Publications by authors named "Ruben Rocha"

15 Publications

  • Page 1 of 1

Behavioral and brain morphological analysis of non-inflammatory and inflammatory rat models of preterm brain injury.

Neurobiol Learn Mem 2021 11 19;185:107540. Epub 2021 Oct 19.

Department of Biomedicine - Unit of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Center of Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal. Electronic address:

Investigations using preclinical models of preterm birth have much contributed, together with human neuropathological studies, for advances in our understanding of preterm brain injury. Here, we evaluated whether the neurodevelopmental and behavioral consequences of preterm birth induced by a non-inflammatory model of preterm birth using mifepristone would differ from those after inflammatory prenatal transient hypoxia-ischemia (TSHI) model. Pregnant Wistar rats were either injected with mifepristone, and pups were delivered on embryonic day 21 (ED21 group), or laparotomized on the 18th day of gestation for 60 min of uterine arteries occlusion. Rat pups were tested postnatally for characterization of developmental milestones and, after weaning, they were behaviorally tested for anxiety and for spatial learning and memory. One month later, brains were processed for quantification of doublecortin (DCX)- and neuropeptide Y (NPY)-immunoreactive cells, and cholinergic varicosities in the hippocampus. ED21 rats did not differ from controls with respect to neonatal developmental milestones, anxiety, learning and memory functions, and neurochemical parameters. Conversely, in TSHI rats the development of neonatal reflexes was delayed, the levels of anxiety were reduced, and spatial learning and memory was impaired; in the hippocampus, the total number of DCX and NPY cells was increased, and the density of cholinergic varicosities was reduced. With these results we suggest that a preterm birth, in a non-inflammatory prenatal environment, does not significantly change neonatal development and adult neurologic outcome. On other hand, prenatal hypoxia and ischemia (inflammation) modifies developmental trajectory, learning and memory, neurogenesis, and NPY GABAergic and cholinergic brain systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nlm.2021.107540DOI Listing
November 2021

Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy.

Eur J Paediatr Neurol 2021 Oct 14;35:74-81. Epub 2021 Oct 14.

Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK; Neonatal and Paediatric Neurology, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address:

Background: Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited.

Aims: To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age.

Methods: Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury.

Results: In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165).

Conclusions: Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2021.10.005DOI Listing
October 2021

Epilepsy in paediatric patients with Parry-Romberg syndrome: A review of the literature.

Seizure 2020 Jan 28;76:89-95. Epub 2020 Jan 28.

Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom.

Background: Parry-Romberg syndrome (PRS) is a rare disorder characterized by unilateral slow progressive facial atrophy that can be associated with neurologic manifestations, namely seizures. There is scarce data about seizures in paediatric patients with PRS. The aim of our work was to clarify the clinical features of paediatric patients with PRS and seizures.

Methods: We performed a literature review based on a literature search using PubMed and EMBASE databases. We included original articles in which the main diagnosis was PRS and the patients were 17 years old or less when the first seizure occurred.

Results: We included 40 patients. Most of the patients had previously normal development and had their first seizure in the first decade of life. Neurologic examination was abnormal in 56 % of patients. Seizures are typically focal, frequently with impaired awareness, and became refractory in about 40 % of patients. Few patients have generalized seizures. On electroencephalogram, epileptic discharges are generally focal, on the same side as the facial atrophy, without a predominant cerebral lobe localization. Brain MRI is almost always abnormal, typically with T2 subcortical hyperintensities, and sometimes brain atrophy or calcifications. In addition to the classic antiepileptic drugs, immunosuppressive drugs should be considered as potential epilepsy treatment.

Conclusion: To the best of our knowledge, this is the first review dedicated to the characteristics of paediatric patients with PRS and epilepsy. Seizures are usually focal, became refractory in 40 %, and have a significant impact on the quality of life and neurodevelopment of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2020.01.017DOI Listing
January 2020

Developing sustainable research careers for KL2 scholars: The importance of an inclusive environment and mentorship.

J Clin Transl Sci 2017 Aug 31;1(4):226-228. Epub 2017 Aug 31.

The Utah Center for Clinical and Translational Science, University of Utah, Salt Lake City, UT, USA.

Introduction: The National Clinical and Translational Science Award (CTSA) Consortium 2.0 has developed common metrics as a collaborative project for all participating sites. Metrics address several important aspects and functions of the consortium, including workforce development. The first workforce development metrics to be proposed for all CTSA hubs include the proportion of CTSA-supported trainees and scholars with sustainable careers in translational research and the diversity and inclusiveness of programs.

Methods And Results: The University of Utah Center for Clinical and Translational Science (CCTS), a CTSA hub, has been actively engaged in mentoring translational scientists for the last decade. We have developed programs, processes, and institutional policies that support translational scientists, which have resulted in 100% of our KL2 scholars remaining engaged in translational science and in increasing the inclusion of individuals under-represented in medicine in our research enterprise. In this paper, we share details of our program and what we believe are evidence-based best practices for developing sustainable translational research careers for all aspiring junior faculty members.

Conclusions: The University of Utah Center for Clinical and Translational Science has been integral in catalyzing interactions across the campus to reverse the negative trends seen nationally in sustaining clinician scientists. Our programs and processes can serve as a model for other institutions seeking to develop translational scientists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/cts.2017.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890311PMC
August 2017

MEF2C haploinsufficiency syndrome: Report of a new MEF2C mutation and review.

Eur J Med Genet 2016 Sep 31;59(9):478-82. Epub 2016 May 31.

Pediatric Neurology Unit, Department of Paediatrics, Centro Hospitalar São João, Porto, Portugal; Neurogenetics Unit, Department of Medical Genetics, Centro Hospitalar São João, Porto, Portugal.

Introduction: MEF2C haploinsufficiency syndrome is characterized by severe intellectual disability, epilepsy, stereotypic movements, minor dysmorphisms and brain abnormalities. We report the case of a patient with a new MEF2C mutation, comparing his clinical and imaging features to those previously reported in the literature.

Case Report: A 10 year-old boy first came to pediatric neurology clinic at the age of 11 months because of severe psychomotor delay, without regression. He presented generalized hypotonia, poor eye contact, hand-mouth stereotypies, strabismus and minor facial dimorphisms. Epileptic seizures started at 26 months of age and were refractory. Brain MRI showed a slight increase in periventricular white matter signal and globally enlarged CSF spaces. Molecular analysis revealed a de novo, pathogenic and causative MEF2C mutation.

Discussion: MEF2C haploinsufficiency syndrome was recently recognized as a neurodevelopmental disorder. Severe intellectual disability with inability to speak and epilepsy are universal features in patients with MEF2C mutations, although mild cognitive and speech disorders have been reported to occur in patients with duplications. Epilepsy might be absent in patients with partial deletions. Abnormal movement patterns are very common in patients with MEF2C haploinsufficiency. Delayed myelination seems to be more commonly observed in patients with MEF2C mutations, while malformations of cortical development were only reported in patients with microdeletions. Although MEF2C haploinsufficiency prevalence is yet to be determined, it should be considered in the differential diagnosis of patients with severe intellectual disability and Rett-like features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2016.05.017DOI Listing
September 2016

Brain Herniation into the Dural Venous Sinus.

J Pediatr 2016 07 9;174:276. Epub 2016 May 9.

Neuropediatrics Unit, Pediatrics Department, Centro Hospitalar de São João, Porto, Portugal.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2016.04.010DOI Listing
July 2016

Expanding the phenotype of IFAP/BRESECK syndrome: a new case with severe hypogammaglobulinemia.

Eur J Med Genet 2013 Nov 30;56(11):603-5. Epub 2013 Sep 30.

Pediatric Department, São João Hospital, Porto, Portugal. Electronic address:

The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome. Some male patients have additional features including brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies and kidney dysplasia/hypoplasia (BRESEK syndrome) sometimes associated with Hirschsprung disease and cleft palate or cryptorchidism (BRESHECK syndrome). We report a 5 months-old male patient with the p.R429H mutation in MBTPS2 protein, which has been reported to be associated with the most severe phenotype of patients with IFAP/BRESHECK syndrome. This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. Additional features not previously reported in IFAP syndrome, include severe hypogammaglobulinemia and congenital rectourethral fistula.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2013.09.005DOI Listing
November 2013

Novel STXBP1 mutations in 2 patients with early infantile epileptic encephalopathy.

J Child Neurol 2015 Apr 26;30(5):622-4. Epub 2013 Mar 26.

Pediatric Neurology Department, Hospital Pediátrico Integrado, Centro Hospitalar São João, Porto, Portugal Genetics Department, Faculdade de Medicina da Universidade do Porto, Portugal.

The authors describe 2 patients with early infantile epileptic encephalopathy caused by 2 novel mutations involving the STXBP1 gene. The authors suggest that in spite of the rarity of STXBP1 mutations, molecular analysis of STXBP1 gene should be performed in patients with early infantile epileptic encephalopathy, after exclusion of ARX mutations in male patients and CDKL5 mutations in female patients. The potential mechanisms explaining the variable clinical phenotypes caused by STXBP1 mutations are discussed and the designation of early-onset epileptic encephalopathies, including an updated genetic classification, is proposed to encompass the epileptic encephalopathies beginning in the first 6 months of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0883073813479169DOI Listing
April 2015

Neuroborreliosis presenting as acute disseminated encephalomyelitis.

Pediatr Emerg Care 2012 Dec;28(12):1374-6

Pediatric Intensive Care Unit, Centro Hospitalar S João, Porto, Portugal.

We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PEC.0b013e318276c51dDOI Listing
December 2012

Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL): a pediatric case report.

J Child Neurol 2013 Dec 17;28(12):1661-3. Epub 2012 Oct 17.

1Pediatrics Resident, Department of Pediatrics, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Porto, Portugal.

The syndrome of transient headache and neurologic deficits associated with cerebrospinal fluid lymphocytosis (HaNDL) is characterized by 1 or more episodes of severe headache, transient neurologic deficits, and lymphocytic pleocytosis in the cerebrospinal fluid. It is a benign and self limited disorder seldom reported in pediatric age. We report the case of a 14-year-old girl who suffered from 2 episodes of headache with transient focal neurologic deficits and pleocytosis consistent with the syndrome of HaNDL. This entity should be taken into account as a differential diagnosis in otherwise healthy children presenting with recurrent headache and acute neurologic deficits. Repeated use of invasive and expensive laboratory and imaging investigations can be avoided when the diagnosis of the syndrome of HaNDL is correctly established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0883073812462063DOI Listing
December 2013

Moyamoya vascular pattern in Alagille syndrome.

Pediatr Neurol 2012 Aug;47(2):125-8

Pediatric Neurology Unit, Department of Pediatrics, Centro Hospital S. João, Porto, Portugal.

We describe a girl with Alagille syndrome and a moyamoya angiographic pattern on magnetic resonance angiography. She was referred for genetic consultation because of posterior embryotoxon and peripheral pulmonary stenosis. Her facial appearance was typical, but she had no cholestasis or vertebral involvement. A heterozygous duplication of one nucleotide (a c.715dupA mutation) not previously described was identified in exon 5 of the JAG1 gene. We review similar cases in the literature and possible pathophysiologic mechanisms (e.g., the Jagged 1 and Notch signaling pathway) of this association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2012.04.014DOI Listing
August 2012

Omalizumab in the treatment of eosinophilic esophagitis and food allergy.

Eur J Pediatr 2011 Nov 2;170(11):1471-4. Epub 2011 Aug 2.

Department of Pediatrics, Hospital S João, EPE, Alameda Prof. Hernâni Monteiro, 4200-319 Oporto, Portugal.

Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance--the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-011-1540-4DOI Listing
November 2011

Immune disease expressed in liver and platelets in an adolescent: a case report.

Ital J Pediatr 2010 Jun 11;36:42. Epub 2010 Jun 11.

Adolescents Unit and Gastrenterology, Hepatology and Nutrition Unit, Pediatrics Department, Braga Hospital, and Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.

We report a case of a 15-year-old boy with autoimmune hepatitis lacking common serologic markers and normal gammaglobulinemia associated with immune thrombocytopenia and family history of psoriasis. He presented to our department with a 4-year history of a cervical posterior lymphadenopathy and recent petechiae. Previous laboratory results 6 months before already showed hepatocellular injury. After exclusion of other causes, the diagnosis of autoimmune hepatitis was made based on clinical grounds, associated immune disorder and histological features of liver biopsy.The authors alert for this atypical presentation of autoimmune hepatitis and associated immune thrombocytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1824-7288-36-42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892502PMC
June 2010

Prognosis of decompensated heart failure: role of NT-proBNP.

Rev Port Cardiol 2007 May;26(5):535-45

Departamento de Medicina, Hospital São João, Semiótica Clínica, Porto, Portugal.

Background: The prognostic value of natriuretic peptides in heart failure (HF) is well established. The objective of this study was to evaluate the role of NT-proBNP in predicting outcome in decompensated HF.

Methods: Patients admitted with decompensated HF to our Internal Medicine Department between November 2002 and April 2004 with at least two measurements of NT-proBNP (within 24 hours of admission and on discharge) were analyzed. Patients discharged alive were followed for up to 6 months. The primary endpoint was death or readmission.

Results: We included 304 patients (72.7+/-11.6 years of age, 53.9% female, 49.3% ischemic etiology). Echocardiography was performed in 73.7%. Left ventricular systolic function (LVSF) was preserved in 20.7%, mildly to moderately depressed in 32.2% and severely depressed in 20.7%. There was a significant decrease in median NT-proBNP levels during hospitalization (from 7006 to 3796 pg/ml, p<0.001). The patients were classified in three groups according to NT-proBNP variation: 1 decreasing by at least 30% (n=162); 2 - no significant variation (n=95); and 3 - increasing by at least 30% (n=47). The primary endpoint was observed in 43% of the patients. In univariate analysis, variables predictive of outcome were: NT-proBNP at discharge (> median: HR=2.72; 95% CI=1.89-3.92): variation in NT-proBNP levels during hospitalization (group 2 vs. group 1 - HR=2.28; 95% CI=1.52-3.42; group 3 vs. group 1 - HR=4.82; 95% CI=3.11-7.49); renal failure (creatinine >2 mg/dL - HR=1.65; 95% CI=1.07-2.53); and treatment with ACE-Is (HR=0.59; 95% CI=0.39-0.89). After adjustment for NYHA class at discharge, pulse pressure, LVSF, renal function and hemoglobin, only NT-proBNP at discharge and NT-proBNP variation remained independent predictors of prognosis (NT-proBNP at discharge > median: HR=2.02; 95% CI=1.28-3.2; NT-proBNP variation: group 2 vs. group 1 - HR=2.24; 95% CI=1.37-3.66; group 3 vs. group 1 - HR=3.85; 95% CI=2.24-6.63).

Conclusion: Our results extend previous reports on the value of NT-proBNP in predicting outcome after discharge in patients hospitalized due to decompensated HF, and demonstrate its potential usefulness and applicability in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2007
-->