This thesis is broken into four chapters. The first two chapters summarize two separate lines of investigation into the role of a putative neurotoxin in the pathogenesis of Huntington's Disease (HD). The third chapter outlines an investigation of the putative role of beta-N-methylamino-L-alanine (BMAA) in the pathogenesis of amyotrophic lateral sclerosis (ALS), while the final chapter details a post-mortem investigation of the contents of biogenic amines and amino acids in the brain of a man who died of a familial form of parkinsonism. Chapter I is a description of a chromatographic technique developed to isolate quinolinic acid (QA), an endogenous compound implicated in the pathogenesis of HD, from deproteinized human sera. A cation exchange column was used to selectively isolate QA, which was eluted with 10 mM HCl. The eluted fractions were analyzed by UV spectrometry to isolate and quantify QA. Once the fractions corresponding the elution of authentic QA were isolated, concentrated and the excess HCl removed, the fractions were added to growing fetal rat striatal explant cultures as an assay of neurotoxicity. Since HD involves the selective degeneration of GABAergic neurons in the striatum, the activity of glutamic acid decarboxylase, the final enzyme in the synthesis of GABA, was used to determine the viability of the cultures. Unfortunately, the method was confounded by the contamination of all effluents by compounds originating from the cation exchange resin, which were discovered to be neurotoxic to the striatal cultures, and as a result the investigation had to be abandoned. Chapter II describes an investigation designed to further characterize the nature of neurotoxicity observed in the sera obtained from patients with HD (Perry et al. 1987). Compounds with the capacity to selectively stimulate neurons at the N-methyl-D-aspartate (NMDA) receptor have been implicated in a variety of neurodegenerative disorders, including HD. Selective antagonists at the NMDA receptor have been shown to protect neurons from the degenerative effects of such "excitotoxins". The investigation described used MK-801, a potent noncompetitive NMDA antagonist, in an attempt to protect fetal rat striatal cultures from the neurodegenerative effects of the sera obtained from HD patients. The results obtained were equivocal. No evidence was obtained to support a role of the NMDA receptor in the mediation of the neurotoxicity, and in addition the neurodegenerative effects of HD sera were not reproduced in the present investigation. A variety of possible explanations for the apparent discrepancy are suggested. Chapter III describes an experiment intended to produce an animal model of ALS based on the observations by Spencer et al. 1987 that chronic oral administration of BMAA in monkeys produced the histological and behavioural characteristics of this disease. In the present investigation synthetic D,L-BMAA was given by gavage to mice over an eleven week period. Since BMAA is known to act at the NMDA receptor, a subset of the mice were also given MK-801 in an effort to protect them from any deleterious effects based on the action of BMAA at this receptor. The animals were sacrificed at the end of the experiment, and biochemical analyses were performed on the striata and cortices of the animals. In addition, neuropathological studies were performed on the spinal cords, basal ganglia and related structures. The results indicated no biochemical or neuropathological abnormality as a result of BMAA administration. Chapter IV describes a post-mortem investigation of a man who was a member of a well described pedigree which carries an autosomal dominant form of parkinsonism. The object of the investigation was to determine post-mortem levels of dopamine, noradrenaline, serotonin and their metabolites, in addition to amino acids in various regions of brain. Although conflicting evidence was obtained during life, neuropathological findings and the present neurochemical analyses confirm the degeneration of the nigrostriatal dopaminergic tract, characteristic of parkinsonism, in this man. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

<p>GM2 gangliosidoses encompass a group of chronic neurodegenerative disorders characterized by metabolic defects in ganglioside catabolism and marked intralysosomal accumulation of GM2 in central nervous system (CNS)-resident neurons. Included in this group are Tay-Sachs and Sandhoff disease. Human cases of Tay-Sachs and Sandhoff disease present with devastating neurological deterioration; however, murine models display drastically divergent phenotypes. Tay-Sachs mice avoid pathology via a sialidase-mediated bypass of β-hexosaminidase A (HEXA) deficiency, though the precise mechanism of avoidance is not fully elucidated. The following work aimed to: i) determine if the murine sialidase-mediated bypass could be potentiated in human cells, and ii) help clarify the mechanism of disease avoidance in Tay-Sachs animals.