The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study.

A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, ≤ 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6). (JAMA1984;251:45-52)

https://jamanetwork.com/journals/jama/articlepdf/390877/jama_251_1_015.pdf

Efficacy of Methylprednisolone in Acute Spinal Cord Injury

Investigation of the role of 5-hydroxytryptophan (5-HT), which functions as a modulator in the central nervous system, across behavioral contexts suggests that a general principle of transmitter function may be derived that is independent of specific behaviors and specific neural loci. A functional principle of 5-HT action in neural information processing in the central nervous system is proposed. Extremes deviations in 5-HT activity result in biases in information processing that may have direct effects on behavior. Such biases may predispose to pathological conditions such as violent suicide and aggression.

Modulatory role of serotonin in neural information processing: implications for human psychopathology.

Modulatory Role of Serotonin in Neural Information Processing

A multi-center double-blind randomized clinical trial was conducted by the National Acute Spinal Cord Injury Study Group to examine the efficacy of high-dose methylprednisolone (1000-mg bolus and 1000 mg daily thereafter for 10 days) compared with that of a standard dose (100-mg bolus and 100 mg daily for 10 days) No significant difference was observed in neurological recovery of motor function, pinprick response, or touch sensation 1 year after injury between the two treatment groups, after adjustment for other potentially confounding factors Analyses that specifically took into account the patients' total steroid dose and relative weight confirmed the lack of a steroid treatment effect The case fatality rate was 107% during the 1st year after injury, and this was not associated with the steroid treatment protocol or the patient's gender Deaths did occur significantly more frequently among patients who were completely (153%) and partially (86%) plegic than among those who were paretic (25%, p = 00005), and among patients aged 50 years or older (386%, p = 00001)

Mullan S

Papers

Seizure susceptibility after manipulation of brain serotonin.

Monoamine changes in experimental head and spinal cord trauma: failure to confirm previous observations.

Dimethyl sulfoxide in the treatment of experimental acute spinal cord injury.

Experimental evaluation of L-dopa penetration in brain.

Experimental therapy after middle cerebral artery occlusion in monkeys.