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Handbook of Clinical Neurology 2020A spinal cord injury (SCI) may result in impairments of motor, sensory, and autonomous functions below the injury level. Worldwide, the prevalence of SCI is 1:1000 and... (Review)
Review
A spinal cord injury (SCI) may result in impairments of motor, sensory, and autonomous functions below the injury level. Worldwide, the prevalence of SCI is 1:1000 and the incidence is between 4 and 9 new cases per 100,000 people per year. Most common causes for traumatic SCI are traffic accidents, falls, and violence. Nowadays, the proportion of patients with tetraplegia and paraplegia is equal. In industrialized countries, the percentage of nontraumatic injuries increases together with age. Most patients with initially preserved motor functions below the injury level show a substantial functional recovery, while three quarters of patients with initially complete SCI remain that way. In SCI, brain-computer interfaces (BCIs) may be used in the subacute phase as part of a restorative therapy program and, later, for control of assistive devices most needed by individuals with high cervical lesions. Research on structural and functional reorganization of the deefferented and deafferented brain after SCI is inconclusive mainly because of varying methods of analysis and the heterogeneity of the investigated populations. A better characterization of study participants with SCI together with documentation of confounding factors such as antispasticity medication or neuropathic pain is indicated.
Topics: Humans; Neuralgia; Paraplegia; Recovery of Function; Spinal Cord; Spinal Cord Diseases; Spinal Cord Injuries
PubMed: 32164868
DOI: 10.1016/B978-0-444-63934-9.00006-8 -
Revue Neurologique May 2021Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an... (Review)
Review
Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an abrupt and complete tetra- or paraplegia. Magnetic resonance imaging is the most valuable tool to show the infarct and to rule out other causes of acute spinal cord syndromes., such as myelitis or acute compressions. Nowadays, in western countries, most spinal cord infarcts are due to aortic diseases (atherosclerosis, aneurysm, dissection) or are of iatrogenic origin (mainly aortic surgery and interventional radiology), while other causes are rare. There is no specific treatment, besides prevention of complications, treatment of the underlying cause and rehabilitation.
Topics: Humans; Infarction; Magnetic Resonance Imaging; Paraplegia; Spinal Cord; Spinal Diseases; Spine
PubMed: 33775442
DOI: 10.1016/j.neurol.2020.12.002 -
The Journal of Clinical Investigation May 2023Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is...
Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is characterized by progressive spastic paraplegia, global developmental delay, and subsequent intellectual disability, secondary microcephaly, and epilepsy. We preformed preclinical studies evaluating an adeno-associated virus (AAV)/AP4M1 gene therapy for SPG50 and describe in vitro studies that demonstrate transduction of patient-derived fibroblasts with AAV2/AP4M1, resulting in phenotypic rescue. To evaluate efficacy in vivo, Ap4m1-KO mice were intrathecally (i.t.) injected with 5 × 1011, 2.5 × 1011, or 1.25 × 1011 vector genome (vg) doses of AAV9/AP4M1 at P7-P10 or P90. Age- and dose-dependent effects were observed, with early intervention and higher doses achieving the best therapeutic benefits. In parallel, three toxicology studies in WT mice, rats, and nonhuman primates (NHPs) demonstrated that AAV9/AP4M1 had an acceptable safety profile up to a target human dose of 1 × 1015 vg. Of note, similar degrees of minimal-to-mild dorsal root ganglia (DRG) toxicity were observed in both rats and NHPs, supporting the use of rats to monitor DRG toxicity in future i.t. AAV studies. These preclinical results identify an acceptably safe and efficacious dose of i.t.-administered AAV9/AP4M1, supporting an investigational gene transfer clinical trial to treat SPG50.
Topics: Humans; Rats; Mice; Animals; Child; Spastic Paraplegia, Hereditary; Genetic Therapy; Dependovirus; Genetic Vectors; Paraplegia
PubMed: 36951961
DOI: 10.1172/JCI164575 -
Der Radiologe Mar 2021
Topics: Humans; Paraplegia
PubMed: 33595676
DOI: 10.1007/s00117-021-00830-6 -
The Journal of Thoracic and... Sep 2022
Topics: Humans; Paraplegia; Spinal Cord
PubMed: 33220961
DOI: 10.1016/j.jtcvs.2020.10.054 -
Handbook of Clinical Neurology 2023Degenerative ataxias and hereditary spastic paraplegias (HSPs) form a continuous, often overlapping disease spectrum sharing not only phenotypic features and underlying... (Review)
Review
Degenerative ataxias and hereditary spastic paraplegias (HSPs) form a continuous, often overlapping disease spectrum sharing not only phenotypic features and underlying genes, but also cellular pathways and disease mechanisms. Mitochondrial metabolism presents a major molecular theme underlying both multiple ataxias and HSPs, thus indicating a heightened vulnerability of Purkinje cells, spinocerebellar tracts, and motor neurons to mitochondrial dysfunction, which is of particular interest for translational approaches. Mitochondrial dysfunction might be the primary (upstream) or secondary (downstream) result of a genetic defect, with underlying genetic defects in nuclear-encoded genes being much more frequent than in mtDNA genes in both, ataxias and HSPs. Here, we outline the substantial number of ataxias, spastic ataxias and HSPs caused by mutated genes implicated in (primary or secondary) mitochondrial dysfunction, highlighting several key "mitochondrial" ataxias and HSPs which are of particular interest for their frequency, pathogenesis and translational opportunities. We then showcase prototypic mitochondrial mechanisms by which disruption of these ataxia and HSP genes contributes to Purkinje cells or corticospinal neuron dysfunction, thus elucidating hypotheses on Purkinje cells and corticospinal neuron vulnerability to mitochondrial dysfunction.
Topics: Humans; Ataxia; Spinocerebellar Ataxias; Spastic Paraplegia, Hereditary; Mitochondrial Diseases; Paraplegia; Mutation
PubMed: 36813322
DOI: 10.1016/B978-0-12-821751-1.00009-9 -
Spinal Cord Jan 2020Randomized controlled trial. (Randomized Controlled Trial)
Randomized Controlled Trial
Advanced weight-bearing mat exercises combined with functional electrical stimulation to improve the ability of wheelchair-dependent people with spinal cord injury to transfer and attain independence in activities of daily living: a randomized controlled trial.
STUDY DESIGN
Randomized controlled trial.
OBJECTIVE
To determine the effects of advanced weight-bearing mat exercises (AWMEs) with/without functional electrical stimulation (FES) of the quadriceps and gastrocnemius muscles on the ability of wheelchair-dependent people with spinal cord injury (SCI) to transfer and attain independence in activities of daily living (ADLs).
SETTING
An outpatient clinic, Iran.
METHODS
People with traumatic chronic paraplegia (N = 16) were randomly allocated to three groups. The exercise group (EX; N = 5) performed AWMEs of quadruped unilateral reaching and tall-kneeling for 24 weeks (3 days/week). Sessions were increased from 10 min to 54 min over the 24-week period. The exercise-FES group (EX + FES; N = 5) performed AWMEs simultaneously with FES of the quadriceps and gastrocnemius muscles. The control group performed no exercise and no FES (N = 6). The primary outcomes were the total Spinal Cord Independence Measure-III (SCIM-III) to reflect independence with ADL, and the sum of the four SCIM-III transfer items to reflect ability to transfer. There were six other outcomes.
RESULTS
The mean (95% CI) between-group differences of the four transfer items of the SCIM-III for the EX vs. control group was 1.8 points (0.2-3.4), and for the EX + FES vs. control group was 2 points (0.4-3.6). The equivalent differences for the total SCIM-III scores were 2.7 points (-0.6-6.0) and 4.1 points (0.8-7.4), respectively. There were no significant between-group differences for any other outcomes.
CONCLUSIONS
Advanced weight-bearing mat exercises improve the ability of wheelchair-dependent people with SCI to transfer and attain independence in ADL.
Topics: Activities of Daily Living; Adult; Combined Modality Therapy; Electric Stimulation Therapy; Exercise Therapy; Female; Humans; Male; Mobility Limitation; Muscle, Skeletal; Outcome Assessment, Health Care; Paraplegia; Spinal Cord Injuries; Weight-Bearing; Wheelchairs
PubMed: 31312016
DOI: 10.1038/s41393-019-0328-7 -
Cells Feb 2020Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. Despite some strategies,... (Review)
Review
Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. Despite some strategies, like cerebrospinal fluid drainage, the occurrence of neurological symptoms, such as paraplegia and paraparesis, remains unpredictable. Beside the major blood supply through conduit arteries, a huge collateral network protects the central nervous system from ischemia-the paraspinous and the intraspinal compartment. The intraspinal arcades maintain perfusion pressure following a sudden inflow interruption, whereas the paraspinal system first needs to undergo arteriogenesis to ensure sufficient blood supply after an acute ischemic insult. The so-called steal phenomenon can even worsen the postoperative situation by causing the hypoperfusion of the spine when, shortly after thoracoabdominal aortic aneurysm (TAAA) surgery, muscles connected with the network divert blood and cause additional stress. Vessels are a conglomeration of different cell types involved in adapting to stress, like endothelial cells, smooth muscle cells, and pericytes. This adaption to stress is subdivided in three phases-initiation, growth, and the maturation phase. In fields of endovascular aortic aneurysm repair, pre-operative selective segmental artery occlusion may enable the development of a sufficient collateral network by stimulating collateral vessel growth, which, again, may prevent spinal cord ischemia. Among others, the major signaling pathways include the phosphoinositide 3 kinase (PI3K) pathway/the antiapoptotic kinase (AKT) pathway/the endothelial nitric oxide synthase (eNOS) pathway, the Erk1, the delta-like ligand (DII), the jagged (Jag)/NOTCH pathway, and the midkine regulatory cytokine signaling pathways.
Topics: Animals; Aortic Aneurysm, Thoracic; Arteries; Collateral Circulation; Humans; Neovascularization, Physiologic; Nitric Oxide; Nitric Oxide Synthase Type III; Paraplegia; Postoperative Complications; Receptors, Notch; Signal Transduction; Spinal Cord; Spinal Cord Ischemia; Vascular Endothelial Growth Factor A
PubMed: 32098337
DOI: 10.3390/cells9020501 -
Neurology Oct 2022
Topics: Humans; Metal Workers; Ataxia; Cerebellar Ataxia; Paraplegia; Spastic Paraplegia, Hereditary; Mutation
PubMed: 35858819
DOI: 10.1212/WNL.0000000000201107 -
Infectious Diseases (London, England) Oct 2023Acute Flaccid Myelitis (AFM) is a neurological condition in the anterior portion of the spinal cord and can be characterised as paraplegia (paralysis of the lower... (Review)
Review
Acute Flaccid Myelitis (AFM) is a neurological condition in the anterior portion of the spinal cord and can be characterised as paraplegia (paralysis of the lower limbs), and cranial nerve dysfunction. These lesions are caused by the infection due to (; a member of the (EV) family belongs to the Enterovirus species within the family and a Polio-like virus. In many cases, the facial, axial, bulbar, respiratory, and extraocular muscles were affected, hence reducing the overall quality of the patient's life. Moreover, severe pathological conditions demand hospitalisation and can cause mortality in a few cases. The data from previous case studies and literature suggest that the prevalence is high in paediatric patients, but careful clinical assessment and management can decrease the risk of mortality and paraplegia. Moreover, the clinical and laboratory diagnosis can be performed by Magnetic resonance imaging (MRI) of the spinal cord followed by Reverse transcription polymerase chain reaction (rRT-PCR) and VP1 seminested PCR assay of the cerebrospinal fluid (CSF), stool, and serum samples can reveal the disease condition to an extent. The primary measure to control the outbreak is social distancing as advised by public health administrations, but more effective ways are yet to discover. Nonetheless, vaccines in the form of the whole virus, live attenuated, sub-viral particles, and DNA vaccines can be an excellent choice to treat these conditions. The review discusses a variety of topics, such as epidemiology, pathophysiology, diagnosis/clinical features, hospitalisation/mortality, management/treatment, and potential future developments.
Topics: Humans; Child; Neuromuscular Diseases; Myelitis; Paralysis; Enterovirus Infections; Enterovirus D, Human; Paraplegia
PubMed: 37368373
DOI: 10.1080/23744235.2023.2228407