uu.seUppsala University Publications
Change search
Refine search result
1 - 39 of 39
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Andersson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Correlation of Botulinum Toxin Dose with Neurophysiological Parameters of Efficacy and Safety in the Glabellar Muscles: A Double-blind, Placebo-controlled, Randomized Study2014In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    Despite the extensive use of botulinum toxin type A (BoNT-A) in treatments for glabellar frown lines, the dose-response effect in the glabellar muscles remains unknown. The aim of this randomized, double-blind, placebo-controlled prospective study was to characterize the neurophysiological parameters that correlate with the effect of BoNT-A in the glabellar muscles and its diffusion to surrounding ocular muscles. Sixteen healthy women were recruited and randomized to 3 different dose-groups of onabotulinumtoxin A (Vistabel (R)) or placebo and followed 24 weeks by neurophysiological examinations. Efficacy of treatment on corrugator supercilii muscles was measured by compound motor action potential (CMAP) and electromyography (EMG). Photographs were used to score glabellar frown lines. Diffusion of the drug to surrounding muscles was assessed by CMAP of the nasalis muscle, EMG and concentric needle electrode jitter analysis (CNE) of the orbicularis oculi muscle. CMAP reduction correlated well with intramuscular BoNT-A dose. Muscle paralysis, measured by EMG, began from 2 weeks and was not entirely reversed at 24 weeks in individuals who received high dose of onabotulinumtoxin. Limited diffusion of orbicularis oculi was detected with CNE. In conclusion, we developed a novel neurophysiological strategy for effect evaluation of BoNT-A in glabellar muscles. CMAP and EMG correlated with given BoNT-A dose and are more defined effect measures than clinical glabellar photo scales.

  • 2.
    Alimohammadi, Mohammed
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Neurophysiological Measures of Efficacy and Safety for Botulinum Toxin Injection in Facial and Bulbar Muscles: Special Considerations2017In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 9, no 11, article id 352Article, review/survey (Refereed)
    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.

  • 3.
    Amandusson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Elf, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Grindlund, Margareta E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Punga, Anna R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis2017In: Journal of clinical neurophysiology, ISSN 0736-0258, E-ISSN 1537-1603, Vol. 34, no 5, p. 400-407Article in journal (Refereed)
    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.

  • 4.
    Askmark, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Haggård, L
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 12, p. 1554-1560Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Vitamin D has important roles both in the autoimmune response and in skeletal muscles. We determined the levels of 25-hydroxy vitamin D [25(OH)D] in patients with MG and in healthy subjects to determine whether vitamin D deficiency is present in MG and whether vitamin D supplementation has beneficial effects on fatigue. METHODS: Plasma levels of 25(OH)D were analyzed in 33 patients with MG (22 males; mean age, 58 years) and in 50 healthy age- and sex-matched blood donors, without vitamin D3 medication. MG composite score (MGC) assessed fatigue. 13 patients with MG without previous vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/day, with a follow-up examination after 2.5-10 months (mean, 6 months). RESULTS: Patients with MG without pre-existing vitamin D3 supplementation (N = 16) had a mean MGC of 4.5 and lower plasma 25(OH)D levels (mean, 51 ± 19 nM) than healthy controls (69 ± 21 nM) (P = 0.017). Seventeen patients had pre-existing vitamin D3 supplementation, because of corticosteroid treatment, and their mean 25(OH)D was 79 ± 22 nM and mean MGC was 5.5. In the 13 patients who received cholecalciferol, 25(OH)D was overall increased at follow-up with 22% (P = 0.033) and MGC score improved with 38% (P = 0.05). CONCLUSIONS: Plasma 25(OH)D levels are significantly lower in patients with MG compared with healthy controls. As vitamin D has beneficial effects on the autoimmune response and on fatigue score in patients with MG, we suggest monitoring this parameter in patients with MG and supplementation with vitamin D3 when 25(OH)D levels are low.

  • 5.
    Chauhan, Mayank
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Muscle-specific regulation of the mTOR signaling pathway in MuSK antibody seropositive (MuSK plus ) experimental autoimmune Myasthenia gravis (EAMG)2013In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 77, no 1-2, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Myasthenia gravis (MG) patients with antibodies against muscle specific tyrosine kinase (MuSK+) typically present focal fatigue and atrophy of the facial and bulbar muscles, including the masseter muscle, whereas leg muscles often are clinically spared. This study addresses the regulation of the mTOR signaling pathway in the masseter muscle versus the leg muscle tibialis anterior (TA). We analyzed muscle morphology, protein levels of mTOR components as well as atrogenes and mitochondrial markers in these muscles of healthy control mice and mice with different clinical severity grades of MuSK+ experimental autoimmune MG (EAMG). Protein levels of mTOR components were reduced in the atrophic masseter muscle of MuSK+ EAMG mice, whereas enhanced accumulation of mTOR components was observed in the TA muscles. Two other muscles: omohyoid and soleus showed intermediate spectra. In conclusion, the anabolic mTOR signaling pathway is differentially regulated even in muscles with the same activity pattern in the same neuromuscular disease. This could in part explain the clinical phenotype in MuSK+ EAMG as well as in muscular dystrophies.

