SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Cerebral and cerebellar white matter tract alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

BACKGROUND: To examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms. METHODS: In a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients. RESULTS: Whole brain tractography presented significantly reduced QA values in patients (0.282 ± 0.056, as compared to controls (0.325 ± 0.046, p < 0.001). 9 fiber clusters of tracts correlated negatively to the dystonia score of patients: the middle cerebellar peduncle and the tracts of both cerebellar hemispheres as well as corpus callosum, forceps minor, the superior cortico-striate tracts and the superior thalamic radiations of both cerebral hemispheres (False Discovery Rate FDR = 0.041). CONCLUSION: The finding of a reduced global structural connectivity within the white matter and of negative correlation of motor system-related tracts, mainly those between the basal ganglia, cortical areas and the cerebellum, fits well to the concept of a general functional disturbance of the motor system in PKAN.

COVID-19 and public transport: an overview and recommendations applicable to Latin America / COVID-19 y transporte público: una revisión y recomendaciones aplicables a América Latina

Abstract The article presents a general overview on COVID-19 transmission in the context of public transport, particularly applicable to decision making in Latin America. Based on recent findings on COVID-19 transmission and the relative importance of each factor (droplets, fomites, and aerosol routes) in such transmission, we seek to update the discussion on the topic that has generally been based on social distance as the only parameter for reducing the risk of transmission and broadens the vision to integrate ventilation, users' behavior (mask and eye protection use, silence while in the transport system) and travel distance. Recommendations to improve mobility conditions reducing the risk of COVID-19 contagion are provided.

Resumen El artículo presenta una revisión de transmisión de COVID-19 en el contexto de transporte público, con aplicación particular para toma de decisiones en América Latina. Con base en los hallazgos recientes sobre transmisión de Covid-19 y la importancia relativa de cada factor (gotículas, fómites y rutas de aerosoles) en dicha transmisión, buscamos actualizar la discusión sobre el tema que generalmente se ha basado en la "distancia social" como parámetro único de reducción de riesgo de transmisión y amplía esta visión para integrar la ventilación, el comportamiento de usuarios (uso de mascarilla, protección ocular, silencio), y la distancia de viaje. Se indican al final recomendaciones para mejorar las condiciones de movilidad en general sin aumentar el riesgo de contagio de Covid-19.

Changes in Cerebral Gray and White Matter in Patients with Pantothenate Kinase-Associated Neurodegeneration: A Long-Term Magnetic Resonance Imaging Follow-Up Study.

OBJECTIVE: To determine the volume changes in gray and white matter during a long-term follow-up in patients suffering from pantothenate kinase-associated neurodegeneration (PKAN). METHODS: Magnetic resonance imaging was repeated in 13 patients and 14 age-matched controls after a mean interval of more than 7 years. T1-weighted sequences were evaluated by fully automated atlas-based volumetry, compared between groups and correlated with disease progression. RESULTS: The patients did not show generalized cerebral atrophy but did show a significantly faster volume reduction in the globus pallidus during follow-up (between -0.96% and -1.02% per year, p < 0.05 adjusted for false discovery rate) than controls, which was significantly related to the progression in their dystonia scores (p = 0.032). CONCLUSION: The volume loss in the globus pallidus over time-together with the accumulation of iron known as the "tiger's eye"-supports the pathophysiologic concept of this nucleus as a center of inhibition and its severe malfunction in PKAN.

Functional connectivity of the motor system in dystonia due to PKAN.

PURPOSE: To demonstrate deviations of functional connectivity within the motor system in dystonic patients suffering from Pantothenate Kinase Associated Neurodegeneration, a genetic and metabolic disease, which is characterized by a primary lesion in the globus pallidus. MATERIAL AND METHODS: Functional Magnetic Resonance Imaging data were measured during resting state in 12 patients suffering from a confirmed mutation of the PANK2 gene. In this region-of-interest based analysis, data were evaluated in respect to correlation of signal time course between basal ganglia, motor-related cortical regions and cerebellum, were related to clinical data and were compared to a control group of 20 healthy volunteers. RESULTS: During resting state, correlation coefficients within the motor system were significantly lower in patients than in controls (0.025 vs. 0.133, p < 0.05). Network analysis by Network Based Statistics showed that these differences mainly affected the connectivity between a sub-network consisting of the basal ganglia and another one, the motor system-related cortical areas (p < 0.05). 6 out of 12 connections, which correlated significantly to duration of disease, were connections between both sub-networks. CONCLUSION: The finding of a reduced functional connectivity within the motor network, between the basal ganglia and cortical motor-related areas, fits well into the concept of a general functional disturbance of the motor system in PKAN.

