Bakgrund: Amyotrofisk lateralskleros (ALS) tillhör gruppen motorneuronsjukdomar. Det är en obotlig neurologisk sjukdom som drabbar cirka 200 personer per år i Sverige. De viljestyrda musklerna i kroppen förtvinar vilket leder till att personen får problem med tal och andning. Sjukdomsförloppet varierar beroende på vilken form av motorneuronsjukdom personen drabbas av, vid ALS avlider personen oftast inom 5 år. Syfte: Syftet med litteraturstudien var att beskriva personers erfarenheter av att leva med ALS samt beskriva de inkluderade vetenskapliga artiklarnas undersökningsgrupp. Metod: En beskrivande litteraturstudie som består av 11 kvalitativa artiklar. Huvudresultat: Några patienter var missnöjda med sjukhusvården, de möttes av okunnig personal och blev skickade mellan olika vårdenheter innan diagnosen kunde fastställas. Det ledde till att patienterna själva fick söka efter svar. Patienterna beskrev flera negativa känslor med diagnosen ALS. Under sjukdomsförloppet uppstod även positiva känslor som gjorde att patienterna fortsatte att kämpa. Patienterna använde sig av olika strategier som existentiella tankar, acceptans för hjälpmedel och att ta hjälp av en utomstående vårdare. Stöd från familj och vänner var betydelsefulla för att uthärda sjukdomen och den förväntade döden. Slutsatser: Personer som drabbats av ALS upplevde en känslomässig bergochdalbana, som pendlade mellan positiva och negativa känslor. För flera patienter var det viktigt att ta en dag i taget för att finna meningsfullhet. Sjukdomsupplevelsen är individuell vid ALS och det är viktigt att sjuksköterskan använder sig av personcentrerad vård. Det är betydelsefullt att sjuksköterskan tar till sig patienters och anhörigas erfarenheter för att bevara dess integritet och autonomi. / Background: Amyotrophic lateral sclerosis (ALS) belongs to a group of motor neuron diseases. It is an incurable neurological disease that affects approximately 200 people per year in Sweden. The involuntary muscles of the body atrophies which causing the person problems to speak and breath. The disease progression varies depending on the version of motor neuron disease the person suffering, at ALS person usually dies within 5 years. Aim: The purpose of this study was to describe people's experiences of living with ALS and describe the study group of the included scientific articles. Method: A descriptive literature study consisting of 11 qualitative articles. Main Results: Some patients were not satisfied with the hospital care, they were met by ignorant staff and were sent between different care units before a diagnosis could be decided. At the end the patients themselves were searching for answers themselves. Patients describe several negative feelings diagnosed with ALS. During the progression of the disease even positive emotions came and encouraged the patients continue to struggle. Patients used different strategies like existential thoughts, acceptance of aid and help from outside caregiver. Support from family and friends were important to cope with the disease and the expected death. Conclusions: People who suffer from ALS experienced an emotional roller coaster, which commuted between positive and negative feelings. For many patients, it was important to take one day at a time to find meaningfulness. The experience from the illness is individual from ALS and it is important that the nurse uses the person-centered care. It is important that the nurse learn from the patients and relatives experience to preserve the integrity and autonomy.

Individuals with multiple sclerosis (MS), especially those living in Latin America, often require assistance from family caregivers throughout the duration of disease. Previous findings suggest that family caregivers may experience positive and negative effects from providing care to individuals with MS, but few studies have examined the impact of MS caregiving on caregivers from Latin America. The current study examined the relationships between MS impairments (functional, neurological, cognitive, behavioral and emotional), unmet family needs (household, informational, financial, social support, health), and caregiver psychosocial functioning (satisfaction with life, anxiety, burden, and depression) in a sample of 81 MS caregivers from Guadalajara, Mexico. Canonical correlations revealed that behavioral impairments were associated with higher burden and decreased satisfaction with life, and that unmet financial, social support, and informational needs were associated with higher caregiver burden. A structural equation model demonstrated the meditational effect of unmet family needs on the relationship between MS impairments and caregiver mental health. These findings suggest that interventions for MS caregivers in Latin America should focus on reducing caregiver burden by addressing unmet family needs for information, financial, and social support while teaching caregivers ways to manage the patient’s behavioral symptoms.

Systemic scleroderma (SSc) is a systemic connective tissue disease affecting skin and internal organs. The pathogenesis of SSc is characterized by inflammation, vasculopathy and fibrosis. No agent has been proven effective in the treatment of SSc. There is a lack of suitable biomarkers for monitoring the disease activity or the response to the treatment of SSc. Therefore our aim was to analyse the extracellular levels of S100A4, Hsp90 (Heat shock protein 90) and IL-35 (interleukin-35) in SSc. S100A4 and Hsp90 have been initially studied in tumours; in some of them considered as suitable prognostic markers and candidates for future therapies. We have recently described the profibrotic role of S100A4 and Hsp90 in the pathogenesis of SSc. Our results showed that inactivation of S100A4 and Hsp90 effectively prevented the development of experimental skin fibrosis. This was consequently confirmed by the analysis of S100A4 and Hsp90 in the peripheral blood of patients with SSc, where significant associations with disease activity and organ involvement were detected. IL-35 may become another potential biomarker of SSc. We detected increased expression of IL-35 in the affected skin, dermal fibroblasts and in serum of patients with SSc. Moreover, the main profibrotic mediator transforming growth factor...

Title: Evaluation of sensation in hands area in patients with multiple sclerosis Objective: Summarize findings about multiple sclerosis and sensation in the hands area. Find suitable testing methods and use them to evaluate the quality of deep sensation in the hands area in patients with multiple sclerosis. Method: With help of selected tests to evaluate the quality of deep sensation in the fingers and palms area in selected probands with multiple sclerosis. Compare the results depending on the current spasticity and condition of the patient. Results: There were founded, that in people with multiple sclerosis the quality of vibrating and discriminating sensation and stereognosis in the hands area is reduced. The quality of statesthesia, kinesthesia, vibrating and discriminating sensation isn't directly linearly dependent on the current spasticity. The quality of stereognosis is directly linearly dependent on the current spasticity. Keywords: sensation, multiple sclerosis, spasticity

No description available.

Introdução: A esclerose múltipla (EM) é uma doença inflamatória autoimune desmielinizante. Diversos estudos evidenciaram a forte associação entre a EM e a expressão do retrovírus endógeno da família W (HERV-W) e do Epstein Barr Vírus (EBV), sem definir seu real papel no desenvolvimento da doença. Objetivo: Investigar a presença de anticorpos anti EBV e a expressão de HERV-W em pacientes com EM e avaliar a correlação entre a atividade clínica e imagiológica da EM com a avaliação quantitativa do HERV-W e EBV. Métodos: Realizamos avaliações clínicas e de ressonância magnética (RM) por 36 meses de 36 pacientes com EM e a comparamos com a análise quantitativa longitudinal do PCR em tempo real do RNA do HERV-W em PBMC e uma análise transversal por ELISA do anti VCA IgG e IgM de EBV. Foram utilizados dois grupos controles sendo o primeiro com 30 indíviduos saudáveis e o segundo com 26 pacientes com outras doenças neurológicas (ODN) para comparação com os títulos de HERV-W e anti- EBV. Resultados: A dosagem do IgG EBV foi estatisticamente maior no grupo EM quando comparado ao grupo controle saudável (p = 0,024) e a expressão de HERV-W foi estatisticamente maior tanto no grupo EM (p = 0,001) como no grupo ODN (p = 0,022) quando comparados com os controles saudáveis nos grupos de pacientes. Nenhuma sorologia IgM do EBV foi positiva. A avaliação longitudinal da expressão relativa do HERV-W não apresentou correlação com nenhum dos parâmetros clínicos ou imagiológicos de avaliação da EM sendo eles: tipo de EM; medicamento em uso; EDSS; taxa anualizada de surtos; novas lesões em T2/FLAIR pela RM; lesões captando gadolíneo pela RM. Conclusão: Existe uma expressão relativa de HERV-W aumentada em pacientes com EM e em ODN quando comparados com controles saudáveis. Os pacientes com EM apresentam valores superiores de anticorpos IgG anti- EBV. Não encontramos nenhuma correlação na avaliação longitudinal entre a atividade clínica e imagiológica de pacientes com EM e a avaliação quantitativa do HERV-W e do anticorpo anti-EBV. / Introduction: Multiple sclerosis (MS) is a demyelinating autoimmune inflammatory disease. Several studies have demonstrated the strong association between MS and the expression of endogenous retrovirus W (HERV-W) and Epstein Barr Virus (EBV), without defining its true role in the development of the disease. Objective: To investigate the presence of anti-EBV antibodies and HERV-W expression in MS patients and to evaluate the correlation between the clinical and imaging activity of MS with the quantitative evaluation of HERV-W and EBV. Method: We performed clinical and magnetic resonance imaging (MRI) evaluations for 36 months of 36 MS patients and compared it with the longitudinal quantitative real-time PCR analysis of HERV-W RNA in PBMC and a cross-sectional analysis by anti-VCA IgG and EBV IgM ELISA. Two control groups were used, the first with 30 healthy subjects and the second with 26 patients with other neurological diseases (OND) for comparison with HERV-W and anti-EBV titers. Results: IgG EBV was statistically higher in the MS group when compared to the healthy control group (p = 0.024). HERV-W expression was statistically higher in the MS group (p = 0.001) and the OND group (p = 0.022) when compared to healthy controls. No IgM EBV serology was positive. The longitudinal evaluation of the relative expression of HERV-W did not present any correlation with the clinical or MRI of the MS group following parameters: type of MS; medication in use; EDSS; annualized rate of relapses; new MRI T2/FLAIR lesions; MRI gadolinium enhancing lesions. Conclusion: There is a relative increased HERV-W expression in patients with MS and in OND when compared with healthy controls. Patients with MS have higher values of anti-EBV IgG antibodies. We found no correlation in the longitudinal evaluation between the clinical and imaging.

The spinal cord is a complex structure responsible for processing sensory inputs and motor outputs. As such, the developmental and spatial organization of cells is highly organized. Diseases affecting the spinal cord, such as Amyotrophic Lateral Sclerosis (ALS), result in the disruption of normal cellular function and intercellular interactions, culminating in neurodegeneration. Deciphering disease mechanisms requires a fundamental understanding of both the normal development of cells within the spinal cord as well as the homeostatic environment that allows for proper function. Biological processes such as cellular differentiation, maturation, and disease progression proceed in an asynchronous and cell type-specific manner. Until recently, bulk measurements of a mixed population of cells have been key in understanding these events. However, bulk measurements can obscure the molecular mechanisms involved in branched or coinciding processes, such as differential transcriptional responses occurring between subpopulations of cells. Measurements in individual cells have largely been restricted to 4 color immunofluorescence assays, which provide a solid but limited view of molecular-level changes. Recently, developments in single cell RNA-sequencing (scRNA-Seq) have provided an avenue of accurately profiling the RNA expression levels of thousands of genes concomitantly in an individual cell. With this increased experimental precision comes the ability to explore pathways that are differentially activated in subpopulations of cells, and to determine the transcriptional programs that underlie complex biological processes. In this dissertation, I will first review the key features of scRNA-Seq and downstream analysis. I will then discuss two applications of scRNA-seq: 1) the in vitro differentiation of mouse embryonic stem cells into motor neurons, and 2) the effect of the ALS-associated gene SOD1G93A expression on cultured motor neurons in a cellular model of ALS.

Introdução: A hemimegalencefalia é uma rara malformação cerebral que envolve o crescimento anormalmente maior de um hemisfério cerebral. Clinicamente, observase macrocefalia, retardo mental, hemiparesia contralateral, hemianopsia e epilepsia intratável. A Esclerose tuberosa é uma doença genética rara, multissistêmica, caracterizada por tumores benignos e manifesta-se clinicamente com epilepsia e atraso cognitivo. A associação das duas patologias é rara, requer acompanhamento multidisciplinar e tratamentos medicamentoso e cirúrgico específicos. Objetivos: Identificar a presença de hemimegalencefalia em pacientes portadores de esclerose tuberosa com epilepsia atendidos no Centro de Cirurgia de Epilepsia (CIREP) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Realizar revisão de literatura sobre esclerose tuberosa e hemimegalencefalia, assim como a associação entre elas. Material e Métodos: Foi realizada revisão da literatura sobre esclerose tuberosa e hemimegalencefalia e também dos prontuários de pacientes que apresentam associação entre essas patologias. Resultados: Foram analisadas 1534 monitorizações por videoeletroencefalograma (VEEG) em crianças e adolescentes no CIREP. Dessas, 25 apresentavam hemimegalencefalia, e apenas duas com esclerose tuberosa associada. Foram, então, relatados os casos com descrição das etapas de avaliações pré-operatórias, cirurgia para o tratamento da epilepsia, e poslterior seguimento clínico, e também dos exames de imagem, neurofisiológicos e neuropatológicos. Conclusões: A associação entre hemimegalencefalia e esclerose tuberosa é uma manifestação rara, com apenas seis casos descritos na literatura. Contudo, tratandose de associação entre as doenças, a abordagem terapêutica e o seguimento dessas crianças com hemimegalencefalia se modifica, tanto na investigação quanto no acompanhamento clínico das manifestações sistêmicas da esclerose tuberosa. Os dois casos descritos apresentaram espasmos assimétricos, sendo iniciado tratamento com vigabatrina e posterior indicação cirúrgica. / Introduction: Hemimegalencephaly is a rare brain malformation that involves an abnormally larger growth of one cerebral hemisphere. Clinically, macrocephaly, mental retardation, contralateral hemiparesis, hemianopsia and intractable epilepsy are observed. Tuberous sclerosis is a rare, multisystemic genetic disease characterized by benign tumors and clinically manifested with epilepsy and cognitive delay. The association of these two pathologies is rare, requiring multidisciplinary care and specific drug and surgical treatment. Objectives: To identify the presence of hemimegalencephaly in patients with tuberous sclerosis with epilepsy attended at the Center for Epilepsy Surgery (CIREP, acronym in Portuguese) of the Clinics Hospital of Ribeirão Preto Medical School. To perform a literature review on tuberous sclerosis and hemimegalencephaly, as well as the association between them. Material and Methods: Review of the literature on tuberous sclerosis and hemimegalencephaly; review of patient records that show the association between these pathologies. Results: 1534 monitoring by VEEG in children and adolescents in CIREP were analyzed. Of these, 25 had hemimegalencephaly, and only two had associated tuberous sclerosis. The cases were reported with descriptions of the stages of preoperative evaluations, surgery for the treatment of epilepsy, with subsequent clinical care, as well as image, neurophysiological and neuropathological examinations. Conclusions: The association between hemimegalencephaly and tuberous sclerosis is a rare manifestation, with only six cases described in the literature. However, considering that it is an association between diseases, the therapeutic approach and the follow-up of these hemimegalencephalic children are specified, both in the investigation and in the clinical care of the systemic manifestations of tuberous sclerosis. Both described cases presented asymmetrical spasms, initiated treatment with vigabatrin with subsequent surgical indication and both presented renal alterations.

