Predictors for hemorrhagic transformation and cerebral edema in stroke patients with first-pass complete recanalization.

BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.

Intermittent Broca's aphasia management in an emergency unit: from theory to practice.

Although Broca's aphasia (BA) may mimic different neurological illness, its sudden onset often requires an emergency approach. In this paper, the management of a case of intermittent BA occurred in a young woman without history of neurological, cardiovascular and arrhythmic diseases is discussed. Diffusion-weighted magnetic resonance imaging showed two areas of hypoperfusion in the terminal branches of the left medial cerebral artery not previously diagnosed by computed tomography. Although there were no eligibility criteria for thrombolysis, patient received intravenous treatment with recombinant tissue-type plasminogen activator (rt-PA) over 1 h and at the end of rt-PA infusion aphasia completely disappeared without neurological sequelae. Transesophageal echocardiography revealed a thrombus in the left atrial appendage not previously detected by transthoracic echocardiography. In the month following the cardioembolic stroke, heart rhythm was monitored for 30 days by an external loop recorder and during this test two episodes of silent lone atrial fibrillation were collected.

Reduced right posterior hippocampal volume in women with recurrent familial pure depressive disorder.

Volumetric changes in mood-relevant distributed limbic/paralimbic structures have been reported in the recent literature on the course of mood disorders. Patients with unipolar and bipolar disorders have been found to have smaller hippocampal and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior cingulate cortex (ACC) volumes in female patients with recurrent familial pure depressive disorder (rFPDD). We used semi-automated software for magnetic resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial recurrent major depression (MD) and 15 healthy female subjects. Analysis of covariance, with whole brain volume as covariate, was used to compare volumetric measurements in the two groups. Volumes of the right hippocampal body and tail were significantly smaller in female patients with familial depressive disorder than in healthy subjects. Our data provide evidence of structural lateralized hippocampal body and tail abnormalities in women with familial history and recurrent episodes of depression. Although global reduction of hippocampal volume has been widely reported, data on lateralized regional reductions in familial recurrent depression had not been previously reported. Reduced volume of the right posterior hippocampus could be a structural endophenotype for recurrent depressive disorders in women.

Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas.

Paraganglioma syndrome includes head and neck paraganglioma and pheochromocytoma, and is classified according to the three susceptibility genes involved, SDHB, SDHC, and SDHD. This study assessed the prevalence of germline mutations in SDHB, SDHC, and SDHD genes in a consecutive population admitted to Padova Hospital consisting of 20 patients with head and neck paraganglioma (HNP). Mutations were identified in the three genes in four affected individuals, three sporadic cases and one with family history of HNP. The novel SDHB p.R242C mutation was identified in a sporadic monolateral carotid body tumor. The SDHC p.Q147X mutation, the first to be described in Italy, was detected in a sporadic monolateral jugulotympanic paraganglioma. The SDHD p.Y114C mutation was identified in two unrelated patients, one familial case of bilateral carotid body tumor and one multiple paraganglioma. SDHB, SDHC, and SDHD molecular screening is important in all HNPs, with or without primary indicators of paraganglioma syndrome, to orient mutation-driven clinical screening for additional HNPs and pheochromocytoma.

Combined use of export catheter and penumbra vacuum thromboaspiration in a challenging case of acute common carotid artery occlusion.

A 76-year-old hypertensive man with previous bilateral iliac stenting was admitted in our center for acute stroke with an NIH score of 20 at 6 h from symptoms onset. The common carotid occlusion with a huge thrombus and a very calcified plaque has been successfully recanalyzed with a combination of coronary total occlusion technique, filter-aided coronary manual thrombectomy and Penumbra vacuum thrombectomy systems.

Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after first-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PURPOSE: Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy. PATIENTS AND METHODS: Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2. RESULTS: A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. CONCLUSION: The BCNU plus irinotecan regimen seems active and non-cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.

The treatment of adults with medulloblastoma: a prospective study.

PURPOSE: To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults. METHODS AND MATERIALS: Patients (> or =18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al.'s classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b-T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of "up-front chemotherapy" were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present. RESULTS: Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% +/- 14% (95% confidence interval [CI] = 52%-100%) vs. 61% +/- 11% (95% CI = 42%-87%). Patients with M- disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% (p = 0.01). CONCLUSION: The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.

Evaluation of vascular grafts based on polyvinyl alcohol cryogels.

