X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

Quantitative 3D investigation of Neuronal network in mouse spinal cord model.

The investigation of the neuronal network in mouse spinal cord models represents the basis for the research on neurodegenerative diseases. In this framework, the quantitative analysis of the single elements in different districts is a crucial task. However, conventional 3D imaging techniques do not have enough spatial resolution and contrast to allow for a quantitative investigation of the neuronal network. Exploiting the high coherence and the high flux of synchrotron sources, X-ray Phase-Contrast multiscale-Tomography allows for the 3D investigation of the neuronal microanatomy without any aggressive sample preparation or sectioning. We investigated healthy-mouse neuronal architecture by imaging the 3D distribution of the neuronal-network with a spatial resolution of 640 nm. The high quality of the obtained images enables a quantitative study of the neuronal structure on a subject-by-subject basis. We developed and applied a spatial statistical analysis on the motor neurons to obtain quantitative information on their 3D arrangement in the healthy-mice spinal cord. Then, we compared the obtained results with a mouse model of multiple sclerosis. Our approach paves the way to the creation of a "database" for the characterization of the neuronal network main features for a comparative investigation of neurodegenerative diseases and therapies.

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Dynamics of allograft fibrosis in pediatric liver transplantation.

Progressive liver allograft fibrosis (LAF) is well known to occur long term, as shown by its high prevalence in late posttransplant liver biopsies (LBs). To evaluate the influence of clinical variables and immunosuppression on LAF progression, LAF dynamic was assessed in 54 pediatric liver transplantation (LT) recipients at 6 months, 3 and 7 years post-LT, reviewing clinical, biochemical data and protocol LBs using METAVIR and the liver allograft fibrosis score, previously designed and validated specifically for LAF assessment. Scoring evaluations were correlated with fibrosis quantification by morphometric analysis. Progressive LAF was found in 74% of long-term patients, 70% of whom had unaltered liver enzymes. Deceased grafts showed more fibrosis than living-related grafts (p = 0.0001). Portal fibrosis was observed in correlation with prolonged ischemia time, deceased grafts and lymphoproliferative disease (p = 0.001, 0.006 and 0.012, respectively). Sinusoidal fibrosis was correlated with biliary complications (p = 0.01). Centrilobular fibrosis was associated with vascular complications (p = 0.044), positive autoantibodies (p = 0.017) and high gamma-globulins levels (p = 0.028). Steroid therapy was not associated with reduced fibrosis (p = 0.83). LAF could be viewed as a dynamic process with mostly progression along the time. Peri- and post-LT-associated factors may condition fibrosis development in a specific area of the liver parenchyma.

Novel histologic scoring system for long-term allograft fibrosis after liver transplantation in children.

The existing systems for scoring fibrosis were not developed to evaluate transplanted livers. Our aim was to design and validate a novel fibrosis scoring system specifically adapted to assess liver allograft fibrosis (LAF). Clinical data, histology, transient elastography (TE) and AST/platelet ratio index (APRI) were reviewed in 38 pediatric liver transplant (LT) recipients. Protocol liver biopsies performed at 6 months and 7 years post-LT were reviewed by three pathologists who assessed LAF using the METAVIR and Ishak systems. LAF was also scored separately in portal (0-3), sinusoidal (0-3) and centrolobular areas (0-3). Scoring evaluations were correlated with fibrosis quantification using morphometry, and also with TE and APRI. Statistical correlations between morphometry and METAVIR were 0.571 (p < 0.000) and 0.566 (p < 0.000) for the Ishak system. The novel score (0-9) for separate assessment of portal, sinusoidal and centrolobular fibrosis showed a better correlation with morphometry (0.731; p < 0.000) and high intra-/interobserver agreement (0.966; p < 0.000 and 0.794; p < 0.000, respectively). No correlation was found between TE or APRI and morphometry or the three histologic scores. In conclusion, this novel semiquantitative fibrosis scoring system seems to more accurately reflect LAF than the existing scoring system and may become a practical tool for staging fibrosis in LT.

[Neuroimaging and definition of transient ischemic attack]. / Neuroimaging e definizione di attacco ischemico transitorio.

