Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.

Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.

Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy.

BACKGROUND: Inherited nemaline myopathy is one of the most common congenital myopathies. This genetically heterogeneous disease is defined by the presence of nemaline bodies in muscle biopsy. The phenotypic spectrum is wide and cognitive involvement has been reported, although not extensively evaluated. METHODS: We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype. RESULTS: One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction. CONCLUSION: We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.

Adult-onset Alexander disease with brainstem and cervical cord enhancing lesions.

Leukodystrophies are a group of genetic diseases with diverse clinical features and prominent involvement of the central nervous system white matter. We describe a 27-year-old man who presented with a progressive neurological disease, and striking involvement of the brainstem and symmetrical white matter lesions on MR scanning. Having excluded several other causes of leukodystrophy, we confirmed Alexander disease when a genetic panel showed a probable pathogenic variant in GFAP: p.Leu359Pro. Clinicians should suspect Alexander disease in people with a progressive neurological motor decline who has pyramidal and bulbar signs and compatible neuroimaging.

Presence Of Non-Steroidal Anti-Inflammatories In Brazilian Semiarid Waters.

Non-steroidal anti-inflammatory drugs (NSAIDs) act as antipyretics, analgesics and anti-inflammatories. Among them, diclofenac and ibuprofen are the most consumed drugs worldwide. During the COVID-19 pandemic, some NSAIDs, such as dipyrone and paracetamol, have been used to alleviate the symptoms of the disease, causing an increase in the concentrations of these drugs in water. However, due to the low concentration of these compounds in drinking water and groundwater, few studies have been carried out on the subject, especially in Brazil. Thus, this study aimed to evaluate the contamination of the surface water, groundwater, and water treated with diclofenac, dipyrone, ibuprofen, and paracetamol at 3 cities (Orocó, Santa Maria da Boa Vista and Petrolândia) in the Brazilian semiarid region, in addition to analyzing the removal of these drugs by conventional water treatment (coagulation, flocculation, sedimentation, filtration and disinfection) in stations to each city. All drugs analyzed were detected in surface and treated waters. In groundwater, only dipyrone was not found. Dipyrone was seen in surface water with a maximum concentration of 1858.02 µg.L-1, followed by ibuprofen (785.28 µg.L-1), diclofenac (759.06 µg.L-1) and paracetamol (533.64 µg.L-1). The high concentrations derive from the increased consumption of these substances during the COVID-19 pandemic. During the conventional water treatment, the maximum removal of diclofenac, dipyrone, ibuprofen and paracetamol was 22.42%; 3.00%; 32.74%; and 1.58%, respectively, which confirms the inefficiency of this treatment in removing drugs. The variation in removal rate of the analyzed drugs is due to the difference in the hydrophobicity of the compounds.

Aseptic meningitis in Fabry disease due to a novel GLA variant: an expanded phenotype?

BACKGROUND: F abry disease (FD) is an X-linked lysosomal storage disorder with accumulation of globotriosylceramide, causing neurologic involvement mainly as acroparesthesias and cerebrovascular disease. Aseptic meningitis has been reported in 11 patients with FD, but no prior study has correlated alpha-galactosidase (GLA) specific variants with meningitis. We present in this manuscript a family in which a novel GLA pathogenic variant was associated with aseptic meningitis in 2 of 5 family members. METHODS: This study began with identifying the proband, then screening family members for FD symptoms and evaluating symptomatic individuals for genetic and biochemical status. All patients underwent magnetic resonance imaging, and those with headache underwent cerebrospinal fluid (CSF) analysis. RESULTS: Five patients (3 females) from a single family were included in this study. Mean age at diagnosis was 20.6 years. Two patients (40%) had aseptic meningitis; one of them also had cerebrovascular events. C-reactive protein and erythrocyte sedimentation rate were elevated during aseptic meningitis episodes. Both patients responded to intravenous methylprednisolone with resolution of fever, headache, and vomiting. One of them recurred and needed chronic immunosuppression with azathioprine. CONCLUSION: We described aseptic meningitis in a family with a novel GLA variant. Meningitis might be a common phenomenon in FD and not a particularity of this variant. Understanding the mechanisms underlying meningitis and its association with cerebrovascular events may lead to a new paradigm of treatment for stroke in these patients. Further prospective studies with CSF collection in patients with FD and recurrent headache could help to elucidate this question.

Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia-Occam's razor or Hickam's dictum: a case report.

BACKGROUND: Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves' disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. CASE PRESENTATION: A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. CONCLUSIONS: With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.

Arginase 1 deficiency presenting as complicated hereditary spastic paraplegia.

INTRODUCTION: Argininemia or arginase deficiency is a metabolic disorder caused by pathogenic variants in ARG1 and consists of a variable association of progressive spastic paraplegia, intellectual disability, and seizures. Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder characterized by lower limb spasticity. This study presents 7 patients with arginase 1 deficiency from 6 different families, all with an initial diagnosis of complicated HSP. METHODS: We evaluated the clinical data of 7 patients belonging to six independent families who were diagnosed with hyperargininemia in a neurogenetics outpatient clinic. RESULTS: All patients had lower limb spasticity and six had global developmental delay. Five individuals had intellectual disability and two had epilepsy. Psychiatric abnormalities were seen in two patients. In two participants of this study, MRI disclosed thinning of the corpus callosum. Molecular diagnosis was made by whole exome sequencing. All variants were present in homozygosis; we identified two novel missense variants, one novel frameshift variant, and one previously published missense variant. DISCUSSION: Clinical diagnosis of early onset complicated hereditary spastic paraplegia was made in all patients. Two patients were initially suspected of having SPG11 due to thinning of the corpus callosum. As argininemia may present with a highly penetrant phenotype of spastic paraplegia associated with additional symptoms, this disease may represent a specific entity amongst the complicated HSPs.

A rare cause of monogenic cerebral small vessel disease and stroke: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL).

BACKGROUND: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is a rare monogenic cause of cerebral small vessel disease. To date, fewer than 15 patients with CARASAL have been described, all of common European ancestry. METHODS: Clinical and imaging phenotypes of two patients are presented. Genetic variants were identified using targeted Sanger and focused exome sequencing, respectively. RESULTS: Both patients carried the same pathogenic p.Arg325Cys mutation in CTSA. One patient of Chinese ethnicity presented with migraine, tinnitus and slowly progressive cognitive impairment with significant cerebral small vessel disease in the absence of typical cardiovascular risk factors. She later suffered an ischaemic stroke. A second patient from Brazil, of Italian ethnicity developed progressive dysphagia and dysarthria in his 50s, he later developed hearing loss and chronic disequilibrium. Magnetic resonance imaging in both cases demonstrated extensive signal change in the deep cerebral white matter, anterior temporal lobes, thalami, internal and external capsules and brainstem. CONCLUSIONS: CARASAL should be considered in patients with early onset or severe cerebral small vessel disease, particularly where there are prominent symptoms or signs related to brainstem involvement, such as hearing dysfunction, tinnitus or dysphagia or where there is significant thalamic and brainstem involvement on imaging.

Incidental magnetic resonance imaging findings leading to an unusual diagnosis: Adult onset Krabbe disease.

BACKGROUND AND PURPOSE: Krabbe disease (KD), or globoid cell leukodystrophy (Online Mendelian Inheritance in Man #245200), is an autosomal recessive lysosomal storage disease caused by mutations in GALC leading to galactocerebrosidase deficiency. Age at onset can vary from early infancy (3-6 months of age) to adulthood, which has rarely been reported. Little is known about the natural history and early manifestations of adult onset KD (AOKD). METHODS: Here, we report a patient with an incidental diagnosis of AOKD and discuss management options in this scenario. RESULTS: A 32-year-old woman came to medical attention because of headache and had brain magnetic resonance imaging findings compatible with AOKD, two pathogenic variants in GALC, and reduced activity of galactocerebrosidase. The jury is still out about the best management of such cases, and clinicians should be aware of this diagnosis, as AOKD is a potentially treatable condition. CONCLUSIONS: AOKD is a rare and potentially treatable condition. More studies on natural history of AOKD are urgently needed to guide the best management of this disease.

Efficiency of the bank filtration technique for diclofenac removal: A review.

Bank filtration (BF) has been employed for more than a century for the production of water with a better quality, and it has been showing satisfactory results in diclofenac attenuation. Considered the most administered analgesic in the world, diclofenac has been frequently detected in water bodies. Besides being persistent in the environment, this compound is not completely removed by the conventional water treatments, drinking water treatment plants (DWTPs) and wastewater treatment plant (WWTPs). BF has a high complexity, whose efficiency depends on the characteristics of the observed pollutant and on the environment where the system in installed, which is why this is a topic that has been constantly studied. Nevertheless, studies present the behavior of diclofenac during the BF process. In this context, this research performed the evaluation of the factors and the biogeochemical processes that influence the efficiency of the BF technique in diclofenac removal. The aerobic conditions, higher temperatures, microbial biomass density, hydrogen potential close to neutrality and sediments with heterogeneous fractions are considered the ideal conditions in the aquifer for diclofenac removal. Nonetheless, there is no consensus on which of these factors has the greatest contribution on the mechanism of attenuation during BF. Studies with columns in laboratory and modeling affirm that the highest degradation rates occur in the first centimeters (5-50 cm) of the passage of water through the porous medium, in the environment known as hyporheic zone, where intense biogeochemical activities occur. Research has shown 100% removal efficiency for diclofenac persistent to compounds not removed during the BF process. However, half of the studies had removal efficiency that ranged between 80 and 100%. Therefore, the performance of more in-depth studies on the degradation and mobility of this compound becomes necessary for a better understanding of the conditions and biogeochemical processes which act in its attenuation.

Apraxia of Eyelid Opening and Blepharospasm in Two Spinocerebellar Ataxia Type 3 Patients.

BACKGROUND: Neuroophthalmological phenotypical particularities of SCA3. PHENOMENOLOGY: Eyelid opening apraxia and asymmetrical blepharospasm. EDUCATIONAL VALUE: To illustrate the phenomenology for purposes of education.

Delineating groundwater contamination risks in southern coastal metropoles through implementation of geochemical and socio-environmental data in decision-tree and geographical information system.

Due to global warming and local anthropogenic pressures, sustainable groundwater resource exploitation in coastal cities is increasingly threatened. For example, the fifth largest Brazilian city, Recife, is considered as a representative hot spot for these issues and illustrates the great challenges facing many urban areas in the southern hemisphere. There, recharge as well as surface water and groundwater quality are altered by frequent droughts and poorly planned environmental management since decades. To maintain access to water, thousands of private wells were dug in order to pump water from the multi-layered aquifer system found under the city. This massive exploitation is causing a chronic lowering of the water levels, as well as seawater intrusion and contaminations by wastewater or polluted surface waters. Through hydrochemical characterization, mainly Cl/Br ratio and Cl concentrations, of wells sampled throughout the metropole, this study first characterizes the main environmental impacts on the resource, i.e. waste waters and seawater. Combining this evaluation with lithological, land-use and socio-environmental data, it was then possible to build decision trees identifying combinations of multiple factors possibly having an impact on contamination types. The well and population densities, the waste and sewage management, as well as the absence of sanitary facilities in houses appeared as critical parameters to target in order to reduce the risk of contamination of the water resource and ensure its preservation. Based on these factors, we created a risk map for contamination types that should help in identifying areas where groundwater resource may present an environmental (and then health) issue for people. Besides, this study shows that the combination of hydrochemical, geomorphological and socio-environmental characterizations of these urban systems featuring very contrasted situations between neighborhoods is a relevant tool to propose further groundwater management strategies.

Adenosine kinase deficiency presenting with tortuous cervical arteries: A risk factor for recurrent stroke.

Adenosine kinase (ADK) deficiency is a very rare inborn error of methionine and adenosine metabolism. It is characterized by developmental delay, hypotonia, epilepsy, facial dysmorphism, failure to thrive, transient liver dysfunction with cholestasis, recurrent hypoglycemia, and cardiac defects. Only 26 cases (16 families) of ADK deficiency have been published since its identification in 2011. Vascular abnormalities in cervical arteries and cerebral stroke have never been reported in this condition. Here, we describe two patients with ADK deficiency and vascular tortuosity leading to stroke in one of them. ADK deficiency is a rare inborn error of methionine metabolism with a complex phenotype that might be associated with cerebrovascular abnormalities and stroke.

Effect of educational intervention on clinical reasoning skills in nursing: A quasi-experimental study.

This study evaluated the effect of an educational intervention based on virtual clinical simulation and problem-based learning using a mobile application in a clinical nursing education context as a tool to improve clinical reasoning skills of students on the second year of nursing graduation. A prospective quasi-experimental study was conducted in the year 2018, and assessments were performed before and after the educational intervention. A random convenience sample (n = 32) of nursing students in the second year of a public university in Brazil was divided equally into experimental and control groups. The experimental group underwent educational intervention about clinical reasoning skills and measured the quality of the Diagnostician Nurse software by LORI 2.0 instrument. The control group experienced the conventional class on clinical reasoning skills. Four clinical cases were used to assess reasoning skills before and after the educational intervention. The data were analyzed using descriptive and inferential statistics. The experimental group showed a statistically significant difference regarding the prioritization of nursing diagnoses (p = 0.014) and a higher final score. There was a statistically significant difference in performance between the pre- and post-test in the grades of the students who participated in the intervention (p = 0.003). The control group also showed statistical significance in the score attributed to the clinical reasoning process (p = 0.015). In addition, the Diagnostician Nurse software had excellent usability and quality evaluations (SUS 87.81 and LORI 4.66, respectively). It is concluded that educational intervention based on virtual clinical simulation and learning problems using the Diagnostician Nurse software is effective as a tool to improve clinical reasoning skills and can support early detection of patients. The educational intervention developed was of high quality and attractive and improved students' motivation for the teaching-learning process.

Measurement data from bobbins of Partially Oriented Yarns: Univariate and multivariate aspects.

In this paper, we present data from measurements made in the textured fibers bobbins in two different conditions, presenting critical quality characteristics such as diameter, mass and density. In order to obtain a significant amount of information, in each of the two conditions, 270 measurements were obtained for each of the quality characteristics. Three different equipments (Automatic Package Analyzer - APA) were used in ten different parts, replicated three times for each of them. Considering the two measurement data collection, an amount of 540 bobbins measurements were obtained. Almeida et al., (2019) applied these measurement data in his study. Taking into account the multicorrelated nature of the information, we also have the representation of the principal components' scores for these measurements, besides the eigenvalues and eigenvectors of the data.