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  • 1. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Khademi, Mohsen
    Dring, Ann M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016Ingår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, nr 1, artikel-id e191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 2.
    Andersson, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Behnam-Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation2002Ingår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 19, nr 1, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 3. Antonsson, Johan
    et al.
    Eriksson, Ola
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Richter, Johan
    Zsigmond, Peter
    Wårdell, Karin
    Diffuse reflectance spectroscopy measurements for tissue-type discrimination during deep brain stimulation.2008Ingår i: Journal of neural engineering, ISSN 1741-2560, Vol. 5, nr 2, s. 185-190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 4.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kvarnbrink, Samuel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Holmlund, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.2012Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, nr 7, s. 2407-2413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 5.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kvarnbrink, Samuel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Holmlund, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors2012Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, nr 7 ; Special Issue, s. 2407-2413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 6.
    Asplund, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Percutaneous Balloon Compression vs Percutaneous Retrogasserian Glycerol Rhizotomy for the Primary Treatment of Trigeminal Neuralgia2016Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, nr 3, s. 421-428Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 7.
    Asplund, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linderoth, Bengt
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    The predictive power of balloon shape and change of sensory functions on outcome of percutaneous balloon compression for trigeminal neuralgia2010Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 113, nr 3, s. 498-507Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The authors have demonstrated that using a pear-shaped balloon when performing percutaneous balloon compression for trigeminal neuralgia results in longer pain relief than non-pear-shaped balloons. Other surgical parameters seemed less important with respect to pain relief. Balloon compression also, in many cases, results in hypesthesia.

  • 8.
    Asplund, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linderoth, Bengt
    Lind, Göran
    Winter, Jaleh
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis2019Ingår i: Operative neurosurgery, ISSN 2332-4252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 9.
    Bergenheim, Tommy A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, London, UK.
    Selective peripheral denervation for cervical dystonia: long-term follow-up2015Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 12, s. 1307-1313Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 10.
    Bergenheim, Tommy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Asplund, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linderoth, Bengt
    Percutaneous retrogasserian balloon compression for trigeminal neuralgia: review of critical technical details and outcomes2013Ingår i: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 79, nr 2, s. 359-368Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 11.
    Bergenheim, Tommy
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malmström, Annika
    Bolander, Hans
    Michanek, Annika
    Stragliotto, Giuseppe
    Damber, Lena
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Björ, Ove
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Registrering av primära hjärntumörer mått på nationell vårdkvalitet. Regionala skillnader avslöjade.2007Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, nr 5, s. 332-341Artikel i tidskrift (Refereegranskat)
  • 12.
    Bergman, J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuolikainen, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis2016Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, s. 511-511Artikel i tidskrift (Refereegranskat)
  • 13.
    Bergman, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Burman, Joachim
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Zetterberg, Henrik
    Jiltsova, Elena
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, nr 20, s. E1893-E1901Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 a1-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. ClinicalTrials.gov 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.

  • 14.
    Bergman, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zetterberg, Henrik
    Blennow, Kaj
    Norgren, Niklas
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden..
    Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS2016Ingår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, nr 5, artikel-id e271Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: 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.

    METHODS: Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year. Levels of neurofilament light polypeptide (NF-L), glial fibrillary acidic protein, microtubule-associated protein tau, and S100 calcium binding protein B were measured in the CSF, and NF-L was also quantified in serum at each time point.

    RESULTS: One month after neurosurgical trauma, there was a distinct peak in NF-L concentration in both CSF and serum. In contrast, the biomarkers S100 calcium binding protein B, glial fibrillary acidic protein, and microtubule-associated protein tau did not show any significant changes. NF-L levels in both CSF and serum peaked at 1 month post surgery, returning to baseline after 6 to 9 months. A strong correlation was observed between the concentrations of NF-L in CSF and serum.

    CONCLUSIONS: The NF-L level, in CSF and serum, appears to be both a sensitive and specific marker for white matter axonal injury. This makes NF-L a valuable tool with which to evaluate acute white matter axonal damage in a clinical setting. Serum analysis of NF-L may become a convenient way to follow white matter axonal damage longitudinally.

  • 15. Björeland, Anders
    et al.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Karlsson, Anna
    Gustavsson, Helen
    Bäck, Sven A J
    Karlsson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bergenheim, Tommy A
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic radiotherapy of brain lesions2008Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, nr 6, s. 1099-1109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 16.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Tisch, Stephen
    Holmberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Bergenheim, Tommy A
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    A family with a hereditary form of torsion dystonia from northern Sweden treated with bilateral pallidal deep brain stimulation2009Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 24, nr 16, s. 2415-2419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 17. Capelle, Hans-Holger
    et al.
    Blahak, Christian
    Schrader, Christoph
    Baezner, Hansjoerg
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Krauss, Joachim K.
    Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery2012Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, nr 2, s. 301-304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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

  • 18.
    Eriksson, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sandström, M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    TREATMENT OF GLIOBLASTOMA: IMPROVEMENTS OVER TWO DECADES AT A SINGLE CENTRE2018Ingår i: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, s. 236-236Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    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.

  • 19.
    Eriksson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kahari, Jenna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vestman, Amanda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Improved treatment of glioblastoma: changes in survival over two decades at a single regional Centre2019Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, nr 3, s. 334-341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 20.
    Fytagoridis, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Sandvik, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Åström, Mattias
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor2012Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, nr 3, s. 258-262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

    Methods 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.

    Results 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.

    Conclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.

  • 21.
    Guo, Dongsheng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nilsson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Haapasalo, Hannu
    Raheem, Olayinka
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors2006Ingår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 111, nr 3, s. 238-346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 22.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Assessment of ability/disability in patients treated with chronic thalamic stimulation for tremor.1998Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 13, nr 1, s. 78-83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 23.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor2002Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 72, nr 1, s. 47-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 24.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    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.2003Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 18, nr 4, s. 373-381Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 25.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Gender differences in disability and health-related quality of life in patients with Parkinson's disease treated with stereotactic surgery2003Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, nr 1, s. 28-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 26.
    Henriksson, Roger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Capala, Jacek
    Michanek, Annika
    Lindahl, Sten-Åke
    Salford, Leif G
    Franzén, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Blomquist, Erik
    Westlin, Jan-Erik
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Boron neutron capture therapy (BNCT) for glioblastoma multiforme.: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).2008Ingår i: Radiother Oncol, ISSN 0167-8140, Vol. 88, nr 2, s. 183-191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 27.
    Henriksson, Roger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Malmström, Annika
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Gertrud
    Trojanowski, Thomas
    Andreasson, Lars
    Blomquist, Erik
    Jonsborg, Sonny
    Edekling, Tomas
    Salander, Pär
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    High-grade astrocytoma treated concomitantly with estramustine and radiotherapy2006Ingår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 78, nr 3, s. 321-326Artikel i tidskrift (Refereegranskat)
  • 28.
    Johansson, Johannes D
    et al.
    Department of Biomedical Engineering, Linköping University, Linköping.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Haj-Hosseini, Neda
    Department of Biomedical Engineering, Linköping University, Linköping.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Eriksson, Ola
    Department of Biomedical Engineering, Linköping University, Linköping.
    Wårdell, Karin
    Department of Biomedical Engineering, Linköping University, Linköping.
    Combined diffuse light reflectance and electrical impedance measurements as a navigation aid in deep brain surgery2009Ingår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 87, nr 2, s. 105-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: The aim of this study is to assess reflected light intensity combined with impedance as a 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 the anatomy, determined from pre- and post-operative MRI and CT. The measurements were performed within minutes, and signal analysis was done post-operatively.

    RESULTS: Reflected light intensity was low from the cortex, lateral ventricle, caudate nucleus and putamen; intermediate from the globus pallidus and thalamus; while it was high from the subcortical white matter, internal capsule and subthalamus. The electrical impedance was less consistent, but generally low in the cortex, intermediate in the subcortical white matter, putamen, globus pallidus and thalamus, and high in the internal capsule and subthalamus.

    CONCLUSION: Reflected light intensity and electrical impedance give complementary information about passed tissue, and the combination seems promising as a navigation aid during stereotactic neurosurgery.

  • 29.
    Lindgren, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sandström, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Jonsson, Yvonne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    VEGF and tPA co-expressed in malignant glioma1997Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 36, nr 6, s. 615-618Artikel i tidskrift (Refereegranskat)
  • 30.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Air Transportation of Patients with Brain Tumours2011Ingår i: Tumors of the Central Nervous system, Volume 3: Brain Tumors (Part 1) / [ed] M.A. Hayat, DORDRECHT: Springer Netherlands, 2011, Vol. 3, s. 339-343Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    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.

  • 31.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Blomquist, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Radiation schedules in relation to obliteration and complications in hypofractionated conformal stereotactic radiotherapy of arteriovenous malformations2010Ingår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, nr 1, s. 24-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: The purpose of this investigation was to assess the obliteration rate and complications following different radiation schedules of hypofractionated conformal stereotactic radiotherapy for cerebral arteriovenous malformations (AVMs). METHODS: Twenty-five patients were treated with 35 Gy in 5 fractions, whereas 31 patients were treated with 30-32.5 Gy (mean: 31.6 +/- 0.23 Gy) in 5 fractions. A complete angiographic follow-up is available for 40 patients. RESULTS: Thirty-seven out of 40 patients (92.5%) have so far shown obliteration of their AVMs after a mean time of 3.2 +/- 0.26 years (range: 2-8 years). The mean AVM volume in these patients was 8.2 +/- 1.0 cm(3) (range: 1.5-29 cm(3)). There was a higher rate of obliteration (88%) in patients treated with 35 Gy compared to those treated with < 35 Gy (78%), even if this was not statistically significant. There was a significantly shorter time to obliteration in patients treated with 35 Gy. All patients who experienced symptomatic radionecrosis belonged to the group treated with 35 Gy. CONCLUSION: A radiation schedule of 35 Gy in 5 fractions may be more effective than a radiation schedule of <35 (30-32.5) Gy in obliterating AVMs. This may, however, be at the price of an increased risk of symptomatic radionecrosis.

  • 32.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases.2009Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, nr 9, s. 1053-1059Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 33.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hypofractionated conformal stereotactic radiotherapy alone or in combination with whole-brain radiotherapy in patients with cerebral metastases2005Ingår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 61, nr 5, s. 1460-1466Artikel i tidskrift (Refereegranskat)
  • 34.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Reproducibility and geometric accuracy of the Fixster system during hypofractionated stereotactic radiotherapy.2008Ingår i: Radiation Oncology, ISSN 1748-717X, Vol. 3, nr 16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Hypofractionated radiotherapy has been used for the treatment of AVMs and brain metastases. Hypofractionation necessitates the use of a relocatable stereotactic frame that has to be applied on several occasions. The stereotactic frame needs to have a high degree of reproducibility, and patient positioning is crucial to achieve a high accuracy of the treatment.

    METHODS:

    In this study we have, by radiological means, evaluated the reproducibility of the isocenter in consecutive treatment sessions using the Fixster frame. Deviations in the X, Y and Z-axis were measured in 10 patients treated with hypofractionated radiotherapy.

    RESULTS:

    The mean deviation in the X-axis was 0.4 mm (range -2.1 - 2.1, median 0.7 mm) and in the Y-axis -0.3 mm (range -1.4 - 0.7, median -0.2 mm). The mean deviation in the Z-axis was -0.6 (range -1.4 - 1.4, median 0.0 mm).

    CONCLUSION:

    There is a high degree of reproducibility of the isocenter during successive treatment sessions with HCSRT using the Fixster frame for stereotactic targeting. The high reducibility enables a safe treatment using hypofractionated stereotactic radiotherapy.

  • 35.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Grayson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hypofractionated stereotactic radiotherapy in medium-sized to large arteriovenous malformations2015Ingår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 22, nr 6, s. 955-958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have reviewed treatment results in terms of obliteration and complications in 24 patients with medium to large sized cerebral arteriovenous malformations (AVMs) (mean volume 18.5 +/- 8.9 cm(3); range: 10-42) treated with hypofractionated stereotactic radiotherapy (HSRT). AVMs are congenital lesions associated with a high morbidity and mortality. Radiosurgery is one option for treatment. However, in larger AVMs with volumes exceeding 10 cm(3) obliteration rates are less favourable and radiation induced complications more frequent. For larger AVMs, volume-staged radiosurgery is one option while another option may be the use of HSRT. Patients were treated with 6-7 Gy in five fractions to a total dose of 30-35 Gy (mean total dose 32.9 +/- 1.6 Gy [standard error of the mean]). Sixteen patients (69.6%) showed obliteration after a mean time of 35.2 +/- 14.8 months (range: 24-60). Only one patient (4.2%) experienced symptomatic radionecrosis. Our treatment with HSRT seems safe and efficient for treatment of medium to large sized AVMs. Treatment results seem to be in line with volume-staged radiosurgery and may be an alternative for AVMs not suitable for single fraction radiosurgery.

  • 36.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Roslin, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Cerebral metabolism during air transport of patients after surgery for malignant glioma2008Ingår i: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 79, nr 7, s. 700-703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 37.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Wikholm, G
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Combined effects of embolisation and hypofractionated conformal stereotactic radiotherapy in arteriovenous malformations of the brain2005Ingår i: INTERVENTIONAL NEURORADIOLOGY, ISSN 1123-9344, Vol. 11, nr 3, s. 223-229Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There are three major treatment options for cerebral AVMs; surgery, embolization and radiosurgery. Embolization may be effective to reduce the size and density but completely obliterates AVMs only in a minority of cases. Radiosurgery may be an alternative to resection, especially in smaller AVMs. Large AVMs have been considered difficult to treat safely and effectively with single fraction radiosurgery. Hypofractionated conformal stereotactic radiotherapy (HCSRT)alone or in combination with embolization may be an alternative treatment. Embolization may reduce the volume and density of AVMs, followed by HCSRT, allowing a safe delivery of a higher total dose of radiation than possible with a single fraction. Sixteen patients with AVMs were treated with embolization and HCSRT. Embolization was performed in 1-6(median 2) sessions. HCSRT was delivered in 5fractions with 6-7 Gy each to the total dose of30–35 Gy. Cerebral angiographies before and after embolization were digitally compared for calculation of volume reduction and luminescence as a measure of AVM density. The mean AVM volume in 15 patients was reduced from11.9 ± 2.1 (1-29, median 10.0) ml to 6.5 ± 2.0(0.5–28, median 3) ml by embolization. The luminescence for all AVMs was significantly higher after than before embolization, indicating that all AVMs were less dense after embolization. Thirteen out of 16 patients (13/16, 81%) treatedwith embolization and HCSRT have so farshown obliteration of their AVMs 2-9 (median4) years after HCSRT. Three patients experienced neurological sequele after embolization, and three patients developed radionecrosis after HCSRT. Using a new method to compare cerebral angiographies in AVMs we report reduction in density and volume after embolization. The obliteration rate of a combined treatment with embolization and HCSRT seems comparable with single fraction radiosurgery although the AVMs in our series are larger than reported in most series treated with single fraction radiosurgery.

  • 38. Lönn, Stefan
    et al.
    Ahlbom, Anders
    Hall, Per
    Feychting, Maria
    Bergenheim, Tommy
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Long-term mobile phone use and brain tumor risk.2005Ingår i: Am J Epidemiol, ISSN 0002-9262, Vol. 161, nr 6, s. 526-35Artikel i tidskrift (Refereegranskat)
  • 39.
    Mao, Feng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Holmlund, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Faraz, Mahmood
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wang, Wanzhong
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Kvarnbrink, Samuel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Regionalt Cancercentrum Stockholm Gotland, Karolinska, Stockholm, Sweden.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma2018Ingår i: Oncogenesis, E-ISSN 2157-9024, Vol. 7, artikel-id 13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recently, a genome-wide association study showed that a single nucleotide polymorphism (SNP) —rs11706832—in intron 2 of the human LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) gene is associated with susceptibility to glioma. However, the mechanism by which rs11706832 affects glioma risk remains unknown; additionally, it is unknown whether the expression levels of LRIG1 are a relevant determinant of gliomagenesis. Here, we investigated the role of Lrig1 in platelet-derived growth factor (PDGF)-induced experimental glioma in mice by introducing mono-allelic and bi-allelic deletions of Lrig1 followed by inducing gliomagenesis via intracranial retroviral transduction of PDGFB in neural progenitor cells. Lrig1 was expressed in PDGFB-induced gliomas in wild-type mice as assessed using in situ hybridization. Intriguingly, Lrig1-heterozygous mice developed higher grade gliomas than did wild-type mice (grade IV vs. grade II/III, p = 0.002). Reciprocally, the ectopic expression of LRIG1 in the TB107 high-grade human glioma (glioblastoma, grade IV) cell line decreased the invasion of orthotopic tumors in immunocompromised mice in vivo and reduced cell migration in vitro. Concomitantly, the activity of the receptor tyrosine kinase MET was downregulated, which partially explained the reduction in cell migration. In summary, Lrig1 is a haploinsufficient suppressor of PDGFB-driven glioma, possibly in part via negative regulation of MET-driven cell migration and invasion. Thus, for the first time, changes in physiological Lrig1 expression have been linked to gliomagenesis, whereby the SNP rs11706832 may affect glioma risk by regulating LRIG1 expression.

  • 40.
    Mörén, Lina
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ghasimi, Soma
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Metabolomic screening of tumor tissue and serum in glioma patients reveals diagnostic and prognostic information2015Ingår i: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 5, nr 3, s. 502-520Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glioma grading and classification, today based on histological features, is not always easy to interpret and diagnosis partly relies on the personal experience of the neuropathologists. The most important feature of the classification is the aimed correlation between tumor grade and prognosis. However, in the clinical reality, large variations exist in the survival of patients concerning both glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers for a more reliable classification of glioma tumors as well as for prognosis. We analyzed relative metabolite concentrations in serum samples from 96 fasting glioma patients and 81 corresponding tumor samples with different diagnosis (glioblastoma, oligodendroglioma) and grade (World Health Organization (WHO) grade II, III and IV) using gas chromatography-time of flight mass spectrometry (GC-TOFMS). The acquired data was analyzed and evaluated by pattern recognition based on chemometric bioinformatics tools. We detected feature patterns in the metabolomics data in both tumor and serum that distinguished glioblastomas from oligodendrogliomas (p(tumor) = 2.46 × 10(-8), p(serum) = 1.3 × 10(-5)) and oligodendroglioma grade II from oligodendroglioma grade III (p(tumor) = 0.01, p(serum) = 0.0008). Interestingly, we also found patterns in both tumor and serum with individual metabolite features that were both elevated and decreased in patients that lived long after being diagnosed with glioblastoma compared to those who died shortly after diagnosis (p(tum)(o)(r) = 0.006, p(serum) = 0.004; AUROCC(tumor) = 0.846 (0.647-1.000), AUROCC(serum) = 0.958 (0.870-1.000)). Metabolic patterns could also distinguish long and short survival in patients diagnosed with oligodendroglioma (p(tumor) = 0.01, p(serum) = 0.001; AUROCC(tumor) = 1 (1.000-1.000), AUROCC(serum) = 1 (1.000-1.000)). In summary, we found different metabolic feature patterns in tumor tissue and serum for glioma diagnosis, grade and survival, which indicates that, following further verification, metabolomic profiling of glioma tissue as well as serum may be a valuable tool in the search for latent biomarkers for future characterization of malignant glioma.

  • 41.
    Mörén, Lina
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Metabolomic profiling of tumor tissue and serum in glioma patients reveals diagnostic and prognostic information2012Ingår i: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, nr Suppl. 6, s. 96-96, artikel-id OM-24Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    High-grade glioma is the most common brain tumor in adults, and the prognosis for patients diagnosed with this type of cancer is still poor. The biological behavior of the tumors is correlated to the classification and the World Health Organization (WHO) grading system, in which the grading reflects the increased aggressiveness. The classification system has been developed and improved over the years, but there are still problems with possible clinical implications. The histological features are not always easy to interpret, and diagnosis relies partly on personal experience of the neuropathologist. The most important component in the classification is the correlation between tumor grade and prognosis; however, the clinical reality shows a large variation in the survival of patients with glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers to obtain a more reliable classification of glioma tumors and also prognostic markers. We have performed a metabolomic profiling study of 81 tissue samples and 96 corresponding serum samples from patients with different glioma diagnoses (glioblastoma or oligodendroglioma) and grades (WHO grades II, IIIs and IV). The samples were analyzed by a global screening strategy using gas chromatography/time of flight mass spectrometry (GC/TOFMS). The acquired data were analyzed and evaluated by chemometrics-based bioinformatics methods in search for metabolite patterns of clinical relevance. We found metabolite patterns in both tissue and serum that distinguished glioblastomas from oligodendrogliomas and oligodendroglioma grade II from oligodendroglioma grade III. Interestingly, we also found metabolites elevated (eg, glycerol-3-phoshate, myo-inositol, ribitol, and fructose) and decreased (eg, octadecanoic acid and maltose) in glioblastoma patients that were associated with long survival (>3 years). Metabolite patterns associated with survival were also found in patients diagnosed with oligodendroglioma. These findings indicate that metabolomic profiling of glioma tissue and serum may be a valuable tool in future characterization of malignant glioma.

  • 42.
    Mörén, Lina
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas2016Ingår i: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 11, artikel-id 51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. Thus, there is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Analysis of alterations in the metabolome may be a source for identification of new biomarker patterns harboring predictive information. Ideally, the biomarkers should be found within an easily accessible compartment such as the blood. Method: Using gas-chromatographic-time-of-flight-mass spectroscopy we have analyzed serum samples from 11 patients with glioblastoma during the initial phase of radiotherapy. Fasting serum samples were collected at admittance, on the same day as, but before first treatment and in the morning after the second and fifth dose of radiation. The acquired data was analyzed and evaluated by chemometrics based bioinformatics methods. Our findings were compared and discussed in relation to previous data from microdialysis in tumor tissue, i.e. the extracellular compartment, from the same patients. Results: We found a significant change in metabolite pattern in serum comparing samples taken before radiotherapy to samples taken during early radiotherapy. In all, 68 metabolites were lowered in concentration following treatment while 16 metabolites were elevated in concentration. All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration. Furthermore, when comparing results from the serum analysis with findings in tumor extracellular fluid we found a common change in metabolite patterns in both compartments on an individual patient level. On an individual metabolite level similar changes in ornithine, tyrosine and urea were detected. However, in serum, glutamine and glutamate were lowered after treatment while being elevated in the tumor extracellular fluid. Conclusion: Cross-validated multivariate statistical models verified that the serum metabolome was significantly changed in relation to radiation in a similar pattern to earlier findings in tumor tissue. However, all individual changes in tissue did not translate into changes in serum. Our study indicates that serum metabolomics could be of value to investigate as a potential marker for assessing early response to radiotherapy in malignant glioma.

  • 43.
    Nilsson, Ida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Karlsson, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Ulrica
    The Efficacy of P6 Acupressure With Sea-Band in Reducing Postoperative Nausea and Vomiting in Patients Undergoing Craniotomy: A Randomized, Double-blinded, Placebo-controlled Study2015Ingår i: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921, Vol. 27, nr 1, s. 42-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Postoperative nausea and vomiting (PONV) is a multifactorial problem after general anesthesia. Despite antiemetic prophylaxis and improved anesthetic techniques, PONV still occurs frequently after craniotomies. P6 stimulation is described as an alternative method for preventing PONV. The primary aim of this study was to determine whether P6 acupressure with Sea-Band could reduce postoperative nausea after elective craniotomy. Secondary aims were to investigate whether the frequency of vomiting and the need for antiemetics could be reduced.

    Methods: In this randomized, double-blinded, placebo-controlled study, patients were randomized into either a P6 acupressure group (n = 43) or a sham group (n = 52). Bands were applied unilaterally at the end of surgery, and all patients were administered prophylactic ondansetron. Postoperative nausea was evaluated with a Numerical Rating Scale, 0 to10, and the frequency of vomiting was recorded for 48 hours.

    Results: We found no significant effect from P6 acupressure with Sea-Band on postoperative nausea or vomiting in patients undergoing craniotomy. Nor was there any difference in the need for rescue antiemetics. Altogether, 67% experienced PONV, and this was especially an issue at >24 hours in patients recovering from infratentorial surgery compared with supratentorial surgery (55% vs. 26%; P = 0.014).

    Conclusions: Unilateral P6 acupressure with Sea-Band applied at the end of surgery together with prophylactic ondansetron did not significantly reduce PONV or the need for rescue antiemetics in patients undergoing craniotomy. Our study confirmed that PONV is a common issue after craniotomy, especially after infratentorial surgery.

  • 44. Palmisano, Sadie
    et al.
    Schwartzbaum, Judith
    Prochazka, Michaela
    Pettersson, David
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Florentzson, Rut
    Harder, Henrik
    Mathiesen, Tiit
    Nyberg, Gunnar
    Siesjo, Peter
    Feychting, Maria
    Role of Tobacco Use in the Etiology of Acoustic Neuroma2012Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 175, nr 12, s. 1243-1251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two previous studies suggest that cigarette smoking reduces acoustic neuroma risk; however, an association between use of snuff tobacco and acoustic neuroma has not been investigated previously. The authors conducted a case-control study in Sweden from 2002 to 2007, in which 451 cases and 710 population-based controls completed questionnaires. Cases and controls were matched on gender, region, and age within 5 years. The authors estimated odds ratios using conditional logistic regression analyses, adjusted for education and tobacco use (snuff use in the smoking analysis and smoking in the snuff analysis). The risk of acoustic neuroma was greatly reduced in male current smokers (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23, 0.74) and moderately reduced in female current smokers (OR = 0.70, 95% CI: 0.40, 1.23). In contrast, current snuff use among males was not associated with risk of acoustic neuroma (OR = 0.94, 95% CI: 0.57, 1.55). The authors' findings are consistent with previous reports of lower acoustic neuroma risk among current cigarette smokers than among never smokers. The absence of an association between snuff use and acoustic neuroma suggests that some constituent of tobacco smoke other than nicotine may confer protection against acoustic neuroma.

  • 45. Pettersson, David
    et al.
    Mathiesen, Tiit
    Prochazka, Michaela
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Florentzson, Rut
    Harder, Henrik
    Nyberg, Gunnar
    Siesjo, Peter
    Feychting, Maria
    Long-term mobile phone use and acoustic neuroma risk2014Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, nr 2, s. 233-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. Methods: We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). Results: Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for 680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. Conclusions: The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

