A solution based on melatonin, tryptophan, and vitamin B6 (Melamil Tripto©) for sedation in newborns during brain MRI.

INTRODUCTION: Melatonin has been studied and used for several years as a sleep-wake cycle modulator in patients with sleep disorders. Experimental evidence has demonstrated the multiple neuroprotective benefits of this indoleamine secreted by the pineal gland. Melatonin is also used in neurological investigations, for its ability to induce sleep in children. In fact, it favors falling asleep during electroencephalogram, Magnetic Resonance Imaging (MRI), and during brainstem auditory evoked potentials. Previous studies are focused on infants and children. No investigation have been performed in neonates, before or during instrumental assessments. MATERIAL AND METHODS: One hundred ten newborns (term and preterm) undergoing brain MRI were enrolled in the study. Thirty minutes before the planned time for the examination, we administered a single dose solution of melatonin- tryptophan-vitamin B6. Twenty minutes after the initial administration of 2 mg, a second dose of 1 mg was administered, if the baby was still awake. If after further 15 min the baby was still not sleeping, an additional dose of 1 mg was administered. RESULTS: In 106 patients we obtained adequate sedation without adverse events, allowing us to perform an adequate quality MRI, with a median time of 25 min to reach sleeping. Only in three patients MRI could not be performed. In patients having a large weight, higher doses of melatonin were necessary to reach sleeping. Considering the pro kg dose of melatonin, the average dose that induced sleepiness in neonates was 0,64 ± 0.16 mg/Kg. CONCLUSION: A solution based on Melatonin- tryptophan-vitamin B6 can be a helpful sedative to administer to neonates undergoing brain MRI, avoiding the use of anesthetics and achieving adequate assessments.

Phlebographic study does not show differences between patients with MS and control subjects.

BACKGROUND AND PURPOSE: Hypothetical correlation between chronic cerebrospinal venous insufficiency and MS has gained the attention of patients and the scientific community. Studies performed by echo-color Doppler ultrasonography have shown different results, and it is necessary to use more objective diagnostic techniques. The aim of our study was to evaluate the presence of stenoses affecting azygos veins and internal jugular veins by use of venography in patients with MS. MATERIALS AND METHODS: We recruited 2 groups of subjects who underwent venography: the study group included 29 patients with MS and the control group included 15 healthy volunteers. The ileo-lumbar plexus, the azygos, and the internal jugular veins were selectively catheterized. We considered any cross-sectional area reduction of the venous lumen >50% to be a significant stenosis. Furthermore, blood pressure was measured in the studied vessels at the stenotic internal jugular veins. RESULTS: Selective venography showed at least 1 significant venous stenosis in 84% of subjects examined, without significant difference between the study group and the control group. Positive venography chronic cerebrospinal venous insufficiency patterns were found in 50% of all subjects examined, without any significant difference between the 2 groups. The multivariate logistic regression analysis failed to assess any significant association between the presence of a positive venography and MS condition. The difference between the median blood pressure of stenotic and nonstenotic internal jugular veins was not statistically significant (P = .46). CONCLUSIONS: Our data exclude any direct correlation between chronic cerebrospinal venous insufficiency and MS because venous abnormalities were equally present in both groups.

Endovascular management of acute stroke.

Ischemic stroke is the third leading cause of death and most common cause of permanent disability in industrialized nations. Eighty-five percent of strokes are ischemic in nature, with an associated mortality between 53% and 92%. The focus of treatment for acute stroke starts with prompt and accurate diagnosis of ischemic brain tissue at risk, followed by time sensitive delivery of therapy that effectively and safely restores flow to that vascular territory. Time-dependent reperfusion therapy is the only proven treatment for Acute Ischemic Stroke. In this paper, we review the clinical and imaging factors that are relevant to guide endovascular treatment decisions; the different approaches of stroke therapy and the devices used with the goal of obtaining the most rapid and complete recanalization possible, while minimizing vascular damage and hemorrhagic complications. It is paid particular attention to indications and outcomes of the different endovascular stroke therapy devices use, as defined in major clinical trials or current clinical practice. Anterior circulation strokes represent the primary focus of this review.

Prevalence study of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: preliminary data.

PURPOSE: This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). MATERIAL AND METHODS: From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI. RESULTS: CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089). CONCLUSIONS: In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

A diffusion longitudinal MR imaging study in normal-appearing white matter in untreated relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Our aim was to evaluate the hypothesis that water diffusion alterations are present in normal-appearing white matter of patients with relapsing-remitting multiple sclerosis (RRMS) and to assess their change with time. MATERIALS AND METHODS: Fifty-four subjects with clinically diagnosed RRMS, with disease duration of less than 12 months and an expanded disability status scale (EDSS) score of <3.5, underwent a diffusion 3T MR imaging study. The apparent diffusion coefficient (ADC) maps generated were compared with those of 18 control subjects. Eighteen of the 54 patients underwent MR imaging assessment at 3 and 6 months after baseline evaluation. Remitting patients were clinically and MR imaging stable for the 2 months before the study. All patients were drug-free for the 3 months before the study, and in the relapsing patients, the MR imaging was always performed before beginning treatment. RESULTS: Mean ADC values showed significant differences when relapsing, remitting, and control patients were compared. The relapsing or remitting phase showed significant difference when compared both with controls (P < .01) and between them (P < .05). Comparing mean ADC values of patients with clinical disability (EDSS <2 versus EDSS >/=2) also provided significant differences with the control group (P < .01). The data of patients showing a relapsing episode during the longitudinal part of the study showed a significant difference compared with data from their remitting phase (P < .01). CONCLUSION: Brain microstructural changes can be detected and correlate with clinical impairment during the stages of MS. These changes modify with time in the relapsing group.

Evaluation of basal ganglia haemodynamic changes with perfusion-weighted magnetic resonance imaging in patients with Parkinson's disease.

PURPOSE: The aim of our study was to assess the regional cerebral blood flow (rCBF) of basal ganglia and thalami in patients with Parkinson's disease (PD) using perfusion-weighted magnetic resonance imaging (PW-MRI). MATERIAL AND METHODS: Twenty subjects affected by idiopathic PD according to the United Kingdom Brain Bank criteria were enrolled in the study. Twenty normal subjects matched for age and gender were included as controls. After 20-day therapy withdrawal, the PD patients underwent PW-MRI. The rCBF was calculated both in patients and in controls. The regions of interest were manually positioned on rCBF maps over the caudate nucleus, the putamen, the external and internal globus pallidus, and over the ventrolateral nucleus of the thalamus. Data were normalised with those obtained from parieto-occipital white matter (POWM). Statistical analysis was performed using a parametric ANOVA test. RESULTS: Patients showed a significant (p<0.01) interhemispheric asymmetry; rCBF values were higher on the more severely affected side. Controls showed no interhemispheric asymmetry. CONCLUSION: Our study suggests that PW-MRI is a valuable tool for assessing haemodynamic changes in PD patients. Haemodynamic change pattern may be useful in the early diagnosis of PD.

Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer.

To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the hemostatic system in patients with solid tumors, we studied patients with locally advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for 21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone (group 1) or in combination with Tam (group 2). One additional group received Tam alone. Plasma samples were evaluated for hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control subjects. During treatment, in the patients given ATRA alone, hypercoagulation markers appeared unmodified. Instead, subjects given Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam groups, hypercoagulation markers were decreased compared with Tam alone. These results suggest that in selected conditions, pre-operative ATRA may modulate the hypercoagulable state of breast cancer patients.

The risk of thrombosis in patients with lupus anticoagulants is predicted by their specific coagulation profile.

Lupus anticoagulants belong to the family of antiphospholipid antibodies. They include two phospholipid-dependent inhibitors of coagulation that may be distinguished on the basis of specific coagulation profiles generated from the comparison of the ratios of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): when the ratio of the KCT exceeds that of the dRVVT, the plasma is allocated to the "KCT" coagulation profile, when the opposite occurs, the plasma is defined to belong to the "dRVVT" coagulation profile group. We prospectively followed-up a historical cohort of 100 consecutive patients with lupus anticoagulants referred to our Institution between January 1988 and October 1997 to investigate the relationship between their coagulation profile at diagnosis and the development of thrombosis during a median follow-up time of 37.5 months (range 1-115 months). Fifty-six patients were allocated to the "dRVVT" coagulation profile, whereas the other 44 displayed the "KCT" profile. Lupus anticoagulants were transient in 17 patients, without differences between the two groups. None of these patients developed clinical events before disappearance of the phospholipid-dependent inhibitors of coagulation. The 83 cases with persistent lupus anticoagulants consistently displayed the same coagulation profile they had been allocated to at entry. Fourteen patients developed 18 thromboembolic events during the follow-up, with an overall rate of thrombosis of 4.2% patients-year. Twelve of them belonged to the "dRVVT" coagulation profile, whereas the other 2 to the "KCT" profile (p = 0.03). The "dRVVT" coagulation profile gave an odds ratio of thrombosis of 5.25 (95% confidence interval [C.I]: 1.17-23.50). Ten of the 14 patients who developed thrombosis during follow-up had already experienced thrombosis: a previous thrombotic event caused an odds ratio of recurrency of 2.72 (95% C.I.: 0.85-8.73) (p = 0.09). By multivariate analysis, the "dRVVT" coagulation profile was still associated with a trend to a higher risk of thrombosis, but the difference did not reach statistical significance. Increased levels of anticardiolipin antibodies (> 40 GPL and/or MPL units) were found in all the 14 patients (p = 0.0064). The "KCT" coagulation profile was significantly associated (p = 0.005) with moderate thrombocytopenia (platelets 50-150 X 10(9)/l). Neither profile was found to represent a risk factor for the development of recurrent miscarriages, neoplastic diseases and death. In conclusion, the "dRVVT" profile appears to have predictive value with respect to the thrombotic complications suffered by patients with antiphospholipid antibodies.

