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Sökning: WFRF:(Axelson Hans W.)

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1.
  • Ahlberg, Mats Steinholtz, et al. (författare)
  • PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
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2.
  • Axelson, Hans W, et al. (författare)
  • Intraoperative Cavernous Nerve Stimulation and Laser-Doppler Flowmetry during Radical Prostatectomy
  • 2013
  • Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095 .- 1743-6109. ; 10:11, s. 2842-2848
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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3.
  • Alm, Per A., et al. (författare)
  • Hemispheric Lateralization of Motor Thresholds in Relation to Stuttering
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10, s. e76824-
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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4.
  • Axelson, Hans W. (författare)
  • Compound Motor Action Potential Interexaminer Variability in Photoguided Placement of the Recording Electrodes
  • 2012
  • Ingår i: Journal of clinical neurophysiology. - 0736-0258 .- 1537-1603. ; 29:3, s. 256-259
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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5.
  • Axelson, Hans W (författare)
  • Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements
  • 2004
  • Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 182:3, s. 295-304
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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6.
  • Axelson, Hans W, et al. (författare)
  • Human motor control consequences of thixotropic changes in muscular short-range stiffness
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 535:Pt 1, s. 279-288
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.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.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.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.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.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.
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7.
  • Axelson, Hans W, et al. (författare)
  • Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy
  • 2002
  • Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 26:4, s. 520-526
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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8.
  • Axelson, Hans W., et al. (författare)
  • No benefit of treatment with cyclophosphamide and autologous blood stem cell transplantation in multifocal motor neuropathy
  • 2008
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 117:6, s. 432-434
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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9.
  • Axelson, Hans W (författare)
  • Signs of muscle thixotropy during human ballistic wrist joint movements
  • 2005
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 99:5, s. 1922-1929
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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10.
  • Axelson, Hans W., et al. (författare)
  • Simplified Evaluation of the Paradoxical Puborectalis Contraction With Surface Electrodes
  • 2010
  • Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 53:6, s. 928-931
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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11.
  • Axelson, Hans W., et al. (författare)
  • Successful localization of the Broca area with short-train pulses instead of "Penfield" stimulation.
  • 2009
  • Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 18:5, s. 374-375
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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12.
  • Axelson, Hans W, et al. (författare)
  • Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP
  • 2009
  • Ingår i: BMJ Case Reports. - : BMJ. - 1757-790X.
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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13.
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14.
  • Axelson, Hans W, et al. (författare)
  • Trigeminal Nerve Stimulation Does Not Acutely Affect Cortical Excitability in Healthy Subjects
  • 2014
  • Ingår i: Brain Stimulation. - : Elsevier BV. - 1935-861X .- 1876-4754. ; 7:4, s. 613-617
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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15.
  • Franck-Larsson, Karin, et al. (författare)
  • Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence
  • 2014
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 49:9, s. 1073-1083
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveFecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms.Materials and methodsTwenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound.ResultsEleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05).ConclusionLower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.
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17.
  • Press, R, et al. (författare)
  • Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP
  • 2014
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 85:6, s. 618-624
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.
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18.
  • Steinholtz, Linda, et al. (författare)
  • GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy : A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.
  • 2024
  • Ingår i: Neuropsychobiology. - : S. Karger. - 0302-282X .- 1423-0224. ; 83:1, s. 17-27
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.
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