Maria Luisa Zedde

Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension

BackgroundTransorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH.MethodsTwenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured.ResultsONSD values were significantly higher in patients (6.50u2009±u20090.67) than controls (5.73u2009±u20090.66; pu2009<u20090.0001). No differences were found in OND values between patients (2.99u2009±u20090.26) and controls (2.93u2009±u20090.41; pu2009=u20090.574). No correlation was demonstrated between ONSD and CSF opening pressure (ru2009=u20090,086) (pu2009=u20090.73). No difference in frequency of IJVVI between patients (11/42 valves, 26xa0%) and controls (9/42, 21xa0%) was observed (pu2009=u20090.777).ConclusionsIncreased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH.Trial registrationNot applicable. Observational, non-interventional study.

B-mode transorbital ultrasononography for the diagnosis of acute optic neuritis. A systematic review

OBJECTIVEnIn patients with acute optic neuritis (AON) transorbital sonography may reveal a thickening of the retrobulbar portion of the optic nerve. Our aim was to systematically review the diagnostic accuracy of ultrasonography of optic nerve diameter (OND) for assessment of AON.nnnMETHODSnMEDLINE, EMBASE (1966-October 2014) was searched to identify studies reporting data on patients with AON (with/without multiple sclerosis) assessed by B-mode transorbital ultrasonography. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated.nnnRESULTSnSeven studies (162 patients) were included. The OND was significantly thicker in the affected eye compared with its unaffected fellow or controls. An increased OND was found in 78-100% of patients. Four studies determined papilledema in 6-43% of patients.nnnCONCLUSIONSnTransorbital sonography is a sensitive, highly accessible and user-friendly technique for the detection of significant optic nerve thickening on the side affected by AON and represents an adjunctive tool for the diagnosis of AON. Compared to visual evoked potentials, TOS may provide different, though complementary, information on the pathophysiology of AON.nnnSIGNIFICANCEnB-mode transorbital ultrasonography provides promising support for the clinical diagnosis of AON.

Propensity Score–Based Analysis of Percutaneous Closure Versus Medical Therapy in Patients With Cryptogenic Stroke and Patent Foramen Ovale The IPSYS Registry (Italian Project on Stroke in Young Adults)

Background—We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study. Methods and Results—Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39–1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33–1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04–0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05–0.68; P=0.011). Conclusions—PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.

Sonography of the optic nerve sheath beyond the hyperacute stage of intracerebral hemorrhage.

PurposeTo evaluate the feasibility and utility of serial measuring of the optic nerve sheath diameter beyond the hyperacute and acute stage of intracerebral hemorrhage (ICH).MethodsFour patients with extensive ICH in the left basal ganglia were followed using ultrasound (US) and cerebral CT scans.ResultsOptic nerve sheath diameter values assessed beyond the acute stage of ICH showed a high correlation (ρxa0=xa00.84, pxa0=xa00.0022) with midline shift of the third ventricle seen on CT scans.ConclusionsOptic nerve sonography can be useful to evaluate patients with extensive ICH beyond the acute stage and help monitoring clinical evolution in these patients, when ICP monitoring is not feasible.RiassuntoO biettiviValutare l′utilità clinica della misurazione seriale del diametro del nervo ottico e dei suoi rivestimenti dopo la fase acuta dell′emorragia cerebrale.MetodiQuattro pazienti con emorragia cerebrale sono stati sottoposti ad ecografia del nervo ottico e tomografia assiale computerizzata (TAC) del cranio.RisultatiI valori del diametro del nervo ottico e dei suoi rivestimenti correlavano in maniera marcata con lo shift della linea mediana del terzo ventricolo evidenziato alla TAC cerebrale.ConclusioniLa sonografia del nervo ottico con la misurazione del diametro del nervo ottico e dei suoi rivestimenti potrebbe costituire un utile strumento nel valutare l’evoluzione clinica dei pazienti con estesa emorragia intracranica, qualora la misurazione della pressione intracranica non fosse eseguibile.

Italian symptomatic intracranial atherosclerosis study (ISIDE): A multicenter transcranial ultrasound evaluation

There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of axa0≥50xa0% stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6xa0%) men, with a mean age of 71.2xa0±xa013.3xa0years. ICAS was recorded in 99 patients (8.7xa0% of the whole sample, 8.9xa0% among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5xa0%). After adjusting for potential confounders, multivariate analysis identified carotid/vertebralxa0≥50xa0% stenosis [odds ratio (OR) 2.59, 95xa0% (confidence interval) CI 1.77–6.33; Pxa0=xa00.02] and hypercholesterolemia (OR 1.38, 95xa0% CI 1.02–1.89; Pxa0=xa00.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9xa0% of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases withxa0≥50xa0% cervical vessel stenoses.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial)

Background and Purpose— Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. Methods— According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. Results— We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60–1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). Conclusions— Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis:

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell’Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24u2009h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19–7.53); SAP:5.46 (1.64–18.74); Δmetalloproteinase 9:1.60 (1.12–2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: pu2009=u20090.0205; model-3 with SAP: pu2009=u20090.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

Development of an education campaign to reduce delays in pre-hospital response to stroke

BackgroundSystematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness.MethodsCampaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced.ResultsIn phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2xa0hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential “patients” and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2xa0hours had been advised by a family member to call EMS. To act on people’s tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination.ConclusionsThe IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process.Trial registrationNCT01881152. Retrospectively registered June 7 2013

Women Stroke Association statement on stroke

We describe the current and future objectives of the Women Stroke Association, a nonprofit multidisciplinary organization promoting research awareness on medical, psychological, and social issues concerning women affected by cerebrocardiovascular disease. In this paper, we deal with only cerebrovascular disease, whereas cardiovascular disorders will be addressed in a future paper. Gender differences in the clinical presentation of cerebrovascular diseases have been repeatedly suggested, and some treatment options may not be as effective and safe in men and women. For many years, women have either been underrepresented or excluded from randomized clinical trials, and the majority of therapeutic research has been carried on predominantly male populations. Furthermore, gender differences have been shown to contribute to different responses to cerebrovascular drugs in women when compared with men, regarding pharmacokinetics, pharmacodynamics, and physiology. In this statement, we discuss main research fields relevant to Women Stroke Associations mission and commitment, highlighting opportunities and critical from the womens health perspective. Future directions and goals of the Women Stroke Association arise from these considerations and represent the associations commitment to combating stroke.