The present study designed and developed blood vessel substitutes (BVSs) composed of polyvinyl alcohol (PVA) cryogels. The in vitro results demonstrated that the coating of the polymer with lyophilized decellularized vascular matrix (DVM) greatly enhanced the adhesion of human umbilical vein endothelial cells (HUVECs). However, when PVA̸DVM BVSs were implanted into the abdominal aorta of Sprague­Dawley rats, DVM was identified as a highly thrombogenic surface resulting in the mortality of all animals 3­4 days after surgery. By contrast, all rats implanted with PVA survived and were sacrificed after 12 months. The luminal surface of the explanted grafts was completely covered by endothelial cells and the inner diameter was similar to that of the original vessel. In conclusion, the present study indicated that PVA may be considered as a promising biomaterial for the fabrication of artificial vessels.

The endemic paraganglioma syndrome type 1: origin, spread, and clinical expression.

CONTEXT: Anecdotal evidence suggests a high incidence in Trentino, Italy, of head and neck paragangliomas (HNPGL), a rare autosomal dominant disease called paraganglioma type 1 syndrome and caused by germ-line mutations of the SDHD gene. OBJECTIVE: The aim of this study was to investigate the origin, spread, and clinical expression of the disease in this geographic region. DESIGN, SETTING, AND PARTICIPANTS: Trentino natives with HNPGL were recruited for establishing clinical expression of the disease, presence of a founder effect, and age of common ancestor. A large sample of the local population was recruited for determination of mutation prevalence and spread. MAIN OUTCOME MEASURES: SDHD genetic testing was offered to first-degree relatives, and clinical surveillance was offered to at-risk carriers. The hypothesis of a founder effect was explored by haplotype analysis, and time to the most recent common ancestor was estimated by decay of haplotype sharing over time. RESULTS: A total of 287 of the 540 recruited individuals from 95 kindreds carried the SDHD c.341A>G p.Tyr114Cys mutation. The prevalent phenotype was bilateral or multiple HNPGL, with low prevalence of pheochromocytoma and malignant forms. Penetrance was high. A common ancestor was dated between the 14th and 15th century, with the mutation spreading from the Mocheni Valley, a geographic, cultural and, presumably, a genetic isolate to 1.5% of the region's population. CONCLUSIONS: A combination of particular demographic, geographical, and historical conditions has resulted in the oldest and largest SDHD founder effect so far characterized and has transformed a rare disease into an endemic disease with major public health implications.

ECM-based triple layered scaffolds for vascular tissue engineering.

The present study focused on the development of three layered small-diameter (<6 mm) extracellular matrix (ECM)-based vessels. These were engineered artificially through the freeze-drying technique. A layer of decellularized bovine aorta (DAM) was deposited on a mandrel and, after lyophilization, it was dipped into a poly-L-lactide acid (PLLA)/polyethylene glycol (PEG) 2000 dichloromethane solution then quickly wrapped with a pre-prepared thin DAM sheet. Mechanical properties of three-layered scaffolds were evaluated by means of uniaxial tensile measurement. Furthermore, human endothelial and smooth muscle cells were seeded on internal and external scaffold surfaces, respectively, and co-cultured for 7 days. Our results demonstrate that i) ECM components provide suitable stimuli for cell adhesion and proliferation, ii) the microporous intermediate PLLA/PEG2000 layer is responsible for the scaffold resistance and iii) the layered deposition technique can be considered a valuable method to obtain layered vascular scaffolds of different sizes and with a good compromise between stiffness and elasticity for optimal cell organization.

Decellularized bovine reinforced vessels for small-diameter tissue-engineered vascular grafts.

The aim of the present study was to investigate the influence of a decellularization protocol on the structure and the mechanical behavior of small-diameter (<6 mm) tibial calf arteries and veins. Calf vessels were decellularized by a detergent-enzymatic method (DEM), partially hydrolyzed with trypsin and subsequently cross-linked using poly(ethylene glycol) diglycidyl ether. Our results showed that i) the DEM can be considered a simple and valuable procedure for the preparation of complete acellular arteries and veins able to preserve a high degree of collagen and elastic fibers, and ii) poly(ethylene glycol) diglycidyl ether cross-linking treatment provides appropriate mechanical reinforcement of blood vessels. Histologically, the decellularized vessels were obtained employing the detergent-enzymatic procedure and their native extracellular matrix histoarchitecture and components remained well preserved. Moreover, the decellularization protocol can be considered an effective method to remove HLA class I antigen expression from small-diameter tibial calf arteries and veins. Cytocompatibility of decellularized cross-linked vessels was evaluated by endothelial and smooth muscle cell seeding on luminal and adventitial vessel surfaces, respectively.

Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status.

PURPOSE: The aim of the present study was to evaluate factors predicting the recurrence pattern after the administration of temozolomide (TMZ), initially concurrent with radiotherapy (RT) and subsequently as maintenance therapy, which has become standard treatment for patients with newly diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Ninety-five patients with newly diagnosed GBM were treated with RT plus TMZ (75 mg/m(2)/d) followed by maintenance TMZ cycles (150 to 200 mg/m(2) for 5 days every 28 days). Assessable MGMT methylation status and magnetic resonance imaging follow-up were mandatory in all cases. RESULTS: After a median follow-up of 18.9 months (range, 6.6 to 44.8 months), 79 patients (83%) had recurrence: inside the RT field in 57 patients (72.2%), outside in 17 patients (21.5%), and at RT margin in five patients (6.3%). MGMT status was correlated with the site of recurrence, which occurred inside, or at the margin of, the RT field in 51 patients (85%) with MGMT unmethylated status and in 11 patients (57.9%) with MGMT methylated status (P = .01). Recurrences outside the RT field occurred after a longer time interval than those inside the RT field (14.9 v 9.2 months, P = .02). CONCLUSION: After the administration of TMZ concomitant with and adjuvant to RT in patients with GBM, the pattern of, and time to, recurrence are strictly correlated with MGMT methylation status.

Hippocampal remodelling after MDMA neurotoxicity: a single case study.

Acute ingestion of MDMA (ecstasy) causes a transient marked increase in serotonin and dopamine at central synapses. Recent studies demonstrated that MDMA induces damage of serotonergic nerve terminals and alters hippocampal processing. Pronounced cognitive deficits in MDMA users affect learning and memory abilities. This pattern of predominant and long-lasting memory dysfunction suggests that the functioning of the hippocampus might be affected by the neurotoxic effects of MDMA. We present the case of a 16-year-old girl who developed an acute organic and psychotic syndrome caused by occasional use of low to moderate dose of MDMA. Serial neuroimaging ((18)F-FDG-PET and brain MRI) were correlated with her neurocognitive performance and clinical evolution. The structural and metabolic changes correlated with a severe cognitive impairment. After 16 months of intensive neuropsychological rehabilitation she showed significant improvement in hippocampal-related memory cognitive functions, which correlated with normalization of her (18)F-FDG-PET and remarkable hippocampal remodelling. This case report indicates that even non-chronic MDMA use may cause subacute toxic encephalopathy in which the clinical evolution is paralleled by neuroimaging changes in specific cerebral areas. The most relevant aspect is the reversibility of the volumetric changes, which may be the structural correlate of an ongoing hippocampal remodelling.

Does the type of carotid artery closure influence the management of recurrent carotid artery stenosis? Results of a 6-year prospective comparative study.

OBJECTIVE: The purpose of the study was to evaluate the results of reoperative surgery and carotid artery stenting (CAS) in cases of recurrent carotid artery stenosis (RCS) and to compare the results of all RCS (reoperative surgery + CAS) with primary carotid endarterectomy (CEA) performed during the study period. SUMMARY BACKGROUND DATA: Consensus has not yet been established on the best treatment for RCS. Recently CAS has emerged as a potential alternative to carotid endarterectomy. METHODS: A 6-year (Jan 2000-Dec 2005) prospective study was performed. Eligible patients were those with symptomatic or asymptomatic RCS > or = 80% at a preoperative angiography or angio-computed tomography. The carotid plaques were classified at a preoperative ultrasonographic scan, according to the five type classification proposed by Geroulakos (Br J Surg 1993;80:1274-7). Patients with type 1 and 2 carotid plaque were not considered for CAS. RESULTS: 56 patients were enrolled. Fifteen patients with a type 1-2 plaque underwent reoperative surgery, 41 with type 3-4 plaque underwent CAS. In 90.6% of primary closure a type 3-4 carotid plaque was found; a type 1-2 was observed in 84.5% of the polytetrafluoroethylene patch closure group. No statistical difference for the 30-day and the 6 year stroke-free rate was observed; similarly no differences emerged between all RCS (reoperative surgery + CAS) performed and primary CEA. CONCLUSIONS: CAS is an acceptable alternative to surgery in the management of RCS. An accurate patient selection is required. Restenosis after CEA and direct closure is mostly associated with fibrous material. In these cases CAS might be the best choice.

Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study.

OBJECTIVES: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. METHODS: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m(2)/daily for 5 days every 4 weeks. RESULTS: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%), respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7-31%). CONCLUSION: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.