</p> <p>Adenoviral overexpression of truncated CCAAT displacement protein (CDP^831-1505) in human Tay-Sachs neuroglia augmented neuraminidase 1/lysosomal sialidase (NEU1) protein levels, which reduced intralysosomal GM2 accumulations. Chromatin immunoprecipitation revealed binding of CDP^831-1505 to the human <em>NEU1</em> promoter in Tay-Sachs neuroglia. These results provide mechanistic and functional evidence supporting therapeutic exploitation of <em>NEU1</em> for Tay-Sachs disease.</p> <p>Comparison of immunological responses of bone marrow-derived macrophages (BMDMs) to pathogen associated molecular patterns (PAMPs) or GM2 demonstrated that Sandhoff macrophages secrete increased TNF and reduced IL-10 following lipopolysaccharide stimulation. GM2 treatment failed to stimulate an immune response. Such behaviour occurred in the absence of clearly observable intralysosomal ganglioside accumulations. Altered LAMP2 protein size, potentially due to aberrant glycosylation, is hypothesized to disrupt autophagosomal/lysosomal fusion. Subsequent autophagosomal accumulation could result in inherent macrophage hypersensitivity and immunologic irritability. Downstream interleukin-10 (IL-10)/signal transducer and activator of transcription 3 (Stat3) axis, mitogen activated protein kinase (MAPK), and glycogen synthase kinase 3-beta (GSK3β) signaling pathways were affected in Sandhoff BMDMs. These data indicate inherent differences in immunological responses of BMDMs from Sandhoff mice, presumably related to their β-hexosaminidase B (HEXB) deficiency.</p> <p>Data presented here provides evidence to suggest a paradigm shift in the neurodegenerative model of Tay-Sachs and Sandhoff Diseases towards one that places immune cells as an initiating factor for widespread neuroinflammation.</p> / Master of Science (MSc)

<p><strong>Objective</strong>: To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex (TSC) undergoing resective epilepsy surgery.</p> <p><strong>Data sources</strong>: Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.</p> <p><strong>Study selection:</strong> We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate.</p> <p><strong>Data extraction</strong>: One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.</p> <p><strong>Data synthesis</strong>: To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.</p> <p><strong>Results</strong>: Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). On univariable analysis, absence of generalized seizure semiology (OR=3.1, 95%CI=1.2-8.2, p=0.022), no or mild developmental delay (OR=7.3, 95%CI=2.1-24.7, p=0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR=3.2, 95%CI=1.4-7.6, p=0.008) and EEG/Magnetic resonance imaging concordance (OR=4.9, 95%CI=1.8-13.5, p=0.002) were associated with a good postoperative seizure outcome.</p> <p><strong>Conclusions</strong>: Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best evidence suggests 4 preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Given the low incidence of children with TSC undergoing epilepsy surgery, large long-term prospective multicenter observational studies are required to further evaluate the predictive factors identified in this review.</p> / Master of Science (MSc)

The functional compartmentalization underlying neuronal polarity makes tightly regulated intracellular transport between the cell body, axons, and dendrites essential for proper development and homeostatic maintenance. Disruptions to neuronal trafficking are a major cause of neurodegenerative disease. Pathogenic variants in the microtubule motor protein KIF1A cause KIF1A Associated Neurological Disorder (KAND), a spectrum of rare neurodegenerative conditions. KAND is clinically and genetically heterogeneous, with a broad phenotypic spectrum and over a hundred pathogenic variants identified. KAND is poorly understood at both the clinical and molecular level, and there is currently no treatment. This work characterizes the natural history of KAND and describes a novel heuristic severity score. This severity score is then used to show how the location of pathogenic missense variants within the KIF1A motor domain correlates with disease severity, providing evidence the clinical phenotypic heterogeneity in KAND reflects and parallels the molecular phenotypes. Insights from the neuropathology of deceased KAND patients is used to focus a histopathologic assessment of the C3-Kif1aLgdg mouse model. C3-Kif1aLgdg/Lgdg mice have a cerebellar axonal torpedo phenotype, paralleling some of the pathological changes seen in the patients. Phenotypically, the C3-Kif1aLgdg mice were found to recapitulate some of the symptoms seen in patients including progressive spasticity and gait abnormalities associated with hind limb paralysis. To model the disease at a cellular level, iPSCs were derived from affected individuals and successfully used to generate neural stem cells and neurons. These patient-derived neurons were found to have increased markers of protein aggregates, a cellular phenotype that can be used to test potential treatments. Taken together, these studies provide foundational knowledge for future therapeutic development.

Thesis (MMed)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Numerous tests exist for the assessment of general cognitive functioning. Most of these tests were developed within the discipline of psychology. Neuropsychological tests are very useful, but have some limitations. Administration of the tests is limited to a psychologist, is very timeconsuming in that it can take 3-8 hours to administer and often need specialized equipment. At the other end of the continuum are very brief screening tests. General practitioners, psychiatrists and occupational therapists, in addition to psychologists, also use these tests. Although useful, the short tests only provide limited information. An intermediate level test streamlining the assessment process between the very short and longer neuropsychological tests is therefore introduced by this study. The Bedside Cognitive Assessment Battery (BCAB) was developed in 1995 and are since used, at Tygerberg Hospital's Memory Clinic, to assess patients and teach students. The test comprehensively assesses the six main classes of cognitive functioning, namely attention and concentration, speech, memory, motor functioning, perceptual functioning and executive functioning. Approximately 35-45 minutes is required for administration and training is needed to administer the BCAB. No specialized equipment is needed for administration. The battery can therefore be used at the bedside, in the office or at old age homes. The aims of this study were to validate the BCAB for use with people aged eighteen years and older, and provide normative values for use in clinical settings. The test was revised in 1997 and 2001, and extensively so in 2002, but was never formally evaluated for validity. Well-known single tests were used to compile the BCAB. Most of these tests have proven validity and reliability, but only for foreign populations. In addition, some items were reformulated and others created by the researchers. The introduction of normative values would also be useful to assist in the delineation of cognitively intact and impaired individuals. This study succeeded in providing a table of normative values. One-hundred-and-sixty Afrikaans and English participants, and fourteen Xhosa participants were assessed in their mother tongue language. This project thus also introduced a Xhosa version of the BCAB. The purpose of the Xhosa version was to address the lack of culturally relevant cognitive assessment instruments. Results were evaluated for the effects of the variables' language, gender, age and education. The effect of language was most noticeable in the Xhosa group. Gender did not affect results as dramatically as age and especially, education. These significant effects on the aforementioned variables have been described in previous reports. The BCAB is thus relevant and useful as a detector of mild to moderate impairment. It can also be used to identify specific impairment. This can narrow down the investigation of psychologists, thus saving time and money. In addition, medical and nonmedical staff can use the BCAB. Some limitations were also identified. The sample used may limit the generalization of results. Some test items also need revision, along with further validation studies. Clinicians are therefore advised to use the BCAB only in addition to complete clinical examinations when making decisions regarding a patient's cognitive status. The BCAB appears to be a valid tool for bedside assessment. However, this study could only set the stage for further research, especially studies concerned with establishing normative values. / AFRIKAANSE OPSOMMING: Verskeie toetse bestaan vir die evaluering van algemene kognitiewe funksionering, waarvan die meeste ontwikkel is binne die sielkunde. Neuro-sielkundige toetse is baie bruikbaar, maar het sekere beperkings. Administrasie van die toetse is beperk tot sielkundiges, maar tydrowend weens 'n tydsduur van drie tot agt uur, en verg dikwels gespesialiseerde toerusting. Aan die ander kant is heelwat kart siftings-toetse beskikbaar. Aigemene praktisyns, sielkundiges en arbeidsterapeute, asook sielkundiges, gebruik dit. Hoewel bruikbaar, bied die kart toetse beperkte inligting. 