Magister Scientiae (Physiotherapy) - MSc(Physio) / Background: Erb's Palsy results from excessive displacement of the head during birth causing traction on the Brachial plexus. In order to define optimal management for Erb's Palsy, reliable data is needed. Aim: The aim of the study was therefore to determine the profile of and caregiver experiences of infants with Erb' Palsy seen at Groote Schuur Hospital. Method: The study was carried out at Groote Schuur Hospital (GHS) in the Western Cape, South Africa. The study used both quantitative and qualitative approaches. A record review was conducted to collect quantitative data which was retrieved from patient files and captured on a data extraction sheet. A convenient sample of caregivers of children with Erb's Palsy were recruited and interviewed for the qualitative component of the study. Quantitative data was analyzed and presented in tables, figures and qualitative data was analyzed thematic and presented narratively. Ethical approval was obtained from the Ethics Committee at the University of the Western Cape and the University of Cape Town. In addition, permission was obtained from the hospital management. Results: The total sample size for the quantitative part was ninety-six (96) files of children with Erb's Palsy. The mean age of the study sample was 3.8 months. The majority (53.1%) of the participants received a mean of 4.1 (SD=1.7) physiotherapy session. In the qualitative phase eight participants were interviewed. Analysis of qualitative data yielded three themes including "experience of mothers as it relates to Erb's Palsy", "mothers' engagement with health care providers" and "personal and environmental factors". Conclusion: The study within this setting indicated that Erb's Palsy was most common among females. The most common documented forms of physiotherapy techniques provided for children with Erb's Palsy in setting were stretching and strengthening exercises as well as therapeutic massage. exercise. Caring for a child with Erb's Palsy resulted in emotional challenges experienced by the mothers of these children.

The rat model of cervical dorsal root injury mimics the avulsion of dorsal roots in humans following brachial plexus injury, a condition that leads to debilitating sensory disturbances and intractable neuropathic pain that is not amenable to repair. This injury disrupts sensory inputs from the dorsal roots to the spinal cord and the damaged axons do not regenerate across the PNS-CNS interface, the dorsal root entry zone. This thesis investigated the role of OECs for repairing DRI-associated neuropathic pain, which has never been previously explored. Chapter 2 of this thesis characterised two DRI models, a partial (2-root) or complete (4-root) deafferentation of the rat forepaw. The 2-root animals developed persistent allodynia and hyperalgesia, whereas in the 4-root DRI, in contrast, reduced sensation (desensitisation) was found within the affected forepaw. The degree of deficits on performing complex, skilled forepaw movements was proportional to the severity of DRI. Sensory control of forepaw movements was permanently abolishes in animals with 4-root DRI. With the goal of repairing DRI-associated neuropathic pain, the efficacy of genetically modified OECs that carry a novel GDNF construct was examined. These modified GDNF-OECs were able to produce GDNF in vitro, however, died rapidly and failed to yield long term GDNF expression after both acute and delayed transplantation into the DRI spinal cord. Unmodified plain OECs were then used. The results show that delayed transplantation of OECs attenuated the development of DRI-associated allodynia and hyperalgesia. Central reorganisations occurred within the dorsal horn following DRI, including reduction in the area of deep dorsal horn, permanent depletion of IB4-labeled axons and restoration of CGRP-labelled afferents in the denervated superficial laminae. The development of neuropathic pain is suggested to be mediated by the aberrant expansion of large myelinated VGLUT1-positive afferents into the superficial laminae, which normally receive nociceptive inputs. The effect of OECs on modulating nociception seems to be mediated by factors other than inhibition of afferent sprouting. In conclusion, the results in this thesis demonstrated the potential effect of OECs for modulating DRI-associated neuropathic pain. This finding could have clinical applicability for resistant pain sequelae resulting from neurotrauma.

Traumatic injuries to the spinal cord and brachial plexus induce a significant inflammatory response in the nervous tissue with progressive degeneration of neurons and glial cells, and cause considerable physical and mental suffering in affected patients. This thesis investigates the effects of the antioxidants N-acetyl-cysteine (NAC) and acetyl-L- carnitine (ALC) on the survival of motoneurons in the brainstem and spinal cord, the expression of pro-apoptotic and pro-inflammatory cell markers, axonal sprouting and glial cell reactions after spinal hemisection in adult rats. In addition, a novel MRI protocol has been developed to analyse the extent of neuronal degeneration in the spinal cord. Rubrospinal neurons and tibial motoneurons were pre-labelled with the fluorescent tracer Fast Blue one week before cervical C3 or lumbar L5 spinal cord hemisection. The intrathecal treatment with the antioxidants NAC (2.4mg/day) or ALC (0.9 mg/day) was initiated immediately after injury using Alzet2002 osmotic mini pumps. Spinal cord injury increased the expression of apoptotic cell markers BAX and caspase 3, induced significant degeneration of rubrospinal neurons and spinal motoneurons with associated decrease in immunoreactivity for microtubule-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker glial fibrillary acidic protein and microglial markers OX42 and ED1 was markedly increased. Treatment with NAC and ALC attenuated levels of BAX, caspase 3, OX42 and ED1 expression after 2 weeks postoperatively. After 4-8 weeks of continuous intratheca ltreatment, NAC and ALC rescued approximately half of the rubrospinal neurons and spinal motoneurons destined to die, promoted axonal sprouting, restored the density of MAP2 and synaptophysin immunoreactivity and reduced the microglial reaction. However, antioxidant therapy did not affect the reactive astrocytes in the trauma zone. The inflammation modulating properties of ALC were also studied using cultures of human microglial cells. ALC increased the microglial production of interleukin IL-6 and BDNF, thereby possibly mediating the anti-inflammatory and pro-regenerative effects shown in vivo. To study degeneration in the spinal cord following pre-ganglionic and post-ganglionic brachial plexus injuries, adult rat models of ventral root avulsion and peripheral nerve injury were used. A novel MRI protocol was employed and the images were compared to morphological changes found in histological preparations. Ventral root avulsion caused degeneration of dendritic branches and axonal terminals in the spinal cord, followed by significant shrinkage of the ventral horn. Extensive astroglial and microglial reactions were detected in the histological preparations. Peripheral nerve injury reduced the density of dendritic branches but did not cause shrinkage of the ventral horn. Quantitative analysis of MRI images demonstrated changes in the ventral horn following ventral root avulsion only, thus validating the developed MRI technique as a possible tool for the differentiation of pre-ganglionic and post-ganglionic nerve injuries.

O uso de robôs como auxiliares na reabilitação, tanto para ganho de função, como para auxiliar na realização de atividades, é encontrado na literatura em estudos envolvendo acidente vascular encefálico. Diversos dispositivos robóticos têm sido desenvolvidos ao longo da última década para oferecer treinamento sensório-motor direcionado para pacientes com doenças neurológicas, como acidente vascular encefálico, propiciando melhora no desempenho motor dos membros superiores nesta população. Poucos estudos são encontrados sobre o uso de robôs em lesão do plexo braquial ou lesão na medula espinhal. Além disso, há pouca produção nacional relacionada a esse tema. Esse trabalho objetivou-se avaliar o uso de um instrumento robótico, Robô MOREw, que foi desenvolvido pela Escola de Engenharia de São Carlos - EESC - USP com o intuito de facilitação e ganho nos movimentos de flexão e extensão de punho. Dessa forma, pretendia-se a verificação do funcionamento do robô como auxiliar de reabilitação através de testes clínicos e sua aplicabilidade com indivíduos que sofreram lesão do plexo braquial ou lesão na medula espinhal. A metodologia escolhida é de Projeto de Produto que utiliza como proposta a divisão do projeto em quatro fases, sendo estas: projeto informacional, projeto conceitual, projeto preliminar e projeto detalhado. Foi dado enfoque ao projeto detalhado em testes de laboratório e clínicos para verificação do funcionamento e aplicabilidade do robô com voluntários. O estudo foi composto por 2 fases: FASE 1 - Adequação do MOREw: 10 participantes sem comprometimentos nos membros superiores e sem lesões associadas verificaram o funcionamento do robô. Após isso, modificações necessárias foram efetuadas. FASE 2 - Aplicabilidade do MOREw: Teste com 5 participantes que apresentaram diminuição do movimento no Membro Superior, sendo 3 com lesão do plexo braquial e 2 com lesão na medula espinhal que jogaram por 30 minutos uma vez por semana, durante 12 semanas. Nos resultados notou-se que as adequações do robô MOREw foram de extrema importância para o funcionamento adequado do equipamento robótico utilizado por sujeitos com limitação dos movimentos de membros superiores, tanto em relação à ergonomia, funcionamento do jogo e possibilidades de ajustes em programas de reabilitação. Os sujeitos que fizeram uso por 3 meses referiram grande satisfação, motivação e demonstraram maior empenho na reabilitação com o auxílio robótico, que foram corroborados pelos testes funcionais que apresentaram discreta melhora em relação à Amplitude de Movimento e Força Muscular dos membros superiores, além da melhora na pontuação na Escala Específica do Paciente. Assim, MOREw é uma opção a ser utilizada na reabilitação com sujeitos com LM e LPB. / The use of robots as aid in rehabilitation to gain function or to assist in activities performance is found in the literature involving stroke. Several robotic devices have been developed over the last decade to provide sensory-motor training in patients with neurological diseases such as stroke, leading to improvement in motor performance of the upper limbs in this population. Few studies using robot assistance are found in injuries like brachial plexus (BPI) or spinal cord (SCI). In addition, there is little national production related to this topic. The aim of this work was to evaluate the use of a robotic instrument, Robot MOREw, which was developed by the Engineering School of São Carlos - EESC - USP with the purpose to facilitate and/or gain wrist flexion and extension movements. Thus, it was intended to verify the functioning of the robot as a rehabilitation aid through clinical tests, and its applicability with individuals who suffered BPI or SCI. The methodology chosen was the Project Product Design that consists of four phases: informational, conceptual, preliminary and detailed project. This study focuses on the detailed project, which was tested at laboratory as well as with volunteers in clinical trials to verify the robot applicability and operation. The study consisted of 2 phases: Phase 1 - Adequacy: 10 participants with no involvement in the upper limbs and without associated lesions verified the robot functionality. After that, changes were made to the equipment. Phase 2 - Applicability: Tested with 5 participants who had decreased movement in the Upper Limb, 3 with BPI and 2 with SCI, using it 30 min once a week for 12 weeks. It was noticed that the MOREw adjustments were of extreme importance for the correct functionality of the equipment that was used by clients with upper limb deficit movements, regarding ergonomics aspects, game functioning and rehabilitation programs adjustments. The clients who used it for 3 months reported great satisfaction, motivation and demonstrated greater commitment to rehabilitation with robotic assistance, confirmed by functional tests that showed a slight improvement in relation to the range of motion and muscular strength of the upper limbs, besides the improvement on the Patient Specific Scale. MOREw can be an option for BPI and SCI rehabilitation.

