Do Repeat Intradetrusor Botulinum Toxin Type A Injections Yield Valuable Results? Clinical and Urodynamic Results after Five Injections in Patients with Neurogenic Detrusor Overactivity

OBJECTIVES: To study repeat intradetrusor botulinum toxin injections for the treatment of neurogenic detrusor overactivity in terms of safety and improvement of continence status and urodynamic parameters. MATERIAL AND METHODS: This study was based on 20 consecutive patients (13 males, 7 females; median age, 41.1 yr) who received at least five intradetrusor injections of botulinum toxin and who were followed by clinical and urodynamic evaluation after at least four injections. The results of 100 injections and corresponding follow-ups were analyzed and compared with baseline. RESULTS: No toxin-related side effects were observed after the first or repeat injections. All patients had a baseline urodynamic study and at least four urodynamic studies after botulinum toxin injections. Clinical continence improved significantly after the first injection and then remained constant after repeat injections. The median reflex volume increased significantly from a median of 200 ml at baseline to values between 440 and 500 ml at follow-up studies. The presence of neurogenic detrusor overactivity decreased significantly by 60-75%. Maximum cystometric capacity increased significantly 2.3-fold. Maximum detrusor pressure during cystometry decreased significantly 5.8-fold from a median of 70 cm H(2)O to values of about 20 cm H(2)O. Median compliance at baseline (60 ml/cm H(2)O) did not change significantly. CONCLUSION: Repeat intradetrusor botulinum toxin A injections are a safe and valuable treatment option for neurogenic detrusor overactivity over a period of several years. The beneficial effect of the toxin on clinical and urodynamic parameters remains constant after repeat injections.     

Brain systems mediating semantic and syntactic processing in deaf native signers: Biological invariance and modality specificity

Studies of written and spoken language suggest that nonidentical brain networks support semantic and syntactic processing. Event-related brain potential (ERP) studies of spoken and written languages show that semantic anomalies elicit a posterior bilateral N400, whereas syntactic anomalies elicit a left anterior negativity, followed by a broadly distributed late positivity. The present study assessed whether these ERP indicators index the activity of language systems specific for the processing of aural-oral language or if they index neural systems underlying any natural language, including sign language. The syntax of a signed language is mediated through space. Thus the question arises of whether the comprehension of a signed language requires neural systems specific for this kind of code. Deaf native users of American Sign Language (ASL) were presented signed sentences that were either correct or that contained either a semantic or a syntactic error (1 of 2 types of verb agreement errors). ASL sentences were presented at the natural rate of signing, while the electroencephalogram was recorded. As predicted on the basis of earlier studies, an N400 was elicited by semantic violations. In addition, signed syntactic violations elicited an early frontal negativity and a later posterior positivity. Crucially, the distribution of the anterior negativity varied as a function of the type of syntactic violation, suggesting a unique involvement of spatial processing in signed syntax. Together, these findings suggest that biological constraints and experience shape the development of neural systems important for language.     

Macrophage activation syndrome in juvenile systemic lupus erythematosus: A multinational multicenter study of thirty‐eight patients

Objective

To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).

Methods

Cases of juvenile SLE–associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.

Results

The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed.

Conclusion

Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

     

Effect of transfusion therapy on cerebral vasculopathy in children with sickle-cell anemia

This retrospective study assessed the long-term effect of transfusional exchange therapy on MRA/MRI abnormalities in 24 homozygous sickle-cell anemia (HbSS) children presenting with abnormal brain MRA. The median time elapsed from baseline to last available MRA was 29 months. Follow-up MRAs showed improvement, stabilization or worsening of cerebrovascular lesions in 11, 6 and 7 patients respectively. Complete normalization of MRA was observed in 6 patients within a mean time of 1.4 years, but stenosis recurred at the same location in the 4 patients in whom transfusion therapy was discontinued. Baseline severe stenosis/occlusion of large cerebral arteries and occurrence of moyamoya syndrome were significantly associated with an absence of improvement of the cerebral vasculopathy. These data emphasize the heterogeneity of the course of cerebrovasculopathy in SS children receiving chronic transfusion. Further studies are needed to determine whether different therapeutic approaches have to be considered according to these different evolutive patterns in SS children.     

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63·98%) and 191 patients (66·8%) had a thrombophilia marker. Eighty nine (46·6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61·8% of patients with high risk of VTE. Among them, 37·7% were treated in the third trimester only and 24·1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0·35%) and two postpartum-related VTE (0·7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0·35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.     

Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course – a randomized,placebo‐controlled and double blind pilot study

Background: Our understanding of the pathogenic role of IgE in atopic dermatitis is incomplete. We asked whether blocking free IgE would alter the course of the disease. Patients and Methods: We administered either omalizumab, a humanized monoclonal mouse antibody against IgE, or placebo subcutaneously for 16 weeks to 20 atopic dermatitis patients and measured immunological and clinical disease parameters. Results: Omalizumab (I) reduced free serum IgE, (II) lowered surface IgE and Fc?RI expression on different peripheral blood mononuclear cells, (III) reduced the saturation of Fc?RI with IgE, (IV) increased the number of free Fc?RI and (V) lowered the number of IgE+, but not of Fc?RI+ cells in skin. The in vivo relevance of these results is evidenced by the increase in the threshold allergen concentration required to give a type I hypersensitivity reaction in the titrated skin test. While not significantly altering the clinical disease parameters, omalizumab treatment led to an improvement of the atopy patch test results in single patients, i.e. an eczematous reaction upon epicutaneous allergen challenge. Conclusions: The interference with immediate and delayed type skin tests may imply that a therapeutic benefit of omalizumab treatment, if present at all, would be seen in patients with acute rather than chronic forms of the disease.