Simona Marcheselli

Role of Monitoring in Management of Acute Ischemic Stroke Patients

Background and Purpose— Although several studies have demonstrated the effectiveness of specialist Stroke Unit (SU) care of stroke patients, there is still disagreement over how these units are best organized. We sought to clarify the role of continuous monitoring of physiological parameters in acute ischemic stroke. Methods— We conducted a prospective study of 268 first-ever ischemic stroke patients admitted to our Cerebrovascular Department and allocated, according to the availability of beds, to the SU or Cerebrovascular Unit (CU). Statistical analysis compared mortality and outcome at discharge, medical and neurological complications, and length of hospitalization in the 2 care settings. Results— Two hundred sixty-eight patients were enrolled. A good outcome at discharge, observed in 114 SU patients (85%) and 78 CU patients (58%) (odds ratio, 2.63; 95% CI, 1.4 to 4.8; P <0.02), was found, on multivariate analysis, to be significantly related to type of care (SU versus CU). A significantly greater proportion of SU patients showed adverse changes in monitored parameters, which required acute medical treatment (SU: 64%; CU: 19%; P <0.0001). The mean duration of these complications was significantly shorter in the SU patients (SU: 1.0 day; CU: 2.4 days; P <0.02), and the outcome in patients experiencing complications covered by the monitoring protocol was significantly better in the SU (66%) than in the CU (35%) group (P <0.0001). Conclusions— Admission of acute stroke patients to a monitoring SU may positively influence their outcome at discharge. Confirmation of our findings in larger trials will indicate the need for a revision of the minimum requirements of SUs, with the addition of monitoring as a new requirement.

Autonomic dysfunction in Parkinson's disease

Abstract. Autonomic dysfunction in patients with Parkinsons disease (PD) has been recognized since the original description by James Parkinson in 1817. Autonomic failure can be the clinical presentation of other diseases like pure autonomic failure (PAF) and multiple system atrophy (MSA). Both the central and peripheral autonomic nervous systems can be affected in PD. Rajput and Rozdilsky described cell loss and Lewy bodies within the sympathetic ganglia and antibodies to sympathetic neurons have been detected in PD patients. Lewy bodies can be seen in autonomic regulatory regions, including the hypothalamus, sympathetic (intermediolateral nucleus of the thoracic cord and sympathetic ganglia), and parasympathetic system (dorsal, vagal, and sacral parasympathetic nuclei). Lewy bodies were also found in the adrenal medulla and in the neural plexi innervating the gut, heart and pelvis. Symptoms of dysautonomia are variable, and include cardiovascular symptoms, gastrointestinal, urogenital, sudomotor and thermoregulatory dysfunction, pupillary abnormalities and sleep and respiratory disorders. They may represent a useful tool in the differential diagnosis of “atypical” or “complicated” parkinsonisms.

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

The THRombolysis and STatins (THRaST) study

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26–2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11–1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18–2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19–0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28–0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

Safety and efficacy of alteplase in the treatment of acute ischemic stroke

After publication of the results of the National Institute of Neurological Disorders and Stroke study, the application of intravenous thrombolysis for ischemic stroke was launched and has now been in use for more than 10 years. The approval of this drug represented only the first step of the therapeutic approach to this pathology. Despite proven efficacy, concerns remain regarding the safety of recombinant tissue-type plasminogen activator for acute ischemic stroke used in routine clinical practice. As a result, a small proportion of patients are currently treated with thrombolytic drugs. Several factors explain this situation: a limited therapeutic window, insufficient public knowledge of the warning signs for stroke, the small number of centers able to administer thrombolysis on a 24-hour basis and an excessive fear of hemorrhagic complications. The aim of this review is to explore the clinical efficacy of treatment with alteplase and consider the hemorrhagic risks.

Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age The Italian Project on Stroke in Young Adults

Background— Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. Methods and Results— We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%–17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%–17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%–1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their &bgr;-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61–0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Conclusions— Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

Vasomotor response to CO2 and L-Arginine in patients with severe internal carotid artery stenosis; pre- and post-surgical evaluation with transcranial Doppler.

BACKGROUND AND AIM Carotid artery disease may cause both thromboembolism and cerebral blood flow disturbances, particularly in subjects with impaired hemodynamic compensatory mechanisms. The aim of this study was to evaluate by transcranial Doppler (TCD) the hemodynamic changes induced by CO2 and L-Arginine stimulation in a selected population with severe unilateral carotid stenosis (70-80%), before and after carotid endarterectomy, in order to determine the effect of surgery in the vascular hemodynamics of these patients. METHODS We studied 20 subjects (mean age 66.4 years) consecutively admitted to our institute with ischemia and unilateral severe internal carotid artery stenosis (70-80%) detected by Color Doppler. All patients underwent arterial digital subtraction angiography to confirm the ultrasonographic evaluation. TCD was performed bilaterally; blood flow velocity was monitored during CO2 and L-Arginine stimulation both in basal conditions and three months after surgery. RESULTS After endarterectomy, mean velocity increased in response to both stimuli with a trend toward statistical significance. A significantly lower reactivity to L-Arginine on the stenotic side was found in the pre-operative phase: this asymmetrical reactivity was no longer observable after carotid endarterectomy. CONCLUSIONS We found a statistically significant difference in L-Arginine reactivity in the stenotic side of patients with severe unilateral internal carotid stenosis. This is probably related to an alteration of the endothelium function due to the carotid pathology, since the abnormalities disappeared three months after endarterectomy.

Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.

Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity: Nitric oxide precursors and cerebral blood velocity

Nitric oxide (NO), a gaseous molecule synthesized in the arteriolar endothelium from the amino acid L-arginine (L-arg), has been identified as the previously described Endothelium-Derived Relaxing Factor (EDRF): nitroderivatives such as nitroglycerin are known to induce vasodilation via NO release. The aim of this study was to evaluate by Transcranial Doppler (TCD) monitoring any changes in cerebral hemodynamics induced by both the infusion of L-arg and the sublingual administration of nitroglycerin in 20 healthy subjects. L-arg infusion induced a significant increase in blood velocity compared to the baseline value (mean +/- S.D. percent change = 18 +/- 8.71; p<0.0001 ) and a slight but significant decrease in Pulsatility Index. By contrast, nitroglycerin was able to cause a significant decrease in blood velocity (mean +/- S.D. percent change = 24.8 +/- 7.68; p<0.0001), while leaving Pulsatility Index unchanged. These data suggest that L-arg and nitroglycerin, both hypothesized to use NO as the final product at the vascular level, result in opposite blood velocity patterns within the cerebral circulation. This may be due to the particular type of artery and/or to the local endothelial environment whereby the released NO may act.