Disease progression in Multiple Sclerosis (MS), an autoimmune disease of the CNS, is widely accepted to be due to persistent myelin loss (demyelination) coinciding with lost nerve cells and nerve fibres (neuroaxonal loss). Current treatments are immunomodulatory and do not address the neuroaxonal or demyelinating pathology of the disease. It is hypothesised that a lack of growth factors within the CNS may result in the failure of remyelination. Therefore, biologics such as recombinant therapeutic proteins used for gene therapy offer a promising therapeutic intervention to the progressive stages of the disease. However, due to the short half-lives of these therapeutics and their pleiotropic effects, there is cause for concern over their safety and efficacy. Using LAP technology (the fusion of the therapeutic protein with the latent associated peptide [LAP] of TGFβ), the half-life of the therapeutic protein can be increased and can be targeted to sites of inflammation and disease. This study aimed to investigate the potential neuroprotective, remyelinating and anti-inflammatory effects of latent versions of the growth factors erythropoietin (EPO), insulin-like growth factor 1 (IGF1) and transforming growth factor beta (TGF) respectively. Firstly, using molecular cloning techniques, these growth factors were individually fused and linked to the LAP of TGF via a matrix metalloproteinase (MMP) cleavage site resulting in three latent growth factors. Secondly, these latent growth factors were shown to be expressed, and to be biologically active in vitro when released by MMP cleavage. Finally, syngeneic fibroblasts were engineered to express the latent growth factors. It was found that, in CREAE, the fibroblasts engineered to produce latent TGF significantly reduced the disease clinical score as compared to controls whilst latent EPO produced by transduced fibroblasts failed to exert a statistically significant effect on disease progression. Nonetheless, this study demonstrates the feasibility of the latency platform technology to generate latent therapeutics with the ability to act as an intervention to disease progression in MS.

Multiple sclerosis (MS) is a chronic central nervous system disease featuring exacerbations of inflammation and demyelination that cause progressively debilitating clinical effects over time. Current treatments for multiple sclerosis are limited in their ability to impact overall disease progression. Research aimed at generation of novel potential therapeutics for MS is needed. Recently, kallikrein 6 (KLK6), a member of the kallikrein (KLK) family of secreted serine proteases, was found to be elevated in the cerebrospinal fluid and brain of MS patients. The fifteen known tissue-based KLKs cleave proteins through a similar mechanism, but have different binding pocket specificity, diverse localization in human tissues, and multiple biological functions. KLKs have been linked to normal human physiology (e.g. KLK4, enamel formation) and disease (e.g. KLK3, prostate cancer). KLK6 is one of the highest expressed serine proteases in the healthy human brain and is expressed predominately in mature oligodendrocytes in both human and mouse brain. The role of KLK6 in oligodendrocyte maturation, myelination, and disease is not fully understood. To evaluate the role of KLK6 in oligodendrocyte maturation, I used a pluripotent in vitro primary cell system to assess the impact of exogenous KLK6 and modulators of the KLK6 pathway on oligodendrocyte maturation. I demonstrate that signaling through KLK6 decreases the number of mature oligodendrocytes in culture, whereas blockade of KLK6 signaling increases the number of mature oligodendrocytes in culture in the presence of triiodothyronine higher than either agent alone. This work suggests that KLK6 modulation impacts oligodendrocyte maturation. To understand the potential impact of KLK6 pathway inhibition on remyelination, I used the toxin cuprizone to induce demyelination in mice. I found that animals treated with a KLK6 inhibitor had increased myelin staining in the corpus callosum compared to vehicle-treated. This work suggests that KLK6 modulates oligodendrocyte maturation and myelination and may be relevant for improving myelin-related therapeutic outcomes, particularly in multiple sclerosis. / 2019-06-12T00:00:00Z