Neuroplasticity during the transition period: How the adolescent brain can recover from aphasia. A pilot study.

BACKGROUND: Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence. OBJECTIVE: We describe a 5-year follow-up of language in three adolescent subjects with post-brain injury aphasia. METHODS: We analysed and scored formal aspects of language three times, language hemispheric dominance twice with dichotic listening test and functional magnetic resonance imaging (fMRI) brain activation patterns that supported expressive and comprehensive language during the recovery period. RESULTS: We found similarities to both paediatric and adult aphasia in these three adolescents. While the level of recovery resembled that of children with aphasia, a more efficient language rehabilitation occurred in those who remained with left hemispheric dominance in the chronic stage, as it is reported in adults. CONCLUSIONS: Our analysis and long-term follow-up provide data for a better understanding on how the injured brain matures during adolescence. More studies with larger samples will help to understand the function of the remaining networks and the recovery from injury in this particular age group.

Stylohyoid Complex (Eagle) Syndrome Starting in a 9-Year-Old Boy.

Background There are only four previous pediatric reports of the glossopharyngeal neuralgic form of the stylohyoid complex syndrome. Stylohyoid complex has merely been described as cases of glossopharyngeal neuralgia in children. Case Report A 12-year-old boy came to our hospital because of recurrent episodes of severe cranial pain (9/10) lasting for 5 to 15 minutes. Pain affected the right tonsillar fossa, ear, and mastoid region. Since the start at the age of 9 years, the frequency of painful episodes has progressively increased: when admitted to our clinics 3 years later, the child was having up to five episodes daily in spite of analgesic, antiepileptic, and antidepressant drugs; he had abandoned school and leisure. Between episodes, neurological examination detected only discomfort to pressure on the right tonsillar fossa. Three-dimensional computed tomography images of the skull base showed an elongated right styloid process and bilateral calcification of the stylohyoid ligament. After surgical excision of the right styloid process and of part of the stylohyoid ligament, the glossopharyngeal painful episodes ceased. The patient remains asymptomatic seven years later. Conclusion In spite of its rarity in childhood, this debilitating but treatable syndrome should be kept in mind for the differential diagnosis of recurrent cranial pain in the pediatric population.

Acquisition of Motor and Cognitive Skills through Repetition in Typically Developing Children.

BACKGROUND: Procedural memory allows acquisition, consolidation and use of motor skills and cognitive routines. Automation of procedures is achieved through repeated practice. In children, improvement in procedural skills is a consequence of natural neurobiological development and experience. METHODS: The aim of the present research was to make a preliminary evaluation and description of repetition-based improvement of procedures in typically developing children (TDC). Ninety TDC children aged 6-12 years were asked to perform two procedural learning tasks. In an assembly learning task, which requires predominantly motor skills, we measured the number of assembled pieces in 60 seconds. In a mirror drawing learning task, which requires more cognitive functions, we measured time spent and efficiency. Participants were tested four times for each task: three trials were consecutive and the fourth trial was performed after a 10-minute nonverbal interference task. The influence of repeated practice on performance was evaluated by means of the analysis of variance with repeated measures and the paired-sample test. Correlation coefficients and simple linear regression test were used to examine the relationship between age and performance. RESULTS: TDC achieved higher scores in both tasks through repetition. Older children fitted more pieces than younger ones in assembling learning and they were faster and more efficient at the mirror drawing learning task. CONCLUSIONS: These findings indicate that three consecutive trials at a procedural task increased speed and efficiency, and that age affected basal performance in motor-cognitive procedures.

A leaky splicing mutation in NFU1 is associated with a particular biochemical phenotype. Consequences for the diagnosis.