Cerebral blood flow in dystonia due to pantothenate kinase-associated neurodegeneration.

BACKGROUND AND PURPOSE: The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron. MATERIAL AND METHODS: Under resting conditions, cerebral blood flow was measured by the magnetic resonance imaging technique of arterial spin labelling in cortical areas and basal ganglia in eight pantothenate kinase-associated neurodegeneration patients and 14 healthy age-matched control subjects and correlated to T2* time of these areas and - in patients - to clinical parameters. RESULTS: Despite highly significant differences of T2* time of the globus pallidus (20 vs 39 ms, p < 0.001), perfusion values of this nucleus were nearly identical in both groups (32 ± 3.3 vs 31 ± 4.0 ml/min/100 g) as well as in total brain gray matter (both 62 ± 6.7 resp. ±10.3 ml/min/100 g), putamen (41 ± 5.4 vs 40 ± 6.1 ml/min/100 g), in selected cortical regions, and the cerebellum. Correlations between perfusion and T2* time to clinical data did not reach significance (p > 0.05). CONCLUSION: The absence of any obvious deviations of perfusion in the group of patients during a resting condition does not support the view that (non-functional) vascular pathology is a major pathogenic factor in pantothenate kinase-associated neurodegeneration in the younger age group. The findings underline the value of the arterial spin technique to measure cerebral blood flow in areas of disturbed susceptibility.

Evaluating the immunogenicity of chemically-synthesised peptides derived from foot-and-mouth disease VP1, VP2 and VP3 proteins as vaccine candidates.

Foot-and-mouth disease (FMD) is one of the most contagious veterinary viral diseases known, having economic, social and potentially devastating environmental impacts. The vaccines currently being marketed/sold around the world for disease control and prevention in bovines do not stimulate the production of antibodies having crossed reactions to different serotypes. This means that if an animal becomes infected by a serotype which has not been included in a vaccine then it will develop the disease. Synthetic peptide vaccines represent a safer option and (depending on the design) can stimulate antibodies protecting against different variants. Based on the forgoing, this work was aimed at evaluating FMDV VP1, VP2 and VP3 protein-derived, modified and chemically-synthesised peptides' ability to induce an immune response for developing a vaccine contributing towards controlling the disease. VP1, VP2 and VP3 proteins' conserved regions were selected for this. Peptides from these regions were chemically synthesised; binding assays were then carried out for ascertaining whether they were involved in BHK-21 cell binding. Selected peptides' structure and location were studied. Peptides which did bind were modified and formulated with Montanide ISA 70 adjuvant; 17 animals were immunised twice with the formulation. The animals were genotyped by amplifying the BoLA-DRB3.2 gene. Blood samples were taken from 17 cattle on day 43 post-first immunisation for studying the formulation's immunogenicity. The sera were used in ELISA, immunofluorescence, flow cytometry, immunoadsorption and seroneutralisation assays. The A24 Cruzeiro and O1 Campos virus serotypes were used for these assays. The results revealed that even though protein exposure and 3D structure might be different amongst serotypes, the antibodies so produced could inhibit virus entry to cells, thereby showing the selected peptides' in vitro protection-inducing ability.

[RELATIONSHIP BETWEEN BULLYING AND SUICIDAL BEHAVIORS IN ADOLESCENTS: A SYSTEMATIC REVIEW]. / Relación entre bullying y conductas suicidas en adolescentes: una revisión sistemática.

Introduction: The relationship between bullying and adolescent suicidal behavior (SB) is manifested by high rates of attempted or committed suicide in victims of abuse. In spite of the importance of the topic, there are few studies that explain the details of the relationship between these variables, which makes it difficult to create effective interventions. The objective of this study was to provide a more detailed view about the relationship between bullying and SB. Method: Systematic review of literature including publications of bibliographic indexes, ScienceDirect and Pubmed using the terms "bullying" AND "suicidal behavior" AND "ado-lescents" AND "school harassment" AND "school mistreatment" and their corresponding in Spanish published from 2012 to 2018. Results: 21 articles of 272 initials that show the details of the relationship between bullying and suicidal behavior were included: age, gender, types and frequencies of victimization (verbal, physical, relational, cyberbullying, sexual and poly-victimization) and their relationship with variables of SB (ideation, planning, attempts and consummate suicide). Conclusions: Communicate that only receiving bullying results in SB minimizes the existence of other modulating factors and worsens the understanding of the relationship between phenomena leading to negligence in potential actions that could be carried out in intervention.

