António Freire | Universidade de Coimbra (original) (raw)

Papers by António Freire

Investigative Ophthalmology & Visual Science, 2008

Brain, 2005

Sensory deficits have been documented in Parkinson's disease, in particular within the visual dom... more Sensory deficits have been documented in Parkinson's disease, in particular within the visual domain. However, ageing factors related to the brain and to neural and non-neural ocular structures could explain some of the previously reported results, in particular the claimed impairment within the koniocellular pathway.This study addressed visual impairment attributable to the magno-(luminance), parvo-(red-green) and koniocellular (blue-yellow) pathways in a population of Parkinson's disease patients. To avoid potentially confounding factors, all subjects underwent a full neurophthalmological assessment which led to exclusion of subjects with increased intraocular pressure, diabetes even in the absence of retinopathy, and ocular abnormalities (from a total of 72 patients' eyes, 12 were excluded). Both parvo-and koniocellular pathways were studied by means of contrast sensitivity (CS) measurements along protan, tritan and deutan axes and also by fitting chromatic discrimination ellipses using eight measured contrast axes. Magnocellular function was assessed, using stimuli that induce a frequency doubling illusion, in 17 locations in the fovea and periphery. Achromatic (luminance modulation) thresholds were significantly higher in Parkinson's disease both in foveal and peripheral locations. A significant impairment was observed along protan and deutan axes, but only marginally along the tritan axis. These results were corroborated by a significant elongation of chromatic discrimination ellipses in our Parkinson's disease group. Correlation analysis showed that achromatic and chromatic CS measures were independent, which implies that multiple visual pathways are affected independently in Parkinson's disease. Magnocellular impairment was significantly correlated with age and disease stage, in contrast to the measured chromatic deficits. We conclude that in Parkinson's disease, independent damage occurs in the early magnoand parvocellular pathways. Furthermore, traditional koniocellular probing strategies in Parkinson's disease may be confounded by ageing factors, which may reconcile the previously reported controversial findings concerning chromatic impairment in Parkinson's disease.

Parkinsonism & Related Disorders, 2007

The BG may play an integrative role in cognitive information processing. The role of the STN is d... more The BG may play an integrative role in cognitive information processing. The role of the STN is different. The P3 potentials related to the increased demand on executive functions but not the standard oddball P3 were recorded on the STN contacts with the best effect on Parkinsonian motor signs. This could suggest that the STN takes part specifically in the processing of executive functions. Conclusion: STN participates on cognitive functions in a different way than a caudate, putamen and pallidum. This might indicate that involvement of STN in cognitive functions is processed outside of standard cortico-basal ganglia-thalamic circuitry.

Oxford Medical Case Reports, 2021

Germline and 2-hit brain somatic variants in DEPDC5 gene, a negative regulator of the mammalian t... more Germline and 2-hit brain somatic variants in DEPDC5 gene, a negative regulator of the mammalian target of rapamycin (mTOR) pathway, are increasingly recognized in patients with focal cortical dysplasia (FCD). Next-generation targeted sequencing identified a heterozygous germline variant in DEPDC5 gene (c.3241A>C, p.Thr1081Pro), classified as of unknown significance, in a patient with clinical features compatible with DEPDC5 phenotype (FCD, focal epilepsy, attention-deficit/hyperactivity disorder and borderline intellectual functioning). This missense variant has previously been reported in two other epileptic patients. Although interpretation of missense variants remains a challenge, DEPDC5 variants in patients with FCD and epilepsy cannot be neglected. Null variants were the most frequently reported in FCD patients, but missense variants have been described as well. The recognition of DEPDC5 phenotype and the appropriate interpretation of the detected variants are essential, sin...

Brain research, Oct 1, 2016

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements ... more Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinson's disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) stud...

Journal of the neurological sciences, Jan 15, 2017

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainste... more Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and verti...

Neuropsychologia, 2009

Motion processing involves multiple hierarchical steps, from the magnocellular pathway, sensitive... more Motion processing involves multiple hierarchical steps, from the magnocellular pathway, sensitive to high temporal frequency modulations, to subsequent motion integration within the visual cortical dorsal stream. We have tested whether motion integration deficits in mild Parkinson disease (PD) can be explained by visual deficits in earlier processing nodes. Contrast sensitivity deficits in the magnocellular pathway, were compared with speed discrimination of local dots moving in random directions, speed and direction discrimination of moving surfaces and motion integration as measured by 2D coherence thresholds (n=27). We have found that low-level magnocellular impairment in PD does not explain deficits in subsequent steps in motion processing. High-level performance was abnormal in particular for tasks requiring perception of coherently moving surfaces. Motion coherence deficits were predictive of visuomotor impairment, corroborating a previous magnetic stimulation study in normal subjects. We conclude that dorsal stream deficits in PD have a high-level visual cortical basis independent of low-level magnocellular damage.

International Journal of Stroke, 2014

Background The greatest potential to reduce the burden of stroke is by primary prevention of firs... more Background The greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the ‘mass’ approach), the ‘high risk’ approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke Riskometer™, has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods 752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke R...

Neurology International

The objective of this study is to assess the impact of recanalization (spontaneous and therapeuti... more The objective of this study is to assess the impact of recanalization (spontaneous and therapeutic) on upper limb functioning and general patient functioning after stroke. This is a prospective, observational study of patients hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery (n = 98). Patients completed a comprehensive rehabilitation program and were followed-up for 24 weeks. The impact of recanalization on patient functioning was evaluated using the modified Rankin Scale (mRS) and Stroke Upper Limb Capacity Scale (SULCS). General and upper limb functioning improved markedly in the first three weeks after stroke. Age, gender, and National Institutes of Health Stroke Scale (NIHSS) score at admission were associated with general and upper limb functioning at 12 weeks. Successful recanalization was associated with better functioning. Among patients who underwent therapeutic recanalization, NIHSS scores ≥16.5 indicate lower general functioning at ...

Frontiers in Neuroscience

Introduction: Focal cortical dysplasias (FCDs) are a group of malformations of cortical developme... more Introduction: Focal cortical dysplasias (FCDs) are a group of malformations of cortical development that constitute a common cause of drug-resistant epilepsy, often subjected to neurosurgery, with a suboptimal long-term outcome. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of FCD. This study aimed to provide an updated review on the genomic and epigenetic advances underlying FCD etiology, to understand a genotype–phenotype correlation and identify priorities to lead future translational research.Methods: A scoping review of the literature was conducted, according to previously described methods. A comprehensive search strategy was applied in PubMed, Embase, and Web of Science from inception to 07 May 2020. References were screened based on title and abstract, and posteriorly full-text articles were assessed for inclusion according to eligibility criteria. Studies with novel gene variants or epigenetic regulatory mechanisms in patients...

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, Jan 17, 2018

To evaluate the utility of positional testing in peripheral and central acute vestibular syndrome... more To evaluate the utility of positional testing in peripheral and central acute vestibular syndrome (pAVS, cAVS, respectively). Prospective; observational. Tertiary referral center. Consecutive AVS patients. Video-oculography in upright, supine and head hanging positions at presentation, 3-month and 1-year follow-up. Positional modulation of spontaneous nystagmus; co-occurrence of central paroxysmal positional nystagmus (CPPN). Fifteen pAVS [mean age (SD), 53.3 (16.6) (11 males)] and 15 cAVS [mean age (SD), 56.5 (17.8) (11 males)] patients were included (p=0.49). Acutely, in supine, in patients whose nystagmus was present in both head rotation sides, 12 of 13 (93%) pAVS and only 4 of 12 (33%) cAVS patients showed direction-fixed positional nystagmus which was stronger when turning the head to the slow phase side. The remaining cAVS patients showed either direction-fixed positional nystagmus which was stronger when turning the head to the fast phase side (5), or direction-changing posi...

Topics in stroke rehabilitation, Jan 13, 2018

To evaluate the potential of neuroimaging, serum biomarkers, stroke etiology, and clinical charac... more To evaluate the potential of neuroimaging, serum biomarkers, stroke etiology, and clinical characteristics as predictors of upper limb functioning 12 weeks after stroke. This was a prospective, observational study of patients (18-85 years-old) hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery. Patients were hospitalized at a stroke rehabilitation center, where they underwent a standardized rehabilitation program. Clinical, imagiology, laboratory (biomarkers: C-reactive protein, D-dimer, and fibrinogen, and S100 calcium binding protein β [S100β]), and functionality assessments were conducted four different times: within 24 hours, and at 48 hours, 3 weeks, and 12 weeks after acute stroke. Upper limb functioning at 12 weeks was significantly associated with Alberta Stroke Program Early CT Score (ASPECTS) score (OR:2.012 [CI:1.349-3.000]; P = 0.001) and S100β protein levels (OR:0.997 [CI:0.994-0.999]; P = 0.007). Advanced age was associated with po...

