171 results on '"Søren H. Sindrup"'
Search Results
2. Axonal Excitability Does Not Differ between Painful and Painless Diabetic or Chemotherapy‐Induced Distal Symmetrical Polyneuropathy in a Multicenter Observational Study
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Andreas C. Themistocleous, Alexander G. Kristensen, Roma Sola, Sandra S. Gylfadottir, Kristine Bennedsgaard, Mustapha Itani, Thomas Krøigård, Lise Ventzel, Søren H. Sindrup, Troels S. Jensen, Hugh Bostock, Jordi Serra, Nanna B. Finnerup, Hatice Tankisi, and David L. H. Bennett
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Polyneuropathies ,Diabetic Neuropathies ,Neurology ,Diabetes Mellitus ,Humans ,Neuralgia ,Antineoplastic Agents ,Neurology (clinical) ,Axons - Abstract
Objective: Axonal excitability reflects ion channel function, and it is proposed that this may be a biomarker in painful (vs painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy-induced distal symmetrical polyneuropathy. Methods: Two hundred thirty-nine participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants who developed chemotherapy-induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibers was measured with the threshold tracking technique. The stimulus site was the median nerve, and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies). Results: Participants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength–duration time constant, and current–threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, and there were only minor changes for chemotherapy-induced polyneuropathy. Interpretation: Axonal excitability did not significantly differ between painful and painless diabetic or chemotherapy-induced polyneuropathy in a multicenter observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated, and although there is some overlap of the "channelome" between these axonal populations, our results suggest that alternative measures such as microneurography are required to understand the relationship between sensory neuron excitability and neuropathic pain. ANN NEUROL 2022;91:506–520.
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- 2022
3. Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment
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Kanita Zubcevic, Merete Petersen, Flemming Winther Bach, Aksel Heinesen, Thomas Peter Enggaard, Thomas Peter Almdal, Jakob Vormstrup Holbech, Lene Vase, Troels Stahelin Jensen, Christian Stevns Hansen, Nanna Brix Finnerup, and Søren H. Sindrup
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Anesthesiology and Pain Medicine - Abstract
Background: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is ‘weak against’. Objectives: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. Methods: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5–50 mg, THC 2.5–25 mg, and CBD/THC 5 mg/2.5 mg–50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. Results: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04–0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11–2.19), THC 0.38 (CI −0.65 to 1.4) and CBD/THC −0.12 (−1.13 to 0.89). Conclusions: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.
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- 2022
4. Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy
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Alexander Gramm Kristensen, Mustapha Itani, Páll Karlsson, Troels S. Jensen, Hatice Tankisi, David L.H. Bennett, Nanna B. Finnerup, Sandra Sif Gylfadottir, Søren H. Sindrup, and Jens R. Nyengaard
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Male ,medicine.medical_specialty ,Biopsy ,Calcitonin Gene-Related Peptide ,Substance P ,Type 2 diabetes ,Calcitonin gene-related peptide ,Gastroenterology ,Article ,Pathogenesis ,chemistry.chemical_compound ,Nerve Fibers ,Diabetic Neuropathies ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Aged ,Skin ,business.industry ,Macrophages ,Correction ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Neurology ,chemistry ,Calcitonin ,Neuropathic pain ,Neuralgia ,Female ,Neurology (clinical) ,business ,Body mass index ,Biomarkers - Abstract
Background and ObjectivesThe mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP).MethodsThe participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers.ResultsThere was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%,p< 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%,p< 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm−2for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm−2for SP and CGRP, respectively,p= 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm−2for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes (p= 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients.DiscussionThe findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.
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- 2022
5. Oxaliplatin Neuropathy: Predictive Values of Skin Biopsy, QST and Nerve Conduction
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Toke de Koning Svendsen, Henrik Daa Schrøder, Per Pfeiffer, Martin Wirenfeldt, Camilla Qvortrup, Thomas Krøigård, David Gaist, and Søren H. Sindrup
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Adult ,Male ,medicine.medical_specialty ,peripheral neuropathy ,Biopsy ,Neural Conduction ,Pain ,quantitative sensory testing ,Nerve fiber ,Gastroenterology ,03 medical and health sciences ,Nerve Fibers ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Aged ,Skin ,Aged, 80 and over ,neuropathic pain ,medicine.diagnostic_test ,business.industry ,Quantitative sensory testing ,oxaliplatin ,Peripheral nerve structure ,Peripheral Nervous System Diseases ,skin biopsies ,Middle Aged ,medicine.disease ,Predictive value ,Oxaliplatin ,Peripheral neuropathy ,medicine.anatomical_structure ,Neurology ,030220 oncology & carcinogenesis ,Neuropathic pain ,Skin biopsy ,Quality of Life ,Female ,Nerve conduction studies ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: Oxaliplatin-induced peripheral neuropathy negatively affects the quality of life for patients with gastrointestinal cancers and may cause neuropathic pain. Measures of peripheral nerve structure or function, such as intraepidermal nerve fiber density (IENFD) during treatment could reduce neuropathy severity through individualized dose reduction. Objective: The aim was to evaluate the predictive values of IENFD, quantitative sensory testing (QST), and nerve conduction studies (NCS) for significant neuropathy and neuropathic pain. Methods: Fifty-five patients were examined prospectively before, during, and six months following treatment using skin biopsies, QST and NCS. Clinically significant neuropathy six months after treatment was defined as reduced Total Neuropathy Score of more than five and neuropathic pain was assessed according to International Association for the Study of Pain criteria. Results: Thirty patients had a clinically significant neuropathy, and 14 had neuropathic pain. Vibration detection threshold (VDT) before treatment was correlated with clinically significant neuropathy six months after treatment (OR 0.54, p = 0.01) and reductions in cold detection threshold (CDT) after 25% of treatment (OR 1.38, p = 0.04) and heat pain threshold (HPT) after 50% of treatment (OR 1.91, p = 0.03) with neuropathic pain. Cut off values of 5 for baseline VDT and changes of more than –0.05 °C and –0.85 °C in CDT and HPT were estimated. Sensitivity and specificity was low to moderate. There was no correlation between changes in IENFD or NCS and significant neuropathy or neuropathic pain. Conclusions: Vibration detection thresholds and thermal detection thresholds may be useful for prediction of clinically significant and painful neuropathy, respectively. However, low to moderate sensitivity and specificity may limit the predictive value in clinical practice.
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- 2021
6. Sensory and motor axonal excitability testing in early diabetic neuropathy
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Henning Andersen, Søren H. Sindrup, Mustapha Itani, Nanna B. Finnerup, Thomas Krøigård, Sandra Sif Gylfadottir, Karolina Snopek Khan, Alexander Gramm Kristensen, Troels S. Jensen, Hatice Tankisi, and Satoshi Kuwabara
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Male ,Diabetic polyneuropathy ,medicine.medical_specialty ,Diabetic neuropathy ,Sensory Receptor Cells ,Axonal excitability testing ,Neural Conduction ,Physical examination ,Sensory system ,Type 2 diabetes ,Audiology ,050105 experimental psychology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Physiology (medical) ,medicine ,Humans ,0501 psychology and cognitive sciences ,Prospective Studies ,Patient group ,Aged ,Type-2 diabetes ,Motor Neurons ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Middle Aged ,medicine.disease ,Axons ,Sensory Systems ,Pathophysiology ,Cross-Sectional Studies ,Early Diagnosis ,Rheobase ,Diabetes Mellitus, Type 2 ,Neurology ,Female ,Nerve conduction studies ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Objective The aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing. Methods One hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). Results Motor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores. Conclusions Changes in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. Significance Less pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.
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- 2021
7. Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain
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Maija Haanpää, Rolf-Detlef Treede, Rainer Freynhagen, Juliane Sachau, Søren H. Sindrup, Troels S. Jensen, Christoph Maier, Jan Vollert, Janne Gierthmühlen, Jeffrey D. Kennedy, Nadine Attal, Thomas R. Tölle, Didier Bouhassira, Märta Segerdahl, Andrew S.C. Rice, Johann Böhmer, Lise Ventzel, Ralf Baron, Per Hansson, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Benedictus Hospital Feldafing, Technische Universität München = Technical University of Munich (TUM), Helsinki University Hospital [Finland] (HUS), Oslo University Hospital [Oslo], Karolinska Institutet [Stockholm], Aarhus University Hospital, Eli Lilly and Company [Indianapolis], Ruhr University Bochum (RUB), Imperial College London, Odense University Hospital (OUH), Heidelberg University, This project has received funding from an Innovative Medicines Initiative 1 EUROPAIN under grant No [115007] and from an Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777500]. This joint undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. (www.imi.europe.eu, European Project: 115007,EC:FP7:SP1-JTI,IMI-JU-01-2008,EUROPAIN(2009), HAL UVSQ, Équipe, and Understanding chronic pain and improving its treatment - EUROPAIN - - EC:FP7:SP1-JTI2009-10-01 - 2015-09-30 - 115007 - VALID
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PRO ,Quality of life ,medicine.medical_specialty ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Sensory system ,Sensory phenotype ,Neuropathic pain ,Emotional well-being ,Physical medicine and rehabilitation ,medicine ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Brief Pain Inventory ,Functionality ,business.industry ,Chronic pain ,Sensory loss ,medicine.disease ,QST ,Anesthesiology and Pain Medicine ,Phenotype ,Neurology ,Hyperalgesia ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Anxiety ,Neuralgia ,Pain catastrophizing ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neurology (clinical) ,medicine.symptom ,Chronic Pain ,business - Abstract
International audience; Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management. Copyright
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- 2022
8. Association of Hospital-Diagnosed Infections and Antibiotic Use With Risk of Developing Guillain-Barré Syndrome
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Reimar W. Thomsen, Lotte Sahin Levison, Henning Andersen, and Søren H. Sindrup
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Denmark ,Population ,Antibiotics ,Guillain-Barre Syndrome/epidemiology ,Guillain-Barre Syndrome ,Infections ,Drug Prescriptions ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Sepsis ,Internal medicine ,Lower respiratory tract infection ,Humans ,Medicine ,Registries ,030212 general & internal medicine ,Child ,education ,Respiratory Tract Infections ,Aged ,Aged, 80 and over ,education.field_of_study ,Guillain-Barre syndrome ,business.industry ,Case-control study ,Infant ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Anti-Bacterial Agents ,Hospitalization ,Case-Control Studies ,Child, Preschool ,Relative risk ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo determine whether hospital-diagnosed and community-treated infections are important Guillain-Barré syndrome (GBS) risk factors, we investigated the magnitude and duration of associated GBS risk.MethodsWe conducted a nationwide population-based case–control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 matched population controls per case. Hospital-diagnosed infections were determined in the 1987–2016 period and community antibiotic prescriptions in the 2004–2016 period. We used conditional logistic regression to examine the relative risk of GBS associated with having a recent infection.ResultsHospital-diagnosed infections within 60 days were observed in 4.3% of 2,414 GBS cases vs 0.3% of 23,909 controls, with a matched odds ratio (OR) of 13.7 (95% confidence interval [CI], 10.2–18.5). The strongest association with subsequent GBS was observed for lower respiratory tract infection, gastrointestinal tract infection, and septicemia. Community antibiotic prescriptions within 60 days were observed in 22.4% of 1,086 GBS cases and 7.8% of 10,747 controls, with a matched OR of 3.5 (95% CI, 3.0–4.1). The risk of GBS declined considerably with time since infection, with high ORs of 21.3 (95% CI, 14.5–31.2) and 4.7 (95% CI, 3.9–5.7) observed within the first month after a hospital-diagnosed infection and a community antibiotic prescription, respectively. However, GBS risk remained increased 2.4-fold (95% CI, 1.1–5.5) and 1.5-fold (95% CI, 1.2–2.0) even in the fifth month after infection.ConclusionThere is a strong, temporal association between community antibiotic use and especially infections necessitating hospitalization and risk of subsequent GBS.