Texture Analysis of Standard Magnetic Resonance Images to Predict Response to Gamma Knife Radiosurgery in Vestibular Schwannomas.

PURPOSE: To search for texture features of routine magnetic resonance imaging to predict tumor volume reduction and transient versus permanent tumor progression of vestibular schwannomas treated by Gamma Knife stereotactic radiosurgery. MATERIALS AND METHODS: Included were 23 patients with vestibular schwannomas treated in our center and followed over a period of 23.7-80.3 months (mean 42.7). Magnetic resonance imaging was performed on a 3-Tesla scanner and included T1-weighted images with and without contrast enhancement, T2-weighted, and fluid-attenuated inversion recovery images. Volumetric results were followed longitudinally over time and correlated to texture features as mean, minimum, maximum, standard deviation, skewness, and kurtosis of normalized signals taken from regions of interest covering the total tumor volume. RESULTS: In total, 14 tumors showed early progression during the first 5-18 months (2 cases permanent, 12 cases transient), whereas 9 tumors regressed immediately after SRS. Kurtosis of T2-weighted image intensity values turned out to predict progression best with a sensitivity and specificity of 71% and 78%. From all texture feature parameters, only the minimum of the normalized T2-weighted image intensity values correlated significantly to the final reduction of tumor volume per month (correlation coefficient = -0.634, P < 0.05, corrected for false discovery rate). CONCLUSIONS: Texture feature analysis helps to predict permanent versus transient enlargement and final volume reduction of schwannomas after SRS. Thus, alternative treatment strategies might be considered, mainly in large tumors, where further clinical deterioration cannot be excluded. To confirm these results, a prospective study including more cases and a longer follow-up period is necessary.

Adaptation of visual cortex to damage of visual pathways in suprasellar tumors before and after gamma knife radiosurgery.

PURPOSE: To demonstrate that lesions of the visual pathways due to suprasellar tumors are accompanied by alterations of the visual cortex and to see if these alterations are reversible after treatment of tumors by gamma knife radiosurgery. MATERIALS AND METHODS: In 36 patients with peri-optic tumors and defects of their visual fields and in an age-matched control group, magnetic resonance imaging was performed before and after treatment. T1 weighted images were evaluated by voxel-based morphometry and correlated to the degree of visual field defects. RESULTS: In patients, grey matter density and cortical thickness were reduced in all parts of the occipital cortex, reaching significance (p < 0.05) in the left superior and middle occipital gyri, with correlation to visual field defects. Follow-up scans showed further reduction in all occipital areas. CONCLUSION: As in other peripheral lesions of the optic system, damage of the optic pathways affects the visual cortex. A prospective follow-up study is needed to determine if these alterations are reversible after successful tumor treatment.

Pretreatment texture analysis of routine MR images and shape analysis of the diffusion tensor for prediction of volumetric response after radiosurgery for meningioma.

OBJECTIVEThe goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).METHODSIn 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5-63.3 months).RESULTSSeveral DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).CONCLUSIONSDTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

Cryptosporidium spp. CP15 and CSL protein-derived synthetic peptides' immunogenicity and in vitro seroneutralisation capability.

Cryptosporidium spp. is a zoonotic intracellular protozoan and a significant cause of diarrhoea in humans and animals worldwide. This parasite can cause high morbidity in immunocompromised people and children in developing countries, livestock being the main reservoir. This study was aimed at performing preliminary tests on Swiss albino weaned mice (ICR) to evaluate the humoral immune response induced against peptides derived from Cryptosporidium parvum CP15 (15 kDa sporozoite surface antigen) and CSL (circumsporozoite-like antigen) proteins. Peptides were identified and characterised using bioinformatics tools and were chemically synthesised. The antibody response was determined and the neutralising effect of antibodies was measured in cell culture. Despite all peptides studied here were capable of stimulating antibody production, neutralising antibodies were detected for just two of the CP15-derived ones. Additional studies aimed at evaluating further the potential of such peptides as vaccine candidates are thus recommended.