'n lntermediere vlak toets om die evaluerings-proses tussen kart en langer neuro-sielkundige toetse te integreer word met hierdie studie beoog. Die Bedkant Kognitiewe Evaluasie Battery (BKEB) is in 1995 ontwikkel en gebruik in die Geheue-kliniek van die Tygerberg Hospitaal om pasiente te evalueer en studente op te lei. Die toets is gerig op die omvattende evaluering van die ses hoof-klasse van kognitiewe funksionering. Hierdie klasse omvat aandag en konsentrasie, spraak, geheue, motoriese funksionering, perseptuele funksionering en uitvoerende funksionering. Sowat 35 tot 45 minute word benodig vir administrasie terwyl opleiding vereis word vir die neem van die toets. Geen gespesialiseerde toerusting is nodig nie. Die battery kan dus by die bedkant, in die kantoor of in ouetehuise gebruik word. Die doelwitte van hierdie studie is om die BKEB te evalueer in gebruik by 18-jariges en ouer, en normatiewe waardes te bepaal vir gebruik in kliniese omgewings. Die toets is in 1997 en 2001 hersien. In 2002 is dit uitvoerig hersien, maar nooit ge-evalueer vir geldigheid nie. Bekende enkel-toetse is gebruik am die BKEB saam te stel. Dit is as geldig en betroubaar bewys, hoewel slegs onder buitelandse bevolkingsgroepe. Hierbenewens is sekere items herformuleer en ander bygewerk deur die navorsers. Normatiewe waardes sal oak handig wees in die afbakening van kognitief normaal-funksionerende en kognitief-ingekorte individue. Hierdie studie het daarin geslaag am 'n tabel van normatiewe waardes daar te stel. Een-honderd-en-sestig Afrikaans- en Engels-sprekendes, en 14 Xhosa-sprekendes is tydens hierdie studie in hulle moedertaal ge-evalueer. Hierdie projek het dus oak 'n Xhosaweergawe van die BKEB geskep. Die doel van die Xhosa-weergawe was am die gebrek aan 'n kultureel toepaslike kognitiewe instrument te beklemtoon. Resultate is ge-evalueer gedagtig aan veranderlikes soos taal, geslag, ouderdom en opleidingsvlak. Taal het die grootste invloed gehad op uitslae van Xhosa-deelnemers. Geslag het nie die uitslae so dramaties bernvloed soos ouderdom, en veral opleidingsvlak nie. Literatuur het meestal die groot uitwerking van hierdie veranderlikes bevestig. Die BKEB is dus relevant en handig in die naspeuring van ligte tot matige kognitiewe ingekortheid. Dit kan ook gebruik word om spesifieke kognitiewe ingekortheid te identifiseer. Die kan die omvang van ondersoek deur sielkundiges vernou, wat kan lei tot In groot besparing in tyd en geld. Hierbenewens kan mediese en nie-mediese personeel aangewend word in die gebruik van die BKEB. Sekere tekortkominge is ge·,dentifiseer. Die steekproef mag egter die veralgemening van die uitslae beperk. Sekere toets-items mag ook hersiening vereis, tesame met verdere geldigheid-studies. Kliniese praktisyns word daarom aangeraai om die BKEB slegs in aanvulling tot omvattende kliniese ondersoeke te gebruik vir besluite m.b.t. In pasient se kognitiewe status. Die BKEB kom voor as In geldige instrument vir bedkant evaluering. Hierdie studie kon egter slegs die tafel dek vir verdere ondersoek, veral t.o.v. studies wat poog om normatiewe waardes daar te stel.

A large percentage of individuals with intractable epilepsies have an accompanying cortical malformation, the underlying cellular mechanisms of which are poorly understood. It is known however that in an animal model for one such malformation, polymicrogyria, epileptogenesis occurs most easily from an adjacent area termed the paramicrogyral region (PMR). Previous studies implicate SS interneurons as a potential contributor to this pathology, which lead to our hypothesis: in PMR, SS interneurons exert a higher modulatory influence on excitatory pyramidal cells, as compared to the same by SS interneurons within homologous control cortex. Using a freeze-lesion model for polymicrogyria in transgenic mice that selectively express either Channelrhodopsin or Archaerhodopsin optogenetic channels in these cells, we assessed the contribution of SS interneurons as it potentially differs between layer V of PMR and control cortex. These studies provided the following biological examples in support of previous extrapolations that indicate SS over-activation within PMR: (1) SS interneuron mediated evocation of inhibitory events in layer V excitatory neurons is more robust in PMR than in control. Similarly, electrically-evoked inhibitory events in these excitatory neurons trend towards being larger, signifying a larger contribution by interneurons. (2) SS interneuron mediated suppression of electrically-evoked responses trends towards being stronger in PMR; and (3) the selective silencing of SS interneurons might not impart an effect on spontaneous inhibitory postsynaptic events.