  • 46.
    Roslin, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ungerstedt, Urban
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Baseline levels of glucose metabolites, glutamate and glycerol in malignant glioma assessed by stereotactic microdialysis.2003Ingår i: J Neurooncol, ISSN 0167-594X, Vol. 61, nr 2, s. 151-160Artikel i tidskrift (Övrigt vetenskapligt)
  • 47.
    Rydvall, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Lynöe, Niels
    Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
    Decision making in a life-threatening cerebral condition: a comparative study of the ethical reasoning of intensive care unit physicians and neurosurgeons2007Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, nr 10, s. 1338-1343Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umea, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The primary aim of the investigation was to study the effect of craniectomy on ICP changes over time in patients with severe TBI treated by an ICP-targeted protocol. In this retrospective study, all patients treated for severe TBI during 1998-2001 who fulfilled the following inclusion criteria were studied: GCS <or= 8 at intubation and sedation, first recorded cerebral perfusion pressure (CPP) of >10 mm Hg, arrival within 24 h of trauma, and need of intensive care for >72 h. Craniectomy was performed when the ICP could not be controlled by evacuation of hematomas, sedation, ventriculostomy, or low-dose pentothal infusion. Ninety-three patients met the inclusion criteria. Mean age was 37.6 years. Twenty-one patients underwent craniectomy as a treatment step. We found a significant reduction of the ICP directly after craniectomy, from 36.4 mm Hg (range, 18-80 mm Hg) to 12.6 mm Hg (range, 2-51 mm Hg). During the following 72 h, we observed an increase in ICP during the first 8-12 h after craniectomy, reaching approximately 20 mm Hg, and later levelling out at approximately 25 mm Hg. The reduction of ICP was statistically significant during the 72 h. The outcome as measured by Glasgow Outcome Scale (GOS) did not significantly differ between the craniectomized group (DC) and the non-craniectomized group (NDC). The outcome was favorable (GOS 5-4) in 71% in the craniectomized group, and in 61% in the non-craniectomized group. Craniectomy is a useful tool in achieving a significant reduction of ICP overtime in TBI patients with progressive intracranial hypertension refractory to medical therapy. The procedure seems to have a satisfactory effect on the outcome, as demonstrated by a high rate of favorable outcome and low mortality in the craniectomized group, which did not significantly differ compared with the non-craniectomized group.

  • 48.
    Sandström, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Patologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model2004Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 91, nr 6, s. 1174-1180Artikel i tidskrift (Refereegranskat)
  • 49.
    Sandström, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model.2008Ingår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 88, nr 1, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM OF THE STUDY:

    The extensive neovascularisation of malignant glioma is mainly influenced by vascular endothelial growth factor (VEGF). The effect of ZD6474, a potent inhibitor of VEGF-receptor-2, was evaluated in combination with either radiotherapy or temozolomide.

    METHODS:

    The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. ZD6474 30 mg/kg was given alone or in combination with radiotherapy 12 Gy x 1 or with temozolomide 100 mg/kg for 3 days. Two different experiments were performed comparing ZD6474 to radiotherapy or temozolomide. For each experiment 28 animals were randomized into four groups.

    RESULTS:

    ZD6474 in combination with radiotherapy significantly decreased tumour area by 66% compared with controls whereas the combination with temozolomide decreased tumour area by 74%.

    CONCLUSIONS:

    ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. These results justify further investigations of these therapies in combination.

  • 50. Shete, Sanjay
    et al.
    Hosking, Fay J
    Robertson, Lindsay B
    Dobbins, Sara E
    Sanson, Marc
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Simon, Matthias
    Marie, Yannick
    Boisselier, Blandine
    Delattre, Jean-Yves
    Hoang-Xuan, Khe
    El Hallani, Soufiane
    Idbaih, Ahmed
    Zelenika, Diana
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Schramm, Johannes
    Linnebank, Michael
    Hemminki, Kari
    Kumar, Rajiv
    Hepworth, Sarah J
    Price, Amy
    Armstrong, Georgina
    Liu, Yanhong
    Gu, Xiangjun
    Yu, Robert
    Lau, Ching
    Schoemaker, Minouk
    Muir, Kenneth
    Swerdlow, Anthony
    Lathrop, Mark
    Bondy, Melissa
    Houlston, Richard S
    Genome-wide association study identifies five susceptibility loci for glioma.2009Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Nature genetics, ISSN 1546-1718, Vol. 41, nr 8, s. 899-904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

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