Thesis (M.S.)--University of Wisconsin--Madison, 1981. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 57-59).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 219-228).

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1964. / Includes bibliographical references (p. 81-82).

Orientador: Eliana Marisa ganem / Resumo: A espasticidade leva a perda na qualidade de vida, capacidade funcional do indivíduo e a alterações psicossociais. O baclofeno é fármaco relaxante muscular de ação central, utilizado no tratamento da espasticidade e é substância análoga ao ácido gama amino-butírico (GABA). Sua administração por via subaracnoidea permite que doses pequenas sejam utilizadas, minimizando efeitos adversos. A pesquisa consistiu em determinar os efeitos da administração de baclofeno em dose única, no espaço subaracnoideo de coelhos, sobre a medula espinal e as meninges. Foram utilizados coelhos, divididos em três grupos: G1, G2 e G3, com injeção no espaço subaracnoideo de soro fisiológico, baclofeno 100 μg e 200 μg respectivamente. Posteriormente foram realizadas as análises histológicas das meninges e medula dos coelhos. Os resultados da presente pesquisa mostram que o baclofeno, independe da dose administrada, causou lesão de tecido nervoso e de meninges em 20% (n=8) dos coelhos estudados. As alterações histológicas foram predominantemente observadas na região posterior das meninges. Podemos concluir que neste modelo experimental em coelhos o baclofeno desencadeou reação inflamatória no tecido nervoso e nas meninges. / Abstract: Spasticity leads to a reduced quality of life, functional capacity limitations, and changes in the psychosocial well-being of an individual. Baclofen is a centrally acting muscle relaxant that is used in the treatment of spasticity and is an analog of gammaamino-butyric acid. Its administration via the subarachnoid route allows the use of small doses, thus minimizing adverse effects. The aim of the study was to determine the effects of administration of a single dose of baclofen into the subarachnoid space of rabbits, on the spinal cord and meninges. Methods: The rabbits were divided into three groups. The first group (G1) was injected with saline solution. The second and third groups (G2 and G3) received 100 and 200 μg of baclofen in the subarachnoid space, respectively. Histological analysis of the meninges and spinal cord in rabbits was subsequently performed. The present findings showed that baclofen, regardless of the administered dose, caused damage to the nerve tissue and meninges in 20% (n = 8) of the tested rabbits. The histological changes were predominantly observed in the posterior portion of the meninges. We conclude that, in this rabbit experimental model, baclofen caused an inflammatory reaction in the nervous tissue and meninges. / Doutor