A method for modeling and simulating neural action potential (AP) propagation along the length of an axon containing a number of Ranvier nodes is proposed in this dissertation. A system identification approach is adopted to represent node of Ranvier (NR) response to current pulse stimulus in the form of transfer function representations for NR excitability. Segments of myelinated internodal (IN) and NR regions are cascaded, representing the remaining downstream axon after a site-of-stimulus introduction of an external current pulse. This cascading network is used to simulate "cable" properties and signal propagation along the length of the axon. This work proposes possible solutions to attenuation losses inherited in the classical myelinated cable models and accounts for neuronal AP velocity as well as introducing signal attenuation and transient delays associated with internodal demyelination. This model could aide as a predictive tool for the diagnosis and analysis of axonal signal integrity associated with demyelination pathology. Possible applications could include functional stimulation control methodologies for axon bundles that may exhibit signal fidelity issues associated with demyelination. It is further proposed that this model may serve as an instructive tool for further development and incorporation of other axon dynamic behaviors such as: relative refractory periods of AP generation, NR AP recovery mechanisms and responses to varied current stimulus input. / by George Jason Morales. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

by Ramanee Darshanee Mahaliyana. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 122-139). / Chapter Chapter 1 --- Head Injury :an overview --- p.1 / Chapter Chapter 2 --- Diffuse Axonal Injury --- p.20 / Chapter Chapter 3 --- Objectives of this study --- p.53 / Chapter Chapter 4 --- Materials and Methods --- p.58 / Chapter Chapter 5 --- Results --- p.66 / Chapter Chapter 6 --- Discussion --- p.98 / Chapter Chapter 7 --- Conclusions --- p.119 / References --- p.122

The prevalence of injuries from improvised explosive devices (IEDs) in recent U.S. military conflicts has highlighted the lack of knowledge of the acute and long-term consequences of blast exposure. Real-world blast exposure is complex and multi-phasic. It is unclear whether the shock wave component of blast exposure (primary blast) can cause traumatic brain injury (TBI); however, other blast components, such as tertiary blast (inertial loading mechanics), have known potential to injure the brain. Clinical and in vivo studies suggest that complex blast loading of the whole body and head can result in acute and delayed behavioral deficits and neurodegeneration, yet tertiary blast exposure or injury to the body can initiate a systemic response that complicates understanding of this pathology. To set safe thresholds for primary blast exposure and design headgear that can guard against primary blast, tolerance criteria for primary blast specific to brain must be defined. We developed and validated a model of primary blast injury for use with in vitro organotypic hippocampal slice cultures (OHSCs) and determined that primary blast without concomitant tertiary blast loading or systemic response can injure isolated brain samples. This work was the first to define a cell death tolerance criterion for OHSCs to primary blast and report that the threshold for deficits in neuron function was below the threshold for cell death. Mild TBI (mTBI) or concussion, by definition, results in an altered mental state that can include loss of consciousness (LOC) for less than 30 minutes, dizziness, confusion, and retrograde amnesia. These symptoms typically subside within a week after injury; however, for some patients who experience multiple concussions over a relatively short period, these symptoms can persist for a year or longer; persistence of mTBI symptoms is called post-concussion syndrome (PCS). Studies suggest an initial mechanical trauma to the brain can initiate a period of time during which the brain is more vulnerable to additional injury. Little is known about this phenomenon; therefore the current standard of care for patients suffering from concussion is rest and removal from activities with a risk of additional brain trauma. During combat deployment, over 89% of service members reported an incidence of altered mental state and over 86% reported LOC following 2 or more exposures to blast. We evaluated the response of OHSCs to repetitive primary blast (shock wave loading) and repetitive tertiary blast (stretch injury) separately, characterizing the period of vulnerability that follows an initial insult to define safe rest-periods after blast-exposure and better understand pathologies of more complex injuries, i.e. combined primary and tertiary blast. Long-term potentiation (LTP) was significantly reduced by 2 primary blast exposures delivered 24 hours apart. An initial shock wave exposure increased tissue vulnerability to subsequent exposure, which lasted as long as 72 hours but not longer than 144 hours. Repetitive primary blast exposure also increased microglial activation. Similarly, a single mild stretch injury initiated a period of heightened vulnerability to subsequent mild stretch that lasted at least 72 hours but not longer than 144 hours long. Repetitive stretch injury significantly increased cell death, nitrite concentration, and astrogliosis and significantly reduced LTP. We also tested delayed administration of memantine as a treatment for repetitive stretch injury. Memantine is approved by the Food & Drug Administration for the treatment of Alzheimer’s disease, and preclinical studies suggest memantine may be neuroprotective following TBI. Cell death was reduced and LTP was rescued by delayed memantine treatment. Along with further preclinical and clinical investigation of repetitive primary and tertiary blast exposure, these studies may aid in setting safe rest periods and identifying new therapies for service members exposed to blast. This research has shown that primary and tertiary blast exposure can injure OHSCs causing cell death, altering neuron function, and increase vulnerability to a subsequent exposure. These studies expand our understanding of the neuropathology of primary and tertiary blast loading and evaluate methods to improve outcome after repetitive injuries with complementary strategies including rest periods and drug-treatment.

