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Rostedt Punga, Anna
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Publications (10 of 42) Show all publications
Sabre, L., Maddison, P., Sadalage, G., Ambrose, P. A. & Rostedt Punga, A. (2018). Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis. Journal of Neuroimmunology, 321, 164-170
Open this publication in new window or tab >>Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis
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2018 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 321, p. 164-170Article in journal (Refereed) Published
Abstract [en]

There are no biomarkers for late onset myasthenia gravis (LOMG; onset > 50 years). We evaluated circulating microRNA in a discovery cohort of 4 LOMG patients and 4 healthy controls and in a prospective diagnostic validation cohort of 73 LOMG patients (48 male) with longitudinal follow-up samples. In immunosuppression naive patients, levels of miRNAs miR-150-5p, miR-21-5p and miR-30e-5p decreased in parallel with clinical improvement after initiation of immunosuppression and their levels positively correlated with the clinical MG composite score. Levels of miR-150-5p and miR-21-5p were lower in patients with ocular compared to generalized LOMG. Circulating miR-150-5p, miR-21-5p and miR-30e-5p correlate with the clinical course in LOMG.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Myasthenia gravis, LOMG, microRNA, miR-150-5p, MGC
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361028 (URN)10.1016/j.jneuroim.2018.05.003 (DOI)000438322000021 ()29804819 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Rostedt Punga, A. & Punga, T. (2018). Circulating microRNAs as potential biomarkers in myasthenia gravis patients.. Annals of the New York Academy of Sciences, 1412(1), 33-40
Open this publication in new window or tab >>Circulating microRNAs as potential biomarkers in myasthenia gravis patients.
2018 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1412, no 1, p. 33-40Article, review/survey (Refereed) Published
Abstract [en]

MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR+) or muscle‐specific tyrosine kinase (MuSK+) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response. Recent studies in AChR+ MG revealed elevated levels of the immuno‐miRNAs miR‐150‐5p and miR‐21‐5p. Of particular importance, levels of miR‐150‐5p were lower in immunosuppressed patients and in patients with clinical improvement following thymectomy. In MuSK+ MG, another profile of circulating miRNAs was found, including upregulation of the let‐7 family of miRNAs. Here, we summarize the potential role of circulating miRNAs as biomarkers in general and in MG, and highlight important considerations for the analysis of circulating miRNA.

Keywords
myasthenia gravis, MG, microRNA, miR-150-5p, miR-21-5p, immunosuppressive, autoimmune disorders
National Category
Neurosciences Biochemistry and Molecular Biology Microbiology in the medical area
Research subject
Clinical Neurophysiology
Identifiers
urn:nbn:se:uu:diva-335288 (URN)10.1111/nyas.13510 (DOI)000423668100004 ()29125182 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048Swedish Cancer Society
Available from: 2017-12-03 Created: 2017-12-03 Last updated: 2018-05-08Bibliographically approved
Lewandowska, M., Bogatikov, E., Hierlemann, A. R. & Rostedt Punga, A. (2018). Long-Term High-Density Extracellular Recordings Enable Studies of Muscle Cell Physiology. Frontiers in Physiology, 9, Article ID 1424.
Open this publication in new window or tab >>Long-Term High-Density Extracellular Recordings Enable Studies of Muscle Cell Physiology
2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1424Article in journal (Refereed) Published
Abstract [en]

Skeletal (voluntary) muscle is the most abundant tissue in the body, thus making it an important biomedical research subject. Studies of neuromuscular transmission, including disorders of ion channels or receptors in autoimmune or genetic neuromuscular disorders, require high-spatial-resolution measurement techniques and an ability to acquire repeated recordings over time in order to track pharmacological interventions. Preclinical techniques for studying diseases of neuromuscular transmission can be enhanced by physiologic ex vivo models of tissue-tissue and cell-cell interactions. Here, we present a method, which allows tracking the development of primary skeletal muscle cells from myoblasts into mature contracting myotubes over more than 2 months. In contrast to most previous studies, the myotubes did not detach from the surface but instead formed functional networks between the myotubes, whose electrical signals were observed over the entire culturing period. Primary cultures of mouse myoblasts differentiated into contracting myotubes on a chip that contained an array of 26,400 platinum electrodes at a density of 3,265 electrodes per mm(2). Our ability to track extracellular action potentials at subcellular resolution enabled study of skeletal muscle development and kinetics, modes of spiking and spatio-temporal relationships between muscles. The developed system in turn enables creation of a novel electrophysiological platform for establishing ex vivo disease models.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2018
Keywords
muscle, spikes, spike analysis, physiology, microelectrode array (MEA) chip, skeletal
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-367028 (URN)10.3389/fphys.2018.01424 (DOI)000446852800001 ()30356837 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048Swedish Research Council, VR-2016-2184Göran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2018-11-28Bibliographically approved
Rostedt Punga, A. & Liik, M. (2018). Reply to "high abnormal rate in the repetitive nerve stimulation test in acute onset myasthenia gravis" [Letter to the editor]. Clinical Neurophysiology, 129(6), 1339-1339
Open this publication in new window or tab >>Reply to "high abnormal rate in the repetitive nerve stimulation test in acute onset myasthenia gravis"
2018 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 129, no 6, p. 1339-1339Article in journal, Letter (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361424 (URN)10.1016/j.clinph.2018.03.004 (DOI)000432717300028 ()29625881 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Westerberg, E., Molin, C. J., Spörndly-Nees, S., Widenfalk, J. & Rostedt Punga, A. (2018). The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study. Medicine (Baltimore, Md.), 97(31), Article ID e11510.
Open this publication in new window or tab >>The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study
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2018 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 97, no 31, article id e11510Article in journal (Refereed) Published
Abstract [en]

There is a need for tailored exercise recommendations to patients with Myasthenia Gravis (MG). A few pilot studies have recently shown that physical exercise in accordance with general recommendations to healthy adults can be applied safely to patients with mild MG symptoms. How physical exercise affects muscle parameters and risk factors for life-style diseases in patients with MG is, however, only poorly known. We evaluated functional skeletal muscle parameters in 11 MG patients, before and after conducting a 12-week supervised physical therapy regimen of aerobic and high-resistance strength training. After the training program, parameters of the proximal leg muscle rectus femoris improved: compound motor action potential (from 4.5 ± 2.6 to 5.3 ± 2.8 mV, p=0.016), isometric muscle force (from 25.2 ± 4.4 to 30.2 ± 3.8 kg; p=0.014) and ultrasound muscle thickness (from 19.6 ± 5.6 to 23.0 ± 3.9 mm, p=0.0098) all increased. Further, physical performance-based measures improved, including the 30-Second Chair Stand Test (median change +2, p=0.0039) as well as the clinical MG composite score (from 3[2-5] to 2 [0-4], p=0.043). These findings indicate that MG patients can improve their functional muscle status as a result of aerobic and high-resistance strength training, especially in proximal leg muscles. This is important knowledge when physical therapy is considered for this patient group, for whom no guidelines on physical exercise currently exist.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
Myasthenia Gravis, physical exercise, neuromuscular, CMAP, resistance training
National Category
Neurology Physiotherapy Sport and Fitness Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-344666 (URN)10.1097/MD.0000000000011510 (DOI)000442259200025 ()30075515 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Note

Title in thesis list of papers: The impact of physical exercise on functional muscle measures in Myasthenia Gravis patients – a single subject design study

Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-10-30Bibliographically approved
Molin, C. J., Sabre, L., Weis, C.-A., Punga, T. & Rostedt Punga, A. (2018). Thymectomy lowers the myasthenia gravis biomarker miR-150-5p. Neurology: Neuroimmunology and neuroinflammation, 5(3), Article ID e450.
Open this publication in new window or tab >>Thymectomy lowers the myasthenia gravis biomarker miR-150-5p
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2018 (English)In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 5, no 3, article id e450Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.

Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).

Results: Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).

Conclusions: Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-356113 (URN)10.1212/NXI.0000000000000450 (DOI)000437787600006 ()29511707 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048NIH (National Institute of Health), U01 NS 42685
Available from: 2018-07-14 Created: 2018-07-14 Last updated: 2018-09-20Bibliographically approved
Amandusson, Å., Elf, K., Grindlund, M. E. & Punga, A. R. (2017). Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis. Journal of clinical neurophysiology, 34(5), 400-407
Open this publication in new window or tab >>Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis
2017 (English)In: Journal of clinical neurophysiology, ISSN 0736-0258, E-ISSN 1537-1603, Vol. 34, no 5, p. 400-407Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Optimizing the diagnostic utility of repetitive nerve stimulation in myasthenia gravis (MG) may include tailoring the examination to clinical phenotype. Therefore, we analyzed all available repetitive nerve stimulation parameters in a large cohort of patients with confirmed MG diagnosis.

METHODS: All repetitive nerve stimulation examinations at the Uppsala University Hospital rendering an MG diagnosis during 1996 to 2014 were analyzed. The deltoid, trapezius, anconeus, nasalis, abductor digiti quinti, and frontalis muscles were examined.

RESULTS: Two hundred one patients with MG were diagnosed. Abnormal amplitude decrement was found in 54% of patients with ocular MG, 77% of patients with predominantly bulbar fatigue, and in 83% of patients with predominantly limb fatigue. The deltoid muscle had the highest sensitivity in all MG subtypes, with a mean of 77% sensitivity in all clinical subtypes, and the most pronounced decrement for amplitude (P = 0.0002) and area (P < 0.0001). Technical issues were rare.

