BACKGROUND: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. METHODS: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. FINDINGS: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. INTERPRETATION: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. FUNDING: EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- krční mícha * zranění MeSH
- krční obratle MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Nogo proteiny * MeSH
- poranění míchy * farmakoterapie MeSH
- senioři MeSH
- spinální injekce * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: The recovery of autonomic functions and the ability to reproduce in particular is of the highest priority to individuals with spinal cord injury (SCI). The potential of epidural spinal cord stimulation (ESCS) for promoting recovery of sensorimotor functions in the chronic phase of SCI has long been studied. In recent years, several studies have emerged confirming the positive effect of ESCS also on the cardiovascular system and neurogenic bladder and bowel. However, the potential of ESCS in restoring sexual function, especially ejaculation, has not yet been addressed. CASE REPORT: Two cases of people with chronic sensorimotor complete SCI in the 4th thoracic spinal segment are presented. Both men were also diagnosed with severe erectile dysfunction and anejaculation. Thanks to ESCS, Participant 1 successfully restored the ejaculatory reflex using PVS in his home environment. His outcome was subsequently verified under clinical conditions. During ESCS, Participant 1 was also able to achieve ejaculation by masturbation; moreover, he conceived a child naturally without the need for IVF. In Participant 2, we then demonstrated the same effect of ESCS on the restoration of the ejaculatory reflex when targeting the stimulation to the same spinal segment. CONCLUSION: This is the first report on the potential of ESCS for restoring the ability to ejaculate in individuals with complete SCI. Confirmation of these results could significantly reduce the need for assisted reproduction and improve the quality of life of men after SCI in the future.
- MeSH
- dospělí MeSH
- ejakulace * fyziologie MeSH
- epidurální prostor MeSH
- erektilní dysfunkce etiologie terapie patofyziologie MeSH
- hrudní obratle MeSH
- lidé MeSH
- míšní stimulace * metody MeSH
- poranění míchy * komplikace patofyziologie terapie rehabilitace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
STUDY DESIGN: A psychometric study. OBJECTIVES: To introduce a novel simple tool designed to evaluate the intensity of the phasic (dynamic) component of spastic motor behavior in spinal cord injury (SCI) people and to assess its reliability and validity. SETTING: The study was developed in the Spinal Cord Unit at University Hospital Motol and Paraple Centre in Prague, Czech Republic. METHODS: The Muscle Excitability Scale (MES) is designed to rate muscle motor response to exteroceptive and proprioceptive stimuli. The impairment rating ranges from zero muscle/muscle group spasm or clonus to generalized spastic response. The selected 0 to 4 scale allows for comparing the MES results with those of the Modified Ashworth Scale (MAS). After long-term use and repeated revisions, a psychometric analysis was conducted. According to the algorithm, two physiotherapists examined 50 individuals in the chronic stage after SCI. RESULTS: The inter-rater reliability of MES for both legs showed κ = 0.52. The intra-rater reliability of MES for both legs showed κ = 0.50. The inter-rater reliability of simultaneously assessed MAS for both legs was higher, with κ = 0.69. The intra-rater reliability of MAS for both legs showed κ = 0.72. Spearman's rank correlation coefficient between MES and spasm frequency of Penn Spasm Frequency Scale (PSFS) was low, while the correlation coefficient between MES and the severity part of PSFS was moderate. CONCLUSIONS: The MES is a complementary tool for assessing the dynamic component of spastic motor behavior in SCI people. It allows a more comprehensive clinical characterization of spastic reflexes when used along with the MAS.
- MeSH
- dospělí MeSH
- kosterní svaly patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- poranění míchy * patofyziologie diagnóza komplikace MeSH
- psychometrie * MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- svalová spasticita * patofyziologie diagnóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The increase of multidrug-resistant (MDR) bacteria in healthcare settings is a worldwide concern. Isolation precautions must be implemented to control the significant risk of transmitting these pathogens among patients. Antibiotic decolonization is not recommended because of the threat of increasing antibiotic resistance. However, restoring gut microflora through faecal microbiota transplantation (FMT) is a hopeful solution. PATIENTS AND METHOD: In 2019-2022, FMT was indicated in seven patients of the Spinal Cord Unit at University Hospital Motol who were colonized with MDR bacterial strains. Five patients tested positive for carriage of carbapenemase-producing Enterobacteriaceae, and two were carriers of vancomycin-resistant enterococci. Isolation measures were implemented in all patients. Donor faeces were obtained from healthy, young, screened volunteers. According to local protocol, 200-300 ml of suspension was applied through a nasoduodenal tube. RESULTS: The mean age of the patients was 43 years. The mean length of previous hospital stay was 93.2 days. All patients were treated with broad-spectrum antibiotics for infectious complications before detecting colonisation with MDR bacteria. MDR organism decolonization was achieved in five patients, and consequently, isolation measures could be removed. Colonization persisted in two patients, one of whom remained colonized even after a third FMT. No adverse events were reported after FMT. CONCLUSION: FMT is a safe and effective strategy to eradicate MDR bacteria, even in spinal cord injured patients. FMT can allow relaxation of isolation facilitates, the participation of patients in a complete rehabilitation program, their social integration, and transfer to follow-up rehabilitation centres.
- Publikační typ
- kazuistiky MeSH
- MeSH
- dekomprese metody MeSH
- elektrická stimulace metody MeSH
- kmenové buňky MeSH
- lidé MeSH
- mícha krevní zásobení patologie MeSH
- nervová tkáň účinky léků ultrastruktura zranění MeSH
- Nogo proteiny terapeutické užití MeSH
- poranění míchy * farmakoterapie klasifikace komplikace rehabilitace terapie MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Úvod: Poranění krční míchy vede mimo jiné k poruše funkce horních končetin. To významně limituje schopnost sebeobsluhy a zvyšuje závislost na okolí. Každé, i sebemenší zlepšení tak může zásadně ovlivnit kvalitu života. K dokumentaci změn na horních končetinách v poúrazovém vývoji byl vytvořen soubor testů GRASSP (graded redefined assessment of strength, sensibility and prehension). Cíl: Představit GRASSP široké odborné veřejnosti a zhodnotit vztah mezi tímto vyšetřením a ostatními standardizovanými testy. Metoda: Soubor tvořilo 52 pacientů s akutně vzniklou krční míšní lézí hospitalizovaných na Spinální jednotce při Klinice rehabilitace a tělovýchovného lékařství 2. LF UK a FN Motol v letech 2019–2021. K hodnocení byly kromě GRASSP použity standardizované testy funkční nezávislosti (SCIM – spinal cord independence measure) a motorické skóre pro horní končetiny. GRASSP tvoří čtyři domény – svalová síla, citlivost, schopnost úchopu a provedení úchopu. Výsledky: Největší rozdíly mezi vyšetřením GRASSP při příjmu a propuštění pacientů byly zaznamenány v doménách schopnost a provedení úchopu. Tyto změny dobře korespondovaly s částí SCIM týkající se sebeobsluhy. Korelace mezi testy GRASSP a SCIM se obecně zvyšovala s dobou uplynulou od vzniku míšní léze. Závěr: GRASSP je vhodný nástroj k hodnocení i drobných změn na horních končetinách u pacientů po poranění krční míchy, který lze využít v akutním i chronickém stadiu míšní léze.
Introduction: Cervical spinal cord injury (SCI) leads, among other impairments, to dysfunction of the upper limbs. It significantly limits the ability to self-care and increases dependence on others. Every improvement, even the smallest, can fundamentally affect the quality of life. The Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) test was created to document changes in the upper limbs in post-traumatic development. Aim: To introduce the GRASSP to the general professional public and to evaluate the relationship between this examination and other standardized tests. Method: The study group consisted of 52 patients with acute cervical spinal cord injury hospitalized at the Spinal Cord Unit in University Hospital Motol between 2019 and 2021. In addition to the GRASSP, standardized Spinal Cord Independence Measure (SCIM) test and upper extremity motor score were used for evaluation. GRASSP deals with four domains – muscle strength, sensitivity, grasp ability, and grasp execution. Results: The greatest differences between the GRASSP examination at admission and discharge of patients were found in the domains of grasp ability and execution. These changes corresponded well with the self-care domain of the SCIM. The correlation between the GRASSP and SCIM tests generally increased within the time since injury. Conclusion: GRASSP is a suitable test for evaluating even minor changes in the upper limbs in patients after cervical SCI, which can be used in both acute and chronic stages of SCI.
- Klíčová slova
- GRASSP,
- MeSH
- diagnostické techniky neurologické MeSH
- dospělí MeSH
- horní končetina patofyziologie MeSH
- krční mícha zranění MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofyziologický monitoring * metody statistika a číselné údaje MeSH
- poranění míchy * komplikace MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
The International standards for neurological classification of spinal cord injury are the most widely used tools for the evaluation of sensorimotor deficit after spinal cord injury. Nevertheless, the examination is time-consuming, even for an experienced therapist. Frequently, mainly in the acute phase, it is replaced by nonstandardized examination which is unable to make a proper classification. Therefore, the Committee of the American Spinal Injury Association developed the expedited version of international standards, which allows to define the neurological level of injury and its severity with the least amount of exam items.
Mezinárodní standardy pro neurologickou klasifikaci míšního poranění jsou široce využívaný nástroj pro zhodnocení senzomotorického deficitu po poranění míchy. Vyšetření je nicméně časově náročné, a to i pro zkušeného terapeuta. Často se především v akutní fázi nahrazuje nestandardizovaným vyšetřením, které neumožní správnou klasifikaci. Proto byla výborem Americké asociace spinálního poranění vytvořena zrychlená verze mezinárodních standardů, kterou je možné definovat neurologickou úroveň léze a její rozsah pomocí co nejmenšího počtu vyšetřovaných položek.
