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.

<p>Both Multiple Sclerosis (MS) and Guillan-Barré syndrome (GBS) are neurological inflammatory demyelinating autoimmune diseases, with a probable antibody contribution. Complement proteins in both MS and GBS does play a role in inflammation and demyelination at pathogenesis, according to earlier scientific evidence. The aim of this examination project work was to investigate systemic and intrathecal complement activation in MS and GBS, to gain further knowledge that might be useful for development of future therapeutics targeting immune responses during those diseases. An additional aim was to develop a new ELISA method for detection of complement iC3.</p><p>By using sandwich ELISA, complement proteins C1q, C4, C3, fH and C3a were measured in plasma and cerebrospinal fluid (CSF) from persons within 4 different diagnostic groups; MS, other neurological diseases (OND), GBS and controls (C). An ELISA method to detect iC3 (hydrolysed C3) was also developed, including usage of SDS-PAGE. Results based on raw data and statistical analysis show significantly elevated levels of C3a (C3a/C3) in MS and decreased C3 in plasma. In CSF low levels of C4 and C3a/C3 in MS were detected, though correlation of C3a and C1q was positive. GBS reveal high levels of all complement proteins analysed in CSF except for C3, and a positive correlation of C3a and C1q as well as C3a and fH was found.</p><p>These results indicate that MS patients have systemic complement activation; however the activation pathway is not determined. Complement activation in MS may also occur intrathecally, with correlation analysis indicating a possible activation via the classical pathway. MS patients suffering from a more acute relapsing-remitting (RR) MS have a more prominent systemic complement activation compared to MS patients responding to beta-interferon treatment. Systemic increased C3a/C3 ratio may be a possible biomarker to distinguish more acute RR MS in an earlier step of MS pathogenesis and should be further investigated. GBS patients have an intrathecal complement activation that seems to occur via the classical pathway.</p>

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.

Introduction: Guillain-Barré syndrome (GBS) is a neurological disease caused by an autoimmune attack on the peripheral nerves. The main symptoms are loss of motor and sensory skills in the upper and lower extremities. Autonomic dysfunction also occurs.Aim: To identify which parameters in neurography examination that are showing pathology at three different stages from the onset of symptoms. To practically perform and evaluate different electrode placements at RR-intervals.Materials and methods: The first part of this study was a retrospective study with results from 58 patients which were diagnosed with GBS in 2010-2020 at the University Hospital in Uppsala. The second part of this study included measurement of the heart rate variation with RR-intervals at different electrode placement in ten healthy volunteers. Results: In part 1 of the project, there were no significant differences between the groups at distal latency in the ulnar nerve, F-latency in the tibial nerve and in the conduction velocity in the sural nerve. However, there were significant differences in the amplitude of the radial nerve. In part 2 of the project, there were significant differences between the electrode placements, and most artifacts were found with electrodes placed on the shoulders.Conclusion: Examination with neurography and RR-intervals plays an important role in the diagnosis of GBS. As the amplitude in the radial nerve was the only one that showed significant differences between the groups, the nerve is recommended to be examined bilaterally. With a high presence of artifacts in RR-intervals with electrodes placed on the shoulders and wrists, placement on the chest is to be recommended.

La structure génétique du fondule barré (Fundulus diaphanus) dans le fleuve Saint Laurent, telle qu'estimée par la variation à huit locus microsatellites, est influencée par des facteurs historiques et contemporains. Premièrement, nous avons montré que la présence d'une zone de contact secondaire entre deux races glaciaires influence le patron d'isolement par la distance global. D'autre part, les signaux génétiques obtenus sont différents dans les zones influencées ou non par la marée, démontrant l'influence de l'hydrographie contemporaine du fleuve sur les mouvements de cette espèce. Dans un deuxième chapitre, nous avons étudié les mouvements de la même espèce à une grande échelle géographique, soit autour de la ville de Québec. En utilisant un système d'informations géographiques permettant de définir des distances qui tiennent compte d'éléments de paysage, nous avons identifié la présence de végétation et de la largeur intertidale comme étant un élément facilitant le flux génique entre populations tandis que les hausses soudaines de profondeur tendent à le restreindre. / Genetic structure of banded killifish (Fundulus diaphanus) in the St. Lawrence River, as estimated by variation at eight microsatellite loci, is influenced by historical and contemporary factors. First, we have shown that secondary contacts between two glacial races influence the global isolation by distance pattern. Furthermore, genetic signal in the tidal and non-tidal sections of the river were different, demonstrating the influence of contemporary waterscape of the St. Lawrence on this species' movements. In a second chapter, we studied the genetic structure at a larger geographical scale, namely around Québec City. Using a geographical information System allowing the integration of waterscape features into distances, we identified vegetation and intertidal width presence as an element facilitating gene flow among killifish populations, while sudden increase in water depth tends to restrict it.

