Bakgrund: Många av patienterna på en neurointensivvårdsavdelning (NIVA) vårdas med respirator under en längre eller kortare period av vårdtiden. Neurointensivvårdspatienterna bedöms ibland utifrån de kriterier för urträning och extubering som används på allmänna intensivvårdspatienter. Detta kan leda till för tidig extubation med reintubation som följd. Syfte: Redogöra för vilka kriterier som ska bedömas hos neurointensivvårdspatienter inför en extubering. Metod: Litteraturstudie. Resultat och slutsats: Neurointensivvårdspatienter behöver uppfylla en kombination av kriterier inför extubation. Hänsyn ska tas till de generella extubationskriterierna avseende andning och cirkulation. Dessutom ska patienten ha en tillräckligt hög medvetandegrad för att kunna följa någon form av uppmaning. Till sist ska patientens förmåga att hålla fri luftväg bedömas genom observation av hostkraft, sekretmängd/konsistens och svalgfunktion. Det behövs ytterligare forskning för att utröna i hur hög grad neurointensivvårdspatienterna behöver vara medvetna inför extubering och på vilket sätt detta bäst bedöms. Forskning behövs kring ett enhetligt tillvägagångssätt för bedömning av hostkraft, sekretmängd/konsistens och svalgfunktion. / Background: Many of the patients cared for in a neurocritical unit are treated with mechanical ventilation for a longer or shorter period of time during their stay in the unit. When weaning or extubating neurocritical patients, they are sometimes assessed according to the criteria for weaning and extubation used in general intensive care patients. This can cause premature extubation, resulting in re-intubation. Aim: Describe the criteria to be assessed in neurocritical patients prior to extubation. Method: Literature review. Results and conclusion: Neurocritical patients need to fulfil a combination of criteria prior to extubation. The general criteria in terms of respiration and circulation must be taken in to consideration, as well as the patient’s level of consciousness. The patient has to be conscious enough to be able to take directions. Lastly the patient’s ability to protect the airway must be assessed by observation of cough strength, the quantities and viscosity of the secretions and the patient’s swallowing function. Further research is required to ascertain the level of consciousness required in the neurocritical patients prior to extubation and in which way the assessment is best carried out. There is also need for further research considering a standardized measurement for assessing cough strength, the quantities and viscosity of secretions and swallowing function in these patients.

Fatigue är ett vanligt förekommande symtom vid multipel skleros (MS). Denna ihållande och svåra trötthet beskrivs ofta som det svåraste MS-relaterade symtomet att hantera. Symtomet har en negativ påverkan på individens funktionella status samt på livskvaliteten. Syftet med litteraturstudien var att belysa upplevelserna av MS-relaterad fatigue samt hur symtomet påverkar det dagliga livet. Som metod användes en systematisk genomgång av tidigare forskning med en induktiv ansats. Forskning visar att fatigue upplevs som en oavbruten förlamande effekt som uppfattas skilja sig mycket från tidigare upplevd trötthet. Fatigue påverkar hela kroppen och leder till att kroppen blir svårare att styra och hantera. Den begränsade förmågan att utföra önskade aktiviteter påverkar individernas liv negativt. Individer med MS blir tvungna att reglera och planera sitt dagliga liv för att undvika och minska graden av fatigue. En bibehållen självkänsla samt en positiv attityd och en acceptans för sjukdomen och symtomet upplevs minska graden av fatigue. Kommande forskning bör fokusera på individanpassade metoder eller strategier som upplevs minska graden av fatigue.

Thesis (Ph.D.)--University of Chicago, 2001. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--Medical College of Ohio, 2003. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Howard Rosenberg. Document formatted into pages: iv, 144 p. Title from title page of PDF document. Includes bibliographical references (p. 104-132).

Myotonic dystrophy is the commonest form of adult muscular dystrophy. Myotonic dystrophy 1 and 2 (DM 1 and DM 2) are autosomal dominant inherited disorders with unusual multisystem clinical features characterized by myotonia, progressive muscle weakness and wasting, cataracts, hypogonadism, frontal balding, cardiac conduction defects and diabetes. Severity varies from asymptomatic to severely affected phenotypes. DM1 presents with predominantly distal weakness whereas DM2 have predominantly proximal weakness.98% of patients identified worldwide present with DM1. DM 1 is caused by the expansion of an unstable CTG trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene on chromosome 19ql3.3. DM 2 is linked to the long arm of chromosome 3q21. It is caused by a tranucleotide, CCTG expansion in intron 1 of the zinc finger protein 9(ZNF9) gene that interferes with processing of a variety of RNAs. All DM mutations can be detected using a combination of the Southern Blot and Polymerase Chain reaction (PCR) techniques. Aim: This study aims to characterize the clinical spectrum and molecular features of myotonic dystrophy patients in KwaZulu - Natal between 1989 and 2005. Methodology: Patients included in this study were obtained from the database of patients diagnosed with Myotonic Dystrophy at the Department of Neurology in KwaZulu-Natal from 1989 to 2005. Patients were subjected to clinical, radiological and neurophysiological assessment. Molecular testing was performed using PCR and Southern blot. Results: Thirty-seven patients with Myotonic Dystrophy were identified. Twenty patients consented and were included into the study. Eighty-five percent of patients were of Indian descent and the remaining fifteen percent were White. No African patients were identified. Sixty-five percent were male and thirty-five percent female. Myotonia was clinically present in all patients. Ninety-five percent of patients presented with predominantly distal weakness of which 40% demonstrated mild weakness, 35% moderate weakness and 25 % severe weakness. No patients were identified with predominantly proximal wasting or weakness. Southern blotting demonstrated expanded CTG repeats (DM1) in all 20 samples analysed. The PCR analysis was unable to demonstrate expanded alleles. Conclusion: This study identified patients presenting with Myotonic dystrophy to the Department of Neurology in KwaZulu-Natal and demonstrated that Myotonic Dystrophy Type 1 remains the commonest clinical and molecular presentation. In addition it substantiated previous research findings wherein no South African of African descent was found to be affected by the disease. There have been no reported cases of Myotonic Dystrophy in African Black patients presenting to the Department of Neurology in Durban, no African Black patients have been diagnosed with Myotonic Dystrophy over the past 20 years. However ,the predominance of Indians in this study is more likely a reflection of referral bias than differing incidence amongst sections of the population. PCR analysis cannot detect trinucleotide repeat expansions beyond 200 repeats and as a result Southern Blotting remains the gold standard in obtaining a molecular diagnosis. A clinical diagnosis is sufficient and molecular confirmation is not an absolute requirement. / Thesis (M.Med)-University of KwaZulu-Natal, Durban, 2006.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for multiple sclerosis (MS) with now more than 600 documented cases in the medical literature. Long-term remission can be achieved with this therapy, but when is it justified to claim that a patient is cured from MS? In attempt to answer this question, the outcome of the Swedish patients is described, mechanisms behind the therapeutic effect are discussed and new tools for demonstration of absence of disease have been developed. In Swedish patients treated with HSCT for aggressive MS, disease free survival was 68 % at five years, and no patient progressed after three years of stable disease. Presence of gadolinium enhancing lesions prior to HSCT was associated with a favorable outcome (disease free survival 79 % vs 46 %, p=0.028). There was no mortality and no patient required intensive care. The immune system of twelve of these patients was investigated further. In most respects HSCT-treated patients were similar to healthy controls, demonstrating normalization. In the presence of a potential antigen, leukocytes from HSCT-treated patients ceased producing pro-inflammatory IL-17 and increased production of the inhibitory cytokine TGF-β1 suggesting restoration of tolerance. Cytokine levels and biomarkers of tissue damage were investigated in cerebrospinal fluid from a cohort of MS patients. The levels were related to clinical and imaging findings. A cytokine signature of patients with relapsing-remitting MS could be identified, characterized by increased levels of CCL22, CXCL10, sCD40L, CXCL1 and CCL5 as well as down-regulation of CCL2. Further, we could demonstrate that active inflammation in relapsing-remitting MS is a tissue damaging process, with increased levels of myelin basic protein and neurofilament light. Importantly, relapsing-remitting MS patients in remission displayed no tissue damage. In secondary progressive MS, moderate tissue damage was present without signs of active inflammation. From a clinical vantage point, it seems that we confidently can claim cure of relapsing-remitting MS patients after five years absence of disease activity. The new tools for evaluation of disease can strengthen this assertion and may enable earlier prediction of outcome.

Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies. To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary. To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies.

La adaptación que ocurre en el sistema auditivo es un fenónemo que todos experimentamos cuando dejamos de oir sonidos irrelevantes, constantes o incluso molestos. La adaptación para sonidos conocidos aumenta también la sensibilidad y la percepción para estímulos nuevos o poco conocidos. Por tanto, la similaridad entre la historia previa de estimulación y la subsiguiente también puede influenciar la adaptación. La adaptación a la estimulación repetida es un fenómeno que se ha visto en diferentes modalidades sensoriales o especies de animales. El curso temporal de la adaptación en corteza auditiva primaria (A1) se ha estudiado principalmente en intervalos entre estímulos muy rápidos (<400ms) y diferentes mecanismos han sido sugeridos (inhibición sináptica, disbalance excitación-inhibición, inhibición lateral, disminución de la excitación, o inhibición aumentada), aunque los mecanismos intrínsecos neuronales casi no han sido considerados. Por otro lado, numerosos estudios han mostrado el efecto que tiene la anestesia sobre la excitabilidad cortical, pudiendo, por tanto, afectar al estudio de la adaptación. Por último, la adaptación podría estar influenciada por estructuras subcorticales (como el colículo inferior o el tálamo) aunque la influencia intracortical también se ha demostrado. El primer estudio presentado en este trabajo tiene como objetivo caracterizar, en la rata despierta en movimiento, el curso temporal de la adaptación auditiva en las neuronas únicas de A1 aisladas con tetrodos. Con este propósito, se estudió cómo el intervalo entre estímulos, la duración o la intensidad de la estimulación previa afectaba a la amplitud de respuesta y su latencia de respuesta. También se estudió el curso temporal durante la estimulación sostenida y el fenómeno de la postadaptación. La comprensión de cómo la actividad neuronal codifica la información sensorial sigue siendo una cuestión fundamental en el campo de la atención auditiva. Así, la codificación de la información temporal es un aspecto clave en A1. El análisis de la “información mutua” de la respuesta neuronal nos permite cuantificar el contenido de la información de la actividad neuronal. Por otro lado, la variabilidad de la respuesta neuronal podría ser un parámetro clave para la codificación de los estímulos relevantes durante una tarea. También, la respuesta neuronal sostenida se ha sugerido que podría aportar información adicional en el animal en comportamiento. Hasta el momento, se desconoce cómo las neuronas únicas de A1 codifican la categoría temporal de los estímulos auditivos. Con este objetivo se registró la actividad de neuronas únicas en A1, por medio de tetrodos, en el animal en comportamiento. Las ratas debían discriminar si dos sonidos idénticos estaban separados por 150 o 300 ms y se ha estudiado el contenido de la información, la variabilidad y las respuestas post-estímulo de la actividad neuronal en el estado atentivo y el pasivo del animal.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Thesis (M. Sc.)--Carleton University, 2002. / Includes bibliographical references (p. 159-161). Also available in electronic format on the Internet.