Biomedical subjects

F Mulas

Publications and source records attributed to F Mulas.

At least 19 recordsLinked to original sources

PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗

PubMed2006

[Language and neurodevelopmental disorders. A review of their clinical characteristics].

INTRODUCTION: Language is a keystone in the normal social and cognitive development of any group of children and early, fitting interventions can largely reduce the repercussions that the deficit has in this area. The article analyses the definition of language as 'the result of a complex nervous activity that allows individuals to communicate mental states by the production of multi-modal signs that symbolise these states in accordance with a linguistic community's own convention'. Other language-related terms are also dealt with. DEVELOPMENT: Different classifications of language disorders are also discussed and we analyse its characteristics in different neurological disorders, such as motor disorders with a central origin, autistic spectrum, learning disorders, mental retardation, and attention deficit and disruptive behaviour disorders. CONCLUSIONS: Disorders affecting language clearly display semiological heterogeneity, and therefore it is advisable to take into account the classifications and terms related to it. It is also necessary to be familiar with the specific features of each alteration in the different neurological disorders so as to be able to reach an accurate diagnosis that allows the implementation of suitable lines of behaviour and interventions. Additionally, this will also allow timely measures to be taken in order to avoid later complications.

Adolescent↗

PubMed2006

[Learning disabilities in epileptic children].

AIMS: To analyse the association between neuropsychological disorders and epilepsy in infancy by searching for the origin in the pathophysiology of epilepsy as a neurological disease and based on the adaptive plasticity of the brain. DEVELOPMENT: The existence of electrical discharges, both in the presence and the absence of clinical seizures, is linked to problems involving attention, recent memory, limitations in the linguistic, visuospatial and executive capabilities, with slowed psychomotor functioning, and this leads to learning difficulties. The early age of onset of epilepsy, the secondary causation, the fact it is refractory to treatment and therefore requires polytherapy, and the negative experience of the disease all have an effect on the association of neuropsychological disorders. The type of epilepsy that can determine the involvement of specific functions, such as memory, is affected in partial epilepsies of the temporal lobe and in generalised epilepsies attention is affected. CONCLUSIONS: Epileptic seizures are not the only manifestation of epilepsy, and children display associated symptoms that make it necessary to carry out a comprehensive neuropsychological evaluation that must include hemisphere-specific examinations of the brain functions.

Child↗

PubMed2006

[Learning difficulties in mathematics in children with attention deficit hyperactivity disorder].

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) and learning difficulties are two diagnostic categories of great social importance and impact, and which are associated in around 25-35% of cases. One explanation offered by researchers to account for this overlap is a deficit in executive functioning (EF). AIMS: 1) To compare EF and applied mathematical knowledge in children with ADHD, difficulties in learning mathematics (DLM) or ADHD + DLM, and to identify the deficiencies they experience. 2) To verify whether the phenotype hypothesis is fulfilled in the case of the ADHD + DLM condition. SUBJECTS AND METHODS: The study involved a quasi-experimental 2 x 2 design, with a sample made up of 78 participants (6-13 years old) who were divided into four groups: ADHD (n = 33), DLM (n = 15), ADHD + DLM (n = 15) and a control group (n = 15). Tests aimed at evaluating different cognitive processes as well as applied mathematical knowledge were administered: inhibitory control (go/no go); verbal working (backward digit-recall and counting memory task) and temporal-visual-spatial memory; short-term memory (direct digit-recall); attention (CPT); calculation speed (Canals) and real-life problems. RESULTS AND CONCLUSIONS: Taking the variables age, gender and intelligence quotient as covariables, results showed that the three groups with problems displayed a deficit of attention and in working memory; the DLM group stood out from the other owing to the presence of a specific deficiency affecting the ability to recall temporal-visual-spatial information. In contrast, deficits in inhibitory control were seen to be specific to ADHD. Finally, findings did not support the phenotype hypothesis, and it was therefore an accumulative profile.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

[Alterations in the pattern of dopaminergic markers in attention-deficit/hyperactivity disorder].

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood onset that can include elements of inattention, hyperactivity and impulsive behavior. It is often treated with stimulant medications such as methylphenidate hydrochloride (MPH). The neurobiology of ADHD is not well understood, but there is converging evidence of the involvement of the catecholamine rich frontal-striatal circuitry. A prominent theory of ADHD is that there is a dysregulation of dopamine neurotransmission in this circuitry. Given support to this theory is the observation from human imaging studies that MPH blocks the dopamine transporter (DAT), the main mechanism for removing dopamine from the synapse; thereby increasing extracellular dopamine levels in the striatum. Genetic and molecular studies have also demonstrated an association between dopamine related genes (e.g., DAT, dopamine D4 and D5 receptors) and ADHD. DEVELOPMENT: Studies using positron emission tomography (PET) and single photon emission tomography indicate alterations in dopamine markers in ADHD. The majority of the existing studies have reported increased DAT binding (ranging between 17 and 70%) in the striatum of both children and adults with ADHD, while a new PET study reported lower DAT binding in the midbrain (where the dopaminergic neurons of the substantia nigra and ventral tegmental area are located) of adolescents with ADHD. Studies using [18F]fluorodopa to assess dopamine synthesis and metabolism have demonstrated abnormalities in presynaptic activity in patients with ADHD; however the nature of these changes appears to be age-dependent. Some limited data also indicate potential alterations in dopamine D2 receptor availability in children with ADHD. CONCLUSIONS: The results from the human brain imaging studies are still not definitive because of discrepancies in the findings. There is a great need to replicate and expand these findings in treatment-naïve patients with ADHD, taking into consideration potential variables such as drug and smoking history, ethnicity, and presence of comorbidity.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

[Techniques for the functional evaluation of neurodevelopmental disorders].

AIM: To review the evaluation of neuropsychological functions by using non-invasive functional neuroimaging methods. DEVELOPMENT: Non-invasive functional neuroimaging methods can be sorted into two broad categories: the first includes those that make use of electromagnetic techniques, such as event-related potentials and magnetoencephalography (MEG), and the second consists of those involving haemodynamic techniques, such as positron emission tomography and functional magnetic resonance imaging. These methods have been employed in particular to evaluate the following functions: attention, perception, imagination, language, working memory, semantic retrieval, episodic memory, episodic memory retrieval, priming and procedural memory. The capacity of MEG, both for analysis and for organising the information it receives, is so large that it takes only a few milliseconds to evaluate brain activity and to create functional maps of the brain in which the brain structure is set out in blocks of cubic centimetres or even millimetres. This makes it possible to generate functional maps of brain activity that are capable of being organised and represented in terms of both time and space. It also enables us to obtain images that result from the signalling activity of sets of nerve cells (especially from the dendritic currents) and the electromagnetic signal that carries this information to the outer surface of the head, where the magnetic flow can be recorded. CONCLUSIONS: With the findings from these studies it has become possible to establish a topographic correlation between the functions and the basic brain processes involved in each paradigm. A growing body of clinical evidence proves the value of using them (especially MEG) with cases of epilepsy, language, dyslexia, autism and attention deficit hyperactivity disorder.

Cerebrovascular Circulation↗

PubMed2005

[Attention deficit hyperactivity disorder therapy update: extended-release methylphenidate].

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a very common condition in neuropaediatric practice and the most widely used medication is methylphenidate (MPT). We discuss the comorbid disorders, diagnosis, aetiopathology and neurochemical bases, and we also stress the importance of pharmacological action on the dopaminergic and noradrenergic pathways, and the problems and benefits of the different formulations of MPT. AIMS: Since extended-release MPT by means of the OROS technique has only recently been commercialised in Spain, we conducted a comparative analysis of immediate-release MPT and extended-release MPT in a series of 93 patients in order to determine which of them is preferable, to evaluate the reasons why this is so, and to analyse the shortcomings and advantages of the two drugs. PATIENTS AND METHODS: We present a study of 93 patients between 6 and 18 years old. Once an initial treatment had been established, changing over to extended-release MPT was proposed. We analysed compliance, effectiveness, safety, the preferences of the family and the degree of control over afternoon symptoms with the new treatment. RESULTS AND CONCLUSIONS: Most of the patients began treatment with immediate-release MPT or other medication. Changing to extended-release MPT brought about greater satisfaction with the control of afternoon symptoms and an improvement in the degree of compliance with respect to the initial treatment with immediate-release MPT or other drugs.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

[The contribution of the cerebellum to cognitive processes].

INTRODUCTION: Apart from its functions involving control over movement, the cerebellum is also related to learning motor sequences and, according to the experimental and clinical evidence we will examine, to cognitive and learning processes that do not exclusively involve motor activity. DEVELOPMENT: The cerebrocerebellar connections act as a vehicle for the afferent information from the sensory-motor cortex, prefrontal cortex, the frontal regions responsible for (expressive) language, parietal cortex, superior colliculus and superior temporal cortex, returning efferences to similar areas that are responsible for attention, visuospatial perception, memory and the regulation of executive and emotional functions. It plays a role in the preparation and anticipation of motor responses, according to sequences experienced previously depending on the information received from the surroundings, thus anticipating the physiological state for carrying out perceptual motor or cognitive tasks. A number of experimental neuroimaging studies, as well as the discovery of a new cell in the neuronal population of the cerebellum, relate the cerebellum to cognitive processing. CONCLUSIONS: Clinical observation of patients with cerebellar lesion or dysfunction, which are related to a deficit in the cognitive functions, suggests a model with which to understand these mechanisms. Long-lasting depression is considered to be the learning mechanism in the cerebellum and is intimately related to the mechanisms involved in neuronal plasticity and in memory.

Cerebellum↗

PubMed2005

[Intrathecal baclofen and Botulinum toxin in infantile cerebral palsy].

INTRODUCTION: Infantile cerebral palsy is considered to be a motor disorder affecting both posture and movement. It is the manifestation of a cerebral lesion that took place during the maturing process of the brain. Spastic cerebral palsy is the most frequent variety. The spasticity presented by these patients strongly influences their functioning and gives rise to several complications that affect their quality of life. AIMS AND DEVELOPMENT: The main aim of this study is to determine a set of suitable and effective therapeutic steps that can be used to improve patients' spasticity and to prevent the complications that stem from them, such as contractures, deformities, surgery, etc. Multiple treatments were used, including physiotherapy, rehabilitation and oral pharmacotherapy, with few satisfactory results. At present there are two very promising therapeutic alternatives for patients with infantile cerebral palsy: Botulinum toxin, which we already have a great deal of experience with, and intrathecal treatment with baclofen. We report on a series of 10 patients aged between 8 and 15 years who had had an intrathecal baclofen infusion pump implanted. To date (maximum follow-up: 12 months), their clinical course has been satisfactory in most cases, with no severe complications related to the surgical technique, except in one individual who presented a fistula that resolved spontaneously. CONCLUSIONS: Intrathecal baclofen seems to be a very useful alternative in the treatment of spasticity to improve the quality of life of these patients and those around them.

Baclofen↗

PubMed2004

[The neuropaediatric and pathogenic clinical bases of autistic spectrum disorder].

INTRODUCTION: The dimension of the autistic spectrum embraces a considerable degree of clinical complexity which is, in turn, an expression of the numerous systems involved in the functioning of the central nervous system. Every day different biological factors are revealed which put in doubt other factors that, in a more objective way, appear to be involved in a particular aetiology. DEVELOPMENT AND CONCLUSIONS: It is clear that exactly what causes autistic spectrum disorder is still unknown and it may be useful to analyse cases with a known aetiology and correlate them with other similar cases, as it is likely to be this association between findings and studies in the future that will probably enable us to better define the bases and the underlying causes of the complex and manifold origin of the autistic spectrum. This will enable a more efficient therapeutic approach to be developed, which, when all is said and done, is what is primarily sought in the management of children with autistic spectrum disorder.

Autistic Disorder↗

PubMed2004

[Functional neuronal plasticity].

INTRODUCTION: Thanks to the contributions made by neuroscientific research and the clinical evidence regarding the functional recovery of the central nervous system in the different motor, cognitive, linguistic and sensory spheres, we now know more about how the brain is built and its modifications. This recovery is possible due to the plasticity of the brain, its capacity to reorganise itself and to modify functions in order to adapt to both external and internal changes. This capacity is inherent to brain cells and allows cortical circuits to be repaired, integrates other cortical areas to carry out modified functions and responds to different disorders. It depends on genetic, neuronal and neurochemical factors and its limits can be manipulated through clinical and pharmacological intervention. DEVELOPMENT: The brain's capacity to adapt itself to changes is crucial in the development of the nervous system and has important repercussions on learning. The neuroanatomical, neurochemical and functional changes that take place during the reorganisation made possible by plasticity will facilitate the recovery acquisition of the functions involved (adaptive plasticity) and may hinder the development of others (maladaptive plasticity). This variability of the possible responses is related to the chronology of the lesion, the site that is affected, the state of the substrata that can take on the function and the type of function that is altered. The mechanisms responsible for facilitating this plasticity are different at any given time (fast and late plasticity), depending on the function that is altered, with expansion of the somatotopic representations in the motor cortex adjacent to the damage, interhemispherical transfer of language or crossed plasticity in the auditory or visual function. The neuropsychological pathology can appear linked to the lesion or secondary to a maladaptive plasticity. CONCLUSIONS: Advancing in our knowledge of the intrinsic mechanisms of brain plasticity and synaptic regulation will lead us to understand the recovery of damaged or lost functions in the brains of children with special needs, and thus allow us to implement favourable clinical and pharmacological interventions.

Central Nervous System↗

PubMed2004

[Cognitive flexibility, an additional symptom of attention deficit hyperactivity disorder. Is it a therapeutically predictive element?].

INTRODUCTION: Cognitive flexibility is a capability acquired during infancy that can be evaluated from the age of 8 onwards. This executive function can affect patients with dorsolateral frontal lesions. Involvement of this function in some children with attention deficit hyperactivity disorder (ADHD) would point to an additional disorder. AIMS: The objective of this study was to report on the involvement of cognitive flexibility in patients with ADHD from the age of 8 years onwards, to establish a correlation with the progressive phenomenon in its development, and to relate the findings from the study of cognitive flexibility with those of the attentional function. PATIENTS AND METHODS: A group of 50 children diagnosed as suffering from ADHD (8 21 years old) and 50 normal children were evaluated. The same subjects were submitted to a study of their attentional functions, their inhibitory control mechanisms as well as their cognitive flexibility. RESULTS: At least 38% of the patients studied showed involvement of cognitive flexibility. No statistically significant relation was observed when data were linked to the age variable, which could point to the absence of the maturation factor, unlike the results observed in the case of sustained attention. Patients with poor cognitive flexibility also present disorders involving attentional discrimination, the control of impulses and interference control. CONCLUSIONS: The group with cognitive rigidity as a symptom added to the attentional disorder could correspond to a complex subtype that does not respond so successfully to stimulants. Consequently, cognitive flexibility studies could reflect an indicator for selecting the type of pharmacological treatment to be employed.

Adolescent↗

PubMed2004

[The neurofunctional foundation of cognitive rigidity in attention deficit hyperactivity disorder: some preliminary findings].

INTRODUCTION: It has been proposed that there is an impairment in cognitive flexibility in children with attention deficit hyperactivity disorder (ADHD). The Wisconsin card sorting test (WCST) is the most widely used neuropsychological test for assessing this process. Previous studies have reported the presence of a subgroup of children with ADHD which has a low cognitive flexibility. In addition this subgroup showed a high resistance to the treatment with stimulant medication. OBJECTIVES: The aim of this study was to examine whether there were different patterns of brain magnetic activity in different subgroups of ADHD, during the performance of a cognitive flexibility task, such as WCST. PATIENTS AND METHODS: We recruited a sample of 18 children, divided into three groups according to DSM IV R diagnostic criteria. Here we present preliminary data based on a subsample of nine children. Brain magnetic activity was registered while the children performed the WCST by means of Magnetoencephalography (MEG). This is a non invasive neuroimaging technique with a high spatio temporal resolution. RESULTS: Preliminary results showed that ADHD mixed group had a higher rate of perseverative responses. In addition, a different pattern of brain magnetic activity was noted in this group, showing less activation in anterior cingulate cortex and dorsolateral prefrontal cortex in the left hemisphere during the first 400 ms. CONCLUSIONS: MEG seems to be an useful tool to describe the brain network that subserves cognitive flexibility in different groups of children. It could have important repercussions in the classification of ADHD, both neuropsychologically and pharmacologically.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Unique origin and low penetrance of the 946delGAG mutation in Valencian DYT1 families.

Mutations in the DYT1 gene cause idiopathic torsion dystonia (ITD) transmitted in families as an autosomal dominant trait with incomplete penetrance. The most common mutation, 946delGAG, has been observed in populations with different ethnic and geographic origins. We have investigated 40 individuals from 22 unrelated families with ITD originating from the Land of Valencia, Spain, for the presence of this mutation and we found 5 patients and 6 unaffected subjects from 4 families who were carriers of the mutation. This finding indicates that 18% of families may be diagnosed as DYT1 and that penetrance is reduced. We detected two different geographic and linguistic origins of the Valencian families. However, by haplotype analysis using D9S1260, D9S1261, D9S63 and D9S1262 as flanking markers, we demonstrated that all affected and unaffected carriers shared a common chromosome confirming identical origin of the mutation in the four families. We postulate a unique origin for the 946delGAG mutation in the Land of Valencia and, based on linguistic criterion, we propose that the mutation might have occurred at the beginning of the second millennium. Genetic analysis of another family from Castilla-La Mancha showed a different haplotype segregating with the disease, suggesting that at least two distinct mutational events for the 946delGAG mutation have occurred in Spain.

Alleles↗

PubMed2003

[The role played by parents in the development and learning of children with attention deficit hyperactivity disorder].

INTRODUCTION: The parents of children with attention deficit hyperactivity disorder (ADHD) undergo high levels of stress, frequent quarrels amongst themselves and limitations in their social life, which are factors that exert an influence on the progress of the disorder and constitute a high priority therapeutic goal. AIMS: 1. To analyse the impact ADHD has on family life: economy, the relations between parents and children and between brothers and sisters, social life, and the feelings and attitudes parents have towards their child. 2. To study possible changes in the use of behavioural modification techniques and in the attributions/expectations of the parents following a programme of counselling. SUBJECTS AND METHODS: In order to accomplish the first objective, 36 couples filled in a questionnaire about family impact, and percentage analyses were carried out. To achieve the second aim, 28 couples, who received counselling in small groups, filled in questionnaires before and after the programme, and comparative analyses were performed using the Wilcoxon interval test. RESULTS: 89% of parents suffer from stress, 64% feel uncomfortable about their child's behaviour, for 68% of them the psychoeducational cost of the child is higher, 50% have quarrels with their partner and 44% report that it makes it more difficult for their brothers and sisters to take part in activities. Significant changes have also been observed in the knowledge parents have about the nature of the disorder and the attributions/expectations they have about their child, together with improvements in the application of behavioural modification techniques. CONCLUSIONS: ADHD exerts a negative effect on the family system; parent counselling has proved to be effective in understanding the pathology and bringing about positive changes in expectations/attributions.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

[Adopted children: risk factors and neuropsychological problems].

In recent years there has been a striking increase in the number of transnational adoptions in our country, which follows the trend already observed in other developed European countries. Major contributing factors to this phenomenon have been the improvements in socioeconomic conditions in our country, the drop in the birth rate, with the corresponding decrease in the number of children available for adoption, and the disappearance of orphanages. This growing demand can be met by developing countries, in which the birth rate is still high and there are only limited chances of being able to maintain offspring. The children that are adopted come mainly from countries in Central and South America, Eastern Europe and Asia. Pathologies that can be expected in adopted children include general paediatric conditions, especially infections (which are often autochthonous ailments in their own country) and malnutrition, as well as neuropsychological and developmental disorders, such as psychomotor retardation, conduct and behavioural disorders, which sometimes stem from conflicts arising in the process of adaptation, communication problems, which occasionally reflect an autistic like disorder, and the problems deriving from the circumstances that condition the donation of the child for adoption (perinatal pathology, maternal drug addiction and withdrawal symptoms, maternal psychopathology.). The pathology, history and prognosis of the adopted child depend on several different factors that act in an accumulative fashion. The country of origin plays a decisive role in the type of pathology, according to the level of the health care system that exists there, the existence of adoption programmes that are regulated by law, etc. The child's age at adoption marks the difference in the optimisation of their development, if they have early access to a stable family unit. Having stayed in institutions and the length of time spent there is a risk factor for presenting a neuropsychological pathology. On many occasions the scarce information available about the child's medical history makes it more difficult to anticipate the appearance of certain problems. The existence of social risk factors in the biological families is a conditioning factor in increased morbidity. We describe a short series of adopted patients who were attended in our Neuropaediatric clinic, and we analyse the above mentioned conditioning variables and the most frequent pathologies.

Adolescent↗

PubMed2002

[The pharmacological approach to the autistic spectrum].

OBJECTIVE: To describe our experience of the drug treatment of children within the autistic spectrum. DEVELOPMENT: We analyze some neuroleptic drugs, the serotonin uptake inhibitors and antiepileptic drugs, emphasizing the most suitable drugs for each symptom we wish to treat and how to do so. CONCLUSIONS: The treatment of children within the autistic spectrum should be specific, meticulous and well controlled by the neuropaediatrician. It should be changed according to the symptoms and never expected to be the same during the patient s entire life. More studies are needed in this field.

Anticonvulsants↗

PubMed2002

[Interdisciplinary diagnosis in early attention].

INTRODUCTION: The diagnosis is an essential element for the therapeutic approach in Early Attention. This is considered from a multifactorial point of view in all aspects of child development. It starts with a programme to follow-up the neurological progress of children at risk and requires the collaboration of professionals trained in medicine, psychology, teaching and the social sciences. OBJECTIVE: For the interdisciplinary group to make a satisfactory diagnosis, and also find a suitable way of informing the family of this, in spite of their emotional turmoil. METHODS: A holistic approach and naturalist methods suitable to the context. CONCLUSIONS: We considered children with developmental disorders from the biological, psychological, social and educational points of view when making a functional diagnosis on which to base a plan for treatment in the 'Early Attention Service'.

Child↗