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Kullman, Anita
Publications (10 of 22) Show all publications
Nord, M., Kullman, A., Hannestad, U. & Dizdar Segrell, N. (2017). Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?. Advances in Parkinsons Disease, 06(01)
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
Nord, M., Zsigmond, P., Kullman, A. & Dizdar Segrell, N. (2017). Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease. Advances in Parkinsons Disease, 6(2), 52-66
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
Zsigmond, P., Nord, M., Kullman, A., Diczfalusy, E., Wårdell, K. & Dizdar (Dizdar Segrell), N. (2014). Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease. Neurology and Clinical Neuroscience, 2(5), 149-155
Open this publication in new window or tab >>Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
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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
Dizdar (Dizdar Segrell), N., Zsigmond, P., Kullman, A. & Nezirevic, D. (2013). Letter: Untitled [Letter to the editor]. Journal of Neuroscience Methods, 212(2), 363-363
Open this publication in new window or tab >>Letter: Untitled
2013 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 212, no 2, p. 363-363Article in journal, Letter (Refereed) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90766 (URN)10.1016/j.jneumeth.2013.01.005 (DOI)000315974200025 ()
Available from: 2013-04-05 Created: 2013-04-05 Last updated: 2018-01-12
Zsigmond, P., Nord, M., Kullman, A., Diczfalusy, E., Wårdell, K. & Dizdar (Segrell), N. (2013). Neurotransmitter levels in basal ganglia during L-dopa and Deep Brain Stimulation treatment in Parkinson’s Disease.
Open this publication in new window or tab >>Neurotransmitter levels in basal ganglia during L-dopa and Deep Brain Stimulation treatment in Parkinson’s Disease
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Bilateral deep brain stimulation of the nucleus subthalamicus (STN DBS) is a wellestablishedtreatment in patients with advanced Parkinson’s disease (PD). The mechanism bywhich STN DBS improves the PD symptoms remains unclear. In a previous perioperativestudy we have shown that there might be alterations of neurotransmitter levels in the Globuspallidum interna (GPi) during STN DBS. In this study we wanted to examine if STN DBSand L-dopa infusion interact and affect the levels of neurotransmitters.

Methods: Five patients with advanced PD took part in the study. During STN surgery microdialysis catheters were inserted bilaterally in the GPi and unilaterally in the right putamen. A study protocol was set up and was followed for three days including STN DBS left side, right side and bilateral. L-dopa infusion with and without concomitant bilateral STN DBS was also performed.

Results: The putaminal dopamine levels increase during STN DBS. In addition an increase of GABA concentrations in the GPi during STN DBS and during L-dopa infusion was found.

Conclusions: These findings can provide evidence that the STN has a direct action on the substantia nigra pars compacta (SNc) and that STN DBS may indirectly release putaminal dopamine. There is also evidence that STN DBS interferes with L-dopa therapy resulting in higher levels of Ldopa in the brain explaining why its possible to decrease L-dopa medication after DBS surgery.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91293 (URN)
Available from: 2013-04-19 Created: 2013-04-19 Last updated: 2017-06-19Bibliographically approved
Diczfalusy, E., Dizdar (Dizdar Segrell), N., Zsigmond, P., Kullman, A., Loyd, D. & Wårdell, K. (2012). Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation. In: IEEE Engineering in Medicine and Biology Society (EMBC), 2012: . Paper presented at 34th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2012), 28 August - 1 September 2012, San Diego, CA, USA (pp. 6438-6441). IEEE
Open this publication in new window or tab >>Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation
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2012 (English)In: IEEE Engineering in Medicine and Biology Society (EMBC), 2012, IEEE , 2012, p. 6438-6441Conference paper, Published paper (Refereed)
Abstract [en]

Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It  was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.

