Browsing by Issue Date, starting with "2021-08"
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- Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin BiopsyPublication . Corrà, Marta; Sousa, Mafalda; Reis, Inês; Tanganelli, Fabiana; Vila-Chã, Nuno; Sousa, Ana Paula; Magalhães, Rui; Sampaio, Paula; Taipa, Ricardo; Maia, LuisIntraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1-3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.
- Timely and Blood-Based Multiplex Molecular Profiling of Acute StrokePublication . Dias, Alexandre; Silva, Isabel; Pinto, Inês Mendes; Maia, LuisStroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood-protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care.
- Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 VariantPublication . Carneiro, Fábio; Duarte, Júlia; Laranjeira, Francisco; Barbosa-Gouveia, Sofia; Couce, María-Luz; Fonseca, Maria JoséPathogenic variants of the ADGRG1 gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous ADGRG1 variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel ADGRG1 variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.
- Inverted Internal Limiting Membrane Flap Technique: Is It the Best Option for Macular Holes?Publication . Silva, Nisa; Ferreira, André; Nawrocka (vel Michalewska), Zofia Anna; Meireles, AngelinaSurgical treatment is generally necessary to repair full-thickness macular holes (FTMH). Although vitrectomy with or without internal limiting membrane (ILM) peeling remains the standard surgical technique, the inverted ILM flap procedure has increasingly assumed a role in the primary surgical repair of FTMHs. Some vitreoretinal surgeons reserve this technique to treat large or myopic holes, whereas others use it routinely in all cases. This paper is a comprehensive review of the current scientific evidence on the anatomical and functional outcomes of the inverted ILM flap technique in the repair of macular holes, following the International Vitreomacular Traction Study (IVTS) group classification.
- Cardiovascular Complications of COVID-19 InfectionPublication . Trêpa, Maria; Hipólito-Reis, António; Oliveira, MarioIntroduction: Reports of cardiovascular complications related to the COVID-19 infection have been frequent. Methods: Narrative review for relevant articles on the topic. The classic cardiovascular risk factors, like age, obesity, diabetes, and hypertension are associated with adverse outcomes in COVID-19 patients. Cardiovascular complications can have a diverse clinical presentation including silent myocardial injury, acute coronary syndromes, thromboembolism, cardiac arrhythmias, and heart failure. There are multiple mechanisms of cardiac injury that are not mutually exclusive. The approach to diagnosis and management should be carried out according to usual practice, while considering the particularities of COVID-19 infection. Conclusion: The interaction between SARS-CoV-2 and the heart is complex and is manifested in multiple ways. Regardless of the clinical presentation, cardiac complications convey a worse prognosis. Patients should be actively monitored and treated accordingly.
- Pons Calcifications and Striatal Necrosis in ADAR1 Aicardi‐Goutières SyndromePublication . Mendes Pinto, Catarina; Freixo, João; Brandão, Ana Filipa; Magalhães, Marina
- Secukinumab on Refractory Lupus NephritisPublication . Costa, Rita; Antunes, Paula; Salvador, Pedro; Oliveira, Pedro; Marinho, AntónioLupus nephritis (LN) is the most frequent severe organ manifestation of systemic lupus erythematosus (SLE). About 30% of patients are refractory to treatment. The authors report a case of treatment of LN with interleukin-17-targeted therapy, demonstrating its possible benefit, after reports of T helper 17 cell involvement in SLE pathogenesis. We present the case of a childbearing age woman with SLE, who developed refractory LN despite all the indicated therapeutic options. During follow up, infection with human papillomavirus was detected, a possible trigger, and the following management was based on this discovery. We currently know that cytokines play a major role in tissue damage and interleukin-17 (IL-17) seems to be a fundamental key in SLE and LN, having shown its expression in renal glomeruli and urinary sediment. Thus, it was decided to start treatment with an anti-IL-17A antibody, secukinumab. After starting secukinumab, clinical and biological features improved and complete renal response was achieved.
- Nephrotic Syndrome as a Cause of Transient Clinical HypothyroidismPublication . Benido Silva, Vânia; Pereira, Maria Teresa; Leal Moreira, Carla; Santos Monteiro, Sílvia; Inácio, Isabel; Cardoso, HelenaNephrotic syndrome may trigger the onset of hypothyroidism, promoting massive urinary protein losses including thyroxine (T4) and triiodothyronine (T3) along with their binding proteins. At an early stage, a clinical and biochemical euthyroid state is expected. However, in patients with prolonged and severe proteinuria, especially with concomitant low thyroid reserve, urinary losses of free and protein-bound thyroid hormones are sufficiently pronounced to induce a subclinical or overt hypothyroidism. Despite its high prevalence in clinical practice, the literature lacks case reports of newly diagnosed clinical hypothyroidism due to NS in adults, making this condition under-recognized. We report a case of a 23-year-old man with previous normal thyroid function who developed overt hypothyroidism due to a severe nephrotic syndrome, requiring supplementation with levothyroxine (LT). After the patient had undergone bilateral nephrectomy, treatment with LT was discontinued and thyroid function normalized.
- Persistently positive anti‐NMDA receptor antibodies in chronic psychotic disorder: foe or innocent bystander?Publication . Araújo, Margarida; Monteiro, Rosário B.; Samões, Raquel; Norton, Andreia; Correia, Ana P.
- Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference CenterPublication . Barbosa-Gouveia, Sofia; Vázquez-Mosquera, María E.; González-Vioque, Emiliano; Álvarez, José V.; Chans, Roi; Laranjeira, Francisco; Martins, Esmeralda; Ferreira, Ana Cristina; Avila-Alvarez, Alejandro; Couce, María L.Next-generation sequencing (NGS) technologies have been proposed as a first-line test for the diagnosis of inborn errors of metabolism (IEM), a group of genetically heterogeneous disorders with overlapping or nonspecific phenotypes. Over a 3-year period, we prospectively analyzed 311 pediatric patients with a suspected IEM using four targeted gene panels. The rate of positive diagnosis was 61.86% for intermediary metabolism defects, 32.84% for complex molecular defects, 19% for hypoglycemic/hyperglycemic events, and 17% for mitochondrial diseases, and a conclusive molecular diagnosis was established in 2-4 weeks. Forty-one patients for whom negative results were obtained with the mitochondrial diseases panel underwent subsequent analyses using the NeuroSeq panel, which groups all genes from the individual panels together with genes associated with neurological disorders (1870 genes in total). This achieved a diagnostic rate of 32%. We next evaluated the utility of a tool, Phenomizer, for differential diagnosis, and established a correlation between phenotype and molecular findings in 39.3% of patients. Finally, we evaluated the mutational architecture of the genes analyzed by determining z-scores, loss-of-function observed/expected upper bound fraction (LOEUF), and haploinsufficiency (HI) scores. In summary, targeted gene panels for specific groups of IEMs enabled rapid and effective diagnosis, which is critical for the therapeutic management of IEM patients.