| 1. |
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| 2. |
- Al Nimer, Faiez, et al.
(författare)
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Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination
- 2016
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Ingår i: Neurology. - 2332-7812. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.
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| 3. |
- Andersson, Ulrika, et al.
(författare)
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Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas
- 2004
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 108:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P= 0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.
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| 4. |
- Andersson, Ulrika, et al.
(författare)
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Heterogeneity in the expression of markers for drug resistance in brain tumors
- 2004
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 23:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (> 50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p < 0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.
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| 5. |
- Andersson, Ulrika, et al.
(författare)
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Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation
- 2002
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Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.
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| 6. |
- Antonsson, Johan, et al.
(författare)
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Diffuse reflectance spectroscopy measurements for tissue type discrimination during deep brain stimulation
- 2008
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Ingår i: Journal of neural engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 5:2, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.
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| 7. |
- Asklund, Thomas, et al.
(författare)
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Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:7, s. 2407-2413
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Tidskriftsartikel (refereegranskat)abstract
- Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.
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| 8. |
- Asplund, Pär, et al.
(författare)
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One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis
- 2019
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Ingår i: Operative Neurosurgery. - : Oxford University Press. - 2332-4252 .- 2332-4260. ; 17:5, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trigeminal neuralgia associated with multiple sclerosis (MS-TN) is comparatively rare and larger series of percutaneous balloon compression (PBC) in such cases are few in the literature.OBJECTIVE: To evaluate the results after PBC for MS-TN with regards to therapeutic effect, side effects, and complications.METHODS: One hundred eleven procedures with PBC performed in 66 cases of MS-TN were analyzed. Therapeutic effect was measured as postoperative time to pain recurrence without medication. All complications were compiled and the sensory function was evaluated in a subgroup of cases.RESULTS: The initial pain free rate was 67% and the median time to pain recurrence was 8 mo. Thirty-six patients were treated with PBC only, and among them, the results were worse if treated 3 to 4 times before, compared to first treatment (P = .009-.034). Patients who had several PBCs had worse results already after the first surgery (P < .001). A significant number of patients had impaired sensation to light touch directly after surgery, which was normalized at the late follow-up. Sensimetric testing showed raised thresholds for perception and pain directly after surgery (P = .004-.03), but these were also normalized at the late follow-up.CONCLUSION: PBC is a treatment that can be effective for many patients with MS-TN. Repeated previous surgeries is a risk factor for an unsatisfactory outcome. However, the patients with multiple surgeries had less satisfactory results already at the first procedure, indicating that a therapy resistant disease can be predicted after the first two PBCs. Postoperative sensory deficits were common but not lasting.
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| 9. |
- 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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| 10. |
- Asplund, Pär, et al.
(författare)
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Percutaneous Balloon Compression vs Percutaneous Retrogasserian Glycerol Rhizotomy for the Primary Treatment of Trigeminal Neuralgia
- 2016
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Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 78:3, s. 421-428
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite >30 years of clinical use, the literature is still sparse when it comes to comparisons between percutaneous balloon compression (PBC) and percutaneous retrogasserian glycerol rhizolysis (PRGR) as treatments for trigeminal neuralgia.OBJECTIVE: To perform a retrospective cohort comparison between PBC and PRGR with regard to therapeutic effect, side effects, and complications.METHODS: Medical records and follow-up data from 124 primary PRGRs performed from 1986 to 2000 and 82 primary PBCs performed from 2000 to 2013 were reviewed. All patients had undergone clinical sensory testing and assessment of sensory thresholds. Analyses were performed to compare duration of pain relief, frequency of sensory disturbances, and side effects.RESULTS: Median duration of pain relief was 21 months after PRGR and 20 months after PBC. Both methods carried a high risk of hypesthesia/hypalgesia (P < .001) that was partly reversed with time. Decreased corneal sensibility was common after PRGR (P < .001) but not after PBC. Dysesthesia was more common after PRGR (23%) compared after PBC (4%; P < .001). Other side effects were noted but uncommon.CONCLUSION: PBC and PRGR are both effective as primary surgical treatment of trigeminal neuralgia. Both carry a risk of postoperative hypesthesia, but in this series, the side effect profile favored PBC. Furthermore, PBC is technically less challenging, whereas PRGR requires fewer resources. Between these 2 techniques, we propose PBC as the primary surgical technique for percutaneous treatment of trigeminal neuralgia on the basis of its lower incidence of dysesthesia, corneal hypesthesia, and technical failures.ABBREVIATIONS: MS, multiple sclerosisPBC, percutaneous balloon compressionPRGR, percutaneous retrogasserian glycerol rhizotomyTN, trigeminal neuralgiaThis is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially.
