In den letzten Jahren gewann das Konzept der Paranodopathien als eigene Krankheitsentität der inflammatorischen Polyneuropathien zunehmend an Bedeutung. Die Forschung konzentrierte sich dabei überwiegend auf die chronisch inflammatorische Polyradikuloneuropathie (CIDP). In dieser Arbeit werden (para-)nodale Antikörper gegen Neurofascin-155, panNeurofascin, Contactin-1 und Caspr-1 in einer großen Kohorte von Patienten mit Guillain-Barré-Syndrom (GBS) und CIDP nachgewiesen. Patienten mit Anti-panNeurofascin-Antikörpern zeigten besonders schwere Verlaufsformen. Patienten mit anderen (para-)nodalen Antikörpern zeigten je nach IgG-Subklasse der Antikörper spezifische klinische Merkmale und ein unterschiedliches Ansprechen auf die Therapie. Die Arbeit zeigt, dass die Bestimmung (para-)nodaler Antikörper bei Patienten mit GBS und CIDP im klinischen Alltag zur Einordung der Prognose und Therapieplanung sinnvoll sein kann. / In the last years the concept of paranodopathy as an own disease entity has gained more relevance. So far, most studies focused on chronic inflammatory polyneuropathy (CIDP). In this study, autoantibodies against neurofascin-155, pan-neurofascin, contactin-1, and capsr-1 in a cohort of Guillain-Barré-syndrome (GBS) and CIDP were detected. All patients with anti-pan-neurofascin-antibodies suffered from a very severe course of disease. Patients with other (para-)nodal autoantibodies showed common clinical features and therapeutic response depending on the autoantibody and their IgG-subclasses. This study shows that (para-)nodal autoantibodies should be determined in GBS and CIDP to estimate clinical course and therapeutic response.

A Síndrome de Guillain-Barré (SGB) é uma neuropatia periférica inflamatória aguda que tem sido definida pelo achado ou história de tetraparesia flácida arreflexa ascendente. Apresentações atípicas podem ser mais frequentes do que tem sido referido na literatura, particularmente na faixa etária infantil. Objetivo: Avaliar dados epidemiológicos e a prevalência de assimetria no exame neurológico em crianças com SGB. Métodos: Foram revisados 40 prontuários de crianças de 0 a 15 anos de idade com o diagnóstico de SGB, atendidas entre janeiro de 2000 e agosto de 2016. Avaliouse a presença de assimetrias no exame neurológico na admissão hospitalar, os desfechos clínicos e as características demográficas e clinico-laboratoriais. Resultados: Dois pacientes apresentaram assimetria no exame neurológico na admissão hospitalar e três pacientes admitidos com tetraparesia simétrica apresentaram um quadro motor assimétrico antes da internação. Uma criança evoluiu para assimetria após ter sido admitida com quadro simétrico. Outros oito casos tinham fraqueza segmentar. A presença de assimetria motora ou fraqueza segmentar se correlacionou com a progressão estática dos sintomas (p=0,004) e observou-se uma tendência desses pacientes serem mais jovens, mas essa diferença não foi significativa (p=0,08). Onze pacientes apresentavam reflexos miotáticos preservados e um paciente exibia hiperreflexia na admissão hospitalar. A maioria dos pacientes foi admitida sem conseguir deambular e, na alta, a maioria deambulava com ou sem apoio. Cinco crianças necessitaram de suporte ventilatório e nenhuma foi a óbito. Conclusão: Uma proporção significativa dos pacientes apresentava quadro motor assimétrico ou segmentar e reflexos miotáticos preservados. Os resultados obtidos delineiam aspectos clínicos atípicos na SGB em crianças e podem ajudar na definição diagnóstica e instituição de tratamento precoce. / Guillain-Barré syndrome (GBS) is an acute, inflammatory, peripheral neuropathy that has been being defined as an ascending flaccid tetraparesis. Atypical presentations can be frequent, particularly in children, leading to greater challenges in the diagnosis. Objectives: To analyze the epidemiological data and the prevalence of motor asymmetries in the neurological examination of children with GBS. Methods: A total of 40 medical records were analyzed, of children aged 0 to 15 years old diagnosed with GBS, admitted from January 2000 to August 2016. We evaluated the presence of motor asymmetries at the hospital admission, the clinical outcomes and the demographic and clinic-laboratorial characteristics. Results: Two patients had motor asymmetries at hospital admission and three patients admitted with symmetric tetraparesis had an initial motor asymmetry before admission. One patient progressed to asymmetric tetraparesis after being initially admitted with symmetric weakness. Eight other cases had segmental weakness at admission. Motor asymmetry and segmental weakness correlated with a static progression of symptoms (p=0.004) and these patients tended to be younger, but this difference was not significant (p=0.08). Eleven patients had preserved deep tendon reflexes and one exhibited hyperreflexia at the hospital admission. Most patients were admitted on wheel-chair or bedridden, and at discharge the majority could walk with or without help. Five children required mechanical ventilation and no patient died. Conclusion: A significant proportion of patients had asymmetric or segmental weakness and preserved deep tendon reflexes. Those results show that the so-called atypical clinical findings in children with GBS are not uncommon, and needs to be kept in mind to allow an earlier diagnosis and treatment.

A Síndrome de Guillain-Barré (SGB) é uma neuropatia periférica inflamatória aguda que tem sido definida pelo achado ou história de tetraparesia flácida arreflexa ascendente. Apresentações atípicas podem ser mais frequentes do que tem sido referido na literatura, particularmente na faixa etária infantil. Objetivo: Avaliar dados epidemiológicos e a prevalência de assimetria no exame neurológico em crianças com SGB. Métodos: Foram revisados 40 prontuários de crianças de 0 a 15 anos de idade com o diagnóstico de SGB, atendidas entre janeiro de 2000 e agosto de 2016. Avaliouse a presença de assimetrias no exame neurológico na admissão hospitalar, os desfechos clínicos e as características demográficas e clinico-laboratoriais. Resultados: Dois pacientes apresentaram assimetria no exame neurológico na admissão hospitalar e três pacientes admitidos com tetraparesia simétrica apresentaram um quadro motor assimétrico antes da internação. Uma criança evoluiu para assimetria após ter sido admitida com quadro simétrico. Outros oito casos tinham fraqueza segmentar. A presença de assimetria motora ou fraqueza segmentar se correlacionou com a progressão estática dos sintomas (p=0,004) e observou-se uma tendência desses pacientes serem mais jovens, mas essa diferença não foi significativa (p=0,08). Onze pacientes apresentavam reflexos miotáticos preservados e um paciente exibia hiperreflexia na admissão hospitalar. A maioria dos pacientes foi admitida sem conseguir deambular e, na alta, a maioria deambulava com ou sem apoio. Cinco crianças necessitaram de suporte ventilatório e nenhuma foi a óbito. Conclusão: Uma proporção significativa dos pacientes apresentava quadro motor assimétrico ou segmentar e reflexos miotáticos preservados. Os resultados obtidos delineiam aspectos clínicos atípicos na SGB em crianças e podem ajudar na definição diagnóstica e instituição de tratamento precoce. / Guillain-Barré syndrome (GBS) is an acute, inflammatory, peripheral neuropathy that has been being defined as an ascending flaccid tetraparesis. Atypical presentations can be frequent, particularly in children, leading to greater challenges in the diagnosis. Objectives: To analyze the epidemiological data and the prevalence of motor asymmetries in the neurological examination of children with GBS. Methods: A total of 40 medical records were analyzed, of children aged 0 to 15 years old diagnosed with GBS, admitted from January 2000 to August 2016. We evaluated the presence of motor asymmetries at the hospital admission, the clinical outcomes and the demographic and clinic-laboratorial characteristics. Results: Two patients had motor asymmetries at hospital admission and three patients admitted with symmetric tetraparesis had an initial motor asymmetry before admission. One patient progressed to asymmetric tetraparesis after being initially admitted with symmetric weakness. Eight other cases had segmental weakness at admission. Motor asymmetry and segmental weakness correlated with a static progression of symptoms (p=0.004) and these patients tended to be younger, but this difference was not significant (p=0.08). Eleven patients had preserved deep tendon reflexes and one exhibited hyperreflexia at the hospital admission. Most patients were admitted on wheel-chair or bedridden, and at discharge the majority could walk with or without help. Five children required mechanical ventilation and no patient died. Conclusion: A significant proportion of patients had asymmetric or segmental weakness and preserved deep tendon reflexes. Those results show that the so-called atypical clinical findings in children with GBS are not uncommon, and needs to be kept in mind to allow an earlier diagnosis and treatment.