by Andy Cheng Shu Kei. / Year shown on spine: 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves [165-175]). / acknowledgements / abstract / Chapter chapter one --- introduction / Chapter 1.1 --- JUSTIFICATION OF RESEARCH --- p.1 / Chapter 1.2 --- STRUCTURE OF THESIS --- p.4 / Chapter chapter two --- literature review / Chapter 2.1 --- ANATOMY OF DIGITAL NERVE --- p.6 / Chapter 2.2 --- FACTORS AFFECTING RESULTS OF SENSIBILITY RECOVERY --- p.10 / Chapter 2.3 --- NEUROPHYSIOLOGY OF NERVE FIBRE / MECHANORECEPTORS --- p.16 / Chapter 2.4 --- NEUROPHYSIOLOGY OF TACTILE STIMULATION --- p.20 / Chapter 2.5 --- SENSIBILITY TESTING FOR FUNCTIONAL SENSIBILITY --- p.26 / Chapter 2.5.1 --- SEMMES-WEINSTEIN MONOFILAMENT / Chapter 2.5.2 --- CONSTANT TWO-POINT DISCRIMINATION / Chapter 2.5.3 --- MOVING TWO-POINT DISCRIMINATION / Chapter 2.5.4 --- SELF EVALUATION / Chapter chapter three --- retrospective study of the sensibility recovery of peripheral nerve injuries / Chapter 3.1 --- INTRODUCTION --- p.38 / Chapter 3.2 --- OBJECTIVES --- p.38 / Chapter 3.3 --- METHODOLOGY --- p.38 / Chapter 3.4 --- RESULTS --- p.42 / Chapter 3.5 --- DISCUSSION AND IMPLICATION --- p.43 / Chapter chapter four --- longitudinal study of the sensibility recovery of digital nerve injuries / Chapter 4.1 --- INTRODUCTION --- p.45 / Chapter 4.2 --- OBJECTIVES --- p.45 / Chapter 4.3 --- METHODOLOGY --- p.46 / Chapter 4.4 --- RESULTS --- p.50 / Chapter 4.5 --- DISCUSSION AND IMPLICATION --- p.57 / Chapter chapter five --- "functional sensibility - normative values and correlation with age, sex,occupation and skin hardness in local chinese population" / Chapter 5.1 --- INTRODUCTION --- p.59 / Chapter 5.2 --- OBJECTIVES --- p.60 / Chapter 5.3 --- METHODOLOGY --- p.60 / Chapter 5.4 --- RESULTS --- p.64 / Chapter 5.5 --- DISCUSSION AND IMPLICATION --- p.84 / Chapter chapter six --- prospective randomised study of early tactile stimulation in digital nerve injuries / Chapter 6.1 --- INTRODUCTION --- p.87 / Chapter 6.2 --- OBJECTIVES --- p.88 / Chapter 6.3 --- METHODOLOGY --- p.89 / Chapter 6.4 --- RESULTS --- p.95 / Chapter 6.5 --- DISCUSSION AND IMPLICATION --- p.115 / Chapter chapter seven --- conclusions and recommendations / Chapter 7.1 --- CONCLUSIONS --- p.121 / Chapter 7.2 --- RECOMMENDATIONS --- p.125 / appendices / Chapter I --- INSTRUCTION MANUAL FOR ASSESSING FUNCTIONAL SENSIBILITY --- p.126 / Chapter II --- CLASSIFICATION OF LEVEL OF FINGER DEXTERITY IN WORK --- p.129 / Chapter III --- RANDOM TABLE IN MAIN STUDY --- p.132 / Chapter IV --- SCHEMATIC DIAGRAM OF INTERNAL STRUCTURE OF TACTILE STIMULATOR --- p.133 / Chapter V --- CONSENT FORM --- p.134 / Chapter VI --- ASSESSMENT FORM IN RETROSPECTIVE STUDY --- p.135 / Chapter VII --- ASSESSMENT FORM IN LONGITUDINAL AND MAIN STUDY(LEFT HAND) --- p.137 / Chapter VIII --- ASSESSMENT FORM IN LONGITUDINAL AND MAIN STUDY(RIGHT HAND) --- p.138 / Chapter IX --- ASSESSMENT FORM IN CORRELATIONAL STUDY --- p.139 / Chapter X --- INTER-RATER VARIATION IN ASSESSING SENSIBILITY RECOVERY IN LONGITUDINAL STUDY --- p.140 / Chapter XI --- NORMATIVE VALUES OF FUNCTIONAL SENSIBILITY AND SKIN HARDNESS --- p.142 / Chapter XII --- INTER-RATER VARIATION IN ASSESSING SENSIBILITY RECOVERY IN MAIN STUDY --- p.162 / references