Difficulties in the development of histological scoring of the inflamed temporal arteries in giant cell arteritis.
Explore the source record for details and available documents.
Biopsy↗
Biomedical subjects
C Nordborg
Publications and source records attributed to C Nordborg.
Early menopause, low body mass index, and smoking are independent risk factors for developing giant cell arteritis.
OBJECTIVE: To assess female sex hormone related variables in a group of women with biopsy positive giant cell arteritis and a control group. METHODS: 49 women with biopsy positive giant cell arteritis, aged 50 to 69 years at the time of diagnosis, answered a questionnaire on hormonal and reproductive factors. The same questions were answered by a large population of women from the same geographical area in connection with routine mammograms. The results were tested statistically, using logistic regression analysis of each variable adjusted for age, and a multivariate logistic regression analysis including age and the variables which differed significantly between giant cell arteritis and controls. RESULTS: From the multivariate logistic regression analysis, three independent variables were associated with an increased risk of having giant cell arteritis: smoking and being an ex-smoker (odds ratio (OR) = 6.324 (95% confidence interval (CI), 3.503 to 11.418), p<0.0001); body mass index (a reduction of 1.0 kg/m2 increased the risk by 10% (OR = 0.898 (0.846 to 0.952), p = 0.0003); and menopause before the age of 43 (OR = 3.521 (1.717 to 7.220), p = 0.0006). CONCLUSIONS: There was a significant association between hormonal and reproduction related factors and the risk of developing giant cell arteritis in women given the diagnosis before the age of 70. The results suggest a possible role of oestrogen deficiency in the pathogenesis of giant cell arteritis. To confirm the results, an extended study will be needed, including women older than 70.
Aged↗
Comparison of experimental nerve injury caused by ultrasonically activated scalpel and electrosurgery.
BACKGROUND: Iatrogenic nerve injury caused by heat from dissection instruments is a significant problem in many areas of surgery. The aim of the present study was to compare the risk of nerve injury for three different dissection instruments: monopolar and bipolar electrosurgery (ES) and an ultrasonically activated (US) instrument. METHODS: The biceps femoris muscle was cut in a standard manner just adjacent to the sciatic nerve using monopolar ES, bipolar ES or US shears. A total of 73 functional experiments were conducted in which the nerve was isolated, divided proximally, and stimulated supramaximally in 37 anaesthetized rats. The electromyographic (EMG) potential was recorded distally before and after each experiment. Nerve dysfunction was defined as more than 10 per cent loss of the evoked EMG potential. Fifty-nine nerves were examined histologically after dissection with the different instruments. The extent of heat damage was determined in four nerves that were divided with ES bipolar scissors and five that were divided with US shears. RESULTS: Reduction in the EMG potential was significantly more frequent in the monopolar ES group than in the US group. Morphological examination also showed significantly less nerve damage in the US group. CONCLUSION: US instruments may be safer than ES for dissection close to nerves.
Animals↗
Microdysgenesis in epilepsy.
Microdysgenesis is a microscopic malformation of cortical development characterized by heterotopic neurones and abnormal cortical architecture. It has been described in primary generalized and partial epilepsy. Its significance in epileptogenesis is controversial, partly due to lack of consensus of diagnostic criteria. Different terms have also been used for the malformation. Several quantitative studies have been performed of the histopathological aberrations associated with microdysgenesis. A majority of the studies have revealed an increased number of heterotopic neurones in specimens from epilepsy patients. However, the quantitative values given for abnormal numbers of white matter neurones vary greatly between studies and there is no consensus yet on quantitative criteria for microdysgenesis. There have also been conflicting results from studies correlating microdysgenesis with clinical data. Both favourable and worse outcome after epilepsy surgery have been reported in patients with increased numbers of white matter neurones and microdysgenesis. While some studies have shown earlier seizure onset and increased frequency of mental retardation in patients with microdysgenesis, others have not. Differences in inclusion criteria and definition might contribute to the contradictory results. There is some evidence that microdysgenesis could be important in epileptogenesis, but the mechanisms involved remain unknown and difficult to investigate. A consensus on what histopathological criteria to use for the diagnosis of microdysgenesis is needed to explore this further and enable comparisons between centres. There are advantages and disadvantages both with quantitative stereological and with qualitative assessments. It is necessary to evaluate these in the decision on diagnostic criteria, if possible taking both qualitative and quantitative aspects into account.
Cerebral Cortex↗
Parenchymal lesions in pharmacoresistant temporal lobe epilepsy: dual and multiple pathology.
OBJECTIVES: Dual pathology is reported in 5-30% of temporal lobe resections performed in pharmacoresistant epilepsy. Dual pathology may be of importance for surgical planning and also for the understanding of the pathogenesis of epilepsy. We describe the frequency of dual or multiple pathology, i.e. more than one histopathological diagnosis, in adults with temporal lobe resections. MATERIAL AND METHODS: Surgical specimens from 33 consecutive patients with resections including mesial as well as neocortical temporal structures were reviewed. All histopathological findings were recorded. Post-mortem specimens from 11 control subjects were also reviewed. RESULTS: Dual or multiple pathology was found in almost half of the epilepsy patients (48%). Hippocampal sclerosis was found in 25 patients (76%), malformations of cortical development in 15 (46%), of which 12 (36%) were microdysgenesis, and low-grade tumours in seven (21%). Apart from mild gliosis, there were no histopathological changes in the control specimens. CONCLUSION: Dual or multiple pathology was a common finding in this group of adults with temporal lobe resections. In order to increase our understanding of how aetiological factors may combine in the development of seizures, we consider it relevant and important to report all histopathological findings in epilepsy surgery series.
Adult↗
Cell-type-specific expression of p53 and p21 in giant cell arteritis.
The aim of the present study was to investigate the expression of TP53 (p53) and CDKN1A (CIP1; p21) in the arterial wall in giant cell arteritis (GCA). Cross-sections from 18 temporal artery biopsies displaying GCA and 8 control arteries were double-stained with monoclonal antibody directed at p53 or p21 on the one hand and alpha-smooth muscle actin, CD68 (macrophage) or CD3 (T-cell) on the other. Nuclear p53 was expressed in CD68-positive cells and smooth muscle cells in 16 of the 18 inflamed arteries. P21-positive nuclei were found in CD68-positive cells in 14 biopsies and in smooth muscle cells in all the specimens. All p53-positive giant cells also contained p21-positive nuclei. In the giant cells, immunopositive nuclei were mixed with negative ones. CD3-positive T-cells did not express p53 or p21. Only one p53-positive smooth muscle cell nucleus was found in the non-GCA controls and, compared with GCA, p21 expression was noted in few smooth muscle nuclei. The presence of p53 and p21 in the same types of cell in GCA indicates that the former protein is functional; p21 expression is induced by wild-type, functional p53 but not by its mutant form. The current observations suggest cellular stress in GCA, the nature of which requires further investigation.
Aged↗
Large-cell medulloblastoma in Aicardi syndrome. Case report and literature review.
An eight-year-old girl with Aicardi syndrome (AIC) developed signs of increased intracranial pressure. A clinical and radiological investigation revealed a tumor in the posterior fossa, which was resected. The histopathological diagnosis was large-cell medulloblastoma. Eight months later, she died of a local recurrence, despite treatment with chemotherapy and radiotherapy according to a PNET protocol. In addition to the growth of a large-cell medulloblastoma at the location of the primary tumor and the meningeal spread of the tumor, the autopsy revealed major cortical and subcortical malformations of the brain. Various benign (e.g., plexus papillomas) and malignant tumors (angiosarcoma, embryonic carcinoma, and hepatoblastoma) have been reported in connection with Aicardi syndrome. A genetic analysis of AIC suggests that the mutation is localized on the distal part of the short arm of the X chromosome, an area that may be of importance for tumor development. This is the first report of a primary malignant brain tumor -- large-cell medulloblastoma -- in a patient with Aicardi syndrome.
Agenesis of Corpus Callosum↗
Giant cell arteritis: epidemiological clues to its pathogenesis and an update on its treatment.
Giant cell arteritis (GCA) is a chronic systemic vasculitis with a marked female predominance and restriction to old age. The disease process distinctly targets large and medium sized arteries, preferentially the aorta and its extracranial branches. Morphological observations indicate that the age and sex distribution of GCA is related to the occurrence of degenerative changes in the arterial wall. GCA is not a truly infectious vasculitis. However, an infection might be a triggering factor. Different centres report an increase in GCA incidence, but annual fluctuations have not been shown to be statistically significant. However, significant seasonal variations have been observed by several groups. The mortality is not increased in adequately treated patients. Although, alternative steroid-sparing agents have been proposed, corticosteroids are still the first treatment choice.
Age Factors↗
The epidemiology of biopsy-positive giant cell arteritis: special reference to changes in the age of the population.
OBJECTIVE: The incidence of giant cell arteritis (GCA) increases with age. The aim of the present study was to investigate whether the increasing incidence of biopsy-proven GCA in Göteborg, Sweden, could be explained in terms of a change in the age composition of the general population. METHODS: All cases of biopsy-verified GCA between 1976 and 1995 were recorded. The annual incidence was calculated for women and men aged 50 yr or older and its relationship with the age composition of the general population was tested statistically. RESULTS: There was a significant positive correlation between age and the risk of developing GCA. In the general population, there was a shift towards higher age; in 1976, the mean age of people 50 yr or older was 63.2 (men) and 65.0 (women), whereas in 1995 it was 65.0 (men) and 68.1 (women). After compensating for this, the incidence of biopsy-proven GCA still increased significantly. Moreover, for women aged 50 yr or older, the risk of developing the disease increased more among younger subjects than older ones. CONCLUSIONS: The increase in the incidence of biopsy-proven GCA between 1976 and 1995 could not be explained merely in terms of the increasing age of the general population. It is most probably related to an increase in the influence of other factors.
Age Distribution↗
Response to B.s. Kasper, acta neuropathol (2002) 103:307.
Explore the source record for details and available documents.
Brain↗
Widespread microdysgenesis in therapy-resistant epilepsy--a case report on post-mortem findings.
Microdysgenesis is a subtle malformation, which is often found in specimens from epilepsy surgery. It is, however, not clear whether the changes are focal or diffuse. A recent autopsy case offered an opportunity to investigate whether microdysgenesis found after temporal lobe surgery was focal or widespread in the brain. The entire brain of a 20-year-old patient who died suddenly and unexpectedly was examined histologically. Microdysgenesis had previously been diagnosed after a left temporal lobectomy performed because of therapy-resistant seizures. A light microscopic examination was performed on specimens stained with Luxol-fast blue-cresyl violet and polyclonal antibodies to glial fibrillary acidic protein. Widespread microdysgenesis with irregular nerve cell distribution in the cortex and an increased number of nerve cells in cortical layer I and in the white matter was found in the right temporal and parietal lobes and bilaterally in the frontal and occipital lobes. The post-mortem examination confirmed the previous diagnosis of microdysgenesis and showed that the changes were widespread in a patient who was operated on because of focal epilepsy.
Adult↗
Distal infantile neuroaxonal dystrophy--a new familial variant with perineuronal argyrophilic bodies.
We report on two sisters with an infantile onset of dyskinetic movements, tonic spasms, seizures and apneic spells. The condition deteriorated to a hypotonic "burnt out" stage by the age of 3 years in the older sister and to a stable dyskinetic condition by the age of 2.5 years in the younger one. A skin biopsy from the older sister revealed myelinated nerve fibers crowded with neurofilaments. The extensive investigation for neurometabolic disorder, magnetic resonance imaging of the brain, and ophthalmological and neurophysiological examinations were not especially revealing. The older sister died at the age of 3 years. The autopsy revealed no apparent loss of nerve cells in the brain and no sign of storage disease. However, silver-stained coarse granules, immunopositive for neurofilament polypeptide, were found around nerve cell bodies in the cortex and in the basal ganglia. Electron microscopy revealed perineuronal membrane-bound profiles filled with filaments. Silver-stained axonal torpedoes were found in the cerebellum, but there were no spheroids. The substantia nigra, the locus ceruleus and the nucleus basalis of Meynert showed extensive perineuronal and perivascular swelling. Homovanillic acid was severely reduced, while 5-hydroxyindoleacetic acid and hydroxymethylphenyl glycol were normal in the cerebrospinal fluid of the severely affected, autopsied case. The two cases are considered to represent a new form of infantile neuroaxonal dystrophy, characterized by the degeneration of perineuronal terminals in the cerebral cortex and in the basal ganglia, as well as by axonal degeneration in the cerebellum and peripheral nerves.
Brain↗
Expression of the IL-6 family cytokines in human brain tumors.
In our RT-PCR screen for cytokine expression in human brain tumors we discovered increased levels of oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), all belonging to the interleukin-6 (IL-6) cytokine family, in most of the tumors. The expression of these cytokines in normal adult brain tissue was found to be very low or below detection limit. OSM expression was elevated in most of the tumors and immunohistochemistry analysis showed that the tumor cells contained OSM in their cytoplasm, suggesting they produce this factor. Overexpression of OSM has not previously been reported in primary human brain tumors. The IL-6 cytokine family acts through a common gp130 receptor subunit that activates the JAK/STAT signaling pathway and therefore they have been suggested to have overlapping effects. Tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase 1 (MMP-1) and MMP-3 and IL-6 have been reported to be regulated by OSM. IL-6 was low or absent in the tumors. TIMP-1, MMP-1 and MMP-3 was expressed in most tumors but with no strict correlation to OSM levels.
Astrocytoma↗
Vessel wall morphometry in giant cell arteritis.
OBJECTIVE: To investigate morphometrically the relationship between the degree of inflammatory reaction and arterial cross-sectional dimensions in giant cell arteritis (GCA). METHODS: The media and intima of cross-sectioned inflamed arteries from GCA patients were outlined. The media circumference and the media and intima cross-sectional areas were measured. The two segments in every biopsy displaying the least and most widespread media inflammation were compared, using a paired Student's t-test. Moreover, paired comparisons were made of the intima area in inflamed and noninflamed sectors in single cross-sections. RESULTS: The segment in each biopsy showing the most widespread media inflammation had the largest circumference and volume of media and intima; the intima cross-sectional area increased disproportionately. The intima was thickest in inflamed sectors in single cross-sections. CONCLUSION: The close spatial correlation between inflammatory media infiltration and the marked intimal expansion supports the contention that promoting factors produced by inflammatory cells play a pathogenetic role in GCA.
Aged↗
Giant cell arteritis. Epidemiology, etiology and pathogenesis.
Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium-sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen-driven disease with local T-cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign-body giant-cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) alpha. Cytoplasmic ER-alpha is also seen in media smooth-muscle cells in GCA and in non-GCA controls, but nucleotide sequence analysis of the ER-alpha gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA.
Aging↗
Are neuronal markers and neocortical graft-host interface influenced by housing conditions in rats with cortical infarct cavity?
The aim was to study if exposure to an enriched environment influenced graft-host interface and neuronal markers in neocortical grafts implanted in cortical infarct cavities 3 weeks after distal ligation of the middle cerebral artery in adult hypertensive rats. Half the rats were exposed to an enriched environment for 2 h daily 5 days a week starting 1 week after the arterial ligation. The brain was fixed by perfusion 4 weeks postgrafting. The immunoreactivity to glial fibrillary acidic protein, microtubule associated protein 2, and synaptophysin was studied in coronal paraffin-embedded sections. A distinct glial border separated the infarct cavity from the surrounding brain in sham-transplanted rats. Most grafts filled the larger part of the infarct cavity. In 8 of 18 transplants, 4 in each experimental group, part of the transplants protruded through the thin glial membrane that delineated the transplant-host interface into the adjacent host brain tissue. Microtubule associated protein 2 immunostained sections indicated bridging of dendrites in the host-transplant interface. Synaptophysin immunoreactivity was significantly higher in grafts than in contralateral cortex. However, graft morphology and neuronal marker immunoreactivity did not differ between rats housed in standard and activity stimulating cages.
Animals↗
Infarct volume and functional outcome after pre- and postoperative administration of metyrapone, a steroid synthesis inhibitor, in focal brain ischemia in the rat.
High blood levels of glucocorticoids are associated with increased mortality, confusion and poor functional outcome in stroke patients. It has been proposed that inhibition of glucocorticoids in acute stroke might be beneficial, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administration of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was administered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb placements and ability to traverse a rotating pole were evaluated pre- and postoperatively. Infarct size, histology and GFAP immunoreactivity were evaluated on 5 microm coronal sections from brains perfused in situ 4 weeks after the ischemic event. Pretreatment did not influence outcome, whereas postoperative administration of metyrapone significantly increased infarct volume (P < 0.05). Post-treated rats performed significantly worse than vehicle-treated rats on the rotating pole 3 weeks after the operation (P < 0.05). Our results do not support the hypothesis that inhibition of glucocorticoid synthesis improves outcome after cerebral ischemia.
Animals↗
The epidemiology of biopsy-positive giant cell arteritis: special reference to cyclic fluctuations.
OBJECTIVE: The aim of this work was to study changes in the incidence of biopsy-proven giant cell arteritis (GCA) over a period of 20 yr in Göteborg, Sweden. METHODS: All cases of biopsy-verified GCA between 1976 and 1995 were included in the study. The annual incidence was calculated for the whole material, for women and men separately, and its fluctuations were tested statistically. In addition, the monthly variation during the last 9 yr could be statistically analysed for the whole material. RESULTS: In total, 665 patients were diagnosed with biopsy-verified GCA during the 20 yr period. The average annual incidence was 22.2/100000 inhabitants over 50 yr of age (women 29.8, men 12.5). The annual incidence increased significantly with time (P<0.001) for both men and women. Statistical analysis did not reveal any cyclic fluctuation in the annual incidence (P=0.26), while the monthly number of positive biopsies showed significant fluctuation with peaks in late winter and autumn (P=0.041). CONCLUSIONS: The annual incidence of biopsy-positive GCA increased during the years 1976 through 1995. The significant seasonal variation, as well as considerable variation in annual incidence, might be due to the influence of exogenous triggering factors, such as infections. Further support for an exogenous aetiology, in terms of a statistically significant cyclic fluctuation of the annual incidence, was not found, however.
Biopsy↗