Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression.

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.

A group of 123 patients with large or critically located arterio-venous malformations (AVMs), operated on between 1990 and 2011 and who underwent preoperative embolization, was assessed in order to clarify the risks of this combined treatment. AVM location, volume, and Spetzler's grade were assessed in each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3 embolization procedures per patient were carried out, using bucrylate and, more recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was observed. Complications occurring after surgery were classified as hemorrhagic (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic complications were more common for AVMs with volumes >20 cm(3) and/or deep feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in grades 4-5. More recently, a triple treatment (radiosurgery + embolization + surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It has been concluded that a combined treatment with embolization and surgery constitutes a reasonable choice for complex cerebral AVMs; the association of radiosurgery may improve the patients outcome.

Operative classification of brain arteriovenous malformation. Part two: validation.

SUMMARY: The most important issue when dealing with a patient with a brain AVM is the decision whether to treat or not. Only after this decision has been made, taking into consideration a number of factors depending on both the patient and the specific type of AVM, can the best option for treatment be chosen. An operative classification of brain AVMs, previously adopted in the Department of Neuroradiology and Neurosurgery of Verona (Italy) and published in this journal, was subjected to validation in a consecutive group of 104 patients clinically followed for at least three years after completion of treatment. This classification, slightly modified from the original version concerning the importance of some specific items, allowed us to assess the indication to treat in each case, whatever type of treatment was offered to the patient.

Gamma knife radiosurgery in the management of arteriovenous malformations of the Basal Ganglia region of the brain.

OBJECTIVES: The authors report the results of gamma knife (GK) radiosurgery on a clinical series of selected patients with basal ganglia arteriovenous malformations (BGAVMs) in the brain. Clinical, epidemiological, anatomical and functional characteristics of BGAVMs and of supratentorial cortical AVMs are comparatively analyzed, and their influence on radiosurgical outcome is discussed. METHODS: At our Department, 33 BGAVMs (21 with FU > 2 years) and 209 cortical AVMs (110 with FU > 2 years) with a radiosurgical volume

[The diagnostic and therapeutic procedures in pulmonary embolism: a survey in the Veneto Region]. / Iter diagnostici e terapeutici nell'embolia polmonare: inchiesta nella Regione Veneto.

BACKGROUND: Pulmonary embolism is one of the most frequent cardiopulmonary diseases, but it is often under- or misdiagnosed. In order to address this issue and to identify flow charts that are commonly used in pulmonary embolism diagnosis and treatment, 191 clinical wards of internal medicine, cardiology, geriatrics, pneumology and intensive care units, located in the Veneto Region, were surveyed. METHODS: An anonymous questionnaire was mailed to each ward in order to collect clinical diagnostic information on all pulmonary embolisms which occurred during 1993. Among the returned questionnaires, 114 (59.6%) had usable information for the analysis. RESULTS: The vast majority of participating centers reported in 1993 less than 10 pulmonary embolism events. No significant differences were observed between internal medicine, geriatrics, pneumology wards and intensive care units. The reported events, however, were slightly higher in the divisions of cardiology with an annual average of 12 events per center. First level diagnostic procedures, such as ECG, chest X-ray and arterial blood gas analysis were chosen and performed in all patients. Interestingly, Doppler echocardiography, which is often not included in official guidelines for pulmonary embolism diagnosis, was performed in 56% of the participating centers. On the contrary, ventilation-perfusion lung scanning, which is considered highly predictive in many diagnostic algorithms, was underutilized (35% perfusion scan, 20% ventilation scan). This underuse was probably due to technical and organizational difficulties. Pulmonary angiography, the most accurate procedure for the diagnosis of pulmonary embolism, was performed in 28% of the patients. During the acute phase, intravenous heparin was commonly used; 91% of patients received the infusion continuously, 4% intermittently. Thrombolysis was performed in 25% of the patients. The preferred drugs were recombinant tissue-plasminogen activator (67%), followed by urokinase (20%) and streptokinase (13%). To start thrombolytic therapy, 20% of the interviewed clinicians considered sufficient the evidence of clinical manifestations of pulmonary embolism confirmed by echocardiographic data. At discharge, prescription of oral anticoagulant drugs was common (78%) for at least 6 months (47%). Standardized procedures for the diagnosis and treatment of pulmonary embolism were already implemented in 13% of the participating centers. CONCLUSIONS: These data suggest a common effort to define unanimous conventional protocols in the management of pulmonary embolism. It should be underlined, however, that a particular attention to the clinical manifestations and a productive collaboration among clinicians with different expertise are required to improve the diagnosis and treatment of pulmonary embolism.

Idiopathic thrombocytopenic purpura treated with steroid therapy does not prevent acute myocardial infarction: a case report.

We report the case of a 65-year-old man affected by idiopathic thrombocytopenic purpura, who developed an acute myocardial infarction after 2 years of steroid therapy. Thrombocytopenia was initially recognized 11 years earlier, and became severe during the past 2 years [platelets (PLTS) 10000-30000/microl]. He was treated with steroids, initially to perform a surgical procedure (prednisone 75 mg/day), subsequently to maintain a platelet count of about 50000/microl (prednisone 12.5 mg/day). After 1 year of treatment, he began to complain about exertional angina and dyspnea. His blood pressure became elevated and cholesterol level raised. The exercise electrocardiogram, previously manifesting ischaemic changes, normalized after 1 month of steroid wash-out; however, steroid therapy was reinstituted (prednisone 5 mg per day). One year later, he suffered an infero-lateral non-Q-wave myocardial infarction. It seems likely that the severe coronary atherosclerosis present in our patient developed despite a low platelet count, under the spur of a heavier risk factor profile. Steroid therapy could have had a role as a precipitating agent of the acute event, and the opportunity of alternative treatments is considered.

Unusual nasal and orbital involvement of glioblastoma multiforme: a case report and review of the literature.

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study.

BACKGROUND: The outcome after treatment for glioblastoma remains poor. Therefore, the authors evaluated the long term efficacy and toxicity of treatment with radiotherapy and concurrent carboplatin plus teniposide followed by three cycles of carmustine in patients who underwent resection for glioblastoma. METHODS: Fifty-six newly diagnosed patients with glioblastoma underwent radiotherapy (1.8-2 gray [Gy]/day, 5 days a week using limited fields up to 60 Gy), and concurrent chemotherapy with carboplatin (350 mg/m2) on Days 1, 22, and 43, and teniposide (50 mg/m2) on Days 1, 2, 3, 22, 23, 24, 43, 44, and 45. Four weeks after the end of radiotherapy, patients were given carmustine (200 mg/m2) every 8 weeks for 3 cycles. Treatment then was suspended, but if disease progression was found, treatment was resumed using different drugs. RESULTS: All 56 patients were evaluated for time to progression (TTP) and median survival time (MST). The TTP was 7.5 months and the MST was 12.5 months. Toxicity manifested as thrombocytopenia and in most cases was acceptable. Four patients (7.1%) had radiation necrosis at 2, 2, 7, and 9 months, respectively, from the end of radiotherapy. CONCLUSIONS: The results obtained in the current study with concurrent radiochemotherapy in patients with glioblastoma are comparable to the best results reported using radiotherapy alone followed by chemotherapy with nitrosoureas.

Pulmonary hypertension associated with human immunodeficiency virus infection. Report of two cases and review of the literature.

Recent reports have suggested a possible association between HIV-1 infection and "idiopathic" pulmonary hypertension (PH), but the pathogenetic role of the viral agent has not been fully defined yet. We report the cases of two white males positive for human immunodeficiency virus type 1 (HIV-1) who presented with clinical and hemodynamic diagnosis of pulmonary hypertension. They were heterosexual, non-hemophiliac, heroin abusers with no signs of clinical AIDS. Neither one of the patients had opportunistic lung infections or any other cause of secondary pulmonary hypertension. In one case, peculiar clinical and electrocardiographic features of PH were associated with signs of thrombotic thrombocytopenic purpura (TTP). The association between PH and HIV-1 infection might be explained by a severe alteration of pulmonary endothelial cell homeostasis secondary to HIV-1 viral infection.

Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study.

A prospective study of a series of 77 patients on adjuvant radiochemotherapy following surgery for high-grade gliomas was conducted to evaluate the risk of deep vein thrombosis and identify risk factors. We found a 20.8% risk of deep vein thrombosis at 12 months (standard error = 4.8%) and a 31.7% risk (standard error = 7.4%) at 24 months (Kaplan-Meier method). Twenty patients (26%) developed deep vein thrombosis with a maximum incidence within the first 7 months after surgery when chemotherapy was still being administered, often with corticosteroids. The risk factors identified were histology (glioblastoma versus anaplastic astrocytoma, P = 0.032, log rank test; 0.0485 L-ratio) and the presence of paresis (P = 0.010, log rank test; 0.0161 L-ratio). A borderline tendency was found for an association between the deep vein thrombosis site and the side of paresis (P = 0.103, Fisher's exact test). Four patients (5%) had massive pulmonary embolism, which was fatal in 3 (4%).

Phase II trial with BCNU plus alpha-interferon in patients with recurrent high-grade gliomas.

A Phase II study with a combination of BCNU and alpha-interferon (IFN) was conducted in patients with high-grade glioma recurrent after surgery and radiation treatment in order to investigate tumor control and toxicity. Twenty-one non-chemotherapy pretreated patients were administered 6 MU alpha-IFN in a 2-h infusion followed by 150 mg/m2 BCNU i.v. on day 1. Three MU alpha-IFN were subsequently administered subcutaneously on alternating days three times a week, until recycling of the whole procedure on day 42. Among 21 patients, partial remission was obtained in 7 (33%; 95% CI = 15-57) and stable disease in 6 (29%; CI = 11-52); overall Kaplan-Meier median time to progression (TTP) was 4.5 months (CI = 4-9) and the overall median survival time (MST) was 7 months (CI = 5-13). In patients who underwent surgical redebulking prior to chemotherapy, TTP and MST were 9 (CI = 7-14) and 15 months (CI = 11.0-39.0); in patients who were not operated on again before chemotherapy, these values were 4 (CI = 2-5; log rank test, p = 0.0026) and 5.5 months (CI = 4-7; log rank test, p = 0.0012) respectively. The results of this regimen in relapsing patients, especially following surgical redebulking, are encouraging; toxicity is acceptable, and further studies on combined alpha-IFN and multiple-agent chemotherapy are warranted.

Endovascular treatment of pial AVMs: technical options, indications and limits in pediatric age patients.

Our study group consisted of 29 patients who underwent endovascular treatment for the presence of pial AVMs. The patients were treated with various embolization methods including "-free flow" embolization (2 cases); embolization with suture threads (2 mm long micro-emboli: 17 cases) and embolization with acrylic glue (10 cases). There were significant angio-architectural and AVM location differences between the pediatric and the adult patient groups. In pediatric patients, the more frequent AVMs were of the mono or few-pedunculated type, then simple direct fistulas and high-flow fistulous-plexiform AVMs and giant infra-tentorial or deep-seated malformations. In mono or few-pedunculated AVMs, the elected treatment was acrylic glue followed by radio-surgery achieving definitive cure in 3 cases. In direct AVFs and elevated flow AVMs, embolization with suture and acrylic glue offered definitive results. Treatment for infra-tentorial and deep-seated AVMs presented the greatest difficulty in pediatric patients. In two of them, embolization with glue enabled radiosurgery (giant cerebellar AVMs). Our experience did not confirm that current endovascular techniques provide definitive treatment in extensive, deep-seated AVMs. Each treatment, in children more so than in adults, requires a risk/benefit evaluation of the method taking into account the natural history data.

Early chemotherapy and concurrent radio-chemotherapy in high grade glioma.

PURPOSE: The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival. PATIENTS AND METHODS: We treated 24 newly diagnosed patients (pts) with BCNU 150 mg/m2 seven days after surgery. Thirty days later, we started radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fields up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m2 on days 1, 22, and 43, and teniposide 50 mg/m2 on days 1, 2, 3, 22, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m2 BCNU were then given at 30 and 70 days, respectively, after the end of the radio-chemotherapy course. Therapy was then suspended, but if disease progression was evident, treatment was resumed with drugs that had not been previously employed. Surgical reintervention was not routinely considered. RESULTS: Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stable disease in 12 (50%). Actuarial estimates of progression free survival (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 weeks; 51 weeks for glioblastoma and was not reached for anaplastic astrocytoma. This regimen was feasible. Of 144 planned cycles, 139 were delivered, and among these only in 13 and 9 cycles the doses were reduced by 75 and 50%, respectively. We did not observe any gastrointestinal toxicity. Grade 2 hematological toxicity occurred in 25% of pts. grade 3 in 4% and neurological toxicity in 3% of the pts during BCNU delivery, probably due to a sharp increase in intracranial pressure. CONCLUSION: Early chemotherapy, concurrent chemo-radiotherapy and brief post-radio-therapy chemotherapy are feasible and well tolerated. The objective response and disease stabilization rates appear similar to previous experiences.

Shape recovery and volume calculation from biplane angiography in the stereotactic radiosurgical treatment of arteriovenous malformations.

PURPOSE: A model for calculating the three-dimensional volume of arteriovenous malformations from biplane angiography. METHODS AND MATERIAL: Three-dimensional (3D) volume reconstruction is easily feasible with axial, coronal, or sagittal computer tomography (CT) and nuclear magnetic resonance (NMR) scans. On the other hand, radiosurgical treatment of arteriovenous malformations (AVM) is exclusively based on two orthogonal stereotactic projections, obtained with angiographic procedures. Most commonly, AVM volumes have been calculated by assimilating the nidus volume to a prolate ellipsoid. We present an algorithm dedicated to 3D structure reconstruction starting from two orthogonal stereotactic projections. This has been achieved using a heuristic approach, which has been widely adopted in the artificial intelligence domain. RESULTS: Tests on phantom of different complexity have shown excellent results. CONCLUSION: The importance of the algorithm is considerable. As a matter of fact: (a) it allows calculations of complex structures far away from regular ellipsoid; (b) it permits shape recovery; (c) it provides AVM visualization on axial planes.

Follow up after spontaneous coronary artery dissection: a report of five cases.

Five cases of spontaneous coronary artery dissection (SCAD) are reported, three in women and two in men (mean age 44 years; range 28-65), all of whom suffered a myocardial infarction. Common risk factors for coronary artery disease were present in the two men; in the female group one patient was taking an oral contraceptive, one was in the postpartum period, and the third was a smoker. Only the three women received intravenous alteplase and their ejection fraction was normal; both men had impaired left ventricular function. Two patients had SCAD of the left anterior descending coronary artery and three of the right coronary artery. Only the two men had angiographic features of coronary atherosclerotic involvement. No patients required surgical revascularisation or percutaneous transluminal coronary angioplasty. At a mean follow up of 27 months (range 6 to 40) all patients were alive and all but one were asymptomatic.