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- 2020
9. 2020 Peripheral Nerve Society Virtual Event
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Søren H. Sindrup, Ingelise Christiansen, Jakob Vormstrup Holbech, Henning Andersen, and Lars Kjøbsted Markvardsen
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Pediatrics ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Tapering ,law.invention ,Clinical trial ,Regimen ,Pharmacotherapy ,Randomized controlled trial ,law ,Medicine ,Neurology (clinical) ,business - Published
- 2020
10. Impact of variability in baseline pain on the placebo response in randomized, placebo-controlled, crossover trials in peripheral neuropathic pain
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Søren H. Sindrup, Mimmi Gillving, Jakob Vormstrup Holbech, Flemming W. Bach, Troels S. Jensen, Dyveke Torgaard Demant, Nanna B. Finnerup, and Lene Vase
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Treatment response ,Placebo ,Neuropathic pain ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Numeric Rating Scale ,Humans ,Medicine ,Retrospective Studies ,Analgesics ,Placebo response ,Cross-Over Studies ,business.industry ,Placebo Effect ,Crossover study ,Peripheral neuropathic pain ,Clinical trial ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Neurology ,Anesthesia ,Neuralgia ,Neurology (clinical) ,business - Abstract
Large placebo responses often negatively affect randomized controlled trials within the pain area. Understanding different possible factors that influence the placebo response is therefore important. In this retrospective analysis, we hypothesized that a large variability in baseline pain score would predict a greater placebo response and analyzed the impact of the coefficient of variation, SD, and difference between the highest and lowest numeric rating scale (NRS) score at baseline on the placebo response. A total of 160 observations on placebo response from 3 controlled clinical trials with a crossover design were included in this study. In general, the placebo response was low with a mean reduction in pain intensity of 0.5 points (range -5 to 7) measured on a 0 to 10 point NRS, and only 15% were placebo responders as defined by more than 30% reduction in NRS pain score from baseline to the end of the placebo treatment period. We found no significant impact of baseline pain coefficient of variation, SD, or the difference between lowest and highest baseline pain score on the placebo response. Placebo response in one trial did not predict placebo response in another trial. A large placebo response was not associated with a large treatment response. In conclusion, in this retrospective data analysis, there was no impact of baseline pain variability on the placebo response in controlled clinical trials with a crossover design in patients with peripheral neuropathic pain.
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- 2022
11. The additional diagnostic value of motor nerve excitability testing in chronic axonal neuropathy
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Thomas Krøigård, Ulrik Sodemann, Laura M. Gaist, Søren H. Sindrup, and Hatice Tankisi
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inorganic chemicals ,Neurosciences. Biological psychiatry. Neuropsychiatry ,behavioral disciplines and activities ,enzymes and coenzymes (carbohydrates) ,Neurology ,Physiology (medical) ,Polyneuropathy ,mental disorders ,Diagnosis ,heterocyclic compounds ,Neurology (clinical) ,Nerve conduction studies ,Nerve excitability testing ,Research Paper ,RC321-571 - Abstract
Highlights • Nerve excitability testing was correlated with conventional nerve conduction studies. • Nerve excitability testing was similar in patients with and without neuropathy and normal nerve conduction. • There is no support for the potential additional diagnostic value of nerve excitability testing in mixed etiology neuropathy., Objective To explore potential differences in motor nerve excitability testing (NET) variables at group levels between patients with a clinical diagnosis of polyneuropathy (PNP), which did not fulfil diagnostic criteria of conventional nerve conduction studies (NCS) and patients without polyneuropathy. Such differences could support a role for NET in increasing the diagnostic sensitivity of NCS in chronic axonal PNP. Methods Motor NET was performed using the median nerve in patients with a clinical suspicion of PNP in addition to conventional NCS, skin biopsies, corneal confocal microscopy and structured clinical evaluation including scoring of neuropathy symptoms and signs. Results Of the 57 patients included, 32 had PNP, half of which had NCS, which fulfilled criteria for PNP (NCS+ PNP). There were no significant differences for any of the NET variables between PNP patients with non-diagnostic conventional NCS (NCS− PNP) and patients without PNP. Rheobase was increased, and Ted (undershoot) and subexcitability were decreased in NCS+ PNP. Sural amplitude, peroneal nerve F-wave latency and tibial nerve F-wave-latency were correlated with subexcitability, and tibial nerve motor amplitude was correlated with rheobase. Conclusions NET was correlated with conventional NCS and no differences were found between NCS− PNP patients and patients without PNP. Significance NET does not seem to offer any additional diagnostic value in chronic mixed etiology neuropathy.
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- 2022
12. A population‐based study of long‐term outcome in treated chronic inflammatory demyelinating polyneuropathy
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Henning Andersen, Søren H. Sindrup, Johannes Jakobsen, and Ali Al-Zuhairy
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Physiology ,Denmark ,Disease duration ,Isokinetic strength ,Chronic inflammatory demyelinating polyneuropathy ,CIDP ,Severity of Illness Index ,Disability Evaluation ,chronic inflammatory demyelinating polyneuropathy ,Cellular and Molecular Neuroscience ,Interquartile range ,Physiology (medical) ,medicine ,Humans ,In patient ,business.industry ,Matched control ,Middle Aged ,medicine.disease ,Population based study ,Cross-Sectional Studies ,Treatment Outcome ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,disability ,outcome ,Severe morbidity ,Female ,Immunotherapy ,prognosis ,Neurology (clinical) ,business - Abstract
Introduction: The effect of long-lasting immune-modulating therapy was studied in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: A population-based, cross-sectional study of treated patients referred to the Danish health-care system between 1985 and 2006. Results: The 51 participating patients had a median disease duration of 16 (interquartile range, 14–21) years. Twenty-seven patients (53%) had discontinued therapy and 46 walked independently. Disability and isokinetic strength were impaired by 17% and 20%, respectively, as compared with matched control subjects. For a few patients long-term CIDP was associated with severe morbidity (6%) and even mortality (1%). Prolongation of time until start of therapy was associated with an increased burden of long-term disability. Discussion: Long-term prognosis in treated CIDP is characterized by limited disability in the majority of patients. Disability is related to delay of therapy. Therefore, more attention should be given to early treatment start in CIDP.
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- 2020
13. Normative reference values for the dorsal sural nerve derived from a large multicenter cohort
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Henning Andersen, Søren H. Sindrup, Mustapha Itani, Sandra Sif Gylfadottir, K.V. Andersen, Alexander Gramm Kristensen, Sándor Beniczky, Thomas Krøigård, Karolina Snopek Khan, Troels S. Jensen, and Hatice Tankisi
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Dorsum ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Sural nerve ,Nerve conduction velocity ,Reference values ,Physiology (medical) ,Polyneuropathy ,Linear regression ,Diagnosis ,RECORDINGS ,Medicine ,Dorsal sural nerve ,UTILITY ,business.industry ,medicine.disease ,Antidromic ,Neurology ,CONDUCTION ,Cohort ,Neurology (clinical) ,Nerve conduction studies ,business ,Nuclear medicine ,PLANTAR ,RC321-571 ,Research Paper - Abstract
Highlights • We determined reference values for the dorsal sural nerve from a large cohort, aged 21-80. • Amplitude and conduction velocity depended on both age and height. • We provide formulas for reference limits., Objectives Dorsal sural nerve conduction studies (NCS) may increase the sensitivity for the diagnosis of polyneuropathy, but clinical use is limited by a lack of reliable normative reference values in all age-groups. The aim of our study was to develop reference values for the dorsal sural nerve, based on a large multicenter cohort of healthy subjects. Methods Bilateral antidromic NCS were performed using standard surface electrodes in 229 healthy subjects (aged 21–80 years; median: 54 years). We assessed the normality of data distribution for amplitudes and conduction velocity (CV) and for their logarithmic (ln) transformation. The effects of age and height were determined using linear regression analysis. Results Sensory potentials were present in all subjects. Logarithmically transformed data were normally distributed. Age2 and height were most significantly associated with amplitude, and age and height with CV, respectively. There was no significant side-difference. Mean amplitudes (right and left) were 4.8 and 4.9 μV and mean CV 46.7 and 46.9 m/s. Reference limits were e (3.712515 – 0.0000956 * age2 – 0.0115883 * height ± 1.96 * 0.51137) for amplitude and e (4.354374 – 0.0021081 * age – 0.0023354 * height ± 1.96 * 0.11161) for CV. Conclusions Dorsal sural nerve NCS are robust and have well defined normative limits. Significance The findings provide a basis for more sensitive NCS in clinical practice and future studies of the diagnostic accuracy of NCS in polyneuropathy.
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- 2021
14. Test‐retest and time dependent variation and diagnostic values of vibratory sensation determined by biothesiometer and the Rydel‐Seiffer tuning fork
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Bolette Wittenberg, Toke de Koning Svendsen, Sandra Sif Gylfadottir, David Gaist, Søren H. Sindrup, Troels S. Jensen, Thomas Krøigård, Laura M. Gaist, and Mustapha Itani
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medicine.medical_specialty ,Sensation ,Physical examination ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Neurological disorder ,Vibratory sensation ,Audiology ,Diagnostic tools ,Vibration ,050105 experimental psychology ,law.invention ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Diabetic Neuropathies ,law ,Predictive Value of Tests ,Rydel-Seiffer ,medicine ,Humans ,0501 psychology and cognitive sciences ,In patient ,Tuning fork ,Original Research ,Neurologic Examination ,biothesiometer ,medicine.diagnostic_test ,business.industry ,Quantitative sensory testing ,05 social sciences ,tuning fork ,medicine.disease ,Rydel‐Seiffer ,Sensory Thresholds ,vibration detection threshold ,polyneuropathy ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,RC321-571 - Abstract
Background and aims Polyneuropathy is a common neurological disorder with many potential causes. An essential part in screening, diagnosis, and follow‐up evaluation of polyneuropathy is testing of the sensory function including vibratory sensation. The graduated Rydel‐Seiffer tuning fork and the biothesiometer have been developed to quantify vibratory sensation through detection thresholds. The aim of this study is to compare the vibration detection thresholds determined by the two instruments regarding intraindividual temporal changes, interindividual variation in healthy subjects and comparison of the diagnostic value in patients with a clinical suspicion of polyneuropathy. Methods Ninety‐four healthy subjects, 98 patients with and 97 patients without a diagnosis of polyneuropathy were included. Quantitative sensory testing including biothesiometry, structured clinical examination, and nerve conduction studies were performed three times during 52 weeks in healthy subjects and once in patients. Results There were no significant changes over time for neither the Rydel‐Seiffer tuning fork nor the biothesiometer, and both had larger between‐subject variation than within‐subject variation. Relative intertrial variability was largest for the biothesiometer. Diagnostic value (sensitivity, specificity, positive predictive value, and negative predictive value) was moderate for both methods (Rydel‐Seiffer tuning fork: 58%, 74%, 70%, 64%; biothesiometer: 47%, 77%, 68%, 59%). Interpretation The Rydel‐Seiffer tuning fork and the biothesiometer have a low test‐retest and time dependent variation. They perform almost equally as diagnostic tools in patients with suspected polyneuropathy with a tendency toward better performance of the tuning fork., The graduated Rydel‐Seiffer tuning fork and the biothesiometer have been developed to quantify vibratory sensation through detection thresholds. We compared intra‐individual temporal changes, inter‐individual variation in healthy subjects and comparison of diagnostic value in patients with a clinical suspicion of polyneuropathy. They both have a low test‐retest and time dependent variation and perform almost equally as diagnostic tools in patients with suspected polyneuropathy with a tendency towards better performance of the tuning fork.