AIM: Transient ischemic attack (TIA) has to be considered an "alarm bell" of a more or less severe organic or systemic vasculopathy. Positive findings at neuroimaging means tissue damage. The purpose of this retrospective study was to assess the role of neuroimaging in the management of patients presenting with TIA, and to consider the relative implications. METHODS: In a consecutive series of 82 patients (53 males, 29 females, mean age: 65.9±13.1 years) admitted for TIA, it was possible to review the history and the clinical data of 66 patients, including ABCD2 score, laboratory including plasmatic D-dimer, and neuroimaging data including computed tomography (CT) and magnetic resonance imaging including diffusion-weighted with apparent diffusion coefficient measure (DWI-ADC) obtained at diagnosis and by a week later (16 by CT, and 50 by DWI-ADC). Thirty-three patients underwent DWI-ADC within 24 hours from symptoms onset. Statistical analysis has been performed by non-parametric tests (χ2 and Mann-Whitney), and logistic regression by a commercially available software. RESULTS: CT and/or DWI-ADC showed signs of acute ischemic lesions in 23/66 (35%) patients. 12 out of the 35 patients with a 24-hour DWI-ADC follow-up were positive. Statistical analysis showed that positive neuroimaging was significantly associated only with familial history of cardiovascular diseases (P<0.012) and previous TIA/stroke (P<0.046). CONCLUSION: In this patients series, at least 35% of patients with TIA had a positive neuroimaging, especially DWI-ADC. Positive neuroimaging seems an independent factor. Patients with TIA need an early assessment by neuroimaging including DWI-ADC, in order to obtain a correct classification and prognosis.

CT and MRI of Wernicke's encephalopathy.

The purpose of this pictorial essay is to present the computed tomography (CT) and magnetic resonance imaging (MRI) findings of Wernicke's encephalopathy, a rare, severe, acute neurological syndrome due to thiamine (vitamin B1) deficiency, associated with high morbidity and mortality. The classical clinical triad, which includes ocular signs, altered consciousness and ataxia, can be found in only one-third of patients. Although chronic alcoholic patients are the most commonly affected, Wernicke's encephalopathy may complicate malnutrition conditions in nonalcoholic patients, in whom it is greatly underestimated. CT and above all MRI of the brain play a fundamental role in diagnosing the condition and ruling out other diseases. MRI is the most sensitive technique and is required in all patients with a clinical suspicion of Wernicke's encephalopathy. Medial thalami, mamillary bodies, tegmentum, periaqueductal region, and tectal plate are typical sites of abnormal MRI signal. The dorsal medulla, red nuclei, cranial nerve nuclei, cerebellum, corpus callosum, frontal and parietal cerebral cortex are less common sites of involvement although they are more frequently affected in nonalcoholic patients. Paramagnetic contrast material may help to identify lesions not otherwise visible.

Coaxial biopsy during percutaneous vertebroplasty in patients with presumed osteoporotic vertebral compression fractures: retrospective review of biopsy results.

PURPOSE: This study retrospectively analysed the results of biopsies obtained during percutaneous vertebroplasty (PVP) in patients with presumed osteoporotic vertebral compression fractures, with a view to highlighting the importance of coaxial biopsy in determining the aetiology of vertebral fractures and planning subsequent treatment. MATERIALS AND METHODS: Between November 2003 and March 2009, 98 patients (78 women; 20 men) with a clinical and imaging suspicion of osteoporotic vertebral compression fractures underwent coaxial biopsy in conjunction with PVP of the thoracic and lumbar vertebrae. Mean age at the time of the procedure was 72.6 years. A pathologist interpreted all the biopsy samples. RESULTS: In 83 patients, the biopsy results were consistent with the presumed osteoporotic aetiology. In two patients, a malignancy was identified. Biopsy samples from 13 patients were considered insufficient or unsuitable by the pathologist for evaluation. CONCLUSIONS: Despite the number of biopsy samples considered insufficient or unsuitable, coaxial biopsy during PVP is useful in verifying the presumed aetiology of vertebral compression fractures, which is often unclear on the basis of clinical and imaging examinations. It is therefore both convenient and advisable to perform a vertebral coaxial biopsy in all patients undergoing a PVP.

No-touch hepatic hilum technique to treat early portal vein thrombosis after pediatric liver transplantation.