  • 6.
    Chroni, Elisabeth
    et al.
    Univ Patras, Sch Med, Dept Neurol, GR-26110 Patras, Greece..
    Dimisianos, Nikolaos
    Univ Patras, Sch Med, Dept Neurol, GR-26110 Patras, Greece..
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece2016In: Acta Neurologica Belgica, ISSN 0300-9009, E-ISSN 2240-2993, Vol. 116, no 1, p. 57-63Article in journal (Refereed)
    Abstract [en]

    Normal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH) D]. A recent study presented deficiency of 25(OH) D levels in Swedish MG patients. We aimed to study 25(OH) D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH) D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age-and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH) D levels (mean 58.8 +/- 16.3 and 62.0 +/- 22.4 nmol/L, respectively) than PNP patients (mean 42.1 +/- 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 +/- 13.8 nmol/L, p = 0.01). Plasma 25(OH) D levels was lower with age in all groups. There were no correlations between 25(OH) D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH) D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls.

  • 7. Chroni, Elisabeth
    et al.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Neurophysiological characteristics of MuSK antibody positive Myasthenia Gravis mice: Focal denervation and hypersensitivity to acetylcholinesterase inhibitors2012In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 316, no 1-2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Myasthenia Gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) typically present with focal fatigue and atrophy of the facial and bulbar muscles, along with unbeneficial reactions upon administration of acetylcholinesterase inhibitors (AChEIs). This study addresses the neurophysiological characteristics in facial versus limb muscles, before and after intraperitoneal injection of AChEIs, in mice immunized with MuSK. We performed in-vivo neurophysiological examinations in the masseter and gastrocnemius muscles of mice with MuSK+experimental autoimmune MG (EAMG) and in healthy control mice before and after administration of AChEIs. Abnormal spontaneous activity (fibrillations) was observed in the masseter muscle of MuSK+mice. Furthermore, 94% of MuSK-immunized mice displayed so called extra discharges (EDs) upon administration of a therapeutic AChEI dose, in contrast to 22% of the control mice, indicating neuromuscular hyperactivity. These findings support functional denervation in the masseter muscle and neuromuscular hypersensitivity already at a standard dose of AChEIs in MuSK+EAMG.

  • 8.
    Chroni, Elisabeth
    et al.
    Univ Patras, Sch Med, Dept Neurol, Patras 26504, Rion, Greece.
    Tendero, Isabel Serrano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology. Autonomous Univ Barcelona, Dept Clin Neurophysiol, Vall dHebron Univ Hosp, Barcelona, Spain.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Usefulness of assessing repeater F-waves in routine studies2012In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 45, no 4, p. 477-485Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Repeater F-waves are sometimes seen in routine studies.

    METHODS: We retrospectively reviewed the clinical significance of repeater F-waves in median, ulnar, and fibular nerve recordings in 50 healthy subjects and groups of 50 patients each with diabetic polyneuropathy, amyotrophic lateral sclerosis, carpal tunnel syndrome, ulnar mononeuropathy, and L5 root lesion. The number of identical F-waves and their repetitions in samples of 20 stimuli were estimated.

    RESULTS: Repeater F-waves occurred significantly more frequently in all nerves and patient groups than in healthy individuals. Their persistence was negatively correlated with that of non-repeater F-waves.

    CONCLUSIONS: Based on the presented material and recording condition it appears that repeater F-waves differentiate between health and disease but not between different types of pathology of motor neurons or their axons. Even in routinely recorded samples of 20 traces, the index of repeater all F-waves could be used as a sign of nerve pathology.

  • 9.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Vitamin D deficiency in patients with primary immune-mediated peripheral neuropathies2014In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 345, no 1-2, p. 184-188Article in journal (Refereed)
    Abstract [en]

    PURPOSE: T cells are important in the immunopathology of immune-mediated peripheral neuropathies (PNP) and activated vitamin D regulates the immune response through increasing the amount of regulatory T cells. An association between vitamin D deficiency and polyneuropathy has been stipulated; hence we assessed whether patients with primary immune-mediated PNP have low vitamin D [25(OH)D] levels.

