Publications by authors named "Franco Simionato"

9 Publications

  • Page 1 of 1

Cerebral thrombi of cardioembolic etiology have an increased content of neutrophil extracellular traps.

J Neurol Sci 2021 04 21;423:117355. Epub 2021 Feb 21.

Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Electronic address:

Background: Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT).

Methods: We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO cells) and NET content (citH3 area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus.

Results: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62).

Conclusion: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
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http://dx.doi.org/10.1016/j.jns.2021.117355DOI Listing
April 2021

Impact of flow and angioarchitecture on brain arteriovenous malformation outcome after gamma knife radiosurgery: the role of hemodynamics and morphology in obliteration.

Acta Neurochir (Wien) 2020 07 26;162(7):1749-1757. Epub 2020 Apr 26.

Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy.

Background: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR).

Methods: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study.

Results: Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37-173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15-4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11-0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors.

Conclusions: Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.
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http://dx.doi.org/10.1007/s00701-020-04351-4DOI Listing
July 2020

Safety and feasibility of lumbar drainage in the management of poor grade aneurysmal subarachnoid hemorrhage.

J Clin Neurosci 2019 Jun 22;64:64-70. Epub 2019 Apr 22.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

The use of lumbar drain (LD) in the aneurysmal subarachnoid hemorrhage (aSAH) has been described to reduce cerebral vasospasm and delayed cerebral ischemia (DCI), with a lack of studies referring to high grade population. The purpose of our study is to assess safety and feasibility of LD in the poor grade aSAH population subjected to endovascular aneurysm occlusion. Twenty-four consecutive poor grade aSAH patients, defined as grade IV and V according to World Federation of Neurological Surgeons (WFNS) classification, subjected to endovascular aneurysm occlusion, were retrospectively reviewed. Details of CSF drainage via LD and related complications were analyzed. Ventriculo-lumbar pressure gradient (VLPG) lower than 6 mmHg was considered in order to start LD use. Good outcome was defined as modified Rankin Scale (mRS) 0-2. LD was started within 72 h since aSAH in 17 cases (70.8%), and in 7 cases (29.2%) it was delayed due to contraindications. The mean LD length was of 13.8 days. The median VLPG during drainage was 2 mmHg (IQR: 0-4). No cases of brain or spinal hemorrhage, permanent neurological worsening due to brain herniation were noted. Three cases (12.5%) of CSF infection and a related death (4.2%) were reported. The use of LD, in association with external ventricular drain (EVD), seems to be safe and feasible in the poor grade aSAH population. VLPG monitoring seems to play a key role in avoiding potentially severe complications.
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http://dx.doi.org/10.1016/j.jocn.2019.04.010DOI Listing
June 2019

Hemorrhagic burden in poor-grade aneurysmal subarachnoid hemorrhage: a volumetric analysis of different bleeding distributions.

Acta Neurochir (Wien) 2019 04 21;161(4):791-797. Epub 2019 Feb 21.

Department of Neuroradiology, Interventional Neuroradiology Division, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy.

Background: Volumetric assessment of aneurysmal bleeding has been evaluated in few studies and emerged as a promising outcome predictor. There is a lack of studies evaluating its impact in the poor-grade population.

Methods: Retrospective review of 63 consecutive poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients, defined as grade IV and V according to the World Federation of Neurological Surgeons (WFNS) classifications. Global intracranial bleeding volume was calculated with its subarachnoid, intracerebral (ICH), and intraventricular (IVH) portions by means of analytical software. Univariate and multivariate analyses were performed in order to identify independent predictors of outcome. Good outcome was defined as modified Rankin Scale (mRS) 0-2 and mortality as mRS 6. The cutoff values of bleeding volumes were derived by receiver operating curve (ROC) analysis.

Results: Mean follow-up was of 12.5 (± 1.5) months. Thirty (47.7%) patients achieved good outcome, whereas 19 (30.2) patients out of 63 died. Global intracranial bleeding resulted as an independent predictor of good outcome (cutoff 24 mL). Furthermore, ICH relative percentage of global volume (10% of total) and pure SAH (64% of total) emerged respectively as independent predictors of worsened and improved outcome. Global bleeding volume (cutoff 51 mL) along with global cerebral edema showed to independently predict mortality in the examined poor-grade aSAH population.