Impact of Zika Virus on adult human brain structure and functional organization.

OBJECTIVE: To determine the impact of Zika virus (ZIKV) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain-Barré Syndrome (GBS)-like manifestations and include symptoms of the central nervous system (CNS). METHODS: In this first case-control neuroimaging study, we obtained structural and functional magnetic resonance images in nine rare adult patients in the subacute phase, and healthy age- and sex-matched controls. ZIKV patients showed atypical descending and rapidly progressing peripheral nervous system (PNS) manifestations, and importantly, additional CNS presentations such as perceptual deficits. Voxel-based morphometry was utilized to evaluate gray matter volume, and resting state functional connectivity and Network Based Statistics were applied to assess the functional organization of the brain. RESULTS: Gray matter volume was decreased bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes. INTERPRETATION: We provide preliminary evidence for a link between ZIKV neurological complications and changes in adult human brain structure and functional organization, comprising both motor-related regions potentially secondary to prolonged PNS weakness, and nonsomatomotor regions indicative of PNS-independent alternations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the ZIKV-related neuroinflammatory mechanisms in adults are urgently needed, this study indicates that ZIKV infection can lead to an impact on the brain.

Inversion recovery sequences improve delineation of optic pathways in the proximity of suprasellar lesions.

INTRODUCTION: In Gamma Knife Radiosurgery (GKRS) of suprasellar lesions, the exact localization of the visual pathways is important to avoid radiation induced optic neuropathy (RION). Reliable identification of the optic nerve, chiasm and tracts can be challenging using routine magnetic resonance imaging, especially in patients with lesions compressing the optic structures or in patients who had prior operation of suprasellar tumors. This study investigates the application of inversion recovery sequences (Fast gray and white matter acquisition T1 inversion recovery, FGATIR) to improve identification of the optic pathway. METHODS: Inversion recovery sequences were performed on 5 healthy volunteers, varying their inversion times between 400 and 500 ms, and between 800 and 1100 ms. Inversion times were optimized to either suppress or to preserve the signal of the optic structures, while increasing or suppressing the signal of processes within the surrounding cisterns. Inversion recovery sequences were performed before radiosurgery on 10 patients with suprasellar tumors that were compressing or displacing the optic structures. Signal intensities of gray and white matter, of CSF and tumors were measured and subtraction images were calculated. RESULTS: Compared to a standard T1-weighted sequence, delineation of the visual pathways was superior on inversion recovery images, both on images with suppression of the optic structures as well on images with suppression of its surrounding tissues, and was rated best on subtraction images. CONCLUSION: For radiosurgery of suprasellar tumors, inversion recovery sequences can be of valuable benefit for accurate delineation of optic pathway and radiosurgical dose planning in order to avoid radiation-induced normal tissue effects.

Prevalencia de vida de uso de cannabis y rendimiento académico en adolescentes / Lifetime prevalence of cannabis use and academic performance in adolescents

Objetivo: Esta investigación compara y establece las diferencias en la prevalencia de vida (consumo alguna vez en la vida) y no prevalencia de vida de uso de cannabis sobre el rendimiento académico en adolescentes escolarizados. Método: En este estudio descriptivo de corte transversal se seleccionó una muestra probabilística de 156 estudiantes y fueron evaluados con una prueba ad hoc de autopercepción. Las técnicas estadísticas utilizadas fueron análisis de frecuencia, descriptivos, t- student, U de Mann Whitney y Chi². Resultados: Los resultados señalan diferencias entre los grupos de prevalencia de uso de cannabis y no prevalencia de uso de cannabis en el número de cursos repetidos, días castigados en el último mes, la nota promedio del último mes, problemas escolares y la preocupación por estos, y dificultades para controlar el comportamiento en los últimos seis meses. No hubo diferencias en la comparación entre hombres y mujeres del grupo de prevalencia de uso de cannabis. Se confirma que el cannabis afecta el rendimiento académico desde algunos factores específicos que afectan por igual a hombres y mujeres. Conclusión: Se concluye que entre el grupo de prevalencia de vida de uso de cannabis hay más repetidores, a su vez, han repetido más cursos, han recibido más castigo en el colegio, tienen calificaciones más bajas, han tenido más problemas escolares y han estado más preocupados respecto a estos, y una mayor dificultad en controlar el comportamiento. En relación con el género no hay diferencias en las consecuencias sobre el rendimiento académico después de probar cannabis.

Objective: This research compares and establishes the differences in the prevalence of life (consumption ever in life) and no lifetime prevalence of cannabis use on academic performance in school adolescents. Method: In this descriptive and cross sectional study 156 students were probabilistically selected and evaluated with an ad-hoc auto-perception test. The techniques used were frequency analysis, descriptive, student t, Mann Whitney and Chi2. Results: The results show differences between groups in the prevalence of cannabis use and no prevalence of cannabis in the number of repeated courses, days punished in the past month, the average of the last month note, school problems and concern for these and difficulty controlling behavior in the past six months. There were no differences in the comparison between men and women in the group prevalence of cannabis use. It confirms that cannabis affects academic performance from some specific factors that affect both men and women. Conclusion: It is concluded that the group of lifetime prevalence of cannabis use more repeaters in turn have repeated more courses, have received more punishment in school, they have lower grades, have more problems in school and have been more worried about these, and greater difficulty in controlling behavior, and that there are no gender-related differences in the effects on academic performance after trying cannabis.

Prevalencia de uso de cannabis: perfil familiar y social de una muestra adolescente / Prevalence of Cannabis Use: Familiar and Social Profile of a Teen Sample

Este estudio describió y estableció diferencias del perfil estructural/dinámico familiar y social de adolescentes de acuerdo a la prevalencia de vida de uso de cannabis. Estudio cuantitativo, descriptivo transversal. Muestra no probabilística de 156 adolescentes incluidos en educación secundaria. Menor apoyo familiar, menor grado de confianza y consumo de sustancias ilegales caracterizó la dinámica de familias de quienes han probado cannabis al menos una vez en la vida. Una mayor cantidad de amigos de quienes han probado cannabis alguna vez consumen cannabis, alcohol, tabaco y otras sustancias. Las parejas de quienes han consumido cannabis no funcionan como factor de protección ya que consumen más sustancias que parejas de quienes nunca han probado cannabis. Los programas de prevención en uso de cannabis deben hacer mayor hincapié en el trabajo del aspecto dinámico de las familias y de los adolescentes en relación con sus pares incluyendo sus parejas.

This study described and established differences in the structural/dynamic family and social profile of adolescents according to the lifetime prevalence of cannabis. Quantitative, descriptive and cross-sectional study. Non-random sample of 156 adolescents included in secondary education. Low family support, less confidence and consumption of illegal substances characterized the dynamics of families of who have tried cannabis at least once in life. A greater number of friends of who have ever used cannabis use more cannabis, alcohol, tobacco and other substances. Couples of who have used cannabis not function as a protective factor as they consume more substances that couples who have never tried cannabis. Cannabis prevention programs have to do a greater emphasis on the work of the dynamic aspects of families and relationships of adolescents with their peers including their partners.

Atrophy, focal spinal cord lesions and alterations of diffusion tensor imaging (DTI) parameters in asymptomatic virus carriers and patients suffering from human T-lymphotrophic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

In tropical spastic paraparesis, spinal cord atrophy is a well-known finding in magnetic resonance imaging. But in contrast to histological reports, focal lesions of the spinal cord have only been described in imaging reports in exceptional acute cases. Here, we looked for such focal lesions and for alterations of diffusion tensor imaging parameters of the long fibre tracts in the usual case of a long-standing and slowly progressive disease. We examined 10 symptomatic patients, 11 seropositive, but asymptomatic human T-lymphotrophic virus type 1 carriers and 18 seronegative volunteers as controls. Sagittal and transversal T2-weighted images were visually assessed for atrophy and focal cord lesions. The spinal cord cross-sectional areas and the segmental cord volumes were measured at all levels. High-resolution diffusion tensor imaging was performed in sagittal planes from the bregma down to the cervical spine. For tractography and calculation of fractional anisotropy and mean diffusivity, we used manufacturer-provided software. Two-thirds of patients showed focal lesions affecting the antero-lateral columns and in two cases also the dorsal columns. Compared to carriers and volunteers, patients presented a significant spinal cord atrophy and a reduction of fractional anisotropy (p < 0.05), correlating more to duration of symptoms than to clinical impairment. Because our carriers did not show a significant atrophy, focal lesions or a change of diffusion tensor imaging parameters, we need further long-term studies to see if these parameters at some stage may be used as early indicators of spinal cord affection in virus carriers.

Identification and monitoring of brain activity based on stochastic relevance analysis of short-time EEG rhythms.

BACKGROUND: The extraction of physiological rhythms from electroencephalography (EEG) data and their automated analyses are extensively studied in clinical monitoring, to find traces of interictal/ictal states of epilepsy. METHODS: Because brain wave rhythms in normal and interictal/ictal events, differently influence neuronal activity, our proposed methodology measures the contribution of each rhythm. These contributions are measured in terms of their stochastic variability and are extracted from a Short Time Fourier Transform to highlight the non-stationary behavior of the EEG data. Then, we performed a variability-based relevance analysis by handling the multivariate short-time rhythm representation within a subspace framework. This maximizes the usability of the input information and preserves only the data that contribute to the brain activity classification. For neural activity monitoring, we also developed a new relevance rhythm diagram that qualitatively evaluates the rhythm variability throughout long time periods in order to distinguish events with different neuronal activities. RESULTS: Evaluations were carried out over two EEG datasets, one of which was recorded in a noise-filled environment. The method was evaluated for three different classification problems, each of which addressed a different interpretation of a medical problem. We perform a blinded study of 40 patients using the support-vector machine classifier cross-validation scheme. The obtained results show that the developed relevance analysis was capable of accurately differentiating normal, ictal and interictal activities. CONCLUSIONS: The proposed approach provides the reliable identification of traces of interictal/ictal states of epilepsy. The introduced relevance rhythm diagrams of physiological rhythms provides effective means of monitoring epileptic seizures; additionally, these diagrams are easily implemented and provide simple clinical interpretation. The developed variability-based relevance analysis can be translated to other monitoring applications involving time-variant biomedical data.

Grey matter alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

BACKGROUND: Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a rare heritable disease marked by dystonia and loss of movement control. In contrast to the well-known "Eye-of-the-Tiger" sign affecting the globus pallidus, little is known about other deviations of brain morphology, especially about grey matter changes. METHODS: We investigated 29 patients with PKAN and 29 age-matched healthy controls using Magnet Resonance Imaging and Voxel-Based Morphometry. RESULTS: As compared to controls, children with PKAN showed increased grey matter density in the putamen and nucleus caudatus and adults with PKAN showed increased grey matter density in the ventral part of the anterior cingulate cortex. A multiple regression analysis with dystonia score as predictor showed grey matter reduction in the cerebellum, posterior cingulate cortex, superior parietal lobule, pars triangularis and small frontal and temporal areas and an analysis with age as predictor showed grey matter decreases in the putamen, nucleus caudatus, supplementary motor area and anterior cingulate cortex. CONCLUSIONS: The grey matter increases may be regarded as a secondary phenomenon compensating the increased activity of the motor system due to a reduced inhibitory output of the globus pallidus. With increasing age, the grey matter reduction of cortical midline structures however might contribute to the progression of dystonic symptoms due to loss of this compensatory control.

Missense PANK2 mutation without "eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).

PURPOSE: To present some unusual MR findings in a group of patients from the south-west of the Dominican Republic suffering from Pantothenate Kinase Associated Neurodegeneration (PKAN). MATERIALS AND METHODS: Twenty patients and one preclinical case homozygous for the PANK2 mutation, 13 heterozygous gene carriers and 14 healthy volunteers were scanned prospectively using a 3 Tesla system. RESULTS: All patients showed the typical signal reduction within the globus pallidus and the substantia nigra. A surprising finding was the absence of the bright spot ("tiger's eye") in the medial part of the pallidum in 6 patients, but not in the preclinical case. Both fractional anisotropy (FA) and mean diffusivity (MD) were increased with high significance in the globus pallidus, whereas a reduction of FA in the anterior parts of the internal capsule was accompanied by an elevation of MD. CONCLUSION: Our findings support the hypothesis that the absence of the "tiger's eye" in PKAN might be secondary, probably caused by an increased accumulation of iron. This could artificially increase FA and MD values and change fiber tracking results. Except for the fronto-basal tracts, white matter was preserved well. This encouraging finding might support efforts to develop further therapeutic strategies in this devastating dystonia.