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- 2021
15. A randomized, controlled trial of a β2-agonist in painful polyneuropathy
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Sandra Sif Gylfadottir, Flemming W. Bach, Søren H. Sindrup, Nanna B. Finnerup, Jakob Vormstrup Holbech, Troels S. Jensen, Mimmi Gillving, and Dyveke Torgaard Demant
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Imipramine ,Terbutaline ,Antidepressive Agents, Tricyclic ,Placebo ,law.invention ,03 medical and health sciences ,Polyneuropathies ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,030202 anesthesiology ,law ,medicine ,Humans ,Pain Measurement ,Sleep disorder ,business.industry ,medicine.disease ,Confidence interval ,Anesthesiology and Pain Medicine ,Treatment Outcome ,Neurology ,Anesthesia ,Neuropathic pain ,Neuralgia ,Neurology (clinical) ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Experimental data have suggested that in neuropathic pain, tricyclic antidepressants may work solely through a β2-agonist action. The aim of this study was to test if the β2-agonist terbutaline relieves painful polyneuropathy. The study was a randomized, double-blind, placebo-controlled and active-controlled, 3-way, cross-over trial among patients with painful polyneuropathy. The treatment periods were of 5 weeks' duration and were preceded by 1 week for washout and 1 week for baseline observations. The patients received terbutaline (5-15 mg), imipramine (30-150 mg), or placebo in a random order. Drug doses depended on age and metabolizer status. The change in total pain recorded from ratings in diaries (numeric rating scale [NRS] 0-10) was the primary outcome, and the change in rating of specific pain symptoms (NRS 0-10), patient global impression of change, and sleep disturbance were secondary outcomes. Forty-seven patients were randomized. The median score for total pain changed from NRS 6.4 to 6.1 from baseline to week 5 on terbutaline with an average effect during the treatment period as compared with placebo of 0.13 (95% confidence interval -0.12 to 0.38, P = 0.32). The median score for total pain on imipramine changed from NRS 6.6 to 4.8 with an average effect as compared with placebo of -1.17 (95% confidence interval -1.42 to -0.92, P < 0.001). Secondary outcomes were also unaltered by terbutaline but improved by imipramine. The β2-agonist terbutaline has no effect in painful polyneuropathy. β2-agonism seems not to be an important mechanism of action of tricyclic antidepressants in neuropathic pain.
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- 2021
16. Author response for 'Test‐retest and time dependent variation and diagnostic values of vibratory sensation determined by biothesiometer and the Rydel‐Seiffer tuning fork'
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David Gaist, Mustapha Itani, Troels Staehlin Jensen, Laura M. Gaist, Toke de Koning Svendsen, Thomas Krøigård, Sandra Sif Gylfadottir, Søren H. Sindrup, and Bolette Wittenberg
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medicine.medical_specialty ,Variation (linguistics) ,law ,medicine ,Vibratory sensation ,Tuning fork ,Audiology ,Mathematics ,law.invention ,Test (assessment) - Published
- 2021
17. A population‐based and cross‐sectional study of the long‐term prognosis in multifocal motor neuropathy
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Søren H. Sindrup, Ali Al-Zuhairy, Johannes Jakobsen, and Henning Andersen
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Male ,medicine.medical_specialty ,peripheral neuropathy ,multifocal motor neuropathy ,Cross-sectional study ,Denmark ,Mismatch negativity ,03 medical and health sciences ,Grip strength ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Outcome Assessment, Health Care ,Epidemiology ,Humans ,Immunologic Factors ,Medicine ,Registries ,Motor Neuron Disease ,Aged ,Muscle Weakness ,business.industry ,General Neuroscience ,Middle Aged ,Prognosis ,medicine.disease ,Cross-Sectional Studies ,Peripheral neuropathy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,epidemiology ,Female ,prognosis ,Neurology (clinical) ,Ankle ,business ,030217 neurology & neurosurgery ,Multifocal motor neuropathy - Abstract
OBJECTIVE: To evaluate the long-term outcome in Danish patients treated for multifocal motor neuropathy (MMN).METHODS: A population-based, cross-sectional study of patients referred to the Danish hospital system between 1985 and 2006.RESULTS: Thirty-four MMN patients were identified, three had died of unrelated diseases, 10 were excluded, one did not reply to study request and 20 were included. The median disease duration was 24 years (IQR: 18.5 - 31.0). Compared to 24 healthy matched control subjects, the Rasch-built Overall Disability Scale for Multifocal Motor Neuropathy was reduced by 9%, the Neuropathy Impairment Score showed a threefold increase, the isokinetic strength was reduced by 29%, the grip strength by 56%, the Timed 25-Foot Walk was prolonged by 13% and the EQ-5D-5L-Index value was impaired by 20%. The isokinetic strength was significantly more impaired at the wrist and ankle as compared to the elbow and knee, and one patient had lost ambulation due to instability at the ankle. Patients were considerably more fatigued and had substantially impaired hand dexterity, while mood, aerobic capacity, social adjustment and working capacity were not affected. Regression analysis showed that lag-time until start of initial therapy lead to impaired long-term outcome without any effect of disease duration.CONCLUSION: Long-term prognosis in treated MMN is characterized by moderate to severe impairment primarily affecting dexterity and stability at the ankle. Our observations support previous observations that the long-term impairment in MMN might be improved following earlier start of therapy and that an effect of disease duration cannot be demonstrated.
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- 2019
18. Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management
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Páll Karlsson, Hatice Tankisi, Sandra Sif Gylfadottir, Brian C. Callaghan, Astrid Juhl Terkelsen, David L.H. Bennett, Karolina Snopek Khan, Morten Charles, Nanna B. Finnerup, Andreas C. Themistocleous, Henning Andersen, Mustapha Itani, Søren H. Sindrup, Troels S. Jensen, Alexander Gramm Kristensen, Signe T Andersen, and Eva L. Feldman
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Pediatrics ,medicine.medical_specialty ,Diabetic neuropathy ,Diabetic Neuropathies/diagnosis ,CLINICAL-MANIFESTATIONS ,030209 endocrinology & metabolism ,Type 2 diabetes ,Disease ,Review Article ,Neuralgia/diagnosis ,law.invention ,implication for management ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Diabetic Neuropathies ,law ,Painful diabetic neuropathy ,Diabetes mellitus ,medicine ,Humans ,NERVE-CONDUCTION ,business.industry ,Diabetes Mellitus, Type 2/complications ,DISTAL SYMMETRIC POLYNEUROPATHY ,ELECTRODIAGNOSTIC-MEDICINE ,SMALL FIBER NEUROPATHY ,medicine.disease ,3. Good health ,Clinical trial ,diagnostic challenges ,THERMAL THRESHOLDS ,Peripheral neuropathy ,Diabetes Mellitus, Type 1 ,CORNEAL CONFOCAL MICROSCOPY ,Diabetes Mellitus, Type 2 ,13. Climate action ,PHYSICAL-MEDICINE ,Neuropathic pain ,AMERICAN-ASSOCIATION ,Diabetes Mellitus, Type 1/complications ,Neuralgia ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,PERIPHERAL NEUROPATHY - Abstract
Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30–40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.
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- 2021
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19. Diagnosis and prevalence of diabetic polyneuropathy:a cross-sectional study of Danish patients with type 2 diabetes
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Alexander Gramm Kristensen, Páll Karlsson, Reimar W. Thomsen, Diana Hedevang Christensen, Søren H. Sindrup, Jens Steen Nielsen, Hatice Tankisi, Brian C. Callaghan, Troels S. Jensen, Nanna B. Finnerup, Sia Kromann Nicolaisen, Sif Gylfadottir, David L.H. Bennett, Thomas Krøigård, Henning Andersen, Mustapha Itani, and Niels Trolle Andersen
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medicine.medical_specialty ,Cross-sectional study ,diagnosis ,Denmark ,prevalence ,Physical examination ,Type 2 diabetes ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Internal medicine ,Diabetes mellitus ,Epidemiology ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Subclinical infection ,neuropathic pain ,medicine.diagnostic_test ,diabetes ,business.industry ,medicine.disease ,Cross-Sectional Studies ,Neurology ,Diabetes Mellitus, Type 2 ,Cohort ,Neurology (clinical) ,polyneuropathy ,business ,Polyneuropathy ,030217 neurology & neurosurgery - Abstract
Background and purpose: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. Methods: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. Results: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. Conclusions: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.
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- 2020
20. Factors with impact on magnitude of the placebo response in randomized, controlled, cross-over trials in peripheral neuropathic pain
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Marit Otto, Søren H. Sindrup, Mimmi Gillving, Karen Lund, Flemming W. Bach, Jakob Vormstrup Holbech, Nanna B. Finnerup, Dyveke Torgaard Demant, Troels S. Jensen, and Lene Vase
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Placebo ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,030202 anesthesiology ,Rating scale ,Numeric Rating Scale ,Humans ,Medicine ,Analgesics ,Placebo response ,Cross-Over Studies ,business.industry ,Placebo Effect ,Peripheral neuropathic pain ,Clinical trial ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Allodynia ,Neurology ,Anesthesia ,Hyperalgesia ,Neuralgia ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
The presence and magnitude of placebo responses is important for the outcome in clinical trials of analgesics. This explorative study aimed at identifying patients and trial-specific factors with impact on this response in randomized, controlled, cross-over trials in peripheral neuropathic pain. Data were derived from 7 trials and included observations on pinprick hyperalgesia, allodynia, and pain on repetitive stimulation. The studies were all performed by the same collaboration group in Denmark. Pain was rated daily using numeric 0 to 10 point rating scales (NRS) and placebo response was calculated as the difference in weekly average or median numeric rating scale from baseline to the last week of treatment. A clinically meaningful placebo response was defined as more than 30% reduction of pain on placebo. In 318 individual observations, the response was on average small (0.17 points, range -4.5 to 6). There was no significant impact on size of placebo response of trial-specific factors such as treatment sequence and chance of having placebo treatment in each period or of the patient-specific factors age, sensory signs, and pain symptoms. The findings were similar in patients having placebo in the first treatment period. There was no marked difference between patients with (n = 43) and without (n = 275) a clinically meaningful placebo response with respect to the patient-specific factors including frequency of sensory signs and symptoms. In conclusion, this study on cross-over trials in peripheral neuropathic pain found no robust impact of trial and patient-specific factors on the placebo response.
