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Leblong E, Piette P, Anne C, Jeanne M, Poyau M, Roy AL, Gallien P. Switox: Retrospective Analysis of Botulinum Toxin Switching in Management of Spasticity. Toxins (Basel) 2025; 17:103. [PMID: 40137876 PMCID: PMC11945378 DOI: 10.3390/toxins17030103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/29/2025] Open
Abstract
This retrospective study investigates botulinum toxin changes in 206 patients with spasticity, following reimbursement adjustments in France. The main objective was to evaluate the tolerance and efficacy of these changes, a topic underexplored due to the common practice of maintaining the same toxin brand. The majority of patients switched from Botox to Xeomin (73.66%), while others switched from Botox to Dysport (14.63%) or from Xeomin to Dysport (11.71%). Dose adjustments varied depending on the switch, with the change from Botox to Xeomin showing the greatest diversity in adjustments. Overall, tolerance was good, with few adverse effects reported, primarily fatigue. Perceived efficacy fluctuated, with some patients noting improvement while others experienced deterioration, but the median remained stable. A majority of patients (57.06%) chose to continue with their new treatment, indicating general satisfaction, though 42.93% preferred to return to their initial treatment. This study highlights the importance of an individualized approach and careful monitoring during toxin changes. The results suggest that toxin switches can be made without an increase in adverse effects. While differences between groups were observed, they were not statistically significant. Placebo and nocebo effects may influence perceptions of efficacy and side effects during treatment changes.
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Affiliation(s)
- Emilie Leblong
- Fondation Saint Helier, 35043 Rennes, France; (P.P.); (C.A.); (M.J.); (M.P.); (A.L.R.); (P.G.)
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Gill R, Banky M, Yang Z, Medina Mena P, Woo CCA, Bryant A, Olver J, Moore E, Williams G. The Effect of Botulinum Neurotoxin-A (BoNT-A) on Muscle Strength in Adult-Onset Neurological Conditions with Focal Muscle Spasticity: A Systematic Review. Toxins (Basel) 2024; 16:347. [PMID: 39195757 PMCID: PMC11359732 DOI: 10.3390/toxins16080347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/28/2024] [Accepted: 08/05/2024] [Indexed: 08/29/2024] Open
Abstract
Botulinum neurotoxin-A (BoNT-A) injections are effective for focal spasticity. However, the impact on muscle strength is not established. This study aimed to investigate the effect of BoNT-A injections on muscle strength in adult neurological conditions. Studies were included if they were Randomised Controlled Trials (RCTs), non-RCTs, or cohort studies (n ≥ 10) involving participants ≥18 years old receiving BoNT-A injection for spasticity in their upper and/or lower limbs. Eight databases (CINAHL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Pubmed, Web of Science) were searched in March 2024. The methodology followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Quality was assessed using the modified Downs and Black checklist and the PEDro scale. Pre-/post-injection agonist, antagonist, and global strength outcomes at short-, medium-, and long-term time points were extracted for analysis. Following duplicate removal, 8536 studies were identified; 54 met the inclusion criteria (3176 participants) and were rated as fair-quality. Twenty studies were analysed as they reported muscle strength specific to the muscle injected. No change in agonist strength after BoNT-A injection was reported in 74% of the results. Most studies' outcomes were within six weeks post-injection, with few long-term results (i.e., >three months). Overall, the impact of BoNT-A on muscle strength remains inconclusive.
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Affiliation(s)
- Renée Gill
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
- School of Physiotherapy, The University of Melbourne, Parkville, Melbourne 3000, Australia (A.B.)
| | - Megan Banky
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
- School of Physiotherapy, The University of Melbourne, Parkville, Melbourne 3000, Australia (A.B.)
| | - Zonghan Yang
- School of Physiotherapy, The University of Melbourne, Parkville, Melbourne 3000, Australia (A.B.)
| | - Pablo Medina Mena
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
| | - Chi Ching Angie Woo
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
| | - Adam Bryant
- School of Physiotherapy, The University of Melbourne, Parkville, Melbourne 3000, Australia (A.B.)
| | - John Olver
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
| | - Elizabeth Moore
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
| | - Gavin Williams
- Department of Physiotherapy, Epworth Rehabilitation Epworth Healthcare Richmond, Melbourne 3121, Australia; (M.B.); (P.M.M.); (C.C.A.W.); (J.O.); (E.M.); (G.W.)