A 'no-touch' hilum technique used to treat early portal vein complications post-liver transplantation in five children with body weight <10 kg is described. Four patients developed thrombosis and one portal flow absence secondary to collateral steal flow. A vascular sheath was placed through the previous laparotomy in the ileocolic vein (n = 2), inferior mesenteric vein (n = 1) or graft umbilical vein (n = 1). Portal clots were mechanically fragmented with balloon angioplasty. In addition, coil embolization of competitive collaterals (n = 3) and stent placement (n = 1) were performed. The catheter was left in place and exteriorized through the wound (n = 2) or a different transabdominal wall puncture (n = 3). A continuous transcatheter perfusion of heparin was subsequently administered. One patient developed recurrent thrombosis 24 h later which was resolved with the same technique. Catheters were removed surgically after a mean of 10.6 days. All patients presented portal vein patency at the end of follow-up. Three patients are alive after 5 months, 1.5 and 3.5 years, respectively; one patient required retransplantation 18 days postprocedure and the remaining patient died of adenovirus infection 2 months postprocedure. In conclusion, treatment of early portal vein complications following pediatric liver transplantation with this novel technique is feasible and effective.

[Long term follow-up of bile duct stenosis treated with interventional radiology in pediatric liver transplantation]. / Seguimiento a largo plazo de las estenosis de la vía biliar tratadas con radiología intervencionista en el trasplante hepático pediátrico.

The reported incidence of biliary strictures following pediatric liver transplantation has ranged between 5-34%, with a higher incidence in segmental grafts. Currently, percutaneous transhepatic balloon dilatation of biliary strictures is considered as the first line treatment owing to its minimal invasiveness. Between 1995-2006, 20 children who underwent liver transplantation developed biliary complications treated with interventional radiology. 16/20 developed biliary stricture, of whom 10 were treated with percutaneous transhepatic balloon dilatation. The mean age at the procedure was 6.6 years (range 8 m--14 years). The allograft types included whole (n=4), split (n=3), and reduced (n=3) livers. The procedure was performed at a mean time post-transplantation of 2.6 years. All patients are alive with a mean follow-up post-procedure of 24 months (range: 4 months-11 years). Currently, only 4 have a normal appearing biliary tree by imaging techniques and 6 developed stricture recurrence; of whom 3 developed biliary cirrhosis (2 splits, 1 reduced), one patient underwent successful rescue surgery, one was treated again percutaneously, and the remaining was lost to followup. In conclusion, treatment of percutaneous transhepatic balloon dilatation of biliary strictures is effective avoiding surgical correction. However, stricture recurrence in the medium- long term follow-up is frequent, particularly in segmental grafts. [corrected]

Seguimiento a largo plazo de las estenosis de la vía biliar tratadas con radiología intervencionista en el trasplante hepático pediátrico / No disponible

La incidencia de estenosis de la vía biliar en el trasplante hepático infantil varía entre un 5-34%, y es más acusada en los injertos segmentarios que en los completos. El tratamiento de estas complicaciones mediante radiología intervencionista evita en algunos casos la cirugía. Entre 1995-2006 se han tratado 20 niños con trasplante hepático y complicaciones de la vía biliar con radiología intervencionista. Dieciséis de ellos presentaron estenosis de la vía biliar, de los cuales en 10se corrigió con dilatación percutánea transparietohepática. La edad media de los niños fue de 6,6 años (rango 8 meses-14 años). Los tipos de injerto incluyen 4 completos y 6 parciales (3 splits, 3 reducidos). Las dilataciones se realizaron a una media de 2,6 años postrasplante. Todos los pacientes están vivos, con un seguimiento medio desde la dilatación de 24 meses (rango 4 meses-11 años). Actualmente, solo4 (40%) presentan una vía biliar de características normales por pruebas de imagen y en 6 (60%) ocurrió una recidiva de la estenosis. De estos 6, 3 han desarrollado cirrosis biliar (2 splits, 1 segmentario), un paciente ha requerido corrección quirúrgica, otro se ha vuelto ha dilatar y el paciente restante se le ha perdido el seguimiento. Las dilataciones percutáneas transparietohepáticas en el tratamiento de las estenosis de la vía biliar, inicialmente son efectivas y evitan la corrección quirúrgica. Sin embargo, las reestenosis a medio-largo plazo son frecuentes, en especial en los injertos parciales (AU)

Incidence of bile duct strictures in the paediatric liver transplant ranges from 5-34%, and is most pronounced in segmental grafts that complete. The treatment of these complications avoided in most cases surgery. Between 1995-2006 have been treated 20 children with liver transplantation and bile duct complication with interventional radiology. Sixteen of them were suffering from bile duct strictures of which 10 were corrected with percutaneous dilation. The average age of children was6.6 years (range 8 months-14 years). The types of graft include 4 complete and 4 partial (3 splits, reduced 3). The dilatation was made at an average of 2.6 years after transplant. All patients are alive, with a mean follow-up from the dilation of24 months (range 4 months-11 years). Currently, only 4 (40%) have a normal bile duct by imaging techniques and 6 (60%) have had a recurrence of biliary strictures. Of these, 3 have developed biliary cirrhosis(2 splits, segmental 1), two patient have required surgical correction, another has been delayed again and the remaining patient has been lost monitoring. The percutaneous dilation in the treatment of strictures of the bileduct is initially effective avoiding surgical correction. However there strictures medium-long term are frequent (AU)

Vasospasm and cerebral infarction from pituitary apoplexy. A case report.