    METHODS: Plasma levels of 25(OH)D were analyzed in 26 patients with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients with motor neuron disease (MND). INCAT score was assessed in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin) scale compared disability among patient groups.

    RESULTS: Mean 25(OH)D value in PNP patients was 40±16nmol/l, compared to 69±21nmol/l in healthy blood donors (p<0.001). MND patients had a higher mean 25(OH)D than PNP patients (59±26nmol/L; p=0.006) and comparable levels to healthy blood donors (p=0.15). Mean 25(OH)D value was not higher in PNP patients with pre-existing vitamin D3 supplementation of 800IU/day (N=6; 35±18nmol/L) than in unsupplemented PNP patients (42±16nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS-R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients (mean 3.5) compared to PNP patients (mean 2.1).

    CONCLUSIONS: All patients with primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had significantly lower 25(OH)D values than healthy control persons and MND patients. We suggest monitoring of vitamin D status in patients with autoimmune PNP, since immune cells are responsive to the ameliorative effects of vitamin D.

  • 10.
    Haggård, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Andersson, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    beta-glucans reduce LDL cholesterol in patients with myasthenia gravis2013In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 67, no 2, p. 226-227Article in journal (Refereed)
    Abstract [en]

    We aimed at evaluating whether beta-glucans could improve low-density lipoprotein (LDL) cholesterol levels and/or glycemic control in patients with myasthenia gravis (MG), in whom statins usually have muscle-related side effects. Fifty-nine MG patients participated in the study and received a daily dietary supplement of 3 g of beta-glucans during 8 weeks. Body mass index (BMI) and blood sample analysis of lipid and glucose status were performed before and after 8 weeks intake of beta-glucans. In the 52 patients who completed the study, there was a significant reduction in total cholesterol, LDL, ApoA1 and ApoB (all P<0.003). However, glycemic control and BMI were unaltered. The present study indicates that 8 weeks daily intake of 3 g of beta-glucans significantly reduces total cholesterol, LDL, ApoA1 and ApoB in MG patients. beta-glucans may therefore be of value in improving lipid status in MG patients, without the muscle-related side effects accompanied by statins.

  • 11.
    Liik, Maarika
    et al.
    Tartu Univ Hosp, Dept Neurol, Tartu, Estonia..
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Repetitive nerve stimulation often fails to detect abnormal decrement in acute severe generalized Myasthenia Gravis2016In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 127, no 11, p. 3480-3484Article in journal (Refereed)
    Abstract [en]

    Objective: We assessed the diagnostic pattern of repetitive nerve stimulation (RNS) test and concentric electrode (CNE) jitter analysis between patients with generalized myasthenia gravis (GMG) with acute versus slow onset. Methods: All examinations that established the diagnosis of GMG at the department of Clinical Neurophysiology, Uppsala University Hospital, were retrospectively analyzed from January 2012 to December 2014. Patients were grouped according to disease duration at neurophysiological evaluation: acute onset (< 4 weeks) or slow onset (>= 4 weeks). Results: We identified 41 patients diagnosed with GMG. Of the nine patients with acute onset GMG (5 women) only one patient had abnormal decrement, whereas of the 32 patients with slow onset (13 women) 26 patients (84%) had abnormal decrement. CNE jitter was abnormal in all. AChR antibody status was comparable (78% versus 84%) whereas the MGFA class was higher in the acute onset group (range: 3A-5) compared to the slow onset group (range: 2A-3B). Conclusions: RNS test is frequently normal in cases of acute severe GMG, including myasthenic crisis. Performing CNE jitter analysis is therefore of crucial importance for a correct early diagnosis. Significance: MG patients with acute severe onset of bulbar or generalized fatigue often have normal findings on RNS test in proximal muscles. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  • 12. Meinen, Sarina
    et al.
    Lin, Shuo
    Rueegg, Markus A.
    Punga, Anna Rostedt
    Fatigue and Muscle Atrophy in a Mouse Model of Myasthenia Gravis Is Paralleled by Loss of Sarcolemmal nNOS2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 8, p. e44148-Article in journal (Refereed)
    Abstract [en]