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| 11. |
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| 12. |
- Bergenheim, A Tommy, et al.
(författare)
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Diplopia after balloon compression of retrogasserian ganglion rootlets for trigeminal neuralgia : technical case report.
- 2008
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4040 .- 0148-396X. ; 62:2, s. E533-4; discussion E534
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Balloon compression of the rootlets behind the trigeminal ganglion for the treatment of trigeminal neuralgia has become an increasingly popular method among neurosurgeons. However, the method has recognized complications, including double vision. Although occurring infrequently, diplopia may cause the patient significant disability. To minimize the risk for this complication, we analyzed our patients with respect to the surgical technique. METHODS: We reviewed our joint consecutive series of 193 patients with trigeminal neuralgia treated with balloon compression. The medical records and the intraoperative x-ray images were analyzed. RESULTS: We identified six patients with double vision postoperatively. In analyzing these occurrences, we found that the balloon was inflated outside Meckel's cave in four patients, the balloon was initially inflated too deeply in one patient, and the anatomy of Meckel's cave was probably aberrant in one patient. In five of the six patients, the symptoms resolved within 5 months. CONCLUSION: By meticulous surgical technique with close attention to the anatomic position and the shape of the inflated balloon, most cases of postcompression diplopia should be avoided.
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| 13. |
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| 14. |
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| 15. |
- Bergenheim, Tommy A, et al.
(författare)
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Selective peripheral denervation for cervical dystonia : long-term follow-up
- 2015
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:12, s. 1307-1313
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 61 procedures with selective peripheral denervation for cervical dystonia were retrospectively analysed concerning surgical results, pain, quality of life (QoL) and recurrences.METHODS: The patients were assessed with the Tsui torticollis scale, Visual Analogue Scale (VAS) for pain and Fugl-Meyer scale for QoL. Evaluations were performed preoperatively, early postoperatively, at 6 months, then at a mean of 42 (13-165) months. All patients underwent electromyogram at baseline, which was repeated in cases who presented with recurrence of symptoms after surgery.RESULTS: Six months of follow-up was available for 55 (90%) of the procedures and late follow-up for 34 (56%). The mean score of the Tsui scale was 10 preoperatively. It improved to 4.5 (p<0.001) at 6 months, and 5.3 (p<0.001) at late follow-up. VAS for pain improved from 6.5 preoperatively to 4.2 (p<0.001) at 6 months and 4 (p<0.01) at late follow-up. The Fugl-Meyer score for QoL improved from 43.3 to 46.6 (p<0.05) at 6 months, and to 51.1 (p<0.05) at late follow-up. Major reinnervation and/or change in the dystonic pattern occurred following 29% of the procedures, and led in 26% of patients to reoperation with either additional denervation or pallidal stimulation.CONCLUSIONS: Selective peripheral denervation remains a surgical option in the treatment of cervical dystonia when conservative measures fail. Although the majority of patients experience a significant relief of symptoms, there is a substantial risk of reinnervation and/or change in the pattern of the cervical dystonia.
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| 16. |
- Bergenheim, Tommy, et al.