Conclusions: Volumetric assessment of aneurysmal bleeding has the potential for identifying cutoff values that independently predict outcome. Further insights into the relative importance of different bleeding volumes may be implicated in better tailoring the management of this dismal aSAH population.
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http://dx.doi.org/10.1007/s00701-019-03846-zDOI Listing
April 2019

Moyamoya disease mimicking the first attack of multiple sclerosis.

J Neurol 2017 May 17;264(5):1005-1007. Epub 2017 Mar 17.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.

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http://dx.doi.org/10.1007/s00415-017-8458-3DOI Listing
May 2017

Treatment Challenges of a Primary Vertebral Artery Aneurysm Causing Recurrent Ischemic Strokes.

Case Rep Neurol Med 2017 10;2017:2571630. Epub 2017 Jan 10.

Stroke Unit, Department of Neurology and Neurophysiology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

. Extracranial vertebral artery aneurysms are a rare cause of embolic stroke; surgical and endovascular therapy options are debated and long-term complication may occur. . A 53-year-old man affected by neurofibromatosis type 1 (NF1) came to our attention for recurrent vertebrobasilar embolic strokes, caused by a primary giant, partially thrombosed, fusiform aneurysm of the left extracranial vertebral artery. The aneurysm was treated by endovascular approach through deposition of Guglielmi Detachable Coils in the proximal segment of the left vertebral artery. Six years later the patient presented stroke recurrence. Cerebral angiography and Color Doppler Ultrasound well characterized the unique hemodynamic condition developed over the years responsible for the new embolic event: the aneurysm had been revascularized from its distal portion by reverse blood flow coming from the patent vertebrobasilar axis. A biphasic Doppler signal in the left vertebral artery revealed a peculiar behavior of the blood flow, alternately directed to the aneurysm and backwards to the basilar artery. Surgical ligation of the distal left vertebral artery and excision of the aneurysm were thus performed. . This is the first described case of NF1-associated extracranial vertebral artery aneurysm presenting with recurrent embolic stroke. Complete exclusion of the aneurysm from the blood circulation is advisable to achieve full resolution of the embolic source.
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http://dx.doi.org/10.1155/2017/2571630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259648PMC
January 2017

Orbital color Doppler ultrasound as noninvasive tool in the diagnosis of anterior-draining carotid-cavernous fistula.

Radiol Med 2016 Apr 6;121(4):301-7. Epub 2015 Dec 6.

Department of Radiology, San Raffaele Scientific Institute - Vita Salute University, Via Olgettina, 60, 20132, Milan, Italy.

Purpose: To investigate the role of orbital color Doppler ultrasound (OCDUS) in the diagnosis of carotid-cavernous fistula (CCF) with anterior drainage and particularly whether a negative OCDUS could avoid an invasive diagnostic cerebral angiography (DSA).

Materials And Methods: Twenty-two consecutive patients with ophthalmic signs suspecting CCF were submitted to ophthalmologic examination, OCDUS and DSA. CCF diagnosis with OCDUS was based on the finding of a reversed, arterialized and low-resistive-index (RI <0.5) blood flow in the superior ophthalmic vein (SOV). Sensibility, specificity, PPV, NPV, and accuracy of OCDUS were calculated considering both patients and eyes, using DSA as gold standard.

Results: DSA demonstrated 20 CCFs in 18 patients. Considering the patients, in 18/22 CCF diagnosis was positive at OCDUS and DSA while 4/22 were negative at both. Considering the eyes, in 24/43 CCF diagnosis was positive at both DSA and OCDUS (total eyes = 43, due to one case of SOV thrombosis). In 19/43 eyes diagnosis was negative at both OCDUS and DSA. So sensitivity, specificity, PPV, NPV, and accuracy of OCDUS in the patients and eyes analysis were all 100 %.

Conclusions: OCDUS is a reliable, noninvasive tool in the diagnosis of CCF; a negative OCDUS could avoid an invasive DSA in patients suspected for anterior-draining CCF.
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http://dx.doi.org/10.1007/s11547-015-0607-0DOI Listing
April 2016

Comparison of 3D TOF-MRA and 3D CE-MRA at 3T for imaging of intracranial aneurysms.