    Myasthenia Gravis (MG) patients suffer from chronic fatigue of skeletal muscles, even after initiation of proper immunosuppressive medication. Since the localization of neuronal nitric oxide synthase (nNOS) at the muscle membrane is important for sustained muscle contraction, we here study the localization of nNOS in muscles from mice with acetylcholine receptor antibody seropositive (AChR+) experimental autoimmune MG (EAMG). EAMG was induced in 8 week-old male mice by immunization with AChRs purified from torpedo californica. Sham-injected wild type mice and mdx mice, a model for Duchenne muscular dystrophy, were used for comparison. At EAMG disease grade 3 (severe myasthenic weakness), the triceps, sternomastoid and masseter muscles were collected for analysis. Unlike in mdx muscles, total nNOS expression as well as the presence of its binding partner syntrophin alpha-1, were not altered in EAMG. Immunohistological and biochemical analysis showed that nNOS was lost from the muscle membrane and accumulated in the cytosol, which is likely the consequence of blocked neuromuscular transmission. Atrophy of all examined EAMG muscles were supported by upregulated transcript levels of the atrogenes atrogin-1 and MuRF1, as well as MuRF1 protein, in combination with reduced muscle fiber diameters. We propose that loss of sarcolemmal nNOS provides an additional mechanism for the chronic muscle fatigue and secondary muscle atrophy in EAMG and MG.

  • 13.
    Molin, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Sabre, Liis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Weis, Cleo-Aron
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Thymectomy lowers the myasthenia gravis biomarker miR-150-5p2018In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 5, no 3, article id e450Article in journal (Refereed)
    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.

  • 14.
    Molin, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Westerberg, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 39716Article in journal (Refereed)
    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.

  • 15.
    Molin, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Widenfalk, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    High-resistance strength training does not affect nerve cross sectional area – An ultrasound study2017In: Clinical Neurophysiology Practice, ISSN 2467-981X, Vol. 2, p. 163-169Article in journal (Refereed)
    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.

  • 16. Phillips, W D
    et al.
    Christadoss, P
    Losen, M
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Shigemoto, K
    Verschuuren, J
    Vincent, A
    Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis2015In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 270, no SI, p. 29-40Article in journal (Refereed)
    Abstract [en]

    Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized.

  • 17.
    Punga, Anna R.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Maj, Marcin
    Lin, Shuo
    Meinen, Sarina
    Rueegg, Markus A.
    MuSK levels differ between adult skeletal muscles and influence postsynaptic plasticity2011In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 33, no 5, p. 890-898Article in journal (Refereed)
    Abstract [en]

    Muscle-specific tyrosine kinase (MuSK) is involved in the formation and maintenance of the neuromuscular junction (NMJ), and is necessary for NMJ integrity. As muscle involvement is strikingly selective in pathological conditions in which MuSK is targeted, including congenital myasthenic syndrome with MuSK mutation and MuSK antibody-seropositive myasthenia gravis, we hypothesized that the postsynaptic response to MuSK-agrin signalling differs between adult muscles. Transcript levels of postsynaptic proteins were compared between different muscles in wild-type adult mice. MuSK expression was high in the soleus and sternomastoid muscles and low in the extensor digitorum longus (EDL) and omohyoid muscles. The acetylcholine receptor (AChR) alpha subunit followed a similar expression pattern, whereas expression of Dok-7, Lrp4 and rapsyn was comparable between the muscles. We subsequently examined muscles in mice that overexpressed a miniaturized form of neural agrin or MuSK. In these transgenic mice, the soleus and sternomastoid muscles responded with formation of ectopic AChR clusters, whereas such clusters were almost absent in the EDL and omohyoid muscles. Electroporation of Dok-7 revealed its important role as an activator of MuSK in AChR cluster formation in adult muscles. Together, our findings indicate for the first time that adult skeletal muscles harbour different endogenous levels of MuSK and that these levels determine the ability to form ectopic AChR clusters upon overexpression of agrin or MuSK. We believe that these findings are important for our understanding of adult muscle plasticity and the selective muscle involvement in neuromuscular disorders in which MuSK is diminished.

  • 18.
    Punga, Anna Rostedt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Andersson, Mats
    Alimohammadi, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Disease specific signature of circulating miR-150-5p and miR-21-5p in myasthenia gravis patients2015In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 356, no 1-2, p. 90-96Article in journal (Refereed)
    Abstract [en]

    Purpose: Reliable biological markers for patients with the autoimmune neuromuscular disorder myasthenia gravis (MG) are lacking. We determined whether levels of the circulating immuno-microRNAs miR-150-5p and miR-21-5p were elevated in sera from clinically heterogeneous MG patients, with and without immunosuppression, as compared to healthy controls and patients with other autoimmune disorders. Methods: Sera from 71 MG patients and 55 healthy controls (HC) were analyzed for the expression levels of miR-150-5p and miR-21-5p with qRT-PCR. Sera were also assayed from 23 patients with other autoimmune disorders (AID; psoriasis, Addison's and Crohn's diseases). Results: 34 MG patients had no immunosuppressive drug treatment (MG-0) and 37 patients were under stable immunosuppressive drug treatment since a 6 months (MG + IMM). Serum levels of miR-150-5p and miR-21-5p were higher in the MG-0 patients compared to HC (p < 0.0001). Further, miR-150-5p levels were 41% lower and miR-21-5p levels were 25% lower in the MG + IMM compared to MG-0 (p = 0.0051 and 0.0419). In the AID patients, mean miR-150-5p and miR-21-5p were comparable with healthy controls (p = 0.66). Conclusions: The immuno-microRNAs miR-150-5p and miR-21-5p show a disease specific signature, which suggests these microRNAs as possible biological autoimmune markers of MG. (C) 2015 The Authors. Published by Elsevier B.V.

  • 19.
    Punga, Anna Rostedt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Eriksson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Alimohammadi, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology. Univ Uppsala Hosp, Dept Dermatol & Venereol, Uppsala, Sweden.
    Regional Diffusion of Botulinum Toxin in Facial Muscles: A Randomised Double-blind Study and a Consideration for Clinical Studies with Split-face Design2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 8, p. 948-951Article in journal (Refereed)
    Abstract [en]

    Despite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic treatments, the potential spreading of BoNTA to surrounding tissues remains unknown. A patient with hemifacial paralysis upon blepharospasm treatment with low dose of BoNTA, prompted us to investigate the spreading effect. A randomised, double-blind study was conducted in which 5 healthy women (33-52 years) were treated with different doses of onabotulinum toxin unilaterally in the corrugator muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks following BoNTA injection. CMAP of the treated glabellar muscles was reduced to approximately 40% in all dose groups. Additionally, contralateral CMAP reduction was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA in facial muscle application, which raises question on the reliability of split-face models in BoNTA studies.

  • 20.
    Punga, Tanel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bartoccioni, Emanuela
    Catholic Univ, Dept Lab Med, Rome, Italy.
    Lewandowska, Marta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Damato, Valentina
    Catholic Univ, Dept Neurol, Rome, Italy.
    Evoli, Amelia
    Catholic Univ, Dept Neurol, Rome, Italy.
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.2016In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 292, p. 21-26Article in journal (Refereed)
    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.

  • 21.
    Punga, Tanel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Le Panse, Rozen
    Andersson, Mats
    Truffault, Frédérique
    Berrih-Aknin, Sonia
    Punga, Anna Rostedt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Circulating miRNAs in myasthenia gravis: miR-150-5p as a new potential biomarker2014In: Annals of clinical and translational neurology, ISSN 2328-9503, Vol. 1, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Myasthenia gravis (MG) is a chronic autoimmune disorder where autoantibodies target the nicotinic acetylcholine receptors (AChR+) in about 85% of cases, in which the thymus is considered to play a pathogenic role. As there are no reliable biomarkers to monitor disease status in MG, we analyzed circulating miRNAs in sera of MG patients to find disease-specific miRNAs.

    METHODS: Overall, 168 miRNAs were analyzed in serum samples from four AChR+ MG patients and four healthy controls using Exiqon Focus miRNA polymerase chain reaction (PCR) Panel I + II. Specific accumulation pattern of 13 miRNAs from the discovery set was subsequently investigated in the sera of 16 AChR+ MG patients and 16 healthy controls. All patients were without immunosuppressive treatment. Selected specific miRNAs were further analyzed in the serum of nine MG patients before and after thymectomy to assess the effect of thymus removal on the accumulation of the candidate miRNAs in patient sera.

    RESULTS: Three miRNAs were specifically dysregulated in AChR+ MG patient sera samples. Hsa-miR150-5p, which induces T-cell differentiation, as well as hsa-miR21-5p, a regulator of Th1 versus Th2 cell responses, were specifically elevated in MG sera. Additionally, hsa-miR27a-3p, involved in natural killer (NK) cell cytotoxicity, was decreased in MG. Hsa-miR150-5p levels had the highest association with MG and were significantly reduced after thymus removal in correlation with disease improvement.

    INTERPRETATION: WE PROPOSE THAT THE VALIDATED MIRNAS: hsa-miR150-5p, hsa-miR21-5p, and hsa-miR27a-3p can serve as novel serum biomarkers in AChR+ MG. Hsa-miR-150-5p could be a helpful marker to monitor disease severity.

