Effect of prednisolone on language function in children with autistic spectrum disorder: a randomized clinical trial

Abstract Objective: To describe the effect of prednisolone on language in children with autism spectrum disorder. This study is based upon two hypotheses: autism etiology may be closely related to neuroinflammation; and, an effective treatment should restore the individual's language skills. Method: This is a prospective, double-blinded, randomized, placebo-controlled clinical trial, carried out in a federal university hospital. The initial patient sample consisted of 40 subjects, which were randomized into two parallel groups. Inclusion criteria were: male gender, 3-7 years of age, and meeting the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) diagnostic criteria. The final sample consisted of 38 patients, of whom 20 were randomized to the placebo group and 18 to the active group. The latter received prednisolone for 24 weeks, at an initial dose of 1 mg/kg/day and a tapering dose from the ninth week onward. Language was measured on four occasions over a 12-month period by applying two Brazilian tools: the Language Development Assessment (ADL) and the Child Language Test in Phonology, Vocabulary, Fluency, and Pragmatics (ABFW). Results: The side effects were mild: two patients had hypertension, five had hyperglycemia, and two had varicella. Prednisolone increased the global ADL score in children younger than 5 years of age who had developmental regression (p = 0.0057). The ABFW's total of communicative acts also responded favorably in those participants with regression (p = 0.054). The ABFW's total of vocal acts showed the most significant results, especially in children younger than 5 years (p = 0.004, power = 0.913). Conclusions: The benefit of prednisolone for language scores was more evident in participants who were younger than five years, with a history of developmental regression, but the trial's low dose may have limited this benefit. The observed side effects do not contraindicate corticosteroid use in autism.

Effect of prednisolone on language function in children with autistic spectrum disorder: a randomized clinical trial.

OBJECTIVE: To describe the effect of prednisolone on language in children with autism spectrum disorder. This study is based upon two hypotheses: autism etiology may be closely related to neuroinflammation; and, an effective treatment should restore the individual's language skills. METHOD: This is a prospective, double-blinded, randomized, placebo-controlled clinical trial, carried out in a federal university hospital. The initial patient sample consisted of 40 subjects, which were randomized into two parallel groups. Inclusion criteria were: male gender, 3-7 years of age, and meeting the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) diagnostic criteria. The final sample consisted of 38 patients, of whom 20 were randomized to the placebo group and 18 to the active group. The latter received prednisolone for 24 weeks, at an initial dose of 1mg/kg/day and a tapering dose from the ninth week onward. Language was measured on four occasions over a 12-month period by applying two Brazilian tools: the Language Development Assessment (ADL) and the Child Language Test in Phonology, Vocabulary, Fluency, and Pragmatics (ABFW). RESULTS: The side effects were mild: two patients had hypertension, five had hyperglycemia, and two had varicella. Prednisolone increased the global ADL score in children younger than 5 years of age who had developmental regression (p=0.0057). The ABFW's total of communicative acts also responded favorably in those participants with regression (p=0.054). The ABFW's total of vocal acts showed the most significant results, especially in children younger than 5 years (p=0.004, power=0.913). CONCLUSIONS: The benefit of prednisolone for language scores was more evident in participants who were younger than five years, with a history of developmental regression, but the trial's low dose may have limited this benefit. The observed side effects do not contraindicate corticosteroid use in autism.

Assessment of acute motor deficit in the pediatric emergency room.

OBJECTIVES: This review article aimed to present a clinical approach, emphasizing the diagnostic investigation, to children and adolescents who present in the emergency room with acute-onset muscle weakness. SOURCES: A systematic search was performed in PubMed database during April and May 2017, using the following search terms in various combinations: "acute," "weakness," "motor deficit," "flaccid paralysis," "child," "pediatric," and "emergency". The articles chosen for this review were published over the past ten years, from 1997 through 2017. This study assessed the pediatric age range, from 0 to 18 years. SUMMARY OF THE DATA: Acute motor deficit is a fairly common presentation in the pediatric emergency room. Patients may be categorized as having localized or diffuse motor impairment, and a precise description of clinical features is essential in order to allow a complete differential diagnosis. The two most common causes of acute flaccid paralysis in the pediatric emergency room are Guillain-Barré syndrome and transverse myelitis; notwithstanding, other etiologies should be considered, such as acute disseminated encephalomyelitis, infectious myelitis, myasthenia gravis, stroke, alternating hemiplegia of childhood, periodic paralyses, brainstem encephalitis, and functional muscle weakness. Algorithms for acute localized or diffuse weakness investigation in the emergency setting are also presented. CONCLUSIONS: The clinical skills to obtain a complete history and to perform a detailed physical examination are emphasized. An organized, logical, and stepwise diagnostic and therapeutic management is essential to eventually restore patient's well-being and full health.

Assessment of acute motor deficit in the pediatric emergency room / Avaliação do déficit motor agudo no ambiente de pronto socorro pediátrico

Abstract Objectives: This review article aimed to present a clinical approach, emphasizing the diagnostic investigation, to children and adolescents who present in the emergency room with acute-onset muscle weakness. Sources: A systematic search was performed in PubMed database during April and May 2017, using the following search terms in various combinations: "acute," "weakness," "motor deficit," "flaccid paralysis," "child," "pediatric," and "emergency". The articles chosen for this review were published over the past ten years, from 1997 through 2017. This study assessed the pediatric age range, from 0 to 18 years. Summary of the data: Acute motor deficit is a fairly common presentation in the pediatric emergency room. Patients may be categorized as having localized or diffuse motor impairment, and a precise description of clinical features is essential in order to allow a complete differential diagnosis. The two most common causes of acute flaccid paralysis in the pediatric emergency room are Guillain-Barré syndrome and transverse myelitis; notwithstanding, other etiologies should be considered, such as acute disseminated encephalomyelitis, infectious myelitis, myasthenia gravis, stroke, alternating hemiplegia of childhood, periodic paralyses, brainstem encephalitis, and functional muscle weakness. Algorithms for acute localized or diffuse weakness investigation in the emergency setting are also presented. Conclusions: The clinical skills to obtain a complete history and to perform a detailed physical examination are emphasized. An organized, logical, and stepwise diagnostic and therapeutic management is essential to eventually restore patient's well-being and full health.

Resumo Objetivos: Apresentar uma abordagem clínica, enfatizar a investigação diagnóstica, voltada para crianças e adolescentes no pronto-socorro com fraqueza muscular de surgimento agudo. Fontes: Foi feita uma pesquisa sistemática na base de dados PubMed entre abril e maio de 2017, com os seguintes termos de pesquisa em várias combinações: "agudo", "fraqueza", "déficit motor", "paralisia flácida", "criança", "pediátrico" e "emergência". Os trabalhos escolhidos para esta revisão foram publicados nos últimos dez anos, de 1997 a 2017. Este trabalho aborda a faixa etária pediátrica, até 18 anos. Resumo dos dados: O déficit motor agudo é uma causa razoavelmente comum para crianças e adolescentes procurarem o pronto-socorro. Os pacientes podem ser classificados como com deficiência motora localizada ou difusa e uma descrição precisa das características clínicas é essencial para possibilitar um diagnóstico diferenciado completo. As duas causas mais comuns de paralisia flácida aguda no pronto-socorro pediátrico são síndrome de Guillain-Barré e mielite transversa, independentemente de outras etiologias serem consideradas, como encefalomielite disseminada aguda, mielite infecciosa, miastenia grave, derrame, hemiplegia alternante da infância, paralisia periódica, encefalite do tronco encefálico e fraqueza muscular funcional. Os algoritmos da investigação de fraqueza aguda localizada ou difusa na configuração de emergência também são apresentados. Conclusões: São enfatizadas as habilidades clínicas para obter um histórico completo e fazer um exame físico detalhado. Um manejo diagnóstico e terapêutico organizado, lógico e por etapas é essencial para eventualmente restaurar o bem-estar e a saúde total do paciente.

Diffusion tensor imaging findings in school-aged autistic children.

OBJECTIVE: To analyze and compare cerebral white matter tracts through diffusion tensor imaging in autistic and normal children. METHODS: This is a case-control study on a sample of eight male, right-handed children diagnosed with autism according to Diagnostic and Statistical Manual of Mental Disorders-4th Edition criteria, and eight healthy age- and sex-matched controls. Imaging studies were performed on a 1.5-T scanner (Symphony Maestro Class, Siemens, Erlangen, Germany). Fractional anisotropy was calculated for the frontopontine and corticospinal tracts, frontal subcortical white matter, anterior cingulate, corpus callosum, striatum, internal capsule, optic radiation, superior and inferior longitudinal fascicles, and cerebellum. Analysis of significance was based on analysis of variance test for the mean fractional anisotropy values. RESULTS: Median age of cases was 9.53 +/- 1.83 years, and of controls, 9.57 +/- 1.36 years. Diffusion tensor imaging findings included significant reduction of fractional anisotropy in the anterior corpus callosum (P= .008), right corticospinal tract (P= .044), posterior limb of right and left internal capsules (P= .003 and .049, respectively), left superior cerebellar peduncle (P= .031), and right and left middle cerebellar peduncles (P= .043 and .039, respectively) in autistic children. CONCLUSIONS: The diffusion tensor imaging findings in children with autistic disorder suggest impairment of white matter microstructure, possibly associated with reduced connectivity in corpus callosum, internal capsule, and superior and middle cerebellar peduncles.

Proton magnetic resonance spectroscopy in children with fetal alcohol spectrum disorders.

OBJECTIVE: To analyze the metabolic constitution of brain areas through proton magnetic resonance spectroscopy in children affected with fetal alcohol spectrum disorder compared with normal children. METHOD: The sample of this case-control study included eight boys with epidemiologic history of in utero exposure to alcohol (median age 13.6+/-3.8 years) who were diagnosed with fetal alcohol spectrum disorder, and eight controls (median age 12.1+/-3,4 years). An 8 cm(3) single voxel approach was used, with echo time 30 ms, repetition time 1500 ms, and 128 acquisitions in a 1.5T scanner, and four brain areas were analyzed: anterior cingulate, left frontal lobe, left striatum, and left cerebellar hemisphere. Peaks and ratios of metabolites N-acetylaspartate, choline, creatine, and myo-inositol were measured. RESULTS: Children with fetal alcohol spectrum disorder showed a decrease in choline/creatine ratio (p=0.020) in left striatum and an increase in myo-inositol/creatine ratio (p=0.048) in left cerebellum compared with controls. There was no statistically significant difference in all peaks and ratios from the anterior cingulate and frontal lobe between the two groups. CONCLUSION: This study found evidence that the left striatum and left cerebellum are affected by intrauterine exposure to alcohol. Additional studies with larger samples are necessary to expand our knowledge of the effects of fetal exposure to alcohol.

Proton magnetic resonance spectroscopy in children with fetal alcohol spectrum disorders / Espectroscopia por ressonância magnética de prótons em crianças com transtornos do espectro alcoólico fetal

OBJECTIVE: To analyze the metabolic constitution of brain areas through proton magnetic resonance spectroscopy in children affected with fetal alcohol spectrum disorder compared with normal children. METHOD: The sample of this case-control study included eight boys with epidemiologic history of in utero exposure to alcohol (median age 13.6±3.8 years) who were diagnosed with fetal alcohol spectrum disorder, and eight controls (median age 12.1±3,4 years). An 8 cm³ single voxel approach was used, with echo time 30 ms, repetition time 1500 ms, and 128 acquisitions in a 1.5T scanner, and four brain areas were analyzed: anterior cingulate, left frontal lobe, left striatum, and left cerebellar hemisphere. Peaks and ratios of metabolites N-acetylaspartate, choline, creatine, and myo-inositol were measured. RESULTS: Children with fetal alcohol spectrum disorder showed a decrease in choline/creatine ratio (p=0.020) in left striatum and an increase in myo-inositol/creatine ratio (p=0.048) in left cerebellum compared with controls. There was no statistically significant difference in all peaks and ratios from the anterior cingulate and frontal lobe between the two groups. CONCLUSION: This study found evidence that the left striatum and left cerebellum are affected by intrauterine exposure to alcohol. Additional studies with larger samples are necessary to expand our knowledge of the effects of fetal exposure to alcohol.

OBJETIVO: Analisar a composição metabólica de áreas encefálicas através da espectroscopia de prótons por ressonância magnética em crianças com transtornos do espectro alcoólico fetal e crianças normais. MÉTODO: A amostra deste estudo de casos-controles incluiu 8 meninos com história epidemiológica de exposição fetal ao álcool (idade mediana 13,6±3,8 anos), diagnosticados com transtorno do espectro alcoólico fetal, e 8 controles (idade mediana 12,1±3,4 anos). Utilizou-se voxel único de 8 cm³, tempo de eco 30 ms, tempo de repetição 1.500 ms, 128 aquisições, em scanner de 1,5T para as seguintes áreas: cíngulo anterior, lobo frontal esquerdo, estriado esquerdo e hemisfério cerebelar esquerdo. Estudaram-se os picos e as razões dos metabólitos N-acetilaspartato, colina, creatina e o mio-inositol. RESULTADOS: As crianças acometidas apresentaram diminuição da razão colina/creatina (p=0,020) no estriado esquerdo, e aumento da razão mio-inositol/creatina (p=0,048) no cerebelo esquerdo. Não houve diferença estatisticamente significativa nos valores encontrados no cíngulo anterior e lobo frontal entre os dois grupos. CONCLUSÃO: Este estudo encontrou evidências de que o estriado e o cerebelo esquerdos são acometidos pela exposição intra-uterina ao álcool. Estudos adicionais com amostras maiores são essenciais para expandir nosso conhecimento dos efeitos da exposição fetal ao álcool.

Proton magnetic resonance spectroscopy in school-aged autistic children.

PURPOSE: This study aims to assess cerebral metabolites in school-aged autistic patients through proton magnetic resonance spectroscopy. METHODS: This case-control study included 10 right-handed male children (median age, 9.53 years +/- 1.80) with autism according to DSM-IV criteria, and 10 healthy age- and sex-matched healthy controls (median age, 8.52 years +/- 1.42). Imaging was performed on a 1.5-T scanner utilizing a single voxel point-resolved spectroscopy (PRESS) technique (TR = 1,500 ms, TE = 30 ms). Four cerebral areas were evaluated: bilateral anterior cingulate, left striatum, left cerebellar hemisphere, and left frontal lobe. Peak areas and ratios to creatine (Cr) of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) were analyzed. RESULTS: Compared with controls, autistic children showed a significant increase in mI (P= .021) and Cho (P= .042) peak areas in anterior cingulate and in mI/Cr ratio in anterior cingulate (P= .037) and left striatum (P= .035). The remaining metabolites and ratios were not significantly different between the 2 groups. CONCLUSIONS: This study found a statistically significant increase in myo-inositol and choline in anterior cingulate and left striatum of autistic children compared with controls. In contrast to previous studies, NAA peak area and NAA/Cr and NAA/Cho ratios had no statistically significant decrease in any of the 4 brain regions.

Central pontine and extrapontine myelinolysis: report of a case with a tragic outcome.

OBJECTIVE: To report a pediatric case of central pontine and extrapontine myelinolysis, a rare neurological disease often associated with rapid correction of hyponatremia. DESCRIPTION: A 15 year-old female adolescent developed locked-in syndrome during severe hyponatremia. Brain magnetic resonance imaging was consistent with the diagnosis of central pontine and extrapontine myelinolysis. COMMENTS: Serum sodium correction should proceed slowly and cautiously, based upon a careful calculation of sodium deficit, in order to minimize metabolic stress and avoid the occurrence of this dreadful complication, which has a tragic outcome in most cases. There is no scientifically proved effective treatment for myelinolysis, and severe cases usually have a dismal prognosis.

Central pontine and extrapontine myelinolysis: report of a case with a tragic outcome

OBJECTIVE: To report a pediatric case of central pontine and extrapontine myelinolysis, a rare neurological disease often associated with rapid correction of hyponatremia.DESCRIPTION: A 15 year-old female adolescent developed locked-in syndrome during severe hyponatremia. Brain magnetic resonance imaging was consistent with the diagnosis of central pontine and extrapontine myelinolysis.COMMENTS: Serum sodium correction should proceed slowly and cautiously, based upon a careful calculation of sodium deficit, in order to minimize metabolic stress and avoid the occurrence of this dreadful complication, which has a tragic outcome in most cases. There is no scientifically proved effective treatment for myelinolysis, and severe cases usually have a dismal prognosis.

Chronic inflammatory demyelinating polyradiculoneuropathy: two cases with cervical spinal cord compression.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder probably due to an immunological disturb. It evolves either in a steadily progressive or in a relapsing and fluctuating course. Weakness is mainly in the lower limbs proximally and distally. The electromyography is demyelinating. The cerebral spinal fluid protein is most of times elevated. Sometimes enlarged nerves are found. There are few cases described with spinal cord compression due to hypertrophic spinal nerve roots. Two patients (females, 66 and 67 years old) with diagnosis of a long standing CIDP are described. In the first one, the evolution was characterized by remission and relapsing course. The second patient had a chronic and progressive course. These patients presented after a long evolution a cervical spinal cord compression syndrome due to hypertrophic cervical roots. Neurologists must be aware of the possibility of development of spinal cord compression by enlarged spinal roots in patients with a long standing CIDP.

[Pseudotumor cerebri secondary to dural sinus thrombosis: pediatric case report]. / Pseudotumor cerebral secundário a trombose venosa dural: relato de caso pediátrico.

Pseudotumor cerebri is a relatively common neurologic syndrome in adolescence. In most cases, etiology is idiopathic, but it may have serious complications, such as blindness, that are related to increased intracranial pressure. The aim of this article is to emphasize the differential diagnosis of pseudotumor cerebri, with special attention to treatable etiologies. We report a case of an 12 year-old adolescent who presented with diplopia and headache 9 days after right-sided otitis media and mastoiditis. Head computerized tomography was normal, but brain magnetic resonance imaging demonstrated thrombosis of ipsilateral transverse and sigmoid sinuses, which responded promptly to early anticoagulation. The conclusion is that magnetic resonance imaging is essential for patients with a clinical diagnosis of pseudotumor cerebri in order to exclude treatable causes, such as dural sinus thrombosis.

Chronic inflammatory demyelinating polyradiculoneuropathy: two cases with cervical spinal cord compression

A polirradiculoneuropatia desmielinizante inflamatória crônica (PDIC) é uma afecção dos nervos periféricos de natureza autoimune, com evolução por surtos de exacerbação e remissão ou de evolver progressivo. O acometimento motor é predominante, com fraqueza proximal e distal nos membros inferiores. A eletroneuromiografia é do tipo desmielinizante com bloqueio de condução nervosa em dois ou mais nervos. Há aumento de proteínas do líquor. Com a evolução da doença pode haver espessamento dos nervos distal e/ou proximalmente. Excepcionalmente ocorre compressão da medula espinhal em qualquer segmento por raízes próximas hipertrofiadas. Foram estudadas duas mulheres de 66 e 67 anos respectivamente com quadro de PDIC de longa evolução. A primeira tinha evolução por surtos e na segunda o evolver era progressivo. Nos dois casos o espessamento proximal dos nervos provocou síndrome de compressão medular alta. Esta complicação deve ser pensada em casos de PDIC de longa duração.

Pseudotumor cerebral secundário a trombose venosa dural: relato de caso pediátrico / Pseudotumor cerebri secondary to dural sinus thrombosis: pediatric case report

O pseudotumor cerebral é uma síndrome neurológica relativamente comum na adolescência. Na maioria dos casos, a etiologia é idiopática, mas pode haver complicações graves, como cegueira, relacionadas com a hipertensão intracraniana. O objetivo deste artigo é enfatizar o diagnóstico diferencial do pseudotumor cerebral, com atenção especial às etiologias tratáveis. Relatamos o caso de um adolescente de 12 anos que se apresentou com diplopia e cefaléia 9 dias após otite média e mastoidite à direita. A tomografia computadorizada do crânio foi normal, mas a ressonância magnética do encéfalo detectou trombose dos seios transverso e sigmóideo ipsilaterais, a qual respondeu à anticoagulação precoce. A conclusão é que a ressonância magnética do encéfalo é essencial nos pacientes com diagnóstico clínico de pseudotumor cerebral para exclusão de causas tratáveis, como a trombose venosa dural.