Eur J Radiol 2013 Dec 12;82(12):e853-9. Epub 2013 Sep 12.

Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences - 2nd University of Naples, Italy. Electronic address:

Purpose: To compare 3T elliptical-centric CE MRA with 3T TOF MRA for the detection and characterization of unruptured intracranial aneurysms (UIAs), by using digital subtracted angiography (DSA) as reference.

Materials And Methods: Twenty-nine patients (12 male, 17 female; mean age: 62 years) with 41 aneurysms (34 saccular, 7 fusiform; mean diameter: 8.85 mm [range 2.0-26.4mm]) were evaluated with MRA at 3T each underwent 3D TOF-MRA examination without contrast and then a 3D contrast-enhanced (CE-MRA) examination with 0.1mmol/kg bodyweight gadobenate dimeglumine and k-space elliptic mapping (Contrast ENhanced Timing Robust Angiography [CENTRA]). Both TOF and CE-MRA images were used to evaluate morphologic features that impact the risk of rupture and the selection of a treatment. Almost half (20/41) of UIAs were located in the internal carotid artery, 7 in the anterior communicating artery, 9 in the middle cerebral artery and 4 in the vertebro-basilar arterial system. All patients also underwent DSA before or after the MR examination.

Results: The CE-MRA results were in all cases consistent with the DSA dataset. No differences were noted between 3D TOF-MRA and CE-MRA concerning the detection and location of the 41 aneurysms or visualization of the parental artery. Differences were apparent concerning the visualization of morphologic features, especially for large aneurysms (>13 mm). An irregular sac shape was demonstrated for 21 aneurysms on CE-MRA but only 13/21 aneurysms on 3D TOF-MRA. Likewise, CE-MRA permitted visualization of an aneurismal neck and calculation of the sac/neck ratio for all 34 aneurysms with a neck demonstrated at DSA. Conversely, a neck was visible for only 24/34 aneurysms at 3D TOF-MRA. 3D CE-MRA detected 15 aneurysms with branches originating from the sac and/or neck, whereas branches were recognized in only 12/15 aneurysms at 3D TOF-MRA.

Conclusion: For evaluation of intracranial aneurysms at 3T, 3D CE-MRA is superior to 3D TOF-MRA for assessment of sac shape, detection of aneurysmal neck, and visualization of branches originating from the sac or neck itself, if the size of the aneurysm is greater than 13 mm. 3T 3D CE-MRA is as accurate and effective as DSA for the evaluation of UIAs.
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http://dx.doi.org/10.1016/j.ejrad.2013.08.052DOI Listing
December 2013

Spinal dural arteriovenous fistulae: analysis of outcome in relation to pretreatment indicators.

Neurosurgery 2004 Oct;55(4):815-22; discussion 822-3

Department of Neurosurgery, Hospital San Raffaele, Milan, Italy.

Objective: The outcome of treatment for a spinal dural arteriovenous fistula is unpredictable. In this study, we reviewed the outcome of patients treated for this condition, in relation to pretreatment indicators.

Methods: We reviewed the records of 37 consecutive patients treated either surgically or endovascularly in our department between 1989 and 2002.

Results: At follow-up, 78% of the patients reported improvement. Those with motor symptoms had the best outcome: improvement was achieved in more than 60% of the patients, amounting to 1 or 2 points on the Aminoff scale. Sensory disorders improved in 43% of cases, pain in 61%, and sphincter impairment in only 37%. Patients with a fistula in the lower thoracic region did better than those with fistulae in other locations.

Conclusion: The clinical state before treatment is certainly relevant in predicting outcome. Age and duration of the symptoms before treatment have no direct relation to the chances of improvement with treatment, particularly when motor improvement is considered. The modality of onset of symptoms and location of the fistula play significant roles, also: a fistula in the lower thoracic segment was associated with more severe symptoms but tended to improve more (83%, P = 0.04) after treatment. Midthoracic and lumbar fistulae showed a lower incidence of improvement (<50%).
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http://dx.doi.org/10.1227/01.neu.0000137630.50959.a7DOI Listing
October 2004