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- 2020
21. Quality of life in chronic inflammatory demyelinating polyneuropathy patients treated with subcutaneous immunoglobulin
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Henning Andersen, Søren H. Sindrup, Lars Kjøbsted Markvardsen, Ali Al-Zuhairy, and Anne Kathrine Ryltoft
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Male ,Chronic inflammatory demyelinating polyneuropathy ,Impaired gait ,Subcutaneous immunoglobulin ,Disability Evaluation ,chronic inflammatory demyelinating polyneuropathy ,0302 clinical medicine ,Quality of life ,030212 general & internal medicine ,Aged, 80 and over ,MMN ,VALUES ,General Medicine ,Middle Aged ,humanities ,Treatment Outcome ,Neurology ,Female ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/psychology ,Adult ,medicine.medical_specialty ,Visual analogue scale ,Injections, Subcutaneous ,Disease duration ,Gait Disorders, Neurologic/etiology ,Immunoglobulins ,CIDP ,subcutaneous immunoglobulin ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Effective treatment ,Muscle Strength ,Immunoglobulins/administration & dosage ,Gait Disorders, Neurologic ,Aged ,business.industry ,Immunization, Passive ,medicine.disease ,Gait ,Immunization, Passive/methods ,Cross-Sectional Studies ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,quality of life ,Quality of Life ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background: Subcutaneous immunoglobulin (SCIG) is effective treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). Quality of life (QoL) increases following switch from intravenous administration to SCIG, but its correlation with clinical functioning is sparsely studied. Aims of the study: The aim of this study is to evaluate the correlation between QoL and clinical functioning in CIDP patients treated with SCIG. Methods: Danish patients with CIDP with a disease duration
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- 2020
22. Statin therapy and risk of polyneuropathy in type 2 diabetes:A danish cohort study
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Søren H. Sindrup, Troels S. Jensen, Diana Hedevang Christensen, Frederik P. Kristensen, Henrik Toft Sørensen, Reimar W. Thomsen, Leif Østergaard, Søren Tang Knudsen, Johnny Kahlert, Brian C. Callaghan, Henning Andersen, and Eva L. Feldman
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Adult ,Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Denmark ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Risk Factors ,Interquartile range ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Propensity Score ,Aged ,Proportional Hazards Models ,Advanced and Specialized Nursing ,business.industry ,Incidence ,Hazard ratio ,Middle Aged ,medicine.disease ,Diabetes Mellitus, Type 2 ,Cohort ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Polyneuropathy ,Cohort study - Abstract
OBJECTIVE Statins may reduce the risk of diabetic polyneuropathy (DPN) as a result of lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy affects the risk of DPN. RESEARCH DESIGN AND METHODS We identified all Danish patients with incident type 2 diabetes during 2002–2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after their first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. RESULTS The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) nonusers; median follow-up time was 6.2 years (interquartile range 3.4–9.6). The incidence rate of DPN events per 1,000 person-years was similar in new users (4.0 [95% CI 3.8–4.2]), prevalent users (3.8 [3.6–3.9]), and nonusers (3.8 [3.7–4.0]). The aHR for DPN was 1.05 (0.98–1.11) in new users and 0.97 (0.91–1.04) in prevalent users compared with statin nonusers. New users had a slightly increased DPN risk during the first year (1.31 [1.12–1.53]), which vanished after >2 years of follow-up. Findings were similar in on-treatment and propensity score–matched analyses and with additional adjustment for pretreatment blood lipid levels. CONCLUSIONS Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.
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- 2020
23. Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex
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Janne Gierthmühlen, Søren H. Sindrup, Sigrid Schuh-Hofer, Ralf Baron, Maija Haanpää, Per Hansson, Nanna B. Finnerup, Harriet I. Kemp, Thomas R. Tölle, Christoph Maier, Romà Solà, Rainer Freynhagen, Donna Kennedy, Ann Sofie Leffler, Jan Vollert, Jordi Serra, Märta Segerdahl, Esther M. Pogatzki-Zahn, Christine H Meyer-Frießem, Didier Bouhassira, Nadine Attal, Rolf-Detlef Treede, Troels S. Jensen, Andrew S.C. Rice, Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Innovative Medicines Initiative, IMI: 115007 Research School, Ruhr University Bochum, RS, RUB Syddansk Universitet, SDU Universität Ulm, UULM Albert-Ludwigs-Universität Freiburg Bundesministerium für Bildung und Frauen, BMBF: 01EM0902 Karolinska Institutet, KI, The IMI EUROPAIN project has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115007. The NEUROPAIN project was supported by an independent investigator-initiated research grant from Pfizer Ltd. German Research Network on Neuropathic pain (DFNS) is supported by the German Ministry of Education and Research (BMBF, Grant No. 01EM0902). The IMI EUROPAIN project is a public-private partnership/ EU-Project for understanding chronic pain and improving its treatment. The NEUROPAIN project for the characterization of subgroups of patients with neuropathic pain is an investigator-initiated European multicentre study with Prof. Dr. R. Baron as principle investigator and ten co-investigator sites. Data for these consortia was collected at the following sites: Johannes Gutenberg-University, Mainz, Germany, University of Schleswig-Holstein, Kiel, Germany, Ruhr University Bochum, Germany, Technical University Munich, Germany, Ludwig-Maximilians-University, Munich, Germany, University of T?bingen, Germany, University of Freiburg, Germany, University of Ulm, Germany, University of Erlangen, Germany, Benedictus Hospital Tutzing, Germany, Aarhus University, Denmark, University of Southern Denmark, Odense, Denmark, Karolinska Institute, Stockholm, Sweden, Imperial College London, UK, Neuroscience Technologies, Barcelona, Spain., Department of Diagnostics and Therapeutics, Clinicum, and Helsinki University Hospital Area
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Male ,Pain Threshold ,HYPERALGESIA ,medicine.medical_specialty ,QUESTIONNAIRE ,Disease ,ANALGESIA ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clinical significance ,TOLERANCE ,030212 general & internal medicine ,Pain Measurement ,DFNS ,PERCEPTION ,business.industry ,Chronic pain ,PAINDETECT ,3126 Surgery, anesthesiology, intensive care, radiology ,16. Peace & justice ,medicine.disease ,EXPERIMENTER GENDER ,PREVALENCE ,Reflex Sympathetic Dystrophy ,Anesthesiology and Pain Medicine ,Complex regional pain syndrome ,GERMAN RESEARCH NETWORK ,Neuropathic pain ,Etiology ,Neuralgia ,Female ,Body region ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,business ,Polyneuropathy ,Complex Regional Pain Syndromes ,030217 neurology & neurosurgery - Abstract
International audience; Background and Aims: Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers. Methods: QST data of 1,252 patients (669 female, 583 male) with PNI (n = 342), PNP (n = 571) or CRPS (n = 339), and average pain intensity reports from previously published studies were included. Absolute and z-values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects. Results: Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (p
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- 2020
24. Statin use and peripheral nerve function-A prospective follow-up study
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Søren Bak, David Gaist, Toke de Koning Svendsen, Thomas Krøigård, Henrik Daa Schrøder, Søren H. Sindrup, Martin Wirenfeldt, Jesper Hallas, and Sören Möller
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Adult ,Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Biopsy ,Neural Conduction ,Toxicology ,030226 pharmacology & pharmacy ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Nerve Fibers ,Statistical significance ,Internal medicine ,Post-hoc analysis ,medicine ,Humans ,Prospective Studies ,Adverse effect ,Aged ,Skin ,Pharmacology ,business.industry ,Peripheral Nervous System Diseases ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Peripheral neuropathy ,Female ,medicine.symptom ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,Cohort study ,Follow-Up Studies - Abstract
PURPOSE: To examine the association between use of statins and risk of deterioration of peripheral nerve function.METHODS: We prospectively followed patients who initiated statin treatment and compared them with statin never-users (non-users). At the time of inclusion and at 1-year follow-up, participants underwent tests for peripheral nerve function (ie nerve conduction studies, quantitative sensory testing), skin biopsies and ratings of symptoms and signs of neuropathy. We selected five tests of nerve function and the intraepidermal nerve fibre density (IENFD) a priori as primary outcomes. We used linear regression to test for differences between statin users and non-users with Holm-Bonferroni-corrected statistical significance level of .05.RESULTS: Comparisons were based on 57 statin users and 46 non-users. Changes in nerve function test results during follow-up were not uniform with regard to direction and were statistically not significant with the exception of IENFD (change in IENFD: statin users 1 fibre/mm vs. non-statin users -2 fibres/mm; P-value = .006). None of the participants developed overt peripheral neuropathy. However, five statin users developed neuropathy-like symptoms and a post hoc analysis showed a significant decrease in vibration sensitivity compared to asymptomatic statin users.CONCLUSION: Statin use was not clearly associated with increased risk of deterioration of peripheral nerve function analysed at a group level. However, given the sample size limitations of our study and the findings of our post hoc analysis, we cannot preclude that peripheral nerve function may be affected in some individuals exposed to statins.
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- 2020
25. Diabetic polyneuropathy and pain, prevalence, and patient characteristics:a cross-sectional questionnaire study of 5,514 patients with recently diagnosed type 2 diabetes
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Troels S. Jensen, Jens Steen Nielsen, Brian C. Callaghan, Reimar W. Thomsen, Søren H. Sindrup, Alexander Gramm Kristensen, Diana Hedevang Christensen, Niels Trolle Andersen, Nanna B. Finnerup, Henning Andersen, Mustapha Itani, Sandra Sif Gylfadottir, Karolina Snopek Khan, and Sia Kromann Nicolaisen
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Male ,Cross-sectional study ,Type 2 diabetes ,PHENOTYPE ,Neuropathic pain ,Cohort Studies ,0302 clinical medicine ,Diabetic Neuropathies ,030202 anesthesiology ,QUALITY-OF-LIFE ,Surveys and Questionnaires ,Prevalence ,Medicine ,EPIDEMIOLOGY ,Depression (differential diagnoses) ,POPULATION ,Pain Measurement ,2. Zero hunger ,COMPLICATIONS ,Patient characteristics ,Middle Aged ,Painful diabetic polyneuropathy ,DEPRESSION ,3. Good health ,Neurology ,Female ,Mental health ,EMOTIONAL DISTRESS ,Polyneuropathy ,Research Paper ,Cohort study ,Quality of life ,medicine.medical_specialty ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,Humans ,Aged ,business.industry ,Odds ratio ,medicine.disease ,Cross-Sectional Studies ,Anesthesiology and Pain Medicine ,Diabetes Mellitus, Type 2 ,RISK-FACTORS ,Neuralgia ,Neurology (clinical) ,business ,Body mass index ,030217 neurology & neurosurgery ,PERIPHERAL NEUROPATHY - Abstract
Supplemental Digital Content is Available in the Text. Diabetic polyneuropathy and painful diabetic polyneuropathy are frequent in early type 2 diabetes, associated with modifiable risk factors, and have major impact on mental health., Most studies of diabetic polyneuropathy (DPN) and painful DPN are conducted in persons with longstanding diabetes. This cross-sectional study aimed to estimate the prevalence of DPN and painful DPN, important risk factors, and the association with mental health in recently diagnosed type 2 diabetes. A total of 5514 (82%) patients (median diabetes duration 4.6 years) enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes cohort responded to a detailed questionnaire on neuropathy and pain. A score ≥4 on the MNSI questionnaire determined possible DPN, whereas pain presence in both feet together with a score ≥3 on the DN4 questionnaire determined possible painful DPN. The prevalence of possible DPN and possible painful DPN was 18% and 10%, respectively. Female sex, age, diabetes duration, body mass index, and smoking were associated with possible DPN, whereas only smoking showed a clear association with possible painful DPN (odds ratio 1.52 [95% confidence interval: 1.20-1.93]). Possible DPN and painful DPN were independently and additively associated with lower quality of life, poorer sleep, and symptoms of depression and anxiety. Possible DPN itself had greater impact on mental health than neuropathic pain. This large study emphasizes the importance of careful screening for DPN and pain early in the course of type 2 diabetes.
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- 2020
26. Small and large fiber sensory polyneuropathy in type 2 diabetes:Influence of diagnostic criteria on neuropathy subtypes
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Alexander Gramm Kristensen, Jens Steen Nielsen, Hatice Tankisi, Thomas Krøigård, Troels S. Jensen, Nanna B. Finnerup, Henning Andersen, Sandra Sif Gylfadottir, Mustapha Itani, Páll Karlsson, Sören Möller, Reimar W. Thomsen, Søren H. Sindrup, and Diana Hedevang Christensen
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Adult ,medicine.medical_specialty ,mixed fiber neuropathy ,small fiber neuropathy ,type 2 diabetes mellitus ,Denmark ,Small Fiber Neuropathy ,Sensory polyneuropathy ,Diagnostic Techniques, Neurological ,Type 2 diabetes ,Severity of Illness Index ,Gastroenterology ,Polyneuropathies ,03 medical and health sciences ,0302 clinical medicine ,diabetic polyneuropathy ,Diabetic Neuropathies ,Diabetic polyneuropathy ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,business.industry ,General Neuroscience ,Type 2 Diabetes Mellitus ,medicine.disease ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Cohort ,Neurology (clinical) ,business ,Polyneuropathy ,large fiber neuropathy ,030217 neurology & neurosurgery - Abstract
BACKGROUND AND AIMS: Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN) and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN.METHODS: This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models.RESULTS: A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4 to 13.1% for SFN, 9.3 to 21.5% for LFN, 51.4 to 83.2% for MFN, and 0.5 to 14.5% for non-classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6 to 13.5% for SFN, 5.6 to 20.6% for LFN, 61.9 to 89.7% for MFN, and 0.0 to 6.3% for NCN.INTERPRETATION: The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose. This article is protected by copyright. All rights reserved.