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, Jan 20, 2018

Stroke is one of the leading causes of disability worldwide. Early prediction of poststroke disab... more Stroke is one of the leading causes of disability worldwide. Early prediction of poststroke disability using clinical models is of great interest, especially in the rehabilitation field. Although some biomarkers and neuroimaging techniques have shown potential predictive value, there are still insufficient data to support their clinical utility in predicting poststroke functional recovery. We aimed to assess the value of serum biomarkers (C-reactive protein [CRP], D-dimer, fibrinogen, and S100β protein) in predicting medium-term (12 weeks) functional outcome in patients with acute ischemic stroke. This is an observational, prospective study in a sample of patients hospitalized for ischemic stroke (N = 131). Peripheral blood levels of biomarkers of interest were determined at admission (CRP, D-dimer, and fibrinogen) or at 48 hours poststroke (S100β protein). Functional status was accessed at 48 hours and 12 weeks poststroke using the modified Rankin Scale (mRS). S100β protein levels ...

Advances in experimental medicine and biology, 2018

Machado-Joseph disease (MJD) also known as Spinocerebellar ataxia type 3, is a hereditary neurode... more Machado-Joseph disease (MJD) also known as Spinocerebellar ataxia type 3, is a hereditary neurodegenerative disease associated with severe clinical manifestations and premature death. Although rare, it is the most common autosomal dominant spinocerebellar ataxia worldwide and has a distinct geographic distribution, reaching peak prevalence in certain regions of Brazil, Portugal and China. Due to its clinical heterogeneity, it was initially described as several different entities and as had many designations over the last decades. An accurate diagnosis become possible in 1994, after the identification of the MJD1 gene. Among its wide clinical spectrum, progressive cerebellar ataxia is normally present. Other symptoms include pyramidal syndrome, peripheral neuropathy, oculomotor abnormalities, extrapyramidal signs and sleep disorders. On the basis of the presence/absence of important extra-pyramidal signs, and the presence/absence of peripheral signs, five clinical types have been def...

European neurology, Jan 13, 2017

Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in man... more Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in many neurodegenerative disorders. The aim of this study was to assess and compare apathy profile in Parkinson's and Huntington's patients using the same comprehensive instruments to measure apathy, cognition and depressive symptoms. We consecutively assessed Parkinson's disease (PD) and Huntington's disease (HD) patients recruited from a Movement Disorders Unit. In all patients, information related to demographics, clinical data, motor score (Movement Disorders Society-Unified Parkinson Disease Rating Scale; Unified Huntington Disease Rating Scale), cognition (Montreal Cognitive Assessment scale), depressive symptoms (Beck Depression Inventory II) and apathy (Apathy Evaluation Scale - clinical version) was collected. Patients with dementia or major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised criteria were exclud...

Acta medica portuguesa, Jan 31, 2017

Parkinson's disease has a significant impact in quality of life, which can be assessed with 3... more Parkinson's disease has a significant impact in quality of life, which can be assessed with 39-item Parkinson's Disease Questionnaire and Parkinson's Disease Quality of Life Questionnaire. This study aimed to evaluate the reliability and validity of these scales in Portuguese patients. Reliability was assessed through internal consistency (Cronbach's alpha) and reproducibility (intraclass correlation coefficient). Regarding construct validity, we performed one-way analysis of variance across different groups according to modified Hoehn and Yahr scale. For criterion validity, we compared both scales with each other and with the Short Form 36-item Health Survey. In a total of 100 patients with Parkinson's disease, Cronbach's alpha ranged for 39-item Parkinson's Disease Questionnaire between 0.66 - 0.98, and for Parkinson's Disease Quality of Life Questionnaire, between 0.78 - 0.98. Intraclass correlation coefficient for 39-item Parkinson's Disease Q...

European neurology, Jan 18, 2016

The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of... more The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET). We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up. From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement ...