| 1. |
- Lundin, Anna-Carin
(författare)
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Tendinosis in Trigger Finger
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 2. |
- Nord, Maria
(författare)
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Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.
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| 3. |
- Khoshnood, Ardavan
(författare)
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Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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| 4. |
- Skoog, Johan
(författare)
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Cardiovascular regulation in women with vasovagal syncope : With special reference to the venous system
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although vasovagal syncope (VVS) is a common clinical condition the mechanisms behind VVS remain elusive. Upright posture is the major trigger of VVS and lower limb blood pooling affecting cardiac output has been proposed as a major determinant. The overall aim of this thesis was twofold. First, to develop new methodology for calculating limb venous compliance. Second, to study lower limb venous volume load and cardiovascular responses during hypovolemic circulatory stress caused by lower body negative pressure (LBNP) in healthy women and women with VVS, emphasizing compensatory mechanisms to maintain central blood volume.Net fluid filtration was associated with an underestimation ofvenous compliance. This could be accounted for with a correctionmodel. Further, a new venous wall model made it possible to adopt thevenous pressure-volume curve through the entire pressure range andthus provide a valid characterization of venous compliance.Calf blood pooling was similar between the groups and was not associated with tolerance to hypovolemic circulatory stress. Venous compliance was reduced at low venous pressures in VVS and correlated with decreased tolerance to circulatory stress. VVS women displayed attenuated sympathetic vasoconstrictor responses during graded circulatory stress, and mobilization of arm capacitance blood as well as capillary fluid absorption from extra- to intravascular space were reduced. Accordingly, more pronounced reductions in cardiac output were found in VVS. Thus, reduced compensatory mechanisms to maintain cardiac output could contribute to the pathogenesis oforthostatic VVS.In healthy women, rapid pooling in the lower limb was associated with higher tolerance to circulatory stress and more efficient cardiovascular responses, in part due to speed-dependent baroreflex-mediated sympathetic activation. In VVS however, rapid lower limb blood pooling was associated with lower tolerance and deficient cardiovascular responses. No speed-dependent baroreflexmediated sympathetic activation was found in VVS, indicating welldefined differences in cardiovascular regulation already in the initial responses to orthostatic stress.
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| 5. |
- Arvidsson, Sandra, 1986-
(författare)
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Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.
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| 6. |
- Sandberg, Olof, 1985-
(författare)
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Metaphyseal Fracture Healing
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general.My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs.First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models.Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology.The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes.To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.
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| 7. |
- Hilborn, Erik, 1988-
(författare)
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The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer : Impact on tamoxifen treatment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different aspects of their role in breast cancer.Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.
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| 8. |
- Joost, Patrick
(författare)
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Mismatch Repair Deficient Cancer Diagnostic Aspects in Colorectal Cancer and the Role of Urological Cancer in Lynch Syndrome
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mismatch repair (MMR) deficiency is carcinogenic and can either have somatic/sporadic causes (i.e. epigenetic silencing or somatic inactivation) or hereditary causes (Lynch syndrome due to a germline mutation in one of the MMR genes ¬- MLH1, MSH2, MSH6, PMS2). The identification of MMR defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment-predictive purposes. The aims of this thesis were to validate the application of the MMR index for the prediction of MMR deficiency in colon cancer (study I), to investigate heterogeneous MMR protein expression in colorectal cancer (study II) and to study urological cancers in Lynch Syndrome (studies III-V). The most common cancers in Lynch syndrome are colorectal cancer and endometrial cancer, but also other tumour types are linked to the syndrome. We investigated the roles of bladder cancer (study III), prostate cancer (study IV) and renal cell cancer (study V) in Lynch syndrome. Study I confirmed that the MMR index is easy to apply and identifies MMR defective colon cancers with high sensitivity (93%) and specificity (76%). The MMR index evaluates features such as expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumour-infiltrating lymphocytes. Study II showed that heterogeneous (retained/lost) MMR protein expression occurred in three distinct patterns, i.e. as intraglandular, clonal and compartmental protein expression. These patterns co-existed in 9/14 tumours and correlated to differences in the MMR status. Attention to this phenomenon is recommended to prevent false-positive or false-negative evaluations of MMR protein immunostaining. Studies III-V linked urinary bladder cancer, prostate cancer and renal cell cancer to Lynch syndrome families. The cancers frequently showed MMR defects in line with the underlying disease-predisposing mutation, indicating that these cancer types should be considered part of the Lynch syndrome tumour spectrum. Urothelial cancer development was predominantly linked to MSH2 mutations. These findings should be considered in risk estimates and surveillance recommendations.
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| 9. |
- Rohini Rajan, Meenu, 1983-
(författare)
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Unraveling Mechanisms of Insulin Resistance in Type 2 Diabetes in Human Adipocytes : Role of extracellular signal regulated kinase 1/2 (ERK1/2) and forkhead box protein 01 (FOX01)
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 Diabetes is characterized by hyperglycemia primarily caused due to insulin resistance in insulin responsive tissues and insufficient production of insulin by the β-cells. Insulin resistance appears to develop first in the expanding adipose tissue during caloric surplus and affects other tissues like liver and muscle by ectopic fat accumulation. In spite of significant research in field of insulin signaling, very little has been known about the mechanisms that lead to insulin resistance and T2D.We aim for network-wide knowledge of insulin signaling in human adipocytes and to identify mechanisms that can induce insulin resistance in diabetic individuals. We have herein focused on the transcriptional control of insulin via ERK and FOXO1, and have used mathematical modelling to gain a systems-level understanding of insulin signaling network.Through the work in this thesis, we present for the first time a dynamic comprehensive model for insulin signaling for the adipocytes, for both metabolic and transcriptional control, and that can simulate data from both normal and diabetic individuals. We described insulin regulation of ERK phosphorylation and showed that both its insulin sensitivity and maxima response to insulin was curtailed in adipocytes from diabetic individuals (Paper I). Our findings indicate that insulin regulated ERK pathway exerts control on transcription not only through phosphorylation of Elk-1 but also through phosphorylation of FOXO1 and exerts translational control via phosphorylation of ribosomal protein S6 (Paper I, II). Furthermore, we showed that insulin-induced FOXO1 phosphorylation or its insulin sensitivity was not impaired in diabetic individuals, although FOXO1 protein level was reduced by 45% in adipocytes from patients with type 2 diabetes. Comprehensive analysis of the detailed insulin signaling model showed that attenuation of the feedback from mTORC1 to IRS1-Ser307 explained dominant part of the insulin resistance seen in adipocytes from diabetic individuals (Paper II). More interestingly, inhibition of FOXO1 with a dominant negative construct of FOXO1, mimicked the diabetic state in the adipocytes, with the similarity extending to both insulin signaling as well as the reduced protein levels, as seen in the diabetic adipocytes. We also show that mTORC1 and FOXO1 maintain each other’s expression/activity in the human adipocytes (Paper II, III). Our findings thus demonstrate that the interplay between mTORC1 and FOXO1 maintains normal insulin signaling in the human adipocytes.
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| 10. |
- Asplund, Pär, 1974-
(författare)
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Percutaneous Balloon Compression for the Treatment of Trigeminal Neuralgia
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Trigeminal neuralgia (TN) is a paroxysmal unilateral facial pain condition. That it is rather rare is of little comfort to those who are affected, as TN is often described as one of the worst pains known to mankind. Advanced age and multiple sclerosis (MS) are risk factors for developing TN. The first line of treatment is medical, primarily with carbamazepine. When medical treatment fails, as it does in many patients, there are several surgical options. One of the minimally invasive options, suitable for patients with comorbidity, is percutaneous balloon compression (PBC). Despite its introduction in the early 1980s, PBC is arguably the least well studied of the minimally invasive procedures for the treatment of TN.Aims. The aim of this thesis was to evaluate the efficacy of PBC, both overall and in MS-TN patients specifically. Further, it intended to identify and evaluate pre- and intraoperative parameters associated with the efficacy of PBC. It also investigated changes in sensory function after PBC, and identified side effects and complications associated with PBC. Finally, it sought to evaluate how efficacy, side effects and complications differed between PBC and another minimally invasive technique; percutaneous retrogasserian glycerol rhizotomy (PRGR).Methods. Cohorts of patients treated with PBC in Umeå and Stockholm, and with PRGR in Umeå, were followed retrospectively. Data from an existing database was combined with data from medical records, radiographs and telephone interviews.Results. After PBC, 90 % of the patients were completely pain free without medication for TN. The median time to recurrence of pain was 28 months. In patients with concurrent MS, the initial success rate was 67 % and the median time to recurrence was 8 months. In patients without MS, who had not previously been treated surgically, the initial success rate was 91 % and the median time to recurrence was 48 months. The procedure could, however, be repeated with good results. A good compression, indicated by a pear-shaped balloon as seen on intraoperative lateral radiograph, was crucial to achieve good pain relief. Postoperative hypoesthesia was present in the majority of patients, but after 3-6 months, sensibility was partly or fully normalized in most patients. Severe complications were rare, but included transient cardiac arrest, meningitis and dysesthesia. The side effects profile was favorable to that of percutaneous retrogasserian glycerol rhizotomy, in that the latter produced more cases of dysesthesia and decreased corneal sensibility. The efficacy of the two treatments were, however, not significantly different.Conclusions. PBC is an effective and relatively safe treatment option for patients with TN refractory to medical treatment. It deserves its place among the standard treatments for TN, and could be considered for those patients eligible for surgery for which open surgery is a less suitable option.
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