Abnormal transcranial Döppler ultrasonography in children with sickle cell disease

BACKGROUND: Stroke is a potentially fatal complication of sickle cell disease in children between 2-16 years and transcranial Döppler has been recommended as a screening method in these cases. OBJECTIVE: The main goal of this study was to correlate transcranial Döppler results to complications related to stroke in sickle cell disease and baseline characteristics of the population. METHODS: This was an observational study of children and adolescents with ages between 2-16 years with sickle cell disease who were followed in three centers. RESULTS: From January 2008 to July 2009, 902 patients were enrolled in this study. The median age was 6.5 years (range: 1.8-15.8), 52.3% were male, 74.4% had hemoglobin SS; 221 (28.6%) had at least one complication associated with sickle cell disease. A total of 773 patients performed transcranial Döppler; in 91.2% this was a method of screening. Conditional or abnormal transcranial Döppler results were more common in patients with sickle cell disease complications versus those without complications (ODDS ratio = 3.18; 95% Confidence interval = 1.92-5.27). There was a significant difference in the frequency of conditional or abnormal transcranial Döppler results in patients with abnormal laboratory results compared to those without abnormalities (OR=4.03); 95% confidence interval = 2.30-7.06. CONCLUSIONS: Conditional or abnormal transcranial Döppler results were significantly more frequent in patients with complications of sickle cell disease confirming the increased risk of stroke in this subgroup of patients. This observation reinforces the recommendation of transcranial Döppler as a screening test for all patients with sickle cell disease with ages between 2 and 16 years.

Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil / Polimorfismos genéticos e doença cerebrovascular em crianças com anemia falciforme do Rio do Janeiro, Brasil

The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of βS-globin gene haplotypes and co-inheritance with α-thalassemia (-α3.7kb) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α3.7kb thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical βS-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95 percent 2.9-81.6) of CVD than the other βS-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population.

Avaliar o papel da talassemia alfa (-α3.7kb), dos haplótipos da globina βS, e mutações nos genes da metileno-tetrahidrofolato redutase (MTHFR-C677T), fator V de Leiden (FV-G1691A) e protrombina (PT-G20210A) como fatores de risco para a doença cerebrovascular em pacientes com anemia falciforme. Foi realizado um estudo de caso controle com 94 crianças portadoras de anemia falciforme, 24 com doença cerebrovascular (DCV) e 70 sem DCV como grupo controle. A frequência de talassemia -α3.7kb foi semelhante em ambos os grupos (p=0,751). Crianças portadoras do haplótipo Bantu/Atípico da globina βS apresentam 15 vezes mais chances de desenvolverem DCV (OR=15,4 IC 95 por cento 2,9-81,6) do que os outros haplótipos. A frequência do polimorfismo MTHFR-C677T foi semelhante em ambos os grupos (p=0,085) e não foi observada mutação nos genes fator V e protrombina. Estudos com maior número de casos são necessários para esclarecer o papel desses polimorfismos genéticos na nossa população.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

BACKGROUND: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. OBJECTIVE: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. METHODS: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. RESULTS: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. CONCLUSION: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.

Efficacy and tolerability of a combination of uridine, cytidine, and vitamin B12 in anemia. A double-blind, comparative study versus nucleotide monotherapy

Background: Deficiency in vitamin B12 is commonly associated with pernicious anemia, presenting a number of clinical symptoms resulting from neurological alterations due to modifications in myelin formation. Treatment consists of oral or parenteral vitamin B12 supplementation. Vitamin B12 has also been shown to have analgesic action whether administered alone or in combination with other therapeutic agents. Oral or parenteral pyrimidine ribonucleotide supplementation may be advantageous in the treatment of peripheral neuropathies. Objectives: To evaluate and compare the efficacy and tolerability of an orally administered combination of vitamin B12, uridine and cytidine, versus administration of the nucleotides alone in the treatment of the signs and symptoms of anemia. Study design: Study goal was normalization of MCV and MCH and serum vitamin B12 as well as improvement in pain and paresthesia among patients presenting these symptoms at Pretreatment. The study was designed as a double-blind, randomized trial in two arms: Group A patients were treated with the vitamin + nucleotide combination Group B patients received nucleotides alone. Treatment lasted 60 days, with two interim visits at 20 and 40 days of treatment and a final evaluation after 60 days of treatment. Setting: Patients were attended in an ambulatory setting of a UNIFESO university hospital. Patients: Eligible patients were between 18-65 years of age, with clinical and laboratory presentation of anemia with or without underlying autoimmune disease, caused by vitamin B12 deficiency. Female patients were not pregnant and were required to use birth control for the duration of the treatment period. Eighty patients were randomized, with 40 patients in each treatment group. Treatment consisted of 3 daily oral doses of: 1.0 mg hydroxocobalamin acetate, 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate for Group A patients, while patients in Group B received 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate in identical capsule forms. Main outcome measure: Primary outcome measures defined in the protocol included improvements in MCV, MCH and vitamin B12 reaching laboratory reference range, 3-point improvements in Global, Pain, and Paresthesia evaluations and a 20% reduction in VAS scores. Results: Normalization of laboratory evaluations occurred only in Group A. Three-point improvement in Global evaluation by the physician was observed only in Group A, while both groups showed improvement in Global evaluation by the patient. Patient's assessment of pain improved only in Group A, although VAS score decrease was noted in both groups both groups also had improvement in paresthesia evaluations. Vital signs did not change, while weight gain was observed in both groups. Adverse events seen in both groups included nausea, diarrhea, headache and abdominal cramps. Alterations in laboratory evaluations were reported in both groups, but could be directly attributed to anemia. Conclusion: The combination of vitamin B12, uridine and cytidine was found to be safe and effective in the treatment of the signs and symptoms of anemia in the population studied. The pain reduction observed in both groups may be attributed to activity of the nucleotides.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin lesions) syndrome: a South America's report

