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Chen Z, Peng T, Zhong M, Zhang Y, Zhang Y, Hou Q, Peng T, Yang X, Zhou H, Liu L, Han M, Tang H, He L, Li J, Niu H, Xu K. Integrated metabolomics and proteomics analysis in children with cerebral palsy exposed to botulinum toxin-A. Pediatr Res 2025:10.1038/s41390-025-04038-5. [PMID: 40247116 DOI: 10.1038/s41390-025-04038-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 08/13/2024] [Accepted: 03/16/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND We previously examined plasma metabolic changes before and after botulinum toxin-A injections of cerebral palsy (CP) children and showed that the glycine, serine and threonine metabolism may play a key role in neuritogenesis. This study analysed untargeted metabolomics combined with proteomics of plasma to discussed which substances are meaningfully changed, to what extent they affect the effects of action. METHODS Blood samples were collected from 91 children with spastic CP at 4 time points: pre-injection (T1), 1 month post-injection (T2), 3 months post-injection (T3) and 6 months post-injection (T4). Differentially changed metabolites and proteins were selected, and co-expression pathways were constructed to explore the key molecular processes. RESULTS A total of 674 proteins and 354 metabolites were identified. The differential metabolites were mainly involved in the linoleic acid metabolism, beta-Alanine metabolism, citrate cycle, pyruvate metabolism and glycolysis or gluconeogenesis. Differential proteins were primarily associated with glucose metabolism, lipid metabolism, immune and inflammation responses. Co-expression pathways showed that ECM-receptor interaction, complement and coagulation cascades, glycolysis or gluconeogenesis, pyruvate metabolism, and linoleic acid metabolism were the main pathways. CONSLUSIONS Our results indicated the botulinum toxin-A predominantly activated the glucose metabolism, lipid metabolism, and immune and inflammation responses, and energy metabolism changed significantly in this process. TRIAL REGISTRATION DETAILS ChiCTR2000033800, Research on the mechanism of botulinum toxin relieving spasticity in children with cerebral palsy. Approval No. 202023041. Registered 13 June 2020, http://www.chictr.org.cn/showproj.html?proj=52267 . IMPACT STATEMENT This is the first study that combined dynamic metabolomics and proteomics analysis to investigate the molecular changes in children with spastic cerebral palsy after botulinum toxin-A injections, which might provide a theoretical reference for the further subsequent study for targets to increase the efficacy and prolong the duration of botulinum toxin-A, and would be a valuable resource for the metabolomics and proteomics field in this group.
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Affiliation(s)
- Zhaofang Chen
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Tingting Peng
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Mengru Zhong
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Yage Zhang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Yuan Zhang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, Shanghai, China
| | - Qingfen Hou
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
- Department of Sports and Health, Guangzhou Sport University, Guangzhou, Guangzhou, China
| | - Tingting Peng
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Xubo Yang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Hongyu Zhou
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Liru Liu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Mingshan Han
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Hongmei Tang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Lu He
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Jinling Li
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China
| | - Huiran Niu
- Genechem Biotechnology Co., Ltd, Shanghai, Shanghai, China
| | - Kaishou Xu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China.
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Free M, Pathare A, Mahgoub Y. Unintended Weight Gain After Treatment of Catatonia With ECT in Autism: Case Report and Literature Review. J ECT 2023; 39:269-270. [PMID: 37310088 DOI: 10.1097/yct.0000000000000935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
ABSTRACT Catatonia is a syndrome with psychomotor, cognitive, and affective symptoms that has been associated with multiple psychiatric and medical conditions, including autism spectrum disorder. Fluctuations in weight can occur within catatonia by means of poor oral intake, treatment with atypical antipsychotics, and often overlooked psychomotor phenomena. We present a case of a patient with autism spectrum disorder and excessive psychomotor activity due to catatonia who initially experienced weight loss despite maintenance of oral intake and required increased caloric intake to maintain her weight. She was treated with electroconvulsive therapy. After the psychomotor phenomena associated with catatonia reduced, she gained 10 lb (4.5 kg) despite no further alterations to medications or diet. This case demonstrates that excessive psychomotor activity seen in catatonia may increase energy expenditure to the severity of altering caloric requirements and that weight is a salient biomarker to be monitored in catatonia, especially with those who have limited communication abilities.
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Affiliation(s)
- Melissa Free
- From the Department of Psychiatry and Behavioral Health, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Aum Pathare
- Department of Psychiatry, Albany Medical Center, Albany, NY
| | - Yassir Mahgoub
- From the Department of Psychiatry and Behavioral Health, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
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Benedičič M, Groleger Sršen K, Grabljevec K, Majdič N, Haber B. Twenty years of intrathecal baclofen therapy in Slovenia: a retrospective single-center analysis of complications. Int J Rehabil Res 2023; 46:209-215. [PMID: 37345419 DOI: 10.1097/mrr.0000000000000586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/23/2023]
Abstract
Since the first implantation in July 2001, the intrathecal baclofen (ITB) therapy for patients with generalized spasticity has been used in Slovenia for 20 years. The aim of this retrospective study was to evaluate the rates of different complications, especially if catheter-related complications were less frequent after the introduction of the coated catheter type in February 2013, and the potential correlation between higher baclofen doses and the incidence of complications. We retrospectively collected data from all patients in the registry during the period from 3 July 2001 to 31 December 2021. Among 138 patients (48 females), 120 patients had the first ITB system implanted at the University Medical Centre Ljubljana. Forty-three complications were reported in 38 patients (27%), with a total complication rate of 0.203/1000 days or 0.074/pump year. The most frequent was catheter-related (0.083/1000 days or 0.030/pump year), followed by skin-related (0.063/1000 days or 0.023/pump year) and pump-related complication (0.026/1000 days or 0.009/pump year). The incidence of catheter-related complications decreased significantly since the use of Ascenda type catheter: 14/7 complications per 88/147 implantations ( P = 0.008). Patients with complications had a statistically significantly higher dose of baclofen: median 400 µg/24h vs. median 300 µg/24h ( P = 0.016). Our retrospective analysis confirmed a significant decrease of catheter-related complications after the implementation of Ascenda type catheter in February 2013. Patients with a higher ITB dose had a statistically significantly higher incidence of complications. The total complication rate was a bit higher as previously reported in other studies, which is consistent with a long follow-up time.
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Affiliation(s)
- Mitja Benedičič
- Department of Neurosurgery, University Medical Centre Ljubljana
| | - Katja Groleger Sršen
- Department for rehabilitation, University Rehabilitation Institute of Republic Slovenia - Soča
- University Ljubljana, Medical Faculty, Ljubljana, Slovenia
| | - Klemen Grabljevec
- Department for rehabilitation, University Rehabilitation Institute of Republic Slovenia - Soča
| | - Neža Majdič
- Department for rehabilitation, University Rehabilitation Institute of Republic Slovenia - Soča
- University Ljubljana, Medical Faculty, Ljubljana, Slovenia
| | - Barbara Haber
- Department of Neurosurgery, University Medical Centre Ljubljana
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Abstract
PURPOSE The purpose of this study was to determine whether symptoms of spasticity, pain, and fatigue are correlated in people with stroke. DESIGN A longitudinal-correlation, mixed-method design was used. METHODS Spasticity, pain, and fatigue symptoms were explored in 22 patients with stroke admitted to three different rehabilitation units certified by the Commission on Accreditation of Rehabilitation Facilities. Data were obtained upon admission, postdischarge, and 1 month after discharge. Demographics, numeric ratings, and a semistructured interview were used to determine associations over time. RESULTS Symptoms of spasticity, pain, and fatigue were quite variable. Fatigue was more likely to impair recovery. Spasticity appears to contain pain experiences. Pain does not appear to be a major factor over time. CONCLUSIONS In this sample of patients with stroke, symptoms of spasticity, pain, and fatigue were correlated. CLINICAL RELEVANCE In managing poststroke spasticity, pain, and fatigue, nurses should recognize that these symptoms are correlated.
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Ifon DE, Ghatas MP, Davis JC, Khalil RE, Adler RA, Gorgey AS. Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report. World J Orthop 2020; 11:453-464. [PMID: 33134108 PMCID: PMC7582109 DOI: 10.5312/wjo.v11.i10.453] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/15/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Severe spasticity may negatively impact functionality and quality of life after spinal cord injury (SCI). Intrathecal baclofen treatment (IBT) is effectively used to manage severe spasticity and reduce comorbidities. However, long-term IBT may have a negative effect on bone mineral content (BMC), bone mineral density (BMD) and body composition (such as percentage fat mass and lean body mass). We demonstrated the negative effects of long-term IBT use in a single case compared with two non-IBT users. CASE SUMMARY A 46-year old Caucasian male Veteran (case) with a 21 year history of complete tetraplegia (complete C6 SCI) was implanted with IBT for 20 years. The case was matched to two participants with different time since injuries [2 (match 1) and 13 (match 2) years] without IBT. Knee BMC and BMD at the epiphysis and metaphysis of the distal femur and proximal tibia were evaluated using dual knee and the dual femur modules of GE Lunar iDXA software. Total and leg body composition assessments were also conducted for the three participants. Potential effect of long-term IBT was demonstrated by changes in BMD, consistent with bone demineralization, at the distal femur and proximal tibia and changes in percentage fat mass and lean mass of legs. The case showed 113% lower BMD at the distal femur, and 78.1% lower at the proximal tibia compared to match 1, moreover the case showed 45% lower BMD at the distal femur, and no observed changes at the proximal tibia compared to match 2. The case had 27.1% and 16.5% greater leg %fat mass compared to match 1 and match 2, respectively. Furthermore, the case had 17.4% and 11.8% lower % leg lean mass compared to match 1 and match 2, respectively. CONCLUSION Long-term IBT may impact bone health and body composition parameters in persons with complete SCI. It may be prudent to encourage regular screening of individuals on long-term IBT considering the prevalence of osteoporosis related fractures, cardiovascular diseases, and metabolic disorders in this population.
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Affiliation(s)
- Dora E Ifon
- Spinal Cord Injury and Disorders Center, Central Virginia VA Health Care System, Richmond, VA 23249, United States
| | - Mina P Ghatas
- Spinal Cord Injury and Disorders Center, Central Virginia VA Health Care System, Richmond, VA 23249, United States
| | - John C Davis
- Spinal Cord Injury and Disorders Center, Central Virginia VA Health Care System, Richmond, VA 23249, United States
| | - Refka E Khalil
- Spinal Cord Injury and Disorders Center, Central Virginia VA Health Care System, Richmond, VA 23249, United States
| | - Robert A Adler
- Medical Service, Central Virginia VA Health Care System, Richmond, VA 23249, United States
- Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, VA 23298, United States
| | - Ashraf S Gorgey
- Spinal Cord Injury and Disorders Center, Central Virginia VA Health Care System, Richmond, VA 23249, United States
- Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA 23298, United States
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Energy expenditure and muscle activity during lying, sitting, standing, and walking in people with motor-incomplete spinal cord injury. Spinal Cord 2018; 56:1008-1016. [PMID: 29955089 DOI: 10.1038/s41393-018-0167-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 11/09/2022]
Abstract
STUDY DESIGN Cross-sectional exploratory study. OBJECTIVES To determine oxygen uptake (VO2), energy expenditure (EE), and muscle activity (MA) during lying (rest), sitting, standing, and walking among ambulatory individuals with spinal cord Injury (SCI) and to compare VO2, EE, and MA between individuals with different levels of ambulation. SETTING Rehabilitation institution with a spinal cord injury unit. METHODS A total of 22 adults with motor-incomplete SCI, ten in a low-ambulation group (non-functional or household walker) and 12 in a high-ambulation group (community or normal walker). VO2 was measured using indirect calorimetry. EE was expressed in metabolic equivalent of task (MET). MA was measured using a wireless surface electromyography device. RESULTS Mean VO2 was 3.19 ml/kg/min. During lying and sitting, EE was below 1.5 METs for all participants. During standing, three participants of the low-ambulation group and none in the high-ambulation group showed MET values of >1.5. In the walking condition, all participants showed MET values above 1.5. MA during stance was higher compared to the sitting condition and significantly higher in the low-ambulation group compared to the high-ambulation group. CONCLUSION Lying, supported- and unsupported sitting, without moving, appear to be sedentary behaviors for ambulatory individuals with a motor-incomplete SCI (MET values of <1.5 and a lack of MA). Walking, but not standing, is a moderate physical activity (>1.5 METs), which can be used by all individuals with motor-incomplete SCI to interrupt sedentary behavior.
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