Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc.

Habilidades psicolinguísticas e escolares em crianças com mielomeningocele / Psycholinguistic and scholastic abilities in children with myelomeningocele

OBJETIVO: Descrever o desempenho de indivíduos com mielomeningocele quanto às habilidades psicolinguísticas e escolares. MÉTODOS: Participaram cinco indivíduos, com idade cronológica entre 9 anos e 10 meses e 11 anos e 7 meses, com diagnóstico de mielomeningocele e lesão lombo-sacral (Grupo 1 - G1), e cinco indivíduos com desenvolvimento típico (Grupo 2 - G2), que foram pareados ao G1 quanto a idade, gênero e grau de escolaridade. A avaliação constou de entrevista com os responsáveis e aplicação dos seguintes testes: Teste de Illinois de Habilidades Psicolinguísticas; Teste de Desempenho Escolar; Teste de Velocidade de Leitura; e Teste de Nomeação Automática Rápida. RESULTADOS: A comparação entre os grupos nos subtestes do Teste de Illinois de Habilidades Psicolinguísticas indicou que os valores máximos obtido pelo G1 corresponderam aproximadamente aos valores mínimos obtidos pelo G2, confirmando a diferença entre eles, exceto para o subteste closura auditiva. No Teste de Desempenho Escolar foram observadas alterações significativas no desempenho do G1 em todas as provas. Nos testes de Velocidade de Leitura e de Nomeação Rápida, os indivíduos do G1 também apresentaram prejuízos consideráveis, cometendo mais erros nas tarefas e realizando a atividade de modo mais lento. CONCLUSÃO: Indivíduos com mielomeningocele apresentam alterações nas habilidades psicolinguísticas, no desempenho escolar, na velocidade de leitura e na nomeação automática rápida.

PURPOSE: To describe the performance of individuals with myelomeningocele regarding psycholinguistic and scholastic abilities. METHODS: Participants were five individuals with myelomeningocele and lumbar sacral abnormalities, and chronological age between 9 years and 10 months and 11 years and 7 months (Group 1 - G1); five subjects with typical development (Group 2 - G2), matched to G1 for age, gender, and educational level. The evaluation consisted of interview with parents/caregivers, and application of the following tests: Illinois Test of Psycholinguistic Abilities (ITPA); School Performance Test; Speed Reading Test; and Rapid Automatized Naming Test. RESULTS: The between-groups comparison in the ITPA subtests showed that the maximum values obtained by G1 corresponded approximately to the minimum values obtained by G2, confirming the difference between the groups, except for the auditory closure subtest. In the Scholastic Performance Test, significant alterations were observed on the performance of G1 in all tasks. In the Speed Reading and Rapid Automatized Naming tests, individuals in G1 also presented considerable deficits, making more mistakes and spending more time than G2 to perform the same tasks. CONCLUSION: Individuals with myelomeningocele present deficits in psycholinguistic abilities, school performance, reading speed, and rapid automatized naming.

Psycholinguistic and scholastic abilities in children with myelomeningocele.

PURPOSE: To describe the performance of individuals with myelomeningocele regarding psycholinguistic and scholastic abilities. METHODS: Participants were five individuals with myelomeningocele and lumbar sacral abnormalities, and chronological age between 9 years and 10 months and 11 years and 7 months (Group 1 - G1); five subjects with typical development (Group 2 - G2), matched to G1 for age, gender, and educational level. The evaluation consisted of interview with parents/caregivers, and application of the following tests: Illinois Test of Psycholinguistic Abilities (ITPA); School Performance Test; Speed Reading Test; and Rapid Automatized Naming Test. RESULTS: The between-groups comparison in the ITPA subtests showed that the maximum values obtained by G1 corresponded approximately to the minimum values obtained by G2, confirming the difference between the groups, except for the auditory closure subtest. In the Scholastic Performance Test, significant alterations were observed on the performance of G1 in all tasks. In the Speed Reading and Rapid Automatized Naming tests, individuals in G1 also presented considerable deficits, making more mistakes and spending more time than G2 to perform the same tasks. CONCLUSION: Individuals with myelomeningocele present deficits in psycholinguistic abilities, school performance, reading speed, and rapid automatized naming.

Achados neuropsicolinguísticos na síndrome de Crouzon: relato de caso / Neuropsycholinguistic findings in Crouzon syndrome: case report

O objetivo do trabalho foi relatar um caso clínico sobre a síndrome de Crouzon, englobando as habilidades neuropsicolinguisticas. O estudo foi realizado com uma criança de oito anos e dois meses, do gênero masculino, com diagnóstico clínico da síndrome de Crouzon. Para a caracterização das habilidades foi realizada avaliação interdisciplinar com fonoaudiólogo, psicólogo e neurologista. A avaliação fonoaudiológica incluiu a avaliação das habilidades comunicativas, da linguagem oral, considerando as habilidades fonológicas, sintáticas, semânticas e pragmáticas, e da linguagem escrita. Para a avaliação neuropsicológica utilizou-se a escala Wechsler Scale for Children. A avaliação neurológica foi centrada no exame de ressonância magnética de encéfalo. O paciente também realizou avaliação audiológica, e apresentou perda auditiva condutiva de grau leve. Na avaliação clínica e formal da linguagem oral foi possível observar alterações nos aspectos fonológico e semântico da linguagem. Já com relação à linguagem escrita, observou-se desempenho aquém do esperado para a idade, caracterizado principalmente por alterações na escrita e na aritmética. Os resultados da avaliação neuropsicológica evidenciaram valores de Quociente Intelectual dentro dos padrões da normalidade. O resultado da ressonância magnética do encéfalo demonstrou alteração estrutural do sistema nervoso central. Pode-se concluir que os achados evidenciaram alterações nas habilidades de linguagem oral e escrita, além da presença de alteração estrutural do sistema nervoso central.

The aim of this study was to relate the neuropsycholinguistic abilities of a male child with eigth years and two months, diagnosed with Crouzon syndrome. The characterization of neropsycholinguitic abilities was based on a interdisciplinary evaluation carried out by a speech-language pathologist, a neurologist, and a psychologist. Speech-language evaluation included the assessment of communication skills, oral (phonological, syntactic, semantic and pragmatic abilities) and written language. The neuropsychological assessment used the Wechsler Scale for Children. The neurological evaluation was focused on the results of magnetic resonance imaging. The subject also carried out an audiological evaluation, which showed mild conductive hearing loss. In the oral language assessment, phonological and semantic deficits were observed. Written language performance was also below the expected for the subject's age, characterized mainly by writing and arithmetic deficits. The neuropsychological evaluation showed normal Intellectual Quotient. The results of the magnetic resonance imaging showed structural alterations of the central nervous system. Thus, the findings evidenced oral and written language deficits, and presence of structural alterations of the central nervous system.

Results of microsurgical treatment of medulla oblongata and spinal cord hemangioblastomas: a comparison of two distinct clinical patient groups.

PURPOSE: To analyze the surgical outcome of a consecutive and single center series of medulla oblongata (MO) and spinal cord hemangioblastomas (HB). PATIENT AND METHODS: We retrospectively reviewed the medical charts of all MO and spinal HB patients operated on in our institution between 1985 and 2002. All patients had pre- and at least one post-operative MRI. McCormick classification was used to assess neurological status and functional outcome. RESULTS: Forty surgical procedures have been performed on 34 patients (19 females and 15 males, mean age of 41 years). Twenty-five (73%) patients had Von Hippel Lindau (VHL) disease confirmed by genetic screening, and nine patients had sporadic disease. Complete clinical, radiological, and genetic studies were done in all cases. The most frequent clinical symptom was pain (28 patient, 85%) followed by motor (42%) and sensitive deficits (42%). Fourteen lesions (19%) were located in the MO, 28 (38%) in the cervical spine, 25 (34%) in the thoracic spine, 4 (5%) in the lumbar spine and 3 (4%) in the Cauda Equina. In the VHL group, 15 patients (60%) presented multiple lesions and 10 a single neurological lesion (40%). A cyst was present in 23% of VHL patients and in 55% of the non-VHL group. A complete removal was achieved in 85% of all cases. No deaths related to surgery occurred. At the end of the follow-up period (mean 60 months) 50% of patients were stabilized, while the condition of 32.35% was improved and of 17.65% worsened. Comparing the clinical evolution considering the presence or not of VHL we have seen that there are no differences in terms of functional outcome between VHL and non-VHL groups. CONCLUSION: Our results confirmed that surgery remains a safe and effective treatment for medulla oblongata and spinal hemangioblastoma. Only symptomatic lesion required surgical treatment. In other cases, especially in VHL patients, a close and regular follow-up (clinical and MRI) is necessary.

Desenvolvimento cognitivo de pacientes com síndrome de Apert e síndrome de Crouzon: modelo multidisciplinar de avaliação / Cognitive development in Apert Syndrome and Crouzon Syndrome patients: a multidisciplinary model for evaluation

As craniossinostoses sindrômicas, dentre as quais são mais frequentes a Síndrome de Apert e a Síndrome de Crouzon, apresentam como desafio em seu tratamento uma abordagem multi e interdisciplinar objetivando um maior desenvolvimento e melhor qualidade de vida para estes pacientes. A Síndrome de Apert e a Síndrome de Crouzon são decorrentes de mutações no gene que codifica o receptor do Fator de Crescimento de Fibroblastos e têm em comum o fechamento precoce das suturas cranianas que cursam por vezes com hipertensão intracraniana. Diversos são os fatores apontados como importantes na determinação do desenvolvimento cognitivo final destes pacientes que podem apresentar desde um desempenho adequado para o convívio social exercendo suas potencialidades intelectuais até indivíduos com atraso importante no desenvolvimento. Fatores como cirurgia craniofacial para descompressão do encéfalo, melhora dos aspectos craniofaciais estéticos e benefícios para a respiração são apontados como relevantes neste desenvolvimento. As alterações encefálicas que podem estar ausentes, serem únicas ou mesmo múltiplas são também apontadas como possíveis determinantes do desenvolvimento cognitivo. O estímulo do meio através da interação com familiares e o ambiente de convívio estimulante são fundamentais. Compilamos trabalhos publicados pelo autor no período 2004 a 2007 que evidenciam a importância dos fatores relacionados ao desenvolvimento cognitivo devendo-se ressaltar a classe socioeconômica das famílias e o nível de instrução dos pais. A qualidade de vida das famílias apresentou uma relação de influência bilateral com o desenvolvimento cognitivo dos pacientes. São apresentados, adicionalmente, resumos de dissertações orientadas pelo autor nos quais é evidenciada a possibilidade de aumento da complexidade do modelo de avaliação através do exame fonoaudiológico. A aplicabilidade do modelo de avaliação no estudo de outras malformações craniofaciais é também caracterizada...

The Apert Syndrome and Crouzon Syndrome are the most common syndromic craniosynostosis. They present as a target in their treatment an inter and multi-disciplinary approach to determine a good development and quality of life for these patients. The Apert Syndrome and Crouzon Syndrome are secondary to the gene mutation that codifies the fibroblast growth factor receptor and present as common characteristic the early closure of the cranial sutures that can determine high levels of intracranial pressure. Many factors are important to determine the final cognitive development of these patients. They can present a normal social life developing ali their intellectual potential as they can present an important retard in their development. The craniofacial surgery to decompress the brain, to ameliorate the esthetics craniofacial aspects and to allow respiratory benefits, is relevant to determine the global development. The brain malformations that can be absent unique or multiple are also presented as related to the cognitive development. The environment where these patients live and the familial integration are very important. We present the articles published by the author from 2004 to 2007 that present the different factors related to the cognitive development of patients with syndromic craniosinostosys and the social and educational aspects of the families presented are the most important factors. The quality of life of the families, are also correlated to the intellectual levei of the patients in a bidirectional aspecto Abstracts of two studies oriented by the author are also presented to show the possibility to expand the evaluation’s model with a speech and language examination. The applicability of the model to study another craniofacial abnormality is presented. As we confirm the utilization of a multidisciplinary model of evaluation with a systematic method we understood by a consistent way the cognitive development of patients with syndromic...

[Crouzon syndrome: factors related to the neuropsychological development and to the quality of life]. / Síndrome de crouzon: fatores envolvidos no desenvolvimento neuropsicologico e na qualidade de vida.

Crouzon syndrome is characterized by cranial and facial abnormalities and exophtalmos. Mental retardation is sometimes observed. The objective of this study was to correlate brain malformations, timing for surgery and also social classification of families and parents education to the neuropsychological evaluation and to the quality of life of these families. Eleven patients with Crouzon syndrome were studied, whose ages were between 16 and 132 months. The multidisciplinary evaluation included : social evaluation, cognitive evaluation, brain studies by magnetic resonance imaging and quality of life evaluation. The intelligence quotient values observed were between 46 and 102 (m=84.2) and was correlated (inverted correlation) to the factor IV of the short-form of the Questionnaire on Resources and Stress. Mental development was not correlated to brain malformation, neither to the age at time of operation or to the level of family environment and parents education.

Síndrome de crouzon: fatores envolvidos no desenvolvimento neuropsicologico e na qualidade de vida / Crouzon syndrome: factors related to the neuropsychological development and to the quality of life

A síndrome de Crouzon é caracterizada por deformidade craniana, alterações faciais e exoftalmia. O retardo no desenvolvimento neuropsicomotor é observado em alguns casos. Este estudo tem como objetivo analisar a influência do momento da cirurgia, da classe sócio-econômica associada ao nível educacional dos pais e da ocorrência de malformações do sistema nervoso central no desenvolvimento cognitivo destes pacientes correlacionando estes achados à qualidade de vida deles e de suas famílias. Foram estudados 11 pacientes com diagnóstico de síndrome de Crouzon com idade entre um ano e quatro meses e treze anos. A avaliação multidisciplinar dos pacientes incluiu, avaliação social, avaliação cognitiva, estudo do encéfalo por ressonância magnética e avaliação da qualidade de vida. O quociente de inteligência variou de 46 a 102 (m=84,2) e foi correlacionado de forma inversa com o Fator 4 do Questionário de Recursos e Estresse Simplificado (incapacidade da criança); não se correlacionou com as alterações encefálicas, com a condição sócio-econômica dos pais e nem com o momento do tratamento neurocirúrgico.

Crouzon syndrome is characterized by cranial and facial abnormalities and exophtalmos. Mental retardation is sometimes observed. The objective of this study was to correlate brain malformations, timing for surgery and also social classification of families and parents education to the neuropsychological evaluation and to the quality of life of these families. Eleven patients with Crouzon syndrome were studied, whose ages were between 16 and 132 months. The multidisciplinary evaluation included : social evaluation, cognitive evaluation, brain studies by magnetic ressonance imaging and quality of life evaluation. The intelligence quotient values observed were between 46 and 102 (m=84.2) and was correlated (inverted correlation) to the factor IV of the short-form of the Questionnaire on Resources and Stress. Mental development was not correlated to brain malformation, neither to the age at time of operation or to the level of family environment and parents education.

Apert syndrome: factors involved in the cognitive development

A síndrome de Apert é caracterizada por cranioestenose, sindactilia simétrica e outras malformações sistêmicas. O retardo no desenvolvimento neuropsicomotor é freqüentemente observado. Este trabalho tem como objetivo analisar as malformações do sistema nervoso central, o momento da cirurgia e a classe sócio-econômica associada ao nível educacional dos pais como variáveis que possam influenciar no desenvolvimento cognitivo. Foram estudados 18 pacientes com diagnóstico de síndrome de Apert com idade entre 14 e 322 meses e as alterações encefálicas foram observadas em 55,6%. O quociente de inteligência variou de 45 a 108 e estava correlacionado com a classe sócio-econômica e com o nível de instrução dos pais; não se correlacionou com as alterações encefálicas nem com o momento do tratamento neurocirúrgico. Em conclusão, a condição sócio-econômica e o nível de instrução dos pais foram relevantes na determinação do desenvolvimento cognitivo destes pacientes.

Apert syndrome: factors involved in the cognitive development.

Apert syndrome is characterized by craniosynostosis, symmetric syndactyly and other systemic malformations, with mental retardation usually present. The objective of this study was to correlate brain malformations and timing for surgery with neuropsychological evaluation. We also tried to determine other relevant aspects involved in cognitive development of these patients such as social classification of families and parents education. Eighteen patients with Apert syndrome were studied, whose ages were between 14 and 322 months. Brain abnormalities were observed in 55.6% of them. The intelligence quotient or developmental quotient values observed were between 45 and 108. Mental development was related to the quality of family environment and parents education. Mental development was not correlated to brain malformation or age at time of operation. In conclusion, quality of family environment was the most significant factor directly involved in mental development of patients with Apert syndrome.

[Prototyping as an alternative to cranioplasty using methylmethacrylate: technical note]. / Prototipagem como forma alternativa para realização de cranioplastia com metilmetacrilato: nota técnica.

The prototyping is a method for reconstruction of human body segments by computer software. It has been used in neurosurgery for cranial reproduction in patients allowing the programming of surgical procedures and the production of prosthesis to reconstruct bone failures in the skull. We present two cases of cranioplasty performed with the use of acrylic prosthesis constructed by prototyping. After 10 months of follow-up, they do not present signs of infection and show good aesthetic result. The advantages pointed at the literature for this method (reduction of surgical time, easy technical handle, and good aesthetic result) were confirmed.

Prototipagem como forma alternativa para realização de cranioplastia com metilmetacrilato: nota técnica / Prototyping as an alternative to cranioplasty using methylmethacrylate: technical note

A prototipagem, método de reconstrução de segmentos do corpo humano através de programas de computação, tem sido usada na neurocirurgia para reproduzir o crânio de pacientes permitindo a programação de atos cirúrgicos e a produção de próteses para reconstruir falhas ósseas no crânio. Apresentamos dois casos de cranioplastia realizadas com o uso de próteses de acrílico construídas por prototipagem. Após 10 meses de acompanhamento, os pacientes não apresentaram sinais de infecção e apresentam bom resultado estético. As vantagens apontadas na literatura para este método (redução do tempo cirúrgico, facilidade técnica e bom resultado estético) foram observadas.