  • 22.
    Rostedt, Anna
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Padua, L
    Stålberg, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Correlation between a patient-derived functional questionnaire and abnormal neuromuscular transmission in myasthenia gravis patients2005In: Clin Neurophysiol, Vol. 116, p. 2058-2064Article in journal (Refereed)
  • 23.
    Rostedt, Anna
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Padua, L
    Stålberg, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Correlation between regional myasthenic weakness and mental aspects of quality of life2006In: Eur J Neurol, Vol. 13, p. 191-193Article in journal (Refereed)
  • 24.
    Rostedt, Anna
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Padua, L
    Stålberg, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    Validation of the Swedish version of the disease-specific Myasthenia Gravis Questionnaire2006In: Neurol Sci, Vol. 27, p. 91-96Article in journal (Refereed)
  • 25.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ahlqvist, Kati
    Bartoccioni, Emanuela
    Scuderi, Flavia
    Marino, Mariapaola
    Suomalainen, Anu
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes2006In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 117, no 7, p. 1434-1443Article in journal (Refereed)
    Abstract [en]

    Objective: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes.Methods: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative andsingle-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens withhistological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear genePOLG1 was sequenced.Results: Five AChR-Ab seropositive [AChR(C)] and 5 seronegative [AChR(K)] patients were MuSK-Ab seropositive [MuSK(C)]. Five of7 neurophysiologically examined MuSK(C) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(K)/AChR(C)patients (23%) (PZ0.012). SFEMG was abnormal in all examined MuSK(C) patients. All 7 biopsied MuSK(C) and 32 MuSK(K) patients(89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(C) and 13 of 20 MuSK(K) patients analyzed had multiplemtDNA deletions but no POLG1 mutations.Conclusions: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(C) and AChR(C) patients. Proximalmyopathy was over-represented in MuSK(C) patients; however, both MuSK(C) and MuSK(K) patients had mild myopathy with frequentmitochondrial abnormalities.Significance: The weakness in MuSK(C) patients is most likely due to disturbed neuromuscular transmission. The frequently encounteredmitochondrial dysfunction in MG warrants further study.

  • 26.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Cholinergic neuromuscular hyperactivity in patients with myasthenia gravis seropositive for MuSK antibody2006In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 34, no 1, p. 111-115Article in journal (Refereed)
    Abstract [en]

    A 75-year-old man with severe oculobulbar myasthenia gravis (MG) treated with acetylcholine esterase inhibitors (AChEIs) was found to have muscle-specific tyrosine kinase (MuSK) antibodies. Neurophysiological examination displayed extra repetitive discharges after the compound motor action potential (CMAP) at low-frequency stimulation, possibly triggered by AChEI. This indicates an abnormal sensitivity to acetylcholine in patients with MuSK antibodies and may be a useful indicator of the adverse effect of AChEI treatment in these patients. Muscle Nerve, 2006

  • 27.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Kaminski, Henry J
    Richman, David P
    Benatar, Michael
    How clinical trials of myasthenia gravis can inform pre-clinical drug development2015In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 270, no SI, p. 78-81Article in journal (Refereed)
    Abstract [en]

    Pre-clinical evaluations often provide the rationale for therapeutic assessments in humans; however, in many diseases an agent found successful in animal models does not show efficacy in human subjects. Our contention is that the approach of rigorous, clinical trials can be used to inform how preclinical assessments should be performed. Clinical trials in humans are carefully designed investigations executed with consideration of critical methodological issues, such as pre-specified entrance criteria and validated, outcome measures coupled with power analysis to identify sample size. Blinding of evaluators of subjective measures and randomization of subjects are also critical aspects of trial performance. Investigative agents are also tested in subjects with active disease, rather than prior to disease induction as in some pre-clinical assessments. Application of standard procedures, including uniform reporting standards, would likely assist in reproducibility of pre-clinical experiments. Adapting methods of clinical trial performance will likely improve the success rate of therapeutics to ultimately achieve human use.

  • 28.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Lin, Shuo
    Oliveri, Filippo
    Meinen, Sarina
    Rüeegg, Markus A.
    Muscle-selective synaptic disassembly and reorganization in MuSK antibody positive MG mice2011In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 230, no 2, p. 207-217Article in journal (Refereed)
    Abstract [en]