Pituitary apoplexy is a potentially life-threatening acute or subacute clinical syndrome occurring from enlargement of the pituitary gland, and pituitary insufficiency, from hemorrhage or ischemia from an unknown pituitary lesion, most frequently being a non-functioning macroadenoma. A close, and multidisciplinary management is required. The purpose of this case report is to increase awareness to pituitary apoplexy presentation and management by reporting clinical features and neuroradiological findings observed in a 70-year-old patient with an unknown pituitary lesion. He presented with pituitary apoplexy and brain ischemia at magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. MR angiography (MRA) showed diffuse vasospasm of anterior and posterior circulation. Both MRI and cytochemical examination of the cerebrospinal fluid ruled out subarachnoid hemorrhage. Due to concomitant diseases, and absence of visual deficit, the management was conservative by medical and substitutive therapy, without surgery. Clinical follow-up showed clearcut improvement, and this was consistent with MRI and MRA evidence of vasospasm regression, and clearcut pituitary lesion shrinkage. Pituitary lesions with hemorrhagic infarction presenting with pituitary apoplexy may be associated with vasospasm and brain ischemia at diagnosis, also in the absence of subarachnoid hemorrhage. A correct MR evaluation of patients with PA should include DWI, ADC maps, and MRA. Notably, early diagnosis of PA-associated vasospasm and cerebral ischemia avoids the possibility of their detection only after neurosurgery.

L-2 Hydroxyglutaric Aciduria: Magnetization Transfer Contrast and Diffusion Weighted Magnetic Resonance Imaging Findings. A case Report.

We describe the case of a 13-year-old male with ù aciduria. Conventional magnetic resonance imaging and diffusion weighted imaging disclosed some previously unreported findings. In particular, we observed an almost total sparing of early myelinated regions, and a restricted diffusion pattern in the dentate nuclei. Magnetization transfer contrast showed a normal range of values in early myelinated regions, and revealed abnormal values in the subcortical temporal white matter, internal capsule and globi palladi.

Is CT still useful in the study protocol of retinoblastoma?

BACKGROUND AND PURPOSE: Intralesional calcium deposition is considered a key element for differentiating retinoblastoma from simulating lesions. Our aim was to assess whether MR imaging associated with ophthalmologic investigations (ophthalmoscopy and ultrasonography) could replace CT in the detection of diagnostic intralesional calcifications in retinoblastoma. MATERIALS AND METHODS: Ophthalmoscopic findings, MR images, CT scans, and histologic examination of 28 retinoblastomas from 23 consecutive children (11 males, 12 females; age range at admission, 1-35 months; mean age, 11 months; median age, 9 months) were retrospectively evaluated. Ultrasonography was performed in 18 patients with 21 retinoblastomas. MR imaging included T2-weighted spin-echo and gradient-echo images, fluid-attenuated inversion recovery images, and T1-weighted spin-echo images with and without contrast enhancement. Clinical data were integrated with MR imaging data to evaluate the utility of both approaches to discover calcifications; particularly, a correlation between intralesional signal-intensity void spots on MR imaging and hyperattenuating areas on CT scans was performed. RESULTS: Ophthalmoscopy detected calcifications in 12 of 28 eyes (42.85%). Ultrasonography detected calcifications in 20 of 21 eyes (95.23%). CT showed hyperattenuating intralesional areas consistent with calcifications in 27 of 28 eyes (96.42%). MR imaging showed intralesional signal-intensity void spots in 25 of 28 eyes (89.28%). All spots detected with MR imaging matched the presence of calcifications on CT scans. Gradient-echo T2*-weighted and fast spin-echo T2-weighted images showed the highest degree of correlation with CT. When we put together ophthalmoscopy, ultrasonography, and MR imaging data, no calcifications detected on CT were missed, and the differential diagnosis was thorough. CONCLUSIONS: A combination of clinical data and MR images may remove potentially harmful ionizing radiation from the study protocol of retinoblastoma.

Impact of valganciclovir on Epstein-Barr Virus polymerase chain reaction in pediatric liver transplantation: preliminary report.

UNLABELLED: Preemptive therapy with ganciclovir has been recommended in the pediatric liver transplant strategy to avoid the development of posttransplant lymphoproliferative disorder (PTLD) from an high Epstein-Barr virus (EBV) is detected. We sought viral load to analyze the response to preemptive therapy with valganciclovir (VGC) in children with liver transplantations and an high quantitative EBV-PCR. METHODS: From June 2005 to December 2007, we tested 979 EBV-PCR among 80 pediatric liver transplant recipients, from those 21/80 PCR were tested from the date of transplantation and 59/80 belonged to the historical cohort (7/59 had a prior history of PTLD). Patients were divided into 2 groups depending upon whether they did (n = 22) or did not (n = 19) receive VGC treatment. The response to VGC was considered complete, if the PCR was negative at 30 and 60 days of treatment; and partial, when the PCR decreased at least 50%. Ganciclovir blood levels tested in 109 cases instances and correlated with the EBV-PCR. RESULTS: A total of 369 (33%) positive PCR were detected in 36/80 patients (mean, 75,000 copies; range = 5000-4,200,000). Among the 22 episodes treated for 30 days, 34% showed complete responses, 41%, partial, and 23%, no response. Among the non-treated group the rates were 6%, 25%, and 68%, respectively (P = .01). However, no differences were observed among those episodes treated for 60 days. At the administered doses, hardly any patient reached the recommended ganciclovir therapeutic level at 2 hours (6 micro/mL). However, the mean PCR was lower when the ganciclovir levels were greater than 4 mg/L when compared with lower levels (P = .03). CONCLUSION: After 30 days of treatment there was a response to VGC in the EBV viral load. There was high interpatient variability of ganciclovir serum concentrations, suggesting the need for pharmacokinetic monitoring to optimize treatment. There was a relationship between the concentration of ganciclovir and the EBV viral load.

Total occlusion of a conus medullaris pial arteriovenous malformation obtained with one session of superselective embolization.

The authors report about a case of the endovascular treatment of a pial arteriovenous malformation (AVM). The lesion was located on the conus medullaris. This injury is a rare spinal AVM. The diagnostic management and surgical treatment was chosen with a collaboration between neurosurgeons and neuroradiologists. The diagnostic management was based on clinical validation and magnetic resonance with angiographic technique as a gold standard. With regard to the surgical treatment of spinal AVM, endovascular and radiotherapy is a decision which should be taken multidisciplinarily. The treatment is crucial in resolving this lesion. The authors describe the case of a 38-year-old girl with clinical findings of progressive radiculomedullary ischemic process caused by the presence of spinal AVM. The angiographic images showed a pial AVM of the conus medullaris fed by an anterior radiculomedullary artery (Adamckiewiz artery) originated from a left T11 dorsospinal artery and by a posterior radiculopial artery originated from the left L1 artery. The draining veins were posterior pial veins, and accessory anterior subpial veins. Even if the first treatment of a pial arteriovenous malformation (AVM) of conus medullaris can be the surgical treatment for posterior localization, a neurointerventional angiographic and modern materials make it possible to reach pial AVMS of conus medullaris avoiding surgery. The authors describe a successful treatment of conus medullaris arteriovenous malformation with a one session of superselective embolization.

Percutaneous vertebroplasty: the follow-up.

PURPOSE: This article reports on our experience treating vertebral fractures with percutaneous vertebroplasty. A clinical and imaging follow-up designed to identify the early (especially pulmonary embolism of bone cement) and late complications of the technique is proposed. MATERIAL AND METHODS: On the basis of the current guidelines, 101 patients were selected: 64 osteoporotic and 37 neoplastic. A total of 173 vertebrae were treated. Procedures were performed with both computed tomography and fluoroscopic guidance. Residual pain was evaluated with a visual analogue scale score immediately after vertebroplasty and 1, 15, 30, 90, 180 and 270 days later. Spine and chest radiographs were obtained 24 h after vertebroplasty; spine radiography was repeated 30 days later. RESULTS: Therapeutic success was obtained in 88% of osteoporotic patients and in 84% of neoplastic patients. Pulmonary cement emboli were identified in four patients, all of whom were asymptomatic. CONCLUSIONS: Percutaneous vertebroplasty is a safe and effective technique for the treatment of osteoporotic and neoplastic vertebral fractures. Clinical and imaging followup allows effective patient monitoring and early detection of possible complications.