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nÃo hà / Background: Botulinum toxin type A (BTX-A), one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release and is a well-known treatment for poststroke spasticity, despite some variations among dose protocols. Spasticity is one of the factors that affect the functional rehabilitation process in stroke. Spasticity arises from the loss of myotatic reflex inhibition, resulting from upper motor neuron lesion. Equinus foot is common in lower limb spasticity after stroke worsening gait pattern and functional independence. The objective of this study is to evaluate the effects of BTX-A different doses on spastic foot in stroke patients in rehabilitation programme and on gait velocity and functional independence of these patients. Methods: This study was a randomized, prospective and double blind trial. Patients were recruited if they had diagnosis of stroke (ischemic or hemorrhagic) with a poststroke period of at least six months and hemiparesis with spastic equinus foot (Ashworth score 3 or 4 in a range from 0 to 5). Twenty-one hemiparetic stroke patients enrolled in a rehabilitation programme were divided into two groups. The first group (n=11) received BTX-A 300UI in spastic foot and the second group (n=10) received BTX-A 100UI. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for passive range of motion for ankle joint, Modified Ashworth Score, time walking 10 meters, clonus score and motor score of Functional Independence Measure (mFIM). Results: Higher dose group had significant improvement in range of motion on week 12 (p=0,021) and in Ashworth score on weeks 8 (p=0,012) and 12 (p < 0,0001) compared with lower dose group. There was slight improvement in clonus score in higher dose group on week 12 without statistical significance. Both groups had improvement in time walking 10 meters and mFIM without significant difference between them in the analyzed sample. There was no significant adverse effect. Conclusions: BTX-A is an important tool in poststroke rehabilitation for spasticity parameters improvement, but there was no significant difference between high and low doses of BTX-A for gait velocity neither for functional independence in the analyzed sample. Future studies with larger number of patients and evaluation of response to BTX-A reapplications are necessary to confirm these findings. / IntroduÃÃo: A toxina botulÃnica tipo A (TbA), uma das mais potentes toxinas biolÃgicas, age atravÃs do bloqueio da transmissÃo neuromuscular via inibiÃÃo da liberaÃÃo de acetilcolina e à um tratamento bem-estabelecido para espasticidade pÃs-AVE, apesar de variaÃÃes entre os protocolos de doses em diferentes centros. Espasticidade à um dos fatores que interferem no processo de reabilitaÃÃo funcional apÃs acidente vascular encefÃlico (AVE). Ela surge por causa da perda da inibiÃÃo do reflexo miotÃtico, resultante de lesÃo do neurÃnio motor superior. O pà equino à comum na espasticidade de membro inferior depois do AVE e sua instalaÃÃo piora o padrÃo de marcha e a independÃncia funcional. O objetivo desse estudo à avaliar os efeitos da TbA em diferentes doses sobre o pà espÃstico de pacientes com sequela de AVE inseridos em programa de reabilitaÃÃo e sobre a velocidade de marcha e independÃncia funcional desses pacientes. Metodologia: Este estudo foi realizado atravÃs de ensaio randomizado, prospectivo e duplo cego. Foram recrutados pacientes com diagnÃstico de AVE (isquÃmico ou hemorrÃgico) com perÃodo pÃs-AVE de pelo menos seis meses e hemiparesia com pà equino espÃstico (escore Ashworth 3 ou 4 em uma escala de 0 a 5). Vinte e um pacientes hemiparÃticos pÃs-AVE inseridos em programa de reabilitaÃÃo foram divididos em dois grupos. O primeiro grupo (n=11) recebeu aplicaÃÃo de 300UI de TbA no pà espÃstico e o segundo grupo (n=10) recebeu 100UI de TbA. Todos os pacientes foram avaliados no tempo zero e 2, 4, 8 e 12 semanas apÃs a injeÃÃo quanto aos seguintes parÃmetros: amplitude de movimento passivo da articulaÃÃo do tornozelo, escala de Ashworth modificada, tempo para andar 10 metros, escore clÃnus de aquileu e escore motor da Medida de IndependÃncia Funcional (MIFm). Resultados: O grupo 300UI TbA teve melhora significativa da amplitude de movimento na 12 semana (p=0,021) e da escala de Ashworth nas 8 (p=0,012) e 12 (p < 0,0001) semanas em comparaÃÃo ao grupo 100UI TbA. Houve tendÃncia à melhora do escore clÃnus na 12 semana no grupo 300UI TbA. Ambos os grupos apresentaram melhora durante o estudo no tempo para andar 10 metros e da MIFm sem diferenÃa significativa entre eles. NÃo foram observados efeitos adversos significativos no decorrer do estudo. ConclusÃes: TbA à uma importante ferramenta na reabilitaÃÃo pÃs-AVE para melhora dos parÃmetros de espasticidade, mas nÃo houve diferenÃa significativa entre dose alta e baixa de TbA para parÃmetros funcionais (velocidade de marcha e independÃncia funcional), na amostra analisada. Estudos futuros com um nÃmero maior de pacientes e avaliaÃÃo de resposta a reaplicaÃÃes de TbA sÃo necessÃrios para confirmaÃÃo desses achados.

Multipel Skleros (MS) är en kronisk autoimmun och neurodegenerativ sjukdom som drabbar det centrala nervsystemet och det är en av de vanligaste orsakerna till funktionsnedsättning hos medelålders och unga vuxna. Ett vanligt symptom är spasticitet som drabbar runt 60% av alla MS-sjuka. Tillståndet leder till stelhet, smärta, spasmer och nedsatt rörlighet. Spasticitet är svårbehandlat och existerande behandlingar ger ofta otillräcklig effekt eftersom den dos som krävs för symptomlindring kan ge svårtolererade biverkningar. Detta litteraturarbete hade som syfte att undersöka hur effektivt det nya cannabisbaserade läkemedlet Sativex är mot spasticitet. Fem olika randomiserade och placebo-kontrollerade studier från databasen Pubmed valdes ut och granskades. Gemensamt för dem var att patientskattade skalor användes som primära effektmått och att studiepopulationen var likartad. I den första studien undersöktes Sativex effekt på flera olika MS-symptom, men det var endast för spasticitet som en signifikant skillnad erhölls (p=0,001). De två följande studierna var snarlika varandra, men det var bara i en av dem som ITT-analysen för det primära effektmåttet visade att Sativex var signifikant överlägset placebo som behandling mot spasticitet (p=0,048 respektive p=0,219). Till den fjärde studien valdes de patienter ut som i en inledningsfas bedömts svara på behandling med Sativex. Resultatet i den studien visade på starkare signifikant skillnad jämfört med de andra studierna (p=0,0002). Den sista studien var en utsättningsstudie och resultaten från den visade att risken för behandlingssvikt var tre gånger högre för de som erhållit placebo jämfört med Sativex (p=0,013). Sett till gruppnivå var resultaten från några av studierna relativt blygsamma, vilket kan bero på att alla patienter inte svarade på behandlingen. De som svarar på behandlingen gör dock oftast det inom fyra veckor så för enskilda patienter kan läkemedlet vara till nytta och väl värt ett behandlingsförsök.