Objetivo: Comparar as relações de custo-efetividade de duas terapias, Imunoglubulina Intravenosa (IgIV) e Plasmaferese (PE), no tratamento da Síndrome de Guillain-Barré sob a perspectiva do sistema público (SUS). O objetivo secundário foi avaliar a adesão às recomendações da Comissão de Medicamentos do HCPA Métodos: estudo transversal com análise econômica de pacientes tratados por Síndrome de Guillain-Barré no período de junho de 2003 a junho de 2008 no Hospital de Clínicas de Porto Alegre (HCPA). Foi realizada análise de custo-efetividade do emprego de IgIV e de PE nestes pacientes, pelo método de minimização de custos, considerando-se somente os custos diretos sanitários, fornecidos pelo sistema gerencial da instituição . Foram excluídos os pacientes que usaram outro tipo de tratamento associado ou isolado. Coletaram-se os dados através da revisão dos prontuários. A gravidade da doença na internação foi classificada como: doença leve, quando caminhar foi possível; doença moderada, quando caminhar foi impossível; doença grave, quando os pacientes necessitaram de ventilação assistida. A incapacidade na alta foi estabelecida pela escala de sete pontos de Hughes. A adesão às recomendações da Comissão de Medicamentos do HCPA, objetivo secundário, foi avaliada através da dose e o esquema de prescrição da IgIV. Resultados: Vinte e cinco participantes (2 a 70 anos) foram incluídos no estudo, cinco tratados com PE, empregando-se Albumina Humana como substituto do plasma, e 20 tratados com IgIV. O custo total do tratamento de um paciente com PE foi R$10.603,88 (± 2.978,12) e o de um que recebeu IgIV foi R$ 32.103,00 (± 21.454,24). O custo total da internação foi de R$45.027,14 (± 32.750,45) para os tratados com PE e de R$ 60.844,28 (±48.590,52) para os que receberam IgIV. Em relação ao desfecho clínico principal, melhora na escala de incapacidade de sete pontos, após o tratamento com uma das alternativas escolhida, a mediana dos pacientes que internaram com grau de gravidade 3 e que foram tratados com PE foi igual a dos que receberam IgIV. Em relação à permanência hospitalar, permanência em UTI e dias de Ventilação Mecânica, não houve diferença estatisticamente significativa entre os dois tratamentos. Conclusões: Quando comparados os custos médios das duas opções terapêuticas, uma delas aparece claramente com menor custo. Quando comparados os desfechos, após o emprego de cada opção terapêutica, estes não revelam diferença. Concluímos que, no HCPA, a opção pelo procedimento Plasmaferese é mais custo efetiva do que o emprego da IgIV. / Objectives: To compare the cost-effectiveness of two distinct therapies, Intravenous Immunoglobulin (IVIg) and Plasma Exchange (PE) in the treatment of Guillain-Barré Syndrome, concerning the public health care system. Compliance to the guidelines of the Pharmacy and Therapeutics Committee of the Hospital de Clínicas de Porto Alegre was a secondary objective. Methods: A cross-sectional, economical analysis was conducted, including patients treated for GBS in the period from June, 2003 through June, 2008 in Hospital de Clínicas de Porto Alegre (HCPA). The cost-effectiveness of the use of IVIg and PE in such patients was studied through the cost minimization method, considering direct medical costs only (2008 currency), yield by the management of the institution. Patients receiving treatments other than PE or IVIg were excluded. Data were collected by chart reviews. Severity of disease on admittance was classified as follows: mild disease, when the patient was able to walk; moderate disease, when the patient was unable to walk, and severe disease, when assisted ventilation was required. Disability on discharge was established by the 7-point scale of Hughes. Compliance to the guidelines of the Pharmacy and Therapeutics Committee was evaluated through the dose and prescription scheme of IVIg. Results: Twenty-five participants (2 to 70 years of age) were included in the study, 5 were submitted to treatment with PE, using human albumin as replacement for plasma, and 20 were treated with IVIg. The total treatment cost for PE in a single patient was US$6,058.85 (±1,701.78 SD), and the same expense for IVIg was US$18,344.57 (± 12,259.56 SD) (p = 0.035). Total inpatient cost was US$25,729.79 (± 18,714.54 SD) in the PE group, and US$34,768.16 (±27,766.01 SD) (p=0.530) in the IVIg group. The main clinical outcome was improvement in the 7-point disability grade scale. The median of that measure in patients admitted with a severity grade 3 treated either with PE and IVIg was the same. Secondary outcomes, such as in-hospital stay, ICU stay, and number of days on mechanical ventilation revealed no statistically significant difference between treatments. Conclusions: As the mean expenses of both therapeutic options are compared, one clearly stands-out as less onerous. Clinical outcomes, when compared, reveal no statistical difference after each treatment. We concluded that, in HCPA, plasma exchange is more cost-effective than intravenous immunoglobulin.

