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  • 101.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Szakacs, Attila
    University of Gothenburg, Sweden.
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Ståhlbrandt, Henriettae
    Highland Hospital, Sweden.
    Darin, Niklas
    University of Gothenburg, Sweden.
    Hallbook, Tove
    University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Altered Brain Microstate Dynamics in Adolescents with Narcolepsy2016In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 10, no 369Article in journal (Refereed)
    Abstract [en]

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional fMRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics.

  • 102.
    Morbelli, Silvia
    et al.
    IRCCS Osped Policlin San Martino, Italy; Univ Genoa, Italy.
    Chincarini, Andrea
    Natl Inst Nucl Phys INFN, Italy.
    Brendel, Matthias
    Ludwig Maximilians Univ Munchen, Germany.
    Rominger, Axel
    Ludwig Maximilians Univ Munchen, Germany; Univ Hosp Bern, Switzerland.
    Bruffaerts, Rose
    Katholieke Univ Leuven, Belgium; Univ Hosp Leuven, Belgium.
    Vandenberghe, Rik
    Katholieke Univ Leuven, Belgium; Univ Hosp Leuven, Belgium.
    Kramberger, Milica G.
    Univ Med Ctr, Slovenia.
    Trost, Maja
    Univ Med Ctr, Slovenia; Univ Ljubljana, Slovenia.
    Garibotto, Valentina
    Geneva Univ Hosp, Switzerland; Univ Geneva, Switzerland.
    Nicastro, Nicolas
    Geneva Univ Hosp, Switzerland; Univ Cambridge, England.
    Frisoni, Giovanni B.
    Geneva Univ Hosp, Switzerland.
    Lemstra, Afina W.
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    van der Zande, Jessica
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Pilotto, Andrea
    Univ Brescia, Italy; FERB ONLUS S Isidoro Hosp, Italy.
    Padovani, Alessandro
    Univ Brescia, Italy.
    Garcia-Ptacek, Sara
    Karolinska Inst, Sweden.
    Savitcheva, Irina
    Karolinska Inst, Sweden.
    Ochoa-Figueroa, Miguel A.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Södersjukhuset, Sweden.
    Davidsson, Anette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Camacho, Valle
    Univ Autonoma Barcelona, Spain.
    Peira, Enrico
    Univ Genoa, Italy.
    Arnaldi, Dario
    Univ Genoa, Italy.
    Bauckneht, Matteo
    IRCCS Osped Policlin San Martino, Italy; Univ Genoa, Italy.
    Pardini, Matteo
    IRCCS Osped Policlin San Martino, Italy; Univ Genoa, Italy.
    Sambuceti, Gianmario
    IRCCS Osped Policlin San Martino, Italy; Univ Genoa, Italy.
    Aarsland, Dag
    Stavanger Univ Hosp, Norway; Kings Coll London, England.
    Nobili, Flavio
    IRCCS Osped Policlin San Martino, Italy; Univ Genoa, Italy.
    Metabolic patterns across core features in dementia with lewy bodies2019In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 85, no 5, p. 715-725Article in journal (Refereed)
    Abstract [en]

    Objective

    To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern.

    Methods

    Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core‐feature–specific patterns controlling for the main confounding variables (Mini‐Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE‐sensitive map.

    Results

    Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral–frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto‐occipital cortex, precuneus, and ventrolateral–frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral–parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum.

    Interpretation

    Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical–imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715–725

  • 103.
    Nilsson, S
    et al.
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå 901 85, Sweden.
    Levi, Richard
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå 901 85, Sweden.
    Nordstrom, A
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå 901 85, Sweden.
    Treatment-resistant sensory motor symptoms in persons with SCI may be signs of restless legs syndrome2011In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 49, no 6, p. 754-756Article in journal (Refereed)
    Abstract [en]

    Study design: Case report on the successful treatment with pramipexole in four men with chronic spinal cord injury (SCI) suffering from refractory symptoms that were previously considered to be manifestations of a post-traumatic spastic syndrome or neuropathic pain.andlt;br /andgt;Objective: To raise awareness among health professionals regarding the diagnostic and therapeutic possibility of restless legs syndrome (RLS) and periodic limb movements (PLMs) in some patients with SCI responding poorly to conventional treatment for spasticity or neuropathic pain.andlt;br /andgt;Setting: Neurorehabilitation department of the Rehabilitation Medicine Center of Northern University Hospital, Umea, Sweden.andlt;br /andgt;Methods: Medical records and clinical data were retrospectively reviewed.andlt;br /andgt;Results: All cases obtained treatment with pramipexole, initially 0.09-0.72 mg day(-1). Two of the cases had RLS and PLMs, one RLS only and one PLMs only. All four reported symptoms in the lower extremities and one also in the upper extremities. Three patients with residual gait function reported RLS score with/without treatment as follows: 32/11, 37/12 and 33/12. One patient with complete paraplegia (with incomplete RLS score) reported 22/10. After a follow-up period of 16, 20, 43 and 49 months, respectively, all four still reported excellent outcomes. Two remained on initial dosage; one had increased dosage from 0.09 to 0.18 mg day(-1) and one from 0.27 to 0.80 mg day(-1) during the follow-up period.andlt;br /andgt;Conclusions: In persons with SCI suffering from infralesional involuntary movements and/or dysesthesia and with poor response to conventional antispastic or analgesic treatment, the possibility of RLS or PLMs should be considered, as these conditions seem eminently treatable. Spinal Cord (2011) 49, 754-756; doi:andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;scandlt;/highlightandgt;.andlt;highlightandgt;2010.164andlt;/highlightandgt;; published online 30 November 2010

  • 104.
    Nord, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Levodopa pharmacokinetics -from stomach to brain: A study on patients with Parkinson’s disease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.

    In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.

    To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.

    List of papers
    1. Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    Open this publication in new window or tab >>Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    2017 (English)In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 06, no 01Article in journal (Refereed) Published
    Abstract [en]

    Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.

    Place, publisher, year, edition, pages
    Scientific Research Publishing, 2017
    National Category
    Neurology Gastroenterology and Hepatology Anesthesiology and Intensive Care Surgery Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-136685 (URN)10.4236/apd.2017.61001 (DOI)
    Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-01-12
    2. The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
    Open this publication in new window or tab >>The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
    Show others...
    2010 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 25, no 3, p. 363-367Article in journal (Refereed) Published
    Abstract [en]

    Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2010
    Keywords
    Parkinsons Disease, levodopa, continuous infusion, COMT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54855 (URN)10.1002/mds.22613 (DOI)000276136900016 ()
    Available from: 2010-04-16 Created: 2010-04-16 Last updated: 2018-01-12
    3. Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
    Open this publication in new window or tab >>Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
    Show others...
    2014 (English)In: Neurology and Clinical Neuroscience, ISSN 2049-4173, Vol. 2, no 5, p. 149-155Article in journal (Refereed) Published
    Abstract [en]

    Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2014
    Keywords
    deep brain stimulation, levodopa, microdialysis, neurotransmitters, Parkinson
    National Category
    Medical Bioscience Medical Biotechnology Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-113590 (URN)10.1111/ncn3.109 (DOI)
    Available from: 2015-01-23 Created: 2015-01-23 Last updated: 2019-02-11Bibliographically approved
    4. Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
    Open this publication in new window or tab >>Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
    2017 (English)In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 6, no 2, p. 52-66Article in journal (Refereed) Published
    Abstract [en]

    Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.

    Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.

    Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.

    Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.

    Place, publisher, year, edition, pages
    Scientific Research Publishing Inc, 2017
    Keywords
    Parkinson’s Disease, Levodopa, Dopamine, Brain, Microdialysis, Deep Brain Stimulation
    National Category
    Neurology Cardiac and Cardiovascular Systems Gastroenterology and Hepatology Anesthesiology and Intensive Care Other Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-139251 (URN)10.4236/apd.2017.62006 (DOI)
    Available from: 2017-07-07 Created: 2017-07-07 Last updated: 2018-01-12Bibliographically approved
  • 105.
    Nord, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Hannestad, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?2017In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 06, no 01Article in journal (Refereed)
    Abstract [en]

    Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.

  • 106.
    Nord, Maria
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease2017In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 6, no 2, p. 52-66Article in journal (Refereed)
    Abstract [en]

    Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.

    Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.

    Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.

    Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.

  • 107.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Dahlstrand, Ulf
    Lund University.
    R Larsson, Magnus
    Lund University.
    Larsson, Elna-Marie
    Aarhus University Hospital.
    Knutsson, Linda
    Lund University.
    Johanson, Aki
    Lund University.
    Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study2010In: JOURNAL OF ECT, ISSN 1095-0680, Vol. 26, no 1, p. 62-67Article in journal (Refereed)
    Abstract [en]

    Background: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression.

    Methods: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated.

    Results: The left as well as the right hippocampal volume increased significantly after ECT.

    Conclusions: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.

  • 108.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Hultén, Martin
    Psychiatric Neuromodulation Unit (PNU), Dept of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
    Landén, Mikael
    Psychiatric Neuromodulation Unit (PNU), Dept of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
    Lundberg, Johan
    Department of Clinical Neuroscience, Karolinska Institutet and Section for Affective Disorders, Northern Stockholm Psychiatry, Stockholm, Sweden.
    von Knorring, Lars
    Department of Neuroscience, Psychiatry, Uppsala university, Uppsala, Sweden.
    Nordenskjöld, Axel
    Department of Psychiatry, Faculty ofMedicine and Health, Örebro University, Örebro, Sweden.
    Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT2015In: The Journal of ECT, ISSN 1095-0680, Vol. 31, no 4, p. 263-267Article in journal (Refereed)
    Abstract [en]

    Objectives: The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013.

    Methods: The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT.

    Results: We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series.

    Conclusions: In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.

  • 109.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Knutsson, Linda
    Department of Medical Radiation Physics, Lund University, Lund, Sweden.
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Johanson, Aki
    Department of Psychiatry, Lund University, Lund, Sweden.
    Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Understanding electroconvulsive therapy (ECT) is of importance not only for optimizing treatment, but could also provide important information about key features of the healing process in depression. Enhanced inhibition (the anticonvulsant hypothesis) is one of several suggested mechanisms of action of ECT. Earlier studies on cerebral blood flow during ECT have given diverging results. Our aim was to study changes in cerebral blood flow in depression treated with ECT and their relation to treatment outcome.

    Methods: We obtained MRI scans in 14 depressed subjects referred for ECT. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) within 1 week before and 2 weeks after a course of ECT. The relative CBF was calculated from mean values in predefined regions of interest in relation to the mean value in the whole brain.

    Results: A significant relative CBF increase in the occipital region (p < 0.05) and a significant relative decrease in the right lateral temporal lobe (p < 0.05) were found in the entire study group. A significant decrease in the right frontal lobe, with a significant anteriorposterior and right-left gradient shift in relative CBF, was a distinguishing feature in patients with ECT-induced remission (n = 8).

    Limitations: This observational study is limited by the risk of random bias and its low number of participants.

    Conclusions: Our results suggest that a decreased relative blood flow in frontal regions may be a hallmark of treatment efficacy in depression treated with ECT.

  • 110.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Larsson, M. R.
    Lund University, Sweden.
    Larsson, E.-M.
    Uppsala University, Sweden.
    Johansson, A.
    Lund University, Sweden.
    Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression2014In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 129, no 4, p. 303-311Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome.

    METHOD:

    Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI.

    RESULTS:

    Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT.

    CONCLUSION:

    The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome.

  • 111.
    Nordenfelt, Patrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Nilsson, Mats
    Futurum, Academy for Health and Care, Jönköping County Council, Jönköping, Sweden.
    Lindfors, Anders
    Department of Pediatrics, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Wahlgren, Carl-Fredrik
    Dermatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden / Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Academy for Health and Care, Jönköping County Council, Jönköping, Sweden,.
    Health-related quality of life in relation to disease activity in adults with hereditary angioedema in Sweden2017In: Allergy and Asthma Proceedings, ISSN 1088-5412, E-ISSN 1539-6304, Vol. 38, no 6, p. 447-455Article in journal (Refereed)
    Abstract [en]

    Background: Health-related quality of life (HR-QoL) is impaired in patients with hereditary angioedema (HAE) but has not yet been satisfactorily described.

    Objective: To study HR-QoL in patients with HAE by combining different HR-QoL instruments with disease activity assessment. Methods: All adults in the Swedish HAE registry were invited to take part in this questionnaire study, which used the generic HR-QoL instruments, EuroQol 5 Dimensions 5 Level (EQ-5D-5L) and the RAND Corporation Short Form 36 (RAND-36), the disease-specific Angioedema Quality of Life instrument (AE-QoL), the recently introduced Angioedema Activity Score (AAS) form, and questionnaires on sick leave and prophylactic medication.

    Results: Sixty-four of 133 adults (26 men, 38 women) between 18 and 91 years old responded. The most affected HR-QoL dimensions in the EQ-5D-5L were pain/discomfort and anxiety/depression; in the RAND-36, energy/fatigue, general health, pain; and, in the AE-QoL, fears/shame and fatigue/mood. Women had lower HR-QoL in the RAND-36 for general health and energy/fatigue (p < 0.05). Patients who reported any AAS of >0 had significantly impaired HR-QoL. There were significant associations (p < 0.05) between the AAS and EQ-5D-5L, between the AAS and all dimensions of the RAND-36 except physical function, and between the AAS and AE-QoL in all dimensions. Nine of 36 patients who reported sick leave during the previous 4 weeks had significantly impaired HR-QoL in all the instruments (p < 0.05). There was no significant difference in HR-QoL in the patients with and the patients without prophylactic medication, except for the nutrition dimension of the AE-QoL (p < 0.05).

    Conclusion: Comprehensive information is obtained by combining different HR-QoL instruments. Pain, anxiety/depression, and fatigue/mood are important aspects of HAE but the AE-QoL disregards pain. HR-QoL was not significantly affected by prophylaxis. Increased disease activity was associated with impaired HR-QoL, which justifies more active disease management.

  • 112.
    Norrbrink, Budh C
    et al.
    Spinalis SCI Unit, Karolinska Hospital and Faculty of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Lund, I
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Hultling, C
    Spinalis SCI Unit, Karolinska Hospital and Faculty of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Levi, Richard
    Frösunda Center, Solna and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Werhagen, L
    Spinalis SCI Unit, Karolinska Hospital and Faculty of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Ertzgaard, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Lundeberg, T
    Spinalis SCI Unit, Karolinska Hospital and Faculty of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Gender related differences in pain in spinal cord injured individuals.2003In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 41, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN:: Out of a population of 456 patients with spinal cord injuries (SCI), 130 having pain were selected after matching, based on gender, age, American Spinal Injury Association (ASIA) impairment grade and level of lesion. OBJECTIVE:: To investigate whether gender differences with regard to pain perception and prevalence exist in a population of patients following spinal cord injury. SETTING:: Spinalis SCI Unit (out-patient clinic), Stockholm, Sweden. METHOD:: 130 patients suffering from pain were assessed over a 12-month period in a yearly health control. RESULTS:: SCI women had a higher prevalence of nociceptive pain than men and their use of analgesics was greater. However, no differences between the sexes could be seen regarding pain and localization, onset, distribution, factors affecting pain, number of painful body regions, pain descriptors, ratings of pain intensities or in pain and life satisfaction. CONCLUSION:: This study showed that SCI men and women describe their pain very similarly. However, SCI women had a higher prevalence of nociceptive pain than men and their use of opiates and non-steroid anti-inflammatory drugs (NSAIDs) was greater.Spinal Cord (2003) 41, 122-128. doi:andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;sj.scandlt;/highlightandgt;.andlt;highlightandgt;3101407andlt;/highlightandgt; [ABSTRACT FROM AUTHOR]

  • 113.
    Nyholm, Dag
    et al.
    Uppsala University Hospital.
    Constantinescu, R
    Sahlgrens University Hospital.
    Holmberg, B
    Sahlgrens University Hospital.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Askmark, H
    Uppsala University Hospital.
    Comparison of apomorphine and levodopa infusions in four patients with Parkinsons disease with symptom fluctuations2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, no 5, p. 345-348Article in journal (Other academic)
    Abstract [en]

    Motor fluctuations in patients with advanced Parkinsons disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed.

    We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail.

    The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary.

    Ratings in moderate to severe off state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion.

    Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

  • 114.
    Palak, A
    et al.
    Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
    Smith, C
    Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
    Abbott, Allan
    Health Sciences, Bond University, Gold Coast, QLD, Australia.
    Rizkallah, N
    Health Sciences, Bond University, Gold Coast, QLD, Australia.
    Motor assessment score. Is it fit for the future?2014In: Special Issue: SMART STROKES 2014 Conference, 28-29 August 2014, Sheraton on the Park, Sydney, NSW, Australia, John Wiley & Sons, 2014, Vol. Vol 9 (Suppl. 2), p. 10-10Conference paper (Other academic)
    Abstract [en]

    Background: The Motor Assessment Scale (MAS) is commonly used to assess functional change in stroke patients. Anecdotal evidence suggests that the scale does not accurately reflect patient outcomes potentially impacting on physiotherapists’ use of the scale.

    Aims: This study aims to investigate physiotherapists use and perceived utility of the MAS to measure functional performance of stroke survivors undergoing rehabilitation.

    Method: A purpose-designed 29-item online survey was distributed to Queensland Rehabilitation Physiotherapy Network members. Open and closed questions were asked regarding demographics, MAS implementation, perception of item subtest hierarchy and levels of difficulty and adherence to scoring guidelines.

    Results: Thirty-one surveys were received; 63% were from physiotherapists in metropolitan centers, 84% from public hospitals and 61% insubacute settings. Approximately half (45%) had been practicing in neurological rehabilitation for 5–10 years. More than 70% of respondents routinely used the MAS. The majority (80%) reported using the recommended guidelines when scoring the MAS, though 55% did not score all subsets of Item 8. Most were dissatisfied with hierarchy and levels of difficulty of item subtests, with no item scoring 100% satisfaction by respondents. Thirty percent of respondents did not use the MAS. Common reasons included: too time consuming (56%), not sensitive to change (22%), lack of confidence in administration (33%), items not relevant for patient function (45%) and ceiling effect (44%).

    Conclusion: MAS use varies across rehabilitation units in Queensland. Difficulties were identified with all items, including use of recommended scoring guidelines. Further research is required to address these issues.

  • 115.
    Peolsson, Anneli
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Wibault, Johanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Dedering, Åsa
    Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Futurum, County Council Jönköping, Sweden .
    Persson, Liselott
    Lunds University, Sweden.
    Löfgren, Håkan
    Ryhov Hospital, Jönköping, Sweden .
    Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial2014In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 15, no 34Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness.

    METHODS/DESIGN:

    This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated.

    DISCUSSION:

    We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease.

  • 116.
    Persson, Josefine
    et al.
    University of Gothenburg, Sweden.
    Aronsson, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Holmegaard, Lukas
    University of Gothenburg, Sweden.
    Redfors, Petra
    University of Gothenburg, Sweden.
    Stenlof, Kaj
    University of Gothenburg, Sweden.
    Jood, Katarina
    University of Gothenburg, Sweden.
    Jern, Christina
    University of Gothenburg, Sweden.
    Blomstrand, Christian
    University of Gothenburg, Sweden.
    Forsberg-Warleby, Gunilla
    University of Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors2017In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 26, no 11, p. 3059-3068Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses QALY-weights. Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses QALY-weights. Cohabitant dyads of 247 stroke survivors aged amp;lt; 70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses QALY-weights. The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients dependency would capture more of the total effect in dyads of stroke survivors.

  • 117.
    Persson, Josefine
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Holmegaard, Lukas
    University of Gothenburg, Sweden.
    Redfors, Petra
    University of Gothenburg, Sweden.
    Svensson, Mikael
    University of Gothenburg, Sweden.
    Jood, Katarina
    University of Gothenburg, Sweden.
    Jern, Christina
    University of Gothenburg, Sweden.
    Blomstrand, Christian
    University of Gothenburg, Sweden.
    Forsberg-Warleby, Gunilla
    University of Gothenburg, Sweden.
    Long-term cost of spouses informal support for dependent midlife stroke survivors2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 6, article id e00716Article in journal (Refereed)
    Abstract [en]

    Objectives: Stroke is a major global disease that requires extensive care and support from society and relatives. The aim of this study was to identify and quantify the long-term informal support and to estimate the annual cost of informal support provided by spouses to their stroke surviving partner. Method: Data were based on the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. One-third of the spouses stated that they provided support to their stroke surviving partner. The magnitude of the support was assessed with a study-specific time-diary and was estimated for independent and dependent stroke survivors based on the scores of the modified Rankin Scale. To deal with skewed data, a two-part econometric model was used to estimate the annual cost of informal support. Result: Cohabitant dyads of 221 stroke survivors aged amp;lt; 70 at stroke onset were included in the study. Spouses of independent stroke survivors (n = 188) provided on average 0.15 hr/day of practical support and 0.48 hr/day of being available. Corresponding figures for spouses of dependent stroke survivors (n = 33) were 5.00 regarding practical support and 9.51 regarding being available. The mean annual cost of informal support provided for independent stroke survivors was estimated at (sic)991 and (sic)25,127 for dependent stroke survivor. Conclusion: The opportunity cost of informal support provided to dependent midlife stroke survivors is of a major magnitude many years after stroke onset and should be considered in economic evaluations of health care.

  • 118.
    Pyykko, Ilmari
    et al.
    University of Tampere, Finland.
    Manchaiah, Vinaya
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Lamar University, TX 77710 USA; Audiol India, India; Manipal University, India.
    Zou, Jing
    University of Tampere, Finland; Second Mil Medical University, Peoples R China.
    Levo, Hilla
    University of Helsinki, Finland.
    Kentala, Erna
    University of Helsinki, Finland.
    Do patients with Menieres disease have attacks of syncope?2017In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 264, p. S48-S54Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the prevalence and associated factors for syncope among patients with Menieres disease (MD). An attack of syncope was defined as a sudden and transient loss of consciousness, which subsides spontaneously and without a localizing neurological deficit. The study used an across-sectional survey design. Information from a database consisting of 961 individuals was collected from the Finnish Meniere Association. The data contained case histories, general health-related quality of life (HRQoL), and impact measurements of the complaints. In the current study sample, syncope occurred in 12.3% of the patients with MD. It was more prevalent among elderly persons and among those with a longer duration of MD. Syncope was significantly associated with disturbances of otolith function reflected as Tumarkin attacks, gait and balance problems, environmental change of pressure, and physical strain. It was also associated with visual blurring; in fact, patients with otolith dysfunction in MD often experience visual field changes. It was also associated with headache, but not with migraine. Syncope was experienced as frightening and HRQoL was significantly worsened. The patient had higher anxiety scores, and suffered more from fatigue. The results demonstrate that neurally mediated syncope occurs in patients with an advanced form of MD who suffer from Tumarkin attacks due to failure in otolith function. The mechanism seems to be triggered through the vestibular sympathetic reflex when the otolith system fails due to disrupted utricular otolithic membrane mediate erroneous positional information from the otolith organ to the vasomotor centres in the brain stem and medulla.

  • 119.
    Pålhagen, Sven E.
    et al.
    Karolinska University Hospital, Sweden.
    Sydow, Olof
    Karolinska University Hospital, Sweden.
    Johansson, Anders
    Uppsala University, Sweden.
    Nyholm, Dag
    Uppsala University, Sweden.
    Holmberg, Bjorn
    Sahlgrens University Hospital, Sweden.
    Widner, Hakan
    Skåne University Hospital, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Linder, Jan
    Norrlands University Hospital, Sweden.
    Hauge, Tove
    Molde Hospital HNR, Norway.
    Jansson, Rasmus
    Sundsvall Hospital, Sweden.
    Bergmann, Lars
    AbbVie Inc, IL USA.
    Kjellander, Susanna
    AbbVie AB, Sweden.
    Marshall, Thomas S.
    AbbVie Inc, IL USA.
    Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinsons disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs2016In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 29, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Background: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinsons disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. Methods: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naive (N = 37), or had previous LCIG treatment for amp;lt;2 (N = 22), or amp;gt;= 2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinsons Disease Rating Scale (UPDRS), 39-item Parkinsons Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. Results: Mean monthly costs per patient ( 8226 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naive patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. Conclusions: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naive patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The longterm safety was consistent with the established LCIG profile. (C) 2016 AbbVie Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 120.
    Rackauskaite, D
    et al.
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of clinical sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Svanborg, Eva
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
    Andersson, E
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of clinical sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Löwhagen, K
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of clinical sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Csajbok, L
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
    Nellgård, B
    Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of clinical sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Prospective study: Long-term outcome at 12-15 years after aneurysmal subarachnoid hemorrhage2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 5, p. 400-407Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have poor outcome. Studies on outcome beyond 1 year post-aSAH are few, and late recovery is poorly investigated, initiating this prospective outcome study on patients 12-15 years after an aSAH. We hypothesized to find; functional improvement > 1 year post-ictus; increased long-term mortality in aSAH patients vs matched controls, and finally to present; predictors of long-term favorable outcome (GOS 4-5).

    METHODS: We prospectively investigated patients, admitted 2000-2003 to the Sahlgrenska University Hospital, 1 year post-ictus using Glasgow Outcome Scale (GOS). The patients were revalidated 12-15 years post-aSAH by structured-telephone interviews (GOS), followed by statistical analysis.

    RESULTS: A total of 158 patients were included, (women n = 114, men n = 44), with a mean age of 55 years at aSAH. Patients treated with surgical clipping had lower mortality. At the follow-up 12-15 years post-aSAH, all 103 survivors (65.2%) were categorized as having; good recovery (39.9%), moderate disability (15.2%), or severe disability (10.1%). Within the patient cohort, 23.6% improved GOS over time. Fifty-five patients died, median at 4 years post-ictus. aSAH patients had 3.5 times increased mortality 12-15 years post-ictus vs matched controls (P < .0001). Patients with favorable outcome at 1 year (67.3%, n = 101) had similar survival probability as control patients. Prognostic indicators of long-term favorable outcome were low age and high GOS at 1-year follow-up, (AUCROC, 0.79).

    CONCLUSIONS: Individual functional improvement was found >1 year post-ictus. Patients with favorable outcome at 1 year had similar long-term life expectancy as the general population. Indicators of long-term favorable prognosis were low age at ictus and high GOS at 1-year follow-up.

  • 121.
    Reich, Martin M.
    et al.
    University Hospital Wuerzburg, Germany; Julius Maximilian University, Germany.
    Brumberg, Joachim
    Julius Maximilian University, Germany; University Hospital, Germany.
    Pozzi, Nicolo G.
    University Hospital Wuerzburg, Germany; Julius Maximilian University, Germany.
    Marotta, Giorgio
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Italy.
    Roothans, Jonas
    Medtron Eindhoven Design Centre, Netherlands.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Medtron Eindhoven Design Centre, Netherlands.
    Musacchio, Thomas
    University Hospital Wuerzburg, Germany; Julius Maximilian University, Germany.
    Lopiano, Leonardo
    University of Turin, Italy.
    Lanotte, Michele
    University of Turin, Italy.
    Lehrke, Ralph
    St Barbara Klin, Germany.
    Buck, Andreas K.
    Julius Maximilian University, Germany; University Hospital, Germany.
    Volkmann, Jens
    University Hospital Wuerzburg, Germany; Julius Maximilian University, Germany.
    Isaias, Ioannis U.
    University Hospital Wuerzburg, Germany; Julius Maximilian University, Germany.
    Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?2016In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 139, p. 2948-2956Article in journal (Refereed)
    Abstract [en]

    Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence ( five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation- induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the ( sub) thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the ( sub) thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs.

  • 122.
    Rincel, Marion
    et al.
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Lépinay, Amandine
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Janthakhin, Yoothana
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Soudain, Gwenaëlle
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Yvon, Sophie
    Univ. Toulouse, Toulouse, France.
    DA SILVA, Stéphanie
    Univ. Toulouse, Toulouse, France.
    Joffre, Corinne
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Aubert, Agnes
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Séré, Alexandra
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Layé, Sophie
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Théodorou, Vassilia
    Univ. Toulouse, Toulouse, France.
    Ferreira, Guillaume
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Darnaudéry, Muriel
    UMR1286, INRA, Nutrition and Integrative Neurobiology (NutriNeuro) Bordeaux France; UMR1286 Univ. Bordeaux, Nutrition et Neurobiologie Intégrée Bordeaux France.
    Maternal high-fat diet and early-life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats.2018In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 223, no 2, p. 883-895Article in journal (Refereed)
    Abstract [en]

    The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous brain functions including stress response and cognitive processes. This brain area is also particularly affected by adversity during early life. Using an animal model in rats, we recently demonstrated that maternal exposure to a high-fat diet (HFD) prevents maternal separation (MS)-induced gene expression alterations in the developing PFC and attenuates several long-term deleterious behavioral effects of MS. In the present study, we ask whether maternal HFD could protect mPFC neurons of pups exposed to early life stress by examining dendritic morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats submitted to MS. Dams were fed either a control or an HFD throughout gestation and lactation, and pups were submitted to MS from PND2 to PND14. We report that maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at adulthood. Furthermore, we show in adult MS rats that PFC-dependent memory extinction deficits are prevented by maternal HFD. Finally, perinatal HFD exposure reverses gut leakiness following stress in pups and seems to exert an anti-stress effect in dams. Overall, our work demonstrates that maternal HFD affects the developing brain and suggests that nutrition, possibly through gut–brain interactions, could modulate mPFC sensitivity to early stress.

  • 123.
    Rosas-Arellano, Abraham
    et al.
    Univ Nacl Autonoma Mexico, Mexico.
    Estrada-Mondragon, Argel
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Pina, Ricardo
    Univ Santiago Chile, Chile; Univ Bernardo OHiggins, Chile.
    Mantellero, Carola A.
    Univ Las Amer, Chile.
    Castro, Maite A.
    Univ Austral Chile, Chile; Univ Austral Chile, Chile.
    The Tiny Drosophila Melanogaster for the Biggest Answers in Huntingtons Disease2018In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 8, article id 2398Article, review/survey (Refereed)
    Abstract [en]

    The average life expectancy for humans has increased over the last years. However, the quality of the later stages of life is low and is considered a public health issue of global importance. Late adulthood and the transition into the later stage of life occasionally leads to neurodegenerative diseases that selectively affect different types of neurons and brain regions, producing motor dysfunctions, cognitive impairment, and psychiatric disorders that are progressive, irreversible, without remission periods, and incurable. Huntingtons disease (HD) is a common neurodegenerative disorder. In the 25 years since the mutation of the huntingtin (HTT) gene was identified as the molecule responsible for this neural disorder, a variety of animal models, including the fruit fly, have been used to study the disease. Here, we review recent research that used Drosophila as an experimental tool for improving knowledge about the molecular and cellular mechanisms underpinning HD.

  • 124.
    Ruborg, Rebecca
    et al.
    Örebro University, Sweden.
    Gunnarsson, Karin
    Örebro University, Sweden.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Örebro University, Sweden; Neuro and Rehabmed Kliniken, Sweden.
    Predictors of post-stroke body temperature elevation2017In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 17, article id 218Article in journal (Refereed)
    Abstract [en]

    Background: Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke. Methods: The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature. Results: Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC -0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein amp;gt; 50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke. Conclusions: In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.

  • 125.
    Samir Samour, Mohamad
    et al.
    University of Western Sydney, Australia.
    Nagi Saulat, Saad
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Western Sydney, Australia.
    Shortland, Peter John
    Western Sydney University, Australia.
    Mahns, David Anthony
    University of Western Sydney, Australia.
    Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants2017In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 18, no 8, p. 994-1005Article in journal (Refereed)
    Abstract [en]

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P amp;lt; .0001), accompanied by the emergence of bilateral cold allodynia in 44% of participants, thus confirming the effectiveness of the model. Placebo-treated participants experienced a bilateral 35% alleviation in muscle soreness (P amp;lt; .0001), with no changes to the prevalence of cold allodynia. In contrast, minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P amp;lt; .0001), additionally, only 10% of minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Perspective: Four repeated Injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in healthy human participants. This hypersensitivity was characterized by bilateral muscular hyperalgesia and cutaneous cold allodynia, symptoms commonly reported in many chronic pain conditions. Minocycline pretreatment abolished the development of this state. Crown Copyright (C) 2017 Published by Elsevier Inc. on behalf of the American Pain Society

  • 126.
    Sandborg, Michael
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Rossitti, Sandro
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Pettersson, Håkan
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Nilsson Althen, Jonas
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Patient organ radiation doses during treatment for aneurismal subarachnoid haemorrhage2011Conference paper (Other academic)
  • 127.
    Schroeder, Jennifer R.
    et al.
    Johns Hopkins Bayview Med Ctr, MD 21224 USA.
    Phillips, Karran A.
    NIDA, MD 21224 USA.
    Epstein, David H.
    NIDA, MD 21224 USA.
    Jobes, Michelle L.
    NIDA, MD 21224 USA.
    Furnari, Melody A.
    NIDA, MD 21224 USA.
    Kennedy, Ashley P.
    NIDA, MD 21224 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Preston, Kenzie L.
    NIDA, MD 21224 USA.
    Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder2018In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 10, p. 2957-2966Article in journal (Refereed)
    Abstract [en]

    Background Preliminary evidence suggested that the PPAR gamma agonist pioglitazone reduces opioid-withdrawal symptoms, possibly by inhibiting increases in proinflammatory cytokines. Methods A randomized, placebo-controlled clinical trial was conducted utilizing two different study designs (entirely outpatient, and a combination of inpatient and outpatient) to evaluate the safety and efficacy of pioglitazone as an adjunct medication for people with opioid physical dependence undergoing a buprenorphine taper. Participants were stabilized on buprenorphine/naloxone (sublingual, up to 16/4 mg/day), then randomized to receive oral pioglitazone (up to 45 mg/day) or placebo before, during, and after buprenorphine taper. Outcome measures included the Subjective Opiate Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale, use of rescue medications to alleviate opioid withdrawal symptoms, and opioid-positive urine specimens. Cerebrospinal fluid (CSF) and plasma were collected during the taper in a subset of participants for measurement of proinflammatory cytokines. Results The clinical trial was prematurely terminated due to slow enrollment; 40 participants per group were required for adequate statistical power to test study hypotheses. Twenty-four participants enrolled; 17 received at least one dose of study medication (6 pioglitazone, 11 placebo). SOWS scores were higher in the pioglitazone arm than in the placebo arm after adjusting for use of rescue medications; participants in the pioglitazone arm needed more rescue medications than the placebo arm during the post-taper phase. SOWS scores were positively correlated with monocyte chemoattractant protein-1 (MCP-1) in CSF (r = 0.70, p = 0.038) and plasma (r = 0.77, p = 0.015). Participants having higher levels of plasma MCP-1 reported higher SOWS, most notably after the buprenorphine taper ended. Conclusions Results from this study provide no evidence that pioglitazone reduces opioid withdrawal symptoms during buprenorphine taper. High correlations between MCP-1 and opioid withdrawal symptoms support a role of proinflammatory processes in opioid withdrawal.

  • 128.
    Sjöström, Dick
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Proteomic study of microbiopsies from women with trapezius muscle pain and from healthy women2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Trapezius myalgia is a pain condition that usually develops in people with repetitive and stressful work tasks, which can lead to chronic widespread pain (CWP). This work compares protein expression levels in healthy women with those in women who have chronic widespread pain, including pain in the trapezius muscle, by using a proteomic approach.  Twodimensional gel electrophoresis and silver staining with a subsequent digital quantification of protein spots was used to detect spots which had significantly higher protein levels in either group. Preparative gels were made and stained with SYPRO Ruby, the protein spots that were significantly different between the groups were picked from the SYPRO Ruby gels and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF.

    The optical density of seven protein spots were significantly decreased in the trapezius muscle of the CWP subjects; however the standard deviations were notably high. Five of the seven proteins could be identified as desmin, creatine kinase B-type, serum albumin, heat shock protein beta-1 and slow skeletal muscle troponin T. Apart from serum albumin, all these proteins can possibly be responsible for pain in the trapezius muscle in CWP.

    In conclusion, this study demonstrates that two-dimensional gel electrophoresis in combination with mass spectrometry is a powerful tool to identify potential biomarkers of musculoskeletal pain in subjects with CWP. The results may provide new insights into the mechanisms and patho-physiology of trapezius myalgia.

  • 129.
    Sköld, C
    et al.
    Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Harms-Ringdahl, K
    Department of Surgical Sciences, Section of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Hultling, C
    Spinalis SCI Research Unit, Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Seiger, A
    Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Simultaneous Ashworth measurements and electromyographic recordings in tetraplegic patients.1998In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 79, no 8, p. 959-965Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A recent prevalence study of 353 spinal cord injured (SCI) individuals in the greater Stockholm area showed problematic spasticity in 30% of this population. To treat spasticity, the evaluation becomes crucial. The modified Ashworth scale (MAS) is the clinically most-used scale to grade degree of spasticity. This study evaluated whether the MAS correlated with electromyographic (EMG) recordings of muscle activity.

    STUDY DESIGN: This cross-sectional study was performed at an outpatient clinic that has the responsibility to do a standardized, yearly follow-up of all SCI patients in the greater Stockholm area. Thirty-eight SCI individuals met the inclusion criteria; 15 of the 38 were randomly selected for the study. They were all motor-complete tetraplegic men; mean age was 33 years and mean time since injury was 9 years. Spasticity evaluation was performed by flexing and extending the knees during simultaneous EMG recordings and MAS assessment of the thigh muscle activity.

    RESULTS: Eighty percent of the individual EMG recordings correlated significantly with the corresponding Ashworth measurements. The spastic resistance, as measured both clinically and electromyographically, was stronger and lasted longer during extension than flexion movements. Spearman coefficients for correlation of quantitative spasticity measures with MAS grades were calculated. EMG and clinical measures of spasticity were more closely correlated for flexion movements. Among EMG parameters, duration of movement-associated electrical activity invariably correlated significantly with the MAS grades (p < .05). Furthermore, Ashworth measurements of movement-associated spasticity showed a positive correlation with the EMG parameters mean, peak, and start to peak of electrical activity. Each increasing grade on the MAS corresponded to increasing myoelectric activity levels for each movement.

    CONCLUSION: EMG parameters were significantly positively correlated with simultaneous MAS measurements of the spastic muscle contraction. The Ashworth scale may therefore accurately reflect the movement-provoked spasticity in motor-complete tetraplegic patients.

  • 130.
    Sköld, C
    et al.
    Department of Clinical Neuroscience and Occupational Therapy and Elderly Care Research Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    Department of Physical Therapy Karolinska Institute, Stockholm, Sweden.
    Seiger, A
    Department of Clinical Neuroscience and Occupational Therapy and Elderly Care Research Karolinska Institute, Stockholm, Sweden.
    Spasticity after traumatic spinal cord injury: nature, severity, and location.1999In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 80, no 12, p. 1548-1557Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess spasticity in a prevalence population of persons with traumatic spinal cord injury (SCI), and determine the degree of correspondence between self-reported spasticity and investigator-elicited spasticity using the modified Ashworth scale.

    DESIGN: Survey of a near total (88%) prevalence population.

    SETTING: Outpatient clinic of a university hospital.

    PATIENTS: A total of 354 individuals with SCI.

    MAIN OUTCOME MEASURES: The survey includes self-reported symptoms, neurologic examination (American Spinal Injury Association [ASIA] classification), physical therapy examination, range of motion (ROM), and complications.

    RESULTS: Presence of problematic spasticity was significantly correlated with cervical incomplete (ASIA B-D) injury. Reports of beneficial effects of spasticity were significantly less common in women. Self-reported problematic spasticity was significantly correlated with extensor spasticity. Spasticity was elicitable by movement provocation in 60% of the patients reporting spasticity. Significant correlations were found between elicitable spasticity and limited ROM.

    CONCLUSION: Flexion, extension, and abduction movements performed with the patient placed in a standardized supine test position are suitable both for test of ROM and degree of spasticity. Spasticity was not elicitable by movement provocation on physical examination in 40% of the patients who reported spasticity, thus indicating that the patient's self-report is an important complement to the clinical assessment. A significant association between spasticity and contractures (reduced ROM) was seen.

  • 131.
    Stenberg, M
    et al.
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, 901 85 Umeå, Sweden..
    Godbolt, AK
    Department of Clinical Sciences, Karolinska Institutet and University Department of Rehabilitation Medicine Stockholm, Danderyd Hospital, 182 88 Stockholm, Sweden..
    Nygren, De Boussard C
    Department of Clinical Sciences, Karolinska Institutet and University Department of Rehabilitation Medicine Stockholm, Danderyd Hospital, 182 88 Stockholm, Sweden..
    Levi, Richard
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, 901 85 Umeå, Sweden..
    Stålnacke, BM
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, 901 85 Umeå, Sweden..
    Cognitive Impairment after Severe Traumatic Brain Injury, Clinical Course and Impact on Outcome: A Swedish-Icelandic Study2015In: Behavioural Neurology, ISSN 0953-4180, E-ISSN 1875-8584, Vol. 2015, p. 12-, article id 680308Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the clinical course of cognitive and emotional impairments in patients with severe TBI (sTBI) from 3 weeks to 1 year after trauma and to study associations with outcomes at 1 year.andlt;br /andgt;Methods: Prospective, multicenter, observational study of sTBI in Sweden and Iceland. Patients aged 18-65 years with acute Glasgow Coma Scale 3-8 were assessed with the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and the Hospital Anxiety and Depression Scale (HADS). Outcome measures were Glasgow Outcome Scale Extended (GOSE) and Rancho Los Amigos Cognitive Scale-Revised (RLAS-R).andlt;br /andgt;Results: Cognition was assessed with the BNIS assessed for 42 patients out of 100 at 3 weeks, 75 patients at 3 months, and 78 patients at 1 year. Cognition improved over time, especially from 3 weeks to 3 months. The BNIS subscales "orientation" and "visuospatial and visual problem solving" were associated with the GOSE and RLAS-R at 1 year.andlt;br /andgt;Conclusion: Cognition seemed to improve over time after sTBI and appeared to be rather stable from 3 months to 1 year. Since cognitive function was associated with outcomes, these results indicate that early screening of cognitive function could be of importance for rehabilitation planning in a clinical setting.

  • 132.
    Stenberg, Maud
    et al.
    Umeå University, Sweden.
    Koskinen, Lars-Owe D.
    Umeå University, Sweden.
    Jonasson, Per
    Umeå University, Sweden.
    Levi, Richard
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Stålnacke, Britt-Marie
    Umeå University, Sweden; Karolinska Institute, Sweden; Danderyd Hospital, Sweden.
    Computed tomography and clinical outcome in patients with severe traumatic brain injury2017In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 31, no 3, p. 351-358Article in journal (Refereed)
    Abstract [en]

    Objective: To study: (i) acute computed tomography (CT) characteristics and clinical outcome; (ii) clinical course and (iii) Corticosteroid Randomisation after Significant Head Injury acute calculator protocol (CRASH) model and clinical outcome in patients with severe traumatic brain injury (sTBI). Methods: Initial CT (CT;) and CT 24 hours post-trauma (CT24) were evaluated according to Marshall and Rotterdam classifications. Rancho Los Amigos Cognitive Scale-Revised (RLAS-R) and Glasgow Outcome Scale Extended (GOSE) were assessed at three months and one year post-trauma. The prognostic value of the CRASH model was evaluated. Results: Thirty-seven patients were included. Marshall CT; and CT24 were significantly correlated with RLAS-R at three months. Rotterdam CT24 was significantly correlated with GOSE at three months. RLAS-R and the GOSE improved significantly from three months to one year. CRASH predicted unfavourable outcome at six months for 81% of patients with bad outcome and for 85% of patients with favourable outcome according to GOSE at one year. Conclusion: Neither CT nor CRASH yielded clinically useful predictions of outcome at one year post injury. The study showed encouragingly many instances of significant recovery in this population of sTBI. The combination of lack of reliable prognostic indicators and favourable outcomes supports the case for intensive acute management and rehabilitation as the default protocol in the cases of sTBI.

  • 133.
    Stensson, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ernberg, Malin
    Karolinska Inst, Sweden; Scandinavian Ctr Orofacial Neurosci, Sweden.
    Mannerkorpi, Kaisa
    Univ Gothenburg, Sweden.
    Kosek, Eva
    Karolinska Inst, Sweden; Lowenstromska Hosp, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The Relationship of Endocannabinoidome Lipid Mediators With Pain and Psychological Stress in Women With Fibromyalgia: A Case-Control Study2018In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 19, no 11, p. 1318-1328Article in journal (Refereed)
    Abstract [en]

    Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress, fibromyalgia (FM) is difficult to diagnose and lacks effective treatments. Endocannabinoids arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (eg, stress and anxiety), and are included in a new emerging "ome," the endocannabinoidome. This case-control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2 AG in 104 women with FM and 116 healthy control subjects. All participants rated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in women with FM than in healthy control subjects; significance remained for OEA and SEA after controlling for body mass index and age. 2-AG correlated positively with FM duration and body mass index, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings. The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM, their biological roles are uncertain with respect to the clinical manifestations of FM. Thus plasma lipids alone are not good biomarkers for FM. Perspective: This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids suitability to work as biomarkers for FM in the clinic were low; however, their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as a baseline during explorative FM pain management. (C) 2018 by the American Pain Society

  • 134.
    Sundelin, Heléne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Jonas F.
    Stockholm, Sweden.
    Author response: Autism and epilepsy: A population-based nationwide cohort study2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 1Article in journal (Other academic)
    Abstract [en]

    n/a

  • 135.
    Sörbo, Ann
    et al.
    Department of Neuro- and Rehabilitation, Southern Älvsborg Hospital, Borås, Sweden.
    Eiving, I.
    Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Rydenhag, B.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Hair Cortisol as a Biomarker of Stress before and after Subarachnoid Hemorrhage: A Case Report2017In: Remedy Open Access, E-ISSN 2573-6078, Vol. 2, article id 1062Article in journal (Refereed)
    Abstract [en]

    The aim was to study stress in the acute and post-acute phase in patients with severe traumaticbrain injury (TBI) or non-traumatic subarachnoid hemorrhage (SAH) who were treated at theneurointensive care unit (NICU). Hair cortisol is a biomarker of stress via alterations in hypothalamuspituitary-adrenal axis activity, where cortisol from plasma is continuously incorporated intogrowing hairs at their roots. As hair grows at an average of 1 cm/month, concentrations of haircortisol can also be used to measure stress levels retrospectively.

    Hair samples were collected at an interval of one month until three months, with the first cut atadmission to the NICU. The patients (or their relatives, if the patient was unable to communicate)were interviewed about psychological or physical stressors during the previous months.

    We present a 28-year-old woman suffering from a subarachnoid hemorrhage (SAH), studied withrepeated haircuts. She experienced the sudden onset of a severe headache. The general practitionersdiagnosed it as migraine or wry neck. Three weeks later, she experienced another attack ofsevere headache. A CT scan showed an SAH. Six months after the SAH, the patient developedhydrocephalus and was successfully treated with a VP shunt. In this case, hair cortisol was elevatedduring the pre-hospital month (probably because of pain and stress due to a sentinel or “warning”leak), during the intensive care period and until two months after the SAH. It then normalized, butit was elevated again at the time at which the patient developed hydrocephalus. At the nine-monthhaircut, her hair cortisol had again normalized.

    This case indicates that hair cortisol measurement is a promising method for studying stress,retrospectively and during recovery, in patients suffering from SAH.

  • 136.
    Tajeddinn, Walid
    et al.
    Novum, Sweden.
    Fereshtehnejad, Seyed-Mohammad
    Novum, Sweden.
    Seed Ahmed, Mohammed
    Novum, Sweden; Kings Coll London, England; University of Khartoum, Sudan.
    Yoshitake, Takashi
    Karolinska Institute, Sweden.
    Kehr, Jan
    Karolinska Institute, Sweden.
    Shahnaz, Tasmin
    Novum, Sweden; Vrinnevi Hospital, Sweden.
    Milovanovic, Micha
    Novum, Sweden; Vrinnevi Hospital, Sweden.
    Behbahani, Homira
    Novum, Sweden.
    Hoglund, Kina
    Novum, Sweden; Gothenburg University, Sweden.
    Winblad, Bengt
    Novum, Sweden.
    Cedazo-Minguez, Angel
    Novum, Sweden.
    Jelic, Vesna
    Novum, Sweden.
    Jaremo, Petter
    Novum, Sweden; Vrinnevi Hospital, Sweden.
    Aarsland, Dag
    Novum, Sweden; Stavanger University Hospital, Norway; Akershus University Hospital, Norway.
    Association of Platelet Serotonin Levels in Alzheimers Disease with Clinical and Cerebrospinal Fluid Markers2016In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 53, no 2, p. 621-630Article in journal (Refereed)
    Abstract [en]

    Introduction: Serotonin (5-HT) is involved in the pathology of Alzheimers disease (AD). Objective: We aimed to measure 5-HT level in platelets in AD and explore its association with cerebrospinal fluid (CSF), AD biomarkers (amyloid-beta 1-42 (A beta(42)), total tau (t-tau), and phosphorylated tau (p-tau)), and clinical symptoms. Methods: 15 patients with AD and 20 patients with subjective cognitive impairment (SCI) were included. 5-HT metabolites were measured, in a specific fraction, using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Results: Significantly lower 5-HT concentrations were observed in AD patients compared to SCI patients both after normalization against total protein (p = 0.008) or platelet count (p = 0.019). SCI patients with lower 5-HT level have higher AD CSF biomarkers, total tau (p = 0.026) and tau/A beta(42) ratio (p = 0.001), compared to those with high 5-HT levels. Conclusion: AD patients have reduced platelet 5-HT levels. In SCI, lower 5-HT content was associated with a higher AD-CSF biomarker burden.

  • 137.
    Terman, Alexei
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology.
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Is aging the price for memory?2005In: Biogerontology (Dordrecht), ISSN 1389-5729, E-ISSN 1573-6768, Vol. 6, no 3, p. 205-210Article in journal (Other academic)
    Abstract [en]

    Aging (senescence) is apparent in animals that possess long-lived postmitotic cells but is negligible in primitive species, such as hydras and other Cnidarians, all of whose cells are constantly renewed by cell division. This repetitive mitotic activity precludes the progressive intracellular accumulation of damaged biomolecules and organelles, which are obvious concomitants of aging in neurons and other long-lived cells of higher animals. We assume that the development of long-lived postmitotic cells, now found in the overwhelming majority of species, represented a useful evolutionary change. Probably, of particular importance was the evolution of long-lived neurons, which are required for long-term memory. However, the appearance of long-lived postmitotic cells not only increased fitness, but also gave rise to the aging process.

  • 138.
    Tobieson, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Rossitti, Sandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Marklund, Niklas
    Department of Clinical Sciences, Neurosurgery, Lund, Sweden.
    Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.2019In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, no 6, p. 1269-1278Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery.

    OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation.

    METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery.

    RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 ± 20 vs 40.6 ± 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery.

    CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone.

  • 139.
    Tomson, Torbjörn
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Nilsson, Bengt Y
    Karolinska Inst, Stockholm, Sweden.
    Levi, Richard
    Karolinska Inst, Stockholm, Sweden.
    Impaired visual contrast sensitivity in epileptic patients treated with carbamazepine.1988In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 45, no 8, p. 897-900Article in journal (Refereed)
    Abstract [en]

    Critical flicker fusion frequencies and visual contrast sensitivity were determined in 27 adult epileptic patients receiving carbamazepine monotherapy and in 24 healthy, drug-free control subjects. Flicker fusion thresholds were the same in patients and control subjects, whereas the contrast sensitivity was significantly reduced in the patient group at all spatial frequencies. There was a significant negative correlation between the plasma concentration of carbamazepine and the contrast sensitivity at 11.4 and 22.8 cycles per degree, indicating that the reduced contrast sensitivity was due to the drug therapy.

  • 140.
    Tropp, Maria
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundqvist, Anna
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Persson, Cecilia
    Department of Clinical Sciences, Lund University, Lund, Sweden.
    Samuelsson, Kersti
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Levander, Sten
    Department of Criminology, Malmö University, Malmo, Sweden.
    Self-ratings of everyday memory problems in patients with aquired brain injury - a tool for rehabilitation2015In: International Journal of Physical Medicine Rehabilitation, E-ISSN 2329-9096, Vol. 3, no 2Article in journal (Refereed)
    Abstract [en]

    Introduction: Memory problems are common in everyday life of patients with acquired brain injury (ABI). Some patients with ABI also have problems with self-monitoring/awareness. The ecological validity of neuropsychological tests for everyday life memory problems is questionable. Can self-report instruments supply complementary information? Aims: 1) To document the frequency/impact of self-reported memory problems in a sample of consecutive referrals of ABI patients using PEEM and REEM. 2) To characterize the instruments with respect to psychometrics and internal consistency. 3) To document differences in memory problem patterns for various kinds/localization of brain lesions, and associated anxiety/ depression symptoms. Methods: A descriptive retrospective study of consecutive referrals of ABI patients was performed. Ratings from the Evaluation of Everyday Memory (EEM), in a patient version (PEEM) and a version for relatives/proxies (REEM) were analysed as well as self-ratings of anxiety and depression. Results: The EEM instruments displayed good psychometric characteristics. The mean PEEM score were close to the tenth percentile of healthy controls. PEEM and REEM versions were strongly inter-correlated. Sex, age, and lesion characteristics did not matter much with one exception. Right-hemisphere lesion patients rated their memory problems significantly lower than the proxy, for all other lesions it was vice versa. Anxiety and depression symptoms were associated with memory problems.

  • 141.
    Tseli, Elena
    et al.
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden.
    Grooten, Wilhelmus Johannes Andreas
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden; Functional Area Occupational Therapy and Physiotherapy, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden.
    Stålnacke, Britt-Marie
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Department of Rehabilitation Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Boersma, Katja
    School of Law, Psychology and Social Work, Örebro University, Örebro, Sweden.
    Enthoven, Paul
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Äng, Björn Olov
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden; Functional Area Occupational Therapy and Physiotherapy, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden; School of Education, Health and Social Studies, Dalarna University, Falun, Sweden.
    Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain: protocol for a systematic review and meta-analysis2017In: Systematic Reviews, E-ISSN 2046-4053, Vol. 6, no 1, article id 199Article in journal (Refereed)
    Abstract [en]

    Background

    Chronic musculoskeletal pain is a major public health problem. Early prediction for optimal treatment results has received growing attention, but there is presently a lack of evidence regarding what information such proactive management should be based on. This study protocol, therefore, presents our planned systematic review and meta-analysis on important predictive factors for health and work-related outcomes following multidisciplinary rehabilitation (MDR) in patients with chronic musculoskeletal pain.

    Methods

    We aim to perform a synthesis of the available evidence together with a meta-analysis of published peer-reviewed original research that includes predictive factors preceding MDR. Included are prospective studies of adults with benign, chronic (> 3 months) musculoskeletal pain diagnoses who have taken part in MDR. In the studies, associations between personal and rehabilitation-based factors and the outcomes of interest are reported. Outcome domains are pain, physical functioning including health-related quality of life, and work ability with follow-ups of 6 months or more. We will use a broad, explorative approach to any presented predictive factors (demographicsymptoms-relatedphysicalpsychosocialwork-related, and MDR-related) and these will be analyzed through (a) narrative synthesis for each outcome domain and (b) if sufficient studies are available, a quantitative synthesis in which variance-weighted pooled proportions will be computed using a random effects model for each outcome domain. The strength of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation.

    Discussion

    The strength of this systematic review is that it aims for a meta-analysis of prospective cohort or randomized controlled studies by performing an extensive search of multiple databases, using an explorative study approach to predictive factors, rather than building on single predictor impact on the outcome or on predefined hypotheses. In this way, an overview of factors central to MDR outcome can be made and will help strengthen the evidence base and inform a wide readership including health care practitioners and policymakers.

  • 142.
    Tuulari, Jetro J.
    et al.
    Univ Turku, Finland; Univ Turku, Finland; Univ Turku, Finland; Turku Univ Hosp, Finland.
    Scheinin, Noora M.
    Univ Turku, Finland; Univ Turku, Finland; Turku Univ Hosp, Finland.
    Lehtola, Satu
    Univ Turku, Finland.
    Merisaari, Harri
    Univ Turku, Finland; Univ Turku, Finland.
    Saunavaara, Jani
    Turku Univ Hosp, Finland.
    Parkkola, Riitta
    Turku Univ Hosp, Finland; Univ Turku, Finland.
    Sehlstedt, Isac
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Karlsson, Linnea
    Univ Turku, Finland; Turku Univ Hosp, Finland; Univ Turku, Finland.
    Karlsson, Hasse
    Univ Turku, Finland; Univ Turku, Finland; Turku Univ Hosp, Finland.
    Björnsdotter Åberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Neural correlates of gentle skin stroking in early infancy2019In: Developmental Cognitive Neuroscience, ISSN 1878-9293, E-ISSN 1878-9307, Vol. 35, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11-36 days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking - the postcentral gyrus and posterior insular cortex - and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development.

  • 143.
    Uusimaa, Johanna
    et al.
    University of Oulu and Oulu University Hospital, Finland.
    Moilanen, Jukka
    University of Oulu and University of Tampere, Finland.
    Vainionpää, Leena
    University of Oulu, Finland.
    Tapanainen, Päivi
    University of Oulu, Finland.
    Lindholm, Päivi
    University of Oulu, Finland.
    Nuutinen, Matti
    University of Oulu, Finland.
    Löppönen, Tuija
    University of Oulu and University of Kuopio, Finland.
    Mäki-Torkko, Elina
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL. University of Oulu, Finland .
    Rantala, Heikki
    University of Oulu, Finland.
    Majamaa, Kari
    Oulu University Hospital and University of Oulu and University of Turku, Finland.
    Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children2007In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 62, no 3, p. 278-287Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.

    METHODS:

    Children with diagnoses commonly associated with mitochondrial diseases were ascertained. Blood DNA from 522 selected children was analyzed for 3243A>G. Children with the mutation were clinically examined. Information on health history before the age of 18 years was collected from previously identified adult patients with 3243A>G. Mutation segregation analysis in buccal epithelial cells was performed in mothers with 3243A>G and their children whose samples were analyzed anonymously.

    RESULTS:

    Eighteen children were found to harbor 3243A>G in a population of 97,609. A minimum estimate for the prevalence of 3243A>G was 18.4 in 100,000 (95% confidence interval, 10.9-29.1/100,000). Information on health in childhood was obtained from 37 adult patients with 3243A>G. The first clinical manifestations appearing in childhood were sensorineural hearing impairment, short stature or delayed maturation, migraine, learning difficulties, and exercise intolerance. Mutation analysis from 13 mothers with 3243A>G and their 41 children gave a segregation rate of 0.80. The mothers with heteroplasmy greater than 50% tended to have offspring with lower or equal heteroplasmy, whereas the opposite was true for mothers with heteroplasmy less than or equal to 50% (p = 0.0016).

    INTERPRETATION:

    The prevalence of 3243A>G is relatively high in the pediatric population, but the morbidity in children is relatively low. The random genetic drift model may be inappropriate for the transmission of the 3243A>G mutation.

  • 144.
    Viola, Federica
    Linköping University, Department of Medical and Health Sciences.
    Automatic Sleep Scoring To Study Brain Resting State Networks During Sleep In Narcoleptic And Healthy Subjects: A Combination Of A Wavelet Filter Bank And An Artificial Neural Network2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Manual sleep scoring, executed by visual inspection of the EEG, is a very time consuming activity, with an inherent subjective decisional component. Automatic sleep scoring could ease the job of the technicians, because faster and more accurate. Frequency information characterizing the main brain rhythms, and consequently the sleep stages, needs to be extracted from the EEG data. The approach used in this study involves a wavelet filter bank for the EEG frequency features extraction. The wavelet packet analysis tool in MATLAB has been employed and the frequency information subsequently used for the automatic sleep scoring by means of an artificial neural network. Finally, the automatic sleep scoring has been employed for epoching the fMRI data, thus allowing for studying brain resting state networks during sleep. Three resting state networks have been inspected; the Default Mode Network, The Attentional Network and the Salience Network. The networks functional connectivity variations have been inspected in both healthy and narcoleptic subjects. Narcolepsy is a neurobiological disorder characterized by an excessive daytime sleepiness, whose aetiology may be linked to a loss of neurons in the hypothalamic region.

  • 145.
    Vågberg, M.
    et al.
    Umeå University, Sweden.
    Axelsson, M.
    University of Gothenburg, Sweden.
    Birgander, R.
    Umeå University, Sweden.
    Burman, J.
    Uppsala University, Sweden.
    Cananau, C.
    Karolinska Institute, Sweden.
    Forslin, Y.
    Karolinska Institute, Sweden.
    Granberg, T.
    Karolinska Institute, Sweden.
    Gunnarsson, M.
    University of Örebro, Sweden.
    von Heijne, A.
    Karolinska Institute, Sweden.
    Jönsson, L.
    Sahlgrens University Hospital, Sweden.
    Karrenbauer, V. D.
    Karolinska Institute, Sweden.
    Larsson, E. -M.
    Uppsala University, Sweden.
    Lindqvist, T.
    Umeå University, Sweden.
    Lycke, J.
    University of Gothenburg, Sweden.
    Lönn, L.
    Karolinska Institute, Sweden.
    Mentesidou, E.
    Karolinska Institute, Sweden.
    Müller, S.
    Karolinska Institute, Sweden.
    Nilsson, P.
    Lund University, Sweden.
    Piehl, F.
    Karolinska Institute, Sweden.
    Svenningsson, A.
    Karolinska Institute, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Wikström, J.
    Uppsala University, Sweden.
    Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 1, p. 17-24Article, review/survey (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

  • 146.
    Wang, Bing
    et al.
    MRI-based age prediction using hidden Markov models.
    Pham, Tuan D
    Bioinformatics Research Group, School of Engineering and Information Technology, The University of New South Wales, Canberra ACT 2600, Australia.
    MRI-based age prediction using hidden Markov models2011In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 199, no 1, p. 140-145Article in journal (Refereed)
    Abstract [en]

    Cortical thinning and intracortical gray matter volume losses are widely observed in normal ageing, while the decreasing rate of the volume loss in subjects withneurodegenerative disorders such as Alzheimer's disease is reported to be faster than the average speed. Therefore, neurodegenerative disease is considered as accelerated ageing. Accurate detection of accelerated ageing based on the magnetic resonance imaging (MRI) of the brain is a relatively new direction of research in computational neuroscience as it has the potential to offer positive clinical outcome through early intervention. In order to capture the faster structural alterations in the brain with ageing, we propose in this paper a computational approach for modelling the MRI-based structure of the brain using the framework of hidden Markov models, which can be utilized for age prediction. Experiments were carried out on healthy subjects to validate its accuracy and its robustness. The results have shown its ability of predicting the brain age with an average normalized age-gap error of two to three years, which is superior to several recently developed methods for brain age prediction.

  • 147.
    Westergren, Samuel
    Linköping University, Faculty of Health Sciences.
    Nivåer av det lysosomala systemets proteiner i hjärnvävnad från Alzheimerpatienter2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Alzheimer's disease is the most common cause of dementia, and when the population becomes larger and older also the number of patients increase. A cerebral atrophy and microscopic findings of extracellular plaques of β-amyloid, intracellular neurofibrillary of phosphorylated tau and loss of nerve cell protrusions, axons, synapses and dendrites are seen during the disease. One of the early pathological changes is the disruption of the neuronal lysosomal network that plays an important role in the degradation of macromolecules. In a previous study elevated levels of proteins of the lysosomal network in cerebrospinal fluid from Alzheimer’s disease patients was demonstrated. The purpose of this study was to measure levels of the lysosomal network system in the brain. The six proteins EEA1, PICALM, LAMP-1, LAMP -2, LC3 and TFEB were analyzed in human brain tissue from five Alzheimer's disease cases and five control cases by Western blot. The results show a significant increase in the temporal cortex of LAMP-1 and LAMP -2 and a significant decrease of LC3 and EEA1 in patients with Alzheimer's disease. In order to draw proper conclusions about how the increased levels in cerebrospinal fluid reflect the different disease mechanisms in the brain it requires further analysis of more patient samples and from other areas of the brain.

  • 148.
    Westgren, N
    et al.
    Spinalis SCI Research Unit and Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    Spinalis SCI Research Unit and Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Quality of life and traumatic spinal cord injury.1998In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 79, no 11, p. 1433-1439Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine associations between major outcome variables after traumatic spinal cord injury (SCI) and quality of life (QL).

    SUBJECTS: Of a total population of 353 SCI patients, 320 participated, 261 men and 59 women living in the greater Stockholm area: 124 were tetraplegic, 176 were paraplegic, and 20 had no classified level. Mean age was 42 years (range, 17 to 78).

    METHOD: The Swedish SF-36 Health Survey was used to assess QL. The SF-36 is a self-administered questionnaire containing 36 items, divided into 8 multi-item dimensions, covering physical function, physical and emotional role function, social function, bodily pain, mental health, vitality and overall evaluation of health. Neurologic, general medical, and psychosocial variables were obtained from the Stockholm Spinal Cord Injury Study (SSCIS) data base. QL indices were analyzed for the SCI group as a whole, as well as for subgroups. Descriptors for subgroups were demographic variables, presence or absence of common medical problems, and subjective evaluation of the degree of impact of the medical problem on well-being/daily activities.

    RESULTS: QL in individuals with SCI was significantly lower in all subscales as compared with a normative population. No difference in QL was seen in subgroups according to extent of lesion, with the exception of physical functioning. Several medical complications such as neurogenic pain, spasticity, and neurogenic bladder and bowel problems were associated with lower QL scores.

    SUMMARY: QL, as defined by SF-36, is better in persons injured many years ago, as compared with those recently injured, suggesting an adaptive process operating over a long period. The presence of complicating medical problems, such as severe pain, problematic spasticity, and incontinence, seem to have more negative effects on QL than the extent of SCI as such.

  • 149.
    Westhall, E.
    et al.
    Lund Univ, Sweden.
    Rosen, I.
    Lund Univ, Sweden.
    Rundgren, M.
    Lund Univ, Sweden.
    Bro-Jeppesen, J.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Kjaergaard, J.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Hassager, C.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Lindehammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Horn, J.
    Univ Amsterdam, Netherlands.
    Ullen, S.
    Skane Univ Hosp, Sweden.
    Nielsen, N.
    Helsingborg Hosp, Sweden.
    Friberg, H.
    Lund Univ, Sweden.
    Cronberg, T.
    Lund Univ, Sweden.
    Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest2018In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 129, no 8, p. 1660-1668Article in journal (Refereed)
    Abstract [en]

    Objective: Investigate the temporal development of EEG and prognosis. Methods: Prospective observational substudy of the Target Temperature Management trial. Six sites performed simplified continuous EEG-monitoring (cEEG) on comatose patients after cardiac arrest, blinded to treating physicians. We determined time-points of recovery of a normal-voltage continuous background activity and the appearance of an epileptiform EEG, defined as abundant epileptiform discharges, periodic/rhythmic discharges or electrographic seizure activity. Results: 134 patients were included, 65 had a good outcome. Early recovery of continuous background activity (within 24 h) occurred in 72 patients and predicted good outcome since 55 (76%) had good outcome, increasing the odds for a good outcome seven times compared to a late background recovery. Early appearance of an epileptiform EEG occurred in 38 patients and 34 (89%) had a poor outcome, increasing the odds for a poor outcome six times compared to a late debut. The time to background recovery and the time to epileptiform activity were highly associated with outcome and levels of neuron-specific enolase. Multiple regression analysis showed that both variables were independent predictors. Conclusions: Time to epileptiform activity and background recovery are independent prognostic indicators. Significance: Patients with early background recovery combined with late appearance of epileptiform activity may have a good outcome. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  • 150.
    Wibault, Johanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Neck disability in patients with cervical radiculopathy and evaluation of structured postoperative physiotherapy2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Non-surgical and surgical approaches to treatment are used in patients with cervical radiculopathy (CR) due to disc disease. Overall, good effects of surgery have been reported on arm pain and neurological symptoms. However, the effects on neck functioning are more uncertain. Studies have shown persistent activity limitations; participation restrictions; and impairments in neck-related body functions after surgery. Structured physiotherapy combining neck-specific exercises with a behavioural approach has been suggested as treatment before as well as after surgery to improve clinical outcomes in patients with CR. Randomized clinical trials of postoperative physiotherapy to inform evidence-based clinical guidelines for the treatment of patients with CR are lacking.

    The overall aim of the thesis was to investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioural approach compared to standard postoperative approach in patients with CR. A further aim was to evaluate the  contribution of different aspects of neck-related body functions and mental functions on preoperative neck disability in these patients.

    A total of 202 patients with CR who were scheduled for surgery were recruited, and randomized preoperatively to either structured postoperative physiotherapy, or standard postoperative approach. Standard postoperative approach was in accordance with Swedish postoperative care, and may have included pragmatic physiotherapy after surgery when needed. Patients were evaluated with a set of questionnaires and clinical examinations before surgery and at 3 and 6 months after surgery. Outcomes included patient-reported measures of pain, neck functioning, global outcome, clinical evaluation of neckrelated body functions, self-efficacy and coping strategies, as well as expectation fulfilment and enablement. Differences between treatment groups were investigated in complete case and per-protocol approaches (Paper III & IV). A sub-sample of patients with CR who were scheduled for surgery were also compared with neck-healthy individuals for assessment of head repositioning accuracy with a cervical range of motion device (Paper I). In patients with CR who were scheduled for surgery, associations between preoperative measures of neck-related body functions, mental functions, and other contextual factors with patientreported neck disability were studied (Paper II).

    With the exception of greater expectation fulfilment in patients who received structured postoperative physiotherapy (p = 0.01), there were no differences between the treatment groups in outcomes at 6 months after surgery. There were no differences reported for changes in  outcomes from before surgery to 6 months after surgery between the groups, but all outcomes significantly improved from baseline in both groups (p<0.001) (Paper III & IV). However, global outcome and frequency of neck pain improved during the postoperative period only in patients who received structured postoperative physiotherapy (p< 0.01) (Paper III). Six months after surgery, patients with at least 50% attendance to treatment sessions in the structured postoperative physiotherapy group reported less neck pain frequency (p = 0.05), and greater expectation fulfilment (p = 0.001), and enablement (p = 0.04) than those who received standard postoperative approach. These patients also had larger improvements in neck functioning, arm pain and catastrophizing during the rehabilitation period from 3 to 6 months after surgery (p< 0.03). Sixty-one percent of the patients who received standard postoperative approach reported additional use ofpostoperative physiotherapy. These patients had a worse surgical outcome compared with patients who reported no additional use of postoperative physiotherapy. In patients with CR who were scheduled for surgery, larger errors in head repositioning accuracy were found compared to neck-healthy individuals (Paper I). Preoperative measures of neck-related body functions, mental functions and other contextual factors explained 73% of the variance in Neck Disability Index scores in patients with CR who were scheduled for surgery (Paper II).

    The results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery. However, CR is a heterogeneous condition and specific subgroups of patients are likely to benefit from different interventions. More studies are needed to inform evidence-based clinical guidelines for the treatment of patients with CR. A broader preoperative assessment in patients with CR improved the description of patient-reported neck disability.

    List of papers
    1. Using the cervical range of motion (CROM) device to assess head repositioning accuracy in individuals with cervical radiculopathy in comparison to neck- healthy individuals
    Open this publication in new window or tab >>Using the cervical range of motion (CROM) device to assess head repositioning accuracy in individuals with cervical radiculopathy in comparison to neck- healthy individuals
    Show others...
    2013 (English)In: Manual Therapy, ISSN 1356-689X, E-ISSN 1532-2769, Vol. 18, no 5, p. 403-409Article in journal (Refereed) Published
    Abstract [en]

    This study had two purposes: to compare head repositioning accuracy (HRA) using the cervical range of motion (CROM) device between individuals with cervical radiculopathy caused by disc disease (CDD; n = 71) and neck- healthy individuals (n = 173); and to evaluate the test–retest reliability of the CROM device in individuals with CDD, and criterion validity between the CROM device and a laser in neck-healthy individuals, with quantification of measurement errors. Parameters of reliability and validity were expressed with intra- class- correlation coefficients (ICCs), and measurement errors with standard error of measurement (SEM) and Bland Altman limits of agreement. HRA (Mdn, IQR) differed significantly between individuals with CDD and neck- healthy individuals after rotation right 2.7° (6.0), 1.7° (2.7); and rotation left 2.7° (3.3), 1.3° (2.7) (p < = 0.021); 31% of individuals with CDD were classified as having impairment in HRA. The test–retest reliability of the CROM device in individuals with CDD showed ICCs of 0.79- 0.85, and SEMs of 1.4°- 2°. The criterion validity between the CROM device and the laser in neck-healthy individuals showed ICCs of 0.43- 0.91 and SEMs of 0.8°- 1.3°. The results support the use of the CROM device for quantifying HRA impairment in individuals with CDD in clinical practice; however, criterion validity between the CROM device and a laser in neck-healthy individuals was questionable. HRA impairment in individuals with CDD may be important to consider during rehabilitation and evaluated with the criterion established with the CROM device in neck-healthy individuals.

    Place, publisher, year, edition, pages
    Elsevier, 2013
    Keywords
    Neck pain, Radiculopathy, Head repositioning accuracy, Measurement
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-98660 (URN)10.1016/j.math.2013.02.004 (DOI)000324341300009 ()
    Note

    Funding Agencies|Swedish Research Council||Swedish Society of Medicine||Medical Research Council of Southeast Sweden||

    Available from: 2013-10-10 Created: 2013-10-10 Last updated: 2017-12-06
    2. Individual factors associated with neck disability in patients with cervical radiculopathy scheduled for surgery: a study on physical impairments, psychosocial factors, and life style habits
    Open this publication in new window or tab >>Individual factors associated with neck disability in patients with cervical radiculopathy scheduled for surgery: a study on physical impairments, psychosocial factors, and life style habits
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    2014 (English)In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 23, no 3, p. 599-605Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE:

    The influence of individual factors on patient-reported outcomes is important in the interpretation of disability and treatment effectiveness. The purpose of this study was to assess how physical impairments, psychosocial factors, and life style habits were associated with neck disability based on the Neck Disability Index (NDI), in patients with cervical radiculopathy scheduled for surgery.

    METHODS:

    This cross-sectional study included 201 patients (105 men, 96 women; mean age 50 years). Data included self-reported measures and a clinical examination. Multiple linear regressions were performed to identify significant influencing factors.

    RESULTS:

    Pain, physical impairments in the cervical active range of motion, low self-efficacy, depression, and sickness-related absences explained 73 % of the variance in NDI scores (p < 0.001).

    CONCLUSION:

    Assessments of physical impairments and psychosocial factors in patients with cervical radiculopathy could improve the description of neck disability and the interpretation of treatment outcomes in longitudinal studies.

    Place, publisher, year, edition, pages
    Springer Berlin/Heidelberg, 2014
    Keywords
    Cervical spine, Radiculopathy, Neck Disability Index, Individual factors, Multiple regression analysis
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-105506 (URN)10.1007/s00586-013-3066-0 (DOI)000332604600018 ()24154827 (PubMedID)
    Available from: 2014-03-28 Created: 2014-03-25 Last updated: 2017-12-05Bibliographically approved
    3. Structured postoperative physiotherapy in patients with cervical radiculopathy: 6-month outcomes of a randomized clinical trial
    Open this publication in new window or tab >>Structured postoperative physiotherapy in patients with cervical radiculopathy: 6-month outcomes of a randomized clinical trial
    Show others...
    2018 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, Vol. 28, no 1, p. 1-9Article in journal (Refereed) Published
    Abstract [en]

    Objective: To investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioral approach to standard postoperative approach in patients with cervical radiculopathy (CR) at 6 months after surgery.

    Design: A prospective multi-center randomized clinical trial.

    Subjects: Patients with CR (n=202, mean age 50.0, SD 8.4) who were scheduled for surgery.

    Methods: Patients were randomized pre-operatively to structured postoperative physiotherapy (n=101) or standard approach (n=101) which in accordance with Swedish usual care may have included pragmatic physiotherapy after surgery when needed. Outcome measures at baseline and at 3 and 6 months follow-up included the Neck Disability Index (NDI), pain intensity in the neck and arm measured with a visual analogue scale (VAS) and global outcome of treatment. Between-group differences were investigated using complete case and per-protocol approaches.

    Results: No between-group difference was found in NDI, VAS, or global outcome at 6 months after surgery (p> 0.18). The NDI and VAS neck and arm pain were improved in both groups from before surgery to 6 months after surgery (p< 0.001). Sixty-one percent of the patients who received SA reported additional use of postoperative physiotherapy. Global outcome improved during the postoperative period in patients who received structured postoperative physiotherapy only (p< 0.01).

    Conclusions: No additional benefit of structured postoperative physiotherapy compared to standard postoperative approach was found at 6 months of follow-up based on patientreported measures of pain, neck disability and global outcome. However, many patients with CR perceived a need for additional treatments after surgery; and the results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery.

    Place, publisher, year, edition, pages
    American Association of Neurological Surgeons, 2018
    Keywords
    Cervical radiculopathy; Postoperative physiotherapy; Neck Disability Index; Global outcome
    National Category
    Neurology Physiotherapy
    Identifiers
    urn:nbn:se:liu:diva-122692 (URN)10.3171/2017.5.SPINE16736 (DOI)000418927300001 ()29087809 (PubMedID)
    Available from: 2015-11-16 Created: 2015-11-16 Last updated: 2019-05-02Bibliographically approved
    4. Neck-related physical function, self-efficacy and coping strategies in patients with cervical radiculopathy: a randomized clinical trial of postoperative physiotherapy
    Open this publication in new window or tab >>Neck-related physical function, self-efficacy and coping strategies in patients with cervical radiculopathy: a randomized clinical trial of postoperative physiotherapy
    Show others...
    2017 (English)In: Journal of Manipulative and Physiological Therapeutics, ISSN 0161-4754, E-ISSN 1532-6586, Vol. 40, no 5, p. 330-339Article in journal (Refereed) Published
    Abstract [en]

    Objective: To compare postoperative rehabilitation with structured physiotherapy to standard approach in patients with cervical radiculopathy (CR) based on measures of neck-related physical function, self-efficacy and coping strategies at 6 months follow-up.

    Design: A randomized clinical trial of postoperative physiotherapy in patients with CR.

    Subjects: Patients (n= 202) with persistent CR who were scheduled for surgery.

    Methods: Patients were preoperatively randomized to receive structured postoperative physiotherapy (SPT, n=101) or standard postoperative approach (SA, n=101). SPT combined neck-specific exercises with a behavioral approach. Baseline, 3-month, and 6-month evaluations included questionnaires and clinical examinations. Neck muscle endurance, active cervical range of motion, self-efficacy, pain catastrophizing (CSQ_CAT), perceived control over pain, and ability to decrease pain were analyzed for between-group differences using complete case and per-protocol approaches.

    Results: No between-group difference was reported at the 6-month follow-up (p = 0.05 to 0.99), but all outcomes had improved from baseline (p<0.001). Patients in the SPT group with ≥50% attendance to treatment sessions showed larger improvements in CSQ_CAT (p= 0.04) during the rehabilitation period from 3 to 6 months after surgery compared to the patients who received SA.

    Conclusion: No between-group difference in outcomes was found at 6 months after surgery based on measures of neck-related physical function, self-efficacy and coping strategies. However, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery, and that there may be a benefit from combining surgery with structured postoperative physiotherapy in patients with CR.

    Keywords
    Cervical radiculopathy, Postoperative physiotherapy, Randomized clinical trial, Physical function, Coping strategies
    National Category
    Neurology Physiotherapy
    Identifiers
    urn:nbn:se:liu:diva-122694 (URN)10.1016/j.jmpt.2017.02.012 (DOI)000404024700003 ()
    Note

    Funding agencies: Swedish Research Council; Swedish Society of Medicine; Medical Research Council of Southeast Sweden; Region Ostergotland; Lions; Futurum (Academy of Health and Care, Region Jonkoping County)

    Available from: 2015-11-16 Created: 2015-11-16 Last updated: 2017-08-21Bibliographically approved
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