A espasticidade é uma das alterações decorrentes do Acidente Vascular Encefálico (AVE) que causa limitação no tônus muscular podendo gerar graves comprometimentos funcionais nos membros superiores. Pela característica do tecido neurológico lesado, frequentemente ocorre a cronificação das sequelas e incapacidades e atuar na minimização desses comprometimentos é objetivo dos profissionais da saúde. No entanto, há dificuldades na escolha da intervenção, análise de sua eficácia e aprimoramento dos estudos na área da reabilitação decorrentes da limitação nas estratégias de avaliação, sendo que nessa área as escalas são utilizadas com frequência. Dessa forma, esse estudo buscou desenvolver e validar a utilização clínica de um instrumento de medida da resistência isométrica ao estiramento passivo do grupo muscular flexor do punho em adultos e idosos com espasticidade decorrente do AVE. Foi desenvolvido um instrumento portátil capaz de medir a resistência da musculatura com um torquímetro. Foram realizados testes para analisar a validade, confiabilidade, sensibilidade e praticabilidade. Os testes foram feitos com os sujeitos sentados e com o antebraço e mão fixados no aparelho em seis diferentes posições do arco do movimento do punho, sendo que a articulação permaneceu estável por 20 segundos em cada posição. Foi realizada a avaliação de 108 sujeitos. A avaliação unilateral foi realizada em 21 sujeitos sem lesão neurológica e 27 sujeitos com AVE. A avaliação bilateral por dois examinadores foi realizada em 60 sujeitos, sendo 19 sem lesão e 41 com lesão neurológica. O instrumento mostrou-se capaz de mensurar as diferenças da resistência da musculatura em cinco das seis posições sendo relevante salientar que o instrumento foi sensível para apresentar a diferença entre população normal e com lesão e posteriormente apresentando a diferença entre lado comprometido e não comprometido. Os testes inter-examinadores mostraram boa correlação, no entanto, considerou-se a distribuição da segunda avaliação mais uniforme, sugerindo que se deve padronizar o uso para que o examinador realize a sequência de avaliação do arco do movimento por, no mínimo, duas vezes. Evidenciou-se ainda que o instrumento foi sensível para graduar a intensidade da sequela utilizando-se da comparação entre o lado não comprometido e o comprometido, sempre que a sequela seja apenas do hemicorpo visto que a graduação atribuída pela Escala Modificada de Ashworth possibilitou identificar correlação com as resistências apenas na avaliação grau 3, sendo que nos demais graus, não houve evidência estatística, corroborando com os também apresentados na literatura. Sugere-se, como continuidade do estudo, correlacionar os dados obtidos da avaliação da resistência estática à dinâmica. Esse instrumento desenvolvido pode ser utilizado para avaliação dos efeitos de órteses posicionadoras de punho, contribuindo assim, para o aprimoramento das estratégias de reabilitação. / Spasticity is one of the changes resulting from stroke which causes limitation in muscle tone and may cause severe functional impairment of the upper limbs. For the feature damaged neurological tissue often occurs chronicity of disabilities and act on these commitments is minimization objective of health professionals. However, there are difficulties in the choice of intervention, analysis and improvement of its effectiveness studies in rehabilitation due to limitations in assessment strategies, and this area scales are frequently used. Thus, this study sought to develop and validate the clinical use of an instrument for measuring isometric resistance to passive stretching of the wrist flexor muscle group in adult and elderly patients with spasticity due to stroke. We developed a portable instrument capable of measuring the muscular strength of a torquemeter. Tests were conducted to examine the validity, reliability, sensitivity and practicability. Tests were performed with the subjects seated with the forearm and hand set in the apparatus in six different positions of the arc of movement of the wrist, and the joint remained stable for 20 seconds at each position. Our evaluation of 108 subjects. The evaluation was performed unilaterally in 21 subjects without neurological injury and 27 subjects with stroke. A bilateral assessment by two examiners was performed in 60 subjects, 19 with and 41 without injury neurological injury. The instrument was able to measure differences in muscle strength in five of the six positions is important to note that the instrument was sensitive to show the difference between normal population and with injury and presents the difference between the affected and non-affected. The tests showed good inter-rater correlation, however, was considered a distribution more uniform the second evaluation, suggesting that it should use to standardize the examiner performs the evaluation sequence of the arc of movement by at least twice . It is further demonstrated that the instrument was sensitive to grade the intensity of the sequel using comparing the committed and uncommitted side where the sequel of the hemisphere is only seen that the graduation given by the Modified Ashworth Scale possible to identify a correlation with resistance only in the evaluation grade 3, and in the remaining degrees, there was no statistical evidence, corroborating also presented in the literature. It is suggested, as a continuation of the study, correlate data obtained from the evaluation of the resistance to static dynamic. This tool developed can be used to assess the effects of splint of wrist, thus contributing to the improvement of rehabilitation strategies.

