Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc.

Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients.

Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.

Warburg Micro syndrome and Martsolf syndrome (MS) are heterogeneous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Causative biallelic germline mutations have been identified in RAB3GAP1, RAB3GAP2, or RAB18, each of which encode proteins involved in membrane trafficking. This report provides an up to date overview of all known disease variants identified in 29 previously published families and 52 new families. One-hundred and forty-four Micro and nine Martsolf families were investigated, identifying mutations in RAB3GAP1 in 41% of cases, mutations in RAB3GAP2 in 7% of cases, and mutations in RAB18 in 5% of cases. These are listed in Leiden Open source Variation Databases, which was created by us for all three genes. Genotype-phenotype correlations for these genes have now established that the clinical phenotypes in Micro syndrome and MS represent a phenotypic continuum related to the nature and severity of the mutations present in the disease genes, with more deleterious mutations causing Micro syndrome and milder mutations causing MS. RAB18 has not yet been linked to the RAB3 pathways, but mutations in all three genes cause an indistinguishable phenotype, making it likely that there is some overlap. There is considerable genetic heterogeneity for these disorders and further gene identification will help delineate these pathways.

Predisposition to epilepsy in fragile X syndrome: does the Val66Met polymorphism in the BDNF gene play a role?

Epilepsy is detected in about 23% of patients with fragile X syndrome (FXS). Absence or reduced levels of the fragile X mental retardation protein (FMRP), a global regulator of translation in neurons and an important factor in synaptic plasticity, produce the observed epileptic patterns. The brain-derived neurotrophic factor (BDNF) gene is a specific regulator of synaptic plasticity, and disturbances in its function cause dendrite abnormalities similar to those observed in FXS. A putative reciprocal regulation of FMRP and BDNF has been hypothesized. The Val66Met polymorphism in the BDNF gene may be involved in the alteration of normal secretion of the mature peptide and may modulate the epileptic phenotype observed in some patients with FXS. We investigated the relationship of this Met66 allele to the prevalence of epilepsy in 77 patients with FXS. No association was observed between this polymorphism and epilepsy in our group of patients. Therefore, it should not be considered a biomarker for developing epilepsy in patients with FXS.

[Cerebral creatine deficiency: first Spanish patients harbouring mutations in GAMT gene]. / Deficiencia cerebral de creatina: primeros pacientes españoles con mutaciones en el gen GAMT.

BACKGROUND AND OBJECTIVE: Brain creatine (Cr) deficiencies are a group of inborn errors of metabolism that are characterized by an absence or severe reduction of brain Cr. Clinically, these patients can display psychomotor/mental retardation and language disorders, commonly associated with epilepsy or movement disorders. Three metabolic defects are known: two affect synthesis - guanidinoacetate metiltransferase (GAMT) and glycine amidinotransferase (AGAT) deficiencies- and one affect the Cr transporter (CRTR). We present the first three Spanish patients with GAMT deficiency, and we compare their clinical phenotype and treatment response with other published cases. PATIENTS AND METHOD: The three patients presented mental retardation, epilepsy and autistic behaviour. Patient 1 also had severe chorea. Diagnosis was done by biochemical and genetic procedures (guanidinoacetate quantification, determination of GAMT activity and mutation analysis in the GAMT gene). RESULTS: An increase of guanidinoacetate was detected in urine and plasma. Brain magnetic resonance spectroscopy revealed low Cr levels. Enzymatic studies revealed a decreased GAMT activity in fibroblasts. Molecular analysis detected pathogenic mutations in the GAMT gene. After the deficiency was confirmed, the patients started treatment with Cr. In addition, patient 2 and 3 received an arginine-restricted diet and ornithine supplements. All them showed a partial improvement. CONCLUSIONS: Patients with GAMT deficiency have an unspecific but relatively constant clinical presentation. Brain Cr deficiency should be considered in patients with mental retardation of unknown aetiology, specially in those with movement disorders or epilepsy. Early diagnosis is important in cases with known treatment such as GAMT deficiency.

PLA2G6-associated neurodegeneration: New insights into brain abnormalities and disease progression.

INTRODUCTION: PLA2G6-associated neurodegeneration (PLAN) comprises a continuum of three phenotypes with overlapping clinical and radiologic features. METHODS: Observational clinical study in a cohort of infantile and childhood onset PLAN patients and genetic analysis of the PLA2G6 gene. We analysed chronological evolution in terms of age at onset and disease course through a 66-item questionnaire. We performed qualitative and quantitative assessment of MRI abnormalities and searched for clinical and radiological phenotype and genotype correlations. RESULTS: Sixteen PLAN patients (mean age: 10.2 years, range 3-33) were evaluated, with a median onset (years) of signs/symptoms as follows: neurological regression (1.5), oculomotor abnormalities (1.5), hypotonia (1.8), gait loss (2.2), pyramidal signs (3.0), axonal neuropathy (3.0), dysphagia (4.0), optic atrophy (4.0), psychiatric symptoms (4.0), seizures (5.9), joint contractures (6.0), dystonia (8.0), bladder dysfunction (13.0) and parkinsonism (15.0). MRI assessment identified cerebellar atrophy (19/19), brain iron deposition (10/19), clava hypertrophy (8/19) and T2/FLAIR hyperintensity of the cerebellar cortex (6/19). The mid-sagittal vermis relative diameter (MVRD) correlated with age at onset of clinical variants, meaning that the earlier the onset, the more severe the cerebellar atrophy. All patients harboured missense, nonsense and frameshift mutations in PLA2G6, including four novel variants. CONCLUSIONS: Cerebellar atrophy was a universal radiological sign in infantile and childhood onset PLAN, and correlated with the severity of the phenotype. Iron accumulation within the globus pallidum and substantia nigra was also a common and strikingly uniform feature regardless of the phenotype.

Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

BACKGROUND: Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. AIM: To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. METHOD: Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. RESULTS: Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. CONCLUSION: Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity.

Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening.

OBJECTIVES: To report the prevalence of creatine transporter deficiency in males with mental retardation and to study whether a protein-rich food intake might be a potential diagnostic pitfall. DESIGN AND METHODS: We determined creatine/creatinine ratio in urine samples from 1600 unrelated male patients with mental retardation and/or autism. Urine creatine was analyzed by HPLC-MS/MS. RESULTS: Thirty-three of 1600 cases showed increased urine creatine/creatinine ratio. Four out of these thirty-three cases were definitively diagnosed with creatine transporter deficiency, while the other 29 were false positive results. Significantly higher values were observed for urine Cr/Crn ratio in healthy volunteers after a meal based on beef or oily fish as compared to eggs, pasta or salad (Wilcoxon test: p<0.005). CONCLUSIONS: False positive results may be observed in biochemical screening for creatine transporter deficiency, and they may be due to intake of meals rich in creatine prior to urine samples analysis.

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function.

BACKGROUND: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. AIMS: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. PATIENTS AND METHODS: Thirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. RESULTS: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum). CONCLUSION: The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult.

Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates.

Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV). Furthermore, a comprehensive neuropsychological battery and magnetic resonance imaging were assessed. The results show that PPVT-III gives limited information on cognitive performance and brain correlates, getting lower intelligence quotient scores. The WNV provides similar outcomes as RCPM, but cases with severe motor impairment were unable to perform it. Finally, the RCPM gives more comprehensive information on cognitive performance, comprising not only visual but also verbal functions. It is also sensitive to the structural state of the brain, being related to basal ganglia, thalamus and white matter areas such as superior longitudinal fasciculus. So, the RCPM may be considered a standardized easy-to-administer tool with great potential in both clinical and research fields of bilateral cerebral palsy.

[Drooling therapy in children with neurological disorders]. / Tratamiento de la sialorrea en niños con patología neurológica.

INTRODUCTION: Drooling is the inability to retain saliva in the mouth and its progression to the digestive tract, being a common problem in pediatric patients with neurological disorders. Three different treatment options are available. AIM: To assess the effectiveness and safety of trihexyphenidyl, scopolamine and botulinum toxin infiltration in the treatment of drooling in children with neurological disorders. PATIENTS AND METHODS: This is an open and prospective type study. We include patients treated in the Neurology Service that present excessive drooling, affecting their quality of life, between 2009 and 2013. RESULTS: We enrolled 46 patients in the study. The treatment with oral trihexyphenidyl was indicated in 46, obtaining good result in 15 (32.6%), three with temporary effect and the rest with lasting effect. Three patients presented side effects (6.5%). Four out of 11 (36.36%) patients treated with scopolamine patch had beneficial effects. One was withdrawn due to lack of efficacy and six due to side effects. Twenty-five patients were infiltrated with botulinum toxin, with a significant decrease of drooling in 16 patients (64%) after the first injection. We observed no significant changes in nine patients. Only one out of 25 showed side effects (mild dysphagia). CONCLUSIONS: Currently there is not a fully effective therapeutic option for drooling. We recommend starting treatment with trihexyphenidyl. A second option could be the scopolamine patch and botulinum toxin as a third option. Botulinum toxin infiltration in salivary glands is shown as an effective and safe alternative in our study.

TITLE: Tratamiento de la sialorrea en niños con patologia neurologica.Introduccion. La sialorrea es la incapacidad para retener la saliva dentro de la boca y su progresion al tracto digestivo, y es un problema frecuente en pacientes pediatricos con patologia neurologica, por lo que se estan utilizando diferentes medidas para su tratamiento. Objetivo. Evaluar la eficacia y seguridad del trihexifenidilo, la escopolamina y la infiltracion de toxina botulinica en el tratamiento del babeo en niños con patologia neurologica. Pacientes y metodos. Es un estudio de tipo abierto y prospectivo. Incluye pacientes atendidos en el servicio de neurologia que presentaban babeo excesivo, con repercusion en su calidad de vida, entre 2009 y 2013. Resultados. En 46 pacientes se indico tratamiento con trihexifenidilo oral, y se obtuvo buena respuesta en 15 (32,6%), tres con efecto transitorio y el resto mantenido. Presentaron efectos secundarios tres pacientes (6,5%). De los 11 pacientes a los que se indicaron parches de escopolamina, se hallo efecto beneficioso en cuatro (36,36%), uno fue retirado por falta de eficacia y seis por efectos secundarios. Veinticinco pacientes fueron infiltrados con toxina botulinica, con disminucion significativa del babeo en 16 (64%) tras la primera infiltracion. No observamos cambios significativos en nueve casos. Solo uno presento efectos secundarios (disfagia leve). Conclusiones. Por no haber una opcion terapeutica totalmente eficaz para los pacientes con sialorrea, recomendamos iniciar el tratamiento con trihexifenidilo; como segunda opcion, los parches de escopolamina, y como tercera opcion, la toxina botulinica. La infiltracion de toxina botulinica en glandulas salivales se muestra como una alternativa eficaz y segura segun nuestra serie.

Perfil y factores pronósticos en el traumatismo craneoencefálico en la edad pediátrica / Prognostic factors and profi le in traumatic brain injury in the paediatric age

INTRODUCCIÓN: El traumatismo craneoencefálico (TCE) es una causa común de muerte y discapacidad en la población pediátrica, aunque la bibliografía en población española sea escasa. Desde la perspectiva de la vulnerabilidad temprana, los hallazgos de investigaciones recientes sugieren que la lesión cerebral temprana tiene peores secuelas y un mayor riesgo de impacto. OBJETIVOS: Analizar el perfil de la inteligencia, las funciones ejecutivas y el comportamiento, y examinar la asociación de la edad a la lesión, la gravedad del TCE y los factores ambientales para los resultados cognitivos y conductuales. PACIENTES Y MÉTODOS: Setenta y un participantes con TCE moderado a grave, con edades entre 6 y 16 años, fueron evaluados con medidas de inteligencia (cociente intelectual), funciones ejecutivas y comportamiento. RESULTADOS: Los niños con TCE tienen un mayor riesgo de discapacidad en todos los aspectos de inteligencia, funciones ejecutivas y comportamiento. Los niños que sufrieron una lesión cerebral traumática en la infancia y preescolar registraron más efectos globales en el cociente intelectual y algunos aspectos de las funciones ejecutivas. CONCLUSIONES: Los factores socioeconómicos y culturales son los mejores predictores para el cociente intelectual y el comportamiento. Estos hallazgos contribuyen a una mejor comprensión de las secuelas de TCE en los niños para ayudar en la planificación de rehabilitación y la readaptación a la vida funcional

INTRODUCTION: Traumatic brain injury (TBI) is a common cause of death and disability in the paediatric population, although the literature on the Spanish population is scarce. From the perspective of early vulnerability, recent research fi ndings suggest that early brain injury has worse sequelae and a higher risk of impact. Aims. To analyse the intelligence profi le, executive functions and behaviour, and examine the association between age at the time of the injury, severity of the TBI and environmental factors for cognitive and behavioural outcomes. PATIENTS AND METHODS: Seventy-one participants with moderate to severe TBI, from 6 to 16 years of age, were assessed with measures of intelligence (intelligence quotient), executive functions and behaviour. RESULTS: Children with TBI are at increased risk of disability in all aspects of intelligence, executive functions and behaviour. Children who suff ered a traumatic brain injury in infancy and the preschool period had more overall eff ects on intelligence quotient and some aspects of the executive functions. CONCLUSIONS: Socioeconomic and cultural factors are the best predictors for intelligence quotient and behaviour. These findings contribute to a better understanding of the sequelae of TBI in children, which will help in rehabilitation planning and re-adaptation to functional life

[Diploid/triploid mosaicism: a variable but characteristic phenotype]. / Mosaicismo diploide/triploide: un fenotipo variable, pero característico.

INTRODUCTION: Diploid/triploid mosaicism is a rare chromosomal abnormality. It is caused by a failure in the postzygotic division during embryonic development. It results in the coexistence of two genetically heterogeneous cell lines (46,XX and 69,XXX) in one individual. His clinical phenotype is characteristic. Pigmentary changes with a distribution pattern following Blaschko's lines abnormalities in other ectoderm-derived tissues are the main diagnostic signs. CASE REPORTS: Three cases of diploid/triploid mosaicism are described, and compared to the previously reported cases. The most frequently observed symptoms were mental retardation, truncal obesity, short stature, hemihypertrophy, small and narrow hands with clino and camptodactyly. Phenotypic characteristics of our three patients were similar to those of previously reported cases. Although there is no single and specific phenotype associated with mosaicism diploid/triploid, there are some dysmorphic features that shape a recognizable malformative syndrome. Peripheral blood lymphocytes karyotype was normal in our patients. Diagnosis was reached performing a fibroblast karyotype from hypopigmented skin. CONCLUSIONS: Intellectual disability associated with truncal obesity, short stature, hemihypertrophy or clino/camptodactyly should suggest to clinicians the possible existence of a diploid/triploid mosaicism. In most cases, karyotype from fibroblasts is needed to reach the diagnosis.

TITLE: Mosaicismo diploide/triploide: un fenotipo variable, pero caracteristico.Introduccion. El mosaicismo diploide/triploide es una alteracion cromosomica poco frecuente. La produce un fallo en la division poscigotica durante el desarrollo embrionario. Da lugar a la coexistencia de dos lineas celulares con diferente constitucion cromosomica (46,XX y 69,XXX) en un mismo individuo. Su fenotipo clinico es caracteristico. Las alteraciones pigmentarias con un patron de distribucion que sigue las lineas de Blaschko son el principal signo guia, asi como las alteraciones de otros tejidos derivados del ectodermo. Casos clinicos. Describimos las caracteristicas clinicas de tres pacientes afectos de mosaicismo diploide/triploide y realizamos una comparacion de su fenotipo clinico con el de los casos publicados previamente en la bibliografia. Las alteraciones observadas con mayor frecuencia fueron alteraciones cutaneas, discapacidad intelectual, obesidad troncular, talla baja, hemihipertrofia, y manos pequeñas y estrechas con clino y camptodactilia. Las caracteristicas fenotipicas de nuestros pacientes fueron similares a las de los casos comunicados previamente. Aunque no existe un fenotipo unico y especifico asociado al mosaicismo diploide/triploide, existen malformaciones caracteristicas que conforman un sindrome malformativo bien definido. El cariotipo realizado en linfocitos de sangre periferica en las tres pacientes fue normal, y se logro el diagnostico mediante cariotipo en fibroblastos cultivados tras biopsia de piel hipopigmentada. Conclusiones. La presencia de discapacidad intelectual asociada a obesidad troncular, talla baja, hemihipertrofia o clino y camptodactilia, ademas de las alteraciones cutaneas, debe hacer pensar en la posible existencia de un mosaicismo diploide/triploide. En la mayoria de los casos, es necesario el estudio del cariotipo en los fibroblastos para llegar al diagnostico.

Eficacia de una nueva intervención de apoyo a padres y escuelas después de un traumatismo craneoencefálico moderado o grave / Efficacy of a new parent and school-supported intervention after moderate and severe childhood traumatic brain injury

Introducción. El traumatismo craneoencefálico es una causa habitual de discapacidad adquirida durante la infancia. Las intervenciones tempranas que se centran en la participación de los padres pueden resultar efectivas para reducir las disfunciones del niño. Objetivo. Determinar la eficacia de un nuevo programa de asesoramiento dirigido a padres y escuelas en comparación con un grupo control. Pacientes y métodos. La muestra principal del estudio se obtuvo de un hospital pediátrico. La muestra final consistió en 42 niños de 6 a 16 años. Resultados. Comparando con los datos normativos, las comparaciones pre y post intragrupos mostraron una mejora significativa en el grupo de intervención parental con respecto al grupo control. Conclusiones. La superioridad del grupo de intervención parental sobre el grupo control no sólo fue estadísticamente significativa, sino también clínicamente sustancial y relevante. Los resultados del estudio sugieren que los niños con traumatismo craneoencefálico moderado o grave pueden beneficiarse de un tratamiento familiar intensivo de apoyo

Introduction. Traumatic brain injury is a common cause of acquired disability during childhood. Early interventions focusing on parenting practices may prove effective at reducing negative child outcomes. Aim. To determine the efficacy of a new counselling program aimed at parents and schools compared to a control group. Patients and methods. The main study sample was obtained from a paediatric hospital. The final sample consisted of 42 children aged between 6 and 16 years old. Results. Comparing with normative data, pre-post comparisons between groups showed a significant improvement in the parent group with respect to the control group. Conclusions. The superiority of the parental intervention group over those of the control group was not only statistically significant, but also clinically substantial and meaningful. The results of this study suggest that children with moderate to severe traumatic brain injury can benefit from an intensive supported family treatment

Screening for the presence of FMR1 premutation alleles in a Spanish population with fibromyalgia.

Fragile X mental retardation 1 (FMR1) premutation carriers, who are at risk of having children with fragile X Syndrome, were initially considered as clinically unaffected. However, recent clinical and molecular studies have shifted this point of view. The incidence of premutation in the general population is substantial. Apart from the well-documented fragile X-associated tremor-ataxia and fragile X premature ovarian insufficiency, there is a broad constellation of symptoms including depression, anxiety, muscle pain, autoimmune and thyroid disease, chronic fatigue, and fibromyalgia that has been described, particularly in females with the premutation (55-200 repeats). Fibromyalgia (FM) is the most common cause of widespread pain and comprises a heterogeneous group of patients, affecting 2-3 % of the general population. We analyzed the FMR1 gene in a cohort of females diagnosed with fibromyalgia in order to assess the incidence of premutated alleles. CGG repeat size was determined in 353 females suffering from FM and results were compared with a control group. Four premutated carriers in the FM group were detected. The observed incidence is higher than that described for a normal female population (1/88 vs 1/250). The early detection of premutation carriers for the FMR1 gene among individuals diagnosed with fibromyalgia is important and would be helpful in correct genetic counseling of patients and their families, who may be at risk of having children with fragile X syndrome, the most common known cause of inherited intellectual disability and autism. Our data should be cautiously interpreted based on just this study; nevertheless, screening for the FMR1 gene in FM patients at least with presentations suggestive of FMR1 gene-related disease seems recommendable.

Impact of histological chorioamnionitis, funisitis and clinical chorioamnionitis on neurodevelopmental outcome of preterm infants.

BACKGROUND: The role of chorioamnionitis in neurodevelopment of preterm infants is not fully understood. AIM: To examine the association between different indicators of intrauterine inflammation (clinical chorioamnionitis, histological chorioamnionitis and funisitis) and neurodevelopmental impairment in very preterm infants. METHODS: Preterm infants with a birth weight of <1500 g or a gestational age of <32 weeks were included. Follow-up evaluation up to 2 years of age consisted of neurological examination, neurodevelopmental assessment and visual and audiologic tests. Outcome data were compared between the chorioamnionitis and the control groups, controlling for gestational age, birth weight and Apgar score at 5 min. RESULTS: One hundred seventy-seven patients comprised the study population (mean gestational age 29±2 weeks, mean birth weight 1167±344 g). Histological chorioamnionitis was present in 49% of placentas, whereas funisitis was observed in 25%. In 57% cases clinical maternal chorioamnionitis was suspected. Follow-up was available for 130 (82%) patients. Infants with funisitis, compared with controls, had a significantly higher incidence of moderate to severe disability (18% vs 5%, OR 4.07; 95% CI 1.10-15.09). CONCLUSION: The results of this study suggest that, unlike a broad definition of histological chorioamnionitis including inflammation of maternal or fetal placental tissues, funisitis may entail a higher risk of moderate to severe disability at 2 years of age in preterm infants.