The POEMS syndrome, also known as Crow-Fukase syndrome, is an unusual systemic disorder described mainly in Asian individuals. It is characterized by the presence of (P)polyneuropathy, (O)organomegaly, (E)endocrinopathy, (M) M-protein, and (S) skin changes. Several other associated condictions such as sclerotic bone lesions, Castleman disease, low-grade fever, edema and hematologic disorders are usually seen. We describe five Brazilian patients with this syndrome. Two patients presented Castleman disease, one patient presented osteosclerotic myeloma and in two patients no associated conditions were found.

A síndrome POEMS, também conhecida como síndrome de Crow-Fukase é uma desordem sistêmica rara descrita principalmente em asiáticos. Ela é caracterizada pela presença de (P) polineuropatia, (O) organomegalia, (E) endocrinopatia, (M) proteína M e (S) alterações de pele. Diversas outras manifestações, tais como lesões osteoescleróticas, doença de Castleman, febre baixa, edema e distúrbios hematológicos são freqüentemente observados. Apresentamos cinco pacientes brasileiros com esta síndrome. Dois pacientes apresentaram diagnóstico de doença de Castleman, um paciente com mieloma osteoesclerótico e em dois pacientes, nenhuma condição associada foi encontrada.

Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial / Psycothic syndrome developing into dementia as a clinical manifestation of mitochondrial DNA deletion

As manifestações das doenças mitocondriais são variadas, acometendo, mais freqüentemente, órgãos com alto metabolismo aeróbico em que são mais abundantes, como, por exemplo, o sistema nervoso. O início dos sintomas em geral é observado na infância havendo relatos de início na idade adulta. Apresentamos caso atípico de doença mitocondrial associada à deleção do DNA mitocondrial em um homem de 39 anos com sintomas psiquiátricos configuraram quadro clínico inicial e somente 12 anos após o início dos sintomas surgiram alterações neurológicas. O diagnóstico da doença mitocondrial foi confirmado por biópsia de músculo sendo documentada deleção do DNA mitocondrial.

The manifestations of mitochondrial disease are variable, affecting more frequently the organs with high aerobic metabolism in which they are more abundant, for example the nervous system. The beginning of symptoms in general is observed at chilhood, but some patients presented on adult age. We present an atypical case associated with mitochondrial DNA deletion. A 39-years-old man with psychiatric symptoms that configured initial clinical picture and only after 12 years of the beginning of symptoms neurological alterations became noticeable. The diagnosis of mitochondrial illness was confirmed by muscle biopsy being documented mitochondrial DNA deletion.

Hoffman's syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Case report

The frequency of myopathy in hypothyroidism ranges from 30 to 80 percent. The major symptoms related are weakness, muscular cramps and myalgia. The pseudohyperthrophic form is called Hoffman's syndrome. The electrophysiological study reveals myopathy, neuropathy or mixed pattern. Laboratorial investigation generally shows increased levels of muscle enzymes and low serum thyroid hormones, with thyrotrophic-stimulating hormone (TSH) elevated. The treatment consists in hormone replacement and the prognosis is good in most of the cases. We report an adult male who developed muscular cramps, myalgia, weakness, pseudohyperthrophy, associated with facial edema and alteration of his voice. The muscle enzymes were increased and T4 was undetectable with a raised level of TSH. The myopathy was the initial manifestation of hypothyroidism in this case

Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent

We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report

Syringohydromyelia or HTLV-I associeted myelopathy/tropical spastic paraparesis: a diagnostic challenge (case report)

Human T-cell lumphotropic virus type I (HTLV-I) associated myelopathy / tropical spastic paraparesis (HAM/TSP) is the most common chronic myelopathy in Brazil. We present the case of a 53 year old man that fulfiled the diagnostic criteria for HAM/TSP but had at the magnetic resonance imaging (MRI) of the spinal cord evidences of syringohydromyelia at the C6-C7 and D2-D7 levels along with Chiari type I malformation. The clinical picture was more typical of HAM/TSP than of syringohydromyelia, which was probably asymptomatic. The present case clearly demonstrates that sorology and neuroimaging should be always use together. We conclude that, specially in places where HTLV-I is endemic, every patient with a spatic paraparesis, even with a radiological picture suggestive of a structural spinal cord lesion, should have a screening test for HTLV-I. The clinical picture must dictate the final direction of the diagnosis.