For many decades people working with spastic patients have searched for better methods of alleviating spasticity and its debilitating effects. Although many methods have been used, no single method has been completely successful. It was not until the nineteen seventies that Selective Posterior Lumbar Rhizotomy (SPLR) was used successfully with spastic patients. In 1980 Peacock started doing this procedure on a large number of spastic patients in South Africa. I became interested in SPLR after seeing the dramatic reduction in spasticity and the improvement in function in my patients who had undergone the procedure. Since observations of improvement up to this point had been subjective, I decided to measure and document the physical status of patients before and after surgery. Twenty-nine patients who underwent Selective Posterior Lumbar Rhizotomy in 1985 were studied. In order to be as objective as possible, crawling and gait analyses were done in addition. All the patients were assessed clinically two days prior to surgery and then between four and fourteen months after surgery. For both preoperative and postoperative assessments, resistance to passive movement, degree of joint stiffness, ability to initiate and inhibit voluntary movement, and the degree of abnormal function in the developmental positions (rolling, sitting, kneeling, crawling, standing and walking) were graded on rating scales. Analyses of gait and crawling were done using a digital camera system. Results of the study indicated that SPLR produced a statistically significant reduction in muscle tone and in joint stiffness. Improvements in voluntary movement and functional movement (rolling, sitting, kneeling, crawling, standing and walking) were also statistically significant. It was concluded that Selective Posterior Lumbar Rhizotomy is a useful method of reducing spasticity and results in improvement of the quality of life in patients with spastic cerebral palsy.

Multiple sclerosis (MS) is a chronic neurological disease where immune cells from the periphery enter the central nervous system and attack the myelin sheaths resulting in damage to the axons. It is an unpredictable disease that affects each person differently. One of the symptoms of MS includes muscle spasticity and depending on the severity it can cause gait and mobility issues. Oral baclofen is the first-line recommendation to treat spasticity in people with MS whose treatment goals include improving mobility or easing pain and discomfort. Baclofen works pre- and post-synaptically as a gamma aminobutyric acid-B agonist at the spinal cord to reduce the amount of excitatory neurotransmitters that are responsible for muscle contractions. Oral baclofen has been used to treat spasticity, however its short half-life of 2-6 hours warrants its need for three times a day dosing schedule. The multiple daily dosing can be a burden to the patient taking it and for the caregiver who will be giving the medication which can negatively affect adherence and acceptability. The goal of the current study was to design and assess baclofen loaded dissolving microneedle (MN) patch on the amount permeated and sustained delivery of baclofen in the management of spasticity. A 1.5 mg/mL MN patch was initially made by dissolving baclofen in polyvinylpyrrolidone (PVP) and fabricated using the mold casting technique. The permeation profile of fabricated baclofen loaded MNs over a predetermined time was assessed in vitro through dermatomed porcine ear skin using Franz Diffusion cells. Employing the use of MNs significantly increased the flux from 2.10 ± 0.35 µg/sq.cm/h to 5.92 ± 4.17 µg/sq.cm/h and the average cumulative amount permeated from 92.67 ± 11.25 µg/sq.cm to 457.11 ± 111.47 µg/sq.cm over 72 h (p<0.05). However, because of baclofen’s hydrophilic nature, drug permeation across skin is limited, so a nanosuspension with reduced particle size was formulated to be used for MN fabrication to increase drug loading and permeation. Baclofen was formulated into a suspension through wet media milling followed by mechanical homogenization using PVP K30 and sodium dodecyl sulfate as stabilizers. The suspension was successfully loaded in dissolving PVP-based MNs. The donor chamber of the cell contained the MN patch mounted onto the porcine skin and the receptor chamber contained phosphate buffered saline. The receptor was sampled over 72 h and analyzed using HPLC. The baclofen suspension loaded MNs produced an average drug flux of 26.51 ± 4.17 µg/sq.cm/h and an average cumulative amount of 1718.96 ± 217.12 µg/sq.cm over 72 h. The use of suspension loaded MNs was found to enhance the permeation and produce a sustained delivery of baclofen across skin and depicts the applicability of fabricated needles for sustained delivery in the management of muscle spasticity in multiple sclerosis.