Mutations in NFU1 were recently identified in patients with fatal encephalopathy. NFU1 is an iron-sulfur cluster protein necessary for the activity of the mitochondrial respiratory chain complexes I-II and the synthesis of lipoic acid. We report two NFU1 compound heterozygous individuals with normal complex I and lipoic acid-dependent enzymatic activities and low, but detectable, levels of lipoylated proteins. We demonstrated a leaky splicing regulation due to a splice site mutation (c.545+5G>A) that produces small amounts of wild type NFU1 mRNA that might result in enough protein to partially lipoylate and restore the activity of lipoic acid-dependent enzymes and the assembly and activity of complex I. These results allowed us to gain insights into the molecular basis underlying this disease and should be considered for the diagnosis of NFU1 patients.

Procedural Learning in Children With Developmental Coordination, Reading, and Attention Disorders.

The aim is to assess repetition-based learning of procedures in children with developmental coordination disorder (DCD), reading disorder (RD) and attention-deficit hyperactivity disorder (ADHD). Participants included 187 children, studied in 4 groups: (a) DCD comorbid with RD and ADHD (DCD+RD+ADHD) (n = 30); (b) RD comorbid with ADHD (RD+ADHD) (n = 48); (c) ADHD (n = 19); and typically developing children (control group) (n = 90). Two procedural learning tasks were used: Assembly learning and Mirror drawing. Children were tested on 4 occasions for each task: 3 trials were consecutive and the fourth trial was performed after an interference task. Task performance by DCD+RD+ADHD children improved with training (P < .05); however, the improvement was significantly lower than that achieved by the other groups (RD+ADHD, ADHD and controls) (P < .05). In conclusion, children with DCD+RD+ADHD improve in their use of cognitive-motor procedures over a short training period. Aims of intervention in DCD+RD+ADHD should be based on individual learning abilities.

[Depressive phenomenology at the outset of neuropaediatric diseases]. / Fenomenología depresiva al inicio de enfermedades neuropediátricas.

INTRODUCTION: Depressive phenomenology, in its diverse nosological forms, affects 8-10% of children and adolescents of general population. Most frequently mood disorders have a primary origin, following poligenic multifactorial model. Moreover there is a non negligible proportion of cases in which depressive symptoms accompany neurological illnesses or they even constitute a part of predominant manifestations at the clinical start of neurologic disease, or mark a point of inflexion in its course. The aim of the present article is to review relevant literature dealing with this topic. DEVELOPMENT: A significative higher frequency of depressive phenomenology, not explainable by hazard, can be an early manifestation in children and adolescents with: epileptic syndromes, sleep disorders, chronic recurrent cephalalgias, several neurometabolic diseases, and intracranial tumors. Points of coincidence have been shown in dysequilibrium of brain neurotransmitters (serotonine, noradrenaline, hyperglutamatergic states) which could not be hypothesized as maintaining both neurological and mood conditions. CONCLUSIONS: The suspiction of a neurological disease should be adopted in cases of mood disorder not easily explainable by familial antecedents or clear biographical stressors. The search for a brain disorder by means of a meticulous anamnesis and neurological clinical and ancillary exams makes possible to discover the brain disorder at a very early stage and ameliorate the chances of accurately manage both the neurological and mood disorders. The simultaneous treatment of both dimension of the illness helps to improve the patients' quality of life.

TITLE: Fenomenologia depresiva al inicio de enfermedades neuropediatricas.Introduccion. La depresion, en sus diversas formas, afecta al 8-10% de niños y adolescentes y en la mayor parte de casos su origen es primario, siguiendo el modelo genetico multifactorial. Pero hay una proporcion de pacientes, no bien cuantificada todavia, en la que la depresion acompaña precozmente una enfermedad neurologica o marca un punto de inflexion en el curso de esta. El objetivo es revisar la bibliografia al respecto. Desarrollo. Se observa fenomenologia depresiva, con una frecuencia significativamente mayor que por azar, en niños y adolescentes afectos de epilepsia, trastornos del sueño, cefaleas primarias cronicas recurrentes, enfermedades neurometabolicas y tumores intracraneales. En varias de estas patologias neuropediatricas se hipotetizan puntos de coincidencia fisiopatologica con la depresion a traves de un deficit de disponibilidad cerebral de serotonina y noradrenalina. No se considera aqui la depresion disadaptativa a una neurodiscapacidad cronica. Conclusiones. En niños y adolescentes, los trastornos del animo sintomaticos de enfermedad neurologica deben sospecharse en ausencia de antecedentes familiares o de experiencias vitales que los expliquen. La busqueda sistematica de anomalias neurologicas y los examenes complementarios permitirian en estos casos abordar precozmente el tratamiento de la enfermedad cerebral causante del cuadro depresivo. A su vez, como ocurre en casos de epilepsia, cefaleas o trastorno del sueño, la terapia farmacologica y psicologica del cuadro depresivo contribuye a mejorar la calidad de vida de los afectados.

AULA virtual reality test as an attention measure: convergent validity with Conners' Continuous Performance Test.

The majority of neuropsychological tests used to evaluate attention processes in children lack ecological validity. The AULA Nesplora (AULA) is a continuous performance test, developed in a virtual setting, very similar to a school classroom. The aim of the present study is to analyze the convergent validity between the AULA and the Continuous Performance Test (CPT) of Conners. The AULA and CPT were administered correlatively to 57 children, aged 6-16 years (26.3% female) with average cognitive ability (IQ mean = 100.56, SD = 10.38) who had a diagnosis of attention deficit/hyperactivity disorder (ADHD) according to DSM-IV-TR criteria. Spearman correlations analyses were conducted among the different variables. Significant correlations were observed between both tests in all the analyzed variables (omissions, commissions, reaction time, and variability of reaction time), including for those measures of the AULA based on different sensorial modalities, presentation of distractors, and task paradigms. Hence, convergent validity between both tests was confirmed. Moreover, the AULA showed differences by gender and correlation to Perceptual Reasoning and Working Memory indexes of the WISC-IV, supporting the relevance of IQ measures in the understanding of cognitive performance in ADHD. In addition, the AULA (but not Conners' CPT) was able to differentiate between ADHD children with and without pharmacological treatment for a wide range of measures related to inattention, impulsivity, processing speed, motor activity, and quality of attention focus. Additional measures and advantages of the AULA versus Conners' CPT are discussed.

[Dysfunction of central coherence in schoolchildren with procedural learning disorder. Reply]. / Disfunción de la coherencia central en niños con trastorno de aprendizaje procedimental. Réplica.

TITLE: Disfuncion de la coherencia central en ninos con trastorno de aprendizaje procedimental. Replica.

[Dysfunction of central coherence in schoolchildren with procedural learning disorder]. / Disfunción de la coherencia central en niños con trastorno de aprendizaje procedimental.

INTRODUCTION: Children with coordination disorder -non verbal learning disorder, procedural learning disorder (PLD)- have difficulties in understanding complex simultaneous visual information. AIM: Validation of two different visual tasks to measure central coherence function of children with PLD. SUBJECTS AND METHODS: A chimeric image and a complex visual story are showed to 200 schoolchildren: 20 of them have PLD, 60 have PLD plus attention deficit/hyperactivity disorder (PLD + ADHD), 60 have non comorbid ADHD, and 60 subjects are typical control children. A chi square test and a discriminant analysis are used to study the performances of the different groups in verbal description of both images. RESULTS: Performance is lower in children with PLD and PLD + ADHD than in those with non-comorbid ADHD or controls. Moreover 93% and 92% of children with poor performance in, respectively, chimeric and complex images, have PLD or PLD + ADHD. Eighty seven per cent of subjects with PLD + ADHD fail in some of the tasks and, by contrast only 15% of children with ADHD do. CONCLUSIONS: Children with PLD have disability in quick understanding of simultaneous complex information and central coherence. The two tasks used in this research are useful to detect these difficulties, with high sensibility and specificity.

[Dichotic listening in Spanish-speaking children: validation of a set of dichotic lists of Spanish words and syllables]. / Test de escucha dicótica para niños hispanohablantes: validación de unas nuevas series de pares de palabras y de sílabas en castellano.

INTRODUCTION: Dichotic listening test can estimate hemispheric dominance for language. AIM: To study the usefulness of a new set of dichotic pairs of Spanish stimuli in middle childhood. SUBJECTS AND METHODS: The stratified control group comprised 40 healthy, right-handed children, aged 3.5- 7.5 years, of both sexes, with average ability at speaking Spanish. The clinical sample comprised 12 children with right spastic hemi-paretic cerebral palsy, average general intelligence and sentence repetition index over -2z. Each listening series is composed of 20 age-appropriate dichotic pairs: one syllable, word, or number; or trains of two or three syllables or numbers. Voice onset time, duration and stress of stimuli were balanced. Hemispheric dominance index (HDI) for language was calculated using a formula with the scores of stimuli from right or left ears. Statistical analysis evaluated the age-related accuracy and discriminant power of each HDI. RESULTS: In the non-forced attention paradigm, the range of HDI is 0-200. Values of HDI ≥ 112 indicate left hemisphere dominance for language, whereas values of HDI ≤ 88 indicate right hemisphere dominance. All 40 typical subjects showed left HDI for language, without influence of age and sex. In contrast, ten out of twelve (83%) right hemiparetic children had right HDI. CONCLUSIONS: The results show that this new set of dichotic pairs is useful in the initial assessment of cerebral dominance for language and valid for use in Spanish speaking children aged 3.5 years or more.

[Brain plasticity for language in children and adolescents]. / Plasticidad cerebral para el lenguaje en el nino y el adolescente.

INTRODUCTION: Plasticity makes possible adaptative modelling of the nervous system to experiences i.e. learning and development. AIM: To review current literature on clinical long term evolution and functional magnetic resonance imaging (fMRI) features of brain remodelling after focal stroke in left perisylvian regions involved in basic language processing during infancy and childhood. DEVELOPMENT: Each of the main neurocognitive subsystems develops with different timing, so altered plasticity and vulnerability are diverse, according with age at insult and its topography. Genetic programming makes human brain capable for installing basic formal linguistic abilities on an associative perisylvian subsystem, highly specialised. A focal lesion of this region leads to remodelling phenomena by disinhibition of contralateral frontal and perisylvian structures and by a more or less efficacious activation of neighboring homolateral cortex, as it has been shown by fMRI studies and DTI tractography. As a result, very early local stroke to language areas is generally well compensated in terms of linguistic behaviour. Meanwhile acquired aphasias into middle and late childhood, even if they have a better prognosis than in adults, they fail to resume without lexical access defaults and/or difficulties in written language. CONCLUSION: Brain plasticity can promote restoration and further development of language following a stroke in left peri-sylvian areas, specially when lesion occurs at perinatal to middle childhood.

[Difficulties in the swift recognition of contradictions in procedural learning disorder: possible central coherence dysfunction]. / Dificultades en la percatacion rapida de incongruencias en el trastorno de aprendizaje procedimental: posible disfuncion de la coherencia central.

INTRODUCTION: Procedural learning disorder, or non-verbal learning disorder, affects the automation of perceptual motor and cognitive skills and routines. AIM: To further our knowledge of the neurocognitive dysfunction in this disorder and, more specifically, to analyse the difficulties experienced when going from recognition of the constituting elements of something to an understanding of the whole. DEVELOPMENT: Contrasting simultaneous visual information and the swift recognition of contradictions are especially difficult abilities for children with procedural learning disorder. CONCLUSIONS: These difficulties may reflect a central coherence dysfunction and can partly account for the deficient ability to adapt their social behaviour displayed by these children.

A preliminary study of the frequency of anti-basal ganglia antibodies and streptococcal infection in attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is often present in patients with post-streptococcal neuropsychiatric disorders such as Sydenham's chorea and PANDAS, in which anti-basal ganglia antibodies (ABGA) have been frequently found. Our study investigates the hypothesis that pharyngeal group A beta-hemolytic streptococcus (GABHS) infections and serum ABGA are more frequent in children with ADHD non-comorbid (nc-ADHD) with obsessive-compulsive disorder or tics than in controls. We compared 22 children with nc-ADHD (DSM-IV-TR) and 22 healthy controls matched by age, gender and season of sample collection, for the frequency of recent GABHS infection and the presence of ABGA. Eleven out of 22 children (51%) with nc-ADHD showed evidence of GABHS infection compared to three out of 22 (14%) controls (P = 0.007). We found positive ABGA in one ADHD subject (4%) and in one control (4%). This preliminary study indicates that frequency of ABGA in children with nc-ADHD does not differ from that in matched controls, despite the fact that our ADHD patients had had more recent GABHS infections than the controls. This suggests that ABGA do not have a role in the pathogenesis of nc-ADHD.

[Alternating hemiplegia of childhood in Spanish population. Study of a series of 17 patients]. / Hemiplejía alternante de la infancia en la población española. Estudio de una serie de 17 pacientes.

BACKGROUND AND OBJECTIVE: Alternating hemiplegia of childhood (AHC) is a rare disease of unknown etiology characterized by early onset of recurrent episodes of hemiplegia, tonic or dystonic attacks and abnormal ocular movements with a fatal outcome to severe encephalopathy. Our aim was to describe the clinical manifestations, precipitating factors, complementary studies results, long-term outcome and response to treatment in a series of AHC patients. PATIENTS AND METHOD: Descriptive, retrospective and multicenter study in 17 Spanish patients aged between 1-24 years who fulfilled diagnostic criteria of AHC. RESULTS: Twelve cases fulfilled criteria of typical AHC and 5 were atypical. Mean age at diagnosis was 26 months and 47% cases had a family history of migraine. Mean age at onset of hemiplegic attacks was 9.3 months. Symptoms disappeared during sleep and precipitating factors were present in 94% cases. Most patients developed mental retardation with ataxia and dysarthria. Work-up tests (metabolic, neurophysiologic and radiologic) were normal or nonspecific. In 3 patients mutations in CACNA1A, ATP1A2 were ruled out. Positive responses to flunarizine was observed in 81%. CONCLUSIONS: The characteristic clinical symptoms are still the clue to make the diagnosis of this disease, with a lack of genetic, biochemical or radiological specific studies. Early diagnosis avoids invasive tests, repeating procedures, using ineffective and potentially toxic treatments, and allows to start treatment with flunarizine without delay. More genetic studies are needed in broader series of patients.

Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.

PURPOSE: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. METHODS: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. RESULTS: We classified patients as: SMEI/SMEB = 55; GEFS+= 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. CONCLUSION: We obtained a frequency of 71%SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes.

Non-verbal development of children with deafness with and without cochlear implants.

Deprivation of sensory input affects neurological development. Our objective was to explore clinically the role of hearing in development of sensorimotor integration and non-verbal cognition. The study involved 54 children (15 males, 839 females; 5 to 9 years old) with severe or profound bilateral prelocutive deafness but without neurological or cognitive impairment. Of these, 25 had received an early cochlear implant (CIm). Patients were compared with 40 children with normal hearing. All were given a battery of non-verbal neuropsychological tests and a balance test, and were timed for simple and complex movement of limbs. Deafness, whether treated by CIm or not, resulted in a delay in development of complex motor sequences and balance. Lack of auditory input was also associated with lower, but non-pathological, scores in visual gnoso-praxic tasks and sustained attention. Such differences were not observed in children with CIm. Hearing contributes to clinical development of spatial integration, motor control, and attention. An early CIm enables good verbal development and might also improve non-verbal capacities.