O uso de robôs como auxiliares na reabilitação, tanto para ganho de função, como para auxiliar na realização de atividades, é encontrado na literatura em estudos envolvendo acidente vascular encefálico. Diversos dispositivos robóticos têm sido desenvolvidos ao longo da última década para oferecer treinamento sensório-motor direcionado para pacientes com doenças neurológicas, como acidente vascular encefálico, propiciando melhora no desempenho motor dos membros superiores nesta população. Poucos estudos são encontrados sobre o uso de robôs em lesão do plexo braquial ou lesão na medula espinhal. Além disso, há pouca produção nacional relacionada a esse tema. Esse trabalho objetivou-se avaliar o uso de um instrumento robótico, Robô MOREw, que foi desenvolvido pela Escola de Engenharia de São Carlos - EESC - USP com o intuito de facilitação e ganho nos movimentos de flexão e extensão de punho. Dessa forma, pretendia-se a verificação do funcionamento do robô como auxiliar de reabilitação através de testes clínicos e sua aplicabilidade com indivíduos que sofreram lesão do plexo braquial ou lesão na medula espinhal. A metodologia escolhida é de Projeto de Produto que utiliza como proposta a divisão do projeto em quatro fases, sendo estas: projeto informacional, projeto conceitual, projeto preliminar e projeto detalhado. Foi dado enfoque ao projeto detalhado em testes de laboratório e clínicos para verificação do funcionamento e aplicabilidade do robô com voluntários. O estudo foi composto por 2 fases: FASE 1 - Adequação do MOREw: 10 participantes sem comprometimentos nos membros superiores e sem lesões associadas verificaram o funcionamento do robô. Após isso, modificações necessárias foram efetuadas. FASE 2 - Aplicabilidade do MOREw: Teste com 5 participantes que apresentaram diminuição do movimento no Membro Superior, sendo 3 com lesão do plexo braquial e 2 com lesão na medula espinhal que jogaram por 30 minutos uma vez por semana, durante 12 semanas. Nos resultados notou-se que as adequações do robô MOREw foram de extrema importância para o funcionamento adequado do equipamento robótico utilizado por sujeitos com limitação dos movimentos de membros superiores, tanto em relação à ergonomia, funcionamento do jogo e possibilidades de ajustes em programas de reabilitação. Os sujeitos que fizeram uso por 3 meses referiram grande satisfação, motivação e demonstraram maior empenho na reabilitação com o auxílio robótico, que foram corroborados pelos testes funcionais que apresentaram discreta melhora em relação à Amplitude de Movimento e Força Muscular dos membros superiores, além da melhora na pontuação na Escala Específica do Paciente. Assim, MOREw é uma opção a ser utilizada na reabilitação com sujeitos com LM e LPB. / The use of robots as aid in rehabilitation to gain function or to assist in activities performance is found in the literature involving stroke. Several robotic devices have been developed over the last decade to provide sensory-motor training in patients with neurological diseases such as stroke, leading to improvement in motor performance of the upper limbs in this population. Few studies using robot assistance are found in injuries like brachial plexus (BPI) or spinal cord (SCI). In addition, there is little national production related to this topic. The aim of this work was to evaluate the use of a robotic instrument, Robot MOREw, which was developed by the Engineering School of São Carlos - EESC - USP with the purpose to facilitate and/or gain wrist flexion and extension movements. Thus, it was intended to verify the functioning of the robot as a rehabilitation aid through clinical tests, and its applicability with individuals who suffered BPI or SCI. The methodology chosen was the Project Product Design that consists of four phases: informational, conceptual, preliminary and detailed project. This study focuses on the detailed project, which was tested at laboratory as well as with volunteers in clinical trials to verify the robot applicability and operation. The study consisted of 2 phases: Phase 1 - Adequacy: 10 participants with no involvement in the upper limbs and without associated lesions verified the robot functionality. After that, changes were made to the equipment. Phase 2 - Applicability: Tested with 5 participants who had decreased movement in the Upper Limb, 3 with BPI and 2 with SCI, using it 30 min once a week for 12 weeks. It was noticed that the MOREw adjustments were of extreme importance for the correct functionality of the equipment that was used by clients with upper limb deficit movements, regarding ergonomics aspects, game functioning and rehabilitation programs adjustments. The clients who used it for 3 months reported great satisfaction, motivation and demonstrated greater commitment to rehabilitation with robotic assistance, confirmed by functional tests that showed a slight improvement in relation to the range of motion and muscular strength of the upper limbs, besides the improvement on the Patient Specific Scale. MOREw can be an option for BPI and SCI rehabilitation.

Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.