Place, publisher, year, edition, pages
IEEE, 2012
Series
IEEE Engineering in Medicine and Biology Society Conference Proceedings, ISSN 1557-170X
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84275 (URN)10.1109/EMBC.2012.6347468 (DOI)000313296506155 ()23367403 (PubMedID)9781424441198 (ISBN)9781424441204 (ISBN)9781457717871 (ISBN)
Conference
34th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2012), 28 August - 1 September 2012, San Diego, CA, USA
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2018-01-12Bibliographically approved
Zsigmond, P., Nezirevic Dernroth, D., Kullman, A., Augustinsson, L.-E. & Dizdar (Dizdar Segrell), N. (2012). Stereptactic microdialysis of the basal ganglia in Parkinson's disease. Journal of Neuroscience Methods, 207(1), 17-22
Open this publication in new window or tab >>Stereptactic microdialysis of the basal ganglia in Parkinson's disease
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2012 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 207, no 1, p. 17-22Article in journal (Refereed) Published
Abstract [en]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious treatment in patients with advanced Parkinson's disease, yet the mechanisms of STN DBS are poorly understood. The aims of this study were to develop a useful method for studying neurotransmitter alterations during DBS and for the pharmacokinetics of L-dopa in brain tissue. Ten patients with Parkinson's disease participated, whereof two had no previous L-dopa medication. The electrodes and catheters were placed using MRI-guided stereotaxic targeting. Two microdialysis probes were placed, one in the right internal globus pallidus, and one in a brachial vein. The quadripolar deep brain electrodes were placed in the right STN. Microdialysates from brain tissue and blood were collected in 15-min fractions at baseline and during DBS. After stimulation new baseline fractions were taken and finally three fractions during continuous intravenous infusion of L-dopa. Clinical evaluation showed that both DBS and L-dopa infusion gave good relief of rigidity and tremor in all ten patients. During DBS the L-dopa levels in the brain increased in some of the patients but did not persist during the whole stimulation period. The concentration in brain increased substantially during intravenous L-dopa infusion. A number of catecholamines and their metabolites were analysed with high pressure liquid chromatography (HPLC). With our study we could show that this model is suitable for the monitoring of neurotransmitters and for pharmacokinetic studies in human brain, although we found that the sampling time was too short to follow the possible alterations in brain activity caused by DBS.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Parkinson's disease; Microdialysis; L-dopa; Pharmacokinetics; Stereotaxy; Neurotransmitter
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-89705 (URN)10.1016/j.jneumeth.2012.02.021 (DOI)
Available from: 2013-03-04 Created: 2013-03-04 Last updated: 2018-01-12
Diczfalusy, E., Zsigmond, P., Dizdar (Dizdar Segrell), N., Kullman, A., Loyd, D. & Wårdell, K. (2011). A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis. Medical and Biological Engineering and Computing, 49(12), 1459-1469
Open this publication in new window or tab >>A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis
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2011 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 49, no 12, p. 1459-1469Article in journal (Refereed) Published
Abstract [en]

Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

Place, publisher, year, edition, pages
Springer Publishing Company, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72911 (URN)10.1007/s11517-011-0841-0 (DOI)000297550600012 ()22081236 (PubMedID)
Available from: 2011-12-09 Created: 2011-12-09 Last updated: 2018-01-12Bibliographically approved
Diczfalusy, E., Åström, M., Didzar, N., Kullman, A., Zsigmond, P. & Wårdell, K. (2010). A finite element model for biochemical monitoring in the brain during deep brain stimulation (poster). In: : . Paper presented at World Congress of Neurotechnology, Rome 11-14 Oct. 2010.
Open this publication in new window or tab >>A finite element model for biochemical monitoring in the brain during deep brain stimulation (poster)
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2010 (English)Conference paper, Published paper (Refereed)
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-59315 (URN)
Conference
World Congress of Neurotechnology, Rome 11-14 Oct. 2010
Available from: 2010-09-13 Created: 2010-09-13 Last updated: 2017-02-10Bibliographically approved
Diczfalusy, E., Åström, M., Dizdar, N., Kullman, A., Zsigmond, P. & Wårdell, K. (2010). A Finite Model for Biochemical Monitoring in the Brain during Deep Brain Stimulation (oral). In: : . Paper presented at Medicinteknikdagarna 2010, 6‐7 oktober, Umeå.
Open this publication in new window or tab >>A Finite Model for Biochemical Monitoring in the Brain during Deep Brain Stimulation (oral)
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2010 (English)Conference paper, Published paper (Refereed)
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-59303 (URN)
Conference
Medicinteknikdagarna 2010, 6‐7 oktober, Umeå
Available from: 2010-09-13 Created: 2010-09-13 Last updated: 2017-02-09Bibliographically approved
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