umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1234567 51 - 100 av 825
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 51.
    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.

  • 52.
    Augustian, Midhumol
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    ur Réhman, Shafiq
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Sandvig, Axel
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Norwegian University of Science and Technology (NTNU), Norway.
    Kotikawatte, Thivra
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Yongcui, Mi
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Evensmoen, Hallvard Røe
    Norwegian University of Science and Technology (NTNU), Norway.
    EEG Analysis from Motor Imagery to Control a Forestry Crane2018Ingår i: Intelligent Human Systems Integration (IHSI 2018) / [ed] Karwowski, Waldemar, Ahram, Tareq, 2018, Vol. 722, s. 281-286Konferensbidrag (Refereegranskat)
    Abstract [en]

    Brain-computer interface (BCI) systems can provide people with ability to communicate and control real world systems using neural activities. Therefore, it makes sense to develop an assistive framework for command and control of a future robotic system which can assist the human robot collaboration. In this paper, we have employed electroencephalographic (EEG) signals recorded by electrodes placed over the scalp. The human-hand movement based motor imagery mentalization is used to collect brain signals over the motor cortex area. The collected µ-wave (8–13 Hz) EEG signals were analyzed with event-related desynchronization/synchronization (ERD/ERS) quantification to extract a threshold between hand grip and release movement and this information can be used to control forestry crane grasping and release functionality. The experiment was performed with four healthy persons to demonstrate the proof-of concept BCI system. From this study, it is demonstrated that the proposed method has potential to assist the manual operation of crane operators performing advanced task with heavy cognitive work load.

  • 53. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, Supplement: S, s. 543-543Artikel i tidskrift (Övrigt vetenskapligt)
  • 54. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 1, s. 43-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

  • 55. Aziz, Tipu Z.
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, Unit of Functional Neurosurgery, London, England.
    To sleep or not to sleep during deep brain stimulation surgery for Parkinson disease?2017Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, nr 19, s. 1938-1939Artikel i tidskrift (Övrigt vetenskapligt)
  • 56.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine and training-related working-memory improvement2013Ingår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 9, s. 2209-2219Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.

  • 57. Ballesteros, Soledad
    et al.
    Prieto, Antonio
    Mayas, Julia
    Pilar, Toril
    Ponce De León Romero, Laura
    Reales, José Manuel
    Waterworth, John
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för informatik.
    Corrigendum: brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial2015Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 7, artikel-id 82Artikel i tidskrift (Refereegranskat)
  • 58. Bartek, Jiri, Jr.
    et al.
    Förander, Petter
    Thurin, Erik
    Wangerid, Theresa
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Regional Cancer Centre Stockholm/Gotland, Stockholm, Sweden.
    Hesselager, Göran
    Jakola, Asgeir Store
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, artikel-id 43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 59. Bas-Hoogendam, Janna Marie
    et al.
    van Steenbergen, Henk
    Pannekoek, J. Nienke
    Fouche, Jean-Paul
    Lochner, Christine
    Hattingh, Coenraad J.
    Cremers, Henk R.
    Furmark, Tomas
    Månsson, Kristoffer N. T.
    Frick, Andreas
    Engman, Jonas
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Carlbring, Per
    Andersson, Gerhard
    Fredrikson, Mats
    Straube, Thomas
    Peterburs, Jutta
    Klumpp, Heide
    Phan, K. Luan
    Roelofs, Karin
    Stein, Dan J.
    van der Wee, Nic. J. A.
    Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder2017Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, nr 10, s. S7-S7Artikel i tidskrift (Refereegranskat)
  • 60. Baugh, Lee A.
    et al.
    Yak, Amelie
    Johansson, Roland S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Flanagan, J. Randall
    Representing multiple object weights: competing priors and sensorimotor memories2016Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 116, nr 4, s. 1615-1625Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size-weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1. These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors.

  • 61.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014Ingår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 11, artikel-id 22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

  • 62.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 4, s. 233-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 63.
    Benatar, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuu, Joanne
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Atassi, Nazem
    David, William
    Cudkowicz, Merit
    Schoenfeld, David
    Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, nr 7, s. E565-E574Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectiveTo examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS).

    MethodsThis was a double-blind, placebo-controlled trial in which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures were performed using a mix of in-person and remote assessments. Primary outcome was safety and tolerability. Secondary outcome was efficacy, with survival as the principal measure. Additional efficacy measures were the rates of decline of the Revised ALS Functional Rating Scale (ALSFRS-R) and percent predicted forced expiratory volume in 6 seconds (FEV6), and the Combined Assessment of Function and Survival (CAFS).

