Acute and subacute diseases causing intrinsic spinal cord damage are confusing and poorly defined clinically and pathologically. of this study is: The purpose 1. To analyse the spectrum of conditions responsible for acute and subacute myelopathy in South Africa. 2. To categorise the clinical presentations and prognosis of the illnesses and to correlate these with aetiology. 3. To assess the validity of diagnostic criteria for acute and subacute myelopathy in general and for the different aetiological groups. 4. To review the literature and to correlate previous studies with the present one. Thirty-four patients fulfilling strict criteria nave been identified over a seven-and-a-half-year period using the Groote Schuur Hospital computer retrieval system. Although the study was essentially retrospective, 11 of these patients were seen personally during their acute illnesses. All these patients have suffered from illnesses causing spinal cord dysfunction in the absence of trauma, physical agents or any extrinsic pressure such as might be caused by tumours or spondylosis. Maximum disability was reached in less than 8 weeks. In 17 patients no cause was identified. The clinical features, laboratory findings and courses have been analysed. Among the results, a high percentage of patients with Brown-Sequard Syndromes were found with possible significance for the pathogenesis of the illness. Seven patients with meningovascular syphilis were analysed as well as 2 additional patients with spinal cord syphilis not fulfilling the strict criteria of the study. Although well known before the penicillin era, this entity is not well described in modern neurological literature. Four patients had myelopathy associated with pulmonary tuberculosis in the absence of tuberculous meningitis or spinal disease. Three of these 4 patients also developed optic neuropathy. The association of these conditions has previously been described in only a very few patients. Two patients had Epstein-Barr virus infections and 1 had an infection with Mycoplasma pneumoniae. Two had systemic lupus erythematosus and 1 had an acute cord infarct following an aortic aneurysm repair. The literature is reviewed and the findings of this study correlated with previous ones. Conclusions regarding terminology, criteria for diagnosis, investigations, course and prognosis are discussed.

Thesis (MScPhysio)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Traumatic spinal cord injury (SCI) remains one of the most serious and devastating injuries often resulting in permanent disability and with life changing implications for the individual and his/her family. Successful reintegration into community life and employment after SCI is considered important goals of rehabilitation as this has been positively associated with quality of life, self esteem and life satisfaction. The International Classification of Functioning, Disability and Health (ICF) allows researchers to identify the impact of environmental factors on functioning and disability. Minimal research, particularly in South Africa, has been done on the impact of the environment on persons living with various health conditions and specifically spinal cord injury. Objectives The main purpose of this study was to describe and compare the level of participation of persons with traumatic SCI at two time points (discharge and six months after discharge) from the inpatient rehabilitation setting and to identify the environmental barriers experienced. Methods A prospective, descriptive study was conducted using consecutive sampling. All patients with traumatic SCI that were discharged from September 1, 2008 from the Western Cape Rehabilitation Centre (WCRC) who were eligible for this study were included. Two questionnaires (one based on the ICF and one purposely-developed) and the International Standards for the Classification of SCI (ISCSCI) were used. Data were analyzed with the statistical software package STATISTICA. Results A person sustaining a traumatic SCI in the Cape Metropolitan area of the Western Cape Province is most likely to be a male, young (20 to 29 years), of the Black or Coloured race and living in the Cape Flats suburbs. More than half of the subjects had a grade eight to ten level of education which together with the lack of employers’ responsibilities towards part-time workers might explain the low percentage (11%) of employment at six months after discharge from the WCRC. Complete paraplegia, occurring mainly in the thoracic cord, was the most common neurological disability found in this study. The most common secondary condition was pain followed by spasticity limiting function. The low incidence of pressure sores and urinary tract infections found in this study contradicts findings of previous studies.The majority of the subjects were discharged to the same house they were living in at the time of their injury. However, due to various architectural barriers, some of them were not able to function independently in their homes. Inaccessibility of public transport, the lack of recreational and sport facilities, lack of social support structures in the community and inadequate financial resources were the main environmental barriers experienced by these individuals. Conclusion The main finding of this study was the low employment rate and the difficulty experienced with reintegration at community level after SCI. The results of this study confirm the significant contribution of environmental factors in participation, especially those of transport and education in return to work. Fourteen years after the publication of the Integrated National Disability Strategy (INDS) White Paper (1997), legislative strategies to ensure that people with disabilities have equal access to social and economic opportunities remain lacking. / AFRIKAANSE OPSOMMING: Agtergrond Traumatiese spinaalkoordbesering (SKB) lei dikwels tot permanente verlamming en dit het lewensveranderende implikasies vir die individu en sy/haar familie. Suksesvolle herintegrasie in die gemeenskap en werkverrigting na SKB is belangrike doelstellings vir rehabilitasie omdat dit positief met lewenskwaliteit, selfrespek en lewens-bevrediging geassosieer word. Die Internasionale Klassifisering van Funksionering, Gestremdheid en Gesondheid (IKF) bied aan navorsers die geleentheid om die impak van omgewingsfaktore op funksionering en gestremdheid te identifiseer. Daar is veral in Suid-Afrika beperkte navorsing oor die impak van die omgewing op mense met verskillende gesondheidstoestande, spesifiek SKB. Doel Die hoofdoel van hierdie studie was om die vlak van deelname van mense met traumatiese SKB op twee verskillende tye te beskryf en te vergelyk, onmiddellik na hulle uit die rehabilitasiesentrum ontslaan is, en ses maande later. Die studie het ook ten doel gehad om die omgewingsfaktore te identifiseer wat deelname negatief beïnvloed. Metode Daar is van ’n beskrywende studie gebruik gemaak. Alle pasiënte met traumatiese SKB wat vanaf 1 September 2008 vanaf die Wes-Kaapse Rehabilitasiesentrum (WKRS) ontslaan is en wat voldoen het aan die insluitingskriteria is ingesluit. Twee vraelyste is gebruik om data in te samel – een is op die IKF gebaseer en een is spesifiek vir die studie ontwikkel. Daar is ook van die Internasionale Standaarde vir die Klassifisering van SKB (ISKSKB) gebruik gemaak om data in te samel. Data is met behulp van STATISTICA, ’n statistiese sagteware pakket, geanaliseer. Resultate Iemand wat ’n traumatiese SKB in die Kaapse metropolitaanse gebied van die Wes-Kaap provinsie opdoen, is mees waarskynlik ’n jong man (20 tot 29 jaar) van die Swart of Kleurling ras wat woonagtig in die voorstede op die Kaapse Vlakte is. Meer as die helfte van die deelnemers in die studie het slegs ’n opvoedingsvlak van graad agt tot tien. Hierdie aspek, tesame met die gebrek aan werkgewers se verantwoordelikheid teenoor deeltydse werknemers is dalk die rede waarom slegs 11% van die deelnemers ses maande na hulle uit die WKRS ontslaan is, werksaam was. Volledige paraplegie, hoofsaaklik as gevolg van ’n besering van die torakale spinaalkoord, was die algemeenste neurologiese besering wat in hierdie studie gevind is. Die algemeenste sekondêre komplikasie wat voorgekom het, was pyn gevolg deur spastisiteit. Die lae voorkoms van druksere en urienweginfeksies in dié studie is in teenstelling met bevindings van vorige studies. Die meeste deelnemers is ontslaan na dieselfde huis waar hulle voor die besering gewoon het, maar as gevolg van verskeie argitektoniese hindernisse, kon sommige van hulle nie onafhanklik binne hulle wonings funksioneer nie. Die ontoeganklikheid van openbare vervoer, die gebrek aan ontspannings- en sportfasiliteite, die gebrek aan sosiale ondersteuningsnetwerke in die gemeenskap en onvoldoende finansiële hulpbronne was die algemeenste omgewingshindernisse wat deur die deelnemers ondervind is. Samevatting Die belangrikste bevinding van dié studie was dat slegs ’n klein persentasie van die deelnemers ses maande na hul ontslaan is, werksaam was en dat herintegrasie in die gemeenskap na ’n SKB baie moeilik is. Die resultate van die studie bevestig die belangrike rol wat omgewingsfaktore by deelname speel, veral die faktore wat te make het met vervoer en die opvoedingsvlak wanneer daar na ’n werk teruggekeer word. Veertien jaar na die publikasie van die Geïntegreerde Nasionale Gestremdheidstrategie in 1997, is wetgewende strategieë om gelyke toegang tot sosiale en ekonomiese geleenthede vir persone met gestremdhede te verseker, steeds gebrekkig.

M.A. / Spinal cord trauma resulting in paraplegia or quadriplegia is one of the most devastating injuries. A frequent complication of spinal cord injury is intractible pain. It compounds a host of personal and social consequences: disruption of personal roles, dysfunctional marital and family relationships, unemployment, financial hardship, depression, anxiety, lowered self-esteem and hopelessness. There is an abundance of research on pain in general, but a dearth of literature on chronic pain in the spinal cord injured population - especially in the South African context. This study examined the psychosocial impact of pain on spinal cord injured patients in a hospital setting. Specifically, it addressed six core research questions, concerned with the physiological components of pain, and the social, affective and rehabilitation consequences of pain for spinal cord injured patients. The effects of etiology and level of lesion, age, gender and culture on the general pain experience were investigated. The purpose of this study was to accurately describe the phenomenon of pain as experienced by spinal cord injured (SCI) patients. The evidence showed that pain was a serious problem for SCI patients. A variety of physical and social modifiers of the pain experience were identified, as were several important temporal features of pain. SCI patients reported high frequencies of social, affective (depression, low selfesteem, suicidal responses and partner relationship problems), and rehabilitation consequences. The etiology of spinal cord injury was found to be related to pain intensity, while the level of the lesion was not associated with pain intensity or frequency. Some effect was found for age, however, gender did not contribute to the variance of any of the dependent variables. The culture of SCI patients plays an important role in both pain perception and the psychosocial and rehabilitation consequences of chronic pain. The results suggest that pain in SCI patients, as in other pain populations, needs to be recognized as a complex, multidimensional phenomena. Successful treatment requires an understanding of the SCI patient's emotional and psychological, as well as his physical requirements. The role of pain assessment is fundamental to any pain management programme.