CONCLUSIONS: These data contribute to further optimization of repetitive nerve stimulation strategies regarding muscle selection and technical performance in the electrodiagnostic workup of MG.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-342566 (URN)10.1097/WNP.0000000000000398 (DOI)000422943000004 ()28872522 (PubMedID)
Funder
Swedish Society of Medicine, SLS-330141Swedish Research Council, VR-523-2014-2048
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-03-12Bibliographically approved
Sabre, L., Westerberg, E., Liik, M. & Punga, A. R. (2017). Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries. Brain and Behavior, 7(4), Article ID e00653.
Open this publication in new window or tab >>Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries
2017 (English)In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 4, article id e00653Article in journal (Refereed) Published
Abstract [en]

Tntroduction: Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. Methods: This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). Results: Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 +/- 2.8) compared to the Swedish patients (3.4 +/- 2.3, p=.0005). Estonian patients also had significantly higher FSS scores (5.0 +/- 1.7) than Swedish patients (3.5 +/- 1.6; p=.001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p=.004). Conclusions: Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
Estonia, fatigue, myasthenia gravis, Sweden
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-322219 (URN)10.1002/brb3.653 (DOI)000399452500009 ()28413704 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2018-03-08Bibliographically approved
Molin, C. J., Widenfalk, J. & Rostedt Punga, A. (2017). High-resistance strength training does not affect nerve cross sectional area – An ultrasound study. Clinical Neurophysiology Practice, 2, 163-169
Open this publication in new window or tab >>High-resistance strength training does not affect nerve cross sectional area – An ultrasound study
2017 (English)In: Clinical Neurophysiology Practice, ISSN 2467-981X, Vol. 2, p. 163-169Article in journal (Refereed) Published
Abstract [en]

ObjectiveThe aim was to study the effect of high-resistance strength training on peripheral nerve morphology, by examining properties of peripheral nerves as well as distal and proximal muscle thickness with ultrasound, comparing healthy individuals who perform and do not perform high-resistance strength training.

MethodsNeuromuscular ultrasound was used to examine cross sectional area (CSA) of the median and musculocutaneous nerves, and muscle thickness of the abductor pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular high-resistance strength training.

ResultsNo difference in nerve CSA was found between trained and untrained individuals although trained individuals had thicker biceps brachii muscles. The CSA of the median nerve in the forearm correlated with participants’ height and was significantly larger in men than women.

ConclusionsIn this cohort, CSA of the median and musculocutaneous nerves was not affected by strength training, whereas gender had a prominent effect both on CSA and muscle thickness.

SignificanceThis is the first study to examine the effect of high-resistance strength training on peripheral nerves with neuromuscular ultrasound.

Keywords
High-resistance strength training, Muscle thickness, Reference values, Nerve remodeling, Nerve cross sectional area
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-356114 (URN)10.1016/j.cnp.2017.07.003 (DOI)
Available from: 2018-07-14 Created: 2018-07-14 Last updated: 2018-10-04Bibliographically approved
Alimohammadi, M. & Rostedt Punga, A. (2017). Neurophysiological Measures of Efficacy and Safety for Botulinum Toxin Injection in Facial and Bulbar Muscles: Special Considerations. Toxins, 9(11), Article ID 352.
Open this publication in new window or tab >>Neurophysiological Measures of Efficacy and Safety for Botulinum Toxin Injection in Facial and Bulbar Muscles: Special Considerations
2017 (English)In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 9, no 11, article id 352Article, review/survey (Refereed) Published
Abstract [en]

Botulinum toxin (BoNT) injections into facial and bulbar muscles are widely and increasingly used as medical treatments for cervical and facial dystonia, facial hemispasm, correction of facial palsy, hyperhidrosis, as well as cosmetic treatment of glabellar lines associated with grief and anger. Although BoNT treatment is generally considered safe, the diffusion of the toxin to surrounding muscles may result in complications, including difficulties swallowing, in a dose-dependent manner. The sensitivity of clinical examination for detecting adverse events after BoNT treatment is limited. Few reports have highlighted the potential effects on other muscles in the facial area due to the spreading of the toxin. The possibilities of spreading and thus unknown pharmacological BoNT effects in non-targeted muscles emphasise the importance of correct administration of BoNT in terms of dose selection, injection points, and appropriate effect surveillance. In this review article, we will focus on novel objective measures of efficacy and safety regarding BoNT treatment of facial muscles and the reasons why this is important.

Keywords
CMAP, botulinum toxin, diffusion, facial muscles, glabella
National Category
Pharmacology and Toxicology
Research subject
Clinical Neurophysiology
Identifiers
urn:nbn:se:uu:diva-335289 (URN)10.3390/toxins9110352 (DOI)000416589800017 ()29084148 (PubMedID)
Available from: 2017-12-03 Created: 2017-12-03 Last updated: 2018-03-12Bibliographically approved
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