- School of Physiotherapy, The University of Melbourne, Parkville, Melbourne 3000, Australia (A.B.)
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Sumsuzzman DM, Khan ZA, Nila IS, Moran VMV, Rajesh M, Yang WJ, Hong Y. Effects of Botulinum Toxin-A for Spasticity and Nociceptive Pain in Individuals with Spinal Cord Injury: A Systematic Review and Meta-Analysis. Ann Rehabil Med 2024; 48:192-202. [PMID: 38950971 PMCID: PMC11217759 DOI: 10.5535/arm.240034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/26/2024] [Accepted: 06/12/2024] [Indexed: 07/03/2024] Open
Abstract
We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.
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Affiliation(s)
- Dewan Md. Sumsuzzman
- Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Korea
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
| | - Zeeshan Ahmad Khan
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
- Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Gimhae, Korea
| | - Irin Sultana Nila
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
- Department of Digital Anti-aging Healthcare, Graduate School of Inje University, Gimhae, Korea
| | - Vanina Myuriel Villagra Moran
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
- Department of Physical Therapy, Graduate School of Inje University, Gimhae, Korea
| | - Madhuvilakku Rajesh
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
- Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Gimhae, Korea
| | - Won Jong Yang
- Department of Rehabilitation Medicine, Medical Corporation, Daegu Medical Foundation The K Hospital, Daegu, Korea
| | - Yonggeun Hong
- Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Korea
- Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea
- Research Center for Aged-life Redesign (RCAR), Inje University, Gimhae, Korea
- Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Gimhae, Korea
- Department of Digital Anti-aging Healthcare, Graduate School of Inje University, Gimhae, Korea
- Department of Physical Therapy, Graduate School of Inje University, Gimhae, Korea
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Mori H, Satoh G, Takashima H, Masuda T, Mano T. Combined rehabilitation therapy with botulinum toxin to the upper limbs for acute spinal cord injury: A case report. Spinal Cord Ser Cases 2024; 10:33. [PMID: 38704389 PMCID: PMC11069564 DOI: 10.1038/s41394-024-00647-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/06/2024] Open
Abstract
INTRODUCTION Patients with spinal cord injury (SCI) and incomplete paralysis may experience muscle immobilization due to functional impairment of agonist and antagonist muscles. This can induce spasticity and pain, with the risk of contracture increasing as the period of immobilization increases. This could be aggravated by pain, which interferes with rehabilitation. There is no established treatment for pain and joint contractures caused by acute SCI. Botulinum therapy plays a role in relieving muscle tension. Here, we report a case of acute SCI in which botulinum therapy was administered. CASE PRESENTATION The patient experienced a C5-cervical SCI due to a road traffic accident, with marked paralysis in the upper and lower limbs below the C5 level. The patient had persistent elbow flexion since the SCI and complained of excruciating pain, making adequate rehabilitation difficult. Botulinum toxin was administered to the biceps and brachialis muscles 15 days after the SCI. After administration, the patient experienced a reduction in pain with relaxation of the elbow flexor muscles, and rehabilitation treatment was resumed. This patient's contracture did not worsen, his pain decreased, and he was able to initiate self-feeding training. DISCUSSION In this case, occupational and physical therapy was administered with botulinum therapy. Together, they successfully reduced pain. Botulinum therapy provides analgesia and muscle relaxation and may lead to functional recovery, and we believe that treatment can be considered even in the acute phase.
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Affiliation(s)
- Haruki Mori
- Department of Rehabilitation, Nara Prefecture General Medical Center, Nara city, Japan
| | - Gosuke Satoh
- Department of Rehabilitation, Nara Prefecture General Medical Center, Nara city, Japan
| | - Hideki Takashima
- Department of Rehabilitation, Nara Prefecture General Medical Center, Nara city, Japan
| | - Takashi Masuda
- Department of Rehabilitation, Nara Prefecture General Medical Center, Nara city, Japan
| | - Tomoo Mano
- Department of Rehabilitation, Nara Prefecture General Medical Center, Nara city, Japan.