Spinal cord injury (SCI) is an acute and devastating event that results in significant and permanent life changes for the individuals who are injured, as well as their families and friends. Depression has received more attention from clinicians and researchers than any other psychological issue among persons with SCI. Measurement of depression in this population has a variety of methodological issues, including inconsistent assessments used (self-report versus clinical interviews), varying definitions of depression, inclusion and exclusion of physical symptoms in the assessment process, and use of measures that do not represent DSM-IV criteria for major depressive disorder. The primary goal of this study was to evaluate the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) and provide descriptive analyses of this measure with persons with SCI. Results showed that somatic symptoms were more frequently endorsed than psychological symptoms in this population. Additionally, scores on the QIDS-SR were significantly associated with a depression diagnosis in the patient's medical chart. However, QIDS-SR scores were not found to be correlated inversely with quality of life scores as predicted. The QIDS-SR was shown to have good internal consistency and convergent validity with patients with SCI. However, it failed to demonstrate construct validity. The QIDS-SR has the potential to be a valid measure with this population and further analysis of the psychometric properties with patients with SCI is warranted.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Chronic hypersensitive pain states can become established following sustained, repeated or earlier noxious stimuli and are notably difficult to treat, especially in cases where nerve injury contributes to the trauma. A key underlying reason is that a variety of plastic changes occur in the central nervous system (CNS) at spinal and potentially also supraspinal levels to upregulate functional activity in pain processing pathways. A major component of these changes is the enhanced function of excitatory amino acid receptors and related signalling pathways. Here we utilised rodent models of neuropathic and inflammatory pain to investigate whether evidence could be found for lasting hypersensitivity following neonatal (or adult) noxious stimuli, in terms of programming hyper-responsiveness to subsequent noxious stimuli, and whether we could identify underlying biochemical mechanisms. We found that neonatal (postnatal day 8, P8) nerve injury induced either long lasting mechanical allodynia or shorter lasting allodynia that nonetheless was associated with hyper-responsiveness to a subsequent noxious formalin stimulus at P42 despite recovery of normal mechanical thresholds. By developing a new micro-scale method for preparation of postsynaptic densities (PSD) from appropriate spinal cord quadrants we were able to show increased formalin-induced trafficking of GluA1- containing AMPA receptors into the PSD of animals that had received (and apparently recovered from) nerve injury at P8. This was associated with increased activation of ERK MAP kinase (a known mediator of GluA1 translocation) and increased expression of the ERK pathway regulator, Sos-1. Synaptic insertion of GluA1, as well as its interaction with a key partner protein 4.1N, was also seen in adults during a nerve injury-induced hypersensitive pain state. Further experiments were carried out to develop and optimise a new technological platform enabling fluorometric assessment of Ca2+ and membrane potential responses of acutely isolated CNS tissue; 30-100 μm tissue segments, synaptoneurosomes (synaptic entities comprising sealed and apposed pre- and postsynaptic elements) and 150 × 150 μm microslices. After extensive trials, specialised conditions were found that produced viable preparations, which could consistently deliver dynamic functional responses. Responsiveness of these new preparations to metabotropic and ionotropic receptor stimuli as well as nociceptive afferent stimulant agents was characterised in frontal cortex and spinal cord. These studies have provided new opportunities for assessment of plasticity in pain processing (and other) pathways in the CNS at the interface of in vivo and in vitro techniques. They allow for the first time, valuable approaches such as microscale measurement of synaptic insertion of GluA1 AMPA receptor subunits and ex vivo assessment of dynamic receptor-mediated Ca2+ and membrane potential responses.

Salamanders have a remarkable ability to regenerate complex body parts including the limb, tail, and central nervous system. Although salamander regeneration has been studied for several hundred years, molecular-level studies have been limited to a relatively few important transcription factors and signaling molecules that are highly conserved among animals. Physiological genomic approaches were used here to investigate spinal cord and limb regeneration. Chapter 2 reports that hundreds of gene expression changes were identified during spinal cord regeneration, showing that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. Chapter 3 presents results that identify the salamander ortholog of mammalian Nogo-A, a gene known to inhibit mammalian nerve axon regeneration. Nogo-A gene expression was characterized during salamander development and adulthood in order to address the roles of Nogo-A in the nervous system. Chapters 4 and 5 use physiological genomic approaches to examine limb regeneration and why this process is dependent upon an intact nerve supply. Results presented in Chapter 4 showed that many processes regulated during early limb regeneration do not depend upon nerve-derived factors, but striking differences arise between innervated and denervated limbs by 14 days after amputation. Chapter 5 identified genes associated with peripheral nerve axon regeneration and identified gene candidates that may be secreted by nerves to support limb regeneration. Lastly, chapter 6 characterizes the expression of a developmentally important family of genes, matrix metalloproteinases, during tail regeneration. These results suggest that matrix metalloproteinases play multiple roles throughout the regeneration process. Primarily, this dissertation presents data from the first genomic studies of salamander regeneration. The results suggest genes such as matrix metalloproteinases, and molecular pathways such as the Wnt and FGF signaling pathways that can be exploited to enhance regenerative ability in humans.

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