Objetivo: Comparar as relações de custo-efetividade de duas terapias, Imunoglubulina Intravenosa (IgIV) e Plasmaferese (PE), no tratamento da Síndrome de Guillain-Barré sob a perspectiva do sistema público (SUS). O objetivo secundário foi avaliar a adesão às recomendações da Comissão de Medicamentos do HCPA Métodos: estudo transversal com análise econômica de pacientes tratados por Síndrome de Guillain-Barré no período de junho de 2003 a junho de 2008 no Hospital de Clínicas de Porto Alegre (HCPA). Foi realizada análise de custo-efetividade do emprego de IgIV e de PE nestes pacientes, pelo método de minimização de custos, considerando-se somente os custos diretos sanitários, fornecidos pelo sistema gerencial da instituição . Foram excluídos os pacientes que usaram outro tipo de tratamento associado ou isolado. Coletaram-se os dados através da revisão dos prontuários. A gravidade da doença na internação foi classificada como: doença leve, quando caminhar foi possível; doença moderada, quando caminhar foi impossível; doença grave, quando os pacientes necessitaram de ventilação assistida. A incapacidade na alta foi estabelecida pela escala de sete pontos de Hughes. A adesão às recomendações da Comissão de Medicamentos do HCPA, objetivo secundário, foi avaliada através da dose e o esquema de prescrição da IgIV. Resultados: Vinte e cinco participantes (2 a 70 anos) foram incluídos no estudo, cinco tratados com PE, empregando-se Albumina Humana como substituto do plasma, e 20 tratados com IgIV. O custo total do tratamento de um paciente com PE foi R$10.603,88 (± 2.978,12) e o de um que recebeu IgIV foi R$ 32.103,00 (± 21.454,24). O custo total da internação foi de R$45.027,14 (± 32.750,45) para os tratados com PE e de R$ 60.844,28 (±48.590,52) para os que receberam IgIV. Em relação ao desfecho clínico principal, melhora na escala de incapacidade de sete pontos, após o tratamento com uma das alternativas escolhida, a mediana dos pacientes que internaram com grau de gravidade 3 e que foram tratados com PE foi igual a dos que receberam IgIV. Em relação à permanência hospitalar, permanência em UTI e dias de Ventilação Mecânica, não houve diferença estatisticamente significativa entre os dois tratamentos. Conclusões: Quando comparados os custos médios das duas opções terapêuticas, uma delas aparece claramente com menor custo. Quando comparados os desfechos, após o emprego de cada opção terapêutica, estes não revelam diferença. Concluímos que, no HCPA, a opção pelo procedimento Plasmaferese é mais custo efetiva do que o emprego da IgIV. / Objectives: To compare the cost-effectiveness of two distinct therapies, Intravenous Immunoglobulin (IVIg) and Plasma Exchange (PE) in the treatment of Guillain-Barré Syndrome, concerning the public health care system. Compliance to the guidelines of the Pharmacy and Therapeutics Committee of the Hospital de Clínicas de Porto Alegre was a secondary objective. Methods: A cross-sectional, economical analysis was conducted, including patients treated for GBS in the period from June, 2003 through June, 2008 in Hospital de Clínicas de Porto Alegre (HCPA). The cost-effectiveness of the use of IVIg and PE in such patients was studied through the cost minimization method, considering direct medical costs only (2008 currency), yield by the management of the institution. Patients receiving treatments other than PE or IVIg were excluded. Data were collected by chart reviews. Severity of disease on admittance was classified as follows: mild disease, when the patient was able to walk; moderate disease, when the patient was unable to walk, and severe disease, when assisted ventilation was required. Disability on discharge was established by the 7-point scale of Hughes. Compliance to the guidelines of the Pharmacy and Therapeutics Committee was evaluated through the dose and prescription scheme of IVIg. Results: Twenty-five participants (2 to 70 years of age) were included in the study, 5 were submitted to treatment with PE, using human albumin as replacement for plasma, and 20 were treated