- Department of Neurology, Nara Medical University, Nara city, Japan.
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Dietz N, Wagers S, Harkema SJ, D'Amico JM. Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events. Arch Phys Med Rehabil 2023; 104:119-131. [PMID: 35750207 DOI: 10.1016/j.apmr.2022.05.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 04/29/2022] [Accepted: 05/06/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.
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Affiliation(s)
- Nicholas Dietz
- Department of Neurological Surgery, University of Louisville, Louisville, KY; Kentucky Spinal Cord Injury Research Center, Louisville, KY
| | - Sarah Wagers
- Department of Neurological Surgery, University of Louisville, Louisville, KY; Kentucky Spinal Cord Injury Research Center, Louisville, KY
| | - Susan J Harkema
- Department of Neurological Surgery, University of Louisville, Louisville, KY; Kentucky Spinal Cord Injury Research Center, Louisville, KY
| | - Jessica M D'Amico
- Department of Neurological Surgery, University of Louisville, Louisville, KY; Kentucky Spinal Cord Injury Research Center, Louisville, KY.
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Güntürk E, Ögüt H, Güler H, Turhanoğlu AD. The effect of oral baclofen and botulinum toxin treatments in hemiplegic spasticity on the nociceptive flexor reflex: A randomized clinical trial. Turk J Phys Med Rehabil 2022; 68:524-531. [PMID: 36589348 PMCID: PMC9791711 DOI: 10.5606/tftrd.2022.9596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 02/15/2022] [Indexed: 12/12/2022] Open
Abstract
Objectives This study aimed to analyze the effect of oral baclofen treatment and botulinum toxin type A (BT-A) injection treatment in hemiplegic patients with spasticity on the electromyographic nociceptive flexor reflex (NFR) threshold. Patients and methods A total of 29 spastic hemiplegic patients (20 males, 9 females; mean age: 52.9±10.1; range, 27 to 64) with Modified Ashworth Scale (MAS) grades 2-4 were included in the prospective, randomized study between May 2018 and March 2019. The patients were divided into two groups: the BT-A group consisted of 15 patients that underwent a BT-A injection and the baclofen group consisted of 14 patients treated with baclofen. Modified Ashworth Scale, Visual Analog Scale (VAS), Barthel daily life activity index, and NFR threshold values were used in the evaluation of the patients before and after the treatment at the sixth week. The motor evaluation of the patients was performed using Brunnstrom motor staging. Results In both groups, MAS and VAS values decreased significantly compared to pretreatment (p<0.05). There was a significant decrease in ankle MAS score (p<0.001) and a significant increase in Brunnstrom hand recovery stages in the BT-A group compared to pretreatment (p=0.020). While the NFR threshold statistically significantly increased in the baclofen group compared to pretreatment (p=0.007), there was no significant change in the BT-A group (p=0.669). Conclusion These results suggest that BT-A injections do not cause a significant change in the NFR threshold in the treatment of spasticity.
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Affiliation(s)
- Ertürk Güntürk
- Department of Physical Medicine and Rehabilitation, Hatay Mustafa Kemal University Faculty of Medicine, Hatay, Türkiye
| | - Halil Ögüt
- Department of Physical Medicine and Rehabilitation, Hatay Mustafa Kemal University Faculty of Medicine, Hatay, Türkiye
| | - Hayal Güler
- Department of Physical Medicine and Rehabilitation, Hatay Mustafa Kemal University Faculty of Medicine, Hatay, Türkiye
| | - Ayşe Dicle Turhanoğlu
- Department of Physical Medicine and Rehabilitation, Hatay Mustafa Kemal University Faculty of Medicine, Hatay, Türkiye
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Bhagwani A, Chopra M, Kumar H. Spinal Cord Injury Provoked Neuropathic Pain and Spasticity, and Their GABAergic Connection. Neurospine 2022; 19:646-668. [PMID: 36203291 PMCID: PMC9537837 DOI: 10.14245/ns.2244368.184] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/10/2022] [Indexed: 12/14/2022] Open
Abstract
Traumatic spinal cord injury (SCI) is the devastating neurological damage to the spinal cord that becomes more complicated in the secondary phase. The secondary injury comes with inevitable long-lasting complications, such as chronic neuropathic pain (CNP) and spasticity which interfere with day to day activities of SCI patients. Mechanisms underlying CNP post-SCI are complex and remain refractory to current medical treatment. Due to the damage, extensive inhibitory, excitatory tone dysregulation causes maladaptive synaptic transmissions, further altering the nociceptive and nonnociceptive pathways. Excitotoxicity mediated GABAergic cell loss, downregulation of glutamate acid decarboxylase enzyme, upregulation of gamma-aminobutyric acid (GABA) transporters, overactivation of glutamate receptors are some of the key evidence for hypoactive inhibitory tone contributing to CNP and spasticity post-SCI. Restoring the inhibitory GABAergic tone and preventing damage-induced excitotoxicity by employing various strategies provide neuroprotective and analgesic effects. The present article will discuss CNP and spasticity post-SCI, understanding their pathophysiological mechanisms, especially GABA-glutamate-related mechanisms, therapeutic interventions targeting them, and progress regarding how regulating the excitatory-inhibitory tone may lead to more targeted treatments for these distressing complications. Taking background knowledge of GABAergic analgesia and recent advancements, we aim to highlight how far we have reached in promoting inhibitory GABAergic tone for SCI-CNP and spasticity.
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Affiliation(s)
- Ankita Bhagwani
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India
| | - Manjeet Chopra
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India
| | - Hemant Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India,Corresponding Author Hemant Kumar Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Opposite Air force Station, Palaj, Gandhinagar-382355, Gujarat, India ,
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Li M, Huang Y, Chen R, Liu N, Fang S. Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study. ACTA ACUST UNITED AC 2021; 54:e11293. [PMID: 34495247 PMCID: PMC8427767 DOI: 10.1590/1414-431x2021e11293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/25/2021] [Indexed: 11/21/2022]
Abstract
There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).
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Affiliation(s)
- Mingheng Li
- Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
| | - Yan Huang
- Department of Acupuncture Rehabilitation, Ganzhou Hospital of Traditional Chinese Medicine, Ganzhou, Jiangxi, China
| | - Rongchun Chen
- Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
| | - Ning Liu
- Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
| | - Shibing Fang
- Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
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Turner LD, Nielsen AL, Lin L, Pellett S, Sugane T, Olson ME, Johnson EA, Janda KD. Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach. RSC Med Chem 2021; 12:960-969. [PMID: 34223161 PMCID: PMC8221255 DOI: 10.1039/d1md00089f] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/03/2021] [Indexed: 12/27/2022] Open
Abstract
Botulinum neurotoxin A (BoNT/A) is categorized as a Tier 1 bioterrorism agent and persists within muscle neurons for months, causing paralysis. A readily available treatment that abrogates BoNT/A's toxicity and longevity is a necessity in the event of a widespread BoNT/A attack and for clinical treatment of botulism, yet remains an unmet need. Herein, we describe a comprehensive warhead screening campaign of bifunctional hydroxamate-based inhibitors for the irreversible inhibition of the BoNT/A light chain (LC). Using the 2,4-dichlorocinnamic hydroxamic acid (DCHA) metal-binding pharmacophore modified with a pendent warhead, a total of 37 compounds, possessing 13 distinct warhead types, were synthesized and evaluated for time-dependent inhibition against the BoNT/A LC. Iodoacetamides, maleimides, and an epoxide were found to exhibit time-dependent inhibition and their k GSH measured as a description of reactivity. The epoxide exhibited superior time-dependent inhibition over the iodoacetamides, despite reacting with glutathione (GSH) 51-fold slower. The proximity-driven covalent bond achieved with the epoxide inhibitor was contingent upon the vital hydroxamate-Zn2+ anchor in placing the warhead in an optimal position for reaction with Cys165. Monofunctional control compounds exemplified the necessity of the bifunctional approach, and Cys165 modification was confirmed through high-resolution mass spectrometry (HRMS) and ablation of time-dependent inhibitory activity against a C165A variant. Compounds were also evaluated against BoNT/A-intoxicated motor neuron cells, and their cell toxicity, serum stability, and selectivity against matrix metalloproteinases (MMPs) were characterized. The bifunctional approach allows the use of less intrinsically reactive electrophiles to intercept Cys165, thus expanding the toolbox of potential warheads for selective irreversible BoNT/A LC inhibition. We envision that this dual-targeted strategy is amenable to other metalloproteases that also possess non-catalytic cysteines proximal to the active-site metal center.
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Affiliation(s)
- Lewis D Turner
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
| | - Alexander L Nielsen
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
- Center for Biopharmaceuticals & Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2 DK-2100 Copenhagen Denmark
| | - Lucy Lin
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
| | - Sabine Pellett
- Department of Bacteriology, University of Wisconsin 1550 Linden Drive Madison WI 53706 USA
| | - Takashi Sugane
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
| | - Margaret E Olson
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
- College of Pharmacy, Roosevelt University Schaumburg IL 60173 USA
| | - Eric A Johnson
- Department of Bacteriology, University of Wisconsin 1550 Linden Drive Madison WI 53706 USA
| | - Kim D Janda
- Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), Scripps Research 10550 N Torrey Pines Road La Jolla CA 92037 USA
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10
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Sun WM, Ma CL, Xu J, He JP. Reduction in post-spinal cord injury spasticity by combination of peripheral nerve grafting and acidic fibroblast growth factor infusion in monkeys. J Int Med Res 2021; 49:3000605211022294. [PMID: 34154433 PMCID: PMC8236803 DOI: 10.1177/03000605211022294] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Spasticity is a frequent complication after spinal cord injury (SCI), but the existing therapies provide only limited relief and are associated with adverse reactions. Therefore, we aimed to develop a novel strategy to ameliorate the spasticity induced by SCI. METHODS This nonrandomized controlled study used a repeated measurement design. The study involved four monkeys, two of which served as controls and only underwent spinal cord hemisection surgery at the T8 spine level. The other two monkeys underwent transplantation of sural nerve segments into the injured sites and long-term infusion of acidic fibroblast growth factor (aFGF). All monkeys received postoperative exercise training and therapy. RESULTS The combined therapy substantially reduced the spasticity in leg muscle tone, patella tendon reflex, and fanning of toes. Although all monkeys showed spontaneous recovery of function over time, the recovery in the controls reached a plateau and started to decline after 11 weeks. CONCLUSIONS The combination of peripheral nerve grafting and aFGF infusion may serve as a complementary approach to reduce the signs of spasticity in patients with SCI.
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Affiliation(s)
- Wei-Ming Sun
- Institute of Life Science, Nanchang University, Nanchang, China.,School of Life Science, Nanchang University, Nanchang, China
| | - Chao-Lin Ma
- Institute of Life Science, Nanchang University, Nanchang, China.,School of Life Science, Nanchang University, Nanchang, China
| | - Jiang Xu
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ji-Ping He
- Center for Neural Interface Design, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA
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11
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Hodge JO, Brandmeir CL, Brandmeir NJ. Neuromodulation Therapies for Spasticity Control: Now and Beyond. Neurol India 2021; 68:S241-S248. [PMID: 33318358 DOI: 10.4103/0028-3886.302464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Spasticity is a major cause of disability following upper motor neuron (UMN) injury. The diagnosis and treatment of spasticity has been a focus of clinicians and researchers alike. In recent years, there have been significant advances both in strategies for spasticity assessment and in the development of novel treatments. Currently, several well-established spasticity management techniques fall into the major categories of physiotherapy, pharmacotherapy, and surgical management. The majority of recent developments in all of these broad categories have focused more on methods of neuromodulation instead of simple symptomatic treatment, attempting to address the underlying cause of spasticity more directly. The following narrative review briefly discusses the causes and clinical assessment of spasticity and also details the wide variety of current and developing treatment approaches for this often-debilitating condition.
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Affiliation(s)
- Johnie O Hodge
- Department of Neurosurgery, Rockefeller Neuroscience Institute, Morgantown, WV, United States
| | - Cheryl L Brandmeir
- Department of Human Performance, West Virginia University, Morgantown, WV, United States
| | - Nicholas J Brandmeir
- Department of Neurosurgery, Rockefeller Neuroscience Institute, Morgantown, WV, United States
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12
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Palazón-García R, Benavente-Valdepeñas AM. Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury. Int J Mol Sci 2021; 22:ijms22094886. [PMID: 34063051 PMCID: PMC8125452 DOI: 10.3390/ijms22094886] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/30/2021] [Accepted: 05/03/2021] [Indexed: 12/18/2022] Open
Abstract
Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.
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Affiliation(s)
- Ramiro Palazón-García
- Physical Medicine and Rehabilitation Department, Hospital Nacional de Parapléjicos, 45004 Toledo, Spain
- Correspondence:
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13
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Zhu C, Wang K, Yu T, Liu H. Effects of botulinum toxin type a on mood and cognitive function in patients with parkinson's disease and depression. Am J Transl Res 2021; 13:2717-2723. [PMID: 34017433 PMCID: PMC8129423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 12/24/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To analyze the effects of botulinum toxin type A (BtA) in the treatment of patients with Parkinson's disease and depression. METHOD 89 patients with Parkinson's disease and depression were assigned into control group and observation group by random number table method, of which 44 patients in the control group were treated with sertraline and 45 patients in the observation group were treated with BtA. The two groups were compared in terms of mood, cognitive function and adverse reactions. RESULTS The Hamilton Depression Self-Assessment Scale (HAMD) scores of the two groups following treatment were lower than those before treatment while the Mini-Mental State Examination (MMSE) scores were higher than those before treatment (P<0.05). The incidence rate of adverse events was 11.11% in the observation group and 29.55% in the control group (P<0.05). The Pittsburgh sleep quality index (PSQI) scores and 39-item PD Questionnaire (PDQ-39) scores after 2 and 3 months of treatment and 2 months after completion of treatment were lower than those before treatment (P<0.05). CONCLUSION Patients with Parkinson's disease and depression receiving BtA treatment can gain treatment effects similar to those of the sertraline, with less adverse reactions.
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Affiliation(s)
- Changzheng Zhu
- Department of Internal Neurology, Zhangqiu District People's Hospital Ji'nan 250200, Shandong, China
| | - Kuijie Wang
- Department of Internal Neurology, Zhangqiu District People's Hospital Ji'nan 250200, Shandong, China
| | - Ting Yu
- Department of Internal Neurology, Zhangqiu District People's Hospital Ji'nan 250200, Shandong, China
| | - Huaqing Liu
- Department of Internal Neurology, Zhangqiu District People's Hospital Ji'nan 250200, Shandong, China
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14
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Zhang J, Zhu L, Tang Q. Electroacupuncture with rehabilitation training for limb spasticity reduction in post-stroke patients: A systematic review and meta-analysis. Top Stroke Rehabil 2020; 28:340-361. [PMID: 32845210 DOI: 10.1080/10749357.2020.1812938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To assess the effectiveness of electroacupuncture (EA) with rehabilitation training in reducing limb spasticity in post-stroke patients. METHODS A systematic review was performed by electronically searching six databases (Medline/Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure, Database for Chinese Technical Periodicals, and Wanfang Data) for randomized controlled trials (RCTs) on EA with rehabilitation training for limb spasticity reduction in post-stroke patients from 1 January 2009 to 1 January 2019. A meta-analysis was performed using SAS 9.3 and RevMan 5.3 software after bibliography screening, data extraction, and risk of bias assessment using the Cochrane handbook. The primary outcome was spasticity. RESULTS A total of 31 RCTs (including 2488 participants) were included. Except for Cai et al.'s study, the quality of other RCTs was not high. All studies performed a descriptive analysis, and 29 RCTs conducted a meta-analysis. The odds ratio (OR) for marked efficiency was 2.35 (95% confidence interval [CI] 1.68-3.27, Z = 5.03, P < .00001). The OR for Modified Ashworth Scale (MAS) classification was 2.42 (95% CI 1.89-3.10, Z = 7.03; P < .00001). The weighted mean difference (WMD) for MAS score was -0.68 (95% CI -0.79 - -0.56, Z = 11.24, P < .00001). The WMD for clinical spasticity index score was -1.50 (95% CI -2.28 - -0.72, Z = 3.79, P = .0002). CONCLUSION EA with rehabilitation training could be a good strategy for reducing limb spasticity after stroke and is better than EA alone or rehabilitation training alone. However, its effectiveness remains to be further verified by large-sample and high-quality RCTs.
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Affiliation(s)
- Jiyao Zhang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Luwen Zhu
- Rehabilitation Center, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Qiang Tang
- Rehabilitation Center, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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15
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Hon AJ, Kraus P. Spasticity Management After Spinal Cord Injury. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2020. [DOI: 10.1007/s40141-020-00280-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Shaw E, Saulino M. Management Strategies for Spinal Cord Injury Pain Updated for the Twenty-First Century. Phys Med Rehabil Clin N Am 2020; 31:369-378. [PMID: 32624100 DOI: 10.1016/j.pmr.2020.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Traumatic spinal cord injury (SCI) often results in several life-altering impairments, including paralysis, sensory loss, and neurogenic bowel/bladder dysfunction. Some of these SCI-related conditions can be accommodated with compensatory strategies. Perhaps no SCI-associated condition is more troublesome and recalcitrant to the treating physiatrist than chronic neuropathic pain. In addition to the expected challenges in treating any chronic pain condition, treatment of SCI-related pain has the added difficulty of disruption of normal neural pathways that subserve pain transmission and attenuation. This article reviews selected treatment strategies for SCI-associated neuropathic pain.
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Affiliation(s)
- Erik Shaw
- Shepherd Spine and Pain Institute, 2020 Peachtree Street Northwest, Atlanta, GA 30309, USA.
| | - Michael Saulino
- Sidney Kimmel Medical College, MossRehab, 60 Township Line Road, Elkins Park, PA 19027, USA
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17
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Wang ZM, Wang ZY, Wei CJ, Jiang YJ. Can Botulinum Toxin Type A effectively treat neuropathic pain in spinal cord injury?: A protocol of systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20702. [PMID: 32569202 PMCID: PMC7310841 DOI: 10.1097/md.0000000000020702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND This protocol aims to assess the efficacy and safety of Botulinum Toxin Type A (BTTA) for the treatment of neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS We will retrieve databases in Cochrane Library, EMBASE, MEDLINE, Excerpta Medica Database, PsychINFO, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the beginning to the March 1, 2020. We will consider any potential studies on assessing the efficacy and safety of BTTA for the treatment of NPP in patients with SCI without limitations of language and publication status. Cochrane risk of bias will be used to assess the risk of bias for all included trials. RevMan 5.3 software will be utilized to synthesize the extracted data and to analyze those data. RESULTS This study will appraise the efficacy and safety based on the current evidence of BTTA for the treatment of NPP in patients with SCI. CONCLUSION This study will exert high quality clinical trials for exploring the efficacy and safety of BTTA in treating NPP in patients with SCI. PROSPERO REGISTRATION NUMBER PROSPERO CRD42020170474.
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18
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High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at? Toxins (Basel) 2020; 12:toxins12050315. [PMID: 32397674 PMCID: PMC7291232 DOI: 10.3390/toxins12050315] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 04/28/2020] [Accepted: 05/07/2020] [Indexed: 11/16/2022] Open
Abstract
Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term “high dosage” indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable.
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19
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Yang R, Cai X, Li J, Liu F, Sun T. Protective Effects of MiR-129-5p on Acute Spinal Cord Injury Rats. Med Sci Monit 2019; 25:8281-8288. [PMID: 31680116 PMCID: PMC6854883 DOI: 10.12659/msm.916731] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Spinal cord injury (SCI) is a severe devastating condition associated with serious disability and neurologic deficits. Aberrant micro RNA (miRNA) expression has been related to a variety of central nervous system diseases including SCI. In the present study, we aimed to discover the role of miR-129-5p on SCI. MATERIAL AND METHODS An acute SCI rat model was induced, following the modified Allen method. A total of 36 rats were randomly assigned into 4 groups (n=9 in every group): Sham group; Model group (SCI+saline); SCI+NC group; and SCI+miR-129-5p group (100 nm solution, every 2 days). Basso-Beattie-Bresnahan (BBB) locomotor rating score was carried out to determine functional recovery. TUNEL (terminal dUTP nick-end labeling) staining was used to evaluate cell apoptosis. Hematoxylin and eosin staining was performed to assess the pathological state of spinal cord. Furthermore, western blot assay was conducted to measure the calpain1 and calpain2 expression. RESULTS Our data suggested that the expression level of miR-129-5p was markedly reduced in rats after SCI. Then miR-129-5p mimic was injected into the vertebral canal. We found that the SCI+miR-129-5p group had a high score in the BBB test compared with the SCI+NC group and the Model group. The overexpression of miR-129-5p obviously reduced tissue loss, damaged cells, and the number of TUNEL positive cells. Moreover, western blot assay exhibited that overexpression of miR-129-5p decreased calpain1, calpain2, and cleaved caspase-3 expression. CONCLUSIONS Our findings suggested that overexpression of miR-129-5p improved neurological function by promoting functional recovery, reducing tissue loss and cell apoptosis in rats in an SCI model, possibly through downregulation of calpain1 and calpain2.
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Affiliation(s)
- Ruifeng Yang
- Department of Orthopedics, Lishui Municipal Central Hospital, Lishui, Zhejiang, China (mainland)
| | - Xiaobin Cai
- Department of Orthopedics, Lishui Municipal Central Hospital, Lishui, Zhejiang, China (mainland)
| | - Jian Li
- Department of Orthopedics, Lishui Municipal Central Hospital, Lishui, Zhejiang, China (mainland)
| | - Feng Liu
- Department of Orthopedics, Lishui Municipal Central Hospital, Lishui, Zhejiang, China (mainland)
| | - Tao Sun
- Department of Orthopedics, Lishui Municipal Central Hospital, Lishui, Zhejiang, China (mainland)
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Xiao XW, Du J, Jiao B, Liao XX, Zhou L, Liu XX, Yuan ZH, Guo LN, Wang X, Shen L, Lin ZY. Novel ATL1 mutation in a Chinese family with hereditary spastic paraplegia: A case report and review of literature. World J Clin Cases 2019; 7:1358-1366. [PMID: 31236401 PMCID: PMC6580333 DOI: 10.12998/wjcc.v7.i11.1358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/23/2019] [Accepted: 04/09/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hereditary spastic paraplegias (HSPs) refer to a group of heterogeneous neurodegenerative diseases characterized by lower limbs spasticity and weakness. So far, over 72 genes have been found to cause HSP (SPG1-SPG72). Among autosomal dominant HSP patients, spastic paraplegia 4 (SPG4/SPAST) gene is the most common pathogenic gene, and atlastin-1 (ATL1) is the second most common one. Here we reported a novel ATL1 mutation in a Chinese spastic paraplegia 3A (SPG3A) family, which expands the clinical and genetic spectrum of ATL1 mutations.
CASE SUMMARY A 9-year-old boy with progressive spastic paraplegia accompanied by right hearing loss and mental retardation for five years was admitted to our hospital. Past history was unremarkable. The family history was positive, and his grandfather and mother had similar symptoms. Neurological examinations revealed hypermyotonia in his lower limbs, hyperreflexia in knee reflex, bilateral positive Babinski signs and scissors gait. The results of blood routine test, liver function test, blood glucose test, ceruloplasmin test and vitamin test were all normal. The serum lactic acid level was significantly increased. The testing for brainstem auditory evoked potential demonstrated that the right side hearing was impaired while the left was normal. Magnetic resonance imaging showed mild atrophy of the spinal cord. The gene panel test revealed that the proband carried an ATL1 c.752A>G p.Gln251Arg (p.Q251R) mutation, and Sanger sequencing confirmed the existence of family co-segregation.
CONCLUSION We reported a novel ATL1 Q251R mutation and a novel clinical phenotype of hearing loss in a Chinese SPG3A family.
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Affiliation(s)
- Xue-Wen Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Juan Du
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, Hunan Province, China
| | - Xin-Xin Liao
- Department of Geriatrics Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Lu Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Xi-Xi Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Zhen-Hua Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Li-Na Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Xin Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Lu Shen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, Hunan Province, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, Hunan Province, China
| | - Zhang-Yuan Lin
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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