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- 2020
27. Pediatric Guillain-Barré Syndrome in a 30-Year Nationwide Cohort
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Diana Hedevang Christensen, Henning Andersen, Søren H. Sindrup, Lars Kjøbsted Markvardsen, Reimar W. Thomsen, and Lotte Sahin Levison
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Population ,Pediatric GBS ,Guillain-Barre Syndrome ,Danish ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,immune system diseases ,Risk Factors ,030225 pediatrics ,Medicine ,Humans ,Registries ,education ,Child ,Paresis ,Retrospective Studies ,education.field_of_study ,GBS characteristics ,Guillain-Barre syndrome ,business.industry ,GBS epidemiology ,Incidence (epidemiology) ,Medical record ,Incidence ,Infant ,Reproducibility of Results ,medicine.disease ,language.human_language ,nervous system diseases ,Neurology ,GBS risk factors ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,language ,GBS validation ,Female ,Neurology (clinical) ,Diagnosis code ,medicine.symptom ,business ,GBS incidence ,030217 neurology & neurosurgery - Abstract
Background Guillain-Barre syndrome is the most common cause of acute flaccid paresis in childhood. Few validated large-scale population-based data are available concerning pediatric Guillain-Barre syndrome, including incidence, risk factors, and initial clinical characteristics. Methods In the Danish National Patient Registry, we identified all children aged below 16 years (N = 212) diagnosed with Guillain-Barre syndrome and admitted to any Danish department of pediatrics between 1987 and 2016. A total of 145 (68%) medical files could be retrieved and reviewed, enabling classification of patients with true Guillain-Barre syndrome. The nationwide Guillain-Barre syndrome incidence rate was calculated and stratified by age, gender, time periods, and season. Risk factors and initial Guillain-Barre syndrome characteristics were assessed by medical record review. Results The positive predictive value of Guillain-Barre syndrome diagnosis codes was 86%. The crude Guillain-Barre syndrome incidence rate was 0.69 per 100,000 person years and peaked at two years of age. The incidence rate was higher among men (0.80) than women (0.58) and was relatively stable over the 30-year period. No seasonal difference of the incidence rate was found. Of the 125 Guillain-Barre syndrome cases, 63% were preceded by infection, whereas none were preceded by surgery or malignant disease. Medically treated pain was documented in 70%, mainly confined to the lower extremities. Conclusions Pediatric Guillain-Barre syndrome diagnoses in the Danish National Patient Registry have high validity, the incidence peaks at age two years, and is preceded by infection in two-thirds of children. Lower extremity pain is a common clinical presentation in the acute setting.
- Published
- 2019
28. Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial
- Author
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Jakob Vormstrup Holbech, Melissa S Kreutzfeldt, Flemming W. Bach, Malin E. Carmland, Niels Trolle Andersen, Søren H. Sindrup, Nanna B. Finnerup, and Troels S. Jensen
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Lacosamide ,Denmark ,Population ,Medicine (miscellaneous) ,Neuropathic pain ,Placebo ,law.invention ,Study Protocol ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,Quality of life ,law ,Internal medicine ,Humans ,Multicenter Studies as Topic ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,education ,Pain Measurement ,Randomized Controlled Trials as Topic ,Voltage-Gated Sodium Channel Blockers ,lcsh:R5-920 ,Analgesics ,education.field_of_study ,Sleep disorder ,business.industry ,Precision medicine ,medicine.disease ,Treatment Outcome ,Neuralgia ,Anxiety ,Female ,medicine.symptom ,lcsh:Medicine (General) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response. Methods This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients’ daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety. Discussion We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain. Trial registration ClinicalTrials.gov, NCT03777956. Registered on 18 December 2018.
- Published
- 2019
29. Long-term follow-up of facilitated subcutaneous immunoglobulin therapy in multifocal motor neuropathy
- Author
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Søren H. Sindrup, Ali Al-Zuhairy, and Johannes Jakobsen
- Subjects
Peripheral neuropathy ,Multifocal motor neuropathy ,Mismatch negativity ,Isometric exercise ,Immunoglobulin G ,law.invention ,Polyneuropathies ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Maintenance therapy ,Randomized controlled trial ,law ,Immunoglobulin ,medicine ,Humans ,030212 general & internal medicine ,Aged ,biology ,business.industry ,Immunization, Passive ,Immunoglobulins, Intravenous ,Middle Aged ,medicine.disease ,Clinical long-term study ,Facilitated subcutaneous immunoglobulin ,Treatment ,Treatment Outcome ,Neurology ,Anesthesia ,Quality of Life ,biology.protein ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Objective: To assess the feasibility, efficacy and patient satisfaction of long-term facilitated subcutaneous immunoglobulin therapy (fSCIG) in multifocal motor neuropathy (MMN). Methods: Twelve patients previously participating in a randomized trial investigating the short-term efficacy of fSCIG were offered to switch to fSCIG maintenance therapy following a variable interval on conventional subcutaneous immunoglobulin. Results: Eight patients were switched to fSCIG maintenance therapy, seven of whom were invited for a follow-up assessment after 18 months (range 13–23 months) of treatment. The age at follow-up was 57 years (range 45–70 years) and patients received a median weekly dose immunoglobulin G of 32.5 g (range 20.0–50.0 g), the dose being unaltered compared to baseline values following completion of the fSCIG trial. In five patients the infusion was biweekly, whereas two patients were infused weekly. The follow-up mean isometric strength normalized to pre-trial values was 107.7% (95% CI 86.4–129.0%) being non-inferior to baseline values (104.7%, 95% CI 97.6–111.8%, P = 0.015). The mean ODSS was 2.0 (95% CI 0.8–3.2) which is identical to the baseline score following completion of the fSCIG trial, the P-value for non-inferiority being
- Published
- 2021
30. The six-spot-step test - a new method for monitoring walking ability in patients with chronic inflammatory polyneuropathy
- Author
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Søren H. Sindrup, Mads Ravnborg, Melissa S Kreutzfeldt, Lars Høj Markvardsen, Henrik Boye Jensen, and Henning Andersen
- Subjects
medicine.medical_specialty ,business.industry ,General Neuroscience ,medicine.disease ,CHRONIC INFLAMMATORY POLYNEUROPATHY ,Walking time ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Floor effect ,Step test ,Physical therapy ,Medicine ,In patient ,030212 general & internal medicine ,Neurology (clinical) ,Analysis of variance ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,After treatment - Abstract
The aim of this study was to evaluate whether the six-spot-step test (SSST) is more suitable for monitoring walking ability in patients with chronic inflammatory polyneuropathy than the timed 25-foot-walking test (T25FW). In the SSST, participants have to walk as quickly as possible across a field measuring 1 × 5 m, while kicking blocks out of five circles on the floor. Sixty-two patients and 61 controls performed the SSST and T25FW. Patients also performed the overall disability sumscore, INCAT sensory sumscore, Medical Research Council sumscore, and 9-hole-peg-test. Twenty-one patients treated with intravenous immunoglobulin (IVIG) every 4-6 weeks were tested prior to and 2-3 weeks after treatment and judged change in their own clinical condition using the patient global impression of change (PGIC) scale. In patients, SSST ranged from 5.7 to 26.8 s and T25FW ranged from 3.6 to 12.9 s. Intra-class correlation between repeated tests was 0.97 for SSST and 0.95 for T25FW. Correlation with the additional tests was stronger for SSST than T25FW. In IVIG-treated patients, the mean change in walking time was -2.3 s for SSST and -0.6 s for T25FW. The SSST showed larger responsiveness in terms of effect size, standardized response means, and relative efficiency. Both ambulation tests correlated moderately to PGIC. The SSST may be superior to the T25FW in terms of dynamic range, floor effect, and responsiveness which makes the SSST a possible alternative for monitoring walking ability in patients with chronic inflammatory polyneuropathy.
- Published
- 2017
31. Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy
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Søren H. Sindrup, Flemming W. Bach, Troels S. Jensen, Jakob Vormstrup Holbech, Dyveke Torgaard Demant, and Nanna B. Finnerup
- Subjects
Adult ,Male ,0301 basic medicine ,Imipramine ,Time Factors ,Pregabalin ,Oxcarbazepine ,Venlafaxine ,law.invention ,Efficacy ,Polyneuropathies ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Randomized controlled trial ,law ,Journal Article ,medicine ,Humans ,Escitalopram ,Aged ,Retrospective Studies ,business.industry ,Venlafaxine Hydrochloride ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Carbamazepine ,030104 developmental biology ,Anesthesiology and Pain Medicine ,Anesthesia ,Neuropathic pain ,Neuralgia ,Anticonvulsants ,Female ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for.Methods: Data from 4 published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy were analysed. The studies had a crossover design, and had nearly similar outcome recordings as well as a thorough baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed.Results: Diabetes as etiology of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years.Conclusion: Despite the small sample size and limited number of drugs included this study suggests that diabetic etiology of polyneuropathy may impact on the efficacy of anticonvulsants, and duration of neuropathic pain may impact on the efficacy of antidepressants.Significance: This study found that duration of pain appears to have an impact on the effect of antidepressants in neuropathic pain and that diabetes as etiology for painful polyneuropathy appears to influence pain relief obtained with anticonvulsants.
- Published
- 2017
32. Statins and polyneuropathy revisited: case-control study in Denmark, 1999-2013
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Toke de Koning Svendsen, Søren H. Sindrup, Luis A. García Rodríguez, Jesper Hallas, David Gaist, Lene Andersen, and Peter Nørregaard Hansen
- Subjects
Pharmacology ,Pediatrics ,medicine.medical_specialty ,education.field_of_study ,Statin ,business.industry ,medicine.drug_class ,Medical record ,Population ,Case-control study ,Odds ratio ,medicine.disease ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,education ,business ,Polyneuropathy ,030217 neurology & neurosurgery - Abstract
Aim In a previous study, we found a positive association between statin use and polyneuropathy risk. Other studies reported equivocal results. The present study aimed to confirm our findings with a design similar to that used in our previous study but with a larger data set. Methods We searched medical registry data to identify patients diagnosed with incident polyneuropathy of no known cause (idiopathic polyneuropathy) between 1999 and 2013; we verified diagnoses through medical records. For each case, we recruited 20 general population controls with no previous history of polyneuropathy. Controls were matched to their respective case for age and gender. We ascertained the prior statin use of cases and controls through a prescription registry. Based on this information, exposure to statins was categorized into ‘ever use’ or ‘never use’. Ever use of statins was classified by how recently they had been used (‘current use’ or ‘past use’); current use was further classified into long-term use (5+ years) and high- or low-intensity use. We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to examine associations between polyneuropathy and statin use. Results We included 370 validated cases and 7400 controls. Ever use of statins was not associated with an elevated risk of polyneuropathy (OR 1.14, 95% CI 0.84, 1.54). Similarly, we found no associations between polyneuropathy risk and current use (OR 1.11, 95% CI 0.79, 1.53), long-term use (OR 1.13, 95% CI 0.66, 1.92) or high-intensity statin use (OR 1.05, 95% CI 0.59, 1.84). Conclusion Statin use was not associated with an increased risk of idiopathic polyneuropathy.