(författare)
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Percutaneous retrogasserian balloon compression for trigeminal neuralgia : review of critical technical details and outcomes
- 2013
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Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750 .- 1878-8769. ; 79:2, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe percutaneous balloon compression (PBC) of the trigeminal rootlets as treatment for trigeminal neuralgia (TN), including history, operative techniques, outcomes, side effects, and some recent findings increasing the likelihood of a positive outcome.METHODS: PBC is indicated in patients with TN in whom microvascular decompression is considered less suitable. The procedure is simplified by the use of biplanar fluoroscopy, although it is usually carried out with C-arm fluoroscopy to facilitate the introduction of the needle and the visualization of the inflated catheter. In the right position, a clearly defined pear shape usually appears after injection of 0.5-0.7 mL of contrast material. The balloon is kept inflated for 1.5-3 minutes. It is crucial to obtain a pear shape because this probably is the most significant factor for obtaining good, long-lasting pain relief.RESULTS: An analysis of 100 consecutive PBC procedures showed an initial success rate of 90% and a median pain-free time without medication of 28 months. Subdividing these patients into primary TN (n = 77) and TN secondary to multiple sclerosis (a = 23), the median pain-free times were 33 months and 24 months (P = 0.2), indicating that the outcome may depend on the preoperative conditions.CONCLUSIONS: Complications and side effects include cardiovascular stress during the procedure, local hemorrhages in the cheek, postoperative sensory disturbance, masseter weakness, infections, and transitory diplopia after surgery. Measures to minimize side effects are proposed. With meticulous technique, PBC is a straightforward, effective, and fast procedure that compares well with other percutaneous therapies for TN.
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| 17. |
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| 18. |
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| 19. |
- Bergman, Joakim, et al.
(författare)
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Intrathecal treatment trial of rituximab in progressive MS : results after a 2-year extension
- 2021
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Ingår i: Journal of Neurology. - : Springer Berlin/Heidelberg. - 0340-5354 .- 1432-1459. ; 268:2, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.Methods: Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.Results: Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.Conclusions: IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.
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| 20. |
- Bergman, Joakim, et al.
(författare)
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Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study
- 2018
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Ingår i: Neurology. - : Wolters Kluwer. - 1526-632X .- 0028-3878. ; 91:20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To perform a phase 1b assessment of the safety and feasibility of intrathecally delivered rituximab as a treatment for progressive multiple sclerosis (PMS) and to evaluate the effect of treatment on disability and CSF biomarkers during a 1-year follow-up period. METHODS: Three doses of rituximab (25 mg with a 1-week interval) were administered in 23 patients with PMS via a ventricular catheter inserted into the right frontal horn and connected to a subcutaneous Ommaya reservoir. Follow-ups were performed at 1, 3, 6, 9, and 12 months. RESULTS: Mild to moderate vertigo and nausea were common but temporary adverse events associated with intrathecal rituximab infusion, which was otherwise well tolerated. The only severe adverse event was a case of low-virulent bacterial meningitis that was treated effectively. Of 7 clinical assessments, only 1 showed statistically significant improvement 1 year after treatment. No treatment effect was observed during the follow-up period among 6 CSF biomarkers. CONCLUSIONS: Intrathecal administration of rituximab was well tolerated. However, it may involve a risk for injection-related infections. The lack of a control group precludes conclusions being drawn regarding treatment efficacy. CLINICALTRIALSGOV IDENTIFIER: NCT01719159. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections. © 2018 American Academy of Neurology.
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| 21. |
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| 22. |
- Bergman, Joakim, et al.
(författare)
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Location matters : highly divergent protein levels in samples from diferent CNS compartments in a clinical trial of rituximab for progressive MS
- 2020
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.Methods: During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively.Results: Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman’s rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF.Conclusion: A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.
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| 23. |
- Bergman, Joakim, et al.
(författare)
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Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.
- 2016
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Ingår i: Neurology® neuroimmunology & neuroinflammation. - 2332-7812. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.
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| 24. |
- Bergman, Joakim, 1989-
(författare)
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Studies of the Biology of Intrathecal Treatment in Progressive MS
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune disease, affecting the central nervous system (CNS). About 85% of afflicted present with a relapsing-remitting form of the disease (RRMS), for which a breakthrough in treatment was made in 2008 with rituximab, an antibody directed towards CD20, a surface antigen on B-cells. These findings also contributed to cementing the importance of the B-cell’s role in MS pathophysiology. However, MS also exist as a progressive phenotype, affecting most MS patients either from onset or after a transition from RRMS, and for progressive MS the same treatment effect of anti-CD20 has not been observed. Still, studies have found follicle-like structures containing B-cells in meninges and subarachnoid space of the cortex in progressive MS brains, supporting the involvement of B-cells. Evidence also support the existence of a chronic, low-grade inflammatory process compartmentalised within the CNS that correlates with the progressive phase of MS, which may present a treatment barrier towards anti-CD20. Peripherally administrated therapeutic antibodies cross the intact blood-brain barrier with low efficiency with only 0.1-0.5% of the plasma concentration occurring in the cerebrospinal fluid (CSF). Intrathecal (IT) administration circumvents the blood-brain barrier, presenting an opportunity to better target the CNS B-cells.Aims: To evaluate the safety and feasibility of intrathecal anti-CD20 therapy with rituximab in progressive MS, its effect on disease progression through clinical parameters, and impact on biomarkers in CSF. Furthermore, this thesis aimed to evaluate the effect on biomarkers representative of cell injury related to insertion of a ventricular catheter for drug administration and to examine the interstitial milieu in the brain through microdialysis (MD).Methods: The thesis is based on the open-label, phase IIb, multicentre clinical trial Intrathecal Treatment Trial in Progressive Multiple Sclerosis (ITT-PMS; EudraCT 2008-002626-11), in which 23 participants received IT treatment with rituximab, and the extended follow-up study, ITT-PMS extension (EudraCT 2012-000721-53). All participants received a ventricular catheter and an Ommaya reservoir for drug administration through a neurosurgical procedure, and 10 participants received a MD catheter in parallel to the ventricular catheter for 10 days. The treatment effect was evaluated by regular clinical evaluations and analyses of CSF. The clinical outcome was evaluated through walking and upper-limb function tests, and by clinical evaluation scales. Levels of selected CSF biomarkers were analysed from the same time-points as the clinical evaluations.Results: After the completion of the extension trial, one clinical parameter (cognitive performance) showed improvement but could most likely be explained by a learning effect. Worsening of walking speed was observed, while the remaining clinical parameters showed no change. Two severe adverse events occurred in the form of low-virulent bacterial meningitis caused by Propionibacterium, but both were treated effectively with antibiotics without residual symptoms. A ‘spike’ was noticed in the level of lumbar CSF neurofilament light (NFL) following surgery but returned to pre-surgery baseline within 6-12 months. No change was observed for any of the other lumbar CSF biomarkers. No meaningful correlation of protein levels was observed when comparing MD samples, ventricular CSF, and lumbar CSF.Conclusions: Intrathecal treatment through intraventricular administration was well tolerated but not without risks. A continued progression was observed in gait impairment. The insertion of the ventricular catheter caused white matter injury, measured through an increase in NFL in lumbar CSF, in direct association with the surgical procedure. No impact was observed on other CSF biomarkers. There was a poor correlation between different CNS compartments regarding protein levels, arguing for caution in drawing conclusions about brain pathophysiology from lumbar CSF samples.
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| 25. |
- Bjoreland, Anders, et al.
(författare)
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Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic radiotherapy of brain lesions
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1099-1109
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Tidskriftsartikel (refereegranskat)abstract
- Hypofractionated conformal stereotactic radiotherapy (HCSRT) is an established method of treating brain lesions such as arteriovenous malformations (AVMs) and brain metastases. The aim of this study was to investigate the reliability of treatment plans in the terms of dose distribution and absorbed dose for HCSRT. Methods and materials. Treatment plans for three different clinical intracerebral targets, AVMs, were transferred to a CT study of a spherical water filled phantom simulating the human head and recalculated for the phantom geometry using a standard treatment planning system utilizing a pencil beam algorithm for dose calculation. The calculated absorbed dose, relative three dimensional (3D) dose distribution and dose conformity were investigated using gel dosimetry normalized to liquid ionization chamber (LIC) measurements. Results. The measured absorbed dose to the dose reference point was found to be within 2% of the calculated dose for all three targets. The measured dose distribution was found to be within 3% and 2 mm of the calculated dose for more than 93% of all points in the target volume for all three targets. Conclusions. The results show that the investigated standard treatment planning system can correctly predict the absorbed dose and dose distribution in different types of intracerebral targets and that the treatment can be delivered according to the plan.
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| 26. |
- Björkblom, Benny, et al.
(författare)
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Distinct metabolic hallmarks of WHO classified adult glioma subtypes
- 2022
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:9, s. 1454-1468
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.METHODS: Cross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors - oligodendroglioma (n=31), astrocytoma (n=31) and glioblastoma (n=162) - were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2-4, and MGMT promoter methylation.RESULTS: Distinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.CONCLUSION: Key metabolic differences exist across adult glioma subtypes.
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| 27. |
- Björkblom, Benny, et al.
(författare)
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Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma
- 2020
-
Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 122:2, s. 221-232
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.
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| 28. |
- Blomstedt, Patric, et al.
(författare)
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A family with a hereditary form of torsion dystonia from northern Sweden treated with bilateral pallidal deep brain stimulation
- 2009
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 24:16, s. 2415-2419
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate pallidal DBS in a non-DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non-DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and "on" stimulation after a mean of 2.5 years (range 1-3) using the Burke-Fahn-Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 +/- 24 to 9 +/- 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia.
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| 29. |
- Capelle, Hans-Holger, et al.
(författare)
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Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery
- 2012
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 27:2, s. 301-304
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. Methods: Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/ Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-FahnMarsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. Results: The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P <.05) and by a mean of 69.5% according to the Burke-FahnMarsden dystonia rating scale (P <.05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P <.05) at long-term follow-up (mean, 41.5 months). Conclusions: Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients. (C) 2011 Movement Disorder Society
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| 30. |
- Eriksson, Maria, et al.
(författare)
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Improved treatment of glioblastoma : changes in survival over two decades at a single regional Centre
- 2019
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 58:3, s. 334-341
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center.Patients and methods: Survival was studied for 571 patients in our region diagnosed with GBM between 1995 and 2015. Samples from 244 patients out of those treated 2005-2015 have been included in a tissue/blood bank and a clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment.Results: The median OS for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995-1996 and 2010-2015, respectively (p<.05). The 2-year survival for the same time periods improved from 7% to 18% (p<.01). After introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased OS was noted and following implementation of intraoperative 5-aminolevulinic acid the number of tumor resection 95% did increase from 33% to 54% (p<.001). Positive prognostic factors for survival were young age, good performance status, absence of inflammatory disease, absence of diabetes or metabolic disease, tumor resection 95%, and completion of postoperative radiochemotherapy.Discussion: The results of this study are consistent with earlier results regarding survival and prognostic factors and confirm results from randomized controlled trials in a clinical setting. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.
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| 31. |
- Eriksson, Maria, et al.
(författare)
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Treatment of Glioblastoma : Improvements over two decades at a single centre
- 2018
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20, s. 236-236
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Glioblastoma (GBM) is a rapidly progressing tumour with a short overall survival. The treatment of GBM has evolved over the last decades and is today multimodal including surgery with maximal tumour resection followed by radiotherapy and chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single centre.PATIENTS AND METHODS: 244 patients treated for GBM 2005 - 2015 has been included in a tissue bank with tumour tissue and/or blood samples. A clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment. Survival was also studied for all 571 patients in our region diagnosed with GBM between 1995 and 2015.RESULTS: The overall median survival for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995–1996 and 2010–2015, respectively (p<0.05). The two-year survival for the same time periods improved from 7.4% to 17.8% (p<0.01). After the introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased survival was noted. The implementation of intraoperative 5-aminolevulinic acid did, in patients that underwent tumour resection, increase the number of total tumour resections (≥95%) from 32.6% to 54.1% (p<0.001). Positive prognostic factors were young age, good performance status, absence of diabetes or metabolic disease, total tumour resection and completion of postoperative radiochemotherapy.CONCLUSIONS: The results of this study are in line with earlier results regarding survival and prognostic factors. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.
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| 32. |
- Fisher, James L., et al.
(författare)
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Loud Noise Exposure and Acoustic Neuroma
- 2014
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 180:1, s. 58-67
-
Tidskriftsartikel (refereegranskat)abstract
- The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.
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| 33. |
- Fytagoridis, Anders, et al.
(författare)
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Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor
- 2012
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 83:3, s. 258-262
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS. less thanbrgreater than less thanbrgreater thanMethods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5+/-10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated. less thanbrgreater than less thanbrgreater thanResults A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time. less thanbrgreater than less thanbrgreater thanConclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.
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| 34. |
- Gunnarsson, Stina, et al.
(författare)
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Patients Expectations Before Initiation of Intrathecal Baclofen Treatment: A Longitudinal Study with 1-Year Follow-Up
- 2023
-
Ingår i: Journal of Rehabilitation Medicine. - : FOUNDATION REHABILITATION INFORMATION. - 1650-1977 .- 1651-2081. ; 55
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate patients expectations, met/unmet expectations and satisfaction with intrathecal baclofen treatment in relation to effect on spasticity, pain intensity, sleep quality, occupational performance, well-being and self-efficacy. Design: A prospective longitudinal study with follow-up at 1 year. Patients: Consecutive patients, age >= 18 years with a disabling spasticity of cerebral or spinal origin selected for intrathecal baclofen treatment at 2 university hospitals in Sweden were included. From August 2016 to June 2019, 35 patients began intrathecal baclofen treatment; 29 patients were included and completed the study. Methods: Baseline and 1-year follow-up included assessment of spasticity by physiotherapists, a semi-structured interview regarding occupational performance using the Canadian Occupational Performance Measure and a questionnaire. Results: Overall satisfaction with treatment and satisfaction with occupational performance were reported as moderate. Important variables that explained satisfaction with occupational performance were improvements in performance, expectations and performance before treatment. Patients had higher expectations compared with the 1-year outcomes regarding occupational performance, spasticity, pain intensity and sleep quality, although improvements were reported. Conclusion: A thorough discussion of goal setting with intrathecal baclofen treatment before implantation is necessary to give patients individual and realistic expectations.
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| 35. |
- Guo, Dongsheng, et al.
(författare)
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Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors
- 2006
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 111:3, s. 238-346
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3–GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3–GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.
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| 36. |
- Hariz, Gun-Marie, et al.
(författare)
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Assessment of ability/disability in patients treated with chronic thalamic stimulation for tremor.
- 1998
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 13:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Chronic thalamic stimulation (CTS) has a documented good effect on tremor in patients with Parkinson's disease (PD) and essential tremor (ET). This study evaluates whether the alleviation of impairment, i.e., tremor, translates into improvement of the patient's ability in performing instrumental activities of daily living (IADL). Thirteen patients were assessed with an occupational therapy tool called Assessment of Motor and Process Skills (AMPS). This observation-based scale rates the patient's motor and process skills needed to perform a given task. The evaluations were done at a mean of 13 months after surgery in the patient's home, and included assessments of IADL with the CTS activated and switched off, respectively. The results showed that most patients improved to variable degrees in their IADL ability when the thalamic stimulation was on. The improvement was more marked in patients operated on for tremor of their dominant hand. The improvement concerned mainly the skill items related to the patients' abilities of coordination, calibration, endurance, and accommodation during IADL task performance. The authors concluded that for some patients with tremor, CTS can improve independence in domestic activities of daily living.
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| 37. |
- Hariz, Gun-Marie, et al.
(författare)
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Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation.
- 2003
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 18:4, s. 373-381
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the impact of pallidotomy and thalamic deep brain stimulation (DBS) on disability of patients with advanced Parkinson's disease and investigated whether the activities of daily living (ADL) section of the Unified Parkinson's Disease Rating Scale (UPDRS) measures disability in everyday life. Nineteen patients who had pallidotomy and 14 patients who had thalamic DBS were followed for a mean of 11 months. Evaluation tools included the UPDRS as well as a generic ADL scale, called ADL taxonomy. The 13 items belonging to the ADL part of the UPDRS were classified into two categories according to whether the items described a disability or impairment. The total scores of the UPDRS Part II (ADL) were ameliorated in both the pallidotomy and the thalamic DBS groups. When analysing separately the scores from the two categories of the ADL part of the UPDRS, i.e., disability and impairment, only patients who underwent pallidotomy showed improvement in disability-related items. These findings were confirmed when evaluating the patients with the ADL taxonomy. The ADL part of the UPDRS contains a mixture of impairment- and disability-related items. This mixture may confound results when evaluating the impact of surgery on ADL.
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| 38. |
- Hariz, Gun-Marie, et al.
(författare)
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Gender differences in disability and health-related quality of life in patients with Parkinson's disease treated with stereotactic surgery
- 2003
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 108:1, s. 28-37
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate eventual differences between women and men with Parkinson's disease (PD) before and after surgery, with respect to clinical status, disability and health-related quality of life (HRQoL). MATERIAL AND METHODS: Twenty-four men and 14 women with PD received a total of 46 surgical procedures (pallidotomy, thalamotomy and deep brain stimulation of the thalamus, pallidum or subthalamic nucleus). The impact of PD on disability and other aspects of HRQoL was analysed separately in men and women before and at a mean of 11 months after surgery, using the following assessment tools: The Unified Parkinson's Disease Rating Scale (UPDRS), the ADL Taxonomy, the Nottingham Health Profile, the Life Satisfaction Questionnaire and a Visual Analogue Scale. RESULTS: At surgery, women had a significantly longer duration of disease than men (mean: 15 vs. 10 years, P < 0.01). They had a higher stage on the Hoehn and Yahr scale and worse scores on UPDRS parts II (ADL) and IV (complications), as well as on the Schwab and England scale and on the ADL Taxonomy. Following surgery, both men and women showed improvement, but women experienced greater benefit than men in ADL, in emotions, and in social life. CONCLUSIONS: Perhaps women with PD should be offered surgery more often and earlier in the course of their disease.
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| 39. |
- Hariz, Gun-Marie, et al.
(författare)
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Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor
- 2002
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 72:1, s. 47-52
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the impact of thalamic deep brain stimulation (DBS) on disability and health-related quality of life in patients with essential tremor.METHODS: Twenty seven consecutive patients were evaluated prospectively, before surgery and at a mean of 12 months (range 6-26) after thalamic DBS. Assessment tools included the Fahn-Tolosa-Marìn tremor rating scale (TRS), activities of daily living (ADL) taxonomy, Nottingham health profile (NHP) and the visual analogue scale (VAS) for measuring impact of disease on life. Additional information on the side effects of, and expectations from surgery was obtained by interview.RESULTS: Thalamic DBS improved the ability of the patients in eating, drinking, writing, home maintenance, hobbies, and participation in society. Activities of daily life requiring bimanual skills were less improved. The emotional condition of the patients was positively affected and the negative impact of the disease on life as a whole, and on social life was decreased. Seventy per cent of the patients considered that the surgical treatment met their expectations.CONCLUSIONS: After thalamic DBS, health-related quality of life including disability in ADL and social life were improved in patients with essential tremor.
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| 40. |
- Henriksson, Roger, et al.
(författare)
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Boron neutron capture therapy (BNCT) for glioblastoma multiforme : a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA)
- 2008
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:2, s. 183-91
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. PATIENT AND METHODS: This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. RESULTS: The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. CONCLUSION: Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.
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| 41. |
- Henriksson, Roger, et al.
(författare)
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High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.
- 2006
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Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 78:3, s. 321-6
-
Tidskriftsartikel (refereegranskat)abstract
- Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.
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| 42. |
- Johansson, Johannes D., 1977-, et al.
(författare)
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Combined diffuse light reflectance and electric impedance measurements for navigation aid in deep brain surgery
- 2009
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Ingår i: Stereotactic and Functional Neurosurgery. - Basel : S. Karger AG. - 1011-6125 .- 1423-0372. ; 87:2, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study is to investigate reflected light intensity combined with impedance for navigation aid during stereotactic neurosurgery.Methods: During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing optical fibres. The signals were compared with anatomy determined from pre- and postoperative MRI and CT. The measurements were performed within minutes and signal analysis was done post-operatively.Results: Reflected light intensity was low from cortex, lateral ventricle, caudate nucleus and putamen. It was intermediate from globus pallidus and thalamus while it was high from subcortical white matter, internal capsule and the subthalamus. The electric impedance was less consistent but generally low in the cortex, intermediate in subcortical white matter, the putamen, the globus pallidus and the thalamus and high in the internal capsule and the subthalamus.Conclusion: Reflected light intensity and electric impedance give complementary information about passed tissue and the combination seems promising for navigation aid during stereotactic neurosurgery.
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| 43. |
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| 44. |
- Johansson, Mikael, et al.
(författare)
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Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model
- 1997
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Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 41:1, s. 237-244
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.
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| 45. |
- Lenfeldt, Niklas, et al.
(författare)
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Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves
- 2004
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 101:6, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.
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| 46. |
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| 47. |
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| 48. |
- Lindvall, Peter, et al.
(författare)
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A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases.
- 2009
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 151:9, s. 1053-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The standard treatment of solitary brain metastases previously has been tumour resection in combination with whole-brain radiation therapy (WBRT). Stereotactic radiotherapy has emerged as a non-invasive treatment option especially for small brain metastases. We now report our results on resection + WBRT or hypofractionated stereotactic irradiation (HCSRT) in the treatment of solitary brain metastases. METHODS: Between 1993 and 2004 patients with metastatic cancer and solitary brain metastases were selected for surgical resection + WBRT or HCSRT alone at the Umeå University Hospital. Fifty-nine patients were treated with surgical resection + WBRT (34 male, 25 female, mean age 63.3 years). Forty-seven patients were treated with HCSRT alone (15 male, 32 female, mean age 64.9 years). FINDINGS: In patients followed radiologically, 28% treated with resection + WBRT showed a local recurrence after a median time of 8.0 months, whereas there was a lack of local control in 16% in the HCSRT group after a median time of 3.0 months. There was a significantly longer survival time for patients treated with resection + WBRT (median 7.9, mean 12.9 months) compared to HCSRT (median 5.0, mean 7.6 months). Even in patients with a tumour volume <10 cc, there was a significantly longer survival in favour of resection + WBRT (median 8.4, mean 17.4 months) compared to HCSRT (median 5.0, mean 7.9 months). CONCLUSION: This retrospective and non-randomised study indicates that surgical resection in combination with WBRT may be an option even for small brain metastases suitable for treatment with HCSRT. Since survival and local control following resection + WBRT was at least as favourable as compared to HCSRT alone, tumour location and expected neurological outcome may be the strongest aspect when selecting treatment modality.
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| 49. |
- Lindvall, Peter, et al.
(författare)
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Air Transportation of Patients with Brain Tumours
- 2011
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Ingår i: Tumors of the Central Nervous system, Volume 3. - DORDRECHT : Springer Netherlands. - 9789400713987 - 9789400713994 ; , s. 339-343
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Bokkapitel (refereegranskat)abstract
- Air transportation of patients to specialised health care services has become ever more important in modern health care. Air transport has the advantage of a swift transport and the possibility to cover large geographical areas. Air transport may be used for the pre and postoperative transport of patients with brain tumours. Preoperative transport of patients harbouring brain tumours seem to be safe in most cases even if there are a few reports reporting clinical deterioration during and after air transport. Results from microdialysis of normal brain tissue and tumour tissue have shown only minor metabolic changes during and after air transport. In case of postoperative air transport of patients operated for brain tumours the presence of intracranial air be associated with an increased risk. Intracranial air can be treated as an ideal gas and will expand as the cabin pressure in the aeroplane decreases. Air trapped in the intracranial cavity cannot easily expand, however, and this may result in an increased intracranial pressure. Therefore it may be recommended that patients with a large amount of intracranial air should be transported with ground transportation or with air transportation where the cabin is pressurized to sea level.
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| 50. |
- Lindvall, Peter, et al.
(författare)
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Cerebral metabolism during air transport of patients after surgery for malignant glioma
- 2008
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Ingår i: Aviation, Space and Environmental Medicine. - 0095-6562 .- 1943-4448. ; 79:7, s. 700-703
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Post-operative air transport of patients following an intracranial procedure is not uncommon. The transport itself may pose a risk, and if there are harmful effects to the brain this should be reflected in the brain metabolism. The aim of this study was to analyze possible alterations in cerebral metabolism that could be caused by air transport.METHODS: Four patients with glioblastomas were operated with a biopsy or a craniotomy. During this procedure microdialysis catheters were placed in tumor tissue or brain adjacent to tumor and in normal cerebral tissue. In this study we have analyzed cerebral glucose metabolites (glucose, lactate / pyruvate ratio), glycerol, and glutamate at five time points during a 24-h period including air transport.RESULTS: Analyzing mean values, there was a small but significant increase in the lactate/pyruvate ratio from 45.18 to 47.78 in normal cerebral tissue after air transport compared to a previous fasting sample. For tumor tissue there was a small decrease in glucose from 1.04 to 0.92 mmol L(-1) and an increase in glutamate from 13.08 to 19.06 micromol L(-1). There were no other significant differences in the analyzed cerebral metabolites after air transport.DISCUSSION: There were only minor differences in levels of cerebral metabolites after air transport compared to a previous fasting sample. Thus it seems that air transportation of the four reported patients did not cause any major cellular damage or metabolic changes as assessed by extracellular glucose, lactate/pyruvate ratio, glycerol, or glutamate.
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