Granulocyte colony-stimulating factor following peripheral-blood progenitor-cell transplant in non-Hodgkin's lymphoma.

PURPOSE: To compare the hematologic recovery after high-dose chemotherapy and circulating peripheral-blood progenitor-cell (PBPC) transplant between patients who received recombinant human granulocyte colony-stimulating factor (G-CSF) (treated group) and those who did not (control group). PATIENTS AND METHODS: From December 1992 through June 1994, two sequential and consecutive cohorts of 20 patients each with histologically proven non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (carmustine [BCNU], cytarabine [Ara-C], etoposide and melphalan [BEAM]) followed by PBPC transplant. The first 20 patients were treated with G-CSF (5 micrograms/kg/d) after PBPC administration. Since the time of platelet and leukocyte recovery in this group was short (< 15 days), with a narrow standard deviation from the mean value, the last 20 patients were not given G-CSF. Hematologic recovery, number of febrile days, rate of documented infections, number of hospital days, duration of gastrointestinal complications, platelet and RBC transfusions, and antibiotic requirements were compared in the two groups. RESULTS: The two groups of patients were comparable according to disease status, histology, stage, bulky disease bone marrow involvement, elevated lactate dehydrogenase (LDH) level, and median number of infused CD34+ cells and colony-forming units granulocyte-macrophage (CFU-GM). The median time to reach 0.5 x 10(9)/L and 1.0 x 10(9)/L neutrophils was 2 days shorter in G-CSF group, but this difference was not statistically significant. The median times to reach 20 x 10(9)/L and 50 x 10(9)/L platelets were, respectively, 10 and 14 days in the G-CSF group and 11 and 16 days in the control group, but again this was not statistically significant. Moreover, when considering clinically relevant end points including the number of documented infections and antibiotic requirements, platelet transfusions, gastrointestinal toxicity, and days of hospitalization, no differences were demonstrated between the two groups. CONCLUSIONS: Provided an optimal dose of circulating progenitors is infused, NHL patients transplanted with PBPC do not benefit by the administration of hematopoietic growth factors.

Hemostatic system activation in patients with lupus anticoagulant and essential thrombocythemia.

Hemostatic system activation was estimated in the plasmas of 39 patients with LAC and 19 patients with ET by measuring concentrations of TAT complex and prothrombin F1+2. The concentrations of FVII, recognized previously as a risk factor for arterial thrombosis, were also measured. None of the patients had active thrombosis during this study. The mean TAT and F1+2 levels in LAC and ET plasmas were higher than the respective values in the plasmas of healthy control subjects. Compared with their respective controls, TAT levels were significantly higher in the LAC group (P < 0.05) and F1+2 was significantly higher in the ET group (P < 0.005). The mean FVIIt and FVIIz was significantly higher (P < 0.05 and P < 0.01, respectively) in LAC than control plasmas. Furthermore, the differences between FVIIt and FVIIz were significantly greater in LAC than control plasmas, indicating increased in vivo proteolysis of FVII in LAC. Although the mean concentrations of these two FVII parameters in ET plasma were not significantly different from those of normal plasmas, the FVII levels were higher in 30% of ET plasmas than the upper limit of controls. Our results are consistent with hypercoagulation in LAC and ET patients, and this may be a contributory factor for the increased rates of thrombosis associated with the two conditions.