Alberto Fernández-Jaén

Cortical Thickness in Fetal Alcohol Syndrome and Attention Deficit Disorder

Fetal alcohol syndrome represents the classic and most severe manifestation of epigenetic changes induced by exposure to alcohol during pregnancy. Often these patients develop attention deficit hyperactivity disorder. We analyzed cortical thickness in 20 children and adolescents with fetal alcohol syndrome and attention deficit hyperactivity disorder (group 1), in 20 patients without fetal alcohol syndrome (group 2), and in 20 control cases. The first group revealed total cortical thickness significantly superior to those of the other two groups. In per-lobe analyses of cortical thickness, group 1 demonstrated greater cortical thickness in the frontal, occipital, and right temporal and left frontal lobes compared with the second group, and in both temporal lobes and the right frontal lobe compared with the control group. This study demonstrated greater cortical thickness in patients with attention deficit hyperactivity disorder and heavy prenatal exposure to alcohol, probably as an expression of immature or abnormal brain development.

An open-label, prospective study of levetiracetam in children and adolescentes with Tourette syndrome

OBJECTIVESnTo evaluate the usefulness of levetiracetam (LEV) for the treatment of tics in patients with Tourette syndrome (TS) by means of a prospective, open-label, 12-week study.nnnMATERIAL AND METHODSnTwenty-nine patients with TS who received LEV to control their tics were admitted to the study. The authors recorded the following variables: initial status (Yale Global Tic Severity Scale - YGTSS - and the scale of Modified Clinical Global Impression -MCGI), the clinical status at 3 months using the same scales, and clinical/medical impression of improvement.nnnRESULTSnThe mean age of the patients studied was 12 years; 25 males (86%) and 4 females (14%). Participants received 800-2000 mg/day of LEV. Of the 29 patients, 21 children (72%) improved according to YGTSS and MCGI scores. Mean YGTSS Total Tic Score at baseline and after treatment with LEV were 67 and 44, respectively. The statistical analysis confirmed a significant improvement with a p-value of <0.001 on the YGTSS and MCGI. In 3 cases, treatment was suspended due to adverse effects.nnnCONCLUSIONSnTreatment with LEV can constitute a treatment option for tics in patients with TS. Double-blind trials of longer duration are needed in larger samples in order to establish both the benefit, as well as what patients are eligible for treatment.

Emotional distraction in boys with ADHD: Neural and behavioral correlates

Although, in everyday life, patients with attention deficit hyperactivity disorder (ADHD) are frequently distracted by goal-irrelevant affective stimuli, little is known about the neural and behavioral substrates underlying this emotional distractibility. Because some of the most important brain responses associated with the sudden onset of an emotional distracter are characterized by their early latency onset and short duration, we addressed this issue by using a temporally agile neural signal capable of detecting and distinguishing them. Specifically, scalp event-related potentials (ERPs) were recorded while 20 boys with ADHD combined type and 20 healthy comparison subjects performed a digit categorization task during the presentation of three types of irrelevant, distracting stimuli: arousing negative (A-), neutral (N) and arousing positive (A+). Behavioral data showed that emotional distracters (both A- and A+) were associated with longer reaction times than neutral ones in the ADHD group, whereas no differences were found in the control group. ERP data revealed that, compared with control subjects, boys with ADHD showed larger anterior N2 amplitudes for emotional than for neutral distracters. Furthermore, regression analyses between ERP data and subjects emotional ratings of distracting stimuli showed that only in the ADHD group, emotional arousal (ranging from calming to arousing) was associated with anterior N2: its amplitude increased as the arousal content of the visual distracter increased. These results suggest that boys with ADHD are more vulnerable to the distracting effects of irrelevant emotional stimuli than control subjects. The present study provides first data on the neural substrates underlying emotional distractibility in ADHD.

Bilateral, wide-spread, mechanical pain sensitivity in children with frequent episodic tension-type headache suggesting impairment in central nociceptive processing.

Introduction: The aim was to investigate bilateral, wide-spread pressure pain hyperalgesia in symptomatic (trigeminocervical) and non-symptomatic (pain-free distant) regions in children with frequent episodic tension-type headache (FETTH). Methods: Twenty-five children, 6 boys and 19 girls (mean age, 8.9u2009±u20091.8 years) with FETTH and 50 age- and sex-matched healthy children (12 boys, 38 girls; mean age: 8.8u2009±u20091.7 years) were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over temporalis muscle, upper trapezius muscle, second metacarpal and tibialis anterior muscles in a blinded design. Results: The results showed that PPT levels were significantly decreased bilaterally over the temporalis, upper trapezius and tibialis muscles, and the second metacarpal in children with FETTH as compared to controls (all sites, Pu2009<u20090.001). No significant differences in the magnitude of PPT decrease between the upper trapezius muscle, second metacarpal and tibialis anterior muscles were found. PPT over both upper trapezius muscles were negatively correlated with the history and intensity of headache (rsu2009=u2009−0.415; Pu2009=u20090.045). Conclusions: The findings revealed bilateral, wide-spread pressure pain hypersensitivity in children with FETTH suggesting that wide-spread central sensitisation is involved in children with this headache pain condition.

Cortical thinning of temporal pole and orbitofrontal cortex in medication-naïve children and adolescents with ADHD

Structural and functional brain studies on attention deficit/hyperactivity disorder (ADHD) have primarily examined anatomical abnormalities in the prefronto-striatal circuitry (especially, dorsal and lateral areas of the prefrontal cortex and dorsal striatum). There is, however, increased evidence that several temporal lobe regions could play an important role in ADHD. The present study used MRI-based measurements of cortical thickness to examine possible differences in both prefrontal and temporal lobe regions between medication-näive patients with ADHD (N = 50) and age- and sex-matched typically developing controls (N = 50). Subjects with ADHD exhibited significantly decreased cortical thickness in the right temporal pole and orbitofrontal cortex (OFC) relative to healthy comparison subjects. These differences remained significant after controlling for confounding effects of age, overall mean cortical thickness and comorbid externalizing conditions, such as oppositional defiant and conduct disorders. These results point to the involvement of the temporal pole and OFC in the neuropathology of ADHD. Moreover, present findings add evidence to the assumption that multiple brain regions and psychological processes are associated with ADHD.

Cortical thickness differences in the prefrontal cortex in children and adolescents with ADHD in relation to dopamine transporter (DAT1) genotype

Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely, recent data indicate that the 10-repeat (10R) DAT1 allele may mediate neuropsychological functioning, response to methylphenidate, and even brain function and structure in children with ADHD. This study aimed to investigate the influence of 10R DAT1 on thickness of the prefrontal cortex in children and adolescents with ADHD. To this end, brain magnetic resonance images were acquired from 33 patients with homozygosity for the 10R allele and 30 patients with a single copy or no copy of the allele. The prefrontal cortex of each MRI scan was automatically parceled into regions of interest (ROIs) based on Brodmann areas (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom severity, comorbidity and medication status. However, patients with two copies of the 10R allele exhibited significantly decreased cortical thickness in right BA 46 relative to patients with one or fewer copies of the allele. No other prefrontal ROI differed significantly between the two groups. Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD.

Gomez–Lopez-Hernandez Syndrome: Two New Cases and Review of the Literature

Gomez-Lopez-Hernandez syndrome, or cerebellotrigeminal-dermal dysplasia, is a rare neurocutaneous syndrome of trigeminal anesthesia, scalp alopecia and cerebellar anomalies. Other features include craniosynostosis, short stature, hypertelorism, down-slanting palpebral fissures, corneal opacities, mediofacial hypoplasia, and turri-brachycephaly. There have been 19 cases documented to date and we report on two additional male patients, 1 and 6 years of age, with typical features, mild mental retardation and dyspraxia. In both cases, MRI findings included rhombencephalosynapsis, a constant neuroimaging feature in this syndrome, comprising fusion of the cerebellar hemispheres with agenesis of the cerebellar vermis. Based on literature and our experience, we propose the presence of trigeminal anesthesia and/or partial alopecia of the scalp to complete the diagnosis of the syndrome.

Atomoxetine for Attention Deficit Hyperactivity Disorder in Mental Retardation

The study objective was to assess the efficacy and tolerability of atomoxetine in the treatment of attention deficit hyperactivity disorder symptoms in patients with mental retardation. In a 16-week, open-label, prospective study, 48 children with mental retardation and attention deficit hyperactivity disorder were recruited; the patients received atomoxetine, with a single final dose of 1.2 mg/kg per day reached at 3 weeks. The measure of efficacy was scores on Clinical Global Impression Severity scale (CGI-S), Conners, and Attention Deficit Hyperactivity Disorder Rating Scale ADHDRS-IV. A statistically significant difference was documented between the mean CGI-S scores before and after treatment: baseline CGI-S = 5.31 (S.D. = 0.85); post-treatment CGI-S = 4.13 (S.D. = 0.97), with a difference of 1.18 points (S.D. = 0.84) and a 95% confidence interval for the difference of 0.92-1.43 (P < 0.001). A statistically significant reduction (P < 0.01) was observed with respect to all the variables of the ADHDRS-IV and Conners scales. Slightly less than one third of the patients (31%) presented adverse events, the majority of which were mild, with irritability being the most frequent event. Atomoxetine appears to be to useful in improving attention deficit hyperactivity disorder symptoms in mentally retarded patients. Larger, randomized, controlled, double-blind studies are required to confirm the efficacy observed in this first study.

Clinical and cognitive response to extended-release methylphenidate (Medikinet) in attention deficit/hyperactivity disorder: efficacy evaluation.

IntroductionThe objective of the study was to assess the efficacy of extended-release methylphenidate (Mph-ER) (Medikinet®; MEDICE Arzneimittel Pütter GmbH & Co KG, Iserlohn, Germany) in the pediatric population with attention deficit/hyperactivity disorder (ADHD); a parallel analysis of the validity of various tools for monitoring short-term clinical response to treatment was made.MethodsThis was a retrospective analysis of 94 children with ADHD who received treatment with Mph-ER. The ADHD Rating Scale-IV (ADHD-RS) was used to assess clinical efficacy. The following neuropsychological tests were used to assess cognitive-attentional efficacy: the faces test, the D2 test, the Magallanes visual attention scale (EMAV; Escalas Magallanes de Attencion Visual), and the Conners’ Continuous Performance Test II (CPT-II). The ADHD-RS scale was completed by the parents at the time of diagnosis and after 3 months of treatment. The tests were taken by patients both without treatment and under the effects of treatment. The results of these variables were transformed into Z values for subsequent analysis.ResultsIn all, 84% of the patients lowered their ADHD-RS score with Mph-ER. Regarding the neuropsychological tests, a significant change was seen when the results of patients without treatment were compared with their later results with treatment. When the order of test conditions was reversed (with and then without treatment), the CPT-II was the only test for which there was still a significant difference.ConclusionMph-ER improved attention and self-control from a clinical and cognitive point of view. Of those studied, the CPT-II was the most effective neuropsychological test for monitoring efficacy of Mph in the short-term.

Efficacy of atomoxetine for the treatment of ADHD symptoms in patients with pervasive developmental disorders: a prospective, open-label study.

Objective: Atomoxetine’s tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners’ Scale, among others. Results: A significant difference was found between pre- and posttreatment scores as well as a significant reduction was found on the scales used. Only five patients presented adverse events. Conclusion: Atomoxetine therefore appears to be a useful drug, pointing to the need for larger, randomized, controlled, double-blind studies to confirm its efficacy versus placebo and in comparison with other treatment options.