Suzana Doneda Mittelstadt

Positive effects of transcranial direct current stimulation in adult patients with attention-deficit/hyperactivity disorder A pilot randomized controlled study

Almost 30% of adult patients with attention-deficit/hyperactivity disorder (ADHD) do not respond or tolerate standard pharmacological interventions. Few clinical investigations addressed the efficacy and tolerability of transcranial direct current stimulation (tDCS), a non-invasive neuromodulatory technique, in the disorder. We performed a double-blind, sham-controlled randomized clinical trial in 17 patients with ADHD. The set up for tDCS was the following: 2mA/20min/day for 5 days with the anode over the right dorsolateral prefrontal cortex and cathode over the left dorsolateral prefrontal cortex. ADHD symptoms were measured by the Adult ADHD Self-Report Scale (ASRS) and impairment with the Sheehan Disability Scale (SDS) in four different time points after stimulation. Participants achieved significant lower ASRS inattention and SDS scores after active tDCS in comparison with sham stimulation group. In addition, we detected a trend for a lower ASRS total score in the active tDCS group. Follow up data analysis revealed a positive interaction between time and treatment in both ASRS inattention, SDS and ASRS total scores. Short-term application of tDCS in adult patients with ADHD improved their symptoms, and this improvement persisted after the end of the stimulation. Future studies with larger sample sizes are needed.

Ghrelin, leptin and adiponectin levels in Gaucher disease type I patients on enzyme replacement therapy

BACKGROUND Gaucher disease type I (GD type I) is characterized by clinical heterogeneity and is associated with metabolic abnormalities such as increased basal metabolic rate. OBJECTIVE To evaluate ghrelin, leptin and adiponectin levels in patients with GD type I on enzyme replacement therapy (ERT). SUBJECTS AND METHODS A cross-sectional study of patients with GD type I (n = 15), matched for sex, age and BMI with healthy controls. The levels of glucose, insulin, ghrelin, leptin and adiponectin were assessed in both groups. Insulin resistance was defined by the index HOMA-IR. RESULTS Eight patients had adequate weight, seven were overweight (4 preobese, 3 obese class I). Eight patients presented metabolic syndrome, five of whom with insulin resistance. The median levels of ghrelin, leptin and adiponectin of the patients did not differ from those of the controls. Ghrelin and adiponectin levels were correlated with each other; inversely correlated with BMI, waist circumference and triglyceride levels; and directly correlated with HDL-cholesterol. Leptin levels were inversely correlated with LDL-cholesterol and directly correlated with BMI, waist circumference, enzyme dosage, triglycerides, insulin, and HOMA-IR. CONCLUSIONS Metabolic syndrome and overweight appear to be common in patients with GD type I on ERT. As leptin was strongly associated with insulin and HOMA index, it could become a biomarker to assess early evidence of insulin resistance in patients with GD. Further studies are needed to investigate the associations found.

Enzyme Replacement Therapy in a Patient with Gaucher Disease Type III: A Paradigmatic Case Showing Severe Adverse Reactions Started a Long Time After the Beginning of Treatment.

INTRODUCTION There are three recombinant enzymes available for the treatment of Gaucher disease (GD): imiglucerase, velaglucerase alfa, and taliglucerase alfa. CASE REPORT A male GD type III patient, 14 years old, genotype p.L444P/L444, diagnosed at 2 years old. He had been treated with imiglucerase for 9 years since the diagnosis. In 2008, however, he presented a severe adverse reaction to imiglucerase, characterized by cough, laryngeal stridor, and periorbital edema. The infusions were suspended for 3 months when imiglucerase was restarted with premedication and a slower infusion rate. After 5 months, he presented a new adverse reaction with vomiting, tachypnea, cough, and periorbital edema. Intradermal testing confirmed IgE-mediated reaction but serological tests were negative. After 2 years and 10 months with no specific treatment and a significant worsening of the clinical picture, taliglucerase alfa was prescribed, with premedication and a slower infusion rate. At the first infusion, he presented moderate adverse reaction and the infusions were suspended. After 2 months, velaglucerase alfa was initiated uneventfully. He maintains day-hospital infusions without premedication and shows improvement of clinical and laboratory parameters. CONCLUSION This is the first report of the use of velaglucerase alfa in patients with GD type III. The use of recombinant enzymes is safe for the majority of GD patients, but severe reactions may occur even many years after the beginning of the treatment. Premedication and slower infusion rate reduce the incidence of adverse reactions but may not solve the problem. This case report further demonstrates the different safety profile among all the recombinant enzymes available for the treatment of GD.

Hyperimmunoglobulinemia in pediatric Gaucher patients in Southern Brazil

To the Editor: We read with great interest the brief report published by Arıkan-Ayyıldız et al. [1] about immunoglobulin abnormalities and enzyme replacement therapy (ERT) in children with Gaucher disease (GD). We would like to point out some issues based on the findings of the cohort of Gaucher patients followed in our clinics. Since 2003, all patients (30 GD type I and 3 GD type III) are followed with clinical assessment and complementary exams every 3 months and after achievement of main goals, laboratory exams, including immunological profile (IgG, IgM, IgA, and IgE, as well as electrophoresis of proteins) are done on a yearly basis [2,3]. Evaluation of immunological data at the diagnosis was performed for 11 patients (9 GD type I and 2 GD type III) who were under the age of 18 years at the diagnosis. All but one pediatric patient (GD type III patient due to allergic reaction) have been receiving ERT with imiglucerase (30 U/kg/inf for GD type I and 60 U/kg/inf for GD type III) every 2 weeks. The mean age at diagnosis was 6.4 years (range: 2–16 years) and the mean age at the start of treatment was 7 years (range: 2–17 years). The mean time of ERT was 12.7 years (range: 8–16 years). We had access to immunological profiles of eight pediatric patients since 2007 (7 GD type I patients and 1 GD type III patient) and four patients since 2008 (3 GD type I patients and 1 GD type III patient). Hyperimmunoglobulinemia was present in 10 (90.9%) pediatric patients at the first evaluation (IgA: 1/10 patients, IgE: 8/10 patients, IgM: 2/10 patients, IgG: 4/10 patients). The only GD type III patient, who was without ERT, presented IgG monoclonal gammopathy, but after a few months, even without treatment, the monoclonal pike disappeared. Four patients (36.4%) presented polyclonal gammopathy at the first evaluation. One GD type I patient (after 19 months of ERT) and one GD type III patient (after 15 months of ERT) resolved their gammopathy. Even in regular therapy with imiglucerase, nine (90%) patients still present with hyperimmunoglobulinemia (IgE: 6/9 patients, IgM: 2/9 patients, IgG: 6/9 patients). Our data differs from previous studies, including the Brief Report by Ayyıldız et al. [4] that reported a frequency of hyperimmunoglobulinemia in pediatric GD patients ranging from 71% to 77% at diagnosis. Ninety percent of our patients presented hyperimmunoglobulinemia at the first evaluation (23–29% of difference from other studies) and 40% of the patients showed increased levels of IgG, similar to what has been reported [4]. After ERT, the number of patients with hyper IgE decreased 14%, hyper IgM increased 2% and hyper IgG increased 26%. None of our patients resolved their gammopathy. Our data suggest that the cohort of patients in Southern Brazil presents more hyperimmunoglobulinemia than the previous reports and ERT was less effective in normalize immunoglobulin levels. We agreed that the initiation of early ERT might help to decrease the risk of malignancies, but other studies are needed.