    MuSK antibody seropositive (MuSK+) Myasthenia Gravis (MG) patients present a distinct selective fatigue, and sometimes atrophy, of bulbar, facial and neck muscles. Here, we study the mechanism underlying the focal muscle involvement in mice with MuSK+ experimental autoimmune MG (EAMG). 8 week-old female wildtype C57BL6 mice and transgenic mice, which express yellow fluorescence protein (YFP) in their motor neurons, were immunized with the extracellular domain of rat MuSK and compared with control mice. The soleus, EDL, sternomastoid, omohyoid, thoracic paraspinal and masseter muscles were examined for pre- and postsynaptic changes with whole mount immunostaining and confocal microscopy. Neuromuscular junction derangement was quantified and compared between muscles and correlated with transcript levels of MuSK and other postsynaptic genes. Correlating with the EAMG disease grade, the postsynaptic acetylcholine receptor (AChR) clusters were severely fragmented with a subsequent reduction also of the presynaptic nerve terminal area. Among the muscles analyzed, the thoracic paraspinal, sternomastoid and masseter muscles were more affected than the leg muscles. The masseter muscle was the most affected, leading to denervation and atrophy and this severity correlated with the lowest levels of MuSK mRNA. On the contrary, the soleus with high MuSK mRNA levels had less postsynaptic perturbation and more terminal nerve sprouting. We propose that low muscle-intrinsic MuSK levels render some muscles, such as the masseter, more vulnerable to the postsynaptic perturbation of MuSK antibodies with subsequent denervation and atrophy. These findings augment our understanding of the sometimes severe, facio-bulbar phenotype of MuSK+ MG.

  • 29.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stålberg, Erik V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, no 3, p. 207-211Article in journal (Refereed)
    Abstract [en]

    Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins.

     

  • 30.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Circulating microRNAs as potential biomarkers in myasthenia gravis patients.2018In: 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)
    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.

  • 31.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ruegg, Markus A.
    Signaling and aging at the neuromuscular synapse: lessons learnt from neuromuscular diseases2012In: Current opinion in pharmacology (Print), ISSN 1471-4892, E-ISSN 1471-4973, Vol. 12, no 3, p. 340-346Article in journal (Refereed)
    Abstract [en]

    The neuromuscular junction (NMJ) is a specialized synapse between motor neurons and skeletal muscle with a complex signaling network that assures highly reliable neuromuscular transmission. Diseases of the NMJ cause skeletal muscle fatigue and include inherited and acquired disorders that affect presynaptic, intrasynaptic or postsynaptic components. Moreover, fragmentation of the NMJ contributes to sarcopenia, the loss of muscle mass during aging. Studies from recent years indicate that the formation and stabilization of NMJs differs between various muscles and that this difference affects their response under pathological conditions. This review summarizes the most important mechanisms involved in the development, maintenance and dysfunction of the NMJ and it discusses their significance in myasthenic disorders and aging and as targets for possible future treatment of NMJ dysfunction.

  • 32.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sawada, Mikio
    Stålberg, Erik V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis2007In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 37, no 3, p. 300-307Article in journal (Refereed)
    Abstract [en]

    The aim of this prospective study was to assess whether extra discharges (EDs), sometimes following the compound muscle action potential, could be used as a neurophysiological indicator of overdose of acetylcholinesterase inhibitors (AChEIs) in patients with myasthenia gravis (MG). The characteristics and frequency of EDs were explored and the correlation of EDs with cholinergic side effects was also determined. Twenty-two MG patients (14 women, 8 men; 61 ± 16 years of age) with daily AChEI treatment were examined. The mean disease duration was 10 years (range 2-62 years) and all patients had been treated with AChEI since MG onset. Both single and repetitive stimulation of the ulnar and accessory nerves were performed before and 60 min after oral pyridostigmine bromide (PB) administration and after additional edrophonium injection. Fatigue, side effects, and AChE activity in blood were assessed before and 60 min after PB intake. The daily dose of PB ranged from 150 to 900 mg/day. Fourteen patients (64%) experienced daily cholinergic adverse effects, and muscarinic side effects correlated with AChE activity. Eleven patients (50%) developed EDs after oral PB. Among the eight patients with daily nicotinic side effects, EDs were significantly (P < 0.05) more common. Additionally, older patients were more prone to develop cholinergic side effects and EDs. Thus, when EDs are found, patients should be asked about daily muscular symptoms, which may be related to AChEI treatment and not solely to MG. Muscle Nerve, 2007

  • 33.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Acetylcholinesterase inhibitors in myasthenia gravis: to be or not to be?2009In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 39, no 6, p. 724-728Article, review/survey (Refereed)
    Abstract [en]

    Myasthenia gravis (MG) is an autoimmune disorder usually caused by antibodies against either the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) at the neuromuscular junction. Neuromuscular transmission failure results in muscle fatigue and weakness that can be treated symptomatically with acetylcholinesterase inhibitors (AChEIs). Long-term treatment with nonselective AChEIs may have considerable drawbacks; thus, this medication is ideally tapered when strength improves. Patients with AChR antibodies respond beneficially to treatment, whereas patients with MuSK antibodies generally do not. Recently, the selective AChEI EN101, which specifically targets the isoform of "read-through" AChE (AChE-R), has been developed and may be of importance for symptomatic relief in AChR-antibody seropositive MG. This article is a review of the mechanisms, therapeutic effects, and drawbacks, with both old and new AChEIs in MG.

