Imaging biomarkers in acute ischemic stroke trials: a systematic review.

BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used. MATERIALS AND METHODS: We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995-2014). RESULTS: Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses. CONCLUSIONS: Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients.

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH-weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model-based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model-based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model-based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model-based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging.

Decision-making in the scheduling of endovascular treatment after brain arteriovenous malformation haemorrhage: a retrospective single centre study.

The appropriate timing for endovascular intervention after brain arteriovenous malformation (bAVM) rupture is not known. This paper aims to determine factors that lead to early endovascular intervention and to investigate whether early intervention has the same complication rate as late intervention in a single centre. All patients who underwent endovascular treatment for a ruptured bAVM at our institution in the period January 2007 and July 2010 were included in this retrospective observational study. Of 50 patients, 33 had early endovascular intervention, defined as within 30 days of haemorrhage and the remaining 17 patients had endovascular treatment at day 30 or beyond. A greater proportion of patients treated within the first 30 days were in neuro-intensive care preoperatively (51.5% vs. 23.5%, p=0.07). A 'high-risk' angioarchitectural feature was identified in more patients who had acute intervention (78.8% vs. 11.8%, p<0.0001) and targeted embolization was also more frequent in this group (48.5% vs. 5.9%, p=0.004). Nidal aneurysms, venous varices and impaired venous outflow (venous stenosis) were the principal 'high risk' features. Clinically apparent complications occurred in 10.8% of procedures with permanent neurological deficit in 3.6%. There was no directly procedure-related mortality. There was no statistically significant difference in the complication rate of early procedures compared with delayed interventions (12.5% vs. 7.4%, p=0.71). Greater initial injury severity and the presence of high-risk lesion characteristics are the factors that lead to early endovascular intervention. Early intervention is associated with a higher complication rate, but this difference is not statistically significant.

Endovascular Coiling of Aneurysm Remnants after Clipping in Patients with Follow-up. A Single Center Experience.

SUMMARY: The vast majority of intracranial aneurysms can be obliterated completely with surgical clipping. However, postoperative remnants occur in about 4 to 8% of patients who undergo postoperative angiography. Endovascular embolization has been successfully performed in patients with postoperative aneurysm remnant and it may represent a therapeutic alternative to surgical reintervention. Twelve aneurysm remnants after surgical clipping were treated with endovascular embolization using GDC. All aneurysms were located in the anterior circulation. Our experience confirms the feasibility and relative safety of this treatment strategy that may be considered a valid alternative to reintervention.

Results of surgical and endovascular treatment of intracranial micro-arteriovenous malformations with emphasis on superselective angiography.

BACKGROUND: The authors retrospectively reviewed the results of two different treatment modalities (surgery and endovascular approach) in patients with intracranial micro-arteriovenous malformations (micro-AVMs). The goal of this study is to evaluate the respective role of surgical treatment and superselective acrylic embolization in the management of micro-AVMs. METHOD: Fourteen patients with micro-AVMs who had been treated by surgical resection or endovascular acrylic embolization during a 6-year period were analyzed. The average age at presentation was 44.6 years (range, 24-65 yr) with no sex dominance. All patients presented with an intracranial haemorrhage, which was superficial in twelve patients and in eloquent brain areas in seven patients. Severe neurological deficits were observed in eleven patients. FINDINGS: Digital subtraction angiography (DSA) demonstrated micro-AVMs in eleven patients (78.5%) while in three patients (21.5%) the micro-AVM was detected only by superselective angiography (SA). Eight patients underwent surgical intervention which led to definitive resection in seven with no peri-operative morbidity. SA was performed in nine patients and followed by successful acrylic embolization of the micro-AVM in seven with haemorrhagic complications in two patients. All fourteen lesions were completely obliterated as demonstrated angiographically. Outcomes were classified according to the Modified Rankin Scale. With a mean long term clinical follow-up of 33 months (range, 8-75 mo), seven patients were Grade 0, six patients were Grade I and one patient was Grade IV. CONCLUSIONS: SA is deemed necessary to visualize micro-AVMs in case of questionable or negative findings also at delayed DSA in young healthy patients with otherwise unexplained intracranial haemorrhage. Obliteration of micro-AVM can be accomplished either surgically or endovascularly; however, the endovascular approach is associated with a defined procedural risk for haemorrhagic complications and long term angiographic follow-up is necessary.

Spontaneous petrous carotid artery occlusive dissection treated by local fibrinolysis and stent deployment.

SUMMARY: This paper reports a case of local thrombolytic therapy followed by stenting of the petrous carotid in a young woman with recurrent transient ischemic attacks from spontaneous dissection. A total of four overlapping balloon-expandable stents were delivered in two different sessions one month apart. The procedure resulted in a potentially efficacious treatment for the prevention or reduction of cerebral damages from ischemia. At followup three months later the patient was symptomfree and DSA revealed a delayed proximal small pseudoaneurysm and a carotid-cavernous fistula. At one year follow-up the patient was still symptom-free with unmodified findings at cerebral angiography.

Disappearance of cerebral arteriovenous malformations after partial endovascular embolisation: four cases with follow-up.

We report four patients with late angiographic follow-up of spontaneous occlusion of residual cerebral arteriovenous malformation after partial embolisation. Discussion is focused on the possible mechanisms leading to obliteration according to the latest concepts on angioarchitectural remodelling, malformation development and evolution with a brief review of the literature.

Rebleeding and ischemia after acute endovascular treatment of ruptured dissecting subarachnoid vertebral artery aneurysms.

SUMMARY: Dissection aneurysms of the vertebral artery represent 3.2% of all cerebral aneurysms and 28% of intracranial dissection aneurysms. Dissection of the vertebral artery in its intracranial segment (V4) usually causes a subarachnoid hemorrhage (SAH) from subadventiatial extension of the vessel wall hematoma. Rarely (one case in seven), the symptomatology is characterized by brain stem ischemia from the vertebral artery and/or postero-inferior cerebellar artery occlusive dissection. The high rebleeding (18-33% with a 10+/-5 day interval between the first and the second bleeding) and mortality (> 45%) rates 1, 13 of this disease prompt emergency treatment usually consisting in endovascular coiling of the dissection aneurysm and/or the dissected segment of the parent vessel. Herein we report our experience in endovascular coiling of acutely ruptured dissecting aneurysms of the vertebral artery dissection in V4 segment. We focus the discussion on the risk of rebleeding and the ischemic complications that my occur after endovascular or surgical treatment.

Idiopatic spinal cord herniation: a treatable cause of Brown-Séquard syndrome.

We report two cases of thoracic idiopathic spinal cord herniation (ISCH) focusing on the peculiar diagnostic and therapeutic issues posed by this rare disorder. In particular MR evaluation of CSF dynamic with a 2D PC cine-MR technique and demonstration of progressive cord herniation on consecutive MR examinations allowed insight on the differential diagnosis and pathophysiological mechanisms of ISCH.

Utility of balloon-assisted guglielmi detachable coiling in the treatment of cerebral aneurysms. A single center retrospective study.

SUMMARY: Balloon-assisted Guglielmi detachable coiling (BAGDC) is a new technical option developed to allow endovascular treatment of wide-necked aneurysms. Aim of the following work is to report a single center experience of BADGC of aneurysms with assessment of its efficacy and safety. BAGDC of wide-necked aneurysms (SNR close to 1) was retrospectively evaluated in 37 patients (28 females, nine males, mean age: 56.6 yrs, range: 27-81 yrs) who underwent the procedure between january 1999 and january 2002 for a total of 45 procedures on 41 aneurysms.Twenty- nine patients presented with SAH from an acutely ruptured aneurysm. In two patients BAGDC failed whereas 35 patients successfully underwent BADGC (39 aneurysms). Twenty-nine patients (31 aneurysms) were available for angiographic follow- up (mean: 10 mo, range: 3-24 mo). At the last angiographic follow-up 29/33 aneurysms (87%) resulted stable and occluded (22 aneurysms with dense and seven with loose packing of the sac and the neck), two aneurysms showed regrowth, one aneurysm showed a neck remnant and another one a sac and neck remnant. Complications directly related to the procedure occurred in five patients (three perforations, one thromboembolism, one femoral AV) with a mortality and morbility rate of 2.7 and 5.4 respectively. BAGDC is a promising adjunct to treatment of wide-necked aneurysms broadening the spectrum of indications for endovascular treament of challenging aneurysms.

Percutaneous transluminal cerebral angioplasty and stenting in acute vertebrobasilar ischemic stroke. Report of two cases.

SUMMARY: Reports of cerebral transluminal angioplasty and stenting in patients with vertebrobasilar ischemic stroke are scanty. Herein we report on the use of "monorail" coronary balloon angioplasty and stent balloon mounted catheters in two patients with acute vertebrobasilar ischemic stroke, focussing on the differences and possible advantages of the "monorail" technique in comparison with the "over-the-wire" technique. In both patients, the clinical picture was characterized by progressive brainstem symptoms followed by acute loss of consciousness related to an atherothrombotic occlusion and subocclusion of the dominant intracranial vertebral artery, respectively. In one patient, superselective thrombolytic therapy and balloon angioplasty resulted in a dissection flap at the vertebrobasilar junction. The latter was treated by successful deployment of a coronary stent. In the other patient, the subocclusive lesion was directly treated by angioplasty and stenting without thrombolytic therapy. The clinical outcome was poor for one patient ("locked in" syndrome) while the other had a complete clinical recovery. In acute atherothrombotic vertebrobasilar stroke transluminal cerebral angioplasty and stenting may be successfully performed allowing vessel recanalization.

MRI of cerebral rheumatoid pachymeningitis: report of two cases with follow-up.

We report the clinical and neuroradiological features of cerebral rheumatoid pachymeningitis with 1 year follow-up in two patients. MRI of the head enabled noninvasive diagnosis of both the meningeal abnormality and its complications, consisting of hypertensive hydrocephalus and superior sagittal sinus thrombosis, respectively. Dural sinus thrombosis, very uncommon in rheumatoid arthritis, was confirmed by phase-contrast MRA. Worsening of the pachymeningitis at follow-up was observed in both patients despite regression or stability of the clinical picture and long-term therapy.

Spinal vascular malformations: MR angiography after treatment.

PURPOSE: To evaluate the role of magnetic resonance (MR) angiography in the assessment of spinal vascular malformation therapy. MATERIALS AND METHODS: Thirty-four patients with spinal vascular malformations (30 dural arteriovenous fistulas, two perimedullary arteriovenous fistulas, and two intramedullary arteriovenous malformations) underwent MR angiography and MR imaging before and after endovascular or surgical treatment. RESULTS: MR angiography showed residual flow in perimedullary vessels in seven patients with dural fistula after embolization with liquid adhesive. In all seven, treatment failure was confirmed with arteriography. Long-lasting disappearance of flow in perimedullary vessels was demonstrated at MR angiography in 22 patients with dural fistula. MR imaging demonstrated normalization of spinal cord volume in 16 of 22 patients and signal intensity on T2-weighted images in three patients. Disappearance of cord enhancement was observed in five of 21 patients and of perimedullary enhanced vessels in six of 13 patients. In one additional patient with dural fistula treated with embolization, early posttreatment MR angiography showed disappearance of flow in perimedullary vessels, which reappeared at follow-up and was consistent with reopening of a small residual fistula. Posttreatment MR angiography demonstrated transient reduction of flow in the nidus in two patients with intramedullary malformations treated with embolization. Permanent disappearance of flow in the perimedullary vessel was seen after endovascular treatment in two patients with perimedullary fistula. CONCLUSION: MR angiography is more sensitive than MR imaging in depicting residual or recurrent flow in peri- or intramedullary vessels, which indicates patency of the vascular malformation.

Cerebral magnetic resonance imaging in a patient with ankylosing spondylitis and multiple sclerosis-like syndrome.

Clinical and cerebral magnetic resonance imaging (MRI) findings in a patient with ankylosing spondylitis (AS) and multiple sclerosis-like (MS-like) syndrome are reported. Cerebral MRI demonstrated multiple, MS-like, scattered foci of signal abnormality, one of which showed contrast enhancement. Lesion dissemination in "space and time" is a hallmark for diagnosis of MS, and its demonstration by enhanced cerebral MRI prompted suspicion of coexistence of MS and AS in our patient.