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The Journal of Clinical Investigation May 2023Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. There are no effective treatments for SPG50 or any other...
Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. There are no effective treatments for SPG50 or any other type of SPG, and current treatments are limited to symptomatic management. In this issue of the JCI, Chen et al. provide promising data from preclinical studies that evaluated the efficacy and safety profiles of an AAV-mediated AP4M1 gene replacement therapy for SPG50. AAV/AP4M1 gene replacement partly rescued functional defects in SPG50 cellular and mouse models, with acceptable safety profiles in rodents and monkeys. This work represents a substantial advancement in therapeutic development of SPG50 treatments, establishing the criteria for taking AAV9/AP4M1 gene therapy to clinical trials.
Topics: Animals; Mice; Neurodegenerative Diseases; Mutation; Paraplegia; Spastic Paraplegia, Hereditary
PubMed: 37183815
DOI: 10.1172/JCI170226 -
European Spine Journal : Official... Jun 2013The most dreaded neurological complications in TB spine occur in active stage of disease by mechanical compression, instability and inflammation changes, while in healed... (Review)
Review
The most dreaded neurological complications in TB spine occur in active stage of disease by mechanical compression, instability and inflammation changes, while in healed disease, these occur due to intrinsic changes in spinal cord secondary to internal salient in long standing kyphotic deformity. A judicious combination of conservative therapy and operative decompression when needed should form a comprehensive integrated course of treatment for TB spine with neurological complications. The patients showing relatively preserved cord with evidence of edema/myelitis with predominantly fluid collection in extradural space on MRI resolve on non-operative treatment, while the patients with extradural compression of mixed or granulomatous nature showing entrapment of spinal cord should be undertaken for early surgical decompression. The disease focus should be debrided with removal of pus caseous tissue and sequestra. The viable bone should only be removed to decompress the spinal cord and resultant gap should be bridged by bone graft. The preserved volume of spinal cord with edema/myelitis and wet lesion on MRI usually would show good neural recovery. The spinal cord showing myelomalacia with reduced cord volume and dry lesion likely to show a poor neural recovery. The internal kyphectomy is indicated for paraplegia with healed disease. These cases are bad risk for surgery and neural recovery. The best form of treatment of late onset paraplegia is the prevention of development of severe kyphosis in initial active stage of disease.
Topics: Decompression, Surgical; Humans; Paraplegia; Spinal Cord Compression; Tuberculosis, Spinal
PubMed: 22565802
DOI: 10.1007/s00586-012-2335-7 -
Der Chirurg; Zeitschrift Fur Alle... Jun 2021Patients with paraplegia develop syndrome-specific complications relevant to visceral surgery, which occur in the context of the acute spinal shock or as a consequence... (Review)
Review
BACKGROUND
Patients with paraplegia develop syndrome-specific complications relevant to visceral surgery, which occur in the context of the acute spinal shock or as a consequence of the progressive neurogenic bowel dysfunction (NBD) with the formation of an elongated colon and/or megacolon. Moreover, acute abdominal emergencies, such as acute appendicitis, cholecystitis, diverticulitis and ileus images, pose particular challenges for the clinician when the clinical signs are atypical or even absent. The expansion of indications for obesity surgery to include patients with a paraplegic syndrome, whose independence and quality of life can be impaired due to the restricted mobility, especially by obesity, is becoming increasingly more important.
OBJECTIVE
This article provides an overview of the special requirements and aspects in the treatment of this special patient collective and to show the evidence of paraplegia-specific visceral surgery treatment.
MATERIAL AND METHODS
Targeted literature search in Medline and Cochrane library (German and English, 1985-2020).
RESULTS AND CONCLUSION
The clinical treatment of paraplegic patients requires in-depth knowledge of the pathophysiological changes at the different height of the paraplegia (upper versus lower motor neuron) and the phase of the disease (spinal shock versus long-term course). Missing or atypical clinical symptoms of acute diseases delay a quick diagnosis and make early diagnosis essential. The evidence for surgical treatment of the acute and chronic consequences of NBD is based on small retrospective series and case reports, as is that for special indications such as obesity surgery.
Topics: Appendicitis; Digestive System Surgical Procedures; Humans; Paraplegia; Quality of Life; Retrospective Studies
PubMed: 33630122
DOI: 10.1007/s00104-021-01364-2 -
Journal of the American Veterinary... Aug 2016
Topics: Animals; Diagnosis, Differential; Lymphoma, B-Cell; Male; Paraplegia; Rats; Rats, Long-Evans; Rodent Diseases; Thoracic Vertebrae
PubMed: 27479281
DOI: 10.2460/javma.249.4.381 -
Journal of Vascular Surgery Jul 2004We undertook a quantitative systematic review of randomized controlled trials (RCTs) and observational studies to determine the effectiveness of cerebrospinal fluid... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We undertook a quantitative systematic review of randomized controlled trials (RCTs) and observational studies to determine the effectiveness of cerebrospinal fluid (CSF) drainage to prevent paraplegia in thoracic aneurysm (TA) and thoracoabdominal aortic aneurysm (TAAA) surgery.
METHODS
We included RCTs and cohort studies that met the following criteria: elective or emergent aneurysm surgery involving the thoracic or thoracoabdominal aorta, documentation of postoperative neurologic deficits, and patient age older than 18 years. We excluded studies that reported results in 10 or fewer patients and duplicate publications. We identified eligible studies by searching computerized databases, our own files, and the reference lists of relevant articles and review articles. Database searching, eligibility decisions, relevance and method quality assessments, and data extraction were performed in duplicate with prespecified criteria.
RESULTS
Of 372 publications identified in our search, 14 met our eligibility criteria. Three RCTs reported 289 patients with type I or type II TAAA. Lower limb neurologic deficits occurred in 12% of patients who underwent CSF drainage and 33% of control subjects (number needed to treat, 9; 95% confidence interval [CI], 5-50). The pooled odds ratio (OR) for development of paraplegia in patients in the CSF drainage group was 0.35 (P =.05; 95% CI, 0.12-0.99). Similar results were found in five cohort studies with a control group (pooled OR, 0.26; P =.0002; 95% CI, 0.13-0.53). When all studies were considered together the pooled OR of TA and TAAA was 0.3 (95% CI, 0.17-0.54). There was no statistical heterogeneity among studies included in the meta-analysis. In six cohort studies without a control group, the incidence of paraplegia in high-risk TA and TAAA was 7.6%.
CONCLUSIONS
Evidence from randomized and nonrandomized trials and from cohort studies support the use of CSF drainage as an adjunct to prevent paraplegia when this adjunct is used in centers with large experience in the management of TAAA.
Topics: Aged; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Cerebrospinal Fluid; Drainage; Female; Humans; Male; Paraplegia; Treatment Outcome; Vascular Surgical Procedures
PubMed: 15218460
DOI: 10.1016/j.jvs.2004.03.017 -
The Journal of Spinal Cord Medicine Nov 2022Extreme conditioning programs (ECPs), such as CrossFit, are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown... (Observational Study)
Observational Study
CONTEXT
Extreme conditioning programs (ECPs), such as CrossFit, are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown if wheelchair users are at an additional risk of musculoskeletal injury during these exercises. Biomechanical characterization is necessary to determine the safety and efficacy of ECPs as an exercise modality for wheelchair users with paraplegia.
OBJECTIVE
To characterize the three-dimensional (3-D) thorax and upper extremity joint kinematics of paraplegic wheelchair athletes during exercises commonly prescribed as part of ECPs.
DESIGN
Observational study.
PARTICIPANTS
Three male wheelchair athletes, average age of 37.1 ± 4.6 years, with spinal cord injury levels of T8, L2, and T10, with varying exercise experience.
METHODS
3-D movement was acquired using motion capture during the performance of four exercises: battle ropes, sled pull, overhead press, and sledgehammer swing. A custom upper extremity inverse kinematics model was applied to compute 3-D joint angles.
OUTCOME MEASURES
3-D peak thorax, glenohumeral, elbow, and wrist joint angles and ranges of motion (ROM), Visual Analog Scale (VAS), and Borg Scale of Perceived Exertion.
RESULTS
Large joint motions were required for the exercises, at times demanding extreme shoulder and/or wrist flexion and extension, abduction, and external rotation, which are concerning for injury risk in wheelchair users. Participants, however, were able to perform the exercises pain free.
CONCLUSION
These quantitative findings highlight that wheelchair athletes may be exposed to potentially injurious positions during common ECP exercises. These findings provide insight that may lead to improved clinical guidelines for prescription and training of exercise regimens, particularly involving ECPs, for wheelchair users.
Topics: Humans; Male; Adult; Wheelchairs; Para-Athletes; Shoulder Joint; Spinal Cord Injuries; Paraplegia; Biomechanical Phenomena
PubMed: 34100694
DOI: 10.1080/10790268.2021.1928868 -
The Ceylon Medical Journal Mar 2006
Topics: Genetic Diseases, Inborn; Humans; Magnetic Resonance Imaging; Molecular Biology; Paraplegia; Prenatal Diagnosis; Spinal Cord Diseases
PubMed: 16898027
DOI: 10.4038/cmj.v51i1.1366 -
The Journal of Spinal Cord Medicine Jul 2014To examine body composition, including the relationship between body mass index (BMI) and total body fat, in women and men with complete motor paraplegia and to make...
OBJECTIVES
To examine body composition, including the relationship between body mass index (BMI) and total body fat, in women and men with complete motor paraplegia and to make comparisons with able-bodied controls.
METHODS
In 13 subjects with traumatic, complete motor paraplegia (six women, seven men) and 39 sex-, age-, and BMI-matched controls from the community (18 women, 21 men), we measured total and regional (upper extremities, trunk, and lower extremities) lean and fat mass using total body dual-energy X-ray absorptiometry.
RESULTS
Both women and men with paraplegia had significantly lower lean mass in their lower extremities, as would be expected, and in their total body when compared with controls. However, they had significantly greater lean mass in their upper extremities than controls (4.4 kg vs. 3.6 kg, P = 0.004 and 8.6 kg vs. 6.7 kg, P < 0.001 in women and men, respectively); all subjects with paraplegia studied used manual wheelchairs. Although total body fat mass was significantly greater in women (P = 0.010) and men (P = <0.001) with paraplegia compared with controls, for the equivalent total body fat mass, BMI was actually lower in women and men with paraplegia than controls (e.g. 20.2 kg/m² vs. 25.0 kg/m², respectively).
CONCLUSION
We report on body composition in persons with complete motor paraplegia, including women on whom limited information is currently available. Our results support the need to define better assessments of obesity in both women and men following spinal cord injury, particularly of central body fat distribution, as BMI underestimates adiposity in this population.
Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Aged, 80 and over; Body Composition; Body Mass Index; Body Weight; Case-Control Studies; Female; Humans; Male; Middle Aged; Paraplegia; Reference Values; Regression Analysis; Sex Characteristics; Spinal Cord Injuries; Young Adult
PubMed: 24090208
DOI: 10.1179/2045772313Y.0000000151 -
The Neurologist Dec 2015A marker predictive of hematoma expansion in the central nervous system could aid the selection of patients for hemostatic or surgical treatment.
INTRODUCTION
A marker predictive of hematoma expansion in the central nervous system could aid the selection of patients for hemostatic or surgical treatment.
CASE REPORT
Here, we present a 83-year-old patient with acute spinal subdural hematoma with paraparesis progressing to paraplegia. A contrast extravasation within the intraspinal hematoma was visualized on spinal MR indicating active bleeding (spinal spot sign). A second acquisition of contrast-enhanced MR images showed progression of contrast extravasation helping to different active bleeding from spinal arteriovenous malformations/fistula.
CONCLUSIONS
A "spinal spot sign" may be important for treatment decisions, notably in patients with incomplete neurological deficits at the time of imaging.
Topics: Aged, 80 and over; Biomarkers; Contrast Media; Hematoma, Subdural, Spinal; Humans; Magnetic Resonance Imaging; Male; Paraplegia
PubMed: 26671742
DOI: 10.1097/NRL.0000000000000062 -
Redox Biology Apr 2023Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (HS) was reported to be protective in a mouse model of spinal cord...
BACKGROUND
Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (HS) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of HS has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia.
METHODS AND RESULTS
Spinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of S-labeled GSSSG rapidly increased S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%).
CONCLUSIONS
Intranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.
Topics: Mice; Male; Female; Animals; Administration, Intranasal; Glutathione Disulfide; Mice, Inbred C57BL; Spinal Cord Ischemia; Sulfur; Paraplegia
PubMed: 36753926
DOI: 10.1016/j.redox.2023.102620