scholarly journals Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Aynur DEMIREL ◽  
Jia LI ◽  
Casey MORROW ◽  
Stephen BARNES ◽  
Jan JANSEN ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Care ◽  
Ketogenic Diet ◽  
Motor Function ◽  
Functional Recovery ◽  
Functional Independence ◽  
Neurological Recovery ◽  
Controlled Study ◽  
Cord Injury

Abstract Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a SCI rat model, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD started during acute care, improved upper extremity motor function, and reduced serum levels of a neuroinflammatory blood protein. The primary goals of the current study are to: 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory functions, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics. Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study, a total of 60 eligible participants ranging in age from 18 to 60 years with acute traumatic SCI (cervical 5 – thoracic 12) American Spinal Injury Association impairment scale (AIS A-C): AIS-A, sensorimotor complete; AIS-B, sensory incomplete/motor complete; and AIS-C, non-functional motor incomplete, are being enrolled. Neurological and functional examinations, resting energy expenditure, blood, urine, and stool collections, and protein analyses related to neurological recovery will be performed within 72 h of injury (baseline measure) and repeated after 5 weeks of KD or SD (discharge measure). We anticipate a completion rate of 80% with a total of 48 participants. Discussion: Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries. Trial registrations: ClinicalTrials.gov, NCT03509571. Registered in April 2018.

scholarly journals Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Aynur DEMIREL ◽  
Jia LI ◽  
Casey MORROW ◽  
Stephen BARNES ◽  
Jan JANSEN ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Total Energy ◽  
Acute Care ◽  
Ketogenic Diet ◽  
Motor Function ◽  
Functional Recovery ◽  
Functional Independence ◽  
Neurological Recovery ◽  
Cord Injury

Abstract Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a rat model of SCI, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD, started during acute care, improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of our proposed study are to 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory function, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study design, 60 participants with acute SCI will be randomly assigned to KD or SD in a 1:1 ratio. We intend to recruit 24 participants for each group with traumatic SCI (C5–T12, American Spinal Injury Association impairment scale A–C, and aged 18–60 years). Patients will be taken to acute care after their injury. Neurological and functional examinations, resting energy expenditure, blood, urine, stool collection and protein analyses related to neuro recovery will be done within 72 h of injury, as baseline measures. Patients received five weeks of KD or SD according to their allocation. The KD is a high-fat, low-carbohydrate diet (3:1 ratio of fat: carbohydrate + protein) that includes ~75% total energy as fat, ~20% as protein, and ~5% as carbohydrate and fiber. The SD includes ~45-50% total energy as carbohydrate and fiber, ~30% total energy as fat, and ~20% total energy as protein. All baseline examinations will be repeated at discharge from the hospital at week 5 (discharge measure). Discussion: The proposed diet intervention is practical and safe and is expected to translate into efficacious early nutritional interventions. Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries such as traumatic brain injury and stroke.

Development and Validation of Crosswalks Between FIM® and SCIM III for Voluntary Musculoskeletal Movement Functions

2021 ◽  
pp. 154596832110338
Author(s):  
Linda A. T. Jones ◽  
Chih-Ying Li ◽  
David Weitzenkamp ◽  
John Steeves ◽  
Susie Charlifue ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Systems Of Care ◽  
Functional Independence Measure ◽  
Correlation Coefficients ◽  
Functional Independence ◽  
Cord Injury ◽  
Parametric Analyses ◽  
Development And Validation

Background. In spinal cord injury, there are multiple databases containing information on functional recovery, but data cannot be pooled or compared due to differences in how function is measured. A crosswalk is needed to link or convert scores between instruments. Objectives. To create a crosswalk between the voluntary musculoskeletal movement items in the Functional Independence Measure (FIM®) and the Spinal Cord Independence Measure III (SCIM III) for spinal cord injury. Methods. Retrospective datasets with FIM® and SCIM III on the same people were used to develop (Swiss dataset, n = 662) and validate (US, n = 119, and Canadian datasets, n = 133) the crosswalks. Three different crosswalk methods (expert panel, equipercentile, and Rasch analysis) were employed. We used the correlation between observed scores on FIM® and SCIM III to crosswalked scores as the primary criterion to assess the strength of the crosswalk. Secondary criteria such as score distributions, Cohen’s effect size, point differences, and subgroup invariance were also evaluated. Results. All three methods resulted in strong correlation coefficients, exceeding the primary criterion value of r = .866 (.897–.972). Assessment of secondary criteria suggests the equipercentile and Rasch methods produced the strongest crosswalks. Conclusions. The Rasch FIM®/SCIM III crosswalk is recommended because it is based on co-calibration of linearized measures, allowing for more sophisticated parametric analyses. The crosswalk will allow comparisons of voluntary musculoskeletal functional recovery across international databases using different functional measures, as well as different systems of care and rehabilitation approaches.

Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa

2010 ◽  
Vol 12 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Masanori Aoki ◽  
Haruhiko Kishima ◽  
Kazuhiro Yoshimura ◽  
Masahiro Ishihara ◽  
Masaki Ueno ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lamina Propria ◽  
Motor Function ◽  
Functional Recovery ◽  
Olfactory Mucosa ◽  
Respiratory Mucosa ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Object The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. Methods Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa–transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. Conclusions Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

scholarly journals Ultrasound stimulation improves inflammatory resolution, neuroprotection, and functional recovery after spinal cord injury

2021 ◽  
Author(s):  
Yu-ri Hong ◽  
Eun-hee Lee ◽  
Ki-su Park ◽  
Mun Han ◽  
Kyoung-Tae Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Motor Function ◽  
Functional Recovery ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Injury Site ◽  
Cord Injury ◽  
Anti Inflammatory

Abstract Spinal cord injury (SCI) is associated with limited functional recovery. Despite advances in neuroscience, realistic therapeutic treatments for SCI remain unavailable. In this study, the effects of non-invasive ultrasound (US) treatment on behavior and inflammatory responses were evaluated in a rat model of SCI. Adult female Sprague–Dawley rats were subjected to spinal cord contusion injury. Two different US parameters (SCIU5: 5% and SCIU40: 40% duty cycle) were applied, and their effects on behavioral recovery after SCI were quantified. Tissue and neuronal responses were detected. Immunofluorescence was used to detect inflammatory markers. In the rat model of SCI, motor function was more effectively restored, and the lesion cavity area was smaller in the SCIU5 group. Furthermore, the SCIU5 protocol elicited an anti-inflammatory response at the injury site by reducing degenerative FJC-labeled neurons, macrophage/microglia activation, and infiltration. Thus, the lesion area decreased, and tissue density increased. Meanwhile, the SCIU40 protocol did not improve motor function or induce an anti-inflammatory response at the injury site. The SCIU5 protocol effectively accelerated the rate of improved exercise performance in the rat model while reducing inflammation. Accordingly, appropriate US stimulation may represent a promising treatment modality for SCI with beneficial anti-inflammatory effects.

scholarly journals Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78765 ◽  
Author(s):  
Femke Streijger ◽  
Ward T. Plunet ◽  
Jae H. T. Lee ◽  
Jie Liu ◽  
Clarrie K. Lam ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Ketogenic Diet ◽  
Motor Function ◽  
Cord Injury

scholarly journals Prediction of functional recovery six months following traumatic spinal cord injury during acute care hospitalization

2017 ◽  
Vol 41 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Andréane Richard- Denis ◽  
Debbie Feldman ◽  
Cynthia Thompson ◽  
Jean-Marc Mac-Thiong
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Care ◽  
Functional Recovery ◽  
Traumatic Spinal Cord Injury ◽  
Cord Injury

scholarly journals Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

2021 ◽  
Author(s):  
Gaëtan Poulen ◽  
Emilie Aloy ◽  
Claire M. Bringuier ◽  
Nadine Mestre-Francés ◽  
Emaëlle V.F. Artus ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Functional Recovery ◽  
Nonhuman Primates ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Post Injury ◽  
Function Recovery ◽  
Cord Injury

AbstractNo curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.

scholarly journals Advanced neurological recovery translates into greater long-term functional independence after acute spinal cord injury

2020 ◽  
Author(s):  
Navid Khosravi-Hashemi ◽  
Rainer Abel ◽  
Lukas Grassner ◽  
Yorck-Bernhard Kalke ◽  
Doris Maier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Functional Independence ◽  
International Standards ◽  
Neurological Recovery ◽  
Cord Injury ◽  
European Multicenter Study ◽  
The Impact

The absence of effective pharmacological interventions in acute traumatic spinal cord injury is a major problem in its management. A critical barrier in identifying such interventions lies in the vast heterogeneity of recovery profiles, which masks the potential efficacy of treatments in clinical trials. To determine the impact of temporal recovery profiles on long-term functional independence, we used EMSCI (European Multicenter Study about Spinal Cord Injury) data. Total motor scores from the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) and the Spinal Cord Independence Measure (SCIM) were used to assess neurological and functional outcomes, respectively. We developed a classification method consisting of thresholding and unsupervised machine learning clustering and applied it to the total motor score profiles. Comparing SCIM scores between classes revealed that functional independence is significantly higher among patients displaying advanced neurological recovery profile. Our study suggests that the evaluation of temporal recovery profiles can provide novel insights in spinal cord injury clinical trials.

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