Methylprednisolone and neurological function 1 year after spinal cord injury

Bracken, Michael B.; Shepard, Mary Jo; Hellenbrand, Karen; Collins, William F.; Leo, Linda S.; Freeman, Daniel F.; Wagner, Franklin C.; Flamm, Eugene S.; Eisenberg, Howard M.; Goodman, Joseph H.; Perot, Phanor L.; Green, Barth A.; Grossman, Robert G.; Meagher, John N.; Young, Wise; Fischer, Boguslav H.; Clifton, Guy L.; Hunt, William E.; Rifkinson, N

doi:10.3171/jns.1985.63.5.0704

Cited by 302 publications

(115 citation statements)

References 13 publications

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“…High V1. 4 Fund work that exploits the insights generated by V1.2 to determine the scope and e ectiveness of harnessing the natural regulators of trauma, in¯ammation and scar formation after SCI, again assessing the outcome by its bene®cial impact on subsequent nerve regeneration rather than on the tissue disruption per se.…”

Section: V13mentioning

confidence: 99%

“…1,4 Experimental studies in adult rats have shown methylprednisolone treatment to reduce lesion size, 5 increase the percentage of spared tissue and restore neurological function, 6 improve locomotor recovery 7 and increase axonal regeneration across Schwann cell grafts. 8 Methylprednisolone treatment combined with delivery of basic ®broblast growth factor was found to have additive bene®cial e ects on reversing neurological de®cits.…”

Section: Proposed Approachmentioning

confidence: 99%

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Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

2000

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Achieving regeneration in the central nervous system represents one of the greatest intellectual and practical challenges in neurobiology, and yet it is an absolute requirement if spinal cord injury patients are to have any hope of recovery. The mission of the International Spinal Research Trust (ISRT), established in 1980, is to raise money speci®cally for spinal research, with a view to ending the permanence of paralysis caused by spinal cord injury. This review summarises some of the major steps forward made in recent years in understanding the mechanisms involved in spinal cord injury and where these discoveries ®t in with the ISRT's overall objectives. We review approaches aimed at (1) preventing immediate adverse reactions to injury such as neuronal death and scar formation; (2) minimising inhibitory properties of the CNS environment and maximising the growth potential of damaged neurons; (3) understanding axonal guidance systems that will be required for directed outgrowth and functional reconnection; and (4) optimising the function of surviving systems. We also discuss infrastructural' prerequisites for applying knowledge gained through spinal research to the clinical condition, including basic scienti®c issues such as developing representative animal models of spinal cord injury and sensitive quantitative methods for assessing growth and functional restoration. In addition, we point out the importance of communication. The need to share knowledge between research groups is vital for advancing our understanding of injury and repair mechanisms. Equally important is the need for communication between basic scientists and clinicians which will be essential for what is the ultimate goal of the ISRT, the development of relevant treatment strategies that will prove bene®cial to the spinal injured patient. Spinal Cord (2000) 38, 449 ± 472

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Section: V13mentioning

confidence: 99%

Section: Proposed Approachmentioning

confidence: 99%

Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

2000

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“…[1][2][3][4] However, its use is also associated with a significant increase in complications related to systemic immunosuppression. Specifically, the incidence of wound infection, sepsis, pneumonia, and the duration of intensive care unit stay are all increased in patients receiving high-dose methylprednisolone.…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine-A-mediated inhibition of p-glycoprotein increases methylprednisolone entry into the central nervous system

Bernards

2005

Spinal Cord

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Study design: Prospective, randomized, pharmacokinetic study. Objective: To determine if cyclosporine-A-mediated inhibition of p-glycoprotein would increase methylprednisolone entry into the central nervous system thereby permitting a reduction in the systemic methylprednisolone dose. Setting: Department of Anesthesiology, University of Washington, Seattle, USA. Methods: Microdialysis probes were used to obtain cerebrospinal fluid and gluteal muscle extracellular fluid samples for measurement of methylprednisolone concentration in pigs. At time zero, a methylprednisolone bolus was given and an infusion started. At 210 min, after reaching a stable methylprednisolone concentration, a cyclosporine-A bolus was given (either 10 or 30 mg/kg) and microdialysis samples collected until 420 min. Plasma samples were collected at 10, 30 min and then every 30 min until the study's end. Results: Cyclosporine-A bolus produced a dose-dependant increase in methylprednisolone concentration in plasma, muscle and cerebrospinal fluid. Importantly, the magnitude of the increase in cerebrospinal fluid was significantly greater than the increase in plasma and muscle. Conclusions: The relatively greater increase in cerebrospinal fluid concentrations of methylprednisolone is consistent with increased penetration of the blood-brain barrier secondary to cyclosporine-mediated p-glycoprotein inhibition. Theoretically, increased methylprednisolone entry into the central nervous system should allow a reduction in the systemic methylprednisolone dose and a consequent decrease in glucocorticoid-mediated side effects.

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“…2,3 In order to demonstrate the ine ectiveness of corticosteroids, a randomized controlled study was conducted by the National Acute Spinal Cord Injury Study group (NASCIS-1). 4 The treatment group received a 1000 mg bolus of methylprednisolone (Mpred) with 1000 mg daily for 10 days, while the control group was given a 100 mg bolus with 100 mg daily for 10 days. There was no signi®cant di erence in neurologic outcome between the two groups.…”

Section: Introductionmentioning

confidence: 99%

Risk of avascular necrosis following short term megadose methylprednisolone treatment

et al. 1998

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We conducted a prospective cohort study to determine whether administration of large doses of the corticosteroid methylprednisolone following spinal cord injury as recommended in the National Acute Spinal Cord Injury Study-2 (NASCIS-2) protocol results in an increased incidence of avascular necrosis (AVN) of the femoral or humeral head. All subjects were patients treated by a spinal cord injury physician in an Acute Spinal Cord Injury Unit between 1989 and 1996 where some received the megadose steroids while others did not. Patients younger than 15 years and older than 75 years were excluded, as were those with any hip or shoulder disease, with pelvic fracture, or with a history of predisposition to AVN by hip dislocation, excessive alcohol consumption, previous high dose steroid use, or systemic lupus erythematosus. Screening for AVN of the femoral and humeral heads was performed at a minimum of 6 months following injury, using magnetic resonance imaging (MRI). The ®lms were read by a radiologist blinded to the treatment protocol received by the individual subject. Among the 59 spinal cord injured patients who received steroids (age 15 ± 64 years (mean 32 years)), ®ve were female. Among the 32 spinal cord injured subjects who did not receive steroids (age 16 to 65 years (mean 34 years)), seven were female. There was no case of AVN found in either group. Using binomial distribution, we conclude that the true incidence of AVN among the methylprednisolone treated group is less than 5% (a50.05) and therefore continue to recommend short term (24 h) methylprednisolone therapy.

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Methylprednisolone and neurological function 1 year after spinal cord injury

Cited by 302 publications

References 13 publications

Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

Cyclosporine-A-mediated inhibition of p-glycoprotein increases methylprednisolone entry into the central nervous system

Risk of avascular necrosis following short term megadose methylprednisolone treatment

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