with IVIg. The total treatment cost for PE in a single patient was US$6,058.85 (±1,701.78 SD), and the same expense for IVIg was US$18,344.57 (± 12,259.56 SD) (p = 0.035). Total inpatient cost was US$25,729.79 (± 18,714.54 SD) in the PE group, and US$34,768.16 (±27,766.01 SD) (p=0.530) in the IVIg group. The main clinical outcome was improvement in the 7-point disability grade scale. The median of that measure in patients admitted with a severity grade 3 treated either with PE and IVIg was the same. Secondary outcomes, such as in-hospital stay, ICU stay, and number of days on mechanical ventilation revealed no statistically significant difference between treatments. Conclusions: As the mean expenses of both therapeutic options are compared, one clearly stands-out as less onerous. Clinical outcomes, when compared, reveal no statistical difference after each treatment. We concluded that, in HCPA, plasma exchange is more cost-effective than intravenous immunoglobulin.

Objetivo: Comparar as relações de custo-efetividade de duas terapias, Imunoglubulina Intravenosa (IgIV) e Plasmaferese (PE), no tratamento da Síndrome de Guillain-Barré sob a perspectiva do sistema público (SUS). O objetivo secundário foi avaliar a adesão às recomendações da Comissão de Medicamentos do HCPA Métodos: estudo transversal com análise econômica de pacientes tratados por Síndrome de Guillain-Barré no período de junho de 2003 a junho de 2008 no Hospital de Clínicas de Porto Alegre (HCPA). Foi realizada análise de custo-efetividade do emprego de IgIV e de PE nestes pacientes, pelo método de minimização de custos, considerando-se somente os custos diretos sanitários, fornecidos pelo sistema gerencial da instituição . Foram excluídos os pacientes que usaram outro tipo de tratamento associado ou isolado. Coletaram-se os dados através da revisão dos prontuários. A gravidade da doença na internação foi classificada como: doença leve, quando caminhar foi possível; doença moderada, quando caminhar foi impossível; doença grave, quando os pacientes necessitaram de ventilação assistida. A incapacidade na alta foi estabelecida pela escala de sete pontos de Hughes. A adesão às recomendações da Comissão de Medicamentos do HCPA, objetivo secundário, foi avaliada através da dose e o esquema de prescrição da IgIV. Resultados: Vinte e cinco participantes (2 a 70 anos) foram incluídos no estudo, cinco tratados com PE, empregando-se Albumina Humana como substituto do plasma, e 20 tratados com IgIV. O custo total do tratamento de um paciente com PE foi R$10.603,88 (± 2.978,12) e o de um que recebeu IgIV foi R$ 32.103,00 (± 21.454,24). O custo total da internação foi de R$45.027,14 (± 32.750,45) para os tratados com PE e de R$ 60.844,28 (±48.590,52) para os que receberam IgIV. Em relação ao desfecho clínico principal, melhora na escala de incapacidade de sete pontos, após o tratamento com uma das alternativas escolhida, a mediana dos pacientes que internaram com grau de gravidade 3 e que foram tratados com PE foi igual a dos que receberam IgIV. Em relação à permanência hospitalar, permanência em UTI e dias de Ventilação Mecânica, não houve diferença estatisticamente significativa entre os dois tratamentos. Conclusões: Quando comparados os custos médios das duas opções terapêuticas, uma delas aparece claramente com menor custo. Quando comparados os desfechos, após o emprego de cada opção terapêutica, estes não revelam diferença. Concluímos que, no HCPA, a opção pelo procedimento Plasmaferese é mais custo efetiva do que o emprego da IgIV. / Objectives: To compare the cost-effectiveness of two distinct therapies, Intravenous Immunoglobulin (IVIg) and Plasma Exchange (PE) in the treatment of Guillain-Barré Syndrome, concerning the public health care system. Compliance to the guidelines of the Pharmacy and Therapeutics Committee of the Hospital de Clínicas de Porto Alegre was a secondary objective. Methods: A cross-sectional, economical analysis was conducted, including patients treated for GBS in the period from June, 2003 through June, 2008 in Hospital de Clínicas de Porto Alegre (HCPA). The cost-effectiveness of the use of IVIg and PE in such patients was studied through the cost minimization method, considering direct medical costs only (2008 currency), yield by the management of the institution. Patients receiving treatments other than PE or IVIg were excluded. Data were collected by chart reviews. Severity of disease on admittance was classified as follows: mild disease, when the patient was able to walk; moderate disease, when the patient was unable to walk, and severe disease, when assisted ventilation was required. Disability on discharge was established by the 7-point scale of Hughes. Compliance to the guidelines of the Pharmacy and Therapeutics Committee was evaluated through the dose and prescription scheme of IVIg. Results: Twenty-five participants (2 to 70 years of age) were included in the study, 5 were submitted to treatment with PE, using human albumin as replacement for plasma, and 20 were treated with IVIg. The total treatment cost for PE in a single patient was US$6,058.85 (±1,701.78 SD), and the same expense for IVIg was US$18,344.57 (± 12,259.56 SD) (p = 0.035). Total inpatient cost was US$25,729.79 (± 18,714.54 SD) in the PE group, and US$34,768.16 (±27,766.01 SD) (p=0.530) in the IVIg group. The main clinical outcome was improvement in the 7-point disability grade scale. The median of that measure in patients admitted with a severity grade 3 treated either with PE and IVIg was the same. Secondary outcomes, such as in-hospital stay, ICU stay, and number of days on mechanical ventilation revealed no statistically significant difference between treatments. Conclusions: As the mean expenses of both therapeutic options are compared, one clearly stands-out as less onerous. Clinical outcomes, when compared, reveal no statistical difference after each treatment. We concluded that, in HCPA, plasma exchange is more cost-effective than intravenous immunoglobulin.

Both Multiple Sclerosis (MS) and Guillan-Barré syndrome (GBS) are neurological inflammatory demyelinating autoimmune diseases, with a probable antibody contribution. Complement proteins in both MS and GBS does play a role in inflammation and demyelination at pathogenesis, according to earlier scientific evidence. The aim of this examination project work was to investigate systemic and intrathecal complement activation in MS and GBS, to gain further knowledge that might be useful for development of future therapeutics targeting immune responses during those diseases. An additional aim was to develop a new ELISA method for detection of complement iC3. By using sandwich ELISA, complement proteins C1q, C4, C3, fH and C3a were measured in plasma and cerebrospinal fluid (CSF) from persons within 4 different diagnostic groups; MS, other neurological diseases (OND), GBS and controls (C). An ELISA method to detect iC3 (hydrolysed C3) was also developed, including usage of SDS-PAGE. Results based on raw data and statistical analysis show significantly elevated levels of C3a (C3a/C3) in MS and decreased C3 in plasma. In CSF low levels of C4 and C3a/C3 in MS were detected, though correlation of C3a and C1q was positive. GBS reveal high levels of all complement proteins analysed in CSF except for C3, and a positive correlation of C3a and C1q as well as C3a and fH was found. These results indicate that MS patients have systemic complement activation; however the activation pathway is not determined. Complement activation in MS may also occur intrathecally, with correlation analysis indicating a possible activation via the classical pathway. MS patients suffering from a more acute relapsing-remitting (RR) MS have a more prominent systemic complement activation compared to MS patients responding to beta-interferon treatment. Systemic increased C3a/C3 ratio may be a possible biomarker to distinguish more acute RR MS in an earlier step of MS pathogenesis and should be further investigated. GBS patients have an intrathecal complement activation that seems to occur via the classical pathway.