  • 34.
    Sabre, Liis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Maddison, Paul
    Univ Nottingham, Hosp NHS Trust, Queens Med Ctr, Dept Neurol, Nottingham, Notts, England.
    Sadalage, Girija
    Univ Nottingham, Hosp NHS Trust, Queens Med Ctr, Dept Neurol, Nottingham, Notts, England.
    Ambrose, Philip Alexander
    Univ Nottingham, Hosp NHS Trust, Queens Med Ctr, Dept Neurol, Nottingham, Notts, England.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis2018In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 321, p. 164-170Article in journal (Refereed)
    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.

  • 35.
    Sabre, Liis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology. Tartu Univ Hosp, Dept Neurol, Tartu, Estonia..
    Westerberg, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Liik, Maarika
    Tartu Univ Hosp, Dept Neurol, Tartu, Estonia..
    Punga, Anna R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 4, article id e00653Article in journal (Refereed)
    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.

  • 36. Schreurs, Annabel
    et al.
    Stålberg, Erik V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Indication of peripheral nerve hyperexcitability in adult-onset subacute sclerosing panencephalitis (SSPE)2008In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 29, no 2, p. 121-124Article in journal (Refereed)
    Abstract [en]

    Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune-resistant measles virus. Diagnostic hallmarks include widespread cortical dysfunction on EEG, myoclonus, white matter abnormalities on neuroradiological examination and the presence of IgG antimeasles antibodies in the cerebrospinal fluid. We present the first case of SSPE with signs of peripheral nerve hyperexcitability, observed as extra discharges following the compound motor action potential at motor nerve stimulation. In addition we demonstrate the importance of SSPE in the differential diagnosis of adult patients with psychiatric and neurological symptoms.

     

  • 37.
    Westerberg, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Lifestyle factors and gender-related differences in clinical subgroups of Myasthenia Gravis in southern SwedenIn: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377Article in journal (Refereed)
    Abstract [en]

    Background: Based on the need for further regional and global epidemiological knowledge on Myasthenia Gravis (MG) and MG subgroups, we conducted a questionnaire-based epidemiological survey in a medium-sized health care region in southern Sweden. The primary aims were to investigate disease-specific items and lifestyle related factors between MG subgroups and matched population controls.

    Methods: All MG patients (n=70) in Jönköping County were invited to participate in a survey, using a standardized disease-specific questionnaire, previously developed by an expert group. This questionnaire contains three parts, including demographic and disease-specific data, lifestyle and health-related aspects as well as co-morbidity and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender matched randomly selected population controls excluding MG were invited to answer the non-disease-specific part of the questionnaire. Statistical tests included student t-test (for parametric data) or Mann–Whitney U test (for nonparametric data) and Chi-square test and Fisher’s exact test for evaluations between MG subgroups. In the case-control analysis conditional logistic regression was used to estimate the adjusted Odds Ratios.

    Results: Forty of the 70 identified MG patients and 188 of the 400 age-and gender matched population controls participated in the study (response rate 57.1%). In the late onset MG (LOMG; N=18) subgroup, the male predominance was higher than previously reported. In the early onset MG (EOMG; N=17) group, time to diagnosis was longer and bulbar weakness was the dominant symptom (65%). EOMG patients had higher fatigue compared to LOMG. Compared to their matched population controls, LOMG patients were obese more often, ate ess fish, smoked more, had a lower educational level and were employed as manual laborers more often. Mental health problems and sickness benefits were more common among MG patients than in controls and MG patients were less regularly doing focused physical activity.

    Conclusions: These findings highlight lifestyle and gender related differences between the EOMG and LOMG subgroups and between MG patients and population controls. Importantly, these lifestyle issues such as cardiovascular risk factors and physical inactivity, as well as mental health problems should be addressed intensively in the clinical follow-up of MG patients.

  • 38.
    Westerberg, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology. Ryhov Cty Hosp, Dept Neurol, Jonkoping, Sweden.
    Molin, Carl Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Lindblad, Ida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study2017In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 56, no 2, p. 207-214Article in journal (Refereed)
    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.

  • 39.
    Westerberg, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Molin, Carl Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Spörndly-Nees, Søren
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Widenfalk, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    The impact of physical exercise on functional muscle measures in Myasthenia Gravis patients – a single subject design studyIn: Medicine®, ISSN 0025-7974Article in journal (Refereed)
    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.

1 - 39 of 39
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf