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  • 1.
    Aare, Sudhakar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Ochala, Julien
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Norman, Holly S
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, nr 24, s. 1334-1350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 2.
    Aare, Sudhakar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Akkad, Hazem
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric
    Research center for genetic medicine.
    Lars, Larsson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model2013Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, nr 8, s. 312-320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

  • 3.
    Aare, Sudhakar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric P
    Research center for genetic medicine.
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model2012Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, nr 18, s. 865-877Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

  • 4.
    Aare, Sudhakar Reddy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Intensive Care Unit Muscle Wasting: Skeletal Muscle Phenotype and Underlying Molecular Mechanisms2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.

    The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

    Delarbeten
    1. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Öppna denna publikation i ny flik eller fönster >>Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Visa övriga...
    2011 (Engelska)Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, nr 24, s. 1334-1350Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

    Nationell ämneskategori
    Neurologi
    Identifikatorer
    urn:nbn:se:uu:diva-164317 (URN)10.1152/physiolgenomics.00116.2011 (DOI)000298403600002 ()22010006 (PubMedID)
    Tillgänglig från: 2011-12-19 Skapad: 2011-12-19 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    2. The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Öppna denna publikation i ny flik eller fönster >>The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Visa övriga...
    2012 (Engelska)Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, nr 18, s. 865-877Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

    Nyckelord
    Sepsis, porcine, muscle wasting, intensive care
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-180380 (URN)10.1152/physiolgenomics.00031.2012 (DOI)000309109100001 ()
    Tillgänglig från: 2012-09-05 Skapad: 2012-09-05 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Öppna denna publikation i ny flik eller fönster >>Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Visa övriga...
    2013 (Engelska)Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, nr 8, s. 312-320Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-180375 (URN)10.1152/physiolgenomics.00123.2012 (DOI)000317662000002 ()23429211 (PubMedID)
    Tillgänglig från: 2012-09-05 Skapad: 2012-09-05 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    4. Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Öppna denna publikation i ny flik eller fönster >>Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Visa övriga...
    2011 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 6, artikel-id e20558Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.

    Nationell ämneskategori
    Fysiologi
    Forskningsämne
    Klinisk neurofysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-155622 (URN)10.1371/journal.pone.0020558 (DOI)000291730000014 ()21698290 (PubMedID)
    Tillgänglig från: 2011-06-27 Skapad: 2011-06-27 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
  • 5.
    Akkad, Hazem
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Corpeno Kalamgi, Rebeca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Masseter Muscle Myofibrillar Protein Synthesis and Degradation in an Experimental Critical Illness Myopathy Model2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 4, s. e92622-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Critical illness myopathy (CIM) is a debilitating common consequence of modern intensive care, characterized by severe muscle wasting, weakness and a decreased myosin/actin (M/A) ratio. Limb/trunk muscles are primarily affected by this myopathy while cranial nerve innervated muscles are spared or less affected, but the mechanisms underlying these muscle-specific differences remain unknown. In this time-resolved study, the cranial nerve innervated masseter muscle was studied in a unique experimental rat intensive care unit (ICU) model, where animals were exposed to sedation, neuromuscular blockade (NMB), mechanical ventilation, and immobilization for durations varying between 6 h and 14d. Gel electrophoresis, immunoblotting, RT-PCR and morphological staining techniques were used to analyze M/A ratios, myofiber size, synthesis and degradation of myofibrillar proteins, and levels of heat shock proteins (HSPs). Results obtained in the masseter muscle were compared with previous observations in experimental and clinical studies of limb muscles. Significant muscle-specific differences were observed, i.e., in the masseter, the decline in M/A ratio and muscle fiber size was small and delayed. Furthermore, transcriptional regulation of myosin and actin synthesis was maintained, and Akt phosphorylation was only briefly reduced. In studied degradation pathways, only mRNA, but not protein levels of MuRF1, atrogin-1 and the autophagy marker LC3b were activated by the ICU condition. The matrix metalloproteinase MMP-2 was inhibited and protective HSPs were up-regulated early. These results confirm that the cranial nerve innervated masticatory muscles is less affected by the ICU-stress response than limb muscles, in accordance with clinical observation in ICU patients with CIM, supporting the model' credibility as a valid CIM model.

  • 6. Alamdari, Nima
    et al.
    Toraldo, Gianluca
    Aversa, Zaira
    Smith, Ira J
    Castillero, Estibaliz
    Renaud, Guillaume
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Qaisar, Rizwan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Jasuja, Ravi
    Hasselgren, Per-Olof
    Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness2012Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 303, nr 10, s. R1090-R1099Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sepsis is associated with impaired muscle function but the role of glucocorticoids in sepsis-induced muscle weakness is not known. We tested the role of glucocorticoids in sepsis-induced muscle weakness by treating septic rats with the glucocorticoid receptor antagonist RU38486. In addition, normal rats were treated with dexamethasone to further examine the role of glucocorticoids in the regulation of muscle strength. Sepsis was induced in rats by cecal ligation and puncture and muscle force generation (peak twitch and tetanic tension) was determined in lower extremity muscles. In other experiments, absolute and specific force as well as stiffness (reflecting the function of actomyosin cross-bridges) were determined in isolated skinned muscle fibers from control and septic rats. Sepsis and treatment with dexamethasone resulted in reduced maximal twitch and tetanic force in intact isolated extensor digitorum longus muscles. The absolute and specific maximal force in isolated muscle fibers was reduced during sepsis together with decreased fiber stiffness. These effects of sepsis were blunted (but not abolished) by RU38486. The results suggest that muscle weakness during sepsis is at least in part regulated by glucocorticoids and reflects loss of contractility at the cellular (individual muscle fiber) level. In addition, the results suggest that reduced function of the cross-bridges between actin and myosin (documented as reduced muscle fiber stiffness) may be involved in sepsis-induced muscle weakness. An increased understanding of mechanisms involved in loss of muscle strength will be important for the development of new treatment strategies in patients with this debilitating consequence of sepsis.

  • 7.
    Alimohammadi, Mohammad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Andersson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Punga, Anna Rostedt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Correlation of Botulinum Toxin Dose with Neurophysiological Parameters of Efficacy and Safety in the Glabellar Muscles: A Double-blind, Placebo-controlled, Randomized Study2014Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, nr 1, s. 32-37Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Alimohammadi, Mohammed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Rostedt Punga, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Neurophysiological Measures of Efficacy and Safety for Botulinum Toxin Injection in Facial and Bulbar Muscles: Special Considerations2017Ingår i: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 9, nr 11, artikel-id 352Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 9.
    Alm, Per A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Logopedi.
    Karlsson, Ragnhild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Sundberg, Madeleine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Axelson, Hans W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hemispheric Lateralization of Motor Thresholds in Relation to Stuttering2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, s. e76824-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control.

  • 10.
    Amandusson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Axelson, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Comparison between adaptive and fixed stimulus paired-pulsetranscranial magnetic stimulation (ppTMS) in normal subjects2017Ingår i: Clinical Neurophysiology Practice, ISSN 2467-981X, s. 91-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    Paired-pulse TMS (ppTMS) examines cortical excitability but may require lengthy test procedures and fine tuning of stimulus parameters due to the inherent variability of the elicited motor evoked potentials (MEPs) and their tendency to exhibit a ‘ceiling/floor effects’ in inhibition trials. Aiming to overcome some of these limitations, we implemented an ‘adaptive’ ppTMS protocol and compared the obtained excitability indices with those from ‘conventional’ fixed-stimulus ppTMS.

    Methods

    Short- and long interval intracortical inhibition (SICI and LICI) as well as intracortical facilitation (ICF) were examined in 20 healthy subjects by adaptive ppTMS and fixed-stimulus ppTMS. The test stimulus intensity was either adapted to produce 500 μV MEPs (by a maximum likelihood strategy in combination with parameter estimation by sequential testing) or fixed to 120% of resting motor threshold (rMT). The conditioning stimulus was 80% rMT for SICI and ICF and 120% MT for LICI in both tests.

    Results

    There were significant (p < 0.05) intraindividual correlations between the two methods for all excitability measures. There was a clustering of SICI and LICI indices near maximal inhibition (‘ceiling effect’) in fixed-stimulus ppTMS which was not observed for adaptive SICI and LICI.

    Conclusions

    Adaptive ppTMS excitability data correlates to those acquired from fixed-stimulus ppTMS.

    Significance

    Adaptive ppTMS is easy to implement and may serve as a more sensitive method to detect changes in cortical inhibition than fixed stimulus ppTMS. Whether equally confident data are produced by less stimuli with our adaptive approach (as already confirmed for motor threshold estimation) remains to be explored.

  • 11.
    Amandusson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Blomqvist, Anders
    Estrogenic influences in pain processing2013Ingår i: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 34, nr 4, s. 329-349Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

  • 12.
    Amandusson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Elf, Kristin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Grindlund, Margareta E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Punga, Anna R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis2017Ingår i: Journal of clinical neurophysiology, ISSN 0736-0258, E-ISSN 1537-1603, Vol. 34, nr 5, s. 400-407Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Askmark, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Haggård, L
    Nygren, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Punga, Anna Rostedt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study2012Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, nr 12, s. 1554-1560Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Axelson, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements2004Ingår i: Acta Physiol Scand, Vol. Nov, nr 182(3), s. 295-304Artikel i tidskrift (Refereegranskat)
  • 15.
    Axelson, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Muscle Thixotropy: Implications for Human Motor Control2005Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Human skeletal muscles possess thixotropic, i.e. history-dependent mechanical properties. This means that the degree of passive muscle stiffness and resting tension is dependent on the immediately preceding history of contractions and length changes. Athletes, for instance, reduce passive muscle stiffness by various types of ‘limbering-up’ procedures, whereas muscle stiffness gradually increases during inactivity.

    Passive resistance of antagonistic muscles may significantly add to the total load during voluntary muscle contractions. This resistance may vary from one moment to another, depending on immediately preceding events. This research was conducted to determine whether history-dependent variations in passive muscular forces influence motor control of voluntary joint movements and steady maintenance of joint positions in healthy subjects.

    In study I, the EMG signal revealed motor compensations for history-dependent variations in passive stiffness of the antagonists during slow voluntary wrist joint movements. Studies II and III demonstrated that the voluntary muscle activity required to maintain a certain wrist joint position was highly influenced by previous changes in forearm muscle length and contractions. Study IV showed that rapid voluntary movements varied in speed and onset time depending on the prevailing degree of muscle resistance, and in addition that the central nervous reaction time required to execute rapid movements was highly influenced by immediately preceding muscle-conditioning procedures.

    History-dependent variations in passive muscular forces seem to be effectively compensated by the motor control system. Presumably, voluntary motor commands to the muscles are automatically adjusted in strength to history-dependent changes in passive muscular forces. Such adjustments occur within the central nervous system, which receives information about the mechanical state of the muscles. Several issues in connection with muscle thixotropy remain unaddressed. For instance, do alterations in the normal thixotropic mechanical behaviour of the muscles impose a particular problem in patients with certain neuromuscular diseases?

    Delarbeten
    1. Human motor control consequences of thixotropic changes in muscular short-range stiffness
    Öppna denna publikation i ny flik eller fönster >>Human motor control consequences of thixotropic changes in muscular short-range stiffness
    2001 Ingår i: J Physiol, Vol. Aug 15, nr 535, s. 279-88Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93032 (URN)
    Tillgänglig från: 2005-05-09 Skapad: 2005-05-09Bibliografiskt granskad
    2. Human motor compensations for thixotropy-dependent changes in resting wrist joint position after large joint movements
    Öppna denna publikation i ny flik eller fönster >>Human motor compensations for thixotropy-dependent changes in resting wrist joint position after large joint movements
    2003 Ingår i: Acta Physiol Scand., Vol. Dec, nr 179(4), s. 389-98Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93033 (URN)
    Tillgänglig från: 2005-05-09 Skapad: 2005-05-09Bibliografiskt granskad
    3. Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements
    Öppna denna publikation i ny flik eller fönster >>Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements
    2004 Ingår i: Acta Physiol Scand, Vol. Nov, nr 182(3), s. 295-304Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93034 (URN)
    Tillgänglig från: 2005-05-09 Skapad: 2005-05-09Bibliografiskt granskad
    4. Signs of muscle thixotropy during human ballistic wrist joint movements
    Öppna denna publikation i ny flik eller fönster >>Signs of muscle thixotropy during human ballistic wrist joint movements
    Artikel i tidskrift (Refereegranskat) Submitted
    Identifikatorer
    urn:nbn:se:uu:diva-93035 (URN)
    Tillgänglig från: 2005-05-09 Skapad: 2005-05-09Bibliografiskt granskad
  • 16.
    Axelson, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Signs of muscle thixotropy during human ballistic wrist joint movementsArtikel i tidskrift (Refereegranskat)
  • 17.
    Axelson, Hans
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hagbarth, Karl-Erik
    Human motor compensations for thixotropy-dependent changes in resting wrist joint position after large joint movements2003Ingår i: Acta Physiol Scand., Vol. Dec, nr 179(4), s. 389-98Artikel i tidskrift (Refereegranskat)
  • 18.
    Axelson, Hans
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hagbarth, Karl-Erik
    Human motor control consequences of thixotropic changes in muscular short-range stiffness2001Ingår i: J Physiol, Vol. Aug 15, nr 535, s. 279-88Artikel i tidskrift (Refereegranskat)
  • 19.
    Axelson, Hans W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Compound Motor Action Potential Interexaminer Variability in Photoguided Placement of the Recording Electrodes2012Ingår i: Journal of clinical neurophysiology, ISSN 0736-0258, E-ISSN 1537-1603, Vol. 29, nr 3, s. 256-259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Interpretation of neurographic data in follow-up studies of patients with neuromuscular disease is sometimes challenging because of the expected variability in repeated tests. In this study, we explored whether the interexaminer variability of the compound motor action potential (CMAP) amplitude is reduced if the examiner is guided by the previously taken photographs of the position of the recording electrodes. The CMAPs were recorded from 20 subjects by unilateral distal stimulation of the median, ulnar, peroneal, and tibial nerve by 4 different technicians. All the subjects were examined on 2 occasions (similar to 1 week apart). On the first occasion, the technicians recorded the CMAP values according to routine protocols. On the second occasion, the technicians had additional guidance from photographs displaying the recording electrode positions from the first study. The CMAP coefficient of variation (CoV) was calculated for each nerve examined by the four technicians. Differences in CoV between the two types of tests (i.e., with or without photographs) were evaluated. When the examiners were guided by the photographs during electrode application, the CMAP CoV for the tibial innervated abductor hallucis (AH) muscle was reduced (P = 0.02) from 18.5% to 13%. There were, however, no significant reductions in CoV for the abductor pollicis brevis (APB, P = 0.23, median nerve), abductor digiti minimi (P = 0.37, ulnar nerve), or extensor digitorum brevis (EDB, P = 0.15, peroneal nerve) muscles. Photographic documentation of the CMAP recording electrodes seems to have a limited overall effect on interexaminer variability in a subsequent study.

  • 20.
    Axelson, Hans W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements2004Ingår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, nr 3, s. 295-304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    This study on healthy subjects explores history-dependent changes in the resting tension of relaxed wrist muscles after moderate joint excursions and the motor control consequences of these changes during voluntary wrist joint position maintenance.

    METHODS:

    Integrated surface electromyogram (IEMG) was recorded from wrist extensor/flexor muscles. Angular position and torque were recorded from the wrist joint. Changes in wrist flexor muscle resting tension were sensed by a force transducer pressed against the tendons.

    RESULTS:

    Consecutive stepwise changes (7.5 degrees ) in wrist joint position (within the dorsiflexed range) were either imposed on relaxed subjects or actively performed while the subjects under visual guidance tried to mimic the passive movements. In relaxed subjects, passive joint torque resistance at a given steady dorsiflexed position either gradually declined or rose depending on the direction of the previous transition movements. In corresponding voluntary contraction experiments, the IEMG amplitude from position holding wrist extensors was found to vary in a similar way as the passive torque resistance. Further, there was a strong correlation between history-dependent changes in extensor IEMG amplitude and stress alterations exhibited by the relaxed antagonist flexors. The above described, slowly subsiding post-movement mechanical and motor adaptations were accelerated by brief forceful cocontractions of the forearm muscles.

    CONCLUSION:

    Moderate stepwise changes in joint position are sufficient to induce history-dependent after-effects in passive muscular resting tension, after-effects which during voluntary position holding are effectively compensated for by the motor control system.

  • 21.
    Axelson, Hans W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Signs of muscle thixotropy during human ballistic wrist joint movements2005Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 99, nr 5, s. 1922-1929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A study was conducted on healthy subjects to determine whether voluntary ballistic wrist flexion movements are influenced by immediately preceding conditioning of the forearm muscles. Single rapid wrist flexion movements were made in response to an auditory "Go" signal. Rectified surface EMG was recorded from wrist flexors and extensors, and joint position was measured by a goniometer. The movements were preceded (2-3 s) by four different conditioning routines: 40-s rest (Rest), 10-s voluntary alternating wrist joint flexion and extension movements (Osc), and 10 s of 25 degrees weak isometric wrist extensor (Ext) or flexor contractions (Flex). When subjects made ballistic movements after Osc compared with Rest, peak velocity was higher (P = 0.02) and movement time shorter (P = 0.06), but there was no difference (P = 0.83) in motor reaction time (time between the onset of the first agonist burst and movement onset). If the movements were preceded by Ext compared with Flex, motor reaction time was longer (P = 0.01), indicating a longer electromechanical delay. There were no indications that postconditioning differences in agonist or antagonist muscle activity could explain the results. It was also demonstrated that, after Rest, peak velocity was lower (P < 0.01) for the first than for the second of a series of repetitive ballistic movements. The observations corresponded to results from passive experiments in which the median nerve was electrically stimulated. In conclusion, history-dependent (thixotropic) changes in skeletal muscle resistance seem to have implications for voluntary ballistic wrist movements. The study also provided evidence that muscle conditioning influences the central nervous reaction time preceding ballistic contractions.

  • 22.
    Axelson, Hans W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Eeg-Olofsson, Karin Edebol
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Simplified Evaluation of the Paradoxical Puborectalis Contraction With Surface Electrodes2010Ingår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 53, nr 6, s. 928-931Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    Paradoxical puborectalis contraction during defecation is one possible explanation for constipation. The degree of paradoxical contraction can be evaluated by intramuscular electromyography from the puborectalis and external anal sphincter muscles. This study aimed to determine whether a noninvasive technique with surface electrodes placed over the subcutaneous part of the external anal sphincter is feasible in the evaluation of paradoxical activity.

    METHODS:

    Twenty-five patients with constipation were studied. Sphincter muscle activity during strain and squeeze maneuvers was recorded using surface electrodes placed 1 cm from the anal verge. In addition, intramuscular recordings were made simultaneously from the external anal sphincter and puborectalis muscles. The degree of paradoxical activation was calculated as a strain/squeeze index. The patients were examined either in the left lateral position or sitting on a commode.

    RESULTS:

    The study revealed significant (P < .01) correlations between indices obtained from the surface anal sphincter recordings and the intramuscular recordings (from the external anal sphincter and the puborectalis muscles).

    CONCLUSION:

    Surface recordings from the external anal sphincter seem to be an equally reliable, less time consuming, and less painful alternative to invasive measurements of paradoxical activity. In a few patients, however, invasive recordings may still be required.

  • 23.
    Axelson, Hans W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hagbarth, K -E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Human motor control consequences of thixotropic changes in muscular short-range stiffness2001Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 535, nr Pt 1, s. 279-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]
    1. The primary aim of the present study was to explore whether in healthy subjects the muscle contractions required for unrestrained voluntary wrist dorsiflexions are adjusted in strength to thixotropy-dependent variations in the short-range stiffness encountered in measurements of passive torque resistance to imposed wrist dorsiflexions.
    2. After a period of rest, only the first movement in a series of passive wrist dorsiflexions of moderate amplitude exhibited clear signs of short-range stiffness in the torque response. During analogous types of voluntary movements, the extensor EMG during the first movement after rest showed a steep initial rise of activity, which apparently served to compensate for the short-range stiffness.
    3. The passive torque resistance to minute repetitive wrist dorsiflexions (within the range of short-range stiffness) was markedly reduced after various types of mechanical agitation. During analogous low-amplitude voluntary wrist dorsiflexions the extensor EMG signals were weaker after than before agitation.
    4. Mechanical agitation also led to enhancement of passive dorsiflexion movements induced by weak constant torque pulses. In an analogous way, the movement-generating capacity of weak voluntary extensor activations (as determined by EMG recordings) was greatly enhanced by mechanical agitation.
    5. The signals from a force transducer probe pressed against the wrist flexor tendons - during passive wrist dorsiflexions - revealed short-range stiffness responses which highly resembled those observed in the torque measurements, suggesting that the latter to a large extent emanated from the stretched, relaxed flexor muscles. During repetitive stereotyped voluntary wrist dorsiflexions, a close correspondence was observed between the degree of short-range stiffness as sensed by the wrist flexor tension transducer and the strength of the initial extensor activation required for movement generation.
    6. The results provide evidence that the central nervous system in its control of voluntary movements takes account of and compensates for the history-dependent degree of inherent short-range stiffness of the muscles antagonistic to the prime movers.
  • 24.
    Axelson, Hans W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Successful localization of the Broca area with short-train pulses instead of "Penfield" stimulation.2009Ingår i: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 18, nr 5, s. 374-375Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Direct electrical stimulation of functional cortical areas is a standard procedure in epilepsy and glioma surgery. Many previous studies support that stimulation of the motor cortex with short-train pulses is a less epileptogenic alternative to the 50–60 Hz ‘Penfield’ technique. However, whether the short-train stimulation is useful also in mapping of speech areas is unclear. In this case report we present a patient with oligodendroglioma near the Broca area. Extraoperative electrical stimulation via a subdural grid electrode was primarily performed to locate the speech area. The cortex was stimulated with short-train pulses (5 pulses, 0.5 pulse duration and 3 ms interpulse interval) in addition to 1–3 s 50 Hz stimulation.The patient had speech arrest from both types of stimulation techniques during a naming task. It was however critical that the short (14.5 ms) train stimulation was synchronized with the presentation of the naming objects. If not, there was no speech arrest. Despite this possible pitfall, this case has encouraged us to further try short-train stimulation in attempts to reduce stimulus-triggered seizures during mapping of eloquent areas.

  • 25.
    Axelson, Hans W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Isberg, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Amandusson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Trigeminal Nerve Stimulation Does Not Acutely Affect Cortical Excitability in Healthy Subjects2014Ingår i: Brain Stimulation, ISSN 1935-861X, E-ISSN 1876-4754, Vol. 7, nr 4, s. 613-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Trigeminal nerve stimulation (TNS) has recently emerged as a new therapeutic option for patients with drug-resistant epilepsy but its potential mechanisms of action are not known. Since other antiepileptic treatments have been shown to alter cortical excitability, thereby reducing the liability to seizures, it has been suggested that cranial nerve stimulation such as TNS may act in the same way.

    OBJECTIVE: To study whether TNS has the potential to alter cortical excitability in healthy subjects.

    METHODS: An adaptive paired-pulse transcranial magnetic stimulation protocol stimulating the dominant hand motor area was used to measure resting motor threshold (rMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and long-interval intracortical inhibition (LICI) before, during, and after 40 min of 120 Hz bilateral external continuous trigeminal nerve stimulation. Neuronavigation was used for guidance.

    RESULTS: TNS was well tolerated by all subjects. No significant changes were seen in the parameters studied.

    CONCLUSION: Unlike for example anti-epileptic drugs and the ketogenic diet, trigeminal nerve stimulation does not seem to alter cortical excitability in healthy subjects. This is the first study on cortical excitability in relation to continuous trigeminal nerve stimulation. It still remains to be proven that TNS has the prerequisites to effectively counteract epileptic events in humans.

  • 26.
    Axelson, Hans W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Intraoperative Cavernous Nerve Stimulation and Laser-Doppler Flowmetry during Radical Prostatectomy2013Ingår i: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 10, nr 11, s. 2842-2848Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction. 

    Erectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity.

    Aim. 

    To test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation.

    Methods. 

    Fifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30-40 seconds biphasic constant current (10-30 mA) with 0.5 millisecond pulse duration.

    Main Outcome Measures. 

    Stimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery.

    Results. 

    Ten patients had stimulus induced increase in Laser Doppler flow unilaterally (N = 7) or bilaterally (N = 3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge.

    Conclusion. 

    This preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery.

  • 27.
    Axelson, Hans W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Melberg, Atle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy2002Ingår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 26, nr 4, s. 520-526Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Consecutive 60-min microdialysis samples were taken from the tibial anterior muscle in 11 healthy subjects and 4 patients with mitochondrial myopathy before (2-3 samples) and after (3-4 samples, 2 controls and 1 patient excluded) sustained isometric foot dorsiflexions. Before exercise, mean concentrations of lactate, pyruvate, hypoxanthine, urate, aspartate, and glutamate did not significantly differ between controls and patients. After exercise, the controls showed significantly increased concentrations of lactate, pyruvate, and urate, decreased hypoxanthine, and no change in aspartate and glutamate. Similar findings were observed in the patients. Plasma lactate was unchanged. Exercise-induced increase in integrated electromyogram amplitude and rated subjective fatigue were correlated to increased post-exercise lactate concentrations, with no obvious difference between the groups. Microdialysis of skeletal muscle allows the detection and monitoring of biochemical changes in the interstitial space. With the exercise protocol used, however, it was not possible to demonstrate any biochemical difference between healthy controls and patients with mitochondrial myopathy.

  • 28.
    Axelson, Hans W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Öberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    No benefit of treatment with cyclophosphamide and autologous blood stem cell transplantation in multifocal motor neuropathy2008Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 117, nr 6, s. 432-434Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction - Patients with multifocal motor neuropathy (MMN) usually respond to intravenous immunoglobulin (IVIG), but because of the short-lasting effect the treatment must be given repeatedly. Remission after treatment with high-dose cyclophosphamide has recently been reported in one patient refractory to IVIG. Case report - Here we report on a patient who responded to IVIG, but temporarily deteriorated dramatically after treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. Today the situation is the same as before the treatment with cyclophosphamide and blood stem cell transplantation, i.e. IVIG is given every 4 weeks. Conclusion - Our patient did not benefit from the treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. The effect of treatment with high-dose cyclophosphamide in MMN seems to be difficult to predict and that should be paid attention to if this type of treatment is considered.

  • 29.
    Axelson, Hans W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Öberg, Gunnar
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP2009Ingår i: BMJ case reports, ISSN 1757-790XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by the occurrence of symmetrical weakness and sensory impairment in arms and legs. The course is relapsing or chronic and progressing. CIDP is considered to be an autoimmune disease, which is supported by the beneficial response to immunomodulating therapies in most patients. We report on a patient with CIDP who has been in remission for more than 3 years after treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP on two occasions.

  • 30.
    Axelson, Hans W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Öberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP2008Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 79, nr 5, s. 612-612Artikel i tidskrift (Refereegranskat)
  • 31.
    Axelson, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Winkler, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Flygt, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Djupsjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hånell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat2013Ingår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 31, nr 1, s. 73-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Recovery is limited following traumatic brain injury (TBI) since injured axons regenerate poorly and replacement of lost cells is minimal. Behavioral improvements could instead be due to plasticity of uninjured brain regions. We hypothesized that plasticity of the uninjured hemisphere occurs contralateral to a focal TBI in the adult rat. Thus, we performed cortical mapping of the cortex contralateral to the TBI using intracortical microstimulation (ICMS). Methods: A focal TBI was induced using the weight-drop technique (n = 5) and sham-injured animals were used as controls (n = 4). At five weeks post-injury, ICMS was used to map the motor area contralateral to the injury. Motor responses were detected by visual inspection and electromyography (EMG). Results: In sham- and brain-injured animals, numerous fore- and hindlimb motor responses contralateral to the stimulation (ipsilateral to the injury) were obtained. Compared to sham-injured controls, there was a markedly increased (p < 0.05) number of fore- and hindlimb responses ipsilateral to the stimulation after TBI. Conclusion: Following focal TBI in the rat, our data suggest reorganization of cortical and/or subcortical regions in the uninjured hemisphere contralateral to a focal TBI leading to an altered responsiveness to ICMS. Although we cannot exclude that these changes are maladaptive, it is plausible that this plasticity process positively influences motor recovery after TBI.

  • 32.
    Backman, Sofia
    et al.
    Skane Univ Hosp, Dept Clin Sci, Div Clin Neurophysiol, S-22185 Lund, Sweden.
    Rosen, Ingmar
    Skane Univ Hosp, Dept Clin Sci, Div Clin Neurophysiol, S-22185 Lund, Sweden.
    Blennow, Mats
    Karolinska Inst, Dept New Born Med, CLINTEC, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Andersson, Thomas
    Karolinska Univ Hosp, Dept Clin Neurophysiol, Stockholm, Sweden.
    Englund, Marita
    Karolinska Univ Hosp, Dept Clin Neurophysiol, Stockholm, Sweden.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hallberg, Boubou
    Karolinska Inst, Dept New Born Med, CLINTEC, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Liedholm, Lars-Johan
    Umea Univ Hosp, Dept Clin Neurophysiol, Umea, Sweden.
    Norman, Elisabeth
    Lund Univ, Skane Univ Hosp, Dept Pediat, Neonatal Intens Care Unit, Lund, Sweden.
    Sailer, Alexandra
    Umea Univ Hosp, Dept Clin Neurophysiol, Umea, Sweden.
    Thordstein, Magnus
    Linkoping Univ, Inst Clin & Expt Med, Dept Clin Neurophysiol, Linkoping, Sweden.
    Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis2018Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, nr 10, s. 1702-1709Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. Conclusion: This paper describes the Swedish consensus document produced by those meetings.

  • 33.
    Banduseela, Varuna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Chen, Yi-wen
    Göransson Kultima, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Norman, Holly
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. Department of Medicine, University of Wisconsin, Madison, Wisconsin.
    Aare, Sudhakar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Radell, Peter
    Eriksson, Lars
    Hoffman, Eric
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania.
    Impaired autophagy, chaperone expression, and protein synthesis in response to critical illness interventions in porcine skeletal muscle2013Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, nr 12, s. 477-486Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Critical illness myopathy (CIM) is characterized by a preferential loss of the motor protein myosin, muscle wasting, and impaired muscle function in critically ill intensive care unit (ICU) patients. CIM is associated with severe morbidity and mortality and has a significant negative socioeconomic effect. Neuromuscular blocking agents, corticosteroids, sepsis, mechanical ventilation, and immobilization have been implicated as important risk factors, but the causal relationship between CIM and the risk factors has not been established. A porcine ICU model has been used to determine the immediate molecular and cellular cascades that may contribute to the pathogenesis prior to myosin loss and extensive muscle wasting. Expression profiles have been compared between pigs exposed to the ICU interventions, i.e., mechanically ventilated, sedated, and immobilized for 5 days, with pigs exposed to critical illness interventions, i.e., neuromuscular blocking agents, corticosteroids, and induced sepsis in addition to the ICU interventions for 5 days. Impaired autophagy as well as impaired chaperone expression and protein synthesis were observed in the skeletal muscle in response to critical illness interventions. A novel finding in this study is impaired core autophagy machinery in response to critical illness interventions, which when in concert with downregulated chaperone expression and protein synthesis may collectively affect the proteostasis in skeletal muscle and may exacerbate the disease progression in CIM.

  • 34. Bialek, Fatima
    et al.
    Rydenhag, Bertil
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Malmgren, Kristina
    Outcomes after resective epilepsy surgery in patients over 50 years of age in Sweden 1990-2009-A prospective longitudinal study2014Ingår i: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 23, nr 8, s. 641-645Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Most epilepsy surgery candidates are young adults. Outcome reports after epilepsy surgery in patients >= 50 years are few and varying. The aim of this study was to describe patient characteristics of older compared to younger adults and analyse seizure, complication and vocational outcomes in a large population-based series. Methods: We analysed data from the Swedish National Epilepsy Surgery Register for 1990-2009 for patients >= 19 years at resective surgery who had completed two-year follow-up. Variables studied were seizure outcome, histo-pathological diagnoses, complications and vocational outcome. Data from patients >= 50 years and 19-49 years at surgery were compared. Results: 558 Adults underwent resective epilepsy surgery 1990-2009 and had two-year follow-up. 12% of the adults (67 patients) were >= 50 years at surgery. Patients >= 50 had longer epilepsy duration, more often had mesial sclerosis and less often had neurodevelopmental tumours and cortical malformations. The proportion of seizure-free patients at two-year follow-up did not differ between those >= 50 and 1949 years (61% versus 61% seizure-free last year, 48% versus 43% completely seizure-free since surgery), neither did the occurrence of major complications (3% in both groups). The vocational situation was mainly stable between baseline and two-year follow-up in both groups, although older patients were less often employed than younger. Conclusion: 12% of adults in the Swedish series were >= 50 years at epilepsy surgery. Seizure outcome was as good for older as for younger adults, and there was no difference in the occurrence of major complications. This constitutes important information in the presurgical counselling process.  

  • 35. Bjellvi, J.
    et al.
    Edelvik, A.
    Ekstedt, G.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Rydenhag, B.
    Malmgren, K.
    Complications of Epilepsy Surgery in Sweden 1996-2010: Results from the Swedish National Epilepsy Surgery Register2012Ingår i: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 53, nr S5, s. 181-181Artikel i tidskrift (Övrigt vetenskapligt)
  • 36. Bjellvi, Johan
    et al.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Rydenhag, Berth
    Malmgren, Kristina
    Complications of epilepsy surgery in Sweden 1996-2010: a prospective, population-based study2015Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 122, nr 3, s. 519-525Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECT Detailed risk information is essential for presurgical patient counseling and surgical quality assessments in epilepsy surgery. This study was conducted to investigate major and minor complications related to epilepsy surgery in a large, prospective series. METHODS The Swedish National Epilepsy Surgery Register provides extensive population-based data on all patients who were surgically treated in Sweden since 1990. The authors have analyzed complication data for therapeutic epilepsy surgery procedures performed between 1996 and 2010. Complications are classified as major (affecting daily life. and lasting longer than 3 months) or minor (resolving within 3 months). RESULTS A total of 865 therapeutic epilepsy surgery procedures were performed between 1996 and 2010, of which 158 were reoperations. There were no postoperative deaths. Major complications occurred in 26 procedures (3%), and minor complications in 65 (7.5%). In temporal lobe resections (n = 523), there were 15 major (2.9%) and 41 minor complications (7.8%); in extratemporal resections (n = 275) there were 9 major (3.3%) and 22 minor complications (8%); and in nonresective procedures (n = 67) there were 2 major (3%) and 2 minor complications (3%). The risk for any complication increased significantly with age (OR 1.26 per 10-year interval, 95% Cl 1.09-1.45). Compared with previously published results from the same register, there is a trend toward lower complication rates, especially in patients older than 50 years. CONCLUSIONS This is the largest reported prospective series of complication data in epilepsy surgery. The complication rates comply well with published results from larger single centers, confirming that epilepsy surgery performed in the 6 Swedish centers is safe. Patient age should be taken into account when counseling patients before surgery.

  • 37. Blizard, David A.
    et al.
    Lionikas, Arimantas
    Vandenberg, David
    Vasilopoulos, Terrie
    Gerhard, Glenn
    Griffith, James
    Klein, Laura
    Stout, Joseph
    Mack, Holly
    Lakoski, Joan
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Spicer, Jeanne
    Vogler, George
    McClearn, Gerald E.
    Blood pressure and heart rate QTL in mice of the B6/D2 lineage sex differences and environmental influences2009Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 36, nr 3, s. 158-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]