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Bergenheim, A. Tommy
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Publications (10 of 66) Show all publications
Eriksson, M., Kahari, J., Vestman, A., Hallmans, M., Johansson, M., Bergenheim, A. T. & Sandström, M. (2019). Improved treatment of glioblastoma: changes in survival over two decades at a single regional Centre. Acta Oncologica, 58(3), 334-341
Open this publication in new window or tab >>Improved treatment of glioblastoma: changes in survival over two decades at a single regional Centre
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2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 334-341Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-158751 (URN)10.1080/0284186X.2019.1571278 (DOI)000462947900011 ()30732527 (PubMedID)
Available from: 2019-05-15 Created: 2019-05-15 Last updated: 2019-05-15Bibliographically approved
Asplund, P., Linderoth, B., Lind, G., Winter, J. & Bergenheim, A. T. (2019). One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis. Operative neurosurgery
Open this publication in new window or tab >>One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis
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2019 (English)In: Operative neurosurgery, ISSN 2332-4252Article in journal (Refereed) Epub ahead of print
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.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
Balloon compression, Multiple sclerosis, Trigeminal neuralgia
National Category
Other Clinical Medicine Neurology Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-158351 (URN)10.1093/ons/opy402 (DOI)30690631 (PubMedID)
Available from: 2019-04-24 Created: 2019-04-24 Last updated: 2019-04-25
Bergman, J., Burman, J., Gilthorpe, J. D., Zetterberg, H., Jiltsova, E., Bergenheim, T. & Svenningsson, A. (2018). Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study. Neurology, 91(20), E1893-E1901
Open this publication in new window or tab >>Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study
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2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, no 20, p. E1893-E1901Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wolters Kluwer, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-154850 (URN)10.1212/WNL.0000000000006500 (DOI)000452514700006 ()30305449 (PubMedID)2-s2.0-85056314572 (Scopus ID)
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-05-07Bibliographically approved
Mao, F., Holmlund, C., Faraz, M., Wang, W., Bergenheim, T., Kvarnbrink, S., . . . Hedman, H. (2018). Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma. Oncogenesis, 7, Article ID 13.
Open this publication in new window or tab >>Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma
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2018 (English)In: Oncogenesis, E-ISSN 2157-9024, Vol. 7, article id 13Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147385 (URN)10.1038/s41389-017-0012-8 (DOI)000429469500001 ()29391393 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-06-09Bibliographically approved
Eriksson, M., Johansson, M., Bergenheim, A. T. & Sandström, M. (2018). TREATMENT OF GLIOBLASTOMA: IMPROVEMENTS OVER TWO DECADES AT A SINGLE CENTRE. Paper presented at 13th Meeting of the European-Association-of-Neurooncology (EANO), OCT 10-14, 2018, Stockholm, SWEDEN. Neuro-Oncology, 20, 236-236
Open this publication in new window or tab >>TREATMENT OF GLIOBLASTOMA: IMPROVEMENTS OVER TWO DECADES AT A SINGLE CENTRE
2018 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, p. 236-236Article in journal, Meeting abstract (Other academic) Published
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.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-157549 (URN)000460645600080 ()
Conference
13th Meeting of the European-Association-of-Neurooncology (EANO), OCT 10-14, 2018, Stockholm, SWEDEN
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-03-26
Tabatabaei, P., Visse, E., Bergström, P., Brännström, T., Siesjö, P. & Bergenheim, A. T. (2017). Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study. Journal of Neuro-Oncology, 131(1), 83-92
Open this publication in new window or tab >>Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study
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2017 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 131, no 1, p. 83-92Article in journal (Refereed) Published
Abstract [en]

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Cytokine, Glioblastoma, Radiotherapy, Microdialysis, Inflammation
National Category
Cancer and Oncology Neurology
Identifiers
urn:nbn:se:umu:diva-131132 (URN)10.1007/s11060-016-2271-1 (DOI)000393065400010 ()27664151 (PubMedID)
Available from: 2017-02-06 Created: 2017-02-06 Last updated: 2019-05-09Bibliographically approved
Mörén, L., Wibom, C., Bergström, P., Johansson, M., Antti, H. & Bergenheim, A. T. (2016). Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas. Radiation Oncology, 11, Article ID 51.
Open this publication in new window or tab >>Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas
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2016 (English)In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 11, article id 51Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2016
Keywords
Glioblastoma, Radiation therapy, Treatment response, Metabolomics, Chemometrics
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-119631 (URN)10.1186/s13014-016-0626-6 (DOI)000373185900001 ()27039175 (PubMedID)
Available from: 2016-05-20 Created: 2016-04-25 Last updated: 2018-06-07Bibliographically approved
Bergman, J., Dring, A., Wuolikainen, A., Gilthorpe, J., Bergenheim, T. & Svenningsson, A. (2016). Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis. Paper presented at 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND. Multiple Sclerosis Journal, 22, 511-511
Open this publication in new window or tab >>Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis
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2016 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 511-511Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2016
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-132859 (URN)000383267202206 ()
Conference
32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND
Note

Supplement 3, Meeting Abstract P1005

Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2018-06-09Bibliographically approved
Al Nimer, F., Elliott, C., Bergman, J., Khademi, M., Dring, A. M., Aeinehband, S., . . . Piehl, F. (2016). Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination. Neurology: Neuroimmunology and neuroinflammation, 3(1), Article ID e191.
Open this publication in new window or tab >>Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination
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2016 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 1, article id e191Article in journal (Refereed) Published
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.

National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-127257 (URN)10.1212/NXI.0000000000000191 (DOI)000384572500009 ()26770997 (PubMedID)
Available from: 2016-11-10 Created: 2016-11-03 Last updated: 2019-05-06Bibliographically approved
Bergman, J., Dring, A., Zetterberg, H., Blennow, K., Norgren, N., Gilthorpe, J., . . . Svenningsson, A. (2016). Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurology: Neuroimmunology and neuroinflammation, 3(5), Article ID e271.
Open this publication in new window or tab >>Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS
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2016 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 5, article id e271Article in journal (Refereed) Published
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.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-131138 (URN)10.1212/NXI.0000000000000271 (DOI)000391169200012 ()27536708 (PubMedID)
Available from: 2017-02-06 Created: 2017-02-06 Last updated: 2018-06-09Bibliographically approved
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