[Central nervous system tuberculosis in children: 1. Clinical and laboratorial presentation]. / Tuberculose do sistema nervoso central em crianças: 1. Apresentação clínica e laboratorial.

Tuberculosis still occupies a remarkable place as a worldwide health problem, chiefly in emerging countries, like Brazil. The central nervous system (CNS) involvement by Mycobacterium tuberculosis is one of the most feared features of disease, because of its high morbidity and mortality. This study aimed to describe some epidemiological, clinical and laboratorial aspects of 52 children in a tertiary pediatric hospital with CNS tuberculosis. At diagnosis, the majority of patients showed low age, compromised nutritional status, previous contact with bacillary individuals, delayed or absent immunization, advanced neurological signs and compatible abnormalities in cerebrospinal fluid (CSF) analysis and in radiological findings. The etiologic agent was identified by staining methods or CSF and other fluids culturing in 40% of patients. In most cases, despite of suggestive clinical, epidemiological and laboratorial picture and feasibility of patients access to health care centres, therapy was started late.

[Central nervous system tuberculosis in children: 2. Treatment and outcome]. / Tuberculose do sistema nervoso central em crianças: 2. Tratamento e evolução.

Neurologic damage is usual after central nervous system (CSN) tuberculosis recovery. Treatment is long, difficult and prone to complications. Many factors are enrolled as prognostic determinants. This study aimed to describe the treatment and outcome of 52 children with CNS tuberculosis of a tertiary pediatric hospital. All of them received standard triple drug regimen, and 41 (78.8%) received corticosteroids as adjunctive therapy. Hydrocephalus was common (28 of 41 tested), but only 8 (15.4%) patients underwent ventricular shunt surgery. Hepatotoxicity to anti tuberculosis drugs occurred in 32 (61.5%) cases, but in only 3 (9.4%) drug substitution was necessary. There were 8 (15.4%) deaths and 24 (46.1%) cases developed neurologic damage after therapy. Patients who did not receive steroids during treatment and those with advanced neurological involvement at diagnosis showed a tendency to worse prognosis.

Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases.

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

The psychiatric symptoms of rheumatic fever.

OBJECTIVE: This study examined the frequency and age at onset of psychiatric disorders among children with rheumatic fever, Sydenham's chorea, or both and a comparison group. METHOD: Twenty children with rheumatic fever, 22 with Sydenham's chorea, and 20 comparison children were assessed by means of a semistructured interview and rating scales for tic disorders and obsessive-compulsive disorder. RESULTS: Obsessive-compulsive symptoms were more frequent in both the Sydenham's chorea and rheumatic fever groups than in the comparison group. The Sydenham's chorea group had a higher frequency of major depressive disorder, tic disorders, and attention deficit hyperactivity disorder (ADHD) than both the comparison and rheumatic fever groups. ADHD symptoms were associated with a higher risk of developing Sydenham's chorea. CONCLUSIONS: Both the rheumatic fever and Sydenham's chorea groups were associated with a higher risk of developing neuropsychiatric disorders than the comparison group. ADHD appears to be a risk factor for Sydenham's chorea in children with rheumatic fever.

Vaccine-associated paralytic poliomyelitis: a case report of domiciliary transmission.

Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C-->U) in the 5' non-coding region, which is strongly related to the higher strain virulence.

Clinical and molecular analysis of spinal muscular atrophy in brazilian patients

As amiotrofias espinhais progressivas (SMAs) constituem as doenças degenerativas de origem genética letais mais comuns do sistema nervoso central e mais freqüentes dentre as doenças autossômicas recessivas após a mucoviscidose. A incidência estimada das SMAs e de aproximadamente 1:10.000 nativivos. Clinicamente, as SMAs säo classificadas em mais grave (doença de Werdnig-Hoffmann, tipo I), intermediária (tipo II) e tardia e benigna (doença de Kugelberg-Welander, tipo III). O gene para os três tipos de SMAs foi mapeado no cromossomo 5q11.2-13.3. Foram identificados dois genes candidatos na mesma regiäo: SMN (sobrevida do neurônio motor) e NAIP (proteína inibidora de apoptose neuronal). Estudamos ambos genes em 87 pacientes brasileiros (20 tipo I, 14 tipo II e 53 tipo III) pertencentes a 74 famílias, utilizando as técnicas de PCR e SSCP. Foi encontrada deleçäo nos exons 7 e/ou 8 do gene SMN em 69 por cento das famílias: 16/20 na tipo I, 9/12 na tipo II e 26/42 na tipo III. Dentre as 51 famílias com deleçäo, 44 tiveram deleçäo no exon 5 do gene NAIP foi encontrada em 7/20 na tipo I, 2/12 na tipo II e 1/42 na tipo III. Näo foi encontrada deleçäo nos genes SMN e NAIP nos 112 progenitores, 26 irmandades assintomáticas e 104 controles normais. Näo houve correlaçäo entre deleçäo de um ou ambos genes com a gravidade do quadro clínico.

Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study.

OBJECTIVE: The incidence and course of neuropsychiatric symptoms were determined in pediatric patients with rheumatic fever. METHOD: The Leyton Obsessional Inventory and National Institute of Mental Health Global Obsessive-Compulsive Scale were used to evaluate children and adolescents who had rheumatic fever with Sydenham's chorea (N=30) or without chorea (N=20). They were assessed three times over 6 months from the onset of rheumatic fever. Psychiatric diagnoses were also determined. RESULTS: Obsessive-compulsive symptoms abruptly appeared and peaked during the 2 months after the onset of rheumatic fever in 21 patients with chorea (70.0%) and were absent in all patients without chorea. Obsessive-compulsive disorder (OCD) was diagnosed in five patients with chorea (16.7%). CONCLUSIONS: The association between Sydenham's chorea and OCD supports suggestions that similar mechanisms involving the basal ganglia underlie both disorders. Obsessive-compulsive symptoms occurred at the beginning of rheumatic fever, so early psychopathological assessments are essential.

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.

PIP: In Brazil and other South and Central American countries where abortion is illegal, misoprostol is widely available and commonly used to induce abortion. However, misoprostol is not very effective as an abortifacient agent and can cause fetal abnormalities. The present study reviewed the cases of 42 infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first trimester of pregnancy and then born with a congenital abnormality. 17 children had equinovarus with cranial nerve deficiencies and 10 had equinovarus as part of a more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (5 cases) and terminal transverse limb defects (9 cases). Congenital hydrocephalus was present in 8 children. The most commonly taken dose of misoprostol was 800 mcg (range, 200-16,000 mcg). Greater awareness of the widespread use of misoprostol to induce abortion should lead to public health interventions to prevent teratogenic effects.

[Neonatal Streptococcus pyogenes meningitis and sagittal sinus thrombosis: case report]. / Meningite neonatal por Streptococcus pyogenes e trombose de seio sagital. Relato de caso.

We report a case of Streptococcus pyogenes meningitis in a 18 days year-old-girl with clinical course complicated by sagittal sinus thrombosis. Some aspects of the pathogenesis, treatment and follow-up of the disease are discussed. The world increase of serious streptococcal infections in the last 10 years, probably will become neonatal Streptococcus pyogenes meningitis more frequent in the future and it is important to be alert for the precocious diagnosis and the possible complications of that potentially lethal infection.

Sydenham's chorea.

Sydenham's chorea (SC) is a disorder of the central nervous system (CNS) characterized by sudden, involuntary, arrhythmic, clonic, and purposeless movements. SC appears to provide a model for understanding various neuropsychiatric dysfunctions. Its relationship with attentional deficits, obsessive-compulsive symptoms (OCS) as well as movement disorders provides support for the hypothesis of the involvement of the corticostriatal loops in the pathophysiology of the disorder.

Sintomas obsessivo-compulsivos e tiques vocais em pacientes com coreia de Sydenham: dados preliminares

Coreia de Sydenham (CS) e uma desordem neuropsiquiatrica, considerada uma compilacao da Febre Reumatica (quadro auto-imune pos-infeccao estreptococcica). Uma incidencia mais alta de sintomas compulsivos obsessivos (SOC) e desordem compulsiva obsessiva (TOC) foi documentado em pacientes de CS. TOC tambem foi descrito mais frequentemente em pacientes com o Sindrome de Tourette (ST) e ha varias linhas de pesquisa sugerindo que algumas formas de TOC podem representar uma expressao variante de ST. O estudo presente visa determinar a frequencia de tiques vocais, alem de sintomas obsessivo-compulsivos na Coreia de Sydenham (CS) e na Febre Reumatica sem CS (RF). Metodo: Foram avaliadas trinta e nove criancas com febre reumatica (22 com o CS e 17 com febre reumatica sem CS) (RF). Os pacientes foram diagnosticados de acordo com os criterios Jones. Foram executadas avaliacoes psiquiatricas e neurologicas em todos os pacientes. A Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological version (K-SADS-E), Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Yale Global Tics Severity Scale (YGTSS) foram administrados a todos os pacientes. Resultados: A amostra de CS apresentou 14 pacientes com tiques vocais (63,64 por cento) e 8 pacientes com SOC (36,36 por cento). A amostra de FR apresentou 5 pacientes com SOC (29,41 por cento) e nenhum com tique vocal. Conclusoes: Os dados sugerem que tiques vocais sao encontrados mais frequentemente em criancas com a Coreia de Sydenham, e SOC sao encontrados, frequentemente, tanto em pacientes com CS como em pacientes com FR sem CS.

[Neonatal bacterial meningitis: prospective study of the long-term outcome of 55 children]. / Meningite bacteriana neonatal: estudo prospectivo da evolução a longo prazo de 55 crianças.

Fifty-five infants who presented bacterial neonatal meningitis were prospectively studied to analyze the frequency and the type of sequelae. All the infants were full term newborns. There were 38 boys and 17 girls; the age of disease onset varied from 3 to 28 days. The causative organism was represented mainly by enterobacteriae. The median time of follow-up was 5 years. The frequency of neurologic sequelae was 63.7%, represented mainly by neuropsychomotor development delay (58.2%), hydrocephaly (45.5%) and convulsions (34.5%). Severe motor abnormalities ocurred in 23.6% of children (quadriplegia, diplegia, hemiparesia and ataxia). Convulsions in the acute phase of the disease and the positive cerebrospinal fluid culture were highly associated to sequelae. The school performance, obtained in 25 children, showed presence of disabilities in 48% of cases, which were significantly associated to mental retardation.

Síndrome do risco de morte súbita infantil / Near sudden infant death syndrome. A case report

A síndrome da morte súbita infantil, ou morte durante o sono, se dá em uma criança normal, após adormecer bem, sem causa aparente. É considerada, como a causa isolada, a mais frequente de morte no primeiro ano de vida, em estatísticas do exterior. Acredita-se ocorrer a morte por um distúrbio funcional dos centros respiratórios levando à apnéia. Em crianças encontradas flácidas em apnéia reversível após estimulaçäo ou ao despertar, denomina-se em "risco" da morte súbita infantil. Apresentamos um caso desta síndrome, com crises de cianose e apnéia durante o sono a partir do oitavo dia de vida. O paciente foi internado, feita a monitorizaçäo respiratória, submetido a registro polissonográfico de 24 horas. Näo foram detectadas causas justificando as apnéias. Foi medicado com aminofilina e constatou-se o desaparecimento das crises de apnéias no segundo mês de vida. Este trabalho permite evidenciar um caso de entidade pouco diagnosticada em nosso meio

Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy.

Misoprostol, a synthetic analog of prostaglandin, has been widely used in Brazil as an abortifacient. Abortion is illegal in Brazil. An uncertain number of these abortion attempts are unsuccessful and the pregnancy continues. We report on 7 patients whose mothers attempted to abort using this drug in the first trimester of gestation without success. The 7 patients presented with limb defects and in 4 of them a diagnosis of Möbius sequence was made.

In search of a genetic basis for the Rett syndrome.

Rett syndrome is a progressive encephalopathy restricted to the female sex. In the present paper a possible genetic cause for this syndrome is discussed, based on data from the literature as well as our own. Our results are in agreement with others regarding no increase in parental age, or in spontaneous abortions rate among the mothers of affected children and with a normal sex ratio among sibs. We have found no chromosome rearrangement detectable with the methods used and no correlation between fra(X) (p22) and the Rett syndrome. We have observed an alteration in the sequence of replication in one of the two types of late-replicating X-chromosome present in normal women, and suggest that this may signify that genes which are active in the late-replicating X-chromosome are inactivated (or vice-versa) in these patients. This fact could be related to the abnormal phenotype observed in Rett syndrome patients.

[The battered child syndrome: neurologic aspects in 7 cases]. / Síndrome da criança espancada: aspectos neurológicos em 7 casos.

Data on 7 cases of battered child syndrome with neurological complications are reviewed. First symptoms were convulsions and bulged fontanel of undetermined origin. At clinical examination the unexpected presence of retinal hemorrhage in 5/7 patients has been the main criteria to diagnostic definition. CT showed the presence of subdural collections in the majority of the patients. A normal CT, however, does not display the possibility of future problems. Successive CT studies have proved useful. In two cases they demonstrated the appearance of diffuse images of central nervous system destruction some weeks later, and probably related to ischaemic troubles in connection with the aggression mechanisms.

Prenatal cytomegalovirus disease and cerebral microgyria: evidence for perfusion failure, not disturbance of histogenesis, as the major cause of fetal cytomegalovirus encephalopathy.

From the study of four personal cases of microgyria related to fetal CMV infection and a review of the literature it is concluded that: 1) Microgyria is a frequent neuropathological finding in this disease - 2) CMV microgyria is the result of an insufficiency of cerebral blood supply and is not due to a disturbance of neurogenesis or histogenesis as a consequence of a direct cytopathic effect of the virus on germinal cells. The way by which the CMV causes cerebral ischemia - angeitis or more probably, transient systemic perfusion failure, - is discussed, but remains obscure. Other viruses may act on the fetal brain by way of circulatory disturbances.

[Sjögren-Larsson syndrome. Clinical and laboratory study of 2 cases]. / Síndrome de Sjögren-Larsson. Estudo clínico e laboratorial de dois casos.

Two cases of Sjögren-Larsson syndrome are reported. In analysing the clinical symptoms and laboratory data the authors established the diagnosis of this rare entity which has an autosomal recessive kind of inheritance.