Mowat-Wilson syndrome: neurological and molecular study in seven patients.

OBJECTIVE: To present a seven-cases serie of Mowat-Wilson syndrome (MWS). METHOD: All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. RESULTS: A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7). CONCLUSION: Physicians who care for patients with mental retardation and epilepsy should be aware of SMW.

Mowat-Wilson syndrome: neurological and molecular study in seven patients / Síndrome de Mowat-Wilson: estudo neurológico e molecular em sete pacientes

Objective To present a seven-cases serie of Mowat-Wilson syndrome (MWS). Method All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. Results A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7). Conclusion Physicians who care for patients with mental retardation and epilepsy should be aware of SMW. .

Objetivo Apresentar uma série de sete casos da síndrome de Mowat-Wilson (SMW). Método Todos os pacientes com estudo positivo para a mutação ZEB2 foram avaliados por um geneticista e um neurologista, com a caracterização clínica e laboratorial. Resultados Todos apresentavam fácies peculiar e retardo mental. A escala de Denver II evidenciou intenso atraso em todos os aspectos, sobretudo motor fino e adaptativo. Microcefalia adquirida foi observada em cinco pacientes. Apenas um paciente não apresentava epilepsia, sendo esta focal e predominando no sono, sendo relatado estado de mal em três pacientes. A crise inicial estava associada à febre na maioria dos pacientes (4/6). O EEG evidenciou atividade epiléptica focal na maioria (5/7). Ao estudo de imagem foi observada agenesia total (4/7) e parcial do corpo caloso (1/7). Conclusão Médicos que lidam com pacientes com retardo mental e epilepsia devem saber distinguir as características peculiares da SMW. .

Oral motor assessment in individuals with Moebius syndrome.

BACKGROUND: Moebius syndrome (MS) is a rare congenital condition that is characterised by facial hypomimia and congenital strabismus caused by complete or partial impairment of the 6th and 7th cranial nerves. MS may be further associated with other nerves or malformations, mainly involving the extremities. The objective of this study was to quantify the decrease in oral motor performance in people with MS compared with normoreactive individuals using the Oral Motor Assessment Scale (OMAS). METHODS: The study group comprised 33 subjects between the ages of 2 and 20 years (average age: 10 ± 5 years) with MS along with 46 age- and gender-matched control subjects. RESULTS: The study group displayed a lower average functional score than the control group (P < 0.0001). A significant lack of lip closure (P = 0.03) and anterior lingual seal during swallowing (P = 0.03) occurred in the study group; in most cases, the individuals with MS were classified as 'subfunctional'. In addition, individuals with MS in the older age group displayed better functional scores than those in the younger group (P = 0.05). CONCLUSIONS: Functional damage to oral motor function in individuals with MS is evident, but differs among patients with respect to severity and the movements that are compromised. However, overall, improvements in the functional patterns of these individuals can be observed as they mature in age.

Angelman syndrome caused by deletion: a genotype-phenotype correlation determined by breakpoint.

OBJECTIVES: Deletion of the chromosome 15q11-q13, the most common genetic mechanism associated with Angelman syndrome (AS), is highly associated with a severe phenotype. However, deletion is not a genetically homogeneous group as it is composed by two main groups: Class I with breakpoints at BP1 (proximal) and BP3 (distal) and Class II present breakpoints at BP2 (proximal) and BP3 (distal). In this study, we aimed to evaluate the impact of the breakpoint on the electroclinical profile. METHODS: We evaluated 16 patients with AS caused by 15q11-13 deletion (6 were Class I; 10 were Class II). We characterized epilepsy features by clinical history obtained from parents and caretakers with a pre-standard questionnaire. These data were corroborated by medical records, contact with previous physicians, and video-EEG monitoring. Suggestive EEG patterns for AS were classified according to the classical description of Boyd et al. (1988). RESULTS: AS patients with BP1-BP3 deletion had significantly more daily and disabling seizures than AS patients with BP1-BP2 deletion. They also presented a significant higher frequency of status epilepticus and epilepsy aggravated by fever. Need for polytherapy was significantly more frequent in BP1-BP3 patients. EEG features were similar in both groups. CONCLUSION: This study shows a significant correlation between the two deletion classes and AS clinical, but not the electrographic phenotype. Epilepsy is more severe and refractory to treatment in patients with larger deletions. Deletion is not a homogeneous group and knowledge on the breakpoint may have a clinical implication and represent an important factor in parental counseling.

Acute hemorrhagic encephalomyelitis in childhood: Case report and literature review.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory immune-mediated disorder which is more common in pediatric patients. The clinical setting is characterized by a rapid onset of encephalopathy and multifocal neurological features. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM. This report shows a 2-year-old patient who presented with the classical features of ADEM and after 8 weeks developed severe neurological worsening. The second magnetic resonance image (MRI) showed hemorrhagic lesions. Differences in prognosis between ADEM and AHEM justify the investigation of AHEM whenever a patient has neurological recrudescence in a known patient of ADEM.

Möbius sequence in a girl and arthrogryposis in her half-brother: distinct phenotypes caused by prenatal injuries.

Möbius sequence is a congenital facial and abducens nerve palsy, frequently associated to abnormalities of extremities. Arthrogryposis multiplex congenital is defined as a congenital fixation of multiple joints seldom of neurogenic origin. Both sequences must have a genetic origin, but usually are sporadic cases related to environmental factors such as drugs exposition and maternal trauma. A 5-year-old girl and a 1-year-old boy were born with Möbius sequence and arthrogryposis multiplex congenital, respectively. During pregnancies, the mother had vaginal bleeding at 7 weeks and used crack (free-based cocaine) in the first trimester, respectively. The girl also has equinovarus talipes and autistic behavior. The boy has arthrogryposis with flexion contractures of the feet and knees. A vascular disruption, due to hemorrhage and cocaine exposure, causing a transient ischemic insult to embryos in a critical period of development may be responsible for distinct phenotypes in these cases.

Guillain-Barré syndrome in children: clinic, laboratorial and epidemiologic study of 61 patients.

The aim of the study was to analyze the epidemiologic, clinical, laboratory and development profile of Guillain-Barré syndrome series studied at the Child Institute, between 1989 and 2000. From the 61 patients that fulfilled the selection criteria, aged between 7 months and 13 years old, no sexual or seasonal variation was observed. Clinical events prior to neurological symptoms (with an average time gap of 20.7 days) were observed in 62.3%, 55% had cranial nerve disturbances, 27.9% dysautonomic symptoms, and 27.9% respiratory dysfunction. Installation time varied from 2-40 days, plateau from 0-28 days and recuperation from 30-480 days; 94% of patients had a complete clinical recuperation. Electrophysiology in 20 patients disclosed an abnormal demyelination pattern in 15, an exclusively motor axonal pattern in 4 and a mixed pattern in 1 patient. The results obtained did not differ from those in the literature but it was observed that boys and older children had a longer recuperation time. It was not possible to correlate electroneurography with clinical abnormalities and evolution due to the reduced number of patients.

Guillain-Barré syndrome in children: clinic, laboratorial and epidemiologic study of 61 patients / Síndrome de Guillain-Barré em crianças: estudo clínico, laboratorial e epidemiologico em 61 pacientes

The aim of the study was to analyze the epidemiologic, clinical, laboratory and development profile of Guillain-Barré syndrome series studied at the Child Institute, between 1989 and 2000. From the 61 patients that fulfilled the selection criteria, aged between 7 months and 13 years old, no sexual or seasonal variation was observed. Clinical events prior to neurological symptoms (with an average time gap of 20.7 days) were observed in 62.3 percent, 55 percent had cranial nerve disturbances, 27.9 percent dysautonomic symptoms, and 27.9 percent respiratory dysfunction. Installation time varied from 2-40 days, plateau from 0-28 days and recuperation from 30-480 days; 94 percent of patients had a complete clinical recuperation. Electrophysiology in 20 patients disclosed an abnormal demyelination pattern in 15, an exclusively motor axonal pattern in 4 and a mixed pattern in 1 patient. The results obtained did not differ from those in the literature but it was observed that boys and older children had a longer recuperation time. It was not possible to correlate electroneurography with clinical abnormalities and evolution due to the reduced number of patients.

O objetivo do estudo foi analisar retrospectivamente, quanto ao perfil clínico, laboratorial, epidemiológico e evolutivo a casuística da síndrome de Guillain-Barré no Instituto da Criança, entre 1989 e 2000. Preencheram os critérios de seleção 61 pacientes, com idades entre 7 meses e 13 anos, e não se observou variação entre sexos nem sazonal. Em 62,3 por cento houve uma afecção precedendo o quadro neurológico, num tempo médio de 20,7 dias; 55 por cento apresentaram acometimento de nervos cranianos, 27,9 por cento distúrbios disautonômicos e 27,9 por cento comprometimento respiratório. A fase de progressão variou de 2 a 40 dias, a de platô de 0 a 28 dias e a de recuperação de 30 a 480 dias e 94 por cento tiveram recuperação total. A eletroneurografia, em 20 pacientes, mostrou padrão desmielinizante em 15, padrão axonal puramente motor em 4 e padrão misto em 1. Os resultados não diferiram dos encontrados na literatura, mas os meninos e os pacientes na faixa etária superior apresentaram maior tempo de recuperação total. Não foi possível estabelecer relação entre resultados da ENMG e o quadro clínico e evolutivo em vista do pequeno numero de pacientes com esse exame.

Encefalopatia de Wernicke em criança com doença de Crohn / Wernicke encephalopathy in a child with Crohn disease

OBJETIVO: Descrever um caso de encefalopatia de Wernicke associada à doença de Crohn na infância. DESCRIÇÃO DO CASO: Menino de cinco anos, com diagnóstico de doença de Crohn por colonoscopia com biópsia há um ano; desde então, fez uso de diversos medicamentos sem resultados terapêuticos. Evoluiu com pancreatite há três meses, quando foi iniciada nutrição parenteral. Apresentou subitamente sonolência, episódios de frases desconexas e alteração da movimentação ocular. O exame neurológico evidenciou nistagmo vertical para cima em todas as posições e nistagmo horizontal no desvio conjugado do olhar. A ressonância magnética do encéfalo mostrou alterações compatíveis com a encefalopatia de Wernicke, sendo instituído o tratamento com tiamina parenteral imediatamente, com reversão completa dos sintomas por volta do 30º dia de tratamento. COMENTÁRIOS: Embora seja uma entidade rara, deve-se suspeitar de encefalopatia de Wernicke frente à presença de fatores de risco, uma vez que o tratamento imediato evita as sequelas neurológicas.

OBJECTIVE: To report a case of Wernicke encephalopathy associated with Crohn disease in childhood. CASE DESCRIPTION: A five year-old boy with Crohn disease, diagnosed by colonoscopy and biopsy one year ago; he has been treated with many different medications without results. During the past year, the patient was diagnosed with pancreatites and has received parenteral nutrition since then. After three months, the child suddenly presented drowsiness, meaningless speech and ocular movement disturbance. Neurologic examination disclosed upbeat nystagmus in all positions and horizontal nystagmus during conjugate deviation of the eyes. Magnetic resonance showed abnormalities consistent with Wernicke encephalopathy. Parenteral thiamine has been administered soon after diagnosis and by the 30th day of treatment, recovery of symptoms was complete. COMMENTS: Despite being a rare entity, neurological symptoms associated to the presence of risk factors such as prolonged parenteral nutrition should suggest Wernicke encephalopathy. Immediate treatment is important to avoid neurological disabilities.

Peripheral polineuropathy in patients with juvenile systemic lupus erythematosus / Polineuropatia periférica em pacientes com lúpus eritematoso sistêmico juvenil

Introdução: A polineuropatia periférica é uma das 19 síndromes neuropsiquiátricas do lúpus eritematoso sistêmico, segundo os critérios de classificação propostos pelo Colégio Americano de Reumatologia (ACR) para síndromes neuropsiquiátricas. No entanto, há descrições raras dessa manifestação, particularmente em populações de lúpus eritematoso sistêmico juvenil (LESJ). Métodos: De 1983 a 2007, 5.079 pacientes foram acompanhados na Unidade de Reumatologia Pediátrica do ICrûHCûFMUSP, e o diagnóstico de LESJ segundo os critérios do ACR foi estabelecido em 228 casos (4,5%). Polineuropatia periférica foi diagnosticada de acordo com as síndromes neuropsiquiátricas do ACR. Resultados: Dos 228 pacientes com LESJ, cinco (2,2%) desenvolveram polineuropatia periférica e foram retrospectivamente descritos. O diagnóstico foi confirmado por eletroneuromiografia, que evidenciou polineuropatia periférica distal, sensitiva e/ou motora, envolvendo quatro membros em dois pacientes e membros inferiores nos demais. Três eram pacientes do sexo feminino e todos tiveram a polineuropatia periférica após o diagnóstico de LESJ. A mediana de idade de início da doença foi de 14 anos, e a mediana de tempo entre o início de LESJ e o diagnóstico da polineuropatia periférica foi de 23 meses. As apresentações clínicas mais comuns foram fraqueza muscular e hiporreflexia. Todos os pacientes apresentavam anticorpos antifosfolípides. O tratamento foi realizado com corticosteroides em todos os pacientes, associado com ciclofosfamida endovenosa em três. Um paciente evoluiu com incapacitação funcional, presença de paresia de membros inferiores e necessidade de cadeira de rodas. Uma paciente faleceu por sepse grave. Conclusões: A polineuropatia periférica é uma manifestação rara no LESJ, grave, por vezes incapacitante e habitualmente associada a anticorpos antifosfolípides.

INTRODUCTION: Peripheral polyneuropathy is one of 19 neuropsychiatric syndromes seen in systemic lupus erythematosus, according to the classification criteria proposed by the American College of Rheumatology (ACR) for neuropsychiatric syndromes. However, this manifestation has not been reported very often, especially in patients with juvenile systemic lupus erythematosus (JSLE). PATIENTS AND METHODS: From 1983 to 2007, 5,079 patients were seen at the Pediatric Rheumatology Unit of the ICr-HC-FMUSP; 228 (4.5%) patients were diagnosed with JSLE according to the criteria of the ACR. Peripheral polyneuropathy was diagnosed according to the criteria for neuropsychiatric syndromes of the ACR. RESULTS: Five (2.2%) out of 228 patients with JSLE developed peripheral polyneuropathy and were described retrospectively. The diagnosis was confirmed by electroneuromyography, which showed the presence of distal peripheral polyneuropathy, sensorial and/or motor, involving all four limbs, in two patients, and the lower limbs, in three patients. Three of those patients were females, and peripheral neuropathy developed after the diagnosis of JSLE. The mean age of onset of the disease was 14 years, and the mean time between the onset of JSLE and the diagnosis of peripheral polyneuropathy was 23 months. The most common clinical presentations included muscular weakness and hyporeflexia. Antiphospholipid antibodies were present in all patients. Treatment consisted of corticosteroids in all patients, associated with intravenous cyclophosphamide in three patients. One patient evolved to functional disability and paresis of the lower limbs, requiring a wheelchair. One female patient died of severe sepsis. CONCLUSIONS: Peripheral polyneuropathy is a rare, severe, and occasionally incapacitating manifestation of JSLE, commonly associated with the presence of antiphospholipid antibodies.

A duplex allele-specific amplification PCR to detect SMN1 deletion.

Spinal muscular atrophy (SMA), the leading genetic cause of death in childhood, is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness, associated with deletions of the survival motor neuron (SMN) gene identified and mapped to chromosome 5q13. SMN is present in two highly homologous copies (SMN1 and SMN2). In the general population, normal individuals (noncarriers) have at least one telomeric (SMN1) copy, and 5% of them have no copies of SMN2. Approximately 95% of SMA patients carry homologous deletions of SMN1 exon(s) 7 (and 8). SMN1 and SMN2 exons 7 and 8 differ only by 1 bp each, and SMA diagnosis might be performed by single-strand conformational polymorphism, PCR amplification followed by restriction fragment length polymorphism (RFLP), multiple ligation-dependent probe amplification, or realtime PCR of SMNs exons 7 and 8. We developed a simpler and cost-effective method to detect SMN1 exon 7 deletion based on allele-specific amplification PCR.

Ketogenic diet for the treatment of refractory epilepsy: a 10 year experience in children.

Ketogenic diet (KD) is a high fat and low carbohydrate diet, which controls refractory epilepsy. We analyzed the KD effects on 54 children of the Children's Institute of the University of São Paulo. Efficacy, tolerability, and adverse effects were studied. Response to KD was effective (E) if seizure control was >75%, good (G) when 50-75%. When possible, we correlated the results with the epileptic syndrome and patient's age. By the second month on diet, 57.4% of the patients had E response and 31.4% G results. At the 6th month, 63.8% had E response and 25.5% G. At the 12th month, 71.8% had E and 25.6% G. At the 24th month, 62.1% had E and 37.9% G. Antiepileptic drugs have been reduced, and generalized epilepsy was the most sensitive. Age-related differences were not observed. Adverse effects were rarely observed. In conclusion, KD proved to be an effective treatment for refractory epilepsy.

Ketogenic diet for the treatment of refractory epilepsy: a 10 year experience in children

Ketogenic diet (KD) is a high fat and low carbohydrate diet, which controls refractory epilepsy. We analyzed the KD effects on 54 children of the Children's Institute of the University of São Paulo. Efficacy, tolerability, and adverse effects were studied. Response to KD was effective (E) if seizure control was >75 percent, good (G) when 50-75 percent. When possible, we correlated the results with the epileptic syndrome and patient's age. By the second month on diet, 57.4 percent of the patients had E response and 31.4 percent G results. At the 6th month, 63.8 percent had E response and 25.5 percent G. At the 12th month, 71.8 percent had E and 25.6 percent G. At the 24th month, 62.1 percent had E and 37.9 percent G. Antiepileptic drugs have been reduced, and generalized epilepsy was the most sensitive. Age-related differences were not observed. Adverse effects were rarely observed. In conclusion, KD proved to be an effective treatment for refractory epilepsy.

A dieta cetogênica (DC) tem alto teor de gordura e baixo de carboidratos e proteínas, sendo usada no tratamento da epilepsia refratária. Analisamos os efeitos da DC em 54 crianças do Instituto da Criança da Universidade de São Paulo. Eficácia, tolerabilidade e efeitos adversos foram estudados. A DC foi considerada eficaz (E) quando houve redução de crises >75 por cento e boa (B) quando a redução foi entre 50-75 por cento. Correlacionamos, quando possível, esses resultados com a síndrome epiléptica e com a idade dos pacientes. Observamos resultados (E) em 57,4 por cento, 63,8 por cento, 71,8 por cento e 62,1 por cento dos pacientes no 2°, 6°, 12° e 24° meses, respectivamente e (B) em 31,4 por cento, 25,5 por cento, 25,6 por cento e 37,9 por cento, respectivamente. Houve redução significativa das drogas antiepilépticas. A DC foi mais eficaz nas epilepsias generalizadas e não houve diferenças quanto a idade. Efeitos adversos foram raros. Em conclusão, a DC é um tratamento antiepiléptico eficaz em casos refratários.

Lesões de pele do tipo acrodermatite enteropática em duas crianças com doença da urina de xarope do bordo / Acrodermatitis enteropathica-like eruption in two children with maple syrup urine disease

Lesões cutâneas semelhantes à acrodermatite enteropática têm sido descritas em pacientes com algumas doenças metabólicas tratadas com dietas hipoprotéicas. Esses pacientes geralmente apresentam baixos níveis séricos de alguns aminoácidos, especialmente da isoleucina. Descrevemos dois pacientes que evoluíram com lesões semelhantes às da acrodermatite enteropática durante o tratamento da doença da urina do xarope de bordo , sem deficiência do zinco. A suplementação da isoleucina determinou rápida melhora das lesões dermatológicas.

Acrodermatitis enteropathica-like cutaneous lesions have been reported in patients with some metabolic disorders that are treated with a low-protein diet. These patients usually have low blood levels of some amino acids, especially isoleucine. We describe two patients who evolved with eruptions resembling acrodermatitis enteropathica while undergoing treatment for maple syrup urine disease, without zinc deficiency. Isoleucine supplementation led to a prompt improvement of the skin disorder.

Cockayne syndrome type A: novel mutations in eight typical patients.

Cockayne syndrome is a rare autosomal recessive neurodegenerative disorder. It is considered to be a heterogeneous condition based on complementation in cell fusion studies, with two major forms, namely CS-A and CS-B. CKN1 is the gene responsible for CS-A, whose mutations disrupt the transcription-coupled repair system of the actively transcribed DNA. Mutation analysis of the CKN1 gene in eight typical CS-A Brazilian patients from six families showed a gene alteration in all of them. We found a total of five novel mutations that were absent from healthy control subjects. Six affected subjects were simple homozygotes and two affected siblings were each compound heterozygotes. While the findings extend the range of mutations in CS-A, there is no obvious genotype-phenotype correlation across the mutational spectrum.

Epilepsy in patients with angelman syndrome caused by deletion of the chromosome 15q11-13.

BACKGROUND: Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, speech disorder, stereotyped jerky movements, and a peculiar behavioral profile, with a happy disposition and outbursts of laughter. Most patients with AS present with epilepsy and suggestive electroencephalographic patterns, which may be used as diagnostic criteria. OBJECTIVE: To study epilepsy and response to treatment in a series of patients with AS determined by deletion. DESIGN: Parent and caregiver interview and medical record review. SETTING: Epilepsy Center at the University of São Paulo. PATIENTS: Nineteen patients with AS determined by deletion of chromosome 15q11-13. MAIN OUTCOME MEASURES: Epilepsy severity, epilepsy evolution, and response to antiepileptic drug treatment. RESULTS: All patients with AS in this group had generalized epilepsy, and 10 (53%) also had partial epilepsy. Main seizure types were atypical absences and myoclonic and tonic-clonic seizures. Mean age at onset was 1 year 1 month. Epilepsy aggravated by fever occurred in 10 patients (53%) and status epilepticus in 16 (84%). Eighteen patients (95%) had previous or current history of daily seizures, of which 14 (64%) had disabling seizures. Multiple seizure types were observed in 13 patients (53%). History of refractory epilepsy was reported in 16 patients (84%). Parents reported improvement, characterized by decrease in seizure frequency or seizure control, at the mean age of 5.3 years. Therefore, most of these patients had a period of refractory epilepsy; however, improvement occurred during late childhood and puberty. The best therapeutic response was obtained with valproic acid alone or in association with phenobarbital or clonazepam. Epilepsy was aggravated by carbamazepine, oxcarbazepine, and vigabatrin. CONCLUSIONS: Patients with AS with deletion have epilepsy with early onset and stereotyped electroclinical profile regarding seizure type, severity, and response to antiepileptic drug treatment. Another feature of AS is the age-related improvement, even in refractory cases, during late childhood and puberty. These characteristics are not specific to this syndrome but, when inserted in the proper clinical context, may anticipate diagnosis. We believe that AS should be considered a differential diagnosis in developmentally delayed infants with severe, generalized, cryptogenic epilepsy; however, a proper electroclinical delineation of each genetic group is mandatory.

Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy.

OBJECTIVE: To evaluate the effectiveness of dexamethasone as an adjunctive therapy to antibiotics in children with meningococcal meningitis. METHOD: A total of 81 children diagnosed with meningococcal meningitis hospitalized in sequence were studied at the University Hospital of São Paulo University, with the objective of evaluating the presence of sequelae in four different groups of patients, following the administration of dexamethasone: Group I - 25 patients who received the first dose at least 10 minutes before the introduction of the antibiotic therapy; Group II - 19 patients who received the corticosteroid concomitantly; Group III - 14 patients for which the dexamethasone was administered after beginning the antibiotic scheme; Group IV - 23 patients that did not receive dexamethasone. The groups were evaluated for homogeneity through the prognostic indexes and clinical and laboratory characteristics, based on the records obtained at hospitalization. RESULTS: Some degree of sequelae occurred in 16 (26.22%) of the survivors and 23 patients (28.39%) coursed with sequelae or died. The mean period of neurological attendance was 36.97 months and neurological alterations were detected in 16.17% of the patients. No significant difference was found between the four groups. There was also no statistical difference in the comparison of the neurological sequelae in the children from group IV with the children of groups I and II or even with groups I, II and III analyzed as a whole. The presence of hearing loss occurred in 11.11% of the patients, again there was no significant difference between the four groups. Psychological evaluation was performed using the WPSSI and WISC tests. A mild mental disability was detected in one patient from group I and another in group III. The overall analysis of the sequelae (neurological, auditory and intellectual level) also did not demonstrate any significant difference between the four groups. Comparing the children from groups I and II together and also groups I, II and III as a whole with the children in group IV also failed to detect a significant difference arising from the use or nonuse of the corticosteroid. CONCLUSION: Dexamethasone was not proven to be effective in decreasing the number of sequelae among patients with meningococcal meningitis.

Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy

OBJETIVO: Avaliar a eficácia da dexametasona como uma terapia adjunta à antibioticoterapia em crianças com meningite meningocócica. MÉTODO: Foram avaliadas 81 crianças com diagnóstico de meningite meningocócica e hospitalizadas sequencialmente no Hospital Universitário da Universidade de São Paulo, com o objetivo de avaliar a presença de sequelas em 4 diferentes grupos de pacientes, segundo a administração da dexametasona: Grupo I - 25 pacientes, que receberam a primeira dose pelo menos 10 minutos antes da introdução da antibioticoterapia; Grupo II - 19 pacientes que receberam o corticosteróide de modo concomitante à antibioticoterapia; Grupo III - 14 pacientes, nos quais a dexametasona foi administrada após o início do esquema antibiótico; Grupo IV - 23 pacientes que não receberam dexametasona. A avaliação das características clínicas e laboratoriais no momento da internação demonstrou que os 4 grupos poderiam ser considerados homogêneos. RESULTADOS: Algum grau de sequela ocorreu em 16 (26,22%) dos sobreviventes e 23 pacientes (28,39%) apresentaram sequelas ou faleceram. O período médio de seguimento neurológico foi 36,97 meses e foram detectadas alterações neurológicas em 16,17% dos pacientes. Não se observaram diferenças significativas em relação a presença de seqüelas neurológicas entre os 4 grupos, não havendo também diferenças entre as crianças do grupo IV em relação ao agrupamento das crianças dos grupos I e II ou mesmo I, II e III. A presença de disacusia ocorreu em 11,11% dos pacientes, também não havendo diferenças entre os 4 grupos. A avaliação psicológica foi realizada através dos testes WPSSI and WISC. Foi detectada a presença de deficiência mental leve em um paciente do grupo I e em outro do grupo III. A avaliação global das sequelas (neurológicas, auditivas e cognitivas) também não mostrou haver diferenças significativas entre os 4 grupos. A comparação conjunta das crianças dos grupos I e II e também dos grupos I, II e III com as do grupo IV, também não permitiu a verificação da presença de diferenças significativas em relação a utilização ou não do corticosteróide. CONCLUSAO: A dexametasona não foi efetiva na redução de sequelas em crianças com meningite meningocóccica.

Möbius sequence in children exposed in utero to misoprostol: neuropathological study of three cases.

BACKGROUND: Misoprostol exposure in the first trimester of pregnancy has been related to congenital malformations, particularly the Möbius sequence and terminal transverse limb defects. CASES: Neuropathological findings of three patients with Möbius sequence related to misoprostol are reported. No previous pathological studies have shown these abnormalities to be associated with misoprostol exposure in utero. The brain stem was cut serially, from the rostral mesencephalum to the caudal aspect of the medulla, and all fragments were stained with hematoxylin-eosin and cresyl violet. Old ischemic-anoxic foci of gliosis, with necrosis and calcification, dorsally situated, were present from the pons to the medulla, involving some cranial nerve nuclei (especially the IV, VII, and XII) that were partially or completely depopulated of neural cells. CONCLUSIONS: The findings suggest a circulatory mechanism to the Möbius sequence, with vascular disruption involving the territory of the subclavian artery, occurring in a critical period of embryonic life between six to eight weeks postconception. These cases add further evidence of the role of misoprostol as a teratogen.