- Published
- 2017
33. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy: randomized controlled trial study
- Author
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Johannes Jakobsen, Henning Andersen, Danish Cidp, Ingelise Christiansen, Niels Kjær Olsen, Lars Høj Markvardsen, and Søren H. Sindrup
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Immunoglobulins ,Chronic inflammatory demyelinating polyneuropathy ,Subcutaneous immunoglobulin ,Infusions, Subcutaneous ,Immunoglobulin G ,law.invention ,Therapy naive ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,First line therapy ,Randomized controlled trial ,law ,medicine ,Humans ,Single-Blind Method ,Muscle Strength ,Aged ,Cross-Over Studies ,biology ,business.industry ,Immunoglobulins, Intravenous ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,030104 developmental biology ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Neurology ,Anesthesia ,Muscle strength ,biology.protein ,Female ,Neurology (clinical) ,business ,Polyneuropathy ,030217 neurology & neurosurgery - Abstract
BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP.METHODS: Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests.RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related.CONCLUSION: In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment.
- Published
- 2016
34. Guillain-Barré syndrome in Denmark: validation of diagnostic codes and a population-based nationwide study of the incidence in a 30-year period
- Author
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Søren H. Sindrup, Henning Andersen, Reimar W. Thomsen, Lotte Sahin Levison, Diana Hedevang Christensen, and Thomas Mellemkjær
- Subjects
Pediatrics ,medicine.medical_specialty ,Guillain-Barre syndrome ,Epidemiology ,business.industry ,Incidence (epidemiology) ,030204 cardiovascular system & hematology ,medicine.disease ,language.human_language ,Confidence interval ,Danish ,03 medical and health sciences ,0302 clinical medicine ,language ,Medicine ,Clinical Epidemiology ,030212 general & internal medicine ,Diagnosis code ,Young adult ,business ,Stroke - Abstract
Lotte Sahin Levison,1 Reimar Wernich Thomsen,2 Diana Hedevang Christensen,2 Thomas Mellemkjær,1 Søren Hein Sindrup,3 Henning Andersen11Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Neurology, Odense University Hospital, Odense, DenmarkPurpose: To validate the diagnostic codes for Guillain-Barré syndrome (GBS) in the Danish National Patient Registry (DNPR). Secondly, to examine 30-year trends in the incidence of GBS in Denmark.Patients and methods: We used the DNPR to identify all patients aged 16 and above diagnosed with a primary GBS diagnosis at any Danish department of neurology between 1987 and 2016. Medical files were reviewed according to the clinical criteria of the National Institute of Neurological Disorders and Stroke Committee and classified according to the Brighton criteria. The incidence rate (IR) was calculated based on data from 1987 to 2016 and stratified by season, gender, and age.Results: Over 30 years, we identified 2,319 patients aged 16 and above in the DNPR. From a validation cohort of 573 patients, we were able to retrieve 425 (74.2%) medical files; 356 GBS diagnoses were confirmed. The overall positive predictive value was 83.8% (95% confidence interval (CI): 80.0–87.0). In 99% of the confirmed patients, the Brighton criteria level 1–3 for GBS were met. The IR was fairly stable over 30 years at 1.77 per 100,000 person years (95% CI: 1.70–1.84). The incidence was higher in the winter season (IR ratio compared with summer: 1.18 (95% CI: 1.09–1.29)), and was strongly associated with male gender (IR ratio vs females: 1.44 (95% CI: 1.33–1.57)). IRs rose with age at diagnosis, particularly after the age of 50 in both men and women and a minor peak was observed for total IR in young adults.Conclusion: Primary diagnostic codes for GBS at Danish departments of neurology have high validity. The DNPR is a well-suited data source for epidemiological research on GBS. The Danish nationwide 30-year GBS IR is stable over time and similar to GBS IRs reported in other European and North American populations.Keywords: registries, positive predictive value, international classification of disease codes, epidemiology
- Published
- 2019
35. Detection of early motor involvement in diabetic polyneuropathy using a novel MUNE method – MScanFit MUNE
- Author
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Alexander Gramm Kristensen, Søren H. Sindrup, Hatice Tankisi, Sif Gylfadottir, Nanna B. Finnerup, Hugh Bostock, Troels S. Jensen, Thomas Krøigård, Henning Andersen, and Mustapha Itani
- Subjects
Adult ,Male ,Recruitment, Neurophysiological ,Mscan ,medicine.medical_specialty ,Diabetic polyneuropathy ,Diabetic neuropathy ,Neural Conduction ,Urology ,Action Potentials ,behavioral disciplines and activities ,050105 experimental psychology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Motor involvement ,Physiology (medical) ,mental disorders ,medicine ,Humans ,0501 psychology and cognitive sciences ,In patient ,Muscle, Skeletal ,CMAP amplitude ,Aged ,Aged, 80 and over ,Motor Neurons ,business.industry ,05 social sciences ,Healthy subjects ,Mean age ,MScanFit MUNE ,Middle Aged ,medicine.disease ,Sensory Systems ,Median nerve ,Motor unit ,Diabetes Mellitus, Type 2 ,Neurology ,Female ,Neurology (clinical) ,Nerve conduction studies ,Abnormality ,business ,DPN ,030217 neurology & neurosurgery - Abstract
Hospital Aim To examine whether a novel MUNE method so called MScanFit MUNE (MScan) can detect early motor involvement in diabetic polyneuropathy (DPN). Methods In this study, 100 patients with diabetes mellitus type II will be prospectively included as a part of International Diabetic Neuropathy Consortium (IDNC) project. Preliminary results of 24 patients (18 males, 6 females, mean age: 63, range: (44–74) will be presented here. Nerve conduction studies (NCS) of three motor (median, peroneal, tibial) and three sensory (bilateral sural and median) nerves and MScan in abductor pollicis brevis (APB) muscle were done in all patients.NCS results were compared to laboratory controls. MScan results were compared to 20 age-matched healthy subjects. Results From NCSs, DPN was classified by Dyck’s criteria. Six of 24 patients (25%) had DPN while 18 patients had normal NCS. None of the 24 patients had decreased CMAP amplitude of median nerve. MScan was abnormal in eight of 24 patients (33%). Of these eight, two patients had DPN and six had normal NCS. Discussion Normal MScan in patients with DPN may be due to length dependent feature of DPN, thereby unaffected upper extremities as these patients had slight sensory neuropathy. However, MScan could detect abnormality in nerves with normal CMAP amplitude and normal NCS. Conclusion MScan may improve electrodiagnosis of DPN by detection of early motor involvement and motor unit loss. Significance MScan is a promising novel method which may be useful in quantifying motor unit loss in different neuromuscular disorders including DPN.
- Published
- 2019
36. Guillain-Barre syndrome in Denmark: a population-based study on epidemiology, diagnosis and clinical severity
- Author
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Henning Andersen, Bart C. Jacobs, Thomas Harbo, Søren H. Sindrup, Charlotte Dornonville de la Cour, L. L. Lassen, Helle Al-Hakem, Bianca van den Berg, Neurology, and Immunology
- Subjects
Adult ,medicine.medical_specialty ,Pediatrics ,Neurology ,Epidemiology ,Denmark ,Population ,Guillain-Barre Syndrome ,Severity of Illness Index ,Guillain–Barré syndrome ,Danish ,03 medical and health sciences ,0302 clinical medicine ,International GBS outcome study ,medicine ,Humans ,030212 general & internal medicine ,education ,Stroke ,Neuroradiology ,Aged ,education.field_of_study ,Guillain-Barre syndrome ,business.industry ,Incidence ,Middle Aged ,medicine.disease ,language.human_language ,Cohort ,language ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Brighton criteria ,IGOS - Abstract
OBJECTIVES: To describe the epidemiology and clinical heterogeneity of Guillain-Barré syndrome (GBS) in Denmark and to compare a population-based cohort to prospectively included patients in the International GBS Outcome Study (IGOS).METHODS: The incidence rate (IR) of GBS in Denmark from September 2012 to December 2015, applying the National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria, was estimated and the level of diagnostic certainty was described with the Brighton criteria. All cases registered with a diagnosis of GBS or other inflammatory neuropathies in the Danish National Hospital Registry were reviewed for diagnostic criteria and for information on treatment and clinical course.RESULTS: A total of 299 GBS cases were confirmed, corresponding to a crude IR of 1.59 (95% CI 1.42-1.78) per 100,000 per year. The Brighton criteria level 1-3 of diagnostic certainty was met in 279 (93%) of the patients. Thirty-five percent of the patients were mildly affected (GBS disability score CONCLUSION: The epidemiology and full clinical spectrum of GBS are described in a population-based study. This includes a larger proportion of milder cases that are underrepresented in prospective cohorts such as IGOS.
- Published
- 2019
37. Randomized trial of facilitated subcutaneous immunoglobulin in multifocal motor neuropathy
- Author
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Søren H. Sindrup, Henning Andersen, Johannes Jakobsen, Lars Kjøbsted Markvardsen, and Ali Al-Zuhairy
- Subjects
Adult ,Male ,medicine.medical_specialty ,peripheral neuropathy ,Dose ,Visual analogue scale ,multifocal motor neuropathy ,Immunoglobulins ,Isometric exercise ,Infusions, Subcutaneous ,Gastroenterology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,clinical trials randomized controlled ,Hyaluronidase ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Motor Neuron Disease ,Aged ,Cross-Over Studies ,treatment ,business.industry ,Immunization, Passive ,Peripheral Nervous System Diseases ,Middle Aged ,medicine.disease ,Confidence interval ,Treatment Outcome ,Peripheral neuropathy ,Neurology ,Patient Satisfaction ,Quality of Life ,Female ,Immunotherapy ,Neurology (clinical) ,business ,immunoglobulin ,030217 neurology & neurosurgery ,medicine.drug ,Multifocal motor neuropathy - Abstract
Background and purpose: To optimize subcutaneous therapy with immunoglobulins, large volume infusion of immunoglobulin G facilitated by pretreatment with hyaluronidase (fSCIG) was compared to conventional infusion of multiple small dosages (cSCIG) in 20 patients with multifocal motor neuropathy. Methods: A randomized, non-inferiority and observer-blinded cross-over design was applied with a treatment period of 24 weeks for each therapy. Results: In 18 patients fSCIG was feasible, two patients leaving the study due to side-effects. The primary study variable, isometric strength, was unchanged, being 100.8% [95% confidence interval (CI) 94.8%–107.1%) in fSCIG and 105.9% (95% CI 99.8%–112.0%) in cSCIG. Secondary end-points of disability, functions, impairments and quality of life showed no differences between the two treatments. Mild and short-lasting generalized side-effects were similar in the two groups, whereas the relative frequency of localized side-effects at the injection site was increased after fSCIG [0.63 (95% CI 0.23–1.00) vs. 0.09 (95% CI 0.00–0.22), P = 0.005]. The preference of the patients favoured fSCIG for two out of five visual analogue scale scores as well as the total mean score of all preferences (P = 0.03). Conclusions: Facilitated SCIG seems effective, feasible and safe. In addition, it is preferred by patients but is accompanied by a higher frequency of short-lasting localized side-effects.
- Published
- 2019
38. Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs
- Author
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Toke de Koning Svendsen, Søren H. Sindrup, Per Pfeiffer, Martin Wirenfeldt, Camilla Qvortrup, Thomas Krøigård, Henrik Daa Schrøder, and David Gaist
- Subjects
Adult ,Male ,peripheral neuropathy ,medicine.medical_treatment ,Biopsy ,Neural Conduction ,nerve conduction studies ,quantitative sensory testing ,Sural nerve ,Antineoplastic Agents ,Nerve conduction velocity ,03 medical and health sciences ,Polyneuropathies ,0302 clinical medicine ,Nerve Fibers ,Sural Nerve ,Neoplasms ,Sensation ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Skin ,Aged, 80 and over ,Neurologic Examination ,Chemotherapy ,business.industry ,oxaliplatin ,Peripheral Nervous System Diseases ,intraepidermal nerve fibre density ,Middle Aged ,medicine.disease ,Oxaliplatin ,Peripheral ,Peripheral neuropathy ,Neurology ,Anesthesia ,Female ,Neurology (clinical) ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background and purpose: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. Methods: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. Results: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. Conclusions: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.
- Published
- 2018
39. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype
- Author
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Dyveke Torgaard Demant, Karen Lund, Jan Vollert, Søren H. Sindrup, Christoph Maier, Märta Segerdahl, Nanna B. Finnerup, and Troels S. Jensen
- Subjects
Adult ,Male ,Pain Threshold ,Lidocaine ,Pain Threshold/drug effects ,Population ,Placebo ,Young Adult ,Double-Blind Method ,Surveys and Questionnaires ,medicine ,Humans ,Pain phenotype ,Anesthetics, Local ,education ,Aged ,Pain Measurement ,education.field_of_study ,Cross-Over Studies ,Neuralgia/drug therapy ,Postherpetic neuralgia ,business.industry ,Hyperalgesia/physiopathology ,Nociceptors ,Middle Aged ,Nerve injury ,medicine.disease ,Crossover study ,Lidocaine/therapeutic use ,Treatment ,Phenotype ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Neurology ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,Nociceptor ,Peripheral neuropathic pain ,Neuralgia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Anesthetics, Local/therapeutic use ,medicine.drug - Abstract
In neuropathic pain with irritable nociceptor (IN) phenotype, upregulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype panel, crossover study with 4-week treatment periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale, and the primary objective was to compare the effect of lidocaine in patients with and without IN phenotype as defined by hypersensitivity and preserved small-fibre function determined by quantitative sensory testing. Forty-six patients with neuropathic pain due to nerve injury or postherpetic neuralgia were randomised. The modified intention-to-treat population comprised 15 patients with irritable nociceptor and 25 patients with nonirritable nociceptor. In the total sample, lidocaine reduced pain by 0.3 numeric rating scale points (95% confidence interval [CI]: 0.1-0.5) and pain-related sleep disturbance by 0.6 points (95% CI: 0.4-0.8) more than placebo (P=0.007 and P < 0.001) and relieved pain by 0.4 verbal score (-1-5) points more (P=0.036). For these measures, there was no significant interaction between treatment and phenotype, but there was a significant interaction for pain paroxysms (0.8, 95% CI: 0.4-1.2, P < 0.001) and deep aching pain (0.6, 95% CI: 0.1-1.0, P=0.013). In conclusion, lidocaine 5% patch had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with IN phenotype. The lack of significant phenotype differences may be caused by too low statistical power.
- Published
- 2015
40. Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy
- Author
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Ingelise Christiansen, Karen Heje, John Vissing, Søren H. Sindrup, Henning Andersen, Lars Høj Markvardsen, and Kristian Overgaard
- Subjects
Male ,Anaerobic Threshold ,Physiology ,Chronic inflammatory demyelinating polyneuropathy ,Subcutaneous immunoglobulin ,Oxygen Consumption/physiology ,chronic inflammatory demyelinating polyneuropathy ,0302 clinical medicine ,Elbow ,Medicine ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology ,Elbow/physiopathology ,VO2 max ,Middle Aged ,Exercise Therapy ,Treatment Outcome ,Anesthesia ,Female ,aerobic training ,Anaerobic exercise ,medicine.medical_specialty ,subcutaneous immunoglobulin ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Oxygen Consumption ,Physiology (medical) ,Journal Article ,Aerobic exercise ,Humans ,Knee ,Muscle Strength ,Exercise ,Aerobic capacity ,business.industry ,Resistance training ,Immunization, Passive ,Resistance Training ,030229 sport sciences ,medicine.disease ,Exercise Therapy/methods ,Knee/physiopathology ,Bicycling ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,quality of life ,Quality of Life ,Muscle strength ,Physical therapy ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Introduction: We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO 2-max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. Results: VO 2-max and muscle strength were unchanged during run-in (−4.9% ± 10.3%, P = 0.80 and −3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO 2-max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. Discussion: Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57: 70–76, 2018.
- Published
- 2018
41. The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy
- Author
-
Flemming W. Bach, Kim Brøsen, Jakob Vormstrup Holbech, Troels S. Jensen, Søren H. Sindrup, and Nanna B. Finnerup
- Subjects
Male ,Imipramine/blood ,Imipramine ,Peripheral Nervous System Agents/blood ,Pregabalin ,Adrenergic Uptake Inhibitors/blood ,Pharmacology ,Neuropathic pain ,030226 pharmacology & pharmacy ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Pregabalin/blood ,Analgesics/blood ,Medicine ,Neuralgia/blood ,Pain Measurement ,Aged, 80 and over ,Analgesics ,Cross-Over Studies ,Adrenergic Uptake Inhibitors ,Drug Synergism ,Middle Aged ,imipramine ,Dose–response relationship ,Treatment Outcome ,Anesthesia ,pregabalin ,Female ,Drug Therapy, Combination ,Polyneuropathy ,medicine.drug ,Adult ,Combination therapy ,interaction ,Polyneuropathies/blood ,03 medical and health sciences ,Polyneuropathies ,Double-Blind Method ,Journal Article ,Humans ,serum concentrations ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Peripheral Nervous System Agents ,medicine.disease ,Crossover study ,Anesthesiology and Pain Medicine ,Neuralgia ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Objective: The aim of this study was to explore the serum concentration-effect relation for first-line drugs in neuropathic pain and to determine if efficacy could be increased. Methods: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin, and their combination in painful polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0 to 10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. Results: In 47 patients, pain was reduced -1.0 (95% confidence interval [CI], -1.5 to -0.6) by imipramine, -0.4 (95% CI, -0.9 to 0.1) by pregabalin, and -1.6 (95% CI, -2.1 to -1.1) by combination therapy. On monotherapy, there was no difference between responders and nonresponders with respect to concentrations of imipramine (mean, 161 vs. 229 nmol/L, P=0.129) and pregabalin (mean, 9.8 vs. 11.7 μmol/L, P=0.178). There was no correlation between drug concentration and pain reduction for imipramine (r=0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine < or ≥100 nmol/L, pregabalin < or ≥10 μmol/L) either for monotherapy or for combination therapy (P=0.161 to 0.797). Isobolographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction. Discussion: There were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not concluded that treatment can be improved by measurement of drug concentration of pregabalin.
- Published
- 2017
42. Asymptomatic loss of intraepidermal nerve fibers with preserved thermal detection thresholds after repeated exposure to severe cold
- Author
-
Søren H. Sindrup, Toke de Koning Svendsen, Thomas Krøigård, and Martin Wirenfeldt
- Subjects
Cold Temperature/adverse effects ,0301 basic medicine ,Adult ,Male ,Pain Threshold ,medicine.medical_specialty ,Greenland ,nerve conduction studies ,quantitative sensory testing ,Nerve fiber ,healthy subject ,Neurologic Examination/methods ,Asymptomatic ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Nerve Fibers ,cold‐induced peripheral neuropathy ,Threshold of pain ,medicine ,Humans ,Peripheral Nervous System Diseases/diagnosis ,Pain Threshold/physiology ,Subclinical infection ,Skin ,Original Research ,Neurologic Examination ,Hyperhidrosis ,business.industry ,Norway ,Quantitative sensory testing ,Healthy subjects ,Peripheral Nervous System Diseases ,Nerve Fibers/physiology ,medicine.disease ,Dermatology ,Skin/innervation ,Cold Temperature ,030104 developmental biology ,Peripheral neuropathy ,medicine.anatomical_structure ,intraepidermal nerve fiber density ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: Cold-induced peripheral neuropathy has been described in individuals exposed to severe cold resulting in pain, hypersensitivity to cold, hyperhidrosis, numbness, and skin changes. Nerve conduction studies and thermal detection thresholds are abnormal in symptomatic patients, and intraepidermal nerve fiber density (IENFD) in skin biopsies is reduced. Case presentation: A 41-year-old male was included as a healthy subject in a study of the spontaneous variability of quantitative sensory testing (QST), nerve conduction studies (NCS), and IENFD. Unexpectedly, IENFD was significantly reduced, whereas the rest of the examination was normal except for reduced vibration detection threshold. The results were confirmed at follow-up examination. The subject had been repeatedly exposed to severe cold resulting in short lasting numbness and paresthesia while living in the eastern part of Greenland and the northern part of Norway. Conclusion: Loss of intraepidermal nerve fibers caused by exposure to severe cold may be asymptomatic, and their function assessed by thermal detection thresholds may be preserved. This case illustrates that QST and IENFD are complementary tests and that subclinical cold-induced peripheral neuropathy may be prevalent in subjects living in or near polar regions which could have implications for the recruitment of healthy subjects.
- Published
- 2017
43. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: A randomised, double-blind, placebo-controlled phenotype-stratified study
- Author
-
Christoph Maier, Søren H. Sindrup, Nanna B. Finnerup, Märtha Segerdahl, Jan Vollert, Troels S. Jensen, Karen Lund, and Dyveke Torgaard Demant
- Subjects
Adult ,Male ,Population ,Oxcarbazepine ,Pain ,Placebo ,Young Adult ,Double-Blind Method ,Humans ,Medicine ,education ,Aged ,Pain Measurement ,Aged, 80 and over ,Voltage-Gated Sodium Channel Blockers ,education.field_of_study ,Cross-Over Studies ,business.industry ,Postherpetic neuralgia ,Peripheral Nervous System Diseases ,Middle Aged ,medicine.disease ,Carbamazepine ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Neurology ,Anesthesia ,Neuropathic pain ,Nociceptor ,Number needed to treat ,Female ,Neurology (clinical) ,business ,Polyneuropathy ,medicine.drug - Abstract
In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype.
- Published
- 2014
44. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles
- Author
-
Maren Reimer, Jan Vollert, Thomas R. Tölle, Jeffrey D. Kennedy, Rolf-Detlef Treede, Maija Haanpää, Philipp Hüllemann, Märta Segerdahl, Andreas Binder, Søren H. Sindrup, Rainer Freynhagen, Christoph Maier, Nadine Attal, Troels S. Jensen, R. Baron, Didier Bouhassira, Giorgio Cruccu, Nanna B. Finnerup, Tina Mainka, Claudia Sommer, Walter Magerl, Jordi Serra, Per Hansson, Andrew S.C. Rice, Clinicum, Neurokirurgian yksikkö, Department of Neurosciences, HUS Neurocenter, and Universitatsklinikum Schleswig - Holstein
- Subjects
SYSTEMIC LIDOCAINE ,Male ,Diabetic neuropathy ,Databases, Factual ,Epidemiology ,International Cooperation ,Neuropathic pain ,PLACEBO-CONTROLLED TRIAL ,Cohort Studies ,DOUBLE-BLIND ,0302 clinical medicine ,Clinical trials ,Anesthesiology ,Surveys and Questionnaires ,Cluster Analysis ,030212 general & internal medicine ,Sensory signs ,Pain Measurement ,Hyperalgesia/physiopathology ,Sensory loss ,11 Medical And Health Sciences ,Middle Aged ,Databases, Factual/statistics & numerical data ,3. Good health ,Europe ,Neurology ,DIABETIC-NEUROPATHY ,Hyperalgesia ,Anesthesia ,GRADING SYSTEM ,Female ,LONG-TERM POTENTIATION ,medicine.symptom ,Life Sciences & Biomedicine ,Research Paper ,Adult ,Pain Threshold ,NEUROGENIC HYPERALGESIA ,Clinical Neurology ,Sensory system ,Europe/epidemiology ,17 Psychology And Cognitive Sciences ,03 medical and health sciences ,Neuralgia/epidemiology ,Threshold of pain ,medicine ,Humans ,Pain Threshold/physiology ,Aged ,Science & Technology ,CUTANEOUS HYPERALGESIA ,Postherpetic neuralgia ,business.industry ,Neurosciences ,POSTHERPETIC NEURALGIA ,medicine.disease ,3126 Surgery, anesthesiology, intensive care, radiology ,QST ,Anesthesiology and Pain Medicine ,neuropathic pain ,sensory signs ,clinical trials ,qst ,epidemiology ,3121 General medicine, internal medicine and other clinical medicine ,GERMAN RESEARCH NETWORK ,Neuralgia ,Neurology (clinical) ,Neurosciences & Neurology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
More than 1100 patients with neuropathic pain were examined using quantitative sensory testing. Independent of the etiology, 3 subtypes with distinct sensory profiles were identified and replicated., Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.
- Published
- 2016
45. O-27 Sensory and motor nerve excitability testing in type 2 diabetics
- Author
-
Alexander Gramm Kristensen, Søren H. Sindrup, Nanna B. Finnerup, Troels S. Jensen, Hatice Tankisi, Sif Gylfadottir, Thomas Krøigård, Henning Andersen, and Mustapha Itani
- Subjects
medicine.medical_specialty ,Diabetic neuropathy ,business.industry ,Motor nerve ,Threshold tracking ,Sensory system ,medicine.disease ,Sensory Systems ,Median nerve ,Pathophysiology ,Physical medicine and rehabilitation ,Neurology ,Physiology (medical) ,Medicine ,Neurology (clinical) ,Analysis of variance ,business ,Nerve excitability - Abstract
Background Previous studies have proposed the utility of nerve excitability testing (NET) with threshold tracking for understanding disease pathophysiology and early diagnosis of diabetic polyneuropathy (DPN). We aimed in this study to elucidate sensory and motor NET changes in DPN. Materials and methods We included 128 diabetics and 31 healthy controls (HC). All participants were examined with Nerve Conduction Studies (NCS) on three motor (tibial, peroneal and median) and three sensory (sural (bilateral) and median) nerves. Patients were divided into two groups, patients with neuropathy (DPN+) and patients without neuropathy (DPN-) using NCS in lower extremities. Motor and sensory NET and NCS on the median nerve were compared between the groups using 3-way ANOVA. Results Out of 27 NET parameters, 7 motor (including TEd(peak), S2 accommodation, TEd40(Accom)) and 2 sensory parameters(accommodation half-time and TEh(slope 101–140 ms)) were significantly different between groups (p Conclusions Overall, the changes in NET were not as prominent as changes in NCS and not in concord with previously reported excitability changes. This may be because NET measures the function of the surviving axons rather than non-functioning axons. We are therefore uncertain of the utility of NET in diagnostics or understanding the mechanisms of DPN. Part of the International Diabetic Neuropathy Consortium research programme, supported by Novo Nordisk Foundation Challenge Programme (Grant No. NNF14OC0011633 ).
- Published
- 2019
46. The six-spot-step test - a new method for monitoring walking ability in patients with chronic inflammatory polyneuropathy
- Author
-
Melissa, Kreutzfeldt, Henrik B, Jensen, Mads, Ravnborg, Lars H, Markvardsen, Henning, Andersen, and Søren H, Sindrup
- Subjects
Adult ,Aged, 80 and over ,Male ,Analysis of Variance ,Movement Disorders ,Walking ,Middle Aged ,Disability Evaluation ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Outcome Assessment, Health Care ,Exercise Test ,Humans ,Female ,Longitudinal Studies ,Aged - Abstract
The aim of this study was to evaluate whether the six-spot-step test (SSST) is more suitable for monitoring walking ability in patients with chronic inflammatory polyneuropathy than the timed 25-foot-walking test (T25FW). In the SSST, participants have to walk as quickly as possible across a field measuring 1 × 5 m, while kicking blocks out of five circles on the floor. Sixty-two patients and 61 controls performed the SSST and T25FW. Patients also performed the overall disability sumscore, INCAT sensory sumscore, Medical Research Council sumscore, and 9-hole-peg-test. Twenty-one patients treated with intravenous immunoglobulin (IVIG) every 4-6 weeks were tested prior to and 2-3 weeks after treatment and judged change in their own clinical condition using the patient global impression of change (PGIC) scale. In patients, SSST ranged from 5.7 to 26.8 s and T25FW ranged from 3.6 to 12.9 s. Intra-class correlation between repeated tests was 0.97 for SSST and 0.95 for T25FW. Correlation with the additional tests was stronger for SSST than T25FW. In IVIG-treated patients, the mean change in walking time was -2.3 s for SSST and -0.6 s for T25FW. The SSST showed larger responsiveness in terms of effect size, standardized response means, and relative efficiency. Both ambulation tests correlated moderately to PGIC. The SSST may be superior to the T25FW in terms of dynamic range, floor effect, and responsiveness which makes the SSST a possible alternative for monitoring walking ability in patients with chronic inflammatory polyneuropathy.
- Published
- 2016
47. Pain phenotype as a predictor for drug response in painful polyneuropathy-a retrospective analysis of data from controlled clinical trials
- Author
-
Troels S. Jensen, Søren H. Sindrup, Flemming W. Bach, Jakob Vormstrup Holbech, and Nanna B. Finnerup
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pregabalin ,Pharmacology ,Placebo ,Neuropathic pain ,Sensory phenotype ,Antidepressive Agents/therapeutic use ,03 medical and health sciences ,Polyneuropathies ,Young Adult ,0302 clinical medicine ,Internal medicine ,Post-hoc analysis ,medicine ,Humans ,030212 general & internal medicine ,Oxcarbazepine ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pain mechanisms ,Analgesics ,business.industry ,Neuralgia/drug therapy ,Anticonvulsants/therapeutic use ,Polyneuropathies/drug therapy ,Antidepressants ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Clinical trial ,Treatment ,Anesthesiology and Pain Medicine ,Phenotype ,Treatment Outcome ,Neurology ,Analgesics/therapeutic use ,Neuralgia ,Anticonvulsants ,Female ,Neurology (clinical) ,Levetiracetam ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,medicine.drug - Abstract
The drugs available for treatment of neuropathic pain have a somewhat disappointing efficacy with many patients left with limited or no effect. Individualized treatment based on phenotype according to presumed underlying pain mechanism(s) has been proposed to improve outcome. We report a retrospective analysis of phenotype-specific effects of several neuropathic pain drugs, which were studied in a series of cross-over, placebo-controlled, clinical trials. The data originate from 7 trials with similar design and outcome recordings, which all had a thorough baseline registration of symptoms, signs and quantitative sensory testing. The latter was used to phenotype patients into subgroups reflecting presumed pain mechanisms. There were a total of 361 patient records distributed over treatments with 4 antidepressants and 4 anticonvulsants. Five of the drugs reduced total pain significantly compared to placebo. Only a few phenotype-specific differences in total pain reduction were found within the investigated drugs. Thus, imipramine reduced total pain 1.84 (CI: 0.02 to 3.67) and pregabalin 0.81 (CI: -0.67 to 2.29) in patients with than without gain of sensory function. Pregabalin showed a better effect in patients with preserved large fiber function with a mean difference in total pain reduction 1.31 (CI: 0.15 to 2.47). No phenotype-specific effects were found for venlafaxine, escitalopram, oxcarbazepine, valproic acid, levetiracetam or St. john's wort. Thus, this post-hoc analysis of 8 drugs with mainly non-selective actions on neuropathic pain mechanisms found limited usefulness of sensory phenotyping in pain as the basis for individualized treatment.
- Published
- 2016
48. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis
- Author
-
Søren H. Sindrup, Claus Madsen, Jakob Vormstrup Holbech, and Masoud Falah
- Subjects
business.industry ,Multiple sclerosis ,Placebo-controlled study ,Placebo ,medicine.disease ,Crossover study ,law.invention ,Anesthesiology and Pain Medicine ,Randomized controlled trial ,law ,Anesthesia ,Neuropathic pain ,Medicine ,Levetiracetam ,business ,SV2A ,medicine.drug - Abstract
Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study. Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.
- Published
- 2011
49. Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy
- Author
-
R. Baron, M. Winkel, Troels S. Jensen, Søren H. Sindrup, R. Lehmann, R. Konder, Judy Ashworth, and T. Meier
- Subjects
business.industry ,Analgesic ,medicine.disease ,Placebo ,law.invention ,Anesthesiology and Pain Medicine ,Randomized controlled trial ,Opioid ,law ,Anesthesia ,Clinical endpoint ,Number needed to treat ,Medicine ,Tramadol ,business ,Polyneuropathy ,medicine.drug - Abstract
GRT9906 is an investigational novel compound with μ-opioid receptor agonism and inhibition of noradrenalin/serotonin re-uptake. In this randomized, double-blind, placebo-controlled, three-way cross-over trial in painful polyneuropathy, the efficacy and safety of GRT9906 was assessed and compared with tramadol. During 4-week treatment periods, daily oral doses of either GRT9906 120-240 mg, or placebo, or tramadol 200-400 mg were given. These were separated by 1-week washout periods. The primary endpoint was the average pain intensity (average of daily current pain intensity over the last 3 days of each treatment period rated on a 0 to 10-point numeric rating scale). One hundred seventeen patients were enrolled and 64 were randomized to one of six treatment sequences. Forty-seven patients qualified for the per protocol analysis. GRT9906 reduced average pain intensity by 2.1 points compared with a reduction of 0.6 points on placebo (p < 0.0001) and 2.4 points on tramadol. GRT9906 also improved scores on the sleep problem scale and the neuropathic pain symptom inventory and scored better than placebo on the patient global impression of change. Numbers needed to treat to obtain one patient with more than 50% pain relief was 3.9 (95% CI 2.4-11.5) for both GRT9906 and tramadol. The most frequently reported adverse events were nausea, fatigue, constipation and sleep disorder for GRT9906 and tramadol. Four patients dropped out due to adverse events during both GRT9906 and tramadol treatment and two dropped out during placebo treatment. In conclusion, in painful polyneuropathy, GRT9906 demonstrated analgesic efficacy with a magnitude of effect comparable with tramadol and was well tolerated.
- Published
- 2011
50. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management
- Author
-
Søren H. Sindrup, G. Rayman, Loretta Vileikyte, Aaron I. Vinik, Bruce A. Perkins, M. Baconja, Solomon Tesfaye, and Andrew J.M. Boulton
- Subjects
medicine.medical_specialty ,Diabetic neuropathy ,Gabapentin ,business.industry ,Endocrinology, Diabetes and Metabolism ,Pregabalin ,medicine.disease ,law.invention ,chemistry.chemical_compound ,Endocrinology ,Pharmacotherapy ,Peripheral neuropathy ,chemistry ,Randomized controlled trial ,law ,Anesthesia ,Internal Medicine ,medicine ,Duloxetine ,Tramadol ,Intensive care medicine ,business ,medicine.drug - Abstract
Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co-morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti-depressants, the selective serotonin and noradrenaline re-uptake inhibitors, anti-convulsants, opiates, membrane stabilizers, the anti-oxidant alpha-lipoic acid and topical agents including capsaicin. Current first-line therapies for painful DPN include tricyclic anti-depressants, the serotonin and noradrenaline re-uptake inhibitor duloxetine and the anti-convulsants pregabalin and gabapentin. When prescribing any of these agents, other co-morbidities and costs must be taken into account. Second-line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone-controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long-term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non-pharmacological approaches.
- Published
- 2011
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