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Rostedt Punga, Anna
Alternative names
Publications (10 of 39) 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
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
Westerberg, E., Molin, C. J., Lindblad, I., Emtner, M. & Rostedt Punga, A. (2017). Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study. Muscle and Nerve, 56(2), 207-214
Open this publication in new window or tab >>Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study
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2017 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 56, no 2, p. 207-214Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients.

METHODS: In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes as well as immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period.

RESULTS: Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period.

CONCLUSIONS: We propose that general recommendations regarding physical exercise safely can be applied to well-regulated MG patients.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-314678 (URN)10.1002/mus.25493 (DOI)000406875000009 ()27935072 (PubMedID)
Funder
Swedish Research Council, 2014-02048Futurum - Academy for Health and Care, Jönköping County Council, Sweden, 520281, 520411Swedish Society of Medicine, SLS-499271
Available from: 2017-02-04 Created: 2017-02-04 Last updated: 2018-03-08Bibliographically approved
Molin, C. J., Westerberg, E. & Rostedt Punga, A. (2017). Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.. Scientific Reports, 7, Article ID 39716.
Open this publication in new window or tab >>Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 39716Article in journal (Refereed) Published
Abstract [en]

This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.

National Category
Medical and Health Sciences Neurology
Research subject
Immunology; Neurology
Identifiers
urn:nbn:se:uu:diva-314679 (URN)10.1038/srep39716 (DOI)000391148300002 ()28045063 (PubMedID)
Funder
Swedish Research Council, 2014-02048Swedish Research Council, 2014-07603Swedish Society of Medicine, SLS-499271Futurum - Academy for Health and Care, Jönköping County Council, Sweden, 520281
Available from: 2017-02-04 Created: 2017-02-04 Last updated: 2018-08-01Bibliographically approved
Punga, T., Bartoccioni, E., Lewandowska, M., Damato, V., Evoli, A. & Punga, A. R. (2016). Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.. Journal of Neuroimmunology, 292, 21-26
Open this publication in new window or tab >>Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.
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2016 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 292, p. 21-26Article in journal (Refereed) Published
Abstract [en]

Myasthenia gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) have predominantly involvement of cranio-bulbar muscles and do not display thymus pathology, as do acetylcholine receptor antibody seropositive (AChR+) MG patients. In search of novel biomarkers for MuSK+ MG, we evaluated circulating serum microRNAs. Four analyzed microRNAs were specifically elevated in MuSK+ MG patient serum samples: let-7a-5p, let-7f-5p, miR-151a-3p and miR-423-5p. The circulating microRNA profile in MuSK+ MG differs from the profile previously observed in the serum of AChR+ MG, thus indicating the etiological difference between these two entities. We propose that the identified microRNAs could serve as potential serum biomarkers for MuSK+ MG.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-282333 (URN)10.1016/j.jneuroim.2016.01.003 (DOI)000372561600003 ()26943954 (PubMedID)
Funder
Swedish Society of Medicine, SLS-330141Swedish Research Council, VR-523-2014-2048
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
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