The needs of patients who are nursed on the ICU are becoming more widely recognised and services are beginning to reflect this. However there is little research into how patients who have suffered from a severe and progressive muscular paralysis called Guillain-Barré Syndrome (GBS) experience the disease and subsequent hospitalisation. The purpose of this study was to explore how these patients experience the different aspects of the illness, including an extended period of paralysis and treatment on an ICU. This is intended to expand upon the limited research in this area and identify how the findings can inform clinical practice and future studies. Method: A systematic literature search identified research in relation to the experiences of individuals who had GBS which was utilised to form the basis of the understanding for this study. Very little systematic research has looked at individuals‟ experiences of Guillain-Barré Syndrome whilst ill and their subsequent recovery. A mixed methods study was carried out with the aim of adding to this research. Interpretative Phenomenological Analysis was selected as the method of analysis for Study 1, which involved interviews with seven participants who had experienced GBS severe enough to need treatment on an ICU. This then enabled quantitative questionnaires to be disseminated which asked about individuals‟ levels of anxiety, depression and Post Traumatic Stress symptomatology both retrospectively and following recovery in Study 2. Results: Study1 found that participants experienced GBS as either a slow and frustrating, or as a rapid and scary onset. The main themes that were developed included: the paralysis being viewed as multiple losses, frustration, difficulties associated with communication loss, vulnerability and frightening hallucinations. Study 2 utilised non-parametric analyses of the data and found that participants experienced high levels of anxiety and depression at the onset of GBS and that some continued to experience anxiety, depression and post traumatic symptoms after recovery from GBS. Generally the profile suggests predominantly anxiety problems during the acute onset phase and then predominantly depression at the time of follow-up. Aspects of post traumatic stress were positively correlated with duration of mechanical ventilation which in turn was related to duration of paralysis. This challenged the hypothesis that GBS patients habituate to the experience of paralysis. Conclusion: For some individuals, GBS was experienced as a frightening event, but one that they could draw positive things from. However, for others, GBS was experienced as a traumatic event and some of these people continued to exhibit signs of psychological distress even after recovery. It remains important for staff to feel able to speak about distressing situations with their patients and to signpost them to other psychological services if appropriate.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Pós-graduação em Medicina Tropical, 2018. / Submitted by Raquel Viana (raquelviana@bce.unb.br) on 2018-07-03T20:52:33Z No. of bitstreams: 1 2018_VirginiaKagureWachira.pdf: 1224251 bytes, checksum: a3d6f560ea24acc2a898579963b67cdd (MD5) / Approved for entry into archive by Raquel Viana (raquelviana@bce.unb.br) on 2018-07-09T18:50:35Z (GMT) No. of bitstreams: 1 2018_VirginiaKagureWachira.pdf: 1224251 bytes, checksum: a3d6f560ea24acc2a898579963b67cdd (MD5) / Made available in DSpace on 2018-07-09T18:50:35Z (GMT). No. of bitstreams: 1 2018_VirginiaKagureWachira.pdf: 1224251 bytes, checksum: a3d6f560ea24acc2a898579963b67cdd (MD5) Previous issue date: 2018-07-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). / Introdução: A síndrome de Guillain-Barré é uma polirradiculoneuropatia desmielinizante inflamatória aguda, de natureza autoimune que afeta o sistema nervoso periférico e geralmente é desencadeada por um processo infeccioso agudo. Vários antecedentes etiológicos infecciosos e não infecciosos têm sido associados com a síndrome. A infecção por bactéria Campylobacter jejuni é a causa mais associada com a síndrome, entre outras infecções como citomegalovírus, vírus Epstein-Barr, sarampo, vírus de influenza A, Mycoplasma pneumoniae, enterovirus D68, hepatite A, B, C e o vírus Zika. Objetivo: Descrever os fatores associados ao desenvolvimento da síndrome de Guillain-Barré por meio de revisão da literatura científica e descrever as publicações com enfoque epidemiológico relacionadas à Sindrome de Guillain-Barré antes, durante e depois da epidemia do vírus Zika no Brasil e no mundo, com foco na sua etiologia. Método: Uma revisão sistemática de estudos epidemiológicos a respeito da etiologia da Síndrome de Guillain-Barré publicados no período de 2007 a 2017, antes, durante e depois da epidemia de Zika vírus. As bases de dados utilizados foram EBSCOhost Reseach Databases, Medical Literature Analysis and Retrieval System Online e Literatura Latino-Americana e do Caribe em Ciências da Saúde. A qualidade dos estudos foi avaliada utilizado Newcastle Ottawa Scale. Seguiu os passos da Preferred Reporting Items for Systematic Reviews and Meta-Analyses para o seu relato. Resultados: Um total de 224 artigos foi identificado após a busca nas bases de dados especificadas e após a aplicação dos critérios de inclusão 34 artigos foram selecionados para o estudo, após a leitura completa. Desses artigos, 17 usaram desenho de caso-controle, oito de coorte, cinco Self Controlled Case Series, dois de Self Controlled Risk Interval e dois com desenhos mistos. A qualidade global dos artigos foi considerada alta em relação à maioria dos itens avaliados. Vários agentes etiológicos tiveram resultados indicativos de associação com a síndrome de Guillain-Barré, entre eles: Campylobacter jejuni, vacina da influenza: pandêmica e sazonal, vírus Zika, Mycoplasma pneumoniae, infecção respiratória e gastrointestinal. No período estudado, não houve aumento anual importante no número de estudos que atenderam os critérios de inclusão apesar dos dois eventos de grande impacto na saúde coletiva: a pandemia do vírus da Influenza H1N1 em 2009 e a epidemia do vírus Zika, a partir de 2015 nas Américas. Os agentes encontrados são, na maioria, os mesmos relatados antes do período do estudo. A relação com cirurgias, vírus chikungunya, vírus Zika e a vacina quadrivalente do papilomavírus humano nas meninas (HPV 4 Gardasil) destacam-se como novidades na lista dos diversas possíveis agentes desencadeadores da síndrome de Guillain-Barré relatados no período estudado. Não foram identificados estudos realizados no Brasil nesse período. Conclusões: Os resultados dessa revisão sistemática podem contribuir para o conhecimento dos principais agentes etiológicos envolvidos no desenvolvimento da síndrome de Guillain-Barré e subsidiar a tomada de decisões em saúde, assim como guiar futuras pesquisas, especialmente no momento em que o Brasil vem vivenciando o aumento de casos da síndrome, chamando atenção da comunidade acadêmica, dos serviços de saúde, da comunidade e da imprensa. / Introduction: Guillain-Barré syndrome is an acute inflammatory demyelinating polyradiculoneuropathy, autoimmune in nature that affects the peripheral nervous system and usually triggered by an acute infectious process. Several background infectious and non-infectious etiological factors have been associated with the syndrome. Camplybocter jejuni infection is commonly associated with the syndrome among other infectious causes like citomegalovírus, Epstein-Barr virus, measles, influenza virus, Mycoplasma pneumoniae, enterovirus D68, hepatite A, B, C and Zika virus. Objective: Describe factors associated with the development of Guillain-Barré syndrome by reviewing scientific literature and describing publications with epidemiological approach related to Gullain-Barré Syndrome before, during and after the epidemic of Zika virus in Brazil and in the world with a focus on its etiology. Method: Systematic review of epidemiological studies about the etiology of Guillain-Barré syndrome published between 2007 and 2017, before, during and after Zika virus epidemic. The data bases used were EBSCOhost Reseach Databases, Medical Literature Analysis and Retrieval System Online and Literatura Latino-Americana e do Caribe em Ciências da Saúde. The quality of the studies was evaluated using the Newcastle Ottawa Scale. The study report followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results: 224 articles were identified after the search in the databases specified and the application of the inclusion criteria, 34 articles were selected for the study after their complete scan. Among the selected articles, 17 had case control design,eight had cohort, five self-controlled case series and two self-controlled risk interval. The quality of the studies was considered good in relation to most of the items evaluated. Many etiological agents had results indicative of association with Guillain-Barré syndrome, among them Campylobacter jejuni, influenza vaccine both pandemic and seasonal vaccines, respiratory infection, gastrointestinal infection among others. The etiological agents found are in most part the same reported prior to the study period. The association with surgeries, chikungunya virus, Zika virus and quadrivalent human papillomavirus vaccine (Gardasil in girls) stand out as new etiological agents in the list of the various possible agents that trigger Guillain-Barré syndrome reported in the study period. There were no Brazilian studies identified during this period. Conclusions: The results of this systematic review can contribute to the knowledge of the main etiological agents involved in the development of Guillain-Barré syndrome and aid in the decision-making process in the health sector, as well as to guide future research especially in Brazil at a time that the increase of cases of the syndrome is attracting the attention of the academic community, health services, the citizens and the press.

M.Cur. / The purpose of this study is to explore and describe the experiences of patients with Guillain-Barré syndrome whilst being nursed in intensive care units, in order to set guidelines for nursing. The researcher made use of the phenomenological approach within the paradigm of qualitative research. The target population consisted of 70 patients of which seven complied with the selection criteria: In-depth interviews, which were taped, were conducted with the patients. Validity and reliability were ensured by using measures as stated by Woods and Catanzaro (1988). Data-analysis was executed by means of Giorgi's method (Omery,1983) and after clearance with an external decoder, it was categorized according to the patients' internal and external environment. The Nursing Theory for the Wholeperson had been used to this purpose. The conclusions of this study indicate that patients with Guillain-Barré syndrome in intensive care units experience deprivation of sleep, pain and fear. Limited communication and loss of autonomy create frustration. Patients become lonely and bored and have a need for constant support from their family and others. Consequent upon the conclusions the researcher developed nine guidelines for the nursing of patients with Guillain-Barré syndrome. These guidelines are in support of the functional approach of the researcher and may be considered an attempt to provide research findings that are applicable to the practice of nursing.

Die (Para-)nodopathie ist neben der primär axonalen und der primär demyelinisierenden Polyneuropathie eine neue Krankheitsentität, die sich durch eine Schädigung der Funktion des Ranvierschen Schnürringes auszeichnet. Die Forschung zu (para-)nodalen Autoantikörpern fokussierte sich bislang hauptsächlich auf Neurofascin-155- und Contactin-1-Autoantikörper der Subklasse IgG4. In dieser Studie wurden die Seren von insgesamt 264 PatientInnen mit CIDP, GBS oder anderen Formen von Polyneuropathien mittels Bindungsassays an murinen Ischiadicuszupfnerven und gegebenenfalls ELISA auf (para-)nodale Autoantikörper gescrennt. Positive Autoantikörperbefunde wurden bei IgG-Autoantikörpern mittels Bindungsassays an transfizierten HEK-293-Zellen und bei IgM-Autoantikörpern mittels Western Blot bestätigt. ELISA Untersuchungen dienten zur näheren Spezifizierung. Weiterhin wurde die zeitabhängige Wirkung von Contactin-1-Autoantikörpern im Zellkulturmodell untersucht. Die im folgenden dargestellten Ergebnisse zeigen, dass die (Para-)nodopathie nicht auf die bisher am häufigsten beschriebene Erkrankung mit IgG4-Autoantikörpern beschränkt werden sollte. Bei dem extrem schwer betroffenen IgG-Patient 1 konnte ein Pan-Neurofascin-IgG3-Autoantikörper nachgewiesen werden. Als charakteristische Symptome für diese Autoantikörper konnten in Übereinstimmung mit weiteren Fallberichten Tetraplegie, Beatmungspflichtigkeit sowie eine schwere Hirnnervenbeteiligung bis zur Locked-In-Symptomatik identifiziert werden. Diese Patienten heben sich deutlich von den PatientInnen mit den bisher hauptsächlich beschriebenen Neurofascin-155-IgG4-Autoantikörpern ab, die wie IgG-Patient 2 charakteristischerweise in jungem Alter an einer CIDP mit Tremor ohne Besserung unter IVIG-Therapie leiden. Es wurden fünf PatientInnen mit Neurofascin-155-IgM-Autoantikörpern identifiziert, die eine akut beginnende Erkrankung mit Tetraparese, Tremor und neuropathischen Schmerzen zeigten. Ob sich dieser Phänotyp als charakteristisch für eine Neurofascin-155-IgM-(Para-)nodopathie bestätigt, sollte in weiteren Studien untersucht werden. Im murinen Zellkulturmodell an cerebellären Neuronen und Spinalganglienneuronen zeigte sich nach Inkubation mit Contactin-1-IgG-Patientenantikörpern eine zeitabhängige, rasch reversible Verminderung der Contactin-1-Protein-Expression in immunhistochemischen Färbungen sowie Western Blots, die durch eine Internalisierung des Contactin-1-Proteins erklärbar wäre. Der Angriff von Autoantikörpern an Spinalganglienneuronen und cerebellären Neurone sollte in weitere pathophysiologische Überlegungen miteinbezogen werden, da hierdurch typische Symptome der (Para-)nodopathie wie eine sensible Ataxie oder ein cerebellärer Tremor erklärt werden könnten. / (Para-)nodopathy is besides primary axonal and primary demyelinating polyneuropathy a new disease entity characterized by damage to the function of the node of ranvier. Research on (para)nodal autoantibodies has up to now mainly focused on neurofascin-155 and contactin-1 autoantibodies of IgG4 subclass. In this study sera from 264 patients with CIDP, GBS, or other forms of polyneuropathies were screened for the presence of (para-)nodal autoantibodies by binding assays on murine sciatic nerve and ELISA. Positive autoantibody findings were confirmed by binding assays on transfected HEK-293 cells for IgG autoantibodies and by western blot for IgM autoantibodies. ELISA assays were used for further specification. Furthermore the time-dependent effect of contactin-1 autoantibodies was investigated in a cell culture model. The results, presented in the following, show that (para-)nodopathy should not be limited to the up to now most commonly described disease with IgG4 autoantibodies. In the extremely severely affected IgG patient 1 pan-neurofascin IgG3 autoantibodies were detected. In accordance with other case reports tetraplegia, the need for artificial ventilation and severe cranial nerve involvement up to locked-in syndrome could be identified as characteristic symptoms for these autoantibodies. These patients clearly differ from the patients with neurofascin-155 IgG4 autoantibodies, which have been mainly described so far and who, like IgG patient 2, characteristically suffer from CIDP with tremor, have a younger age of onset and do not show improvement under IVIG therapy. Five patients with neurofascin-155 IgM autoantibodies were identified, who showed acute onset disease with tetraparesis, tremor, and neuropathic pain. Whether this phenotype is confirmed to be characteristic of neurofascin-155 IgM (para-)nodopathy should be investigated in further studies. In the murine cell culture model of cerebellar granule neurons and dorsal root ganglion neurons, incubation with contactin-1 IgG patient antibodies showed a time-dependent, rapidly reversible decrease in contactin-1 protein expression in immunohistochemical staining as well as western blots, which could be explained by internalization of contactin-1 protein. The effect of autoantibodies on dorsal root ganglion neurons and cerebellar granule neurons should be considered in further pathophysiological considerations, as this could explain typical symptoms of (para-)nodopathy such as sensory ataxia or cerebellar tremor.

OBJETIVOS: Determinar los grados de fuerza muscular y la relación que tienen con los subtipos del síndrome de Guillain Barré en los pacientes afectados desde el año 2009 al 2013 del Instituto Nacional de Ciencias Neurológicas. MATERIALES Y MÉTODOS: Estudio de tipo descriptivo, correlacional, retroprospectivo, transversal; se estudio a 31 pacientes que fueron afectados con el Síndrome del Guillain Barré entre los años 2009 al 2013 del Instituto Nacional de Ciencias Neurológicas entre los 20 a los 79 años de edad; se utilizó como instrumentos el test manual de exploración muscular o test de fuerza muscular manual y se relacionó la variable con el subtipo del Síndrome de Guillain Barré extraída de los datos de la historia clínica de los pacientes. RESULTADOS: Los resultados del cruce de las variables subtipo de Síndrome de Guillain Barré y los grados de Fuerza muscular (divididas en dos grupos: con alteración funcional o sin alteración funcional) por medio de tablas de contingencia con la utilización de las pruebas de Chi –cuadrado el grado de los significancia de p > 0,05, con lo cual no se p grados de Fuerza Muscular no podrán ser probadas. Se observaron que las alteraciones de los grados de fuerza muscular a nivel funcional están presenten a predominio de los grupos musculares de los segmentos distales, tanto de miembros superiores como miembros inferiores. CONCLUSIONES: No se pudo demostrar la relación entre los subtipos del Síndrome de Guillain Barré, las posibles causas de los resultados aún se mantienen en discusión para futuras investigaciones. Las alteraciones de los grados de fuerza muscular funcional son predominantes en los segmentos distales. / OBJECTIVES: To determine the degree of muscle strength and the relationship they have with the subtypes of Guillain Barre syndrome in patients affected from 2009 to 2013 of the Instituto Nacional de Ciencias Neurológicas. MATERIALS AND METHODS: Descriptive, correlational, retroprospective, transversal; 31 patients who were affected with Guillain Barre Syndrome from 2009 to 2013 of the Instituto Nacional de Ciencias Neurológicas, the age range is 20 to 79 years old; Manual muscle test was used as instruments and it was related with the subtype of Guillain Barré syndrome, that data was extracted from medical records of patients. RESULTS: The results from the intersection of variables subtype of Guillain Barré and degrees of muscular strength (divided into two groups: those with functional impairment or without functional impairment ) using contingency tables and using Chi -square test the significance level of p> 0.05 , I was not found a significant difference between between subtypes of Guillain Barre syndrome and degrees of muscle strength. It was found degrees of muscle strenght alteration at the functional level a of the distal muscle groups in the upper limbs and lower limbs. CONCLUSIONS: it was not found a significant correlation between between subtypes of Guillain Barré and degrees of muscle strength. The possible causes of the results still are found under discussion for future studies. Alterations in the levels of functional muscle strength are predominant in the distal segments. KEYBOARDS: Subtype Guillain Barre Syndrome, Muscular Strength, degree of functional muscle strength, muscle strength degree of functional impairment.

In this project two novel murine autoimmune models were to be established in an attempt to further investigate the nervous system disorders of Multiple Sclerosis and Guillain Barré Syndrome. Previous experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) models have demonstrated that T cells play a major role in these diseases. Which roles CD4 and CD8 T cells specifically have in the initiation, propagation and termination of an autoimmune nervous system disorder remains controversial. To this end two transgenic mice specifically expressing the neo-antigen (Ag) ovalbumin (OVA) in either the central nervous system (CNS) or peripheral nervous system (PNS) were to be generated. The myelin basic protein (MBP) is a major component of the myelin sheath both within the CNS and the PNS. Therefore the MBP promoter was employed for its distinct regulatory elements to facilitate exclusive CNS or PNS OVA expression. The adoptive transfer of OVA specific MHCI restricted (OT-I) and MHCII restricted (OT-II) TCR Tg T cells extended the OVA Tg mouse model by allowing potentially encephalitogenic T cells to be tracked in vivo. Specificity for the target Ag should enable the dynamic role of antigen specific T cells in neuroinflammatory diseases to be revealed in more detail. / Im Rahmen der vorliegenden Arbeit wurden zwei neue Mausmodelle für Autoimmunerkrankungen etabliert, um weitere Fortschritte bei der Aufklärung der zellulären und molekularen Interaktionen bei den Erkrankungen des Nervensystems Multiple Sklerose und Guillain Barré Syndrom zu erzielen. In früheren Experimenten mit EAE (experimentelle autoimmune Enzephalomyelitis) und EAN (experimentelle autoimmune Neuritis) konnte bereits gezeigt werden, dass T-Zellen eine Hauptrolle bei diesen Erkrankungen spielen, wobei jedoch die Bedeutung von CD4 bzw. CD8 T-Zellen im Einzelnen noch nicht aufgeklärt ist. Zu diesem Zwecke sollten zwei transgene (Tg) Mauslinien generiert werden, die speziell entweder im peripheren (PNS) oder im zentralen (ZNS) Nervensystem das Zielantigen OVA exprimieren. MBP ist eine Hauptkomponente der Myelinscheide sowohl im ZNS als auch im PNS. Daher kam der Myelin Basic Protein (MBP) Promoter zum Einsatz, dessen unterschiedliche regulatorischen Elemente eine Expression von intaktem OVA ausschließlich im ZNS bzw. ausschließlich im PNS steuern können. Eine Erweiterung dieser OVA tg Mausmodelle stellte der adoptive Transfer von OVA spezifischen MHCI-restringierten OTI und MHCII-restringierten OTII T-Zellen dar, da es so möglich wurde, potentiell enzephalitogene T-Zellen in vivo zu verfolgen. Dadurch sollte ebenfalls eine detailliertere Darstellung der dynamischen Rolle von antigenspezifischen T-Zellen bei neuroinflammatorischen Erkrankungen ermöglicht werden.

Kürzlich wurden bei immunvermittelten Neuropathien Autoantikörper gegen Proteine des paranodalen axoglialen Komplexes beschrieben. Deren Charakteristika, Prävalenzen, pathophysiologische Relevanz sowie Bedeutung für Diagnostik und Therapie sind jedoch noch nicht abschließend erforscht. In dieser Studie wurden daher Seren und Plasmapheresematerial (PE-Material) von 150 Patienten mit inflammatorischen Neuropathien, nämlich 105 mit chronisch inflammatorischer demyelinisierender Polyneuropathie (CIDP), 21 mit Guillain- Barré-Syndrom (GBS) und 24 mit multifokaler motorischer Neuropathie (MMN), welche etablierte diagnostische Kriterien der jeweiligen Krankheit erfüllen, sowie 74 Kontrollen mittels immunhistochemischen Färbungen an murinen Zupfnervenpräparaten und/oder ELISA (Enzyme-linked Immunosorbent Assay) auf Autoantikörper gegen die paranodalen Proteine Caspr, Contactin-1 und Neurofascin- 155 untersucht. Bei positivem Ergebnis wurde deren Spezifität mittels immunhistochemischen Färbungen an transfizierten HEK (Human embryonic kidney)- 293-Zellen und Präinkubationsversuchen bestätigt. Es wurden die IgG-Subklassen und die Antikörpertiter bestimmt und das Komplementbindungsverhalten unter Zugabe von intravenösen Immunglobulinen (IVIG) mit zellbasierten und ELISA-basierten Methoden analysiert. Klinische Merkmale und das Therapieansprechen Antikörper-positiver Patienten wurden ermittelt und mit den experimentellen Ergebnissen in Zusammenhang gesetzt. IgG-Autoantikörper gegen Contactin-1 konnten bei vier Patienten mit CIDP nachgewiesen werden, IgG-Autoantikörper gegen Caspr bei einem Patienten mit CIDP und einer Patientin mit GBS. Es konnten keine weiteren Autoantikörper bei CIDP-Patienten, GBS-Patienten, MMN-Patienten oder bei den Kontrollen detektiert werden. Die Prävalenz von Autoantikörpern gegen axogliale paranodale Proteine liegt somit in dieser Studie bei jeweils 4,76% bei CIDP und GBS und 0% bei MMN. Die Antikörper gehörten bei Patienten in der akuten Erkrankungsphase (zwei der CIDP-Patienten mit Anti-Contactin-1-Autoantikörpern und eine GBS-Patientin mit Anti-Caspr-Autoantikörpern) hauptsächlich den Subklassen IgG1 und IgG3 an, bei Patienten in der chronischen Phase (zwei der CIDP-Patienten mit Anti-Contactin-1-Autoantikörpern, ein CIDP-Patient mit Anti-Caspr-Autoantikörpern) überwog die Subklasse IgG4. Experimentell kam es zur Komplementbindung und -aktivierung abhängig vom Gehalt der Subklassen IgG1-3, nicht aber IgG4; diese konnte durch die Zugabe von IVIG dosisabhängig gemindert werden. Alle Autoantikörper-positiven CIDP-Patienten zeigten einen GBS-artigen Beginn mit einer schweren motorischen Beteiligung. Anti-Contactin-1-positive Patienten kennzeichnete klinisch zusätzlich das Vorkommen einer Ataxie und eines Tremors, Anti-Caspr-positive Patienten das Vorkommen starker neuropathischer Schmerzen. Elektrophysiologisch standen neben Hinweisen auf eine Leitungsstörung Zeichen einer axonalen Schädigung im Vordergrund. Als histopathologisches Korrelat lagen eine nodale Architekturstörung und ein Axonverlust vor. Die Patienten zeigten nur in der Anfangsphase der Erkrankung ein Ansprechen auf IVIG. Bei drei CIDP-Patienten mit IgG4-Autoantikörpern (zwei Patienten mit Anti-Contactin-1-Antikörpern und ein Patient mit Anti-Caspr-Antikörpern) wurde eine Therapie mit Rituximab durchgeführt. Diese führte zu einer Titerreduktion und zur zeitgleichen klinischen und elektrophysiologischen Befundbesserung bei zwei Patienten. Die in dieser Arbeit angewandten Screeningmethoden führten zum erfolgreichen Nachweis von Autoantikörpern gegen paranodale axogliale Proteine. Die Patienten mit positivem Autoantikörpernachweis definieren eine kleine Untergruppe mit ähnlichen klinischen Merkmalen im Kollektiv der Patienten mit inflammatorischen Polyneuropathien. Histopathologische Merkmale sowie das Therapieansprechen auf antikörperdepletierende Therapie sprechen in Kombination mit den Ergebnissen weiterer Studien zu paranodalen Autoantikörpern für eine pathogenetische Relevanz der Autoantikörper. Mit einem charakteristischen, am Schnürring ansetzenden Pathomechanismus könnten Neuropathien mit Nachweis von paranodalen Autoantikörpern der kürzlich eingeführten Entität der Nodo-Paranodopathien angehören. Die Komplementaktivierung und das Therapieansprechen der Patienten auf IVIG stehen möglicherweise in Zusammenhang mit der prädominanten IgG-Subklasse. Diese könnte auch in Bezug auf die Chronifizierung eine Rolle spielen. Der Nachweis von Autoantikörpern gegen paranodale Proteine hat wohlmöglich in Zukunft direkte Konsequenzen auf das diagnostische und therapeutische Prozedere bei Patienten mit CIDP und GBS; weitere klinische und experimentelle Daten aus größeren, prospektiven Studien sind jedoch zum weiteren Verständnis und zur Charakterisierung dieser Entität notwendig. / Autoantibodies against proteins of the paranodal axoglial complex have been described in recent studies on immune-mediated neuropathies. Nevertheless, their characteristics, prevalences, pathophysiological relevance and impact on diagnostics and therapy have not been fully investigated. Therefore, sera and plasmapheresis material (PE-material) of 150 patients with inflammatory neuropathy, including 105 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 21 patients with Guillain-Barré-Syndrome (GBS) and 24 patients with multifocal motor neuropathy (MMN), fulfilling established diagnostic criteria for the respective disease, as well as 74 controls were screened for autoantibodies against the paranodal proteins caspr, contactin-1 and neurofascin-155 via immunohistochemic staining of murine teased fiber preparations and/or ELISA (Enzyme-linked Immunosorbent Assay). In the event of a positive result, their specificity was confirmed via immunohistochemic staining on transfected HEK (human embryonic kidney)-293-cells and preincubation experiments. IgG subclasses and antibody titers in human material were analysed and complement binding to the autoantibodies, also under the influence of therapeutic immunoglobulins (IVIG), was investigated in cell based assays and ELISA based assays. Clinical features and therapy response in antibody-positive patients were evaluated and compared to the experimental results. IgG-autoantibodies against contactin-1 were found in four patients with CIDP, IgG-autoantibodies against caspr were found in one patient with CIDP and one with GBS. No further autoantibodies were detected neither in patients with CIDP, GBS and MMN nor in the controls. The prevalences of autoantibodies against axoglial paranodal proteins in this study therefore are at 4,76% in CIDP and GBS and 0% in MMN. In the acute phase of the disease, autoantibodies of the IgG1 and IgG3 subclass could be detected (in two CIDP patients with anti-contactin-1 antibodies and one GBS patient with anti-caspr antibodies), whereas patients in the chronic phase of the disease showed IgG4-autoantibodies (two CIDP patients with anti-contactin-1 antibodies and one CIDP patient with anti-caspr antibodies). Complement binding and activation in vitro depended on the amount of the IgG subclasses IgG1-IgG3, but not IgG4. Complement binding could be reduced by IVIG dose-dependently. All CIDP-patients with autoantibodies showed a GBSlike onset with severe motor involvement. Additional features of anti-contactin-1 positive neuropathy were ataxia and tremor, of anti-caspr positive disease neuropathic pain. Electrophysiological studies revealed signs of conduction failure accompanied by striking signs of axonal damage. As a histopathologic correlate, a disruption of the nodal architecture and axonal loss were found. Patients only responded well to IVIG in the beginning of the disease. Three patients with autoantibodies of the IgG4 subclass (two patients with anti-contactin-1 and one patient with anti-caspr) were treated with rituximab, leading to a titer reduction accompanied by clinical and electrophysiological improvement in two patients. The screening methods used in this study are suitable for the detection of autoantibodies against paranodal proteins. Antibody-positive patients define a small subgroup of patients with inflammatory polyneuropathy that is characterized by distinct clinical features. Histopathological findings and therapy response to antibody- depleting treatment in this study as well as findings of further studies argue in favour of a pathogenetic relevance of the autoantibodies. Neuropathies associated with paranodal autoantibodies could belong to the new entity of nodo-paranodopathies, sharing a characteristic pathomechanism with the node of Ranvier being the site of attack. Complement binding and activation as well as response to IVIG could be related to the predominant IgG subclass of the autoantibodies. It could also influence the course and chronification of the disease. Therefore, detection of autoantibodies against paranodal proteins might have a direct impact on diagnostic and therapeutic strategies in patients with CIDP and GBS in the future. Nevertheless, further clinical and experimental data, including data from bigger and prospective studies are needed to understand and fully characterize this novel entity.