Diagnostic accuracy and the first genotype-phenotype correlation in glycogen storage disease type V.

BACKGROUND: Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors. METHODS: We retrospectively reviewed all GSDV cases with follow-up in both Pediatric and Adult Metabolic Diseases consultations. We included 28 cases and assessed their hospital record for clinical information. RESULTS: Over 90% of our cases had late diagnoses, with more than 50% being diagnosed in adulthood despite symptom onset in preschool (very late diagnosis). Diagnostic age was lower in patients exhibiting myoglobinuria. Interestingly, patients with a positive family history of GSDV had similar rates of very late diagnoses, likely since the index case was already detected very late in life. Finally, we observe that the R50* variant is associated with increased myoglobinuria and CK elevation, in a dosage-dependent manner. CONCLUSION: We concluded that GSDV is severely underdiagnosed, and that some clinical and analytical aspects of the condition can be more indicative of this diagnosis. Furthermore, we propose for the first time a genotype-phenotype correlation in GSDV. IMPACT: GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed. We observed the first genotype-phenotype correlation in GSDV, regarding the common R50* variant. Awareness of GSDV for pediatricians and the overall medical community is vital.

Desafios à implementação de evidência na prevenção de infeções urinárias em unidades de cuidados continuados: Contributos para a gestão / Challenges to the implementation of evidence in the prevention of urinary infections in long-term care units: Contributions to management

As infeções do trato urinário (ITU) associadas aos cuidados de saúde são um problema, tendo consequências para as pessoas, organizações e profissionais. Nas unidades de cuidados continuados integrados (UCCI), esta problemática tem importância acrescida, tendo em conta o facto da população alvo dos cuidados ser mais idosa. A literatura salienta que as práticas baseadas em evidências melhoram os resultados em saúde, mas, muitas vezes, os cuidados não são prestados com base em evidências científicas. Faz parte do perfil de competências do enfermeiro gestor garantir cuidados baseados em evidências, garantindo cuidados mais seguros e de qualidade. Desta forma, este estudo visa identificar e compreender os desafios e estratégias de gestão para a implementação de evidência na prevenção de infeções urinárias em UCCI ? RNCCI, neste contexto seguiu-se um estudo qualitativo e descritivo, com recurso a entrevistas semiestruturadas a enfermeiros coordenadores das UCCI da região centro de Portugal que aceitaram participar no estudo. A colheita da informação foi realizada de forma presencial ou através de plataformas digitais. O tratamento dos dados foi efetuado com base no modelo de análise de conteúdo proposto por Bardin. A identificação das estratégias usadas pelos enfermeiros coordenadores para ultrapassar esses desafios na implementação da evidência torna-se crucial para uma melhoria da qualidade dos cuidados. As estratégias adequadas devem ser utilizadas no desenvolvimento de boas práticas nestas unidades, de modo a serem superadas as barreiras na implementação de evidências científicas relacionadas com a prevenção de infeções urinárias, contribuindo para cuidados mais seguros e com maior qualidade.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Multisystemic RFC1-Related Disorder: Expanding the Phenotype Beyond Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Results from a Retrospective Observational Study in a Tertiary Hospital.

Introduction - Glycogen storage disease type V (GSDV, MIM #232600) is an autosomal recessive metabolic myopathy caused by pathogenic variants in the PYGM gene. The characteristic symptoms of exercise intolerance, myalgia, and cramps, which improve after a few minutes of rest, are frequently unrecognized in affected children. When there is clinical suspicion, the initial approach with a forearm exercise test has diagnostic value by detecting low post-exercise plasma lactate-to-ammonia ratio values. The diagnostic algorithm is followed by genetic testing if the results suggest myophosphorylase deficiency. Methods - This was a retrospective observational study conducted based on reviewing medical records of patients with GSDV in a tertiary hospital. We assessed demographic variables, including the timing of onset and diagnosis, relevant clinical characteristics, and whether genetic testing was performed, including its results. Results/Case Report - Our goal was to review the GSDV cases in our center to assess our cohort's diagnostic timing and clinical and genetic characteristics. We identified 28 patients from 24 families, three with consanguinity. The mean age at the time of the study was 43 years. While most (26/28; 93%) recalled their first symptoms in childhood/adolescence, only 25% (7/28) were diagnosed then. All patients had exercise intolerance and CK elevation, while about half reported the second wind phenomenon. Genetic testing was performed in 22 patients, revealing biallelic PYGM variants (9 homozygous, 13 compound heterozygous) as the most common (p.R50*). Conclusion - GSDV is rare and presents in the pediatric age, with subtle manifestations often underestimated for decades. A late diagnosis may negatively impact the psychosocial development of affected children. It is essential to recognize some unique features that facilitate diagnosis: history of exercise intolerance, the second wind sign, and high resting serum CK levels. Identifying the disease-causing variants in PYGM is currently the gold standard for diagnosis as it is less invasive than performing a muscle biopsy, and may promptly diagnose the condition and avoid wrongful labelling of patients.

Long-term spatial memory across large spatial scales in Heliconius butterflies.

Locating food in heterogeneous environments is a core survival challenge. The distribution of resources shapes foraging strategies, imposing demands on perception, learning and memory, and associated brain structures. Indeed, selection for foraging efficiency is linked to brain expansion in diverse taxa, from primates1 to Hymenopterans2. Among butterflies, Heliconius have a unique dietary adaptation, actively collecting and feeding on pollen, providing a source of essential amino acids as adults, negating reproductive senescence and facilitating an extended longevity3. Several lines of evidence suggest that Heliconius learn the spatial location of pollen resources within an individual's home range4, and spatial learning may be more pronounced at these large spatial scales. However, experimental evidence of spatial learning in Heliconius, or any other butterfly, is so far absent. We therefore tested the ability of Heliconius to learn the spatial location of food rewards at three ecologically-relevant spatial scales, representing multiple flowers on a single plant, multiple plants within a locality, and multiple localities. Heliconius were able to learn spatial information at all three scales, consistent with this ability being an important component of their natural foraging behaviour.

Retrospective Study of 57 Patients Submitted to Dorsal Root Entry Zone Lesioning by Radiofrequency for Brachial Plexus Avulsion Pain.

BACKGROUND: Dorsal root entry zone (DREZ) lesioning may be used to treat neuropathic pain in patients with traumatic brachial plexus injuries. The clinical outcome after surgery is variable in the medical literature. We aimed to report the surgical outcome after DREZ lesioning by radiofrequency and to analyze prognostic factors such as the presence of a spinal cord injury identified before surgery. METHODS: We conducted a retrospective study that included 57 patients who had experienced traumatic brachial plexus injuries and exhibited neuropathic pain that did not respond to conservative treatment methods. They were submitted to DREZ lesioning. We defined the inclusion and exclusion criteria, collected sociodemographic and clinical characteristics, and identified and classified spinal cord lesions based on magnetic resonance imaging. We applied statistical tests to evaluate the association between pain intensity after surgery and the radiological profile and sociodemographic characteristics. RESULTS: Immediately after surgery, the pain outcome was considered good or excellent in 50 patients (89.28%). At the last follow-up, it was good or excellent in 39 patients (68.43%). There was no association (P > 0.05) between the pain outcome and the variables analyzed (time interval between trauma and DREZ lesioning, presence of spinal cord injury, age, the number of avulsed roots, and the type of pain). CONCLUSIONS: DREZ lesioning using radiofrequency represents a significant therapeutic approach for managing neuropathic pain after a traumatic brachial plexus injury. Importantly, we found that the presence of a spinal cord injury is not associated with the surgical outcome.

An SPG7 mutation as a novel cause of monogenic progressive muscular atrophy.

BACKGROUND: Progressive muscular atrophy (PMA) is a rare adult-onset neurological disease that is characterized by isolated lower motor neuron degeneration. While it is still disputable whether PMA is a subtype of amyotrophic lateral sclerosis (ALS) or an isolated disorder, it is well-established as a clinically defined entity. About 5% of PMA cases are monogenic, and the implicated genes largely overlap with those causing monogenic ALS. CASE DESCRIPTION: Here we describe a 68-year-old female patient with progressive and asymmetric upper-limb weakness throughout an 18-month period, with muscle atrophy, dysphagia and slurring of speech. The lower limbs were unaffected, and there was no sign of upper motor neuron dysfunction. Comprehensive genetic testing for single nucleotide and copy-number variants revealed a pathogenic monoallelic variant c.1529C>T, p.(Ala510Val) in the SPG7 gene. DISCUSSION: Pathogenic biallelic SPG7 variants have been originally associated with hereditary spastic paraplegia, but other phenotypes are nowadays known to be linked to these variants, such as ALS. However, there is no report of this (or any) other SPG7 variant in association with PMA, whether it progressed to ALS or not. In conclusion, we present the first known case of PMA associated with a monoallelic SPG7 mutation.

No evidence of social learning in a socially roosting butterfly in an associative learning task.

Insects may acquire social information by active communication and through inadvertent social cues. In a foraging setting, the latter may indicate the presence and quality of resources. Although social learning in foraging contexts is prevalent in eusocial species, this behaviour has been hypothesized to also exist between conspecifics in non-social species with sophisticated behaviours, including Heliconius butterflies. Heliconius are the only butterfly genus with active pollen feeding, a dietary innovation associated with a specialized, spatially faithful foraging behaviour known as trap-lining. Long-standing hypotheses suggest that Heliconius may acquire trap-line information by following experienced individuals. Indeed, Heliconius often aggregate in social roosts, which could act as 'information centres', and present conspecific following behaviour, enhancing opportunities for social learning. Here, we provide a direct test of social learning ability in Heliconius using an associative learning task in which naive individuals completed a colour preference test in the presence of demonstrators trained to feed randomly or with a strong colour preference. We found no evidence that Heliconius erato, which roost socially, used social information in this task. Combined with existing field studies, our results add to data which contradict the hypothesized role of social learning in Heliconius foraging behaviour.

External Ophthalmoplegia and Brainstem White Matter Lesions: Presentation of Myotonic Dystrophy Type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is an autosomal dominant condition which phenotype can be extremely variable considering its multisystem involvement, including the central nervous system. Neuromuscular findings are facial and distal extremities muscle weakness, muscle atrophy and myotonia. Standard diagnosis is obtained with molecular testing to detect CTG expansions in the myotonic dystrophy protein of the kinase gene. Brain magnetic resonance imaging typically shows characteristic subcortical white matter (WM) abnormalities located within anterior temporal lobes. CASE REPORT: We present a 39-year-old male patient with a progressive external ophthalmoplegia, facial and limb muscle weakness, percussion myotonia and atypical brain magnetic resonance imaging findings, showing confluent brainstem WM lesions, affecting the pons, a rare radiologic feature in this disorder. Genetic testing confirmed the diagnosis for DM1. CONCLUSION: This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.

Predictive factors for return to work or study and satisfaction in traumatic brachial plexus injury individuals undergoing rehabilitation: A retrospective follow-up study of 101 cases.

BACKGROUND: An important focus of rehabilitation is thereturn to the meningful occupations which may include work and school activities. PURPOSE: The aim of this study is to investigate predictive factors for return to work/study in traumatic brachial plexus injury patients undergoing rehabilitation and to investigate the level of satisfaction with treatment. STUDY DESIGN: Retrospective observational study with at least 1 year of follow-up. METHODS: One hundred and one individuals with traumatic brachial plexus injury enrolled in this study. Primary outcomes were return to work/study and satisfaction with treatment. A secondary outcome was the self-perception of what influenced return to work. Sociodemographic and related to injury data, rehabilitation interventions, muscle strength, and disability were analyzed as predictors. Associations were investigated using univariable and discriminant analysis and considered a level of significance of P < .05. RESULTS: Return to work/study occurred in 55% of the patients who participated in this study. Muscle strength discerned those who returned to work. Time interval between trauma and surgery and age were lower in those who returned to work. Thirty-one patients answered the question regarding self-perception of what influenced return to work. They indicated "necessity", "rehabilitation", "my desire" and "not become depressed". Satisfaction was graded between 8.9 and 9.5 in 95% of the cases. CONCLUSIONS: Return to work/study was related to muscle strength improvement and those who returned were younger and had less time elapsed from trauma. Individual factors and rehabilitation were pointed out as helpful in aiding return to work. Satisfaction with treatment was high. These findings can help to optimize goals in the rehabilitation environment.

Predictors of cognitive dysfunction in hereditary transthyretin amyloidosis with liver transplant.

BACKGROUND: Cognitive dysfunction is part of the broad spectrum of clinical manifestations in older untreated hereditary transthyretin amyloidosis patients with peripheral polyneuropathy. OBJECTIVE: The objective of this study is to systematically explore cognitive dysfunction in ATTRV30M amyloidosis patients whose disease course was modified by liver transplant (LT). METHODS: A series of 269 carriers of TTRVal30Met mutation treated with LT underwent a neuropsychological assessment. Clinical charts were reviewed to identify focal neurological episodes (FNEs), cognitive complaints and laboratory results. Chi-square and Mann-Whitney tests explored potential predictors of cognitive dysfunction. RESULTS: Cognitive dysfunction was identified in 35 patients (13%)-14 (5%) had mild and 21 (8%) had moderate dysfunction. In comparison to normal cognition, both mild and moderate cognitive dysfunction patients had older age, higher mPND score and elevated NT-proBNP and Cystatin C values. Mild cognitive dysfunction was associated with longer disease duration and history of FNEs, whereas moderate dysfunction was related to older age at disease onset and more cognitive complaints and depression symptoms. CONCLUSIONS: Consistent with the natural history of the disease, older age and higher severity of the disease are significantly associated and potentially predictors of cognitive dysfunction in ATTRV30M patients treated with LT. The level of cognitive dysfunction may depend on some clinical variables.

Corrigendum: Clinical 3-D gait assessment of patients with polyneuropathy associated with hereditary transthyretin amyloidosis.

[This corrects the article DOI: 10.3389/fneur.2020.605282.].

Gait Characterization and Analysis of Hereditary Amyloidosis Associated with Transthyretin Patients: A Case Series.

Hereditary amyloidosis associated with transthyretin (ATTRv), is a rare autosomal dominant disease characterized by length-dependent symmetric polyneuropathy that has gait impairment as one of its consequences. The gait pattern of V30M ATTRv amyloidosis patients has been described as similar to that of diabetic neuropathy, associated with steppage, but has never been quantitatively characterized. In this study we aim to characterize the gait pattern of patients with V30M ATTRv amyloidosis, thus providing information for a better understanding and potential for supporting diagnosis and disease progression evaluation. We present a case series in which we conducted two gait analyses, 18 months apart, of five V30M ATTRv amyloidosis patients using a 12-camera, marker based, optical system as well as six force platforms. Linear kinematics, ground reaction forces, and angular kinematics results are analyzed for all patients. All patients, except one, showed a delayed toe-off in the second assessment, as well as excessive pelvic rotation, hip extension and external transverse rotation and knee flexion (in stance and swing phases), along with reduced vertical and mediolateral ground reaction forces. The described gait anomalies are not clinically quantified; thus, gait analysis may contribute to the assessment of possible disease progression along with the clinical evaluation.

Validity of range of motion, muscle strength, sensitivity, and Tinel sign tele-assessment in adults with traumatic brachial plexus injury.

BACKGROUND: The COVID-19 pandemic and the need for social distancing created challenges for accessing and providing health services. Telemedicine enables prompt evaluation of patients with traumatic brachial plexus injury, even at a distance, without prejudice to the prognosis. The present study aimed to verify the validity of range of motion, muscle strength, sensitivity, and Tinel sign tele-assessment in adults with traumatic brachial plexus injury (TBPI). METHODS: A cross-sectional study of twenty-one men and women with TBPI admitted for treatment at a Rehabilitation Hospital Network was conducted. The participants were assessed for range of motion, muscle strength, sensitivity, and Tinel sign at two moments: in-person assessment (IPA) and tele-assessment (TA). RESULTS: The TA muscle strength tests presented significant and excellent correlations with the IPA (the intra-rater intraclass correlation coefficient, ICC ranged between 0.79 and 1.00 depending on the muscle tested). The agreement between the TA and IPA range of motion tests ranged from substantial to moderate (weighted kappa coefficient of 0.47-0.76 (p < 0.05) depending on the joint), and the kappa coefficient did not indicate a statistically significant agreement in the range of motion tests of supination, wrist flexors, shoulder flexors, and shoulder external rotators. The agreement between the IPA andTA sensitivity tests of all innervations ranged from substantial to almost perfect (weighted kappa coefficient 0.61-0.83, p < 0.05) except for the C5 innervation, where the kappa coefficient did not indicate a statistically significant agreement. The IPA versus TA Tinel sign test showed a moderate agreement (weighted kappa coefficient of 0.57, p < 0.05). CONCLUSIONS: The present study demonstrated that muscle strength tele-assessment is valid in adults with TBPI and presented a strong agreement for many components of TA range of motion, sensitivity, and Tinel sign tests.

The "microwave oven" practice in Brazil.

This article presents a forensic case of an unusual illegal cremation of a person using a process colloquially known as the "microwave oven" practice in Brazil. The microwave process involves two actions: placing the victim in a tire stack and then setting the structure on fire using flammable substances to accelerate the progression. A similar practice, identified as "necklacing", has also been reported in other countries such as South Africa. This report presents a case of microwave oven cremation of a body found in a rural area of Minas Gerais, Brazil. The forensic work helped determine the biological profile and identity of the victim using radiological comparisons. Although the microwave oven cremation practice is rare, it can impose challenges for investigators. Therefore, fully understanding this practice can be helpful to the academic and forensic communities.

Neuromuscular Choristoma: Report of Five Cases With CTNNB1 Sequencing.

Neuromuscular choristoma (NMC) are lesions of the peripheral nervous system characterized by an admixture of skeletal muscle fibers and nerves fascicles that are frequently associated with desmoid fibromatosis (DF). Mutations in CTNNB1, the gene for ß-catenin protein, are common in DF and related to its pathogenesis. They are restricted to exon 3, with 3 point mutations: T41A, S45F, and S45P. To understand the pathogenesis of NMC, we tested CTNNB1 status in 5 cases of NMC whether or not they were associated with DF. The screening of mutations in CTNNB1 gene was based on amplicon deep sequencing using the ION Proton platform. Three patients had the S45F mutation; in 2 the mutation was common to both lesions and in one the DF was wild type while the NMC had the S45F mutation. One patient had a T41A mutation in the NMC and no associated DF. In the last patient, the DF lesion had a T41A mutation; there was no lesion with the S45P mutation. The presence of similar CTNNB1 mutations in NMC/DF-associated lesions and sporadic DF reinforces the relationship between both lesions and points to a common pathogenic mechanism.

The Chemistry and Chemical Ecology of Lepidopterans as Investigated in Brazil.

The interdisciplinary field of Chemical Ecology in Brazil is currently composed of groups that emerged through the pioneering studies of Keith Spalding Brown Jr. and José Tércio Barbosa Ferreira. Following Keith Brown 's steps, José Roberto Trigo continued investigating the role of plant natural products in mediating the association among insects and their host plants, mainly in the Order Lepidoptera. The role of pyrrolizidine alkaloids in those associations was investigated extensively by Brown and Trigo, and most of what is currently known on this subject is based on their studies. The present work acknowledges their contribution to the Brazilian chemical ecology field and on insect-plant communication studies mediated by different chemical compounds.