrombolysis in myocardial infarction and thrombolysis in brain ischemia (TIBI) criteria, respectively. Independent readers blinded to digital subtraction angiography performed validation of TIBI flow grades. The interrater reliability for assessment of TIBI grades was investigated. Results— We evaluated time-linked real-time digital subtraction angiography transcranial Doppler images from 96 diagnostic digital subtraction angiography runs during intra-arterial reperfusion procedures in 62 acute ischemic stroke patients (mean age, 59±17 years; 58% men; median baseline National Institutes of Health Stroke Scale score, 18 [interquartile range 12–21]; median time from symptom onset to intra-arterial procedure initiation, 240 minutes [interquartile range 163–308]). The interrater reliability for evaluation of TIBI grades and assessment of recanalization was good (Cohen &kgr;: 0.838 and 0.874, respectively; P<0.001). Compared with angiography, transcranial Doppler had the following accuracy parameters for detection of complete recanalization (TIBI 4 and 5 versus thrombolysis in myocardial infarction 3, flow grades): sensitivity, 88% (95% confidence interval, 72%–96%); specificity, 89% (79%–95%); positive predictive value, 81% (65%–91%); negative predictive value, 93% (84%–98%); and overall accuracy 89% (80%–94%). Conclusions— At laboratories with high-interrater reliability, TIBI criteria can accurately predict brain recanalization in real time as compared with thrombolysis in myocardial infarction angiographic scores.

Cerebral sinus venous thrombosis in inflammatory bowel diseases

BACKGROUND It has been estimated that 1.3-6.4% of patients with inflammatory bowel diseases (IBD) are complicated by cerebral venous thrombosis (CVT) at some point of time during the course of their disease. METHODS We retrospectively reviewed and subsequently analyzed data from 65 case reports of IBD patients with CVT. Our sources included MEDLINE and EMBASE, and the references of retrieved articles were also screened. RESULTS Patients with CVT and IBD were significantly younger than CVT patients without IBD. Female patients were complicated more frequently but at an older age when compared with males. The incidence of ulcerative colitis was almost double compared with Crohns disease. Active disease was detected in 78.4% of the cases and the proportions of patients with active ulcerative colitis or active Crohns disease were almost equal. The predominant neurological symptom in these patients was persistent headache (80%) and the most common site of CVT was the superior sagittal sinus (50.7%). Severe iron deficiency anemia was highlighted as a significant risk factor for thrombosis in nearly half of the patients. Transient coagulation abnormalities and hereditary thrombogenic mutations were identified in 23 and 20% of the case reports, respectively. CONCLUSION The overall outcome was very good, especially in those patients who were treated acutely with heparin or low molecular weight heparin, suggesting that heparin administration is related with improved neurological outcome and decreased mortality rates even in IBD patients complicated with CVT.

Patient compliance with SSRIs and gabapentin in painful diabetic neuropathy.

BackgroundAnticonvulsants are widely used for treatment of painful diabetic neuropathy. Selective serotonin reuptake inhibitors (SSRIs) are not first-line drugs but are commonly prescribed medicines for chronic pain. The majority of patients are hesitant to use these drug groups, thus their compliance remains an issue. ObjectiveTo compare patient compliance and the effectiveness of 2 SSRIs (paroxetine or citalopram) and 1 anticonvulsant (gabapentin) in patients with painful diabetic neuropathy. MethodsThis was a 6 months prospective trial in 101 patients with painful diabetic neuropathy and minimum score of 2 on a pain intensity scale ranging of 0 to 4. Compliance was assessed with patient interviews and pill counts. Adverse events, early discontinuation or satisfaction with treatment were also evaluated. ResultsPatients receiving SSRIs reported greater satisfaction and fewer concerns of the side-effects with their treatment (P<0.05) compared with the patients taking gabapentin. There was statistically significant better mood in the SSRI group (P<0.05). Overall, 43.5% of those taking SSRIs noticed no effect on the pain control, 50% felt better, and 6.5% felt worse. Among the patients taking gabapentin, 51% felt better, 40.5% noticed no effect, and 8.5% felt worse. Finally, on the pill count, more patients on SSRIs (93.5%) than on gabapentin (82.9%) were taking over the 75% of their medication (P<0.05). ConclusionsThe lack of negative effects on quality of life, the better compliance, and the comparable efficiency of SSRIs suggest that these drugs may be considered as alternative to gabapentin in painful diabetic neuropathy.