    ResultsThirty-eight participants were randomized. Thirty-six (19 placebo, 17 arimoclomol) were included in the prespecified intent-to-treat analysis. Apart from respiratory function, groups were generally well-balanced at baseline. Adverse events occurred infrequently, and were usually mild and deemed unlikely or not related to study drug. Adjusting for riluzole and baseline ALSFRS-R, survival favored arimoclomol with a hazard ratio of 0.77 (95% confidence interval [CI] 0.32-1.80). ALSFRS-R and FEV6 declined more slowly in the arimoclomol group, with treatment differences of 0.5 point/month (95% CI -0.63 to 1.63) and 1.24 percent predicted/month (95% CI -2.77 to 5.25), respectively, and the CAFS similarly favored arimoclomol.

    ConclusionsThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. Although not powered for therapeutic effect, the consistency of results across the range of prespecified efficacy outcome measures suggests a possible therapeutic benefit of arimoclomol.

    Clinicaltrials.gov identifierNCT00706147.

    Classification of evidenceThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. The study lacked the precision to conclude, or to exclude, an important therapeutic benefit of arimoclomol.

  • 64.
    Benatar, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuu, Joanne
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lombardi, Vittoria
    Malaspina, Andrea
    Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion2018Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 84, nr 1, s. 130-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To evaluate neurofilament light (NfL) as a biomarker of the presymptomatic phase of amyotrophic lateral sclerosis (ALS).

    Methods: The study population includes 84 individuals at risk for developing ALS, 34 controls, 17 ALS patients, and 10 phenoconverters (at-risk individuals observed both before and after the emergence of clinically manifest disease). At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation (in SOD1, C9orf72, TARDBP, FUS, VCP, etc), but who, at the time of enrollment, demonstrated no clinical symptoms or signs (including electromyographic evidence) of manifest disease. NfL in serum and cerebrospinal fluid (CSF) were quantified using an electrochemiluminescence immunoassay.

    Results: Serum and CSF NfL are substantially higher in ALS patients compared to controls and at-risk individuals and remain relatively stable over time. Among phenoconverters, however, NfL levels were elevated (ie, above the range observed in controls) as far back as approximate to 12 months preceding the emergence of the earliest clinical symptoms or signs of disease.

    Interpretation: Serum (and CSF) NfL are informative biomarkers of presymptomatic ALS, providing a new tool to quantify presymptomatic disease progression and to potentially predict the timing of clinical phenoconversion. As such, quantification of NfL may aid the design and implementation of early therapeutic intervention for affected individuals and/or disease prevention trials for individuals at short-term risk of developing ALS. 

  • 65.
    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.

  • 66.
    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.

  • 67.
    Bergh, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Structural investigation of SOD1 aggregates in ALS: identification of prion strains using anti-peptide antibodies2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative syndrome characterized by progressive degeneration of motor neurons that result in muscle wasting. The symptoms advance gradually to paralysis and eventually death. Most patients suffer from sporadic ALS (sALS) but 10% report a familial predisposition. Mutations in the gene encoding super­oxide dismutase-1 (SOD1) were the first identified cause of ALS. The disease mecha­nism is debated but there is a consensus that mutations in this protein confer a cytotoxic gain of function. SOD1 aggregates in motor neurons are hallmarks of ALS both in patients and in transgenic mouse models expressing a mutated form of human SOD1 (hSOD1). Recently, our group showed that SOD1 aggregates are present also in sALS patients, thus indicating a broader involvement of this protein in ALS. Misfolding and aggregation of SOD1 are dif­ficult to study in vivo since aggregate concentration in the central nervous system (CNS) is exceedingly low. The aim of this thesis was to find a method circumventing this problem to investigate the hSOD1 aggregate structure, distribution and spread in ALS disease.

    Many studies provide circumstantial evidence that the wild-type hSOD1 protein can be neurotoxic. We developed the first homozygous mouse model that highly overexpresses the wild-type enzyme. These mice developed an ALS-like syndrome and become terminally ill after around 370 days. Motor neuron loss and SOD1 aggregate accumulation in the CNS were observed. This lends further support to the hypothesis of a more general involve­ment of SOD1 in human disease.

    A panel of polyclonal antibodies covering 90% of the SOD1 protein was developed by our laboratory. These antibodies were shown to be highly specific for misfolded SOD1. Aggre­gated hSOD1 was purified from the CNS of terminally ill hSOD1 mice. Disordered segments in aggregated hSOD1 could be identified with these antibodies. Two aggregate strains with different structural architectures, molecular properties, and growth kinetics, were found using this novel method. The strains, denoted A and B, were also associated with different disease progression. Aggregates formed in vitro were structurally different from these strains. The results gave rise to questions about aggregate development and possible prion-like spread. To investigate this, inoculations of purified strain A and B hSOD1 seeds was performed in lumbar spinal cords of 100-day old mice carrying a hSOD1G85R mutation. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill 200 days earlier than mice inoculated with control preparation. Interestingly, a tem­plated spread of aggregates along the neuraxis was concomitantly observed, with strain A and B provoking the buildup of their respective hSOD1 aggregate structure. The phenotypes initiated by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. To further establish the importance of hSOD1 aggregates in human disease, purification and inoculation of aggregate seeds from spinal cords of ALS patients and mice carrying the hSOD1G127X mutation were performed. Inoculation of both human and mouse seeds as described above, induced strain A aggregation and premature fatal ALS-like disease.

    In conclusion, the data presented in this thesis provide a new, straightforward method for characterization of aggregate strains in ALS, and plausibly also in other neurodegen­erative diseases. Two different prion strains of hSOD1 aggregates were identified in mice that resulted in ALS-like disease. Emerging data suggest that prion-like growth and spread of hSOD1 aggregation could be the primary pathogenic mechanism not only in hSOD1 transgenic models, but also in human ALS.

  • 68.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Johansson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Attention in Older Adults: A Normative Study of the Integrated Visual and Auditory Continuous Performance Test for Persons Aged 70 Years2015Ingår i: Clinical Neuropsychologist (Neuropsychology, Development and Cognition: Section D), ISSN 1385-4046, E-ISSN 1744-4144, Vol. 29, nr 5, s. 595-610Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Our objective was to present normative data from 70-year-olds on the Integrated Visual and Auditory Continuous Performance Test (IVA), a computerized measure of attention and response control. Method: 640 participants (330 men and 310 women), all aged 70years, completed the IVA, as well as the Mini-Mental State Examination and the Geriatric Depression Scale. Results: Data were stratified by education and gender. Education differences were found in 11 of 22 IVA scales. Minor gender differences were found in six scales for the high-education group, and two scales for the low-education group. Comparisons of healthy participants and participants with stroke, myocardial infarction, or diabetes showed only minor differences. Correlations among IVA scales were strong (all r > .34, p < .001), and those with the widely used Mini-Mental State Examination were weaker (all r < .21, p < .05). Skewed distributions of normative data from primary IVA scales measuring response inhibition (Prudence) and inattention (Vigilance) represent a weakness of this test. Conclusions: This study provides IVA norms for 70-year-olds stratified by education and gender, increasing the usability of this instrument when testing persons near this age. The data presented here show some major differences from original IVA norms, and explanations for these differences are discussed. Explanations include the broad age-range used in the original IVA norms (66-99years of age) and the passage of 15years since the original norms were collected.

  • 69.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning2017Ingår i: Brain Injury: Accepted Abstracts from the International Brain Injury Association’s 12th World Congress on Brain Injury, 2017, Vol. 31, s. 755-755Konferensbidrag (Refereegranskat)
    Abstract [en]

    Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.

  • 70.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning2018Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, nr 4, s. 266-274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

    Setting: Neurorehabilitation clinic.

    Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

    Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

    Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

    Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

  • 71.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway Medicine.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway.
    Pharmaco-fMRI in Patients With Traumatic Brain Injury: A Randomized Controlled Trial With the Monoaminergic Stabilizer (-)-OSU61622019Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 34, nr 3, s. 189-198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the effects of monoaminergic stabilizer (-)-OSU6162 on brain activity, as measured by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients in the chronic phase of traumatic brain injury suffering from fatigue.

    SETTING: Neurorehabilitation clinic.

    PARTICIPANTS: Patients with traumatic brain injury received either placebo (n = 24) or active treatment (n = 28). Healthy controls (n = 27) went through fMRI examination at one point and were used in sensitivity analysis on normalization of BOLD response.

    DESIGN: Randomized, double-blinded, placebo-controlled design.

    MAIN MEASURES: Effects on BOLD signal changes from before to after treatment during performance of a fatiguing attention task.

    RESULTS: The fMRI results revealed treatment effects within the right occipitotemporal cortex and the right orbitofrontal cortex. In these regions, the BOLD response was normalized relative to healthy controls at the postintervention fMRI session. No effects were seen in regions in which we previously observed activity differences between patients and healthy controls while performing this fMRI task, such as the striatum.

    CONCLUSION: (-)-OSU6162 treatment had influences on functional brain activity, although the normalized regional BOLD response was observed in regions that were not a priori hypothesized to be sensitive to this particular treatment, and was not accompanied by any effects on in-scanner test performance or on fatigue.

  • 72.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    White matter hyperintensities increases with traumatic brain injuryseverity: associations to neuropsychological performance and fatigueManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.

    Methods: A total of 59 patients with TBI and 27 age- and gender- matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.

    Results: WMH lesions were more common in patients with TBI than in healthy controls (p = 0.032), and increased with higher TBI severity (p = 0.025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > 0.05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = –0.33, p = 0.026).

    Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. However, these lesions do not seem to explain the decreased cognitive functioning or the increased fatigue in patients with TBI.

  • 73.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Schuit, Robert
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    The effects of (-)-OSU6162 on chronic fatigue in patients with traumatic brain injury: a randomized controlled trial2017Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 32, nr 2, s. E46-E54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the effects of the monoaminergic stabilizer (-)-OSU6162 on mental fatigue in patients with traumatic brain injury.

    SETTING: Single-center Neurorehabilitation Clinic.

    DESIGN: Randomized, double-blind, placebo-controlled trial.

    PARTICIPANTS: Sixty-four subjects with traumatic brain injury were randomized to treatment (n = 33) and placebo (n = 31).

    MAIN MEASURES: The effects of (-)-OSU6162 at a dose of 15 mg twice a day were evaluated using self-assessment scales and neuropsychological tests measuring mental fatigue.

    RESULTS: No difference between groups was observed on any scale at baseline. At follow-up, both groups showed significant improvement on the Fatigue Severity Scale and the Mental Fatigue Scale (both Ps < .01). Similarly, the performance of both groups increased significantly on many neuropsychological tests. However, no significant between-group difference in changes on these scales was observed before or after adjustment for confounders except for one neuropsychological test favoring the control group. Sensitivity analyses showed significantly greater changes in levels of prolactin and folic acid and heart rate (all Ps < .05) in the treatment group. The mean plasma concentration after 4 weeks of treatment was 0.14 (range, 0.01-0.32) μM, which was lower than expected.

    INTERPRETATION: Treatment with (-)-OSU6162 had no significant effect on mental fatigue in patients with traumatic brain injury compared with placebo.

  • 74.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Locus coeruleus promotes survival of dopamine neurons in ventral mesencephalon: An in oculo grafting study2009Ingår i: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 216, nr 1, s. 158-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Parkinson's disease is a neurodegenerative disorder where dopamine neurons in the substantia nigra of ventral mesencephalon undergo degeneration. In addition to the loss of dopamine neurons, noradrenaline neurons in the locus coeruleus degenerate, actually to a higher extent than the dopamine neurons. The interaction between these two nuclei is yet not fully known, hence this study was undertaken to investigate the role of locus coeruleus during development of dopamine neurons utilizing the intraocular grafting model. Fetal ventral mesencephalon and locus coeruleus were implanted either as single grafts or co-grafts, placed in direct contact or at a distance. The results revealed that the direct attachment of locus coeruleus to ventral mesencephalon enhanced graft volume and number of tyrosine hydroxylase (TH)-positive neurons in ventral mesencephalic grafts. Cell counts of subpopulations of TH-positive neurons also immunoreactive for aldehyde dehydrogenase 1-A1 (ALDH1) or calbindin, revealed improved survival of ALDH1/TH-positive neurons. However, the number of calbindin/TH-positive neurons was not affected. High density of dopamine-beta-hydroxylase (DBH)-positive innervation in the ventral mesencephalon placed adjacent to locus coeruleus was correlated to the improved survival. Ventral mesencephalic tissue, implanted at a distance to locus coeruleus, did not demonstrate improved survival, although DBH-positive nerve fibers were detected. In conclusion, the direct contact of locus coeruleus resulting in dense noradrenergic innervation of ventral mesencephalon is beneficial for the survival of ventral mesencephalic grafts. Thus, when trying to rescue dopamine neurons in Parkinson's disease, improving the noradrenergic input to the substantia nigra might be worth considering.

  • 75.
    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.

  • 76.
    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.

  • 77.
    Bergman, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Svenningsson, A.
    Liv, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Burman, J.
    Poor correlation between protein levels in different CNS compartments in patients with progressive MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 432-433Artikel i tidskrift (Övrigt vetenskapligt)
  • 78.
    Bergström, L.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Ögren, Joachim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Recurrent ischemic stroke in patients with diabetes mellitus - incidence, trend over time and predictors2015Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 39, s. 14-14Artikel i tidskrift (Övrigt vetenskapligt)
  • 79.
    Bergström, Lisa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Lars
    Ögren, Joachim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    One-year incidence, time trends, and predictors of recurrent ischemic stroke in Sweden from 1998-2010: An observational studyManuskript (preprint) (Övrigt vetenskapligt)
  • 80.
    Bergström, Petra
    et al.
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    von Otter, Malin
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Staffan
    Institute of Mathematical Sciences, Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.
    Nilsson, Ann-Charloth
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Michael
    Institute of Neuroscience and Physiology, Centre for Brain Repair and Rehabilitation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hammarsten, Ola
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK.
    Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis2014Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 15, nr 1-2, s. 130-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.

  • 81. Berk, John L.
    et al.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Obici, Laura
    Sekijima, Yoshiki
    Zeldenrust, Steven R.
    Yamashita, Taro
    Heneghan, Michael A.
    Gorevic, Peter D.
    Litchy, William J.
    Wiesman, Janice F.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Corato, Manuel
    Lozza, Alessandro
    Cortese, Andrea
    Robinson-Papp, Jessica
    Colton, Theodore
    Rybin, Denis V.
    Bisbee, Alice B.
    Ando, Yukio
    Ikeda, Shu-ichi
    Seldin, David C.
    Merlini, Giampaolo
    Skinner, Martha
    Kelly, Jeffery W.
    Dyck, Peter J.
    Repurposing Diflunisal for Familial Amyloid Polyneuropathy: A Randomized Clinical Trial2013Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 310, nr 24, s. 2658-2667Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. OBJECTIVE To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umea), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012. INTERVENTION Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years. MAIN OUTCOMES AND MEASURES The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey [SF-36]) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data. RESULTS By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007). CONCLUSIONS AND RELEVANCE Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy.

  • 82. Berntsson, Shala G.
    et al.
    Merrell, Ryan T.
    Amirian, E. Susan
    Armstrong, Georgina N.
    Lachance, Daniel
    Smits, Anja
    Zhou, Renke
    Jacobs, Daniel I.
    Wrensch, Margaret R.
    Olson, Sara H.
    Il'yasova, Dora
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Schildkraut, Joellen
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S.
    Jenkins, Robert B.
    Bernstein, Jonine L.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Bondy, Melissa L.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study2018Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, nr 6, s. 1432-1442Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.

    Methods: The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures.

    Results: Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.

    Conclusions: Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

  • 83.
    Birznieks, Ingvars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Jenmalm, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Goodwin, Antony W
    University of Melbourne, Victoria.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Encoding of direction of fingertip forces by human tactile afferents2001Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, nr 20, s. 8222-8237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode the direction of fingertip forces at magnitudes, rates, and directions comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to a standard site on the fingertip while recording impulse activity in 196 tactile afferents with receptive fields distributed over the entire terminal phalanx. Forces were applied in one of five directions: normal force and forces at a 20 degrees angle from the normal in the radial, distal, ulnar, or proximal directions. Nearly all afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and fast adapting (FA)-I afferents were broadly tuned to a preferred direction of force. Among afferents of each type, the preferred directions were distributed in all angular directions with reference to the stimulation site, but not uniformly. The SA-I population was biased for tangential force components in the distal direction, the SA-II population was biased in the proximal direction, and the FA-I population was biased in the proximal and radial directions. Anisotropic mechanical properties of the fingertip and the spatial relationship between the receptive field center of the afferent and the stimulus site appeared to influence the preferred direction in a manner dependent on afferent type. We conclude that tactile afferents from the whole terminal phalanx potentially contribute to the encoding of direction of fingertip forces similar to those that occur when subjects manipulate objects under natural conditions.

  • 84.
    Biström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, O.
    Alonso-Magdalena, L.
    Jons, D.
    Gunnarsson, M.
    Vrethem, M.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Leptin levels are associated with multiple sclerosis risk2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 904-904Artikel i tidskrift (Övrigt vetenskapligt)
  • 85.
    Björk, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Andersson, Emelie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Arbetsterapeuters erfarenheter av interventioner för personer med Parkinsons sjukdom: en kvalitativ studie2011Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
  • 86.
    Bladh, Stina
    et al.
    Department of Health Sciences, Lund University, Lund, Sweden.
    Nilsson, Maria H
    Department of Health Sciences, Lund University, Lund, Sweden.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Westergren, Albert
    School of Health and Society, Kristianstad University, Kristianstad, Sweden.
    Hobart, Jeremy
    Department of Clinical Neuroscience, Peninsula Medical School, Plymouth, UK.
    Hagell, Peter
    Department of Health Sciences, Lund University, Lund, Sweden.
    Psychometric performance of a generic walking scale (Walk-12G) in Multiple Sclerosis and Parkinson's disease2012Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 259, nr 4, s. 729-738Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Walking difficulties are common in neurological and other disorders, as well as among the elderly. There is a need for reliable and valid instruments for measuring walking difficulties in everyday life since existing gait tests are clinician rated and focus on situation specific capacity. The Walk-12G was adapted from the 12-item multiple sclerosis walking scale as a generic patient-reported rating scale for walking difficulties in everyday life. The aim of this study is to examine the psychometric properties of the Walk-12G in people with multiple sclerosis (MS) and Parkinson’s disease (PD). The Walk-12G was translated into Swedish and evaluated qualitatively among 25 people with and without various neurological and other conditions. Postal survey (MS, n = 199; PD, n = 189) and clinical (PD, n = 36) data were used to test its psychometric properties. Respondents considered the Walk-12G relevant and easy to use. Mean completion time was 3.5 min. Data completeness was good (<5% missing item responses) and tests of scaling assumptions supported summing item scores to a total score (corrected item-total correlations >0.6). Coefficient alpha and test–retest reliabilities were >0.9, and standard errors of measurement were 2.3–2.8. Construct validity was supported by correlations in accordance with a priori expectations. Results are similar to those with previous Walk-12G versions, indicating that scale adaptation was successful. Data suggest that the Walk-12G meets rating scale criteria for clinical trials, making it a valuable complement to available gait tests. Further studies involving other samples and application of modern psychometric methods are warranted to examine the scale in more detail.

  • 87. Blasco, Helene
    et al.
    Bernard-Marissal, Nathalie
    Vourc'h, Patrick
    Guettard, Yves Olivier
    Sunyach, Claire
    Augereau, Olivier
    Khederchah, Joelle
    Mouzat, Kevin
    Antar, Catherine
    Gordon, Paul H.
    Veyrat-Durebex, Charlotte
    Besson, Gerard
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salachas, Francois
    Meininger, Vincent
    Camu, William
    Pettmann, Brigitte
    Andres, Christian R.
    Corcia, Philippe
    A Rare Motor Neuron Deleterious Missense Mutation in the DPYSL3 (CRMP4) Gene is Associated with ALS2013Ingår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, nr 7, s. 953-960Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dihydropyrimidinase-like 3 (DPYSL3) or Collapsin Response Mediator Protein 4a (CRMP4a) expression is modified in neurodegeneration and is involved in several ALS-associated pathways including axonal transport, glutamate excitotoxicity, and oxidative stress. The objective of the study was to analyze CRMP4 as a risk factor for ALS. We analyzed the DPYSL3/CRMP4 gene in French ALS patients (n=468) and matched-controls (n=394). We subsequently examined a variant in a Swedish population (184 SALS, 186 controls), and evaluated its functional effects on axonal growth and survival in motor neuron cell culture. The rs147541241:A>G missense mutation occurred in higher frequency among French ALS patients (odds ratio=2.99) but the association was not confirmed in the Swedish population. In vitro expression of mutated DPYSL3 in motor neurons reduced axonal growth and accelerated cell death compared with wild type protein. Thus, the association between the rs147541241 variant and ALS was limited to the French population, highlighting the geographic particularities of genetic influences (risks, contributors). The identified variant appears to shorten motor neuron survival through a detrimental effect on axonal growth and CRMP4 could act as a key unifier in transduction pathways leading to neurodegeneration through effects on early axon development.

  • 88.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Analysis of deep brain stimulation and ablative lesions in surgical treatment of movement disorders: with emphasis on safety aspects2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background The last decade has witnessed a renaissance of functional stereotactic neurosurgery in the treatment of patients with movement disorders, especially advanced Parkinson’s disease (PD), essential tremor (ET) and dystonia. Ablative lesions such as thalamotomy and pallidotomy have been gradually replaced by the technique of chronic deep brain stimulation (DBS) applied to targets in the basal ganglia and thalamus, and assumed to be more lenient to the brain than stereotactic radiofrequency lesions. Since the aim of functional neurosurgery is to alleviate symptoms of these chronic, progressive, non-fatal diseases, and to improve life quality of the patients, it is imperative that the surgical procedures remain safe and do not result in complications mitigating any anticipated positive effect of the surgery on the symptoms of the disease.

    Aim The aim of this thesis is to evaluate, compare and analyse the safety of various surgical procedures used to treat patients with movement disorders, and to document side effects and complications both peri operatively and in a long term follow-up. Further to compare the effects of pallidotomy and pallidal DBS, and to evaluate the longterm efficacy of Vim-DBS.

    Method 256 consecutive surgical procedures, 129 DBS and 127 stereotactic lesions, were reviewed with respect to complications in 197 treated patients. In a series of 119 patients operated on with DBS during a 10 year period, the occurrence of hardware related complications (infection, breakage, erosion etc) was documented and analysed. Additionally, the interference of external magnetic field with the stimulation was documented. In one patient operated on with subthalamic nucleus DBS, a highly unusual and unexpected psychiatric side effect was carefully analysed. In 5 patients operated on with both methods (lesion and DBS) on each hemisphere, respectively, the effect and side effects of each method were compared. The long term effect and side effects of thalamic DBS was analysed in a series of patients with ET followed for 7 years.

    Results There were no deaths and few severe neurological complications in this material. Unilateral ablative lesions in the pallidum were well tolerated by patients with advanced PD, while for tremor, thalamic DBS was much safer than thalamotomy, even if its effect on certain aspects of tremor could show some decrease of efficacy over time. Some of the side effects of lesioning are transient while most but not all side effects of DBS are reversible. Hardware-related complications were not uncommon especially in the early “learning curve” period, and the DBS technique, being a life-long therapy, will necessitate a life long follow up of patients. Provided safety protocols are followed and provided patient’s and carer’s education and awareness, external electromagnetic interference should not constitute a risk for patients with DBS. PD patients undergoing STN DBS should be carefully selected to avoid psychiatric or cognitive side effects, due to this brain target´s proximity to, and involvment in, non-motor associative and limbic circuitry.

    Conclusions In terms of mortality and morbidity, modern stereotactic neurosurgery for movement disorders, both ablation and DBS, is a safe procedure even in advanced stages of disease. Symptoms of PD, ET and dystonia can be alleviated mainly with DBS and even unilaterally with pallidal lesions, at the expense of, in most cases, minor side-effects.

  • 89.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hyperhidrosis caused by deep brain stimulation in the posterior subthalamic area2017Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 380, s. 277-279Artikel i tidskrift (Refereegranskat)
  • 90.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Imhotep and the discovery of cerebrospinal fluid2014Ingår i: Anatomy Research International, ISSN 2090-2743, E-ISSN 2090-2751, Vol. 2014, artikel-id 256105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned.

  • 91.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Orthopedic surgery in ancient Egypt2014Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, nr 6, s. 670-676Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Ancient Egypt might be considered the cradle of medicine. The modern literature is, however, sometimes rather too enthusiastic regarding the procedures that are attributed an Egyptian origin. I briefly present and analyze the claims regarding orthopedic surgery in Egypt, what was actually done by the Egyptians, and what may have been incorrectly ascribed to them.

    METHODS: I reviewed the original sources and also the modern literature regarding surgery in ancient Egypt, concentrating especially on orthopedic surgery.

    RESULTS: As is well known, both literary sources and the archaeological/osteological material bear witness to treatment of various fractures. The Egyptian painting, often claimed to depict the reduction of a dislocated shoulder according to Kocher's method, is, however, open to interpretation. Therapeutic amputations are never depicted or mentioned in the literary sources, while the specimens suggested to demonstrate such amputations are not convincing.

    INTERPRETATION: The ancient Egyptians certainly treated fractures of various kinds, and with varying degrees of success. Concerning the reductions of dislocated joints and therapeutic amputations, there is no clear evidence for the existence of such procedures. It would, however, be surprising if dislocations were not treated, even though they have not left traces in the surviving sources. Concerning amputations, the general level of Egyptian surgery makes it unlikely that limb amputations were done, even if they may possibly have been performed under extraordinary circumstances.

  • 92.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fytagoridis, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    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.
    Unilateral caudal Zona incerta deep brain stimulation for Parkinsonian tremor2012Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, nr 10, s. 1062-1066Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.

    Methods: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.

    Results: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.

    Conclusion: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsoniantremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.

  • 93.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Fytagoridis, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Tisch, S
    Deep brain stimulation of the posterior subthalamic area in the treatment of tremor2009Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, nr 1, s. 31-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Several studies have described lesional therapy in the posterior subthalamic area (PSA) in the treatment of various movement disorders. Recently, some publications have illustrated the effect of deep brain stimulation (DBS) in this area in patients with Parkinson's disease, essential tremor, MS-tremor, and other forms of tremor. Even though the clinical series is small, the reported benefits prompted us to explore DBS in this area in the treatment of tremor.

    METHOD: Five patients with tremor were operated using unilateral DBS of the PSA. Two patients had dystonic tremor, one primary writing tremor, one cerebellar tremor and the other neuropathic tremor. All patients were assessed before and 1 year after surgery using items 5 and 6 (tremor of the upper extremity), 11-14 (hand function), and when appropriate item 10 (handwriting) from the essential tremor rating scale.

    FINDINGS: The mean improvement on stimulation after 1 year was 87%. A pronounced and sustained microlesional effect was seen in several of the patients, and while the mean improvement off stimulation was 56% the reduction in the three patients with the most pronounced effect was 89%. The two patients with dystonic tremor did also become free of the dystonic symptoms and pain in the treated arm. No severe complication occurred.

    CONCLUSIONS: DBS of the PSA in this small group of patients had an excellent effect on the different forms of tremor, except for the neuropathic tremor where the effect was moderate. These preliminary results suggest PSA to be an effective target for the treatment of various forms of tremor. Further studies concerning indications, safety and efficacy of DBS in the posterior subthalamic area are required.

  • 94.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Pallidotomy versus pallidal stimulation2006Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 12, nr 5, s. 296-301Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on–off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22–60) after the pallidotomy and 22 months (range 12–33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20–26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.

  • 95.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up2007Ingår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, nr 5, s. 504-509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 – 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

    Read More: http://informahealthcare.com/doi/abs/10.1080/02688690701552278

  • 96.
    Blomstedt, Patric
    et al.
    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. Unit of Functional Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK.
    Closed loop stimulation for tremor was invented in 19802019Ingår i: Brain Stimulation, ISSN 1935-861X, E-ISSN 1876-4754, Vol. 12, nr 4, s. 1072-1073Artikel i tidskrift (Refereegranskat)
  • 97.
    Blomstedt, Patric
    et al.
    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. Unit of Functional Neurosurgery, University College of London, Institute of Neurology, London, UK.
    The paper that wrote itself – A ghost story2018Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, nr 9, s. 1509-1510Artikel i tidskrift (Refereegranskat)
  • 98.
    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.
    Are complications less common in deep brain stimulation than in ablative procedures for movement disorders?2006Ingår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 84, nr 2-3, s. 72-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The side effects and complications of deep brain stimulation (DBS) and ablative lesions for tremor and Parkinson’s disease were recorded in 256 procedures (129 DBS and 127 lesions). Perioperative complications (seizures, haemorrhage, confusion) were rare and did not differ between the two groups. The rate of hardware-related complications was 17.8%. In ventral intermediate (Vim) thalamotomies, the rate of side effects was 74.5%, in unilateral Vim-DBS 47.3%, while in 7 bilateral Vim-DBS 13 side effects occurred. Most of the side effects of Vim-DBS were reversible upon switching off, or altering, stimulation parameters. In unilateral pallidotomy, the frequency of side effects was 21.9%, while in bilateral staged pallidotomies it was 33.3%. Eight side effects occurred in 11 procedures with pallidal DBS. In 22 subthalamic nucleus DBS procedures, 23 side effects occurred, of which 8 were psychiatric or cognitive. Unilateral ablative surgery may not harbour more postoperative complications or side effects than DBS. Some of the side effects following lesioning are transient and most but not all DBS side effects are reversible. In the Vim DBS is safer than lesioning, while in the pallidum, unilateral lesions are well tolerated.

    Copyright © 2006 S. Karger AG, Basel

  • 99.
    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.
    Deep brain stimulation for movement disorders before DBS for movement disorders2010Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 16, nr 7, s. 429-433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Deep brain stimulation (DBS) is an established surgical treatment for Parkinson's disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD. This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using "therapeutic electrical stimulation" through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson's disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.

  • 100.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Silberstein, P
    Lees, A
    Limousin, P
    Yelnik, J
    Agid, Y
    Acute severe depression induced by intraoperative stimulation of the Substatia Nigra: a case-report2008Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 14, nr 3, s. 253-256Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    We present a 62 years old man with Parkinson's disease (PD) who underwent bilateral stimulation in the subthalamic nucleus (STN). During the intraoperative evaluation, stimulation through the lowest contact in the right STN area, induced an acute depressive state, during which the patient was crying and expressing that he did not want to live. The patient returned to his normal state of mood within seconds after the cessation of stimulation. Repeated blinded stimulations resulted in the same response. Immediate postoperative magnetic resonance imaging (MRI) revealed that the lowest contact of the right electrode was located